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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. Mobile Data Collection Applications: A Proof of Concept

    International Nuclear Information System (INIS)

    Chang, J

    2006-01-01

    This project's goal is to provide a proof of concept for mobile data collection applications, and identify the best ways such applications could be implemented and used. Such an application should decrease the time and resources users now need to devote to redundant data processes, and provide an easy of locating and retrieving data at a later time. The two types of available mobile devices, Personal Digital Assistants and Tablet Personal Computers, each have their particular strengths that suggest themselves for certain types of applications. As such, parallel data collection applications have been developed, with a common web application for uploading information to the database. While these aspects have been developed and proven, it still remains to refine these applications, develop the tables to hold their data, and field-test with users for their feedback

  3. Application of an ex vivo cellular model of circadian variation for bipolar disorder research: a proof of concept study.

    Science.gov (United States)

    Bamne, Mikhil N; Ponder, Christine A; Wood, Joel A; Mansour, Hader; Frank, Ellen; Kupfer, David J; Young, Michael W; Nimgaonkar, Vishwajit L

    2013-09-01

    Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRCs) were also generated following forskolin challenge and the phase response patterns were characterized. Period length and PRCs could be estimated reliably from the constructs. There were no significant case-control differences in period length, with a nonsignificant trend for differences in PRCs following the phase-setting experiments. An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Collecting standardised oral health data via mobile application: A proof of concept study in the Netherlands.

    Directory of Open Access Journals (Sweden)

    Joost C L den Boer

    Full Text Available FDI World Dental Federation, founded as Fédération Dentaire Internationale, has taken the initiative to develop the Oral Health Observatory, a mobile application to conduct oral health surveys worldwide. The aim is to collect reliable standardized international data on oral health and oral health care via a network of dentists. A proof of concept study project was set up in the Netherlands to test the methodology and to validate the approach. Data about caries, gingivitis, oral self-care and oral health related quality of life were analysed and compared to datasets validated in other studies. The Android app embeds three questionnaires addressing oral health history, status and patient behaviour. One questionnaire was completed by the patient and two by the dentist. The proof of concept study involved two phases: in the first phase, five dentists, regular participants in KNMT-surveys, evaluated the usability of the app; after the first phase, the app was adjusted for a second phase. For this phase an extra 15 dentists were recruited from a group of 20 other dentists: five of them declined to participate. Attention was paid to ensuring there was a proportional representation of gender, age and region. In the second phase the five first and 15 new participants collected data on up to a maximum of 38 patients. Data from this 653 patients correspond with results from previously published surveys on the prevalence of caries and gingivitis in the Netherlands. Hence demonstrating an association between caries and gingivitis with oral self-care, problems eating and experiencing oral pain. This proof of concept study shows that the app makes it possible to collect reliable information on oral health in a short period of time. Both dentists and patients evaluated the methodology as user-friendly. Altogether, the results of this proof of concept study are promising.

  5. Collecting standardised oral health data via mobile application: A proof of concept study in the Netherlands.

    Science.gov (United States)

    den Boer, Joost C L; van Dijk, Ward; Horn, Virginie; Hescot, Patrick; Bruers, Josef J M

    2018-01-01

    FDI World Dental Federation, founded as Fédération Dentaire Internationale, has taken the initiative to develop the Oral Health Observatory, a mobile application to conduct oral health surveys worldwide. The aim is to collect reliable standardized international data on oral health and oral health care via a network of dentists. A proof of concept study project was set up in the Netherlands to test the methodology and to validate the approach. Data about caries, gingivitis, oral self-care and oral health related quality of life were analysed and compared to datasets validated in other studies. The Android app embeds three questionnaires addressing oral health history, status and patient behaviour. One questionnaire was completed by the patient and two by the dentist. The proof of concept study involved two phases: in the first phase, five dentists, regular participants in KNMT-surveys, evaluated the usability of the app; after the first phase, the app was adjusted for a second phase. For this phase an extra 15 dentists were recruited from a group of 20 other dentists: five of them declined to participate. Attention was paid to ensuring there was a proportional representation of gender, age and region. In the second phase the five first and 15 new participants collected data on up to a maximum of 38 patients. Data from this 653 patients correspond with results from previously published surveys on the prevalence of caries and gingivitis in the Netherlands. Hence demonstrating an association between caries and gingivitis with oral self-care, problems eating and experiencing oral pain. This proof of concept study shows that the app makes it possible to collect reliable information on oral health in a short period of time. Both dentists and patients evaluated the methodology as user-friendly. Altogether, the results of this proof of concept study are promising.

  6. Toward a Proof of Concept Cloud Framework for Physics Applications on Blue Gene Supercomputers

    International Nuclear Information System (INIS)

    Dreher, Patrick; Scullin, William; Vouk, Mladen

    2015-01-01

    Traditional high performance supercomputers are capable of delivering large sustained state-of-the-art computational resources to physics applications over extended periods of time using batch processing mode operating environments. However, today there is an increasing demand for more complex workflows that involve large fluctuations in the levels of HPC physics computational requirements during the simulations. Some of the workflow components may also require a richer set of operating system features and schedulers than normally found in a batch oriented HPC environment. This paper reports on progress toward a proof of concept design that implements a cloud framework onto BG/P and BG/Q platforms at the Argonne Leadership Computing Facility. The BG/P implementation utilizes the Kittyhawk utility and the BG/Q platform uses an experimental heterogeneous FusedOS operating system environment. Both platforms use the Virtual Computing Laboratory as the cloud computing system embedded within the supercomputer. This proof of concept design allows a cloud to be configured so that it can capitalize on the specialized infrastructure capabilities of a supercomputer and the flexible cloud configurations without resorting to virtualization. Initial testing of the proof of concept system is done using the lattice QCD MILC code. These types of user reconfigurable environments have the potential to deliver experimental schedulers and operating systems within a working HPC environment for physics computations that may be different from the native OS and schedulers on production HPC supercomputers. (paper)

  7. Distributed electrical time domain reflectometry (ETDR) structural sensors: design models and proof-of-concept experiments

    Science.gov (United States)

    Stastny, Jeffrey A.; Rogers, Craig A.; Liang, Chen

    1993-07-01

    A parametric design model has been created to optimize the sensitivity of the sensing cable in a distributed sensing system. The system consists of electrical time domain reflectometry (ETDR) signal processing equipment and specially designed sensing cables. The ETDR equipment sends a high-frequency electric pulse (in the giga hertz range) along the sensing cable. Some portion of the electric pulse will be reflected back to the ETDR equipment as a result of the variation of the cable impedance. The electric impedance variation in the sensing cable can be related to its mechanical deformation, such as cable elongation (change in the resistance), shear deformation (change in the capacitance), corrosion of the cable or the materials around the cable (change in inductance and capacitance), etc. The time delay, amplitude, and shape of the reflected pulse provides the means to locate, determine the magnitude, and indicate the nature of the change in the electrical impedance, which is then related to the distributed structural deformation. The sensing cables are an essential part of the health-monitoring system. By using the parametric design model, the optimum cable parameters can be determined for specific deformation. Proof-of-concept experiments also are presented in the paper to demonstrate the utility of an electrical TDR system in distributed sensing applications.

  8. Development of a Proof of Concept Low Temperature Superfluid Magnetic Pump with Applications

    Science.gov (United States)

    Jahromi, Amir E.

    State of the art particle and photon detectors such as Transition Edge Sensors (TES) and Microwave Kinetic Inductance Detectors (MKID) use large arrays of sensors or detectors for space science missions. As the size of these space science detectors increases, future astrophysics missions will require sub-Kelvin coolers over larger areas. This leads to not only increased cooling power requirements, but also a requirement for distributed sub-Kelvin cooling. Development of a proof of concept Superfluid Magnetic Pump is discussed 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, or active magnetic regenerative refrigerators. Due to its superior thermal transport properties this pump can also be used as a simple circulator of sub-Lambda 4He to distribute cooling over large surface areas. The pump discussed in this work 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 Pascal. 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 put to test in suitable sub Kelvin refrigeration systems. Numerical modeling of an Active Magnetic Regenerative Refrigerator (AMRR) that uses the Superfluid Magnetic Pump (SMP) to circulate liquid 3He-4He through a magnetic regenerator is presented as a potential application of such a pump.

  9. Augmented Reality Application for Training in Maritime Operations. A Proof of Concept AR Application Developed for Microsoft HoloLens

    OpenAIRE

    Xue, Hui

    2017-01-01

    Augmented reality (AR) is an advanced technology that integrates augmentations with the real world. This technology has been used to provide training and education along with other purposes. This work has been focused on enriching the learning experience of the maritime trainee by applying AR technology. In this work, a proof of concept AR application (App) is developed for the training of the maritime students. The App was designed to introduce the selected stations and panel in the Kongsber...

  10. Modeling Child–Nature Interaction in a Nature Preschool: A Proof of Concept

    Directory of Open Access Journals (Sweden)

    Peter H. Kahn

    2018-05-01

    Full Text Available This article provides a proof of concept for an approach to modeling child–nature interaction based on the idea of interaction patterns: characterizations of essential features of interaction between humans and nature, specified abstractly enough such that countless different instantiations of each one can occur – in more domestic or wild forms – given different types of nature, people, and purposes. The model draws from constructivist psychology, ecological psychology, and evolutionary psychology, and is grounded in observational data collected through a time-sampling methodology at a nature preschool. Through using a nature language that emphasizes ontogenetic and phylogenetic significance, seven keystone interaction patterns are described for this nature preschool: using one’s body vigorously in nature, striking wood on wood, constructing shelter, being in solitude in nature, lying on earth, cohabiting with a wild animal, and being outside in weather. These 7 interactions patterns are then brought together with 13 other patterns published elsewhere to provide a total of 20 keystone interaction patterns that begin to fill out the model, and to show its promise. Discussion focuses on what the model aims to be in terms of both product and process, on what work the model can currently do, and how to further develop the model.

  11. Proof of concept and dose estimation with binary responses under model uncertainty.

    Science.gov (United States)

    Klingenberg, B

    2009-01-30

    This article suggests a unified framework for testing Proof of Concept (PoC) and estimating a target dose for the benefit of a more comprehensive, robust and powerful analysis in phase II or similar clinical trials. From a pre-specified set of candidate models, we choose the ones that best describe the observed dose-response. To decide which models, if any, significantly pick up a dose effect, we construct the permutation distribution of the minimum P-value over the candidate set. This allows us to find critical values and multiplicity adjusted P-values that control the familywise error rate of declaring any spurious effect in the candidate set as significant. Model averaging is then used to estimate a target dose. Popular single or multiple contrast tests for PoC, such as the Cochran-Armitage, Dunnett or Williams tests, are only optimal for specific dose-response shapes and do not provide target dose estimates with confidence limits. A thorough evaluation and comparison of our approach to these tests reveal that its power is as good or better in detecting a dose-response under various shapes with many more additional benefits: It incorporates model uncertainty in PoC decisions and target dose estimation, yields confidence intervals for target dose estimates and extends to more complicated data structures. We illustrate our method with the analysis of a Phase II clinical trial. Copyright (c) 2008 John Wiley & Sons, Ltd.

  12. Rethinking the data model: the drillbit proof-of-concept library

    International Nuclear Information System (INIS)

    Ebke, Johannes; Waller, Peter

    2014-01-01

    The focus of many software architectures of the LHC experiments is to deliver a well-designed Event Data Model (EDM). Changes and additions to the stored data are often expensive, requiring large amounts of CPU time, disk storage and man-power. In addition, differing needs between groups of physicists lead to a tendency for common data formats to grow in terms of contained information whilst still not managing to service all needs. We introduce a new way of thinking about the data model based on the Dremel column store architecture published by Google. We present an EDM concept based on Dremel, which has the potential to significantly reduce the storage requirement for these common formats, decrease the time needed for independent physicists to compare their results and improve the speed at which data reprocessings can feasibly take place. The Dremel low-level encoding is implemented in a proof-of-concept C++ library called Drillbit, and it is shown that using a different encoding of the current data could save as much as 20% of disk space on average across a wide number of real-world derived data sets.

  13. Application Development for Optimizing Patient Placement on Aeromedical Evacuation Flights: Proof-of-Concept

    Science.gov (United States)

    2018-01-12

    PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Brittany Fouts, Jennifer Serres, Ray Hill, Frank Ciarallo 5d. PROJECT NUMBER 5e. TASK NUMBER 5f...APPENDIX A – Flowchart for Graphical Prototype ...................................................................... 9 APPENDIX B – Proof-of-Concept App...would like to thank the programming team at the Department of Operational Analysis at the Air Force Institute of Technology at Wright-Patterson Air

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

    International Nuclear Information System (INIS)

    Ahmed Hassan

    2004-01-01

    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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Endoventricular Deep Brain Stimulation of the Third Ventricle: Proof of Concept and Application to Cluster Headache.

    Science.gov (United States)

    Chabardès, Stéphan; Carron, Romain; Seigneuret, Eric; Torres, Napoleon; Goetz, Laurent; Krainik, Alexandre; Piallat, Brigitte; Pham, Pascale; David, Olivier; Giraud, Pierrick; Benabid, Alim Louis

    2016-12-01

    The third ventricle (3rd V) is surrounded by centers related to satiety, homeostasis, hormones, sleep, memory, and pain. Stimulation of the wall of the 3rd V could be useful to treat disorders related to dysfunction of the hypothalamus. To assess safety and efficacy of endoventricular electrical stimulation of the hypothalamus using a floating deep brain stimulation (DBS) lead laid on the floor of the 3rd V to treat refractory cluster headaches (CH). Seven patients, aged 24 to 60 years, experiencing chronic CH (mean chronic duration 5.8 ± 2.5 years) were enrolled in this pilot, prospective, open study assessing the safety and potential efficacy of chronic DBS of the 3rd V. Number of attacks was collected during baseline and was compared with those occurring at 3, 6, and 12 months postoperation. Any side effects that occurred during or after surgery were reported. Effect on mood was assessed using the Hospital Anxiety and Depression scale during baseline and at 6 and 12 months postoperation. Insertion of the lead into the posterior 3rd V and chronic stimulation was feasible and safe in all patients. The voltage ranged from 0.9 to 2.3 volts. The most common side effect was transient trembling vision during stimulation. At 12 months, 3 of 7 patients were pain free, 2 had 90% improvement, 1 of 7 had 75% improvement, and 1 of 7 was not significantly improved. This proof of concept demonstrates the feasibility, safety, and potential efficacy of 3rd V DBS using an endoventricular road that could be applied to treat various diseases involving hypothalamic areas. CCH, chronic cluster headacheCH, cluster headacheDBS, deep brain stimulationHAD, hospital anxiety depressionONS, occipital nerve stimulationPAG, periaqueductal gray matterPH, posterior hypothalamusPVG, periventricular gray matter3rd V, third ventricle.

  2. Calculation of bedload transport in Swiss mountain rivers using the model sedFlow: proof of concept

    Directory of Open Access Journals (Sweden)

    F. U. M. Heimann

    2015-01-01

    Full Text Available Fully validated numerical models specifically designed for simulating bedload transport dynamics in mountain streams are rare. In this study, the recently developed modelling tool sedFlow has been applied to simulate bedload transport in the Swiss mountain rivers Kleine Emme and Brenno. It is shown that sedFlow can be used to successfully reproduce observations from historic bedload transport events with plausible parameter set-ups, meaning that calibration parameters are only varied within ranges of uncertainty that have been pre-determined either by previous research or by field observations in the simulated study reaches. In the Brenno river, the spatial distribution of total transport volumes has been reproduced with a Nash–Sutcliffe goodness of fit of 0.733; this relatively low value is partially due to anthropogenic extraction of sediment that was not considered. In the Kleine Emme river, the spatial distribution of total transport volumes has been reproduced with a goodness of fit of 0.949. The simulation results shed light on the difficulties that arise with traditional flow-resistance estimation methods when macro-roughness is present. In addition, our results demonstrate that greatly simplified hydraulic routing schemes, such as kinematic wave or uniform discharge approaches, are probably sufficient for a good representation of bedload transport processes in reach-scale simulations of steep mountain streams. The influence of different parameters on simulation results is semi-quantitatively evaluated in a simple sensitivity study. This proof-of-concept study demonstrates the usefulness of sedFlow for a range of practical applications in alpine mountain streams.

  3. 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

  4. 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

    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.

  5. 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.

  6. Proof of concept of an artificial muscle: theoretical model, numerical model, and hardware experiment.

    Science.gov (United States)

    Haeufle, D F B; Günther, M; Blickhan, R; Schmitt, S

    2011-01-01

    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, the contraction dynamics of this CE concept were analyzed in a numerical simulation of quick release experiments against different loads. A hyperbolic force-velocity relation was found. The results correspond to measurements of the contraction dynamics of a technical prototype. Deviations from the theoretical prediction could partly be explained by the low stiffness of the SE, which was modeled analog to the metal spring in the hardware prototype. The numerical model and hardware prototype together, are a proof of this CE concept and can be seen as a well-founded starting point for the development of Hill-type artificial muscles. This opens up new vistas for the technical realization of natural movements with rehabilitation devices. © 2011 IEEE

  7. 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

    2018-01-01

    : electrical grid layer, ICT & network emulation layer and control layer. DiSC-OPAL, a toolbox built for OPAL-RT real time grid simulation; comprising of models for wide variety of controllable flexible assets, stochastic power sources for wind and solar power plants, real consumption data’s and electrical...

  8. 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.

  9. 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. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Long-distance travel modeling: proof of concept : research results digest.

    Science.gov (United States)

    2016-04-01

    This research project was established to provide ADOT with direction on the best sources of data and best practices for updating its long-distance personal travel models to better reflect observed travel behavior. Its original intent was to recommend...

  11. Poroelastic Modeling as a Proof of Concept for Modular Representation of Coupled Geophysical Processes

    Science.gov (United States)

    Walker, R. L., II; Knepley, M.; Aminzadeh, F.

    2017-12-01

    We seek to use the tools provided by the Portable, Extensible Toolkit for Scientific Computation (PETSc) to represent a multiphysics problem in a form that decouples the element definition from the fully coupled equation through the use of pointwise functions that imitate the strong form of the governing equation. This allows allows individual physical processes to be expressed as independent kernels that may be then coupled with the existing finite element framework, PyLith, and capitalizes upon the flexibility offered by the solver, data management, and time stepping algorithms offered by PETSc. To demonstrate a characteristic example of coupled geophysical simulation devised in this manner, we present a model of a synthetic poroelastic environment, with and without the consideration of inertial effects, with fluid initially represented as a single phase. Matrix displacement and fluid pressure serve as the desired unknowns, with the option for various model parameters represented as dependent variables of the central unknowns. While independent of PyLith, this model also serves to showcase the adaptability of physics kernels for synthetic forward modeling. In addition, we seek to expand the base case to demonstrate the impact of modeling fluid as single phase compressible versus a single incompressible phase. As a goal, we also seek to include multiphase fluid modeling, as well as capillary effects.

  12. 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.

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

    Science.gov (United States)

    2012-12-01

    base pour construire de telles simulations et pourrait être adaptée à d’autres expériences à un coût relativement bas. Perspectives : Les leçons...systems (such as culture , [ Culture ]). This seven-dimensional framework advocates that systems be viewed from the physical, individual, functional...structural, normative, social, and informational dimensions. The human factors include modelling stress, trust, risk factors, and cultural factors

  14. Gallbladder Cryoablation: Proof of Concept in a Swine Model for a Percutaneous Alternative to Cholecystectomy

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, Hugh C. J., E-mail: hugh.mcgregor@ucsf.edu; Saeed, Maythem, E-mail: maythem.saeed@ucsf.edu; Surman, Andrew, E-mail: andrew.surman@ucsf.edu; Ehman, Eric C., E-mail: eric.ehman@ucsf.edu; Hetts, Steven W., E-mail: steven.hetts@ucsf.edu; Wilson, Mark W., E-mail: mark.wilson@ucsf.edu; Conrad, Miles B., E-mail: miles.conrad@ucsf.edu [University of California San Francisco, Department of Radiology and Biomedical Imaging (United States)

    2016-07-15

    PurposeTo investigate the feasibility of percutaneous gallbladder cryoablation (GBC) under CT guidance in a swine model with histopathologic correlation.Materials and MethodsInstitutional Animal Care and Use Committee approval was obtained for this study protocol. Five pigs underwent GBC. Under CT guidance, 3–4 cryoprobes were positioned percutaneously at the gallbladder margins. Thermocouple probes were placed percutaneously at the gallbladder fundus, neck, free wall, and gallbladder fossa. Two freeze–thaw cycles ranging from 10 to 26 min were performed. The subjects were sacrificed 5 h after cryoablation. The gallbladder and bile ducts were resected, stained, and examined microscopically.ResultsGBC was completed in all subjects. A 10-mm ablation margin was achieved beyond all gallbladder walls. Thermocouple probes reached at least −20 °C. Intra-procedural body temperature decreased to a minimum of 35 °C but recovered after the procedure. Intra- and post-procedural vital signs otherwise remained within physiologic parameters. Non-target ablation occurred in the stomach and colon of the first two subjects. Histology demonstrated complete denudation of the gallbladder epithelium, hemorrhage, and edema within the muscularis layer, and preservation of the microscopic architecture of the common bile duct in all cases.ConclusionPercutaneous gallbladder cryoablation is feasible, with adequate ablation margins obtained and histologic changes demonstrating transmural necrosis. Adjacent structures included in the ablation may require conservative ablation zones, hydrodissection, or continuous saline lavage.

  15. Gallbladder Cryoablation: Proof of Concept in a Swine Model for a Percutaneous Alternative to Cholecystectomy

    International Nuclear Information System (INIS)

    McGregor, Hugh C. J.; Saeed, Maythem; Surman, Andrew; Ehman, Eric C.; Hetts, Steven W.; Wilson, Mark W.; Conrad, Miles B.

    2016-01-01

    PurposeTo investigate the feasibility of percutaneous gallbladder cryoablation (GBC) under CT guidance in a swine model with histopathologic correlation.Materials and MethodsInstitutional Animal Care and Use Committee approval was obtained for this study protocol. Five pigs underwent GBC. Under CT guidance, 3–4 cryoprobes were positioned percutaneously at the gallbladder margins. Thermocouple probes were placed percutaneously at the gallbladder fundus, neck, free wall, and gallbladder fossa. Two freeze–thaw cycles ranging from 10 to 26 min were performed. The subjects were sacrificed 5 h after cryoablation. The gallbladder and bile ducts were resected, stained, and examined microscopically.ResultsGBC was completed in all subjects. A 10-mm ablation margin was achieved beyond all gallbladder walls. Thermocouple probes reached at least −20 °C. Intra-procedural body temperature decreased to a minimum of 35 °C but recovered after the procedure. Intra- and post-procedural vital signs otherwise remained within physiologic parameters. Non-target ablation occurred in the stomach and colon of the first two subjects. Histology demonstrated complete denudation of the gallbladder epithelium, hemorrhage, and edema within the muscularis layer, and preservation of the microscopic architecture of the common bile duct in all cases.ConclusionPercutaneous gallbladder cryoablation is feasible, with adequate ablation margins obtained and histologic changes demonstrating transmural necrosis. Adjacent structures included in the ablation may require conservative ablation zones, hydrodissection, or continuous saline lavage.

  16. 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

  17. The Ocean Carbon States Database: a proof-of-concept application of cluster analysis in the ocean carbon cycle

    Science.gov (United States)

    Latto, Rebecca; Romanou, Anastasia

    2018-03-01

    In this paper, we present a database of the basic regimes of the carbon cycle in the ocean, the ocean carbon states, as obtained using a data mining/pattern recognition technique in observation-based as well as model data. The goal of this study is to establish a new data analysis methodology, test it and assess its utility in providing more insights into the regional and temporal variability of the marine carbon cycle. This is important as advanced data mining techniques are becoming widely used in climate and Earth sciences and in particular in studies of the global carbon cycle, where the interaction of physical and biogeochemical drivers confounds our ability to accurately describe, understand, and predict CO2 concentrations and their changes in the major planetary carbon reservoirs. In this proof-of-concept study, we focus on using well-understood data that are based on observations, as well as model results from the NASA Goddard Institute for Space Studies (GISS) climate model. Our analysis shows that ocean carbon states are associated with the subtropical-subpolar gyre during the colder months of the year and the tropics during the warmer season in the North Atlantic basin. Conversely, in the Southern Ocean, the ocean carbon states can be associated with the subtropical and Antarctic convergence zones in the warmer season and the coastal Antarctic divergence zone in the colder season. With respect to model evaluation, we find that the GISS model reproduces the cold and warm season regimes more skillfully in the North Atlantic than in the Southern Ocean and matches the observed seasonality better than the spatial distribution of the regimes. Finally, the ocean carbon states provide useful information in the model error attribution. Model air-sea CO2 flux biases in the North Atlantic stem from wind speed and salinity biases in the subpolar region and nutrient and wind speed biases in the subtropics and tropics. Nutrient biases are shown to be most important in

  18. The Ocean Carbon States Database: a proof-of-concept application of cluster analysis in the ocean carbon cycle

    Directory of Open Access Journals (Sweden)

    R. Latto

    2018-03-01

    Full Text Available In this paper, we present a database of the basic regimes of the carbon cycle in the ocean, the ocean carbon states, as obtained using a data mining/pattern recognition technique in observation-based as well as model data. The goal of this study is to establish a new data analysis methodology, test it and assess its utility in providing more insights into the regional and temporal variability of the marine carbon cycle. This is important as advanced data mining techniques are becoming widely used in climate and Earth sciences and in particular in studies of the global carbon cycle, where the interaction of physical and biogeochemical drivers confounds our ability to accurately describe, understand, and predict CO2 concentrations and their changes in the major planetary carbon reservoirs. In this proof-of-concept study, we focus on using well-understood data that are based on observations, as well as model results from the NASA Goddard Institute for Space Studies (GISS climate model. Our analysis shows that ocean carbon states are associated with the subtropical–subpolar gyre during the colder months of the year and the tropics during the warmer season in the North Atlantic basin. Conversely, in the Southern Ocean, the ocean carbon states can be associated with the subtropical and Antarctic convergence zones in the warmer season and the coastal Antarctic divergence zone in the colder season. With respect to model evaluation, we find that the GISS model reproduces the cold and warm season regimes more skillfully in the North Atlantic than in the Southern Ocean and matches the observed seasonality better than the spatial distribution of the regimes. Finally, the ocean carbon states provide useful information in the model error attribution. Model air–sea CO2 flux biases in the North Atlantic stem from wind speed and salinity biases in the subpolar region and nutrient and wind speed biases in the subtropics and tropics. Nutrient biases are shown

  19. The Ocean Carbon States Database: A Proof-of-Concept Application of Cluster Analysis in the Ocean Carbon Cycle

    Science.gov (United States)

    Latto, Rebecca; Romanou, Anastasia

    2018-01-01

    In this paper, we present a database of the basic regimes of the carbon cycle in the ocean, the 'ocean carbon states', as obtained using a data mining/pattern recognition technique in observation-based as well as model data. The goal of this study is to establish a new data analysis methodology, test it and assess its utility in providing more insights into the regional and temporal variability of the marine carbon cycle. This is important as advanced data mining techniques are becoming widely used in climate and Earth sciences and in particular in studies of the global carbon cycle, where the interaction of physical and biogeochemical drivers confounds our ability to accurately describe, understand, and predict CO2 concentrations and their changes in the major planetary carbon reservoirs. In this proof-of-concept study, we focus on using well-understood data that are based on observations, as well as model results from the NASA Goddard Institute for Space Studies (GISS) climate model. Our analysis shows that ocean carbon states are associated with the subtropical-subpolar gyre during the colder months of the year and the tropics during the warmer season in the North Atlantic basin. Conversely, in the Southern Ocean, the ocean carbon states can be associated with the subtropical and Antarctic convergence zones in the warmer season and the coastal Antarctic divergence zone in the colder season. With respect to model evaluation, we find that the GISS model reproduces the cold and warm season regimes more skillfully in the North Atlantic than in the Southern Ocean and matches the observed seasonality better than the spatial distribution of the regimes. Finally, the ocean carbon states provide useful information in the model error attribution. Model air-sea CO2 flux biases in the North Atlantic stem from wind speed and salinity biases in the subpolar region and nutrient and wind speed biases in the subtropics and tropics. Nutrient biases are shown to be most important

  20. How much is left in your "sleep tank"? Proof of concept for a simple model for sleep history feedback.

    Science.gov (United States)

    Dorrian, Jillian; Hursh, Steven; Waggoner, Lauren; Grant, Crystal; Pajcin, Maja; Gupta, Charlotte; Coates, Alison; Kennaway, David; Wittert, Gary; Heilbronn, Leonie; Vedova, Chris Della; Banks, Siobhan

    2018-02-02

    Technology-supported methods for sleep recording are becoming increasingly affordable. Sleep history feedback may help with fatigue-related decision making - Should I drive? Am I fit for work? This study examines a "sleep tank" model (SleepTank ™ ), which is analogous to the fuel tank in a car, refilled by sleep, and depleted during wake. Required inputs are sleep period time and sleep efficiency (provided by many consumer-grade actigraphs). Outputs include suggested hours remaining to "get sleep" and percentage remaining in tank (Tank%). Initial proof of concept analyses were conducted using data from a laboratory-based simulated nightshift study. Ten, healthy males (18-35y) undertook an 8h baseline sleep opportunity and daytime performance testing (BL), followed by four simulated nightshifts (2000 h-0600 h), with daytime sleep opportunities (1000 h-1600 h), then an 8 h night-time sleep opportunity to return to daytime schedule (RTDS), followed by daytime performance testing. Psychomotor Vigilance Task (PVT) and Karolinska Sleepiness Scale were performed at 1200 h on BL and RTDS, and at 1830 h, 2130 h 0000 h and 0400 h each nightshift. A 40-minute York Driving Simulation was performed at 1730 h, 2030 h and 0300 h on each nightshift. Model outputs were calculated using sleep period timing and sleep efficiency (from polysomnography) for each participant. Tank% was a significant predictor of PVT lapses (p performance and sleepiness measures indicated relatively good predictive value. Results provide tentative evidence that this "sleep tank" model may be an informative tool to aid in individual decision-making based on sleep history. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Analysis of the Effect of Environmental Conditions in Conducting Amphibious Assaults Using a Ship Simulator/Vessel-Response Model Proof-of-Concept Study

    Science.gov (United States)

    2017-05-01

    the exit interview conducted at the conclusion of the testing period. Appendix B summarizes the recommendations the craftmasters made for improving ...the “Go/No-Go” condition. Unlike USACE applications , where that scenario is known by interviewing harbor pilots, the Go/No-Go conditions are...summarizes a proof-of-concept study for demonstrating the application of these technologies to allow commanders to determine the feasibility of surface

  2. Possible application of silicon photomultiplier technology to detect the presence of spirit and intention: three proof-of-concept experiments.

    Science.gov (United States)

    Schwartz, Gary E

    2010-01-01

    Research investigating the survival of consciousness hypothesis has been hampered by the lack of an independent measure of the purported presence of spirit (POS). Although numerous anecdotes involving electronic devices (including tape recorders, answering machines, and computers) claim that POS can be detected with sensitive electromagnetic sensors, little systematic laboratory research has investigated this possibility. The purpose of this exploratory laboratory research was to test the feasibility of using a state-of-the-art silicon photomultiplier system to detect low photon levels potentially associated with POS. A PCDMini photon counting device manufactured by sensL provided a sensitive measure of sums of photons over time. Three proof-of-concept experiments were conducted. Each included multiple five-minute trials of "invited spirit" conditions as well as baseline controls. One experiment included a set of 10 noninvited control trials as well as controls for experimenter intention per se. Data were collected as part of a university laboratory devoted to researching advances in consciousness and health. The participants were purported spirits presumably motivated to participate in the research. The primary intervention was the experimenter's intention for purported spirits to enter the light-tight chamber on specified trials. In a light-tight chamber, the PCDMini device software counted and displayed individual sums of typically 13 to 25 photon detections per approximately 90-milliseconds time periods (in complete darkness, most time periods contained zero photons detected); the number of photon sums could be counted precisely in five-minute periods. The average number of photon sums was found to be significantly higher in purported POS trials compared with noninvited trials. Matched control trials as well as explicit experimenter intention trials showed no effects. Silicon photomultiplier devices may be sufficiently sensitive to investigate the POS and

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    identification 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

  4. 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...... 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....... 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...

  5. A proof-of-concept for linking the global meteorological model, MPAS-A with the air quality model, CMAQ

    Science.gov (United States)

    Researchers who perform air quality modeling studies usually do so on a regional scale. Typically, the boundary conditions are generated by another model which might have a different chemical mechanism, spatial resolution, and/or map projection. Hence, a necessary conversion/inte...

  6. Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

    Directory of Open Access Journals (Sweden)

    Morten Andersen

    Full Text Available The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies. Only a few studies have described the development of MPNs by mathematical models, and none have addressed the role of inflammation for clonal evolution and disease progression. Herein, we aim at using mathematical modelling to substantiate the concept of chronic inflammation as an important trigger and driver of MPNs.The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal evolution and an important driving force for MPN disease progression. Our findings support intervention at the earliest stage of cancer development to target the malignant clone and dampen concomitant inflammation.

  7. Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development

    DEFF Research Database (Denmark)

    Andersen, Morten; Sajid, Zamra; Pedersen, Rasmus K.

    2017-01-01

    The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs.......The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks...... or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal...

  8. Are reflective models appropriate for very short scales? Proofs of concept of formative models using the Ten-Item Personality Inventory.

    Science.gov (United States)

    Myszkowski, Nils; Storme, Martin; Tavani, Jean-Louis

    2018-04-27

    Because of their length and objective of broad content coverage, very short scales can show limited internal consistency and structural validity. We argue that it is because their objectives may be better aligned with formative investigations than with reflective measurement methods that capitalize on content overlap. As proofs of concept of formative investigations of short scales, we investigate the Ten Item Personality Inventory (TIPI). In Study 1, we administered the TIPI and the Big Five Inventory (BFI) to 938 adults, and fitted a formative Multiple Indicator Multiple Causes model, which consisted of the TIPI items forming 5 latent variables, which in turn predicted the 5 BFI scores. These results were replicated in Study 2, on a sample of 759 adults, with, this time, the Revised NEO Personality Inventory (NEO-PI-R) as the external criterion. The models fit the data adequately, and moderate to strong significant effects (.37<|β|<.69, all p<.001) of all 5 latent formative variables on their corresponding BFI and NEOPI-R scores were observed. This study presents a formative approach that we propose to be more consistent with the aims of scales with broad content and short length like the TIPI. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

    Joe, Jeffrey Clark; Boring, Ronald Laurids; Herberger, Sarah Elizabeth Marie; Mandelli, Diego; Smith, Curtis Lee

    2015-01-01

    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.

  10. 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.

  11. A 4D global respiratory motion model of the thorax based on CT images: A proof of concept.

    Science.gov (United States)

    Fayad, Hadi; Gilles, Marlene; Pan, Tinsu; Visvikis, Dimitris

    2018-05-17

    Respiratory motion reduces the sensitivity and specificity of medical images especially in the thoracic and abdominal areas. It may affect applications such as cancer diagnostic imaging and/or radiation therapy (RT). Solutions to this issue include modeling of the respiratory motion in order to optimize both diagnostic and therapeutic protocols. Personalized motion modeling required patient-specific four-dimensional (4D) imaging which in the case of 4D computed tomography (4D CT) acquisition is associated with an increased dose. The goal of this work was to develop a global respiratory motion model capable of relating external patient surface motion to internal structure motion without the need for a patient-specific 4D CT acquisition. The proposed global model is based on principal component analysis and can be adjusted to a given patient anatomy using only one or two static CT images in conjunction with a respiratory synchronized patient external surface motion. It is based on the relation between the internal motion described using deformation fields obtained by registering 4D CT images and patient surface maps obtained either from optical imaging devices or extracted from CT image-based patient skin segmentation. 4D CT images of six patients were used to generate the global motion model which was validated by adapting it on four different patients having skin segmented surfaces and two other patients having time of flight camera acquired surfaces. The reproducibility of the proposed model was also assessed on two patients with two 4D CT series acquired within 2 weeks of each other. Profile comparison shows the efficacy of the global respiratory motion model and an improvement while using two CT images in order to adapt the model. This was confirmed by the correlation coefficient with a mean correlation of 0.9 and 0.95 while using one or two CT images respectively and when comparing acquired to model generated 4D CT images. For the four patients with segmented

  12. 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.

  13. 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.

  14. Bipedal gait model for precise gait recognition and optimal triggering in foot drop stimulator: a proof of concept.

    Science.gov (United States)

    Shaikh, Muhammad Faraz; Salcic, Zoran; Wang, Kevin I-Kai; Hu, Aiguo Patrick

    2018-03-10

    Electrical stimulators are often prescribed to correct foot drop walking. However, commercial foot drop stimulators trigger inappropriately under certain non-gait scenarios. Past researches addressed this limitation by defining stimulation control based on automaton of a gait cycle executed by foot drop of affected limb/foot only. Since gait is a collaborative activity of both feet, this research highlights the role of normal foot for robust gait detection and stimulation triggering. A novel bipedal gait model is proposed where gait cycle is realized as an automaton based on concurrent gait sub-phases (states) from each foot. The input for state transition is fused information from feet-worn pressure and inertial sensors. Thereafter, a bipedal gait model-based stimulation control algorithm is developed. As a feasibility study, bipedal gait model and stimulation control are evaluated in real-time simulation manner on normal and simulated foot drop gait measurements from 16 able-bodied participants with three speed variations, under inappropriate triggering scenarios and with foot drop rehabilitation exercises. Also, the stimulation control employed in commercial foot drop stimulators and single foot gait-based foot drop stimulators are compared alongside. Gait detection accuracy (98.9%) and precise triggering under all investigations prove bipedal gait model reliability. This infers that gait detection leveraging bipedal periodicity is a promising strategy to rectify prevalent stimulation triggering deficiencies in commercial foot drop stimulators. Graphical abstract Bipedal information-based gait recognition and stimulation triggering.

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

    Science.gov (United States)

    Kamoi, Shun; Pretty, Christopher; Docherty, Paul; Squire, Dougie; Revie, James; Chiew, Yeong Shiong; Desaive, Thomas; Shaw, Geoffrey M; Chase, J Geoffrey

    2014-01-01

    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.

  16. A modular magnetic anastomotic device for minimally invasive digestive anastomosis: proof of concept and preliminary data in the pig model.

    Science.gov (United States)

    Diana, Michele; Mutter, Didier; Lindner, Véronique; Vix, Michel; Chung, Hyunsoo; Demartines, Nicolas; Marescaux, Jacques

    2014-05-01

    The aim of our study was to assess the feasibility of minimally invasive digestive anastomosis using a modular flexible magnetic anastomotic device made up of a set of two flexible chains of magnetic elements. The assembly possesses a non-deployed linear configuration which allows it to be introduced through a dedicated small-sized applicator into the bowel where it takes the deployed form. A centering suture allows the mating between the two parts to be controlled in order to include the viscerotomy between the two magnetic rings and the connected viscera. Eight pigs were involved in a 2-week survival experimental study. In five colorectal anastomoses, the proximal device was inserted by a percutaneous endoscopic technique, and the colon was divided below the magnet. The distal magnet was delivered transanally to connect with the proximal magnet. In three jejunojejunostomies, the first magnetic chain was injected in its linear configuration through a small enterotomy. Once delivered, the device self-assembled into a ring shape. A second magnet was injected more distally through the same port. The centering sutures were tied together extracorporeally and, using a knot pusher, magnets were connected. Ex vivo strain testing to determine the compression force delivered by the magnetic device, burst pressure of the anastomosis, and histology were performed. Mean operative time including endoscopy was 69.2 ± 21.9 min, and average time to full patency was 5 days for colorectal anastomosis. Operative times for jejunojejunostomies were 125, 80, and 35 min, respectively. The postoperative period was uneventful. Burst pressure of all anastomoses was ≥ 110 mmHg. Mean strain force to detach the devices was 6.1 ± 0.98 and 12.88 ± 1.34 N in colorectal and jejunojejunal connections, respectively. Pathology showed a mild-to-moderate inflammation score. The modular magnetic system showed enormous potential to create minimally invasive digestive anastomoses, and may represent

  17. Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study

    Directory of Open Access Journals (Sweden)

    Bruna M. Ascoli

    2017-05-01

    Full Text Available Abstract Introduction The rationale of mesenchymal stem cells (MSCs as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX. Methods Wistar rats (n=65 received one oral daily dose of LDX (10 mg/kg or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells or lithium (47.5 mg/kg as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004, and lithium reversed LDX-related hyperactive behavior (p0.05 in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

  18. New Alcohol and Onyx Mixture for Embolization: Feasibility and Proof of Concept in Both In Vitro and In Vivo Models

    Energy Technology Data Exchange (ETDEWEB)

    Saeed Kilani, Mohammad, E-mail: msaeedkilani@gmail.com, E-mail: mohammadalikilani@yahoo.com [Centre Hospitalier Universitaire (CHRU) de Lille, Hôpital cardiologique (France); Zehtabi, Fatemeh, E-mail: fatemeh.zehtabi@gmail.com; Lerouge, Sophie, E-mail: Sophie.Lerouge@etsmtl.ca [école de technologie supérieure (ETS) & CHUM Research center (CRCHUM), Department of Mechanical Engineering (Canada); Soulez, Gilles, E-mail: gilles.soulez.chum@ssss.gouv.qc.ca [Centre Hospitalier de l’Université de Montréal, Department of Radiology (Canada); Bartoli, Jean Michel, E-mail: jean-michel.bartoli@ap-hm.fr [University Hospital Timone, Department of Medical Imaging (France); Vidal, Vincent, E-mail: Vincent.VIDAL@ap-hm.fr [Centre Hospitalier Universitaire (CHRU) de Lille, Hôpital cardiologique (France); Badran, Mohammad F., E-mail: mfbadran@hotmail.com [King Faisal Specialist Hospital and Research Center, Radiology Department (Saudi Arabia)

    2017-05-15

    IntroductionOnyx and ethanol are well-known embolic and sclerotic agents that are frequently used in embolization. These agents present advantages and disadvantages regarding visibility, injection control and penetration depth. Mixing both products might yield a new product with different characteristics. The aim of this study is to evaluate the injectability, radiopacity, and mechanical and occlusive properties of different mixtures of Onyx 18 and ethanol in vitro and in vivo (in a swine model).Materials and MethodsVarious Onyx 18 and ethanol formulations were prepared and tested in vitro for their injectability, solidification rate and shrinkage, cohesion and occlusive properties. In vivo tests were performed using 3 swine. Ease of injection, radiopacity, cohesiveness and penetration were analyzed using fluoroscopy and high-resolution CT.ResultsAll mixtures were easy to inject through a microcatheter with no resistance or blockage in vitro and in vivo. The 50%-ethanol mixture showed delayed copolymerization with fragmentation and proximal occlusion. The 75%-ethanol mixture showed poor radiopacity in vivo and was not tested in vitro. The 25%-ethanol mixture showed good occlusive properties and accepted penetration and radiopacity.ConclusionMixing Onyx and ethanol is feasible. The mixture of 25% of ethanol and 75% of Onyx 18 could be a new sclero-embolic agent. Further research is needed to study the chemical changes of the mixture, to confirm the significance of the added sclerotic effect and to find out the ideal mixture percentages.

  19. Robotically Assisted Sonic Therapy as a Noninvasive Nonthermal Ablation Modality: Proof of Concept in a Porcine Liver Model.

    Science.gov (United States)

    Smolock, Amanda R; Cristescu, Mircea M; Vlaisavljevich, Eli; Gendron-Fitzpatrick, Annette; Green, Chelsey; Cannata, Jonathan; Ziemlewicz, Timothy J; Lee, Fred T

    2018-05-01

    Purpose To determine the feasibility of creating a clinically relevant hepatic ablation (ie, an ablation zone capable of treating a 2-cm liver tumor) by using robotically assisted sonic therapy (RAST), a noninvasive and nonthermal focused ultrasound therapy based on histotripsy. Materials and Methods This study was approved by the institutional animal use and care committee. Ten female pigs were treated with RAST in a single session with a prescribed 3-cm spherical treatment region and immediately underwent abdominal magnetic resonance (MR) imaging. Three pigs (acute group) were sacrificed immediately following MR imaging. Seven pigs (chronic group) were survived for approximately 4 weeks and were reimaged with MR imaging immediately before sacrifice. Animals underwent necropsy and harvesting of the liver for histologic evaluation of the ablation zone. RAST ablations were performed with a 700-kHz therapy transducer. Student t tests were performed to compare prescribed versus achieved ablation diameter, difference of sphericity from 1, and change in ablation zone volume from acute to chronic imaging. Results Ablation zones had a sphericity index of 0.99 ± 0.01 (standard deviation) (P < .001 vs sphericity index of 1). Anteroposterior and transverse dimensions were not significantly different from prescribed (3.4 ± 0.7; P = .08 and 3.2 ± 0.8; P = .29, respectively). The craniocaudal dimension was significantly larger than prescribed (3.8 ± 1.1; P = .04), likely because of respiratory motion. The central ablation zone demonstrated complete cell destruction and a zone of partial necrosis. A fibrous capsule surrounded the ablation zone by 4 weeks. On 4-week follow-up images, ablation zone volumes decreased by 64% (P < .001). Conclusion RAST is capable of producing clinically relevant ablation zones in a noninvasive manner in a porcine model. © RSNA, 2018.

  20. 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.

  1. Guiding periodontal pocket recolonization: a proof of concept.

    Science.gov (United States)

    Teughels, W; Newman, M G; Coucke, W; Haffajee, A D; Van Der Mei, H C; Haake, S Kinder; Schepers, E; Cassiman, J-J; Van Eldere, J; van Steenberghe, D; Quirynen, M

    2007-11-01

    The complexity of the periodontal microbiota resembles that of the gastro-intestinal tract, where infectious diseases are treatable via probiotics. In the oropharyngeal region, probiotic or replacement therapies have shown some benefit in the prevention of dental caries, otitis media, and pharyngitis, but their effectiveness in the treatment of periodontitis is unknown. Therefore, this study addressed the hypothesis that the application of selected beneficial bacteria, as an adjunct to scaling and root planing, would inhibit the periodontopathogen recolonization of periodontal pockets. Analysis of the data showed, in a beagle dog model, that when beneficial bacteria were applied in periodontal pockets adjunctively after root planing, subgingival recolonization of periodontopathogens was delayed and reduced, as was the degree of inflammation, at a clinically significant level. The study confirmed the hypothesis and provides a proof of concept for a guided pocket recolonization (GPR) approach in the treatment of periodontitis.

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

    Directory of Open Access Journals (Sweden)

    Frank Cerra

    2015-11-01

    Full Text Available 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.

  3. 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

    2017-07-01

    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, 43(7), 53-62.]. Copyright 2017, SLACK Incorporated.

  4. 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.

  5. 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.

  6. 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

  7. Y-90 SPECT ML image reconstruction with a new model for tissue-dependent bremsstrahlung production using CT information: a proof-of-concept study

    Science.gov (United States)

    Lim, Hongki; Fessler, Jeffrey A.; Wilderman, Scott J.; Brooks, Allen F.; Dewaraja, Yuni K.

    2018-06-01

    While the yield of positrons used in Y-90 PET is independent of tissue media, Y-90 SPECT imaging is complicated by the tissue dependence of bremsstrahlung photon generation. The probability of bremsstrahlung production is proportional to the square of the atomic number of the medium. Hence, the same amount of activity in different tissue regions of the body will produce different numbers of bremsstrahlung photons. Existing reconstruction methods disregard this tissue-dependency, potentially impacting both qualitative and quantitative imaging of heterogeneous regions of the body such as bone with marrow cavities. In this proof-of-concept study, we propose a new maximum-likelihood method that incorporates bremsstrahlung generation probabilities into the system matrix, enabling images of the desired Y-90 distribution to be reconstructed instead of the ‘bremsstrahlung distribution’ that is obtained with existing methods. The tissue-dependent probabilities are generated by Monte Carlo simulation while bone volume fractions for each SPECT voxel are obtained from co-registered CT. First, we demonstrate the tissue dependency in a SPECT/CT imaging experiment with Y-90 in bone equivalent solution and water. Visually, the proposed reconstruction approach better matched the true image and the Y-90 PET image than the standard bremsstrahlung reconstruction approach. An XCAT phantom simulation including bone and marrow regions also demonstrated better agreement with the true image using the proposed reconstruction method. Quantitatively, compared with the standard reconstruction, the new method improved estimation of the liquid bone:water activity concentration ratio by 40% in the SPECT measurement and the cortical bone:marrow activity concentration ratio by 58% in the XCAT simulation.

  8. Injury profile SIMulator, a Qualitative aggregative modelling framework to predict injury profile as a function of cropping practices, and abiotic and biotic environment. II. Proof of concept: design of IPSIM-wheat-eyespot.

    Science.gov (United States)

    Robin, Marie-Hélène; Colbach, Nathalie; Lucas, Philippe; Montfort, Françoise; Cholez, Célia; Debaeke, Philippe; Aubertot, Jean-Noël

    2013-01-01

    IPSIM (Injury Profile SIMulator) is a generic modelling framework presented in a companion paper. It aims at predicting a crop injury profile as a function of cropping practices and abiotic and biotic environment. IPSIM's modelling approach consists of designing a model with an aggregative hierarchical tree of attributes. In order to provide a proof of concept, a model, named IPSIM-Wheat-Eyespot, has been developed with the software DEXi according to the conceptual framework of IPSIM to represent final incidence of eyespot on wheat. This paper briefly presents the pathosystem, the method used to develop IPSIM-Wheat-Eyespot using IPSIM's modelling framework, simulation examples, an evaluation of the predictive quality of the model with a large dataset (526 observed site-years) and a discussion on the benefits and limitations of the approach. IPSIM-Wheat-Eyespot proved to successfully represent the annual variability of the disease, as well as the effects of cropping practices (Efficiency = 0.51, Root Mean Square Error of Prediction = 24%; bias = 5.0%). IPSIM-Wheat-Eyespot does not aim to precisely predict the incidence of eyespot on wheat. It rather aims to rank cropping systems with regard to the risk of eyespot on wheat in a given production situation through ex ante evaluations. IPSIM-Wheat-Eyespot can also help perform diagnoses of commercial fields. Its structure is simple and permits to combine available knowledge in the scientific literature (data, models) and expertise. IPSIM-Wheat-Eyespot is now available to help design cropping systems with a low risk of eyespot on wheat in a wide range of production situations, and can help perform diagnoses of commercial fields. In addition, it provides a proof of concept with regard to the modelling approach of IPSIM. IPSIM-Wheat-Eyespot will be a sub-model of IPSIM-Wheat, a model that will predict injury profile on wheat as a function of cropping practices and the production situation.

  9. 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.

  10. 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.

  11. Using Patterns for Multivariate Monitoring and Feedback Control of Linear Accelerator Performance: Proof-of-Concept Research

    International Nuclear Information System (INIS)

    Cordes, Gail Adele; Van Ausdeln, Leo Anthony; Velasquez, Maria Elena

    2002-01-01

    The report discusses preliminary proof-of-concept research for using the Advanced Data Validation and Verification System (ADVVS), a new INEEL software package, to add validation and verification and multivariate feedback control to the operation of non-destructive analysis (NDA) equipment. The software is based on human cognition, the recognition of patterns and changes in patterns in time-related data. The first project applied ADVVS to monitor operations of a selectable energy linear electron accelerator, and showed how the software recognizes in real time any deviations from the optimal tune of the machine. The second project extended the software method to provide model-based multivariate feedback control for the same linear electron accelerator. The projects successfully demonstrated proof-of-concept for the applications and focused attention on the common application of intelligent information processing techniques

  12. 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.

  13. Integrating data from multiple sources for insights into demographic processes: Simulation studies and proof of concept for hierarchical change-in-ratio models.

    Science.gov (United States)

    Nilsen, Erlend B; Strand, Olav

    2018-01-01

    We developed a model for estimating demographic rates and population abundance based on multiple data sets revealing information about population age- and sex structure. Such models have previously been described in the literature as change-in-ratio models, but we extend the applicability of the models by i) using time series data allowing the full temporal dynamics to be modelled, by ii) casting the model in an explicit hierarchical modelling framework, and by iii) estimating parameters based on Bayesian inference. Based on sensitivity analyses we conclude that the approach developed here is able to obtain estimates of demographic rate with high precision whenever unbiased data of population structure are available. Our simulations revealed that this was true also when data on population abundance are not available or not included in the modelling framework. Nevertheless, when data on population structure are biased due to different observability of different age- and sex categories this will affect estimates of all demographic rates. Estimates of population size is particularly sensitive to such biases, whereas demographic rates can be relatively precisely estimated even with biased observation data as long as the bias is not severe. We then use the models to estimate demographic rates and population abundance for two Norwegian reindeer (Rangifer tarandus) populations where age-sex data were available for all harvested animals, and where population structure surveys were carried out in early summer (after calving) and late fall (after hunting season), and population size is counted in winter. We found that demographic rates were similar regardless whether we include population count data in the modelling, but that the estimated population size is affected by this decision. This suggest that monitoring programs that focus on population age- and sex structure will benefit from collecting additional data that allow estimation of observability for different age- and

  14. 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"). Published by Elsevier B.V.

  15. A novel duplex ddPCR assay for the diagnosis of schistosomiasis japonica: proof of concept in an experimental mouse model.

    Science.gov (United States)

    Weerakoon, Kosala G; Gordon, Catherine A; Cai, Pengfei; Gobert, Geoffrey N; Duke, Mary; Williams, Gail M; McManus, Donald P

    2017-07-01

    The current World Health Organization strategic plan targets the elimination of schistosomiasis as a public health problem by 2025 and accurate diagnostics will play a pivotal role in achieving this goal. DNA-based detection methods provide a viable alternative to some of the commonly used tests, notably microscopy and serology, for the diagnosis of schistosomiasis. The detection of parasite cell-free DNA in different clinical samples is a recent valuable advance, which provides significant benefits for accurate disease diagnosis. Here we validated a novel duplex droplet digital PCR assay for the diagnosis of Chinese (SjC) and Philippine (SjP) strains of Schistosoma japonicum infection in a mouse model. The assay proved applicable for both SjC and SjP infections and capable of detecting infection at a very early intra-mammalian stage in conveniently obtainable samples (urine and saliva) as well as in serum and feces. The target DNA copy numbers obtained in the assay showed a positive correlation with the infection burden assessed by direct traditional parasitology. The potential to detect parasite DNA in urine and saliva has important practical implications for large-scale epidemiological screening programmes in the future, particularly in terms of logistical convenience, and the assay has the potential to be a valuable additional tool for the diagnosis of schistosomiasis japonica.

  16. Natural tuning: towards a proof of concept

    Science.gov (United States)

    Dubovsky, Sergei; Gorbenko, Victor; Mirbabayi, Mehrdad

    2013-09-01

    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.

  17. Towards Additive Manufacture of Functional, Spline-Based Morphometric Models of Healthy and Diseased Coronary Arteries: In Vitro Proof-of-Concept Using a Porcine Template

    Directory of Open Access Journals (Sweden)

    Rachel Jewkes

    2018-02-01

    Full Text Available The aim of this study is to assess the additive manufacture of morphometric models of healthy and diseased coronary arteries. Using a dissected porcine coronary artery, a model was developed with the use of computer aided engineering, with splines used to design arteries in health and disease. The model was altered to demonstrate four cases of stenosis displaying varying severity, based on published morphometric data available. Both an Objet Eden 250 printer and a Solidscape 3Z Pro printer were used in this analysis. A wax printed model was set into a flexible thermoplastic and was valuable for experimental testing with helical flow patterns observed in healthy models, dominating the distal LAD (left anterior descending and left circumflex arteries. Recirculation zones were detected in all models, but were visibly larger in the stenosed cases. Resin models provide useful analytical tools for understanding the spatial relationships of blood vessels, and could be applied to preoperative planning techniques, but were not suitable for physical testing. In conclusion, it is feasible to develop blood vessel models enabling experimental work; further, through additive manufacture of bio-compatible materials, there is the possibility of manufacturing customized replacement arteries.

  18. Towards Additive Manufacture of Functional, Spline-Based Morphometric Models of Healthy and Diseased Coronary Arteries: In Vitro Proof-of-Concept Using a Porcine Template.

    Science.gov (United States)

    Jewkes, Rachel; Burton, Hanna E; Espino, Daniel M

    2018-02-02

    The aim of this study is to assess the additive manufacture of morphometric models of healthy and diseased coronary arteries. Using a dissected porcine coronary artery, a model was developed with the use of computer aided engineering, with splines used to design arteries in health and disease. The model was altered to demonstrate four cases of stenosis displaying varying severity, based on published morphometric data available. Both an Objet Eden 250 printer and a Solidscape 3Z Pro printer were used in this analysis. A wax printed model was set into a flexible thermoplastic and was valuable for experimental testing with helical flow patterns observed in healthy models, dominating the distal LAD (left anterior descending) and left circumflex arteries. Recirculation zones were detected in all models, but were visibly larger in the stenosed cases. Resin models provide useful analytical tools for understanding the spatial relationships of blood vessels, and could be applied to preoperative planning techniques, but were not suitable for physical testing. In conclusion, it is feasible to develop blood vessel models enabling experimental work; further, through additive manufacture of bio-compatible materials, there is the possibility of manufacturing customized replacement arteries.

  19. Distributed learning: Developing a predictive model based on data from multiple hospitals without data leaving the hospital - A real life proof of concept.

    Science.gov (United States)

    Jochems, Arthur; Deist, Timo M; van Soest, Johan; Eble, Michael; Bulens, Paul; Coucke, Philippe; Dries, Wim; Lambin, Philippe; Dekker, Andre

    2016-12-01

    One of the major hurdles in enabling personalized medicine is obtaining sufficient patient data to feed into predictive models. Combining data originating from multiple hospitals is difficult because of ethical, legal, political, and administrative barriers associated with data sharing. In order to avoid these issues, a distributed learning approach can be used. Distributed learning is defined as learning from data without the data leaving the hospital. Clinical data from 287 lung cancer patients, treated with curative intent with chemoradiation (CRT) or radiotherapy (RT) alone were collected from and stored in 5 different medical institutes (123 patients at MAASTRO (Netherlands, Dutch), 24 at Jessa (Belgium, Dutch), 34 at Liege (Belgium, Dutch and French), 48 at Aachen (Germany, German) and 58 at Eindhoven (Netherlands, Dutch)). A Bayesian network model is adapted for distributed learning (watch the animation: http://youtu.be/nQpqMIuHyOk). The model predicts dyspnea, which is a common side effect after radiotherapy treatment of lung cancer. We show that it is possible to use the distributed learning approach to train a Bayesian network model on patient data originating from multiple hospitals without these data leaving the individual hospital. The AUC of the model is 0.61 (95%CI, 0.51-0.70) on a 5-fold cross-validation and ranges from 0.59 to 0.71 on external validation sets. Distributed learning can allow the learning of predictive models on data originating from multiple hospitals while avoiding many of the data sharing barriers. Furthermore, the distributed learning approach can be used to extract and employ knowledge from routine patient data from multiple hospitals while being compliant to the various national and European privacy laws. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

  20. Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

    Science.gov (United States)

    Imbs, Diane-Charlotte; El Cheikh, Raouf; Boyer, Arnaud; Ciccolini, Joseph; Mascaux, Céline; Lacarelle, Bruno; Barlesi, Fabrice; Barbolosi, Dominique; Benzekry, Sébastien

    2018-01-01

    Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC-bearing mice. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizumab and chemotherapy. Combining this data with a mathematical model of tumor growth under therapy accounting for the normalization effect, we predicted an optimal delay of 2.8 days between bevacizumab and chemotherapy. This prediction was confirmed experimentally, with reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged survival (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a similar increase in efficacy, thus emphasizing the utility of modeling support to identify optimal scheduling. The model could also be a useful tool in the clinic to personally tailor regimen sequences. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  1. Kernel-based adaptive learning improves accuracy of glucose predictive modelling in type 1 diabetes: A proof-of-concept study.

    Science.gov (United States)

    Georga, Eleni I; Principe, Jose C; Rizos, Evangelos C; Fotiadis, Dimitrios I

    2017-07-01

    This study aims at demonstrating the need for nonlinear recursive models to the identification and prediction of the dynamic glucose system in type 1 diabetes. Nonlinear regression is performed in a reproducing kernel Hilbert space, by the Approximate Linear Dependency Kernel Recursive Least Squares (KRLS-ALD) algorithm, such that a sparse model structure is accomplished. The method is evaluated on seven people with type 1 diabetes in free-living conditions, where a change in glycaemic dynamics is forced by increasing the level of physical activity in the middle of the observational period. The univariate input allows for short-term (≤30 min) predictions with KRLS-ALD reaching an average root mean square error of 15.22±5.95 mgdL -1 and an average time lag of 17.14±2.67 min for an horizon of 30 min. Its performance is considerably better than that of time-invariant (regularized) linear regression models.

  2. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 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.

  4. Vehicle infrastructure integration proof of concept : results and findings summary-vehicle : final report

    Science.gov (United States)

    2009-05-18

    This document describes the objectives and the approach to the testing of the VII Proof of Concept system. A summary of the test results and findings for both the major system functions and the applications designed for the system, are presented alon...

  5. Systems for Teaching Complex Texts: A Proof-of-Concept Investigation

    Science.gov (United States)

    Fisher, Douglas; Frey, Nancy

    2016-01-01

    In this article we investigate the systems that need to be in place for students to learn from increasingly complex texts. Our concept, drawn from past research, includes clear learning targets, teacher modeling, collaborative conversations, close reading, small group reading, and wide reading. Using a "proof of concept" model, we follow…

  6. 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...

  7. "Mobile technology to improve heart failure outcomes: A proof of concept paper".

    Science.gov (United States)

    Athilingam, Ponrathi; Jenkins, Bradlee A; Zumpano, Heather; Labrador, Miguel A

    2018-02-01

    Heart failure (HF) causes significant symptom burden and human suffering with considerable economic burden due to hospital readmissions. Targeted interventions to encourage and support self-management behavior is warranted. To test the proof of concept of a mobile application (HeartMapp) in improving self-care management of patients with heart failure. An exploratory inquiry used a field study strategy with purposeful sampling and constant comparative analysis to test the proof of concept of HeartMapp using The Business Model Canvas framework. A total of 125 individuals, who were identified as potential candidates to use the HeartMapp completed the interview over a seven-week period in 2016. Constant comparative analysis indicated themes that Skilled Nursing Facilities had increased readmissions. Participants from Skilled Nursing Facilities reported concern on lack of staffing, star rating, and malpractice claims. Two types of patients were identified as early adapters of technology and those in denial. Health care facilities reported challenges on transitional care, nurses struggle with engagement of patients on self-care management. To avoid readmission penalty, hospitals task home care agencies to keep the patients home for 30-days. While home care agencies rely on remote telemonitoring reported that current telemonitoring devices are costly to maintain, thus exploring novel technology. The Business Model Canvas provided directions for future testing of HeartMapp for its usability as an adjunct device in home health setting to improve self-management and enhance communication with providers, and ultimately reduce readmissions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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

  10. Proof of Concept for Efficient Application of Quantum Chemical Techniques to Model Enviromental Mercury Depletion Reactions Through Transition State Theory

    Science.gov (United States)

    2018-01-02

    SECURITY CLASSIFICATION OF: 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 13. SUPPLEMENTARY NOTES 12. DISTRIBUTION AVAILIBILITY STATEMENT 6...redox reactions. The existence of mercury either in elemental (Hg0) or in oxidized divalent Hg2+ forms affects mercury availability and mobility within...halides formation in presence of water molecules (as water is present in upper atmosphere). Although we could locate the low barrier for the Hg—Br

  11. 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

    Topographic factor, LS, in USLE (U.S. Department of Agriculture (USDA) Soil Conservation Service (SCS) 1983...0.000221 m/yr) based on the Universal Soil Loss Equation ( USLE ) as de- scribed by Dortch et al. (2010). This erosion rate includes use of a sedi...area of 0.619 m2 results in an erosion rate of 4.43 E-4 m/yr. The Universal Soil Loss Equation ( USLE ) was applied within the Hydro-Geo- ERDC/EL TR-11

  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. 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.

  15. Biocatalytic coatings for air pollution control: a proof of concept study on VOC biodegradation.

    Science.gov (United States)

    Estrada, José M; Bernal, Oscar I; Flickinger, Michael C; Muñoz, Raúl; Deshusses, Marc A

    2015-02-01

    Although biofilm-based biotechnologies exhibit a large potential as solutions for off-gas treatment, the high water content of biofilms often causes pollutant mass transfer limitations, which ultimately limit their widespread application. The present study reports on the proof of concept of the applicability of bioactive latex coatings for air pollution control. Toluene vapors served as a model volatile organic compound (VOC). The results showed that Pseudomonas putida F1 cells could be successfully entrapped in nanoporous latex coatings while preserving their toluene degradation activity. Bioactive latex coatings exhibited toluene specific biodegradation rates 10 times higher than agarose-based biofilms, because the thin coatings were less subject to diffusional mass transfer limitations. Drying and pollutant starvation were identified as key factors inducing a gradual deterioration of the biodegradation capacity in these innovative coatings. This study constitutes the first application of bioactive latex coatings for VOC abatement. These coatings could become promising means for air pollution control. © 2014 Wiley Periodicals, Inc.

  16. 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. Published by Elsevier Ltd.

  17. 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.

  18. 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

  19. Proof-of-concept study of a marine ion-selective optical sensing instrument

    Science.gov (United States)

    Sobron, P.; Thompson, C.; Bamsey, M.

    2013-12-01

    We have developed a proof-of-concept instrument for real-time in-situ characterization of the ion chemistry of the ocean. Our instrument uses optical sensors equipped with ion-selective membranes which exhibit a change in an optical property that can be correlated with the concentration of a specific ion. We have implemented a system for multi-ion sensing that includes the use of a single spectrometer in tandem with a fiber optic multiplexer that is capable of reading a suite of attached optrodes, each of them dedicated to a unique ion. In this abstract we report the experimental characterization of calcium and potassium optrodes as a template for ion-selective optrodes and their application to the characterization of the oceans. The tests were performed at the Controlled Environment Systems Research Facility of the University of Guelph. Guelph's optrode housing was tested by immersing it in a 1/2 strength Hoagland's hydroponic solution to test functionality of the K+ and Ca2+ optrodes in this environment. Our results demonstrate the feasibility of recording spectral information in sub-minute times from more than one optrode simultaneously in a given aqueous system. This proof-of-concept study has allowed us to measure parameters of interest and comparison to analytical predictions for critical subsystems of a deployable system, and demonstrates maturity of the multi-ion sensing optrode technology. Critical advantages of our optrode system are that it: (1) enables concurrent measurements of multiple ionic species relevant in ocean sciences; (2) has high time and spatial resolution; (3) has low limits of detection; (4) uses low-cost, low-mass, energy efficient optoelectronics. Our system has the potential for facilitating new observational, experimental, and analytic capabilities in ocean sciences, including: (a) health and environment monitoring; (b) aquaculture; (c) global change, e.g. ocean acidification; and (d) origin of life research. Proof-of-concept setup at

  20. Magnetic Gimbal Proof-of-Concept Hardware performance results

    Science.gov (United States)

    Stuart, Keith O.

    1993-01-01

    The Magnetic Gimbal Proof-of-Concept Hardware activities, accomplishments, and test results are discussed. The Magnetic Gimbal Fabrication and Test (MGFT) program addressed the feasibility of using a magnetic gimbal to isolate an Electro-Optical (EO) sensor from the severe angular vibrations induced during the firing of divert and attitude control system (ACS) thrusters during space flight. The MGFT effort was performed in parallel with the fabrication and testing of a mechanically gimballed, flex pivot based isolation system by the Hughes Aircraft Missile Systems Group. Both servo systems supported identical EO sensor assembly mockups to facilitate direct comparison of performance. The results obtained from the MGFT effort indicate that the magnetic gimbal exhibits the ability to provide significant performance advantages over alternative mechanically gimballed techniques.

  1. 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.

  2. Generation of composite Persea americana (Mill.) (avocado) plants: A proof-of-concept-study.

    Science.gov (United States)

    Prabhu, S Ashok; Ndlovu, Buyani; Engelbrecht, Juanita; van den Berg, Noëlani

    2017-01-01

    Avocado (Persea americana (Mill.)), an important commercial fruit, is severely affected by Phytophthora Root Rot in areas where the pathogen is prevalent. However, advances in molecular research are hindered by the lack of a high-throughput transient transformation system in this non-model plant. In this study, a proof-of-concept is demonstrated by the successful application of Agrobacterium rhizogenes-mediated plant transformation to produce composite avocado plants. Two ex vitro strategies were assessed on two avocado genotypes (Itzamna and A0.74): In the first approach, 8-week-old etiolated seedlings were scarred with a sterile hacksaw blade at the base of the shoot, and in the second, inch-long incisions were made at the base of the shoot (20-week-old non-etiolated plants) with a sterile blade to remove the cortical tissue. The scarred/wounded shoot surfaces were treated with A. rhizogenes strains (K599 or ARqua1) transformed with or without binary plant transformation vectors pRedRootII (DsRed1 marker), pBYR2e1-GFP (GFP- green fluorescence protein marker) or pBINUbiGUSint (GUS- beta-glucuronidase marker) with and without rooting hormone (Dip 'N' Grow) application. The treated shoot regions were air-layered with sterile moist cocopeat to induce root formation. Results showed that hormone application significantly increased root induction, while Agrobacterium-only treatments resulted in very few roots. Combination treatments of hormone+Agrobacterium (-/+ plasmids) showed no significant difference. Only the ARqua1(+plasmid):A0.74 combination resulted in root transformants, with hormone+ARqua1(+pBINUbiGUSint) being the most effective treatment with ~17 and 25% composite plants resulting from strategy-1 and strategy-2, respectively. GUS- and GFP-expressing roots accounted for less than 4 and ~11%, respectively, of the total roots/treatment/avocado genotype. The average number of transgenic roots on the composite plants was less than one per plant in all treatments

  3. Think You Can Shrink? A Proof-of-Concept Study for Men's Health Education Through Edutainment.

    Science.gov (United States)

    Ungar, Thomas; Norman, Cameron D; Knaak, Stephanie

    2017-01-01

    Connecting people to useful, actionable health resources is a substantive challenge that sits at the heart of health communication. Digital media provides means of producing, distributing and revising content and creates possibilities for new and multiple channels for reaching and engaging audiences, particularly when combined with social media. While there is much promise of digital media forms to deliver audiences and promote engagement, the health communication landscape is still largely hit-and-miss with few 'best practice' examples to follow. Proof-of-concept studies allow for a structured, focused exploration of ways to leverage the potential of digital media and learn what approaches have the promise to invest resources in amid a sea of possible options. Think You Can Shrink? (TYCS) is a multi-episode web series modelled on a reality TV show format. The show's key objective is to educate men and demonstrate, through modelling, ways men can support other men to encourage help-seeking behaviours and greater health communication, which in turn, may also lead to better health outcomes. Given the newness of the approach, the project was launched as a proof-of-concept study to explore: (a) whether this approach could engage the interest of men, (b) what initial impact this approach might induce and (c) the kind of audiences this approach might most appeal to.

  4. Application of a nonrandomized stepped wedge design to evaluate an evidence-based quality improvement intervention: a proof of concept using simulated data on patient-centered medical homes.

    Science.gov (United States)

    Huynh, Alexis K; Lee, Martin L; Farmer, Melissa M; Rubenstein, Lisa V

    2016-10-21

    Stepped wedge designs have gained recognition as a method for rigorously assessing implementation of evidence-based quality improvement interventions (QIIs) across multiple healthcare sites. In theory, this design uses random assignment of sites to successive QII implementation start dates based on a timeline determined by evaluators. However, in practice, QII timing is often controlled more by site readiness. We propose an alternate version of the stepped wedge design that does not assume the randomized timing of implementation while retaining the method's analytic advantages and applying to a broader set of evaluations. To test the feasibility of a nonrandomized stepped wedge design, we developed simulated data on patient care experiences and on QII implementation that had the structures and features of the expected data from a planned QII. We then applied the design in anticipation of performing an actual QII evaluation. We used simulated data on 108,000 patients to model nonrandomized stepped wedge results from QII implementation across nine primary care sites over 12 quarters. The outcome we simulated was change in a single self-administered question on access to care used by Veterans Health Administration (VA), based in the United States, as part of its quarterly patient ratings of quality of care. Our main predictors were QII exposure and time. Based on study hypotheses, we assigned values of 4 to 11 % for improvement in access when sites were first exposed to implementation and 1 to 3 % improvement in each ensuing time period thereafter when sites continued with implementation. We included site-level (practice size) and respondent-level (gender, race/ethnicity) characteristics that might account for nonrandomized timing in site implementation of the QII. We analyzed the resulting data as a repeated cross-sectional model using HLM 7 with a three-level hierarchical data structure and an ordinal outcome. Levels in the data structure included patient ratings

  5. 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.

  6. Proof of Concept for a Simple Smartphone Sky Monitor

    Science.gov (United States)

    Kantamneni, Abhilash; Nemiroff, R. J.; Brisbois, C.

    2013-01-01

    We present a novel approach of obtaining a cloud and bright sky monitor by using a standard smartphone with a downloadable app. The addition of an inexpensive fisheye lens can extend the angular range to the entire sky visible above the device. A preliminary proof of concept image shows an optical limit of about visual magnitude 5 for a 70-second exposure. Support science objectives include cloud monitoring in a manner similar to the more expensive cloud monitors in use at most major astronomical observatories, making expensive observing time at these observatories more efficient. Primary science objectives include bright meteor tracking, bright comet tracking, and monitoring the variability of bright stars. Citizen science objectives include crowd sourcing of many networked sky monitoring smartphones typically in broader support of many of the primary science goals. The deployment of a citizen smartphone array in an active science mode could leverage the sky monitoring data infrastructure to track other non-visual science opportunities, including monitoring the Earth's magnetic field for the effects of solar flares and exhaustive surface coverage for strong seismic events.

  7. Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting: Proof-of-Concept Study.

    Science.gov (United States)

    Phan, Thanh G; Beare, Richard; Chen, Jian; Clissold, Benjamin; Ly, John; Singhal, Shaloo; Ma, Henry; Srikanth, Velandai

    2017-05-01

    There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval-capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km 2 and MMC 1164 km 2 ) or with AUS (model 1c, RMH 1244 km 2 and AUS 1685 km 2 ), with no statistical difference between models ( P =0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km 2 and ALF 676 km 2 ), significantly different from both models 1a and 1c (both P AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs. © 2017 American Heart Association, Inc.

  8. 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

    OpenAIRE

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

    2016-01-01

    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-ba...

  9. 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.

  10. 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.

  11. 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.

  12. Narrative Constructions for the Organization of Self Experience: Proof of Concept via Embodied Robotics.

    Science.gov (United States)

    Mealier, Anne-Laure; Pointeau, Gregoire; Mirliaz, Solène; Ogawa, Kenji; Finlayson, Mark; Dominey, Peter F

    2017-01-01

    It has been proposed that starting from meaning that the child derives directly from shared experience with others, adult narrative enriches this meaning and its structure, providing causal links between unseen intentional states and actions. This would require a means for representing meaning from experience-a situation model-and a mechanism that allows information to be extracted from sentences and mapped onto the situation model that has been derived from experience, thus enriching that representation. We present a hypothesis and theory concerning how the language processing infrastructure for grammatical constructions can naturally be extended to narrative constructions to provide a mechanism for using language to enrich meaning derived from physical experience. Toward this aim, the grammatical construction models are augmented with additional structures for representing relations between events across sentences. Simulation results demonstrate proof of concept for how the narrative construction model supports multiple successive levels of meaning creation which allows the system to learn about the intentionality of mental states, and argument substitution which allows extensions to metaphorical language and analogical problem solving. Cross-linguistic validity of the system is demonstrated in Japanese. The narrative construction model is then integrated into the cognitive system of a humanoid robot that provides the memory systems and world-interaction required for representing meaning in a situation model. In this context proof of concept is demonstrated for how the system enriches meaning in the situation model that has been directly derived from experience. In terms of links to empirical data, the model predicts strong usage based effects: that is, that the narrative constructions used by children will be highly correlated with those that they experience. It also relies on the notion of narrative or discourse function words. Both of these are validated in

  13. An adaptive two-stage dose-response design method for establishing proof of concept.

    Science.gov (United States)

    Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R

    2013-01-01

    We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.

  14. Narrative Constructions for the Organization of Self Experience: Proof of Concept via Embodied Robotics

    Directory of Open Access Journals (Sweden)

    Anne-Laure Mealier

    2017-08-01

    Full Text Available It has been proposed that starting from meaning that the child derives directly from shared experience with others, adult narrative enriches this meaning and its structure, providing causal links between unseen intentional states and actions. This would require a means for representing meaning from experience—a situation model—and a mechanism that allows information to be extracted from sentences and mapped onto the situation model that has been derived from experience, thus enriching that representation. We present a hypothesis and theory concerning how the language processing infrastructure for grammatical constructions can naturally be extended to narrative constructions to provide a mechanism for using language to enrich meaning derived from physical experience. Toward this aim, the grammatical construction models are augmented with additional structures for representing relations between events across sentences. Simulation results demonstrate proof of concept for how the narrative construction model supports multiple successive levels of meaning creation which allows the system to learn about the intentionality of mental states, and argument substitution which allows extensions to metaphorical language and analogical problem solving. Cross-linguistic validity of the system is demonstrated in Japanese. The narrative construction model is then integrated into the cognitive system of a humanoid robot that provides the memory systems and world-interaction required for representing meaning in a situation model. In this context proof of concept is demonstrated for how the system enriches meaning in the situation model that has been directly derived from experience. In terms of links to empirical data, the model predicts strong usage based effects: that is, that the narrative constructions used by children will be highly correlated with those that they experience. It also relies on the notion of narrative or discourse function words. Both of

  15. Narrative Constructions for the Organization of Self Experience: Proof of Concept via Embodied Robotics

    Science.gov (United States)

    Mealier, Anne-Laure; Pointeau, Gregoire; Mirliaz, Solène; Ogawa, Kenji; Finlayson, Mark; Dominey, Peter F.

    2017-01-01

    It has been proposed that starting from meaning that the child derives directly from shared experience with others, adult narrative enriches this meaning and its structure, providing causal links between unseen intentional states and actions. This would require a means for representing meaning from experience—a situation model—and a mechanism that allows information to be extracted from sentences and mapped onto the situation model that has been derived from experience, thus enriching that representation. We present a hypothesis and theory concerning how the language processing infrastructure for grammatical constructions can naturally be extended to narrative constructions to provide a mechanism for using language to enrich meaning derived from physical experience. Toward this aim, the grammatical construction models are augmented with additional structures for representing relations between events across sentences. Simulation results demonstrate proof of concept for how the narrative construction model supports multiple successive levels of meaning creation which allows the system to learn about the intentionality of mental states, and argument substitution which allows extensions to metaphorical language and analogical problem solving. Cross-linguistic validity of the system is demonstrated in Japanese. The narrative construction model is then integrated into the cognitive system of a humanoid robot that provides the memory systems and world-interaction required for representing meaning in a situation model. In this context proof of concept is demonstrated for how the system enriches meaning in the situation model that has been directly derived from experience. In terms of links to empirical data, the model predicts strong usage based effects: that is, that the narrative constructions used by children will be highly correlated with those that they experience. It also relies on the notion of narrative or discourse function words. Both of these are validated

  16. The proof-of-concept experiment for the spiral line induction accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Putnam, S D; Bailey, V L; Smith, J; Lidestri, J; Thomas, H; Lackner, H; Nishimoto, H [Pulse Sciences, Inc., San Leandro, CA (United States)

    1997-12-31

    A proof-of-concept experiment (POCE) for the Spiral Line Induction Accelerator (SLIA) is underway at Pulse Sciences, Inc. to demonstrate a new compact high current ({>=} few kiloamperes) recirculating induction accelerator for high power ({>=} 100 kW) commercial processing and other applications. Hardware has been fabricated to generate 9.5 MeV electron beams at 2 and 10 kA by recirculating the beam for two passes through each of two 1.5 MeV accelerating units. Initial experiments have demonstrated acceleration of 2 and 10 kA beams to 5.5 MeV by transport around a complete turn with two passes through a single accelerating unit and work is currently in progress to complete the full POCE. Experimental results to date are reported. (author). 5 figs., 14 refs.

  17. Opportunities and pitfalls in clinical proof-of-concept: principles and examples.

    Science.gov (United States)

    Chen, Chao

    2018-04-01

    Clinical proof-of-concept trials crucially inform major resource deployment decisions. This paper discusses several mechanisms for enhancing their rigour and efficiency. The importance of careful consideration when using a surrogate endpoint is illustrated; situational effectiveness of run-in patient enrichment is explored; a versatile tool is introduced to ensure a strong pharmacological underpinning; the benefits of dose-titration are revealed by simulation; and the importance of adequately scheduled observations is shown. The general process of model-based trial design and analysis is described and several examples demonstrate the value in historical data, simulation-guided design, model-based analysis and trial adaptation informed by interim analysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Ionospheric Data Assimilation and Targeted Observation Strategies: Proof of Concept Analysis in a Geomagnetic Storm Event

    Science.gov (United States)

    Kostelich, Eric; Durazo, Juan; Mahalov, Alex

    2017-11-01

    The dynamics of the ionosphere involve complex interactions between the atmosphere, solar wind, cosmic radiation, and Earth's magnetic field. Geomagnetic storms arising from solar activity can perturb these dynamics sufficiently to disrupt radio and satellite communications. Efforts to predict ``space weather,'' including ionospheric dynamics, require the development of a data assimilation system that combines observing systems with appropriate forecast models. This talk will outline a proof-of-concept targeted observation strategy, consisting of the Local Ensemble Transform Kalman Filter, coupled with the Thermosphere Ionosphere Electrodynamics Global Circulation Model, to select optimal locations where additional observations can be made to improve short-term ionospheric forecasts. Initial results using data and forecasts from the geomagnetic storm of 26-27 September 2011 will be described. Work supported by the Air Force Office of Scientific Research (Grant Number FA9550-15-1-0096) and by the National Science Foundation (Grant Number DMS-0940314).

  19. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. 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

  1. 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

  2. Development of e-Juba, a preliminary proof of concept unmanned ...

    African Journals Online (AJOL)

    Development of e-Juba, a preliminary proof of concept unmanned aerial vehicle designed to facilitate the transportation of microbiological test samples from remote rural clinics to National Health Laboratory Service laboratories.

  3. Vehicle Infrastructure Integration Proof of Concept Executive Summary – Vehicle Submitted

    Science.gov (United States)

    2009-05-19

    This report summarizes a program of work resulting from a Cooperative Agreement between USDOT and the VII Consortium to develop and test a Proof of Concept VII system based on DSRC wireless communication between an infrastructure and mobile terminals...

  4. 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...January 2017 Flow-Control Systems Proof of Concept for Snowmelt Runoff at McMurdo Station, Antarctica Rosa Affleck U.S. Army Engineer Research and...runoff can be extreme where the flow can overwhelm both the drainage system and the operations and maintenance (O&M) crew. CRREL has been involved

  5. Timing Sunsets with Smartphones: Proof of Concept for a Citizen Science Project that Quantifies the Atmosphere and Supports Astronomical Observations

    Science.gov (United States)

    Wilson, Teresa; Kantamneni, A.; Bartlett, J. L.; Nemiroff, R. J.

    2014-01-01

    Current models that predict the times of sunrise and sunset are only accurate, typically, to a few minutes. Variations in atmospheric refraction contribute to the differences between computed and observed times. At high latitudes, slight changes in refraction can cause the Sun to remain continuously above the horizon instead of appearing to set. A substantial collection of observations would help constrain atmospheric models, which should, in turn, complement astronomical observations through improved understanding of air stability, refraction, and transparency. We report on a small project recording data from a few smartphones as a proof of concept for a possible larger scale citizen science effort.

  6. 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.

  7. 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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  9. 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.

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

    Science.gov (United States)

    Wu, Grace; DiBlasi, Robert M.; Saxon, Eugene; Austin, Glenn; Ginsburg, Amy Sarah

    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 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. PMID:27999601

  11. 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.

  12. 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.

  13. Analysis and Test Correlation of Proof of Concept Box for Blended Wing Body-Low Speed Vehicle

    Science.gov (United States)

    Spellman, Regina L.

    2003-01-01

    process, the failure prediction was used to help gain acceptance and confidence in this new tool. The correlated models and process were to be used to analyze the full BWB-LSV airframe design. The analysis and correlation with test results of the proof of concept box is presented here, including the comparison of the Nastran and Hypersizer results.

  14. 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.

  15. Motivated Forgetting in Early Mathematics: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Gerardo Ramirez

    2017-12-01

    Full Text Available Educators assume that students are motivated to retain what they are taught. Yet, students commonly report that they forget most of what they learn, especially in mathematics. In the current study I ask whether students may be motivated to forget mathematics because of academic experiences threaten the self-perceptions they are committed to maintaining. Using a large dataset of 1st and 2nd grade children (N = 812, I hypothesize that math anxiety creates negative experiences in the classroom that threaten children’s positive math self-perceptions, which in turn spurs a motivation to forget mathematics. I argue that this motivation to forget is activated during the winter break, which in turn reduces the extent to which children grow in achievement across the school year. Children were assessed for math self-perceptions, math anxiety and math achievement in the fall before going into winter break. During the spring, children’s math achievement was measured once again. A math achievement growth score was devised from a regression model of fall math achievement predicting spring achievement. Results show that children with higher math self-perceptions showed reduced growth in math achievement across the school year as a function of math anxiety. Children with lower math interest self-perceptions did not show this relationship. Results serve as a proof-of-concept for a scientific account of motivated forgetting within the context of education.

  16. 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.

  17. Metacognitive executive function training for young children with ADHD: a proof-of-concept study.

    Science.gov (United States)

    Tamm, Leanne; Nakonezny, Paul A

    2015-09-01

    Executive functions (EF) are impaired in children with attention-deficit/hyperactivity disorder (ADHD). It may be especially critical for interventions to target EF in early childhood given the developmental progression of EF deficits that may contribute to later functional impairments. This proof-of-concept study examined the initial efficacy of an intervention program on EF and ADHD. We also examined child performance on three neurocognitive tasks assessing cognitive flexibility, auditory/visual attention, and sustained/selective attention. Children with ADHD (ages 3-7) and their parents were randomized to receive an intervention targeting metacognitive EF deficits (n = 13) or to a waitlist control condition (n = 12). Linear model analysis of covariance compared groups on parent EF ratings, blinded clinician ratings of ADHD symptoms and improvement, and child performance on neurocognitive measures. Children who received the intervention significantly improved on parent ratings of attention shifting and emotion regulation in addition to clinician ratings of inattention. Moderate effect sizes showed additional intervention effects on parent ratings of inhibition, memory, and planning, and clinician ratings of hyperactivity/impulsivity and overall improvement. Small effect sizes were observed for improvement on child neurocognitive measures. Although replication with a larger sample and an active control group is needed, EF training with a metacognitive focus is a potentially promising intervention for young children with ADHD.

  18. Estimating Highway Volumes Using Vehicle Probe Data - Proof of Concept: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Yi [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Young, Stanley E [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Sadabadi, Kaveh [University of Maryland; SekuBa, PrzemysBaw [University of Maryland; Markow, Denise [I95 Corridor Coalition

    2018-03-13

    This paper examines the feasibility of using sampled commercial probe data in combination with validated continuous counter data to accurately estimate vehicle volume across the entire roadway network, for any hour during the year. Currently either real time or archived volume data for roadways at specific times are extremely sparse. Most volume data are average annual daily traffic (AADT) measures derived from the Highway Performance Monitoring System (HPMS). Although methods to factor the AADT to hourly averages for typical day of week exist, actual volume data is limited to a sparse collection of locations in which volumes are continuously recorded. This paper explores the use of commercial probe data to generate accurate volume measures that span the highway network providing ubiquitous coverage in space, and specific point-in-time measures for a specific date and time. The paper examines the need for the data, fundamental accuracy limitations based on a basic statistical model that take into account the sampling nature of probe data, and early results from a proof of concept exercise revealing the potential of probe type data calibrated with public continuous count data to meet end user expectations in terms of accuracy of volume estimates.

  19. Water-Soluble Dried Blood Spot in Protein Analysis: A Proof-of-Concept Study.

    Science.gov (United States)

    Rosting, Cecilie; Gjelstad, Astrid; Halvorsen, Trine Grønhaug

    2015-08-04

    In the present work human chorionic gonadotropin (hCG) was used as a model protein in a proof-of-concept study combining water-soluble dried blood spot (DBS) material in liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based protein analysis. A water-soluble material consisting of commercially available carboxymethyl cellulose (CMC) was evaluated as sampling material for this purpose. The material dissolved readily at physiological pH. Different sample preparation methods were evaluated, and in the final method, 15 μL of whole blood was deposited and dried on CMC before the whole spot was dissolved prior to cleanup by immunoaffinity extraction, tryptic digest, and preconcentration by solid-phase extraction (SPE). The results indicated complete dissolution of hCG from the spots, acceptable limit of detection (LOD) (0.1 IU/mL), linearity (R(2) = 0.959), accuracy (16%), and precision (≤22%). Long-term stability (45 days) of hCG in dried spots at reduced temperatures (≤8 °C) was also demonstrated. The analyte recovery was comparable to the commercially available nonsolvable cellulose material (FTA DMPK-C card).

  20. Forward Genetic Screening Using Behavioral Tests in Zebrafish: A Proof of Concept Analysis of Mutants.

    Science.gov (United States)

    Gerlai, Robert; Poshusta, Tanya L; Rampersad, Mindy; Fernandes, Yohaan; Greenwood, Tammy M; Cousin, Margot A; Klee, Eric W; Clark, Karl J

    2017-01-01

    The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens. We generated mutant lines using transposon-based insertional mutagenesis, allowing us to bias mutant selection with target genes expressed within the brain. Furthermore, we employed an efficient and fast behavioral pre-selection in which we investigated the locomotory response of 5-day post-fertilization old larval fish to hyperosmotic shock. Based on this assay, we selected five lines for our lower throughput secondary adult behavioral screen. The latter screen utilized tests in which computer animated image presentation and video-tracking-based automated quantification of behavior allowed us to compare heterozygous zebrafish with their wild-type siblings on their responses to a variety of stimuli. We found significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed, including changes in response to social or fear inducing stimuli, to handling and novelty, or in habituation to novelty. We discuss the pros and cons of behavioral phenotyping and of the use of different forward genetic methods in biomedical research with zebrafish.

  1. 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

  2. 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.

  3. Automated joint space width quantification of hand and wrist joints : a proof of concept study

    NARCIS (Netherlands)

    Huo, Yinghe; Veldhuizen, Renske D; van der Heijde, Desiree M; Besselink, Nick J; Jacobs, Johannes W G; van Laar, Jacob M; Viergever, Max A; Vincken, Koen L; Lafeber, Floris P; De Hair, Maria JH

    2016-01-01

    Objective. To compare as proof of concept the sensitivity to change of automated quantification of radiographic wrist and hand joint space width (JSW) with scoring JSW according to the Sharp/van der Heijde scoring method (SHS) in two strategy groups of a treat-to-target and tight-control early

  4. 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

    Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given i...

  5. Fast time-resolved aerosol collector: proof of concept

    Science.gov (United States)

    Yu, X.-Y.; Cowin, J. P.; Iedema, M. J.; Ali, H.

    2010-10-01

    Atmospheric particles can be collected in the field on substrates for subsequent laboratory analysis via chemically sensitive single particle methods such as scanning electron microscopy with energy dispersive x-ray analysis. With moving substrates time resolution of seconds to minutes can be achieved. In this paper, we demonstrate how to increase the time resolution when collecting particles on a substrate to a few milliseconds to provide real-time information. Our fast time-resolved aerosol collector ("Fast-TRAC") microscopically observes the particle collection on a substrate and records an on-line video. Particle arrivals are resolved to within a single frame (4-17 ms in this setup), and the spatial locations are matched to the subsequent single particle analysis. This approach also provides in-situ information on particle size and number concentration. Applications are expected in airborne studies of cloud microstructure, pollution plumes, and surface long-term monitoring.

  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. 3D-printed orthodontic brackets - proof of concept.

    Science.gov (United States)

    Krey, Karl-Friedrich; Darkazanly, Nawras; Kühnert, Rolf; Ruge, Sebastian

    Today, orthodontic treatment with fixed appliances is usually carried out using preprogrammed straight-wire brackets made of metal or ceramics. The goal of this study was to determine the possibility of clinically implementing a fully digital workflow with individually designed and three-dimensionally printed (3D-printed) brackets. Edgewise brackets were designed using computer-aided design (CAD) software for demonstration purposes. After segmentation of the malocclusion model generated based on intraoral scan data, the brackets were digitally positioned on the teeth and a target occlusion model created. The thus-defined tooth position was used to generate a template for an individualized arch form in the horizontal plane. The base contours of the brackets were modified to match the shape of the tooth surfaces, and a positioning guide (fabricated beforehand) was used to ensure that the brackets were bonded at the correct angle and position. The brackets, positioning guide, and retainer splint, digitally designed on the target occlusion model, were 3D printed using a Digital Light Processing (DLP) 3D printer. The archwires were individually pre-bent using the template. In the treatment sequence, it was shown for the first time that, in principle, it is possible to perform treatment with an individualized 3D-printed brackets system by using the proposed fully digital workflow. Technical aspects of the system, problems encountered in treatment, and possible future developments are discussed in this article.

  8. Rolling cylinder phase 1: proof of concept and first optimization

    Energy Technology Data Exchange (ETDEWEB)

    Margheritini, L.; Taraborrelli, V.

    2011-07-15

    The Rolling Cylinder is an innovative wave energy device at first stage of development at the time this report is created. The report is aimed at the first stage testing of the Rolling Cylinder wave energy device. This phase includes tests in regular waves and irregular waves, realized in two different set of tests. The optimized short model for the rolling cylinder resulted to have 7 sets of fins with relative distance between two consecutive sets = 0.20 m, 6 fins par set with a thickness of 0.75 mm and a draft d = 0.36 m that features half blade emerging from mean water level. In this case the maximum efficiencies were: 1) 8.7% for RW3. 2) 7.3% for RW4. 3) 6.3% for RW5. These results under typical regular waves (RW3-5) were very close to the results with 4 sets of fins with relative distance between two consecutive sets = 0.40 m, 6 fins par set, 0.75 mm thickness and draft = 0.36 m: 1) 7.2% for RW3. 2) 6.9% for RW4. 3) 6.2% for RW5. It must be noticed that the short model does not have the necessary length to perform optimally under the target wave conditions. The optimal device length has been calculated to be comparable to the wave length of the most energetic/probable wave conditions, i.e. RW3 and RW4. Under this consideration, the short model is only 1/3 of the total length of a complete device that should then be = 4.2 m (105 m in full scale). A first rough estimation of the power production for the rolling cylinder has been conducted using the results from regular wave tests. It has been concluded that for a fixed device (not floating), 105 m long with 23 sets of fins, 6 fins par set, draft of 9 m, similar geometry and fin's elasticity than the model tested in the present report, as well as possibility of adjusting the load to the incoming wave condition (gearing), the yearly energy production of 241 MWh/y (minus the losses in the power take off system), corresponding to a mechanic efficiency of 19%. Result must be validated with irregular wave tests

  9. The larynx ruler to measure height and profile of vocal folds: a proof of concept.

    Science.gov (United States)

    Desuter, Gauthier; Mertens, Benjamin; Delchambre, Alain; van Lith-Bijl, Julie; van Benthem, Peter Paul; Sjögren, Elisabeth

    2017-01-01

    Glottic leakage during phonation is a direct consequence of unilateral vocal fold (VF) paralysis. This air leakage can be in the horizontal plane and in the vertical plane. Presently, there is no easily applicable medical device allowing noninvasive, office-based measurement of the relative vertical position of the VFs. The larynx ruler (LR) is a laser-based measuring device that could meet the previously stated need, using a flexible endoscope. This study represents a proof of concept regarding the use of the LR in assessing VF relative positions in the vertical plane. One fresh male human cadaver larynx, free of neurologic and anatomic disease, was explored with the LR system through the operative channel of a flexible gastroenterology video-endoscope. The tip of the video-endoscope was located in the laryngeal vestibule. The right crico-arytenoid joint was posteriorly disarticulated. Tilting of the VF was obtained by pulling or pushing the arytenoid cartilage with a mosquito forceps fixed to the stump of the previously sectioned superior tip of the posterior crico-arytenoid muscle allowing anterior and posterior tilting of the arytenoid cartilage in order to induce an elevation or a depression of the VF process. Ten "push" and ten "pull" sessions were performed. The distance from the tip of the video-endoscope to each illuminated pixel of the laser beam was recorded. The level difference between the left and right VFs was measured for each recording. Data provided by the LR were consistently in accordance with the movements applied on the VFs. The accuracy of 0.2 mm of the LR is compatible with the envisioned applications for the human larynx. The LR system represents a feasible technique to evaluate respective vertical position of VFs in the human larynx. Technical limitations were identified that will require improvements before experimental use on human beings.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Michaël Hinderdael

    2017-02-01

    Full Text Available 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.

  12. 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.

  13. 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.

  14. Automated joint space width quantification of hand and wrist joints: a proof of concept study.

    Science.gov (United States)

    Huo, Yinghe; Veldhuizen, Renske D; van der Heijde, Desiree M; Besselink, Nick J; Jacobs, Johannes W G; van Laar, Jacob M; Viergever, Max A; Vincken, Koen L; Lafeber, Floris P; de Hair, Maria J H

    2016-01-01

    To compare as proof of concept the sensitivity to change of automated quantification of radiographic wrist and hand joint space width (JSW) with scoring JSW according to the Sharp/van der Heijde scoring method (SHS) in two strategy groups of a treat-to-target and tight-control early rheumatoid arthritis (RA) study. Digital radiographs were assessed for JSW changes of 134 patients of the 236 patients participating in the second Computer Assisted Management in Early Rheumatoid Arthritis trial, of whom both baseline and year 2 radiographs were available (year 1 radiographs n=125). Of those 134 patients, 70 started with methotrexate and prednisone (MTX+Pred) and 64 with MTX and placebo (MTX+Plac). JSW change over 1 and 2 years of the hands and wrists was assessed, applying both the joint space narrowing (JSN) subscore of the SHS by 2 readers and the automated assessment with the JSW quantification software 'JSQ'. For both methods, progression of JSW change of the hand and wrist was analysed using linear mixed modelling (dependent variable 'JSW', factor 'strategy group', covariate 'follow-up time in years', interaction term 'strategy group*follow-up time'; radiographs of baseline, year 1 and year 2 were used). For each method the standardised mean difference (SMD) for the change in JSW from baseline to year 2 between the treatment strategies was obtained using a non-parametric method. Patient characteristics of the current subpopulation were similar to those of the whole study population. JSN of the hand and wrist according to SHS at 2 years was present in 16 vs. 23% in the MTX+Pred group vs. the MTX+Plac group. The mean yearly progression rates of JSW change of the hands and wrists using JSQ were -0.00mm (95% confidence interval (CI) -0.01; 0.01) for MTX+Pred vs. -0.02mm (95%CI -0.03; -0.01) for MTX+Plac, p=0.045, and using SHS JSN they were 0.19 units (95%CI 0.09; 0.30) vs. 0.30 units (95%CI 0.14; 0.45) for MTX+Pred vs. MTX+Plac, p=0.271. The SMD for the change from

  15. Space network scheduling benchmark: A proof-of-concept process for technology transfer

    Science.gov (United States)

    Moe, Karen; Happell, Nadine; Hayden, B. J.; Barclay, Cathy

    1993-01-01

    This paper describes a detailed proof-of-concept activity to evaluate flexible scheduling technology as implemented in the Request Oriented Scheduling Engine (ROSE) and applied to Space Network (SN) scheduling. The criteria developed for an operational evaluation of a reusable scheduling system is addressed including a methodology to prove that the proposed system performs at least as well as the current system in function and performance. The improvement of the new technology must be demonstrated and evaluated against the cost of making changes. Finally, there is a need to show significant improvement in SN operational procedures. Successful completion of a proof-of-concept would eventually lead to an operational concept and implementation transition plan, which is outside the scope of this paper. However, a high-fidelity benchmark using actual SN scheduling requests has been designed to test the ROSE scheduling tool. The benchmark evaluation methodology, scheduling data, and preliminary results are described.

  16. Process control plan for Single Shell Tank (SST) Saltcake Dissolution Proof of Concept

    International Nuclear Information System (INIS)

    ESTEY, S.D.

    2001-01-01

    This document describes the process controls for the tank 241-U-107 (U-107) saltcake dissolution proof-of-concept operations. Saltcake dissolution is defined as a method by which water-soluble salts will be retrieved from the Hanford Site radioactive waste tanks utilizing dissolution as the mobilizing mechanism. The proof-of-concept operations will monitor the retrieval process and transfer at least 100 kgal of fluid from tank U-107 to the double-shell tank (DST) system during the performance period. Tank U-107 has been identified as posing the highest long-term risk to the Columbia River of all single shell tanks (SSTs). This is because of the high content of mobile, long-lived radionuclides mostly in the saltcake waste in the tank. To meet current contractual and consent decree commitments, tank U-107 is being prepared for interim stabilization in August 2001. It is currently scheduled for saltcake retrieval in 2023, near the end of the SST retrieval campaign because of a lack of infrastructure in U-Farm. The proof-of-concept test will install a system to dissolve and retrieve a portion of the saltcake as part of, and operating in parallel with, the standard interim stabilization system to be installed on tank U-107. This proof-of-concept should provide key information on spray nozzle selection and effective spray patterns, leak detection, monitoring, and mitigation (LDMM) and in-tank saltcake solubility data that will help in the design of a full-tank retrieval demonstration system

  17. Improving Dialysis Adherence for High Risk Patients Using Automated Messaging: Proof of Concept

    OpenAIRE

    Som, A.; Groenendyk, J.; An, T.; Patel, K.; Peters, R.; Polites, G.; Ross, W. R.

    2017-01-01

    Comorbidities and socioeconomic barriers often limit patient adherence and self-management with hemodialysis. Missed sessions, often associated with communication barriers, can result in emergency dialysis and avoidable hospitalizations. This proof of concept study explored using a novel digital-messaging platform, EpxDialysis, to improve patient-to-dialysis center communication via widely available text messaging and telephone technology. A randomized controlled trial was conducted through W...

  18. Development of a small prototype for a proof-of-concept of OpenPET imaging

    International Nuclear Information System (INIS)

    Yamaya, Taiga; Yoshida, Eiji; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Tsuji, Atsushi; Mitsuhashi, Takayuki; Tashima, Hideaki; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo; Kinouchi, Shoko; Inaniwa, Taku; Sato, Shinji; Nakajima, Yasunori; Kawai, Hideyuki; Haneishi, Hideaki; Suga, Mikio

    2011-01-01

    The OpenPET geometry is our new idea to visualize a physically opened space between two detector rings. In this paper, we developed the first small prototype to show a proof-of-concept of OpenPET imaging. Two detector rings of 110 mm diameter and 42 mm axial length were placed with a gap of 42 mm. The basic imaging performance was confirmed through phantom studies; the open imaging was realized at the cost of slight loss of axial resolution and 24% loss of sensitivity. For a proof-of-concept of PET image-guided radiation therapy, we carried out the in-beam tests with 11 C radioactive beam irradiation in the heavy ion medical accelerator in Chiba to visualize in situ distribution of primary particles stopped in a phantom. We showed that PET images corresponding to dose distribution were obtained. For an initial proof-of-concept of real-time multimodal imaging, we measured a tumor-inoculated mouse with 18 F-FDG, and an optical image of the mouse body surface was taken during the PET measurement by inserting a digital camera in the ring gap. We confirmed that the tumor in the gap was clearly visualized. The result also showed the extension effect of an axial field-of-view (FOV); a large axial FOV of 126 mm was obtained with the detectors that originally covered only an 84 mm axial FOV. In conclusion, our initial imaging studies showed promising performance of the OpenPET.

  19. Disease models of chronic inflammatory airway disease : applications and requirements for clinical trials

    NARCIS (Netherlands)

    Diamant, Zuzana; Clarke, Graham W.; Pieterse, Herman; Gispert, Juan

    Purpose of reviewThis review will discuss methodologies and applicability of key inflammatory models of respiratory disease in proof of concept or proof of efficacy clinical studies. In close relationship with these models, induced sputum and inflammatory cell counts will be addressed for

  20. Proof of concept of a workflow methodology for the creation of basic canine head anatomy veterinary education tool using augmented reality.

    Directory of Open Access Journals (Sweden)

    Roxie Christ

    Full Text Available Neuroanatomy can be challenging to both teach and learn within the undergraduate veterinary medicine and surgery curriculum. Traditional techniques have been used for many years, but there has now been a progression to move towards alternative digital models and interactive 3D models to engage the learner. However, digital innovations in the curriculum have typically involved the medical curriculum rather than the veterinary curriculum. Therefore, we aimed to create a simple workflow methodology to highlight the simplicity there is in creating a mobile augmented reality application of basic canine head anatomy. Using canine CT and MRI scans and widely available software programs, we demonstrate how to create an interactive model of head anatomy. This was applied to augmented reality for a popular Android mobile device to demonstrate the user-friendly interface. Here we present the processes, challenges and resolutions for the creation of a highly accurate, data based anatomical model that could potentially be used in the veterinary curriculum. This proof of concept study provides an excellent framework for the creation of augmented reality training products for veterinary education. The lack of similar resources within this field provides the ideal platform to extend this into other areas of veterinary education and beyond.

  1. Proof of concept of a workflow methodology for the creation of basic canine head anatomy veterinary education tool using augmented reality.

    Science.gov (United States)

    Christ, Roxie; Guevar, Julien; Poyade, Matthieu; Rea, Paul M

    2018-01-01

    Neuroanatomy can be challenging to both teach and learn within the undergraduate veterinary medicine and surgery curriculum. Traditional techniques have been used for many years, but there has now been a progression to move towards alternative digital models and interactive 3D models to engage the learner. However, digital innovations in the curriculum have typically involved the medical curriculum rather than the veterinary curriculum. Therefore, we aimed to create a simple workflow methodology to highlight the simplicity there is in creating a mobile augmented reality application of basic canine head anatomy. Using canine CT and MRI scans and widely available software programs, we demonstrate how to create an interactive model of head anatomy. This was applied to augmented reality for a popular Android mobile device to demonstrate the user-friendly interface. Here we present the processes, challenges and resolutions for the creation of a highly accurate, data based anatomical model that could potentially be used in the veterinary curriculum. This proof of concept study provides an excellent framework for the creation of augmented reality training products for veterinary education. The lack of similar resources within this field provides the ideal platform to extend this into other areas of veterinary education and beyond.

  2. The larynx ruler to measure height and profile of vocal folds: a proof of concept

    Directory of Open Access Journals (Sweden)

    Desuter G

    2017-07-01

    Full Text Available Gauthier Desuter,1,2 Benjamin Mertens,3 Alain Delchambre,3 Julie van Lith-Bijl,1,4 Peter Paul van Benthem,2 Elisabeth Sjögren2 1Otolaryngology, Head & Neck Surgery Department, Voice & Swallowing Clinic, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium; 2Otolaryngology, Head & Neck Surgery Department, LUMC, University of Leiden, Leiden, the Netherlands; 3BEAMS Department, Ecole Polytechnique de Bruxelles, Université libre de Bruxelles, Brussels, Belgium; 4Otolaryngology Department, Flevoziekenhuis, Almere, the Netherlands Introduction: Glottic leakage during phonation is a direct consequence of unilateral vocal fold (VF paralysis. This air leakage can be in the horizontal plane and in the vertical plane. Presently, there is no easily applicable medical device allowing noninvasive, office-based measurement of the relative vertical position of the VFs. The larynx ruler (LR is a laser-based measuring device that could meet the previously stated need, using a flexible endoscope. This study represents a proof of concept regarding the use of the LR in assessing VF relative positions in the vertical plane. Materials and methods: One fresh male human cadaver larynx, free of neurologic and anatomic disease, was explored with the LR system through the operative channel of a flexible gastroenterology video-endoscope. The tip of the video-endoscope was located in the laryngeal vestibule. The right crico-arytenoid joint was posteriorly disarticulated. Tilting of the VF was obtained by pulling or pushing the arytenoid cartilage with a mosquito forceps fixed to the stump of the previously sectioned superior tip of the posterior crico-arytenoid muscle allowing anterior and posterior tilting of the arytenoid cartilage in order to induce an elevation or a depression of the VF process. Ten “push” and ten “pull” sessions were performed. The distance from the tip of the video-endoscope to each illuminated pixel of the

  3. 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

  4. Successful Proof of Concept of Family Planning and Immunization Integration in Liberia

    Science.gov (United States)

    Cooper, Chelsea M; Fields, Rebecca; Mazzeo, Corinne I; Taylor, Nyapu; Pfitzer, Anne; Momolu, Mary; Jabbeh-Howe, Cuallau

    2015-01-01

    non-pilot facilities, possibly due to higher than average background dropout rates at pilot sites prior to the intervention in Lofa and the disproportionate effect of data from 1 large facility in Bong. The project provided considerable basic support to assess this proof of concept. However, results suggest that introducing a simple model that is minimally disruptive to existing immunization service delivery can facilitate integration. The model is currently being scaled-up to other counties in Liberia, which could potentially contribute to increased postpartum contraceptive uptake, leading to longer birth intervals and improved health outcomes for children and mothers. PMID:25745121

  5. 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

  6. Development of a small prototype for a proof-of-concept of OpenPET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamaya, Taiga; Yoshida, Eiji; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Tsuji, Atsushi; Mitsuhashi, Takayuki; Tashima, Hideaki; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo; Kinouchi, Shoko [Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Inaniwa, Taku; Sato, Shinji [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nakajima, Yasunori [Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, Kanagawa 226-8503 (Japan); Kawai, Hideyuki; Haneishi, Hideaki; Suga, Mikio, E-mail: taiga@nirs.go.jp [Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522 (Japan)

    2011-02-21

    The OpenPET geometry is our new idea to visualize a physically opened space between two detector rings. In this paper, we developed the first small prototype to show a proof-of-concept of OpenPET imaging. Two detector rings of 110 mm diameter and 42 mm axial length were placed with a gap of 42 mm. The basic imaging performance was confirmed through phantom studies; the open imaging was realized at the cost of slight loss of axial resolution and 24% loss of sensitivity. For a proof-of-concept of PET image-guided radiation therapy, we carried out the in-beam tests with {sup 11}C radioactive beam irradiation in the heavy ion medical accelerator in Chiba to visualize in situ distribution of primary particles stopped in a phantom. We showed that PET images corresponding to dose distribution were obtained. For an initial proof-of-concept of real-time multimodal imaging, we measured a tumor-inoculated mouse with {sup 18}F-FDG, and an optical image of the mouse body surface was taken during the PET measurement by inserting a digital camera in the ring gap. We confirmed that the tumor in the gap was clearly visualized. The result also showed the extension effect of an axial field-of-view (FOV); a large axial FOV of 126 mm was obtained with the detectors that originally covered only an 84 mm axial FOV. In conclusion, our initial imaging studies showed promising performance of the OpenPET.

  7. Idaho National Engineering and Environmental Laboratory Environmental Technologies Proof-of-Concepts. Final report FY-96

    Energy Technology Data Exchange (ETDEWEB)

    Barrie, S.L.; Carpenter, G.S.; Crockett, A.B. [and others

    1997-04-01

    The Idaho National Engineering and Environmental Laboratory Environmental Technologies Proof-of-Concept Project was initiated for the expedited development of new or conceptual technologies in support of groundwater fate, transport, and remediation; buried waste characterization, retrieval, and treatment; waste minimization/pollution prevention; and spent fuel handling and storage. In Fiscal Year 1996, The Idaho National Engineering and Environmental Laboratory proposed 40 development projects and the Department of Energy funded 15. The projects proved the concepts of the various technologies, and all the technologies contribute to successful environmental management.

  8. Idaho National Engineering and Environmental Laboratory Environmental Technologies Proof-of-Concepts. Final report FY-96

    International Nuclear Information System (INIS)

    Barrie, S.L.; Carpenter, G.S.; Crockett, A.B.

    1997-04-01

    The Idaho National Engineering and Environmental Laboratory Environmental Technologies Proof-of-Concept Project was initiated for the expedited development of new or conceptual technologies in support of groundwater fate, transport, and remediation; buried waste characterization, retrieval, and treatment; waste minimization/pollution prevention; and spent fuel handling and storage. In Fiscal Year 1996, The Idaho National Engineering and Environmental Laboratory proposed 40 development projects and the Department of Energy funded 15. The projects proved the concepts of the various technologies, and all the technologies contribute to successful environmental management

  9. Addressing asthma and obesity in children with community health workers: proof-of-concept intervention development

    OpenAIRE

    Martin, Molly A; Rothschild, Steven K.; Lynch, Elizabeth; Christoffel, Katherine Kaufer; Pag?n, Militza M.; Rodriguez, Jose Luis; Barnes, Anna; Karavolos, Kelly; Diaz, Antonieta; Hoffman, Lucretia M.; Plata, Diana; Villalpando, Sandra

    2016-01-01

    Background The objective of this study was to design and test the feasibility and impact of a community health worker (CHW) intervention for comorbid asthma and obesity. Methods Using a proof of concept study design, we collected pre/post outcomes from a single intervention cohort of urban low-income in a single community area. A community-based participatory research approach was employed. Forty-six children and their caregivers were recruited. Children were 5?12 years old with physician-dia...

  10. ISOCELL trademark proof-of-concept for retrieval of wastes and contaminated soil

    International Nuclear Information System (INIS)

    Chatwin, T.D.; Krieg, R.K.

    1992-01-01

    ISOCELL TM cryogenic technology is designed to immobilize buried hazardous, radioactive, and mixed waste and contaminated soil by creating a block of frozen waste and soil that can be safely retrieved, stored, transported, and treated with a minimum of dust or aerosol production. A ''proof-of-concept'' test of the ISOCELL process was conducted in clean soil by RKK, Ltd., for the Idaho National Engineering Laboratory (INEL). Results indicate ISOCELL technology successfully froze moist soil into a solid block capable of being lifted and retrieved. Test conditions were compared to characteristics of possible buried waste sites in the INEL

  11. 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.

  12. Kinesthetic stimulation for obstructive sleep apnea syndrome: An "on-off" proof of concept trial.

    Science.gov (United States)

    Hernández, Alfredo I; Pérez, Diego; Feuerstein, Delphine; Loiodice, Corinne; Graindorge, Laurence; Guerrero, Gustavo; Limousin, Nadège; Gagnadoux, Frédéric; Dauvilliers, Yves; Tamisier, Renaud; Prigent, Arnaud; Mabo, Philippe; Amblard, Amel; Senhadji, Lotfi; Pépin, Jean-Louis

    2018-02-15

    Obstructive sleep apnea (OSA) occurs when the upper airway narrows or collapses due to the loss of upper airway muscle activation at sleep onset. This study investigated the effectiveness of triggered kinesthetic stimulation in patients with OSA. This proof-of-concept, open-label, multicenter prospective study was conducted on 24 patients with severe OSA. During a one night evaluation, kinesthetic stimulation was intermittently delivered in 30 minute periods. The duration of apneas and hypopneas during Stim on and Stim off periods were compared. Five hospital-based university centers in France participated. Sleep studies were evaluated by a single scorer at a core laboratory (CHU Grenoble). Results show that during the Stim on phases, statistically significant decreases in durations of apneas and hypopneas were observed in 56% and 46% of patients, respectively. Overall, 75% of patients showed an improvement in apneas or hypopneas durations. The mean reduction in durations for patients with a significant decrease was 4.86 seconds for apneas and 6.00 seconds for hypopneas. This proof of concept study is the first to identify kinesthetic stimulation as a potentially effective therapy for OSA. These data justify evaluation in a controlled study.

  13. Evaluating a Proof-of-Concept Approach of the German Health Telematics Infrastructure in the Context of Discharge Management.

    Science.gov (United States)

    Hübner, Ursula; Schulte, Georg; Sellemann, Björn; Quade, Matthias; Rottmann, Thorsten; Fenske, Matthias; Egbert, Nicole; Kuhlisch, Raik; Rienhoff, Otto

    2015-01-01

    Although national eHealth strategies have existed now for more than a decade in many countries, they have been implemented with varying success. In Germany, the eHealth strategy so far has resulted in a roll out of electronic health cards for all citizens in the statutory health insurance, but in no clinically meaningful IT-applications. The aim of this study was to test the technical and organisation feasibility, usability, and utility of an eDischarge application embedded into a laboratory Health Telematics Infrastructure (TI). The tests embraced the exchange of eDischarge summaries based on the multiprofessional HL7 eNursing Summary standard between a municipal hospital and a nursing home. All in all, 36 transmissions of electronic discharge documents took place. They demonstrated the technical-organisation feasibility and resulted in moderate usability ratings. A comparison between eDischarge and paper-based summaries hinted at higher ratings of utility and information completeness for eDischarges. Despite problems with handling the electronic health card, the proof-of-concept for the first clinically meaningful IT-application in the German Health TI could be regarded as successful.

  14. 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.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Matt Boyd

    Full Text Available 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.

  17. Proof-of-concept experimental study of damage detection of concrete piles using embedded piezoceramic transducers

    International Nuclear Information System (INIS)

    Wang, R L; Gu, H; Song, G; Mo, Y L

    2013-01-01

    This paper presents a proof-of-concept experimental study of an innovative active-sensing approach for damage detection of concrete piles by using embedded piezoceramic transducers. In the proposed active-sensing approach, one piezoceramic transducer is used as an actuator to generate a stress wave to propagate through the concrete pile and the other distributed piezoceramic transducers are used as sensors to detect the wave response. Cracks or damage inside the concrete structure act as stress relief in the wave propagation path. The amplitude of the wave and the transmission energy will decrease due to the existence of cracks or damage. Experiments were performed on two bored piles instrumented with embedded piezoceramic transducers. The experimental results demonstrate the effectiveness of the proposed approach for pile damage detection. (fast track communication)

  18. Measuring Light Pollution with Fisheye Lens Imagery from A Moving Boat – A Proof of Concept

    Directory of Open Access Journals (Sweden)

    Andreas Jechow

    2017-06-01

    Full Text Available Near all-sky imaging photometry was performed from a boat on the Gulf of Aqaba to measure the night sky brightness in a coastal environment. The boat was not anchored, and therefore drifted and rocked. The camera was mounted on a tripod without any inertia/motion stabilization. A commercial digital single lens reflex (DSLR camera and fisheye lens were used with ISO setting of 6400, with the exposure time varied between 0.5 s and 5 s. We find that despite movement of the vessel the measurements produce quantitatively comparable results apart from saturation effects. We discuss the potential and limitations of this method for mapping light pollution in marine and freshwater systems. This work represents the proof of concept that all-sky photometry with a commercial DSLR camera is a viable tool to determine light pollution in an ecological context from a moving boat.

  19. A proof-of-concept implementation of persistence in a hierarchical storage system

    International Nuclear Information System (INIS)

    Grossman, R.; Qin, Xiao; Lifka, D.

    1992-01-01

    The concept of providing transparent access to a collection of files in a mass storage system is a familiar one. The goal of this project was to investigate the feasibility of providing similar access to a collection of persistent, complex objects. We describe an architecture for interfacing a persistent store of complex objects to a hierarchical storage system. Persistent object stores support the uniform creation, storage, and access of complex objects, regardless of their lifetimes. In other words, a mechanism is provided so that persistent objects outlive the processes which create them and can be accessed in a uniform manner by other processes. We validated this architecture by implementing a proof-of-concept system and testing the system on two stores of data. These tests indicate that this architecture supports the creation. storage and access of very large persistent object stores

  20. Carbon footprinting of emergency medical services systems: a proof-of-concept study.

    Science.gov (United States)

    Blanchard, Ian; Brown, Lawrence H

    2009-01-01

    In this proof-of-concept study, we evaluated the availability of emergency medical services (EMS) system energy consumption data required to calculate a carbon footprint. Two diverse North American EMS systems with more than 125,000 combined annual unit responses agreed to report their energy consumption for the last fiscal or calendar year using a data-collection tool based on Carbon Trust recommendations. They also identified the source of information (e.g., bills, logs, receipts), whether the amounts reported were directly measured or estimated, and whether any of the amounts were prorated from shared facilities (e.g., electricity for a shared office building). For this proof-of-concept study, we report only descriptive data about the availability of data and aggregate carbon emissions. Both systems reported diesel fuel, gasoline, and electricity consumption. One system used natural gas; one system used aviation fuel. Direct measurement of consumption using utility bills and statements was possible for these energy types. One system prorated natural gas and electricity usage; one system was able to estimate commercial air travel. Annual carbon dioxide (CO(2)) emissions for these two systems totaled 11.1 million pounds of CO(2). The largest source of CO(2) emissions was diesel fuel (39%), followed by electricity (23%). These EMS systems were able to provide the data necessary to determine their carbon footprints. Future research could include broader study to establish EMS-specific norms for carbon emissions, benchmarking of these metrics between different EMS systems, and the assessment of programs designed to reduce EMS carbon emissions.

  1. 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

  2. Cardiac output-based fluid optimization for kidney transplant recipients: a proof-of-concept trial.

    Science.gov (United States)

    Corbella, Davide; Toppin, Patrick Jason; Ghanekar, Anand; Ayach, Nour; Schiff, Jeffery; Van Rensburg, Adrian; McCluskey, Stuart A

    2018-04-10

    Intravenous fluid management for deceased donor kidney transplantation is an important, modifiable risk factor for delayed graft function (DGF). The primary objective of this study was to determine if goal-directed fluid therapy using esophageal Doppler monitoring (EDM) to optimize stroke volume (SV) would alter the amount of fluid given. This randomized, proof-of-concept trial enrolled 50 deceased donor renal transplant recipients. Data collected included patient characteristics, fluid administration, hemodynamics, and complications. The EDM was used to optimize SV in the EDM group. In the control group, fluid management followed the current standard of practice. The groups were compared for the primary outcome of total intraoperative fluid administered. There was no difference in the mean (standard deviation) volume of intraoperative fluid administered to the 24 control and 26 EDM patients [2,307 (750) mL vs 2,675 (842) mL, respectively; mean difference, 368 mL; 95% confidence interval (CI), - 87 to + 823; P = 0.11]. The incidence of complications in the control and EDM groups was similar (15/24 vs 17/26, respectively; P = 0.99), as was the incidence of delayed graft failure (8/24 vs 11/26, respectively; P = 0.36). Goal-directed fluid therapy did not alter the volume of fluid administered or the incidence of complications. This proof-of-concept trial provides needed data for conducting a larger trial to determine the influence of fluid therapy on the incidence in DGF in deceased donor kidney transplantation. www.clinicaltrials.gov (NCT02512731). Registered 31 July 2015.

  3. 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

  4. Contact-free monitoring of vessel graft stiffness - proof of concept as a tool for vascular tissue engineering.

    Science.gov (United States)

    Hoenicka, Markus; Kaspar, Marcel; Schmid, Christof; Liebold, Andreas; Schrammel, Siegfried

    2017-10-01

    Tissue-engineered vessel grafts have to mimic the biomechanical properties of native blood vessels. Manufacturing processes often condition grafts to adapt them to the target flow conditions. Graft stiffness is influenced by material properties and dimensions and determines graft compliance. This proof-of-concept study evaluated a contact-free method to monitor biomechanical properties without compromising sterility. Forced vibration response analysis was performed on human umbilical vein (HUV) segments mounted in a buffer-filled tubing system. A linear motor and a dynamic signal analyser were used to excite the fluid by white noise (0-200 Hz). Vein responses were read out by laser triangulation and analysed by fast Fourier transformation. Modal analysis was performed by monitoring multiple positions of the vessel surface. As an inverse model of graft stiffening during conditioning, HUV were digested proteolytically, and the course of natural frequencies (NFs) was monitored over 120 min. Human umbilical vein showed up to five modes with NFs in the range of 5-100 Hz. The first natural frequencies of HUV did not alter over time while incubated in buffer (p = 0.555), whereas both collagenase (-35%, p = 0.0061) and elastase (-45%, p direct measurement of stiffness as an important biomechanical property, obviating the need to monitor surrogate parameters. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study.

    Science.gov (United States)

    Colliez, Florence; Safronova, Marta M; Magat, Julie; Joudiou, Nicolas; Peeters, André P; Jordan, Bénédicte F; Gallez, Bernard; Duprez, Thierry

    2015-01-01

    The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation ('Global T1' combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons ('Lipids T1') would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48-72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; pbrain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects.

  6. Prototype Food and Nutrient Database for Dietary Studies: Branded Food Products Database for Public Health Proof of Concept

    Science.gov (United States)

    The Prototype Food and Nutrient Database for Dietary Studies (Prototype FNDDS) Branded Food Products Database for Public Health is a proof of concept database. The database contains a small selection of food products which is being used to exhibit the approach for incorporation of the Branded Food ...

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

    NARCIS (Netherlands)

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

    2017-01-01

    Objective: 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. Significance: Elacridar is highly demanded for

  8. Pilot program (proof of concept) to mitigate Phytophthora ramorum at an infested nursery based on a systems approach

    Science.gov (United States)

    Gary Chastagner; Marianne Elliott

    2017-01-01

    The primary purpose of this program was to demonstrate proof of concept of certain mitigation approaches at a repeat P. ramorum-positive nursery site in Washington. Approaches included steam treatment of infested soil areas; creating a gravel “sandwich” above steam-treated and potentially infested soil surfaces; improving drainage systems; required...

  9. Evaluation of the Wii Balance Board for walking aids prediction: proof-of-concept study in total knee arthroplasty.

    Science.gov (United States)

    Pua, Yong-Hao; Clark, Ross A; Ong, Peck-Hoon

    2015-01-01

    To provide proof-of-concept for the validity of the Wii Balance Board (WBB) measures to predict the type of walking aids required by inpatients with a recent (≤4 days) total knee arthroplasty (TKA). A cross-sectional sample of 89 inpatients (mean age, 67.0±8 years) with TKA was analyzed. A multivariable proportional odds prediction model was constructed using 8 pre-specified predictors – namely, age, sex, body mass index, knee pain, knee range-of-motion, active knee lag, and WBB-derived standing balance. The type of walking aids prescribed on day 4 post-surgery was the outcome of interest – an ordinal variable with 4 categories (walking stick, narrow- and broad-base quadstick, and walking frame). Women, increasing body mass index, and poorer standing balance were independently associated with greater odds for requiring walking aids with a larger base-of-support. The concordance-index of the prediction model was 0.74. The model comprising only WBB-derived standing balance had nearly half (44%) the explanatory power of the full model. Adding WBB-derived standing balance to conventional demographic and knee variables resulted in a continuous net reclassification index of 0.60 (95%CI,0.19-1.01), predominantly due to better identification of patients who required walking aids with a large base-of-support (sensitivity gain). The WBB was able to provide quantitative measures of standing balance which could assist healthcare professionals in prescribing the appropriate type of walking aids for patients. Further investigation is needed to assess whether using the WBB could lead to meaningful changes in clinical outcomes such as falls.

  10. Evaluation of the Wii Balance Board for walking aids prediction: proof-of-concept study in total knee arthroplasty.

    Directory of Open Access Journals (Sweden)

    Yong-Hao Pua

    Full Text Available To provide proof-of-concept for the validity of the Wii Balance Board (WBB measures to predict the type of walking aids required by inpatients with a recent (≤4 days total knee arthroplasty (TKA.A cross-sectional sample of 89 inpatients (mean age, 67.0±8 years with TKA was analyzed. A multivariable proportional odds prediction model was constructed using 8 pre-specified predictors – namely, age, sex, body mass index, knee pain, knee range-of-motion, active knee lag, and WBB-derived standing balance. The type of walking aids prescribed on day 4 post-surgery was the outcome of interest – an ordinal variable with 4 categories (walking stick, narrow- and broad-base quadstick, and walking frame.Women, increasing body mass index, and poorer standing balance were independently associated with greater odds for requiring walking aids with a larger base-of-support. The concordance-index of the prediction model was 0.74. The model comprising only WBB-derived standing balance had nearly half (44% the explanatory power of the full model. Adding WBB-derived standing balance to conventional demographic and knee variables resulted in a continuous net reclassification index of 0.60 (95%CI,0.19-1.01, predominantly due to better identification of patients who required walking aids with a large base-of-support (sensitivity gain.The WBB was able to provide quantitative measures of standing balance which could assist healthcare professionals in prescribing the appropriate type of walking aids for patients. Further investigation is needed to assess whether using the WBB could lead to meaningful changes in clinical outcomes such as falls.

  11. Adaptive tight frame based medical image reconstruction: a proof-of-concept study for computed tomography

    International Nuclear Information System (INIS)

    Zhou, Weifeng; Cai, Jian-Feng; Gao, Hao

    2013-01-01

    A popular approach for medical image reconstruction has been through the sparsity regularization, assuming the targeted image can be well approximated by sparse coefficients under some properly designed system. The wavelet tight frame is such a widely used system due to its capability for sparsely approximating piecewise-smooth functions, such as medical images. However, using a fixed system may not always be optimal for reconstructing a variety of diversified images. Recently, the method based on the adaptive over-complete dictionary that is specific to structures of the targeted images has demonstrated its superiority for image processing. This work is to develop the adaptive wavelet tight frame method image reconstruction. The proposed scheme first constructs the adaptive wavelet tight frame that is task specific, and then reconstructs the image of interest by solving an l 1 -regularized minimization problem using the constructed adaptive tight frame system. The proof-of-concept study is performed for computed tomography (CT), and the simulation results suggest that the adaptive tight frame method improves the reconstructed CT image quality from the traditional tight frame method. (paper)

  12. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study.

    Science.gov (United States)

    Bandodkar, Amay J; Jia, Wenzhao; Yardımcı, Ceren; Wang, Xuan; Ramirez, Julian; Wang, Joseph

    2015-01-06

    We present a proof-of-concept demonstration of an all-printed temporary tattoo-based glucose sensor for noninvasive glycemic monitoring. The sensor represents the first example of an easy-to-wear flexible tattoo-based epidermal diagnostic device combining reverse iontophoretic extraction of interstitial glucose and an enzyme-based amperometric biosensor. In-vitro studies reveal the tattoo sensor's linear response toward physiologically relevant glucose levels with negligible interferences from common coexisting electroactive species. The iontophoretic-biosensing tattoo platform is reduced to practice by applying the device on human subjects and monitoring variations in glycemic levels due to food consumption. Correlation of the sensor response with that of a commercial glucose meter underscores the promise of the tattoo sensor to detect glucose levels in a noninvasive fashion. Control on-body experiments demonstrate the importance of the reverse iontophoresis operation and validate the sensor specificity. This preliminary investigation indicates that the tattoo-based iontophoresis-sensor platform holds considerable promise for efficient diabetes management and can be extended toward noninvasive monitoring of other physiologically relevant analytes present in the interstitial fluid.

  13. Evaluation of early efficacy endpoints for proof-of-concept trials.

    Science.gov (United States)

    Chen, Cong; Sun, Linda; Li, Chih-Lin

    2013-03-11

    A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

  14. 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.

  15. Targeting Endothelial Adhesion Molecule Transcription for Treatment of Inflammatory Disease: A Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Liam M. Ashander

    2016-01-01

    Full Text Available Targeting the endothelial adhesion molecules that control leukocyte trafficking into a tissue has been explored as a biological therapy for inflammatory diseases. However, these molecules also participate in leukocyte migration for immune surveillance, and inhibiting the physiological level of an adhesion molecule might promote infection or malignancy. We explored the concept of targeting endothelial adhesion molecule transcription during inflammation in a human system. Intercellular adhesion molecule 1 (ICAM-1 mediates leukocyte migration across the retinal endothelium in noninfectious posterior uveitis. We observed an increase in the transcription factor, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1, in parallel with ICAM-1, in human retinal endothelial cells treated with tumor necrosis factor-alpha (TNF-α, and identified putative binding sites for NF-κB1 within the ICAM-1 regulatory region. We targeted induced NF-κB1 expression in endothelial cells with small interfering (siRNA. Knockdown of NF-κB1 significantly decreased cell surface expression of ICAM-1 protein induced by TNF-α but did not reduce constitutive ICAM-1 expression. Consistently, NF-κB1 knockdown significantly reduced leukocyte binding to cell monolayers in the presence of TNF-α but did not impact baseline binding. Findings of this proof-of-concept study indicate that induced transcription of endothelial adhesion molecules might be targeted therapeutically for inflammatory disease in humans.

  16. Performing particle image velocimetry using artificial neural networks: a proof-of-concept

    Science.gov (United States)

    Rabault, Jean; Kolaas, Jostein; Jensen, Atle

    2017-12-01

    Traditional programs based on feature engineering are underperforming on a steadily increasing number of tasks compared with artificial neural networks (ANNs), in particular for image analysis. Image analysis is widely used in fluid mechanics when performing particle image velocimetry (PIV) and particle tracking velocimetry (PTV), and therefore it is natural to test the ability of ANNs to perform such tasks. We report for the first time the use of convolutional neural networks (CNNs) and fully connected neural networks (FCNNs) for performing end-to-end PIV. Realistic synthetic images are used for training the networks and several synthetic test cases are used to assess the quality of each network’s predictions and compare them with state-of-the-art PIV software. In addition, we present tests on real-world data that prove ANNs can be used not only with synthetic images but also with more noisy, imperfect images obtained in a real experimental setup. While the ANNs we present have slightly higher root mean square error than state-of-the-art cross-correlation methods, they perform better near edges and allow for higher spatial resolution than such methods. In addition, it is likely that one could with further work develop ANNs which perform better that the proof-of-concept we offer.

  17. Meteorite as raw material for Direct Metal Printing: A proof of concept study

    Science.gov (United States)

    Lietaert, Karel; Thijs, Lore; Neirinck, Bram; Lapauw, Thomas; Morrison, Brian; Lewicki, Chris; Van Vaerenbergh, Jonas

    2018-02-01

    Asteroid mining as such is not a new concept, as it has been described in science fiction for more than a century and some of its aspects have been studied by academia for more than 30 years. Recently, there is a renewed interest in this subject due the more and more concrete plans for long-duration space missions and the need for resources to support industrial activity in space. The use of locally available resources would greatly improve the economics and sustainability of such missions. Due to its economy in material, use of additive manufacturing (AM) provides an interesting route to valorize these resources for the production of spare parts, tools and large-scale structures optimized for their local microgravity environment. Proof of concept has already been provided for AM of moon regolith. In this paper the concept of In-Situ Resource Utilization is extended towards the production of metallic objects using powdered iron meteorite as raw material. The meteorite-based powder was used to produce a structural part but further research is needed to obtain a high density part without microcracks.

  18. A proof-of-concept transient diagnostic expert system for BWRs [Boiling Water Reactors

    International Nuclear Information System (INIS)

    Yoshida, K.; Naser, J.A.

    1988-05-01

    A proof-of-concept transient diagnostic expert system has been developed to identify the cause and the type of an abnormal transient in a boiling water nuclear power plant. For this expert system development, the calculational results of the simulation code RETRAN were used as the knowledge source. The knowledge extracted from the RETRAN analyses was transformed into IF-THEN rules in the knowledge base for the expert system. An important feature of this expert system is the introduction of certainty factors to allow diagnosis even in the cases where data may be either missing or marked as invalid. To increase the capability of this diagnostic system to distinguish between similiar transients, backward chaining reasoning is used to support the forward chaining reasoning with certainty factors. Through this effort, it has been demonstrated that an expert system can be successfully used to create a transient diagnostic system. It has also successfully demonstrated that RETRAN can be used as the knowledge source for developing the knowledge base of the diagnostic system

  19. 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.

  20. 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.

  1. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

    Science.gov (United States)

    Bogenschutz, Michael P; Forcehimes, Alyssa A; Pommy, Jessica A; Wilcox, Claire E; Barbosa, P C R; Strassman, Rick J

    2015-03-01

    Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. NCT02061293. © The Author(s) 2015.

  2. Proof-of-concept study of an at-home, engaging, digital intervention for pediatric ADHD.

    Directory of Open Access Journals (Sweden)

    Naomi O Davis

    Full Text Available Pharmacological and behavioral therapies have limited impact on the distinct neurocognitive impairments associated with ADHD, and existing cognitive training programs have shown limited efficacy. This proof-of-concept study assessed treatment acceptability and explored outcomes for a novel digital treatment targeting cognitive processes implicated in ADHD.Participants included 40 children with ADHD and 40 children without ADHD. Following psychiatric screening, ADHD ratings, and baseline neuropsychological measures, participants completed 28-days of at-home treatment. Neuropsychological assessment was repeated at end-of-study along with treatment satisfaction measures.Eighty-four percent of treatment sessions were completed and ratings showed strong intervention appeal. Significant improvements were observed on a computerized attention task for the ADHD group and a highly impaired ADHD High Severity subgroup. There was no change for the non-ADHD group. Spatial working memory also improved for the ADHD group and the ADHD High Severity subgroup.Findings provide preliminary support that this treatment may improve attention, working memory, and inhibition in children with ADHD. Future research requires larger-scale randomized controlled trials that also evaluate treatment impact on functional impairments.ClinicalTrials.gov NCT01943539.

  3. 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.

  4. Feasibility of international data collection and feedback on post-operative pain data: proof of concept.

    Science.gov (United States)

    Zaslansky, R; Chapman, C R; Rothaug, J; Bäckström, R; Brill, S; Davidson, E; Elessi, K; Fletcher, D; Fodor, L; Karanja, E; Konrad, C; Kopf, A; Leykin, Y; Lipman, A; Puig, M; Rawal, N; Schug, S; Ullrich, K; Volk, T; Meissner, W

    2012-03-01

    Post-operative pain exacts a high toll from patients, families, healthcare professionals and healthcare systems worldwide. PAIN-OUT is a research project funded by the European Union's 7th Framework Program designed to develop effective, evidence-based approaches to improve pain management after surgery, including creating a registry for feedback, benchmarking and decision support. In preparation for PAIN-OUT, we conducted a pilot study to evaluate the feasibility of international data collection with feedback to participating sites. Adult orthopaedic or general surgery patients consented to participate between May and October 2008 at 14 collaborating hospitals in 13 countries. Project staff collected patient-reported outcomes and process data from 688 patients and entered the data into an online database. Project staff in 10 institutions met the enrolment criteria of collecting data from at least 50 patients. The completeness and quality of the data, as assessed by rate of missing data, were acceptable; only 2% of process data and 0.06% of patient-reported outcome data were missing. Participating institutions received access to select items as Web-based feedback comparing their outcomes to those of the other sites, presented anonymously. We achieved proof of concept because staff and patients in all 14 sites cooperated well despite marked differences in cultures, nationalities and languages, and a central database management team was able to provide valuable feedback to all. © 2011 European Federation of International Association for the Study of Pain Chapters.

  5. A contact-free volumetric measurement of facial volume after third molar osteotomy: proof of concept.

    Science.gov (United States)

    Brüllmann, Dan; Jürchott, Lena Marie; John, Christoph; Trempler, Christina; Schwanecke, Ulrich; Schulze, Ralf K W

    2014-01-01

    The present study tested the reliability of an optical scanning device for the objective assessment of postoperative facial swelling. Twenty control subjects bearing a defined volume of water (10-30 mL) in an intraorally carried balloon were tested to assess the measurement accuracy of the device. As a proof of concept, facial volumes of 59 surgical cases were recorded before osteotomy and 1 and 7 days after intervention with the use of a structured light scanner. The median difference between the applied and the measured volumes was 0.67 mL for the control test with the artificial swelling simulated using water balloons. For subjects having third molar osteotomy, extraoral volume increased to 5.29 cm(3) 1 day after surgery (95% CI 5.22-8.52) and decreased to 0.00 mL (95% CI 0.85-2.55) after 7 days. Contact-free visible-light 3-dimensional scanning is reliable for the objective assessment of postoperative facial swelling. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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.

  8. 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.

  9. Volcanic ash dosage calculator: A proof-of-concept tool to support aviation stakeholders during ash events

    Science.gov (United States)

    Dacre, H.; Prata, A.; Shine, K. P.; Irvine, E.

    2017-12-01

    The volcanic ash clouds produced by Icelandic volcano Eyjafjallajökull in April/May 2010 resulted in `no fly zones' which paralysed European aircraft activity and cost the airline industry an estimated £1.1 billion. In response to the crisis, the Civil Aviation Authority (CAA), in collaboration with Rolls Royce, produced the `safe-to-fly' chart. As ash concentrations are the primary output of dispersion model forecasts, the chart was designed to illustrate how engine damage progresses as a function of ash concentration. Concentration thresholds were subsequently derived based on previous ash encounters. Research scientists and aircraft manufactures have since recognised the importance of volcanic ash dosages; the accumulated concentration over time. Dosages are an improvement to concentrations as they can be used to identify pernicious situations where ash concentrations are acceptably low but the exposure time is long enough to cause damage to aircraft engines. Here we present a proof-of-concept volcanic ash dosage calculator; an innovative, web-based research tool, developed in close collaboration with operators and regulators, which utilises interactive data visualisation to communicate the uncertainty inherent in dispersion model simulations and subsequent dosage calculations. To calculate dosages, we use NAME (Numerical Atmospheric-dispersion Modelling Environment) to simulate several Icelandic eruption scenarios, which result in tephra dispersal across the North Atlantic, UK and Europe. Ash encounters are simulated based on flight-optimal routes derived from aircraft routing software. Key outputs of the calculator include: the along-flight dosage, exposure time and peak concentration. The design of the tool allows users to explore the key areas of uncertainty in the dosage calculation and to visualise how this changes as the planned flight path is varied. We expect that this research will result in better informed decisions from key stakeholders during

  10. Enrichment of circulating tumor cells from a large blood volume using leukapheresis and elutriation: proof of concept.

    Science.gov (United States)

    Eifler, Robert L; Lind, Judith; Falkenhagen, Dieter; Weber, Viktoria; Fischer, Michael B; Zeillinger, Robert

    2011-03-01

    The aim of this study was to determine the applicability of a sequential process using leukapheresis, elutriation, and fluorescence-activated cell sorting (FACS) to enrich and isolate circulating tumor cells from a large blood volume to allow further molecular analysis. Mononuclear cells were collected from 10 L of blood by leukapheresis, to which carboxyfluorescein succinimidyl ester prelabeled CaOV-3 tumor cells were spiked at a ratio of 26 to 10⁶ leukocytes. Elutriation separated the spiked leukapheresates primarily by cell size into distinct fractions, and leukocytes and tumor cells, characterized as carboxyfluorescein succinimidyl ester positive, EpCAM positive and CD45 negative events, were quantified by flow cytometry. Tumor cells were isolated from the last fraction using FACS or anti-EpCAM coupled immunomagnetic beads, and their recovery and purity determined by fluorescent microscopy and real-time PCR. Leukapheresis collected 13.5 x 10⁹ mononuclear cells with 87% efficiency. In total, 53 to 78% of spiked tumor cells were pre-enriched in the last elutriation fraction among 1.6 x 10⁹ monocytes. Flow cytometry predicted a circulating tumor cell purity of ~90% giving an enrichment of 100,000-fold following leukapheresis, elutriation, and FACS, where CaOV-3 cells were identified as EpCAM positive and CD45 negative events. FACS confirmed this purity. Alternatively, immunomagnetic bead adsorption recovered 10% of tumor cells with a median purity of 3.5%. This proof of concept study demonstrated that elutriation and FACS following leukapheresis are able to enrich and isolate tumor cells from a large blood volume for molecular characterization. Copyright © 2010 International Clinical Cytometry Society.

  11. Combined ecological momentary assessment and global positioning system tracking to assess smoking behavior: a proof of concept study.

    Science.gov (United States)

    Mitchell, John T; Schick, Robert S; Hallyburton, Matt; Dennis, Michelle F; Kollins, Scott H; Beckham, Jean C; McClernon, F Joseph

    2014-01-01

    Ecological momentary assessment (EMA) methods have provided a rich assessment of the contextual factors associated with a wide range of behaviors including alcohol use, eating, physical activity, and smoking. Despite this rich database, this information has not been linked to specific locations in space. Such location information, which can now be easily acquired from global positioning system (GPS) tracking devices, could provide unique information regarding the space-time distribution of behaviors and new insights into their determinants. In a proof of concept study, we assessed the acceptability and feasibility of acquiring and combining EMA and GPS data from adult smokers with attention deficit hyperactivity disorder (ADHD). Participants were adults with ADHD who were enrolled in a larger EMA study on smoking and psychiatric symptoms. Among those enrolled in the latter study who were approached to participate (N = 11), 10 consented, provided daily EMA entries, and carried a GPS device with them during a 7-day assessment period to assess aspects of their smoking behavior. The majority of those eligible to participate were willing to carry a GPS device and signed the consent (10 out of 11, 91%). Of the 10 who consented, 7 participants provided EMA entries and carried the GPS device with them daily for at least 70% of the sampling period. Data are presented on the spatial distribution of smoking episodes and ADHD symptoms on a subset of the sample to demonstrate applications of GPS data. We conclude by discussing how EMA and GPS might be used to study the ecology of smoking and make recommendations for future research and analysis.

  12. Sharing Data between Mobile Devices, Connected Vehicles and Infrastructure Task 8 : D2X Hub Proof-of-Concept Test Evaluation Report.

    Science.gov (United States)

    2017-10-25

    The Task 8 D2X Hub Proof-of-Concept Test Evaluation Report provides results of the experimental data analysis performed in accordance with the experimental plan for the proof-of-concept version of the prototype system. The data set analyzed includes ...

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

    International Nuclear Information System (INIS)

    Rüegsegger, Michael B.; Steiner, Patrick; Kowal, Jens H.; Geiser, Dominik; Pica, Alessia; Aebersold, Daniel M.

    2014-01-01

    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

  14. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Computing under-ice discharge: A proof-of-concept using hydroacoustics and the Probability Concept

    Science.gov (United States)

    Fulton, John W.; Henneberg, Mark F.; Mills, Taylor J.; Kohn, Michael S.; Epstein, Brian; Hittle, Elizabeth A.; Damschen, William C.; Laveau, Christopher D.; Lambrecht, Jason M.; Farmer, William H.

    2018-01-01

    Under-ice discharge is estimated using open-water reference hydrographs; however, the ratings for ice-affected sites are generally qualified as poor. The U.S. Geological Survey (USGS), in collaboration with the Colorado Water Conservation Board, conducted a proof-of-concept to develop an alternative method for computing under-ice discharge using hydroacoustics and the Probability Concept.The study site was located south of Minturn, Colorado (CO), USA, and was selected because of (1) its proximity to the existing USGS streamgage 09064600 Eagle River near Minturn, CO, and (2) its ease-of-access to verify discharge using a variety of conventional methods. From late September 2014 to early March 2015, hydraulic conditions varied from open water to under ice. These temporal changes led to variations in water depth and velocity. Hydroacoustics (tethered and uplooking acoustic Doppler current profilers and acoustic Doppler velocimeters) were deployed to measure the vertical-velocity profile at a singularly important vertical of the channel-cross section. Because the velocity profile was non-standard and cannot be characterized using a Power Law or Log Law, velocity data were analyzed using the Probability Concept, which is a probabilistic formulation of the velocity distribution. The Probability Concept-derived discharge was compared to conventional methods including stage-discharge and index-velocity ratings and concurrent field measurements; each is complicated by the dynamics of ice formation, pressure influences on stage measurements, and variations in cross-sectional area due to ice formation.No particular discharge method was assigned as truth. Rather one statistical metric (Kolmogorov-Smirnov; KS), agreement plots, and concurrent measurements provided a measure of comparability between various methods. Regardless of the method employed, comparisons between each method revealed encouraging results depending on the flow conditions and the absence or presence of ice

  16. A novel stereotactic frame for real PET-guided biopsies: A preclinical proof-of-concept.

    Science.gov (United States)

    Cortes-Rodicio, J; Sanchez-Merino, G; Garcia-Fidalgo, M A; Tobalina-Larrea, I

    2017-09-01

    To design, build and test a stereotactic device that allows PET image-guided biopsies to be performed. An initial prototype consisting of four main pieces, one of which contains radioactive markers to make it visible in the PET images, was built using a 3D printer. Once the device is mounted, a spherical coordinate system is built with the entrance needle point in the skin as the origin of coordinates. Two in-house software programs, namely getCoord.ijm, which obtains the spherical coordinates of the tumour tissue to be biopsied, and getNeedle.ijm, which virtualizes the inner needle tip once the puncture has taken place, were written. This prototype was tested on an FDG-doped phantom to characterize both the accuracy of the system and the procedure time. Up to 11 complete biopsy procedures were conducted. The mean total procedure time was less than 20min, which is less than the procedure time of conventional standard CT-guided biopsies. The overall accuracy of the system was found to be 5.0±1.3mm, which outperforms the criterion used in routine clinical practice when targeting tumours with a diameter of 10mm. A stereotactic frame to conduct real PET image-guided biopsies has been designed and built. A proof-of-concept was performed to characterize the system. The procedure time and accuracy of the system were found to meet the current needs of physicians performing biopsies. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  17. Proof of Concept: Design and Initial Evaluation of a Device to Measure Gastrointestinal Transit Time.

    Science.gov (United States)

    Wagner, Robert H; Savir-Baruch, Bital; Halama, James R; Venu, Mukund; Gabriel, Medhat S; Bova, Davide

    2017-09-01

    Chronic constipation and gastrointestinal motility disorders constitute a large part of a gastroenterology practice and have a significant impact on a patient's quality of life and lifestyle. In most cases, medications are prescribed to alleviate symptoms without there being an objective measurement of response. Commonly used investigations of gastrointestinal transit times are currently limited to radiopaque markers or electronic capsules. Repeated use of these techniques is limited because of the radiation exposure and the significant cost of the devices. We present the proof of concept for a new device to measure gastrointestinal transit time using commonly available and inexpensive materials with only a small amount of radiotracer. Methods: We assembled gelatin capsules containing a 67 Ga-citrate-radiolabeled grain of rice embedded in paraffin for use as a point-source transit device. It was tested for stability in vitro and subsequently was given orally to 4 healthy volunteers and 10 patients with constipation or diarrhea. Imaging was performed at regular intervals until the device was excreted. Results: The device remained intact and visible as a point source in all subjects until excretion. When used along with a diary of bowel movement times and dates, the device could determine the total transit time. The device could be visualized either alone or in combination with a barium small-bowel follow-through study or a gastric emptying study. Conclusion: The use of a point-source transit device for the determination of gastrointestinal transit time is a feasible alternative to other methods. The device is inexpensive and easy to assemble, requires only a small amount of radiotracer, and remains inert throughout the gastrointestinal tract, allowing for accurate determination of gastrointestinal transit time. Further investigation of the device is required to establish optimum imaging parameters and reference values. Measurements of gastrointestinal transit time

  18. 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

  19. Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.

    Science.gov (United States)

    Nagele, Peter; Duma, Andreas; Kopec, Michael; Gebara, Marie Anne; Parsoei, Alireza; Walker, Marie; Janski, Alvin; Panagopoulos, Vassilis N; Cristancho, Pilar; Miller, J Philip; Zorumski, Charles F; Conway, Charles R

    2015-07-01

    N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p nitrous oxide and placebo, p nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Transhiatal Chest Drainage After Hybrid Ivor Lewis Esophagectomy: Proof of Concept Study.

    Science.gov (United States)

    Asti, Emanuele; Sironi, Andrea; Bonitta, Gianluca; Bernardi, Daniele; Bonavina, Luigi

    2018-04-01

    Intercostal pleural drainage is standard practice after transthoracic esophagectomy but has some drawbacks. We hypothesized that a transhiatal pleural drain introduced through the subxyphoid port site incision at laparoscopy can be as effective as the intercostal drainage and may enhance patient recovery. A proof of concept study was designed to assess a new method of pleural drainage in patients undergoing hybrid Ivor Lewis esophagectomy (laparoscopy and right thoracotomy). The main study aims were safety and efficacy of transhiatal pleural drainage with a 15 Fr Blake tube connected to a portable vacuum system. Pre- and postoperative data, mean duration, and total and daily output of drainage were recorded in an electronic database. Postoperative complications were scored according to the Dindo-Clavien classification. Between June 2015 and December 2016, 50 of 63 consecutive patients met the criteria for inclusion in the study. No conversions from the portable vacuum system to underwater seal and suction occurred. There was no mortality. The overall morbidity rate was 40%. Two patients (4%) required reoperation for hemothorax and chylothorax, respectively. Percutaneous catheter drainage for residual pneumothorax was necessary in 2 patients (4%) on postoperative day 2. The mean duration of drainage was 7 days (interquartile range [IQR] = 2), and the total volume of drain output was 1580 mL (IQR = 880). No pleural effusion on chest X-ray was detected at the 3-month follow-up visit. Transhiatal pleural drainage is safe and effective after hybrid Ivor Lewis esophagectomy and could replace the intercostal drain in selected patients.

  1. Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

    Science.gov (United States)

    Murrough, James W; Wade, Elizabeth; Sayed, Sehrish; Ahle, Gabriella; Kiraly, Drew D; Welch, Alison; Collins, Katherine A; Soleimani, Laili; Iosifescu, Dan V; Charney, Dennis S

    2017-08-15

    At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t 19 =5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t 19 =4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. Open-label, proof-of-concept design. Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Using Big Data in oncology to prospectively impact clinical patient care: A proof of concept study.

    Science.gov (United States)

    Dougoud-Chauvin, Vérène; Lee, Jae Jin; Santos, Edgardo; Williams, Vonetta L; Battisti, Nicolò M L; Ghia, Kavita; Sehovic, Marina; Croft, Cortlin; Kim, Jongphil; Balducci, Lodovico; Kish, Julie A; Extermann, Martine

    2018-04-17

    Big Data is widely seen as a major opportunity for progress in the practice of personalized medicine, attracting the attention from medical societies and presidential teams alike as it offers a unique opportunity to enlarge the base of evidence, especially for older patients underrepresented in clinical trials. This study prospectively assessed the real-time availability of clinical cases in the Health & Research Informatics Total Cancer Care™ (TCC) database matching community patients with cancer, and the impact of such a consultation on treatment. Patients aged 70 and older seen at the Lynn Cancer Institute (LCI) with a documented malignancy were eligible. Geriatric screening information and the oncologist's pre-consultation treatment plan were sent to Moffitt. A search for similar patients was done in TCC and additional information retrieved from Electronic Medical Records. A report summarizing the data was sent and the utility of such a consultation was assessed per email after the treatment decision. Thirty one patients were included. The geriatric screening was positive in 87.1% (27) of them. The oncogeriatric consultation took on average 2.2 working days. It influenced treatment in 38.7% (12), and modified it in 19.4% (6). The consultation was perceived as "somewhat" to "very useful" in 83.9% (26). This study establishes a proof of concept of the feasibility of real time use of Big Data for clinical practice. The geriatric screening and the consultation report influenced treatment in 38.7% of cases and modified it in 19.4%, which compares very well with oncogeriatric literature. Additional steps are needed to render it financially and clinically viable. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. 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

  6. RNA Interference Technology to Control Pest Sea Lampreys - A Proof-of-Concept

    Science.gov (United States)

    Heath, George; Childs, Darcy; Docker, Margaret F.; McCauley, David W.; Whyard, Steven

    2014-01-01

    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. PMID:24505485

  7. 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.

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

    Science.gov (United States)

    Heath, George; Childs, Darcy; Docker, Margaret F; McCauley, David W; Whyard, Steven

    2014-01-01

    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.

  9. 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.

  10. The detection of hepatocellular carcinoma (HCC) from patients' breath using canine scent detection: a proof-of-concept study.

    Science.gov (United States)

    Kitiyakara, Taya; Redmond, Susan; Unwanatham, Nattawut; Rattanasiri, Sasivimol; Thakkinstian, Amarin; Tangtawee, Pongsatorn; Mingphruedhi, Somkit; Sobhonslidsuk, Abhasnee; Intaraprasong, Pongphob; Kositchaiwat, Chomsri

    2017-09-13

    . Our results show that this is possible with an accuracy of 78% (p < 0.001 when compared to chance alone), and are thus a proof of concept. Further refinement of the process of detection will be needed before clinical application.

  11. Allocentric spatial memory testing predicts conversion from mild cognitive impairment to dementia: an initial proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Ruth A Wood

    2016-12-01

    Full Text Available The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer’s disease (AD and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from mild cognitive impairment to dementia.Fifteen patients with mild cognitive impairment underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT and Trail Making Test B (TMT-B. At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen’s d = 2.52. The predictive accuracies of the comparator measures were as follows: CSF tau/β-amyloid1-42 ratio 92% (d = 1.81, RAVLT 64% (d = 0.41, TMT-B 78% (d = 1.56, and hippocampal volume 77% (d = 0.65. CSF tau levels were strongly negative correlated with 4MT scores (r = -0.71. This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, noninvasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents which may be more efficacious when given

  12. Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.

    Science.gov (United States)

    Wood, Ruth A; Moodley, Kuven K; Lever, Colin; Minati, Ludovico; Chan, Dennis

    2016-01-01

    The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer's disease (AD), and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment (MCI) due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from MCI to dementia. Fifteen patients with MCI underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test "B" (TMT-B). At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen's d  = 2.52). The predictive accuracies of the comparator measures were as follows: CSF tau/β-amyloid 1-42 ratio 92% ( d  = 1.81), RAVLT 64% ( d  = 0.41), TMT-B 78% ( d  = 1.56), and hippocampal volume 77% ( d  = 0.65). CSF tau levels were strongly negatively correlated with 4MT scores ( r  = -0.71). This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, non-invasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents, which may be more efficacious when given earlier in

  13. Novel application of a Wii remote to measure spasticity with the pendulum test: Proof of concept.

    Science.gov (United States)

    Yeh, Chien-Hung; Hung, Chi-Yao; Wang, Yung-Hung; Hsu, Wei-Tai; Chang, Yi-Chung; Yeh, Jia-Rong; Lee, Po-Lei; Hu, Kun; Kang, Jiunn-Horng; Lo, Men-Tzung

    2016-01-01

    The pendulum test is a standard clinical test for quantifying the severity of spasticity. In the test, an electrogoniometer is typically used to measure the knee angular motion. The device is costly and difficult to set up such that the pendulum test is normally time consuming. The goal of this study is to determine whether a Nintendo Wii remote can replace the electrogroniometer for reliable assessment of the angular motion of the knee in the pendulum test. The pendulum test was performed in three control participants and 13 hemiplegic stroke patients using both a Wii remote and an electrogoniometer. The correlation coefficient and the Bland-Altman difference plot were used to compare the results obtained from the two devices. The Wilcoxon signed-rank test was used to compare the difference between hemiplegia-affected and nonaffected sides in the hemiplegic stroke patients. There was a fair to strong correlation between measurements from the Wii remote and the electrogoniometer (0.513

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

    International Nuclear Information System (INIS)

    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

    2013-01-01

    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

  15. 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.

  16. 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

  17. 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.

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

    Science.gov (United States)

    2016-06-01

    Identifying emerging patterns of strategic importance.  Routing relevant information among tactical decision support tools.  Supporting continuous...management framework that supports decision-making at all levels by:  Identifying emerging patterns of strategic importance.  Routing relevant...creating new channels of interaction (e.g., fishermen, boating community, cruise ship tourists , coastal population, etc.) A.7 Channels Through the pilot

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

    Science.gov (United States)

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

    2016-04-01

    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. The authors scanned a volunteer's dentition with an intraoral scanner (Lava Chairside Oral Scanner C.O.S., 3M). A digital impression was used to design 2 multicomponent orthodontic appliances. Biocompatible acrylic baseplates were produced with the aid of a 3D printer. The metal springs and clasps were produced by a bending robot. The fit of the 2 appliances was assessed by 2 experienced orthodontists. The authors assessed both orthodontic appliances with the volunteer's dentition and found the fit to be excellent. Clinicians can fully produce a multicomponent dental appliance consisting of both an acrylic baseplate and other parts, such as clasps, springs, or screws, using a digital workflow process without the need for a physical model of the patient's dentition. Plaster models can be superfluous for orthodontic treatment as digital models can be used in all phases of a full digital workflow in orthodontics. The arduous task of making a multicomponent dental appliance that involves bending wires can possibly be replaced by a computer, design software, a 3D printer, and a bending robot. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  20. 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

  1. 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

  2. Real-time modulation of visual feedback on human full-body movements in a virtual mirror: development and proof-of-concept.

    Science.gov (United States)

    Roosink, Meyke; Robitaille, Nicolas; McFadyen, Bradford J; Hébert, Luc J; Jackson, Philip L; Bouyer, Laurent J; Mercier, Catherine

    2015-01-05

    Virtual reality (VR) provides interactive multimodal sensory stimuli and biofeedback, and can be a powerful tool for physical and cognitive rehabilitation. However, existing systems have generally not implemented realistic full-body avatars and/or a scaling of visual movement feedback. We developed a "virtual mirror" that displays a realistic full-body avatar that responds to full-body movements in all movement planes in real-time, and that allows for the scaling of visual feedback on movements in real-time. The primary objective of this proof-of-concept study was to assess the ability of healthy subjects to detect scaled feedback on trunk flexion movements. The "virtual mirror" was developed by integrating motion capture, virtual reality and projection systems. A protocol was developed to provide both augmented and reduced feedback on trunk flexion movements while sitting and standing. The task required reliance on both visual and proprioceptive feedback. The ability to detect scaled feedback was assessed in healthy subjects (n = 10) using a two-alternative forced choice paradigm. Additionally, immersion in the VR environment and task adherence (flexion angles, velocity, and fluency) were assessed. The ability to detect scaled feedback could be modelled using a sigmoid curve with a high goodness of fit (R2 range 89-98%). The point of subjective equivalence was not significantly different from 0 (i.e. not shifted), indicating an unbiased perception. The just noticeable difference was 0.035 ± 0.007, indicating that subjects were able to discriminate different scaling levels consistently. VR immersion was reported to be good, despite some perceived delays between movements and VR projections. Movement kinematic analysis confirmed task adherence. The new "virtual mirror" extends existing VR systems for motor and pain rehabilitation by enabling the use of realistic full-body avatars and scaled feedback. Proof-of-concept was demonstrated for the assessment of

  3. An Innovate Robotic Endoscope Guidance System for Transnasal Sinus and Skull Base Surgery: Proof of Concept.

    Science.gov (United States)

    Friedrich, D T; Sommer, F; Scheithauer, M O; Greve, J; Hoffmann, T K; Schuler, P J

    2017-12-01

    Objective  Advanced transnasal sinus and skull base surgery remains a challenging discipline for head and neck surgeons. Restricted access and space for instrumentation can impede advanced interventions. Thus, we present the combination of an innovative robotic endoscope guidance system and a specific endoscope with adjustable viewing angle to facilitate transnasal surgery in a human cadaver model. Materials and Methods  The applicability of the robotic endoscope guidance system with custom foot pedal controller was tested for advanced transnasal surgery on a fresh frozen human cadaver head. Visualization was enabled using a commercially available endoscope with adjustable viewing angle (15-90 degrees). Results  Visualization and instrumentation of all paranasal sinuses, including the anterior and middle skull base, were feasible with the presented setup. Controlling the robotic endoscope guidance system was effectively precise, and the adjustable endoscope lens extended the view in the surgical field without the common change of fixed viewing angle endoscopes. Conclusion  The combination of a robotic endoscope guidance system and an advanced endoscope with adjustable viewing angle enables bimanual surgery in transnasal interventions of the paranasal sinuses and the anterior skull base in a human cadaver model. The adjustable lens allows for the abandonment of fixed-angle endoscopes, saving time and resources, without reducing the quality of imaging.

  4. Using fluorescence lymphangiography to define the ileocolic mesentery: proof of concept for the watershed area using real-time imaging.

    Science.gov (United States)

    Keller, D S; Joshi, H M; Rodriguez-Justo, M; Walsh, D; Coffey, J C; Chand, M

    2017-09-01

    Recent advances in mesenteric science have demonstrated that the mesentery is a continuous structure with a 'watershed' area at the mesenteric apex between the right colon and terminal ileum, where lymphatic flow can proceed either proximally or distally. With this new understanding of the anatomy, functional features are emerging, which can have an impact on surgical management. Fluorescence lymphangiography or lymphoscintigraphy with indocyanine green allows real-time visualization of lymphatic channels, which highlights sentinel lymph nodes and may facilitate identification of the ideal margins for mesenteric lymphadenectomy during bowel resection for colon cancer. By using this novel technology, it is possible to demonstrate a watershed area in the ileocolic region and may facilitate more precise mesenteric dissection. In the present study, we provide proof of concept for the ileocolic watershed area using fluorescence lymphangiography.

  5. Proof of concept Laplacian estimate derived for noninvasive tripolar concentric ring electrode with incorporated radius of the central disc and the widths of the concentric rings.

    Science.gov (United States)

    Makeyev, Oleksandr; Lee, Colin; Besio, Walter G

    2017-07-01

    Tripolar concentric ring electrodes are showing great promise in a range of applications including braincomputer interface and seizure onset detection due to their superiority to conventional disc electrodes, in particular, in accuracy of surface Laplacian estimation. Recently, we proposed a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2 that allows cancellation of all the truncation terms up to the order of 2n. This approach has been used to introduce novel multipolar and variable inter-ring distances concentric ring electrode configurations verified using finite element method. The obtained results suggest their potential to improve Laplacian estimation compared to currently used constant interring distances tripolar concentric ring electrodes. One of the main limitations of the proposed (4n + 1)-point method is that the radius of the central disc and the widths of the concentric rings are not included and therefore cannot be optimized. This study incorporates these two parameters by representing the central disc and both concentric rings as clusters of points with specific radius and widths respectively as opposed to the currently used single point and concentric circles. A proof of concept Laplacian estimate is derived for a tripolar concentric ring electrode with non-negligible radius of the central disc and non-negligible widths of the concentric rings clearly demonstrating how both of these parameters can be incorporated into the (4n + 1)-point method.

  6. Proof of Concept Coded Aperture Miniature Mass Spectrometer Using a Cycloidal Sector Mass Analyzer, a Carbon Nanotube (CNT) Field Emission Electron Ionization Source, and an Array Detector

    Science.gov (United States)

    Amsden, Jason J.; Herr, Philip J.; Landry, David M. W.; Kim, William; Vyas, Raul; Parker, Charles B.; Kirley, Matthew P.; Keil, Adam D.; Gilchrist, Kristin H.; Radauscher, Erich J.; Hall, Stephen D.; Carlson, James B.; Baldasaro, Nicholas; Stokes, David; Di Dona, Shane T.; Russell, Zachary E.; Grego, Sonia; Edwards, Steven J.; Sperline, Roger P.; Denton, M. Bonner; Stoner, Brian R.; Gehm, Michael E.; Glass, Jeffrey T.

    2018-02-01

    Despite many potential applications, miniature mass spectrometers have had limited adoption in the field due to the tradeoff between throughput and resolution that limits their performance relative to laboratory instruments. Recently, a solution to this tradeoff has been demonstrated by using spatially coded apertures in magnetic sector mass spectrometers, enabling throughput and signal-to-background improvements of greater than an order of magnitude with no loss of resolution. This paper describes a proof of concept demonstration of a cycloidal coded aperture miniature mass spectrometer (C-CAMMS) demonstrating use of spatially coded apertures in a cycloidal sector mass analyzer for the first time. C-CAMMS also incorporates a miniature carbon nanotube (CNT) field emission electron ionization source and a capacitive transimpedance amplifier (CTIA) ion array detector. Results confirm the cycloidal mass analyzer's compatibility with aperture coding. A >10× increase in throughput was achieved without loss of resolution compared with a single slit instrument. Several areas where additional improvement can be realized are identified.

  7. 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.

  8. Proof of concept for the simplified breakdown of cellulose by combining Pseudomonas putida strains with surface displayed thermophilic endocellulase, exocellulase and β-glucosidase.

    Science.gov (United States)

    Tozakidis, Iasson E P; Brossette, Tatjana; Lenz, Florian; Maas, Ruth M; Jose, Joachim

    2016-06-10

    The production and employment of cellulases still represents an economic bottleneck in the conversion of lignocellulosic biomass to biofuels and other biocommodities. This process could be simplified by displaying the necessary enzymes on a microbial cell surface. Such an approach, however, requires an appropriate host organism which on the one hand can withstand the rough environment coming along with lignocellulose hydrolysis, and on the other hand does not consume the generated glucose so that it remains available for subsequent fermentation steps. The robust soil bacterium Pseudomonas putida showed a strongly reduced uptake of glucose above a temperature of 50 °C, while remaining structurally intact hence recyclable, which makes it suitable for cellulose hydrolysis at elevated temperatures. Consequently, three complementary, thermophilic cellulases from Ruminiclostridium thermocellum were displayed on the surface of the bacterium. All three enzymes retained their activity on the cell surface. A mixture of three strains displaying each one of these enzymes was able to synergistically hydrolyze filter paper at 55 °C, producing 20 μg glucose per mL cell suspension in 24 h. We could establish Pseudomonas putida as host for the surface display of cellulases, and provided proof-of-concept for a fast and simple cellulose breakdown process at elevated temperatures. This study opens up new perspectives for the application of P. putida in the production of biofuels and other biotechnological products.

  9. Novel Biochar-Plant Tandem Approach for Remediating Hexachlorobenzene Contaminated Soils: Proof-of-Concept and New Insight into the Rhizosphere.

    Science.gov (United States)

    Song, Yang; Li, Yang; Zhang, Wei; Wang, Fang; Bian, Yongrong; Boughner, Lisa A; Jiang, Xin

    2016-07-13

    Volatilization of semi/volatile persistent organic pollutants (POPs) from soils is a major source of global POPs emission. This proof-of-concept study investigated a novel biochar-plant tandem approach to effectively immobilize and then degrade POPs in soils using hexachlorobenzene (HCB) as a model POP and ryegrass (Lolium perenne L.) as a model plant growing in soils amended with wheat straw biochar. HCB dissipation was significantly enhanced in the rhizosphere and near rhizosphere soils, with the greatest dissipation in the 2 mm near rhizosphere. This enhanced HCB dissipation likely resulted from (i) increased bioavailability of immobilized HCB and (ii) enhanced microbial activities, both of which were induced by ryegrass root exudates. As a major component of ryegrass root exudates, oxalic acid suppressed HCB sorption to biochar and stimulated HCB desorption from biochar and biochar-amended soils, thus increasing the bioavailability of HCB. High-throughput sequencing results revealed that the 2 mm near rhizosphere soil showed the lowest bacterial diversity due to the increased abundance of some genera (e.g., Azohydromonas, Pseudomonas, Fluviicola, and Sporocytophaga). These bacteria were likely responsible for the enhanced degradation of HCB as their abundance was exponentially correlated with HCB dissipation. The results from this study suggest that the biochar-plant tandem approach could be an effective strategy for remediating soils contaminated with semi/volatile organic contaminants.

  10. Design and Proof-of-Concept Use of a Circular PMMA Platform with 16-Well Sample Capacity for Microwave-Accelerated Bioassays.

    Science.gov (United States)

    Mohammed, Muzaffer; Aslan, Kadir

    2013-01-01

    We demonstrate the design and the proof-of-concept use of a new, circular poly(methyl methacrylate)-based bioassay platform (PMMA platform), which affords for the rapid processing of 16 samples at once. The circular PMMA platform (5 cm in diameter) was coated with a silver nanoparticle film to accelerate the bioassay steps by microwave heating. A model colorimetric bioassay for biotinylated albumin (using streptavidin-labeled horse radish peroxidase) was performed on the PMMA platform coated with and without silver nanoparticles (a control experiment), and at room temperature and using microwave heating. It was shown that the simulated temperature profile of the PMMA platform during microwave heating were comparable to the real-time temperature profile during actual microwave heating of the constructed PMMA platform in a commercial microwave oven. The model colorimetric bioassay for biotinylated albumin was successfully completed in ~2 min (total assay time) using microwave heating, as compared to 90 min at room temperature (total assay time), which indicates a ~45-fold decrease in assay time. Our PMMA platform design afforded for significant reduction in non-specific interactions and low background signal as compared to non-silvered PMMA surfaces when employed in a microwave-accelerated bioassay carried out in a conventional microwave cavity.

  11. Fabrication of an interim complete removable dental prosthesis with an in-office digital light processing three-dimensional printer: A proof-of-concept technique.

    Science.gov (United States)

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

    2018-04-30

    This report describes a proof of concept for fabricating an interim complete removable dental prosthesis with a digital light processing 3-dimensional (3D) printer. Although an in-office 3D printer can reduce the overall production cost for an interim complete removable dental prosthesis, the process has not been validated with clinical studies. This report provided a preliminary proof of concept in developing a digital workflow for the in-office additively manufactured interim complete removable dental prosthesis. Copyright © 2018 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  12. Magnetic air capsule robotic system: proof of concept of a novel approach for painless colonoscopy.

    Science.gov (United States)

    Valdastri, P; Ciuti, G; Verbeni, A; Menciassi, A; Dario, P; Arezzo, A; Morino, M

    2012-05-01

    Despite being considered the most effective method for colorectal cancer diagnosis, colonoscopy take-up as a mass-screening procedure is limited mainly due to invasiveness, patient discomfort, fear of pain, and the need for sedation. In an effort to mitigate some of the disadvantages associated with colonoscopy, this work provides a preliminary assessment of a novel endoscopic device consisting in a softly tethered capsule for painless colonoscopy under robotic magnetic steering. The proposed platform consists of the endoscopic device, a robotic unit, and a control box. In contrast to the traditional insertion method (i.e., pushing from behind), a "front-wheel" propulsion approach is proposed. A compliant tether connecting the device to an external box is used to provide insufflation, passing a flexible operative tool, enabling lens cleaning, and operating the vision module. To assess the diagnostic and treatment ability of the platform, 12 users were asked to find and remove artificially implanted beads as polyp surrogates in an ex vivo model. In vivo testing consisted of a qualitative study of the platform in pigs, focusing on active locomotion, diagnostic and therapeutic capabilities, safety, and usability. The mean percentage of beads identified by each user during ex vivo trials was 85 ± 11%. All the identified beads were removed successfully using the polypectomy loop. The mean completion time for accomplishing the entire procedure was 678 ± 179 s. No immediate mucosal damage, acute complications such as perforation, or delayed adverse consequences were observed following application of the proposed method in vivo. Use of the proposed platform in ex vivo and preliminary animal studies indicates that it is safe and operates effectively in a manner similar to a standard colonoscope. These studies served to demonstrate the platform's added advantages of reduced size, front-wheel drive strategy, and robotic control over locomotion and orientation.

  13. 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.

  14. Inducing Hepatitis C Virus Resistance After Pig Liver Transplantation-A Proof of Concept of Liver Graft Modification Using Warm Ex Vivo Perfusion.

    Science.gov (United States)

    Goldaracena, N; Spetzler, V N; Echeverri, J; Kaths, J M; Cherepanov, V; Persson, R; Hodges, M R; Janssen, H L A; Selzner, N; Grant, D R; Feld, J J; Selzner, M

    2017-04-01

    Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR-122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS). Miravirsen absorption, miR-122 sequestration, and miR-122 target gene derepression were determined before and after LT. The effect of miravirsen treatment on HCV infection of hepatoma cells was also assessed. NEVLP improved miravirsen uptake versus CS. Significant miR-122 sequestration and miR-122 target gene derepression were seen with NEVLP but not with CS. In vitro data confirmed miravirsen suppression of HCV replication after established infection and prevented HCV infection with pretreatment of cells, analogous to the pretreatment of grafts in the transplant setting. In conclusion, miravirsen delivery during NEVLP is a potential strategy to prevent HCV reinfection after LT. This is the first large-animal study to provide "proof of concept" for using NEVLP to modify and optimize liver grafts for transplantation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Analyzing a steady-state phenomenon using an ensemble of sequential transient events: A proof of concept on photocurrent of bacteriorhodopsin upon continuous photoexcitation

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Chang-Wei; Chu, Li-Kang, E-mail: lkchu@mx.nthu.edu.tw [Department of Chemistry, National Tsing Hua University, 101, Sec. 2, Kuang-Fu Rd., Hsinchu 30013, Taiwan (China); Ho, Ching-Hwa [Interdisplinary Program of Science, National Tsing Hua University, 101, Sec. 2, Kuang-Fu Rd., Hsinchu 30013, Taiwan (China)

    2014-10-14

    The proton pump activity of bacteriorhodopsin in aqueous solution upon excitation with modulated continuous light was monitored electrochemically and analyzed by superimposing a series of transient proton translocation events Hᵢ⁺(t). An evolution function f(t)=(he{sup –lt}+k)/(h+k) , including a decay and a stationary offset, was introduced to weight the contribution of the individual transient events evolving with time in the envelope of the steady-state event. The evolution of the total proton concentration can be treated as an ensemble of weighted sequential transient events, H{sub total}⁺(t)=Σ{{sub i=0}sup n}Hᵢ⁺(t)∙f(t), and the temporal profile of the photocurrent is derived by differentiating the proton concentration with respect to time, (table) . The temporal profiles of the bacteriorhodopsin photocurrent in pH range of 6.3–8.1 were analyzed using a well-defined kinetics model and restricted mathematical formulization, and fitted temporal behaviors agreed with the observations. This successful proof-of-concept study on analyzing a steady-state phenomenon using an ensemble of sequential transient events can be generalized to quantify other phenomena upon continuous stimulation, such as estimation of the light-driven ion pump activities of the photosynthetic proteins upon illumination.

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

    Science.gov (United States)

    2011-06-23

    ... reporting services to the regulated community for the NPDES program (e.g., NPDES permitted facilities). This open platform model would likely be similar to the Internal Revenue Service (IRS) model for electronic... Federal and state levels, to strengthen that performance, and to transform EPA's water quality and...

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

    Science.gov (United States)

    2016-06-01

    Application of Firepower JavaScript Object Notation xvi JTAC Joint Terminal Attack Controller KILSWITCH Kinetic Integrated Low-cost SoftWare...SUMMARY This chapter discussed the basics of the close air support mission, the importance of standardized procedures and quality training for the pilots...Bowman et al. 1999). In that article , the authors discuss the importance of direct experience and how it relates to education. They comment that

  18. 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.

  19. 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

  20. Volumetric MR-Guided High-Intensity Focused Ultrasound with Direct Skin Cooling for the Treatment of Symptomatic Uterine Fibroids : Proof-of-Concept Study

    NARCIS (Netherlands)

    Ikink, Marlijne E; van Breugel, Johanna M M; Schubert, Gerald; Nijenhuis, Robbert J; Bartels, LW; Moonen, Chrit T W; van den Bosch, Maurice A A J

    2015-01-01

    Objective. To prospectively assess the safety and technical feasibility of volumetric magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation with direct skin cooling (DISC) during treatment of uterine fibroids. Methods. In this proof-of-concept study, eight patients were

  1. Proof-of-Concept of the Phytoimmobilization Technology for TNX Outfall Delta: Final Report; FINAL

    International Nuclear Information System (INIS)

    Kaplan, D.I.

    2001-01-01

    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

  2. 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.

  3. 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

  4. Design and test of a biosensor-based multisensorial system: a proof of concept study.

    Science.gov (United States)

    Santonico, Marco; Pennazza, Giorgio; Grasso, Simone; D'Amico, Arnaldo; Bizzarri, Mariano

    2013-12-04

    Sensors are often organized in multidimensional systems or networks for particular applications. This is facilitated by the large improvements in the miniaturization process, power consumption reduction and data analysis techniques nowadays possible. Such sensors are frequently organized in multidimensional arrays oriented to the realization of artificial sensorial systems mimicking the mechanisms of human senses. Instruments that make use of these sensors are frequently employed in the fields of medicine and food science. Among them, the so-called electronic nose and tongue are becoming more and more popular. In this paper an innovative multisensorial system based on sensing materials of biological origin is illustrated. Anthocyanins are exploited here as chemical interactive materials for both quartz microbalance (QMB) transducers used as gas sensors and for electrodes used as liquid electrochemical sensors. The optical properties of anthocyanins are well established and widely used, but they have never been exploited as sensing materials for both gas and liquid sensors in non-optical applications. By using the same set of selected anthocyanins an integrated system has been realized, which includes a gas sensor array based on QMB and a sensor array for liquids made up of suitable Ion Sensitive Electrodes (ISEs). The arrays are also monitored from an optical point of view. This embedded system, is intended to mimic the working principles of the nose, tongue and eyes. We call this setup BIONOTE (for BIOsensor-based multisensorial system for mimicking NOse, Tongue and Eyes). The complete design, fabrication and calibration processes of the BIONOTE system are described herein, and a number of preliminary results are discussed. These results are relative to: (a) the characterization of the optical properties of the tested materials; (b) the performance of the whole system as gas sensor array with respect to ethanol, hexane and isopropyl alcohol detection

  5. Design and Test of a Biosensor-Based Multisensorial System: A Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Marco Santonico

    2013-12-01

    Full Text Available Sensors are often organized in multidimensional systems or networks for particular applications. This is facilitated by the large improvements in the miniaturization process, power consumption reduction and data analysis techniques nowadays possible. Such sensors are frequently organized in multidimensional arrays oriented to the realization of artificial sensorial systems mimicking the mechanisms of human senses. Instruments that make use of these sensors are frequently employed in the fields of medicine and food science. Among them, the so-called electronic nose and tongue are becoming more and more popular. In this paper an innovative multisensorial system based on sensing materials of biological origin is illustrated. Anthocyanins are exploited here as chemical interactive materials for both quartz microbalance (QMB transducers used as gas sensors and for electrodes used as liquid electrochemical sensors. The optical properties of anthocyanins are well established and widely used, but they have never been exploited as sensing materials for both gas and liquid sensors in non-optical applications. By using the same set of selected anthocyanins an integrated system has been realized, which includes a gas sensor array based on QMB and a sensor array for liquids made up of suitable Ion Sensitive Electrodes (ISEs. The arrays are also monitored from an optical point of view. This embedded system, is intended to mimic the working principles of the nose, tongue and eyes. We call this setup BIONOTE (for BIOsensor-based multisensorial system for mimicking NOse, Tongue and Eyes. The complete design, fabrication and calibration processes of the BIONOTE system are described herein, and a number of preliminary results are discussed. These results are relative to: (a the characterization of the optical properties of the tested materials; (b the performance of the whole system as gas sensor array with respect to ethanol, hexane and isopropyl alcohol

  6. 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 EC 50 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.

  7. Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

    Science.gov (United States)

    Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

    2016-01-01

    Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID

  8. 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.

  9. First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-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 (T 1/2  = 4.04 hours, E β+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.

  10. 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.

  11. 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

    2017-10-31

    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. 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. 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. 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.

  12. Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study.

    Science.gov (United States)

    Zentner, Isaac; Schlecht, Hans P; Khensouvann, Lorna; Tamuhla, Neo; Kutzler, Michele; Ivaturi, Vijay; Pasipanodya, Jotam G; Gumbo, Tawanda; Peloquin, Charles A; Bisson, Gregory P; Vinnard, Christopher

    2016-06-01

    The cost and complexity of current approaches to therapeutic drug monitoring during tuberculosis (TB) therapy limits widespread use in areas of greatest need. We sought to determine whether urine colorimetry could have a novel application as a form of therapeutic drug monitoring during anti-TB therapy. Among healthy volunteers, we evaluated 3 dose sizes of rifampin (150 mg, 300 mg, and 600 mg), performed intensive pharmacokinetic sampling, and collected a timed urine void at 4 h post-dosing. The absorbance peak at 475 nm was measured after rifamycin extraction. The optimal cutoff was evaluated in a study of 39 HIV/TB patients undergoing TB treatment in Botswana. In the derivation study, a urine colorimetric assay value of 4.0 × 10(-2) Abs, using a timed void 4 h after dosing, demonstrated a sensitivity of 92 % and specificity of 60 % to detect a peak rifampin concentration (Cmax) under 8 mg/L, with an area under the ROC curve of 0.92. In the validation study, this cutoff was specific (100 %) but insensitive (28 %). We observed similar test characteristics for a target Cmax target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC0-8) target of 24.1 mg•hour/L. The urine colorimetric assay was specific but insensitive to detect low rifampin serum concentrations among HIV/TB patients. In future work we will attempt to optimize sampling times and assay performance, with the goal of delivering a method that can translate into a point-of-care assessment of rifampin exposure during anti-TB therapy.

  13. Virtual Travel Training for Autism Spectrum Disorder: Proof-of-Concept Interventional Study.

    Science.gov (United States)

    Simões, Marco; Bernardes, Miguel; Barros, Fernando; Castelo-Branco, Miguel

    2018-03-20

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and repetitive patterns of behavior, which can lead to deficits in adaptive behavior. In this study, a serious game was developed to train individuals with ASD for an important type of outdoor activity, which is the use of buses as a means of transportation. The aim of this study was to develop a serious game that defines a "safe environment" where the players became familiar with the process of taking a bus and to validate if it could be used effectively to teach bus-taking routines and adaptive procedures to individuals with ASD. In the game, players were placed in a three-dimensional city and were submitted to a set of tasks that involved taking buses to reach specific destinations. Participants with ASD (n=10) underwent between 1 to 3 training sessions. Participants with typical development (n=10) were also included in this study for comparison purposes and received 1 control session. We found a statistically significant increase in the measures of knowledge of the process of riding a bus, a reduction in the electrodermal activity (a metric of anxiety) measured inside the bus environments, and a high success rate of their application within the game (93.8%). The developed game proved to be potentially useful in the context of emerging immersive virtual reality technologies, of which use in therapies and serious games is still in its infancy. Our findings suggest that serious games, using these technologies, can be used effectively in helping people with ASD become more independent in outdoor activities, specifically regarding the use of buses for transportation. ©Marco Simões, Miguel Bernardes, Fernando Barros, Miguel Castelo-Branco. Originally published in JMIR Serious Games (http://games.jmir.org), 20.03.2018.

  14. Inferring regional vertical crustal velocities from averaged relative sea level trends: A proof of concept

    Directory of Open Access Journals (Sweden)

    Bâki Iz H.

    2017-02-01

    Full Text Available 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.

  15. Proof of Concept of an Irradiance Estimation System for Reconfigurable Photovoltaic Arrays

    Directory of Open Access Journals (Sweden)

    Vincenzo Li Vigni

    2015-06-01

    Full Text Available In order to reduce the mismatch effect caused by non-uniform shadows in PV arrays, reconfigurable interconnections approaches have been recently proposed in the literature. These systems usually require the knowledge of the solar radiation affecting every solar module. The aim of this work is to evaluate the effectiveness of three irradiance estimation approaches in order to define which can be well suited for reconfigurable PV arrays. It is presented a real-time solar irradiance estimation device (IrradEst, implementing the three different estimation methods. The proposed system is based on mathematical models of PV modules enabling to estimate irradiation values by sensing a combination of temperature, voltage and current of a PV module. Experimental results showed generally good agreement between the estimated irradiances and the measurements performed by a standard pyranometer taken as reference. Finally one of the three methods was selected as possible solution for a reconfigurable PV system.

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

    Science.gov (United States)

    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

    2014-03-01

    We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing,and analysis was employed for the first time. Sweat chloride and chloride ion transport (NPD) 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. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators.

  17. 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.

  18. Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study.

    Science.gov (United States)

    Cicora, Federico; Mos, Fernando; Petroni, Jorgelina; Casanova, Matías; Reniero, Liliana; Roberti, Javier

    2015-01-01

    Belatacept provides effective immunosuppression while avoiding the nephrotoxicities associated with calcineurin inhibitors (CNIs). However, existing belatacept-based regimens still have high rates of acute rejection. We hypothesized that therapy with belatacept, mycophenolic acid (MMA), steroids and induction therapy with rabbit anti-thymocyte globulin Fresenius (ATGF), rejection rate could be reduced. Prospective, single center, proof-of-concept study including males and females aged ≥18years, Epstein-Barr virus (EBV)-seropositive recipients of a first, HLA non-identical, live or deceased donor kidney allograft. Only patients with a calculated panel reactive antibody score of 0% were included. Three donors were positive for Chagas disease. Six of twelve patients had at least one infection and five were readmitted to the hospital for treatment. One patient had a Trypanosoma cruzi infection via the graft treated successfully. Median cold ischemia time for the transplant patients with a deceased donor was 21.5h. Mean serum creatinine levels at 1, 3 and 6months were 1.76±0.59, 1.55±0.60 and 1.49±0.60mg/dl, respectively. Two of twelve patients experienced clinical, biopsy-proven rejection, successfully treated with methylprednisolone. No patient developed post-transplant lymphoproliferative disorder (PTLD) or any other malignancy and no patient lost their graft or died during follow-up. The potential of this approach makes it worthy of further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Intra-Target Microdosing - A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans.

    Science.gov (United States)

    Burt, T; MacLeod, D; Lee, K; Santoro, A; DeMasi, D K; Hawk, T; Feinglos, M; Rowland, M; Noveck, R J

    2017-09-01

    Intra-Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18 F-fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well-tolerated. Results are consistent with ITM proof-of-concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  20. Optimal cost-effective designs of Phase II proof of concept trials and associated go-no go decisions.

    Science.gov (United States)

    Chen, Cong; Beckman, Robert A

    2009-01-01

    This manuscript discusses optimal cost-effective designs for Phase II proof of concept (PoC) trials. Unlike a confirmatory registration trial, a PoC trial is exploratory in nature, and sponsors of such trials have the liberty to choose the type I error rate and the power. The decision is largely driven by the perceived probability of having a truly active treatment per patient exposure (a surrogate measure to development cost), which is naturally captured in an efficiency score to be defined in this manuscript. Optimization of the score function leads to type I error rate and power (and therefore sample size) for the trial that is most cost-effective. This in turn leads to cost-effective go-no go criteria for development decisions. The idea is applied to derive optimal trial-level, program-level, and franchise-level design strategies. The study is not meant to provide any general conclusion because the settings used are largely simplified for illustrative purposes. However, through the examples provided herein, a reader should be able to gain useful insight into these design problems and apply them to the design of their own PoC trials.

  1. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. 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.

  3. 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.

  4. Effects of tolcapone on working memory and brain activity in abstinent smokers: A proof-of-concept study

    Science.gov (United States)

    Ashare, Rebecca L.; Wileyto, E. Paul; Ruparel, Kosha; Goelz, Patricia M.; Hopson, Ryan D.; Valdez, Jeffrey N.; Gur, Ruben C.; Loughead, James; Lerman, Caryn

    2014-01-01

    Background Dopamine levels in the prefrontal cortex (PFC) are thought to play an important role in cognitive function and nicotine dependence. The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson’s disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. We tested whether tolcapone alters working memory-related brain activity and performance in abstinent smokers. Methods In this double-blind crossover study, 20 smokers completed 8 days of treatment with tolcapone and placebo. In both medication periods, smokers completed blood oxygen level-dependent (BOLD) fMRI scans while performing a working memory N-back task after 24 h of abstinence. Smokers were genotyped prospectively for the COMT val158met polymorphism for exploratory analysis. Results Compared to placebo, tolcapone modestly improved accuracy (p = 0.017) and enhanced suppression of activation in the ventromedial prefrontal cortex (vmPFC) (p = 0.002). There were no effects of medication in other a priori regions of interest (dorsolateral PFC, dorsal cingulate/medial prefrontal cortex, or posterior cingulate cortex). Exploratory analyses suggested that tolcapone led to a decrease in BOLD signal in several regions among smokers with val/val genotypes, but increased or remained unchanged among met allele carriers. Tolcapone did not attenuate craving, mood, or withdrawal symptoms compared to placebo. Conclusions Data from this proof-of-concept study do not provide strong support for further evaluation of COMT inhibitors as smoking cessation aids. PMID:24095246

  5. Stimulating neural plasticity with real-time fMRI neurofeedback in Huntington's disease: A proof of concept study.

    Science.gov (United States)

    Papoutsi, Marina; Weiskopf, Nikolaus; Langbehn, Douglas; Reilmann, Ralf; Rees, Geraint; Tabrizi, Sarah J

    2018-03-01

    Novel methods that stimulate neuroplasticity are increasingly being studied to treat neurological and psychiatric conditions. We sought to determine whether real-time fMRI neurofeedback training is feasible in Huntington's disease (HD), and assess any factors that contribute to its effectiveness. In this proof-of-concept study, we used this technique to train 10 patients with HD to volitionally regulate the activity of their supplementary motor area (SMA). We collected detailed behavioral and neuroimaging data before and after training to examine changes of brain function and structure, and cognitive and motor performance. We found that patients overall learned to increase activity of the target region during training with variable effects on cognitive and motor behavior. Improved cognitive and motor performance after training predicted increases in pre-SMA grey matter volume, fMRI activity in the left putamen, and increased SMA-left putamen functional connectivity. Although we did not directly target the putamen and corticostriatal connectivity during neurofeedback training, our results suggest that training the SMA can lead to regulation of associated networks with beneficial effects in behavior. We conclude that neurofeedback training can induce plasticity in patients with Huntington's disease despite the presence of neurodegeneration, and the effects of training a single region may engage other regions and circuits implicated in disease pathology. © 2017 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  6. Treatment of Wound Healing Disorders of Radial Forearm Free Flap Donor Sites Using Cold Atmospheric Plasma: A Proof of Concept.

    Science.gov (United States)

    Hartwig, Stefan; Doll, Christian; Voss, Jan Oliver; Hertel, Moritz; Preissner, Saskia; Raguse, Jan Dirk

    2017-02-01

    The treatment of wound healing disturbances of the radial forearm free flap donor site after reconstructive surgery is typically long and burdensome and often requires additional surgery. Cold atmospheric plasma is a promising approach to overcome these impairments. The aim of this proof of concept study was to evaluate the clinical outcome of plasma irradiation in patients with wound healing disorders with exposed brachial tendons of the radial forearm. Four patients (mean age 64.2 years, range 44 to 80) who had undergone radial forearm free flap procedures and developed wound healing disturbance leading to exposed flexor tendons were included in the present prospective case series. In addition to routine wound care, all sites were irradiated with cold atmospheric plasma. The primary outcome variable was complete wound closure. In all patients, complete wound repair in terms of the absence of tendon exposure was observed within a mean treatment time of 10.1 weeks (range 4.9 to 16). No undesirable side effects were observed, and no inflammation or infection occurred. Cold atmospheric plasma could offer a reliable conservative treatment option for complicated wound healing disturbances. This was exemplarily shown in the case of radial forearm free flap donor site morbidity with exposed flexor tendons in the present study. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

    Science.gov (United States)

    Goetz, Elena L; Hariri, Ahmad R; Pizzagalli, Diego A; Strauman, Timothy J

    2013-02-01

    Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. Response bias, the participants' propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the COMT genotype (Val/Val) associated with relatively increased phasic dopamine signaling and cognitive flexibility. The combination of success in promotion goal pursuit and Val/Val genotype appears to facilitate responding to reward opportunities in the environment. This study is among the first to integrate an assessment of self-regulatory style with an examination of genetic variability that underlies responsiveness to positive outcomes in goal pursuit.

  8. Proof of concept for molecular velcro based on the attractive interaction between porphyrin and pyridine containing copolymers

    Directory of Open Access Journals (Sweden)

    M. Sievers

    2018-06-01

    Full Text Available In this short communication, we investigated the synthesis and mixing of porphyrin and pyridine functionalized copolymers as a proof of concept for a velcro-like interaction. A functionalized porphyrin monomer with one polymerizable side chain was synthesized following a rational synthetic pathway. Subsequent copolymerization and careful removal of residual free porphyrin led to poly(n-butyl acrylate-co-5,10,15-triphenyl-20-(3-vinylphenylporphyrin. The immobilized porphyrin was transformed into the corresponding zinc(II complex, which is capable of the coordinative binding of one pyridine moiety. Complete metallation was proven by absorption spectroscopy. 4-Vinylpyridine was immobilized by copolymerization with n-butyl acrylate, too. Via controlled radical polymerization conditions, the molecular weight of poly(n-butyl acrylate-co-4-vinylpyridine was limited to one tenth of the molecular weight of the porphyrin containing copolymer. This large difference in the molecular weight easily allowed identifying the polymers in the mixture of both. With the help of diffusion ordered nuclear magnetic resonance spectroscopy, the complete and temperature-stable precipitation of the porphyrin containing copolymer was observed, proving the expected attractive interaction and supramolecular network formation.

  9. Parameters recorded by software of non-invasive ventilators predict COPD exacerbation: a proof-of-concept study.

    Science.gov (United States)

    Borel, Jean-Christian; Pelletier, Julie; Taleux, Nellie; Briault, Amandine; Arnol, Nathalie; Pison, Christophe; Tamisier, Renaud; Timsit, Jean-François; Pepin, Jean-Louis

    2015-03-01

    To assess whether daily variations in three parameters recorded by non-invasive ventilation (NIV) software (respiratory rate (RR), percentage of respiratory cycles triggered by the patient (%Trigg) and NIV daily use) predict the risk of exacerbation in patients with chronic obstructive pulmonary disease (COPD) treated by home NIV. Patients completed the EXACT-Pro questionnaire daily to detect exacerbations. The 25th and 75th percentiles of each 24 h NIV parameter were calculated and updated daily. For a given day, when the value of any parameter was >75th or 75th, 'low value' <25th). Stratified conditional logistic regressions estimated the risk of exacerbation when ≥2 days (for RR and %Trigg) or ≥3 days (for NIV use) out of five had an 'abnormal value'. Sixty-four patients were included. Twenty-one exacerbations were detected and medically confirmed. The risk of exacerbation was increased when RR (OR 5.6, 95% CI 1.4 to 22.4) and %Trigg (OR 4.0, 95% CI 1.1 to 14.5) were considered as 'high value' on ≥2 days out of five. This proof-of-concept study shows that daily variations in RR and %Trigg are predictors of an exacerbation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. 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.

  11. Body weight-supported bedside treadmill training facilitates ambulation in ICU patients: An interventional proof of concept study.

    Science.gov (United States)

    Sommers, Juultje; Wieferink, Denise C; Dongelmans, Dave A; Nollet, Frans; Engelbert, Raoul H H; van der Schaaf, Marike

    2017-10-01

    Early mobilisation is advocated to improve recovery of intensive care unit (ICU) survivors. However, severe weakness in combination with tubes, lines and machinery are practical barriers for the implementation of ambulation with critically ill patients. The aim of this study was to explore the feasibility of Body Weight-Supported Treadmill Training (BWSTT) in critically ill patients in the ICU. A custom build bedside Body Weight-Supported Treadmill was used and evaluated in medical and surgical patients in the ICU. Feasibility was evaluated according to eligibility, successful number of BWSTT, number of staff needed, adverse events, number of patients that could not have walked without BWSTT, patient satisfaction and anxiety. Twenty participants, underwent 54 sessions BWSTT. Two staff members executed the BWSTT and no adverse events occurred. Medical equipment did not have to be disconnected during all treatment sessions. In 74% of the sessions, the participants would not have been able to walk without the BWSTT. Patient satisfaction with BWSTT was high and anxiety low. This proof of concept study demonstrated that BWSTT is safe, reduces staff resource, and facilitates the first time to ambulation in critically ill patients with severe muscle weakness in the ICU. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 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.

  13. Blade-Mounted Flap Control for BVI Noise Reduction Proof-of-Concept Test

    Science.gov (United States)

    Dawson, Seth; Hassan, Ahmed; Straub, Friedrich; Tadghighi, Hormoz

    1995-01-01

    This report describes a wind tunnel test of the McDonnell Douglas Helicopter Systems (MDHS) Active Flap Model Rotor at the NASA Langley 14- by 22-Foot Subsonic Tunnel. The test demonstrated that BVI noise reductions and vibration reductions were possible with the use of an active flap. Aerodynamic results supported the acoustic data trends, showing a reduction in the strength of the tip vortex with the deflection of the flap. Acoustic results showed that the flap deployment, depending on the peak deflection angle and azimuthal shift in its deployment schedule, can produce BVI noise reductions as much as 6 dB on the advancing and retreating sides. The noise reduction was accompanied by an increase in low frequency harmonic noise and high frequency broadband noise. A brief assessment of the effect of the flap on vibration showed that significant reductions were possible. The greatest vibration reductions (as much as 76%) were found in the four per rev pitching moment at the hub. Performance improvement cam results were inconclusive, as the improvements were predicted to be smaller than the resolution of the rotor balance.

  14. Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept.

    Science.gov (United States)

    Peyrode, Caroline; Weber, Valérie; Voissière, Aurélien; Maisonial-Besset, Aurélie; Vidal, Aurélien; Auzeloux, Philippe; Gaumet, Vincent; Borel, Michèle; Dauplat, Marie-Mélanie; Quintana, Mercedes; Degoul, Françoise; Rédini, Françoise; Chezal, Jean-Michel; Miot-Noirault, Elisabeth

    2016-11-01

    To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosarcoma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [ 3 H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99m Tc-NTP 15-5 scintigraphic imaging of PGs, 1 H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the tolerability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma. Mol Cancer Ther; 15(11); 2575-85. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Biodegradation of Mg-14Li alloy in simulated body fluid: A proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Xiao-Bo Chen

    2018-03-01

    Full Text Available High corrosion kinetics and localised corrosion progress are the primary concerns arising from the clinical implementation of magnesium (Mg based implantable devices. In this study, a binary Mg-lithium (Li alloy consisting a record high Li content of 14% (in weight was employed as model material aiming to yield homogenous and slow corrosion behaviour in a simulated body fluid, i.e. minimum essential medium (MEM, in comparison to that of generic Mg alloy AZ31 and biocompatible Mg-0.5Zn-0.5Ca counterparts. Scanning electron microscopy examination reveals single-phase microstructural characteristics of Mg-14Li (β-Li, whilst the presence of insoluble phases, cathodic to α-Mg matrix, in AZ31 and Mg-0.5Zn-0.5Ca. Though slight differences exist in the corrosion kinetics of all the specimens over a short-term time scale (no longer than 60 min, as indicated by potentiodynamic polarisation and electrochemical impedance spectroscopy, profound variations are apparent in terms of immersion tests, i.e. mass loss and hydrogen evolution measurements (up to 7 days. Cross-sectional micrographs unveil severe pitting corrosion in AZ31 and Mg-0.5Zn-0.5Ca, but not the case for Mg-14Li. X-ray diffraction patterns and X-ray photoelectron spectroscopy confirm that a compact film (25 μm in thickness consisting of lithium carbonate (Li2CO3 and calcium hydroxide was generated on the surface of Mg-14Li in MEM, which contributes greatly to its low corrosion rate. It is proposed therefore that the single-phase structure and formation of protective and defect-free Li2CO3 film give rise to the controlled and homogenous corrosion behaviour of Mg-14Li in MEM, providing new insights for the exploration of biodegradable Mg materials.

  16. 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.

  17. 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.

  18. 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

    2015-04-02

    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 methodology in applied ethnopharmacological research. 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. 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 silybin A, silybin B and hydrastine and berberine on CYP2C9 and CYP3A4/5, respectively, results which more

  19. 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.

  20. AGuIX, a theranostic nano-particle to improve image-guided radiation therapy: a proof of concept in pancreatic cancer

    International Nuclear Information System (INIS)

    Detappe, Alexandre

    2017-01-01

    Previous studies demonstrated AGuIX ability to act as an efficient radiosensitizer under the presence of preclinical radiations or monoenergetic radiation beams for multiple cancer models. The preclinical irradiation (220 kV) has been shown effective in activating high atomic number (Z) nanoparticles. The energy peak is close to the k-edge of the different high-Z elements used (50.2 keV for the gadolinium), leading to a strong photoelectric effect. Auger electrons generation and biological effects occur afterwards creating a local dose enhancement. However, clinical treatments use a higher energy beam (≥6 MV). At these energy ranges, the photoelectric probability is less important, decreasing the direct interaction of the nanoparticles with the incoming photons. We performed a proof of concept on a pancreatic tumor model, known for its low survival rates, with preclinical and clinical radiation beams to evaluate the efficacy of the AGuIX. To increase the efficacy of the clinical radiation beam without modifying the nanoparticle structure in order to obtain a dose enhancement close to the one observed with the preclinical beam, we evaluated key clinical beam parameters to understand and increase the mechanisms of interaction between the incident photons and the high-Z nanoparticles. Hence, we evaluated analytically the impact of the radiation beam under different conditions of irradiation, confirming the potential of the AGuIX with a preclinical beam, and finally shown their significant efficacy under a clinical setup. This study is the first to evaluate the potential of a high-Z nanoparticle to act as radiosensitizer following low dose intravenous injections. (author)

  1. 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.

  2. 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.

  3. Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity

    Directory of Open Access Journals (Sweden)

    Feng Liu

    2017-10-01

    Full Text Available Abstract Background It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA, a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC trial for a follow-on compound using the lessons learnt from the lead compound. Methods The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid “S” shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. Results It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response

  4. Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity.

    Science.gov (United States)

    Liu, Feng; Walters, Stephen J; Julious, Steven A

    2017-10-02

    It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log

  5. Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study.

    Science.gov (United States)

    Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K

    2018-05-21

    Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

  6. Fostering Spontaneous Visual Attention in Children on the Autism Spectrum: A Proof-of-Concept Study Comparing Singing and Speech.

    Science.gov (United States)

    Thompson, Grace Anne; Abel, Larry Allen

    2018-01-22

    Children on the autism spectrum are reported to have lower rates of social gaze as early as toddlerhood, and this pattern persists across the lifespan. Finding ways to promote more natural and spontaneous engagement in social interactions may help to boost developmental opportunities in the child's home and community settings. This proof-of-concept study hypothesized that a video of a singer would elicit more attention to the performer, particularly to her face, than a video of her reading a story, and that the child's familiarity with the material would enhance attention. Sixteen children on the autism spectrum (7-10 years old) watched 4 videos 1 min long comprising a favorite song or story, and an unfamiliar song and story. Eye movements were recorded, and three-way repeated measures ANOVAs examined the proportion of total valid visual dwell time and fixations, in each trial and each target area. For proportion of both dwell time and fixation counts, children were significantly more likely to look at the performer's face and body and less at the prop during singing than story-telling and when familiar rather than unfamiliar material was presented. These findings raise important issues for supporting children to naturally initiate looking toward a person's face. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Children on the autism spectrum may have difficulty looking at people, particularly their faces. In this study, children watched videos of someone singing or reading a story. The results show that children look more at the person if they were singing and if the story was familiar to them. Using songs and familiar stories may be a way to help children with autism to naturally engage with others. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

  7. 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.

  8. 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

  9. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.

    Science.gov (United States)

    Washington, Chad W; Derdeyn, Colin P; Dhar, Rajat; Arias, Eric J; Chicoine, Michael R; Cross, DeWitte T; Dacey, Ralph G; Han, Byung Hee; Moran, Christopher J; Rich, Keith M; Vellimana, Ananth K; Zipfel, Gregory J

    2016-02-01

    Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients. A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms. Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%). The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.

  10. 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…

  11. 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...

  12. BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

    Science.gov (United States)

    Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

    2015-01-01

    Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory

  13. Design of the Growth hormone deficiency and Efficacy of Treatment (GET) score and non-interventional proof of concept study.

    Science.gov (United States)

    Kann, Peter H; Bergmann, Simona; Bidlingmaier, Martin; Dimopoulou, Christina; Pedersen, Birgitte T; Stalla, Günter K; Weber, Matthias M; Meckes-Ferber, Stefanie

    2018-02-13

    The adverse effects of growth hormone (GH) deficiency (GHD) in adults (AGHD) on metabolism and health-related quality of life (HRQoL) can be improved with GH substitution. This investigation aimed to design a score summarising the features of GHD and evaluate its ability to measure the effect of GH substitution in AGHD. The Growth hormone deficiency and Efficacy of Treatment (GET) score (0-100 points) assessed (weighting): HRQoL (40%), disease-related days off work (10%), bone mineral density (20%), waist circumference (10%), low-density lipoprotein cholesterol (10%) and body fat mass (10%). A prospective, non-interventional, multicentre proof-of-concept study investigated whether the score could distinguish between untreated and GH-treated patients with AGHD. A 10-point difference in GET score during a 2-year study period was expected based on pre-existing knowledge of the effect of GH substitution in AGHD. Of 106 patients eligible for analysis, 22 were untreated GHD controls (9 females, mean ± SD age 52 ± 17 years; 13 males, 57 ± 13 years) and 84 were GH-treated (31 females, age 45 ± 13 years, GH dose 0.30 ± 0.16 mg/day; 53 males, age 49 ± 15 years, GH dose 0.25 ± 0.10 mg/day). Follow-up was 706 ± 258 days in females and 653 ± 242 days in males. The GET score differed between the untreated control and treated groups with a least squares mean difference of + 10.01 ± 4.01 (p = 0.0145). The GET score appeared to be a suitable integrative instrument to summarise the clinical features of GHD and measure the effects of GH substitution in adults. Exercise capacity and muscle strength/body muscle mass could be included in the GET score. NCT number: NCT00934063 . Date of registration: 02 July 2009.

  14. Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study.

    Science.gov (United States)

    Lédée, N; Gridelet, V; Ravet, S; Jouan, C; Gaspard, O; Wenders, F; Thonon, F; Hincourt, N; Dubois, M; Foidart, J M; Munaut, C; Perrier d'Hauterive, S

    2013-02-01

    Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing pregnancy of the corresponding fertilized oocytes among selected transferred embryos. Here we present a proof of concept study aimed at evaluating the impact of including FF G-CSF quantification in the embryo transfer decisions. FF G-CSF was quantified with the Luminex XMap technology in 523 individual FF samples corresponding to 116 fresh transferred embryos, 275 frozen embryos and 131 destroyed embryos from 78 patients undergoing ICSI. Follicular G-CSF was highly predictive of subsequent implantation. The receiving operator characteristics curve methodology showed its higher discriminatory power to predict ongoing pregnancy in multivariate logistic regression analysis for FF G-CSF compared with embryo morphology [0.77 (0.69-0.83), P Embryos were classified by their FF G-CSF concentration: Class I over 30 pg/ml (a highest positive predictive value for implantation), Class II from 30 to 18.4 pg/ml and Class III Embryos derived from Class I follicles had a significantly higher implantation rate (IR) than those from Class II and III follicles (36 versus 16.6 and 6%, P Embryos derived from Class I follicles with an optimal morphology reached an IR of 54%. Frozen-thawed embryos transfer derived from Class I follicles had an IR of 37% significantly higher than those from Class II and III follicles, respectively, of 8 and 5% (P embryos but also 10% of the destroyed embryos were derived from G-CSF Class I follicles. Non-optimal embryos appear to have been transferred in 28% (22/78) of the women, and their pregnancy rate was significantly lower than that of women who received at least one optimal embryo (18 versus 36%, P = 0.04). Monitoring FF G-CSF for the selection of embryos with a better potential for pregnancy might improve the effectiveness of IVF by reducing the time and cost

  15. Treatment of Sarcopenia with Bimagrumab: Results from a Phase II, Randomized, Controlled, Proof-of-Concept Study.

    Science.gov (United States)

    Rooks, Daniel; Praestgaard, Jens; Hariry, Sam; Laurent, Didier; Petricoul, Olivier; Perry, Robert G; Lach-Trifilieff, Estelle; Roubenoff, Ronenn

    2017-09-01

    To assess the effects of bimagrumab on skeletal muscle mass and function in older adults with sarcopenia and mobility limitations. A 24-week, randomized, double-blind, placebo-controlled, parallel-arm, proof-of-concept study. Five centers in the United States. Community-dwelling adults (N = 40) aged 65 and older with gait speed between 0.4 and 1.0 m/s over 4 m and an appendicular skeletal muscle index of 7.25 kg/m 2 or less for men and 5.67 kg/m 2 or less for women. Intravenous bimagrumab 30 mg/kg (n = 19) or placebo (n = 21). Change from baseline in thigh muscle volume (TMV), subcutaneous and intermuscular fat, appendicular and total lean body mass, grip strength, gait speed, and 6-minute walk distance (6MWD). Thirty-two (80%) participants completed the study. TMV increased by Week 2, was sustained throughout the treatment period, and remained above baseline at the end of study in bimagrumab-treated participants, whereas there was no change with placebo treatment (Week 2: 5.15 ± 2.19% vs -0.34 ± 2.59%, P < .001; Week 4: 6.12 ± 2.56% vs 0.16 ± 3.42%, P < .001; Week 8: 8.01 ± 3.70% vs 0.35 ± 3.32%, P < .001; Week 16: 7.72 ± 5.31% vs 0.42 ± 5.14%, P < .001; Week 24: 4.80 ± 5.81% vs -1.01 ± 4.43%, P = .002). Participants with slower walking speed at baseline receiving bimagrumab had clinically meaningful and statistically significantly greater improvements in gait speed (mean 0.15 m/s, P = .009) and 6MWD (mean 82 m, P = .022) than those receiving placebo at Week 16. Adverse events in the bimagrumab group included muscle-related symptoms, acne, and diarrhea, most of which were mild in severity and resolved by the end of study. Treatment with bimagrumab over 16 weeks increased muscle mass and strength in older adults with sarcopenia and improved mobility in those with slow walking speed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  16. 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

  17. Pediatric microdose study of [(14)C]paracetamol to study drug metabolism using accelerated mass spectrometry: proof of concept.

    Science.gov (United States)

    Mooij, Miriam G; van Duijn, Esther; Knibbe, Catherijne A J; Windhorst, Albert D; Hendrikse, N Harry; Vaes, Wouter H J; Spaans, Edwin; Fabriek, Babs O; Sandman, Hugo; Grossouw, Dimitri; Hanff, Lidwien M; Janssen, Paul J J M; Koch, Birgit C P; Tibboel, Dick; de Wildt, Saskia N

    2014-11-01

    Pediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons. The objective of this study was to present pilot data of an oral [(14)C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children. In an open-label microdose pharmacokinetic pilot study, infants (0-6 years of age) received a single oral [(14)C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and [(14)C]AAP and metabolites ([(14)C]AAP-Glu and [(14)C]AAP-4Sul) were measured by accelerator mass spectrometry. Ten infants (aged 0.1-83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [(14)C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (C max) [(14)C]AAP 1.68 (0.75-4.76) ng/L, [(14)C]AAP-Glu 0.88 (0.34-1.55) ng/L, and [(14)C]AAP-4Sul 0.81 (0.29-2.10) ng/L. Dose-normalized oral [(14)C]AAP C max approached median intravenous average concentrations (C av): 8.41 mg/L (3.75-23.78 mg/L) and 8.87 mg/L (3.45-12.9 mg/L), respectively. We demonstrate the feasibility of using a [(14)C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children.

  18. 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

  19. Advancing the citizen scientist's contributions to documenting and understanding natural hazards: a proof of concept for linking crowdsourced and remotely sensed data on landslide hazards in El Salvador

    Science.gov (United States)

    Anderson, E. R.; Griffin, R.; Markert, K. N.

    2017-12-01

    Scientists, practitioners, policymakers, and citizen groups, share a role in ensuring "that all sectors have access to, understand and can use scientific information for better informed decision-making" (Sendai Framework 2015-2030). When it comes to understanding hazards and exposure, inventories on disaster events are often limited. Thus, there are many opportunities for citizen scientists to engage in improving the collective understanding—and ultimately reduction—of disaster risk. Landslides are very difficult to forecast on spatial and temporal scales meaningful for early warning and evacuation. Heuristic hazard mapping methods are very common in regional hazard zonation and rely on expert knowledge of previous events and local conditions, but they often lack a temporal component. As new data analysis packages are becoming more open and accessible, probabilistic approaches that consider high resolution spatial and temporal dimensions are becoming more common, but this is only possible when rich inventories of landslide events exist. The work presented offers a proof of concept on incorporating crowd-sourced data to improve landslide hazard model performance. Starting with a national inventory of 90 catalogued landslides in El Salvador for a study period of 1998 to 2011, we simulate the addition of over 600 additional crowd-sourced landslide events that would have been identified through human interpretation of high resolution imagery in the Google Earth time slider feature. There is a noticeable improvement in performance statistics between static heuristic hazard models and probabilistic models that incorporate the events identified by the "crowd." Such a dynamic incorporation of crowd-sourced data on hazard events is not so far-fetched. Given the engagement of "local observers" in El Salvador who augment in situ hydro-meteorological measurements, the growing access to Earth observation data to the lay person, and immense interest behind connecting citizen

  20. Cone beam CT imaging with limited angle of projections and prior knowledge for volumetric verification of non-coplanar beam radiation therapy: a proof of concept study

    Science.gov (United States)

    Meng, Bowen; Xing, Lei; Han, Bin; Koong, Albert; Chang, Daniel; Cheng, Jason; Li, Ruijiang

    2013-11-01

    registration significantly improved the reconstructed image quality, with a reduction of mostly 2-3 folds (up to 100) in root mean square image error. The proposed algorithm provides a remedy for solving the problem of non-coplanar CBCT reconstruction from limited angle of projections by combining the PICCS technique and rigid image registration in an iterative framework. In this proof of concept study, non-coplanar beams with couch rotations of 45° can be effectively verified with the CBCT technique.

  1. 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

  2. WE-AB-BRB-01: Development of a Probe-Format Graphite Calorimeter for Practical Clinical Dosimetry: Numerical Design Optimization, Prototyping, and Experimental Proof-Of-Concept

    International Nuclear Information System (INIS)

    Renaud, J; Seuntjens, J; Sarfehnia, A

    2015-01-01

    Purpose: In this work, the feasibility of performing absolute dose to water measurements using a constant temperature graphite probe calorimeter (GPC) in a clinical environment is established. Methods: A numerical design optimization study was conducted by simulating the heat transfer in the GPC resulting from irradiation using a finite element method software package. The choice of device shape, dimensions, and materials was made to minimize the heat loss in the sensitive volume of the GPC. The resulting design, which incorporates a novel aerogel-based thermal insulator, and 15 temperature sensitive resistors capable of both Joule heating and measuring temperature, was constructed in house. A software based process controller was developed to stabilize the temperatures of the GPC’s constituent graphite components to within a few 10’s of µK. This control system enables the GPC to operate in either the quasi-adiabatic or isothermal mode, two well-known, and independent calorimetry techniques. Absorbed dose to water measurements were made using these two methods under standard conditions in a 6 MV 1000 MU/min photon beam and subsequently compared against TG-51 derived values. Results: Compared to an expected dose to water of 76.9 cGy/100 MU, the average GPC-measured doses were 76.5 ± 0.5 and 76.9 ± 0.5 cGy/100 MU for the adiabatic and isothermal modes, respectively. The Monte Carlo calculated graphite to water dose conversion was 1.013, and the adiabatic heat loss correction was 1.003. With an overall uncertainty of about 1%, the most significant contributions were the specific heat capacity (type B, 0.8%) and the repeatability (type A, 0.6%). Conclusion: While the quasi-adiabatic mode of operation had been validated in previous work, this is the first time that the GPC has been successfully used isothermally. This proof-of-concept will serve as the basis for further study into the GPC’s application to small fields and MRI-linac dosimetry. This work has been

  3. In-line carbon nanofiber reinforced hollow fiber-mediated liquid phase microextraction using a 3D printed extraction platform as a front end to liquid chromatography for automatic sample preparation and analysis: A proof of concept study.

    Science.gov (United States)

    Worawit, Chanatda; Cocovi-Solberg, David J; Varanusupakul, Pakorn; Miró, Manuel

    2018-08-01

    A novel concept for automation of nanostructured hollow-fiber supported microextraction, combining the principles of liquid-phase microextraction (LPME) and sorbent microextraction synergically, using mesofluidic platforms is proposed herein for the first time, and demonstrated with the determination of acidic drugs (namely, ketoprofen, ibuprofen, diclofenac and naproxen) in urine as a proof-of-concept applicability. Dispersed carbon nanofibers (CNF) are immobilized in the pores of a single-stranded polypropylene hollow fiber (CNF@HF) membrane, which is thereafter accommodated in a stereolithographic 3D-printed extraction chamber without glued components for ease of assembly. The analytical method involves continuous-flow extraction of the acidic drugs from a flowing stream donor (pH 1.7) into an alkaline stagnant acceptor (20 mmol L -1 NaOH) containing 10% MeOH (v/v) across a dihexyl ether impregnated CNF@HF membrane. The flow setup features entire automation of the microextraction process including regeneration of the organic film and on-line injection of the analyte-laden acceptor phase after downstream neutralization into a liquid chromatograph (LC) for reversed-phase core-shell column-based separation. Using a 12-cm long CNF@HF and a sample volume of 6.4 mL, linear dynamic ranges of ketoprofen, naproxen, diclofenac and ibuprofen, taken as models of non-steroidal anti-inflammatory drugs, spanned from ca. 5-15 µg L -1 to 500 µg L -1 with enhancement factors of 43-97 (against a direct injection of 10 µL standards into LC), and limits of detection from 1.6 to 4.3 µg L -1 . Relative recoveries in real urine samples ranged from 97% to 105%, thus demonstrating the reliability of the automatic CNF@HF-LPME method for in-line matrix clean-up and determination of drugs in urine at therapeutically relevant concentrations. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. 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

  5. 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.

  6. Multidimensional profiling of components in complex mixtures of natural products for metabolic analysis, proof of concept: application to Quillaja saponins.

    Science.gov (United States)

    Bankefors, Johan; Nord, Lars I; Kenne, Lennart

    2010-02-01

    A method for separation and detection of major and minor components in complex mixtures has been developed, utilising two-dimensional high-performance liquid chromatography (2D-HPLC) combined with electrospray ionisation ion-trap multiple-stage mass spectrometry (ESI-ITMS(n)). Chromatographic conditions were matched with mass spectrometric detection to maximise the number of components that could be separated. The described procedure has proven useful to discern several hundreds of saponin components when applied to Quillaja saponaria Molina bark extracts. The discrimination of each saponin component relies on the fact that three coordinates (x, y, z) for each component can be derived from the retention time of the two chromatographic steps (x, y) and the m/z-values from the multiple-stage mass spectrometry (z(n), n=1, 2, ...). Thus an improved graphical representation was obtained by combining retention times from the two-stage separation with +MS(1) (z(1)) and the additional structural information from the second mass stage +MS(2) (z(2), z(3)) corresponding to the main fragment ions. By this approach three-dimensional plots can be made that reveal both the chromatographic and structural properties of a specific mixture which can be useful in fingerprinting of complex mixtures. 2009 Elsevier B.V. All rights reserved.

  7. 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.

  8. Dynamic infrared thermography (DIRT) for assessment of skin blood perfusion in cranioplasty: a proof of concept for qualitative comparison with the standard indocyanine green video angiography (ICGA).

    Science.gov (United States)

    Rathmann, P; Chalopin, C; Halama, D; Giri, P; Meixensberger, J; Lindner, D

    2018-03-01

    Complications in wound healing after neurosurgical operations occur often due to scarred dehiscence with skin blood perfusion disturbance. The standard imaging method for intraoperative skin perfusion assessment is the invasive indocyanine green video angiography (ICGA). The noninvasive dynamic infrared thermography (DIRT) is a promising alternative modality that was evaluated by comparison with ICGA. The study was carried out in two parts: (1) investigation of technical conditions for intraoperative use of DIRT for its comparison with ICGA, and (2) visual and quantitative comparison of both modalities in a proof of concept on nine patients. Time-temperature curves in DIRT and time-intensity curves in ICGA for defined regions of interest were analyzed. New perfusion parameters were defined in DIRT and compared with the usual perfusion parameters in ICGA. The visual observation of the image data in DIRT and ICGA showed that operation material, anatomical structures and skin perfusion are represented similarly in both modalities. Although the analysis of the curves and perfusion parameter values showed differences between patients, no complications were observed clinically. These differences were represented in DIRT and ICGA equivalently. DIRT has shown a great potential for intraoperative use, with several advantages over ICGA. The technique is passive, contactless and noninvasive. The practicability of the intraoperative recording of the same operation field section with ICGA and DIRT has been demonstrated. The promising results of this proof of concept provide a basis for a trial with a larger number of patients.

  9. Flexible mechanoprosthesis made from woven ultra-high-molecular-weight polyethylene fibres : proof of concept in a chronic sheep model

    NARCIS (Netherlands)

    Basir, Amir; Grobben, Remco B.; Cramer, Maarten Jan; van Herwaarden, Joost A.; Vink, Aryan; Pasterkamp, Gerard; Kluin, Jolanda; Gründeman, Paul F.

    2017-01-01

    OBJECTIVES: Ultra-high-molecular-weight polyethylene (UHMWPE) fibres are flexible, have high tensile strength, and platelet and bacterial adhesion is low. Therefore, UHMWPE may overcome limitations of current mechanical valves and bioprostheses. In this study, the biocompatibility and functionality

  10. Flexible mechanoprosthesis made from woven ultra-high-molecular-weight polyethylene fibres: proof of concept in a chronic sheep model

    NARCIS (Netherlands)

    Basir, Amir; Grobben, Remco B.; Cramer, Maarten Jan; van Herwaarden, Joost A.; Vink, Aryan; Pasterkamp, Gerard; Kluin, Jolanda; Gründeman, Paul F.

    2017-01-01

    OBJECTIVES: Ultra-high-molecular-weight polyethylene (UHMWPE) fibres are flexible, have high tensile strength, and platelet and bacterial adhesion is low. Therefore, UHMWPE may overcome limitations of current mechanical valves and bioprostheses. In this study, the bio-compatibility and functionality

  11. 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

  12. 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

  13. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

    Science.gov (United States)

    Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

    2015-01-01

    Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

  14. Pharmacodynamic evaluation of intragastric pH and implications for famotidine dosing in the prophylaxis of non-steroidal anti-inflammatory drug induced gastropathy-a proof of concept analysis.

    Science.gov (United States)

    Kent, Jeffery D; Holt, Robert J; Jung, Donald; Tidmarsh, George F; Grahn, Amy Y; Ball, Julie; Peura, David A

    2014-01-01

    Famotidine given at a dose of 80 mg/day is effective in preventing NSAID-induced gastropathy. The aim of this proof of concept study was to compare twice a day (BID) vs 3-times a day (TID) administration of this total dose of famotidine on intragastric pH in healthy volunteers. Two analyses were undertaken: (1) a 13 subject controlled cross-over 24-h intragastric pH evaluation of the BID and TID administration of 80 mg/day of famotidine, as well as measures for drug accumulation over 5 days (EudraCT, number 2006-002930-39); and (2) a pharmacokinetic (PK)/pharmacodynamic (PD) model which predicted steady-state famotidine plasma concentrations and pH of the two regimens. For the cross-over study, gastric pH was above 3.5 for a mean of 20 min longer for TID dosing compared to BID dosing on Day 1. On Day 5, the mean time above this threshold was higher with the BID regimen by ∼25 min. For pH 4, subjects' gastric pH was above this pH value for a mean of 25 min longer for TID dosing compared to BID dosing on Day 1. For Day 5, the pH was above 4 for ∼45 min longer with the TID regimen as compared with the BID regimen. The mean 24-h gastric pH values when taken in the upright position trended higher for the TID dosing period compared to the BID regimen on Day 1. The steady-state simulation model indicated that, following TID dosing, intragastric pH will be above 3 for 24 h vs 16 h for the BID regimen. There was no evidence for plasma accumulation of famotidine with TID dosing as compared to BID dosing from either analysis. The data indicate that overall more time is spent above the acidic threshold pH values when 80 mg/day of famotidine is administered TID vs BID. Key limitations included small study size with a short duration and lack of a baseline examination, but was compensated for by the cross-over and PK/PD modeling design. Although most of the comparisons in this proof of concept study were not statistically significant these results have

  15. 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

  16. Whole-cell bioreporters and risk assessment of environmental pollution: A proof-of-concept study using lead

    International Nuclear Information System (INIS)

    Zhang, Xiaokai; Qin, Boqiang; Deng, Jianming; Wells, Mona

    2017-01-01

    As the world burden of environmental contamination increases, it is of the utmost importance to develop streamlined approaches to environmental risk assessment in order to prioritize mitigation measures. Whole-cell biosensors or bioreporters and speciation modeling have both become of increasing interest to determine the bioavailability of pollutants, as bioavailability is increasingly in use as an indicator of risk. Herein, we examine whether bioreporter results are able to reflect expectations based on chemical reactivity and speciation modeling, with the hope to extend the research into a wider framework of risk assessment. We study a specific test case concerning the bioavailability of lead (Pb) in aqueous environments containing Pb-complexing ligands. Ligands studied include ethylene diamine tetra-acetic acid (EDTA), meso-2,3 dimercaptosuccinic acid (DMSA), leucine, methionine, cysteine, glutathione, and humic acid (HA), and we also performed experiments using natural water samples from Lake Tai (Taihu), the third largest lake in China. We find that EDTA, DMSA, cysteine, glutathione, and HA amendment significantly reduced Pb bioavailability with increasing ligand concentration according to a log-sigmoid trend. Increasing dissolved organic carbon in Taihu water also had the same effect, whereas leucine and methionine had no notable effect on bioavailability at the concentrations tested. We find that bioreporter results are in accord with the reduction of aqueous Pb 2+ that we expect from the relative complexation affinities of the different ligands tested. For EDTA and HA, for which reasonably accurate ionization and complexation constants are known, speciation modeling is in agreement with bioreporter response to within the level of uncertainty recognised as reasonable by the United States Environmental Protection Agency for speciation-based risk assessment applications. These findings represent a first step toward using bioreporter technology to streamline

  17. Whole-cell bioreporters and risk assessment of environmental pollution: A proof-of-concept study using lead.

    Science.gov (United States)

    Zhang, Xiaokai; Qin, Boqiang; Deng, Jianming; Wells, Mona

    2017-10-01

    As the world burden of environmental contamination increases, it is of the utmost importance to develop streamlined approaches to environmental risk assessment in order to prioritize mitigation measures. Whole-cell biosensors or bioreporters and speciation modeling have both become of increasing interest to determine the bioavailability of pollutants, as bioavailability is increasingly in use as an indicator of risk. Herein, we examine whether bioreporter results are able to reflect expectations based on chemical reactivity and speciation modeling, with the hope to extend the research into a wider framework of risk assessment. We study a specific test case concerning the bioavailability of lead (Pb) in aqueous environments containing Pb-complexing ligands. Ligands studied include ethylene diamine tetra-acetic acid (EDTA), meso-2,3 dimercaptosuccinic acid (DMSA), leucine, methionine, cysteine, glutathione, and humic acid (HA), and we also performed experiments using natural water samples from Lake Tai (Taihu), the third largest lake in China. We find that EDTA, DMSA, cysteine, glutathione, and HA amendment significantly reduced Pb bioavailability with increasing ligand concentration according to a log-sigmoid trend. Increasing dissolved organic carbon in Taihu water also had the same effect, whereas leucine and methionine had no notable effect on bioavailability at the concentrations tested. We find that bioreporter results are in accord with the reduction of aqueous Pb 2+ that we expect from the relative complexation affinities of the different ligands tested. For EDTA and HA, for which reasonably accurate ionization and complexation constants are known, speciation modeling is in agreement with bioreporter response to within the level of uncertainty recognised as reasonable by the United States Environmental Protection Agency for speciation-based risk assessment applications. These findings represent a first step toward using bioreporter technology to streamline

  18. 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.

  19. First-in-Man Computed Tomography-Guided Percutaneous Revascularization of Coronary Chronic Total Occlusion Using a Wearable Computer: Proof of Concept.

    Science.gov (United States)

    Opolski, Maksymilian P; Debski, Artur; Borucki, Bartosz A; Szpak, Marcin; Staruch, Adam D; Kepka, Cezary; Witkowski, Adam

    2016-06-01

    We report a case of successful computed tomography-guided percutaneous revascularization of a chronically occluded right coronary artery using a wearable, hands-free computer with a head-mounted display worn by interventional cardiologists in the catheterization laboratory. The projection of 3-dimensional computed tomographic reconstructions onto the screen of virtual reality glass allowed the operators to clearly visualize the distal coronary vessel, and verify the direction of the guide wire advancement relative to the course of the occluded vessel segment. This case provides proof of concept that wearable computers can improve operator comfort and procedure efficiency in interventional cardiology. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  20. Gene Disruption in Scedosporium aurantiacum: Proof of Concept with the Disruption of SODC Gene Encoding a Cytosolic Cu,Zn-Superoxide Dismutase.

    Science.gov (United States)

    Pateau, Victoire; Razafimandimby, Bienvenue; Vandeputte, Patrick; Thornton, Christopher R; Guillemette, Thomas; Bouchara, Jean-Philippe; Giraud, Sandrine

    2018-02-01

    Scedosporium species are opportunistic pathogens responsible for a large variety of infections in humans. An increasing occurrence was observed in patients with underlying conditions such as immunosuppression or cystic fibrosis. Indeed, the genus Scedosporium ranks the second among the filamentous fungi colonizing the respiratory tracts of the CF patients. To date, there is very scarce information on the pathogenic mechanisms, at least in part because of the limited genetic tools available. In the present study, we successfully developed an efficient transformation and targeted gene disruption approach on the species Scedosporium aurantiacum. The disruption cassette was constructed using double-joint PCR procedure, and resistance to hygromycin B as the selection marker. This proof of concept was performed on the functional gene SODC encoding the Cu,Zn-superoxide dismutase. Disruption of the SODC gene improved susceptibility of the fungus to oxidative stress. This technical advance should open new research areas and help to better understand the biology of Scedosporium species.

  1. Using measures of wellbeing for impact evaluation: Proof of concept developed with an Indigenous community undertaking land management programs in northern Australia.

    Science.gov (United States)

    Larson, Silva; Stoeckl, Natalie; Jarvis, Diane; Addison, Jane; Prior, Sharon; Esparon, Michelle

    2018-05-05

    Combining insights from literature on the Theory of Change, Impact Evaluation, and Wellbeing, we develop a novel approach to assessing impacts. Intended beneficiaries identify and rate factors that are important to their wellbeing, their satisfaction with those factors now, and before an intervention. Qualitative responses to questions about perceived changes and causes of change are linked to quantitative data to draw inferences about the existence and/or importance of impact(s). We use data from 67 Ewamian people, in a case study relating to Indigenous land management, to provide proof of concept. 'Knowing that country is being looked after' and 'Having legal right/access to the country' were identified as important to wellbeing, with perceptions that Native Title determination, declared Indigenous Protected Area and associated land management programs have had a significant and positive impact on them. Further method testing might determine the utility of this approach in a wide range of settings.

  2. 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).

  3. Whole-body vibration as a mode of dyspnoea free physical activity: a community-based proof-of-concept trial.

    Science.gov (United States)

    Furness, Trentham; Joseph, Corey; Welsh, Liam; Naughton, Geraldine; Lorenzen, Christian

    2013-11-11

    The potential of whole-body vibration (WBV) as a mode of dyspnoea free physical activity for people with chronic obstructive pulmonary disease (COPD) is unknown among community-based settings. Furthermore, the acute effects of WBV on people with COPD have not been profiled in community-based settings. The aim of this community-based proof-of-concept trial was to describe acute effects of WBV by profiling subjective and objective responses to physical activity. Seventeen community-dwelling older adults with COPD were recruited to participate in two sessions; WBV and sham WBV (SWBV). Each session consisted of five one-minute bouts interspersed with five one-minute passive rest periods. The gravitational force was ~2.5 g for WBV and ~0.0 g for SWBV. Reliability of baseline dyspnoea, heart rate, and oxygen saturation was first established and then profiled for both sessions. Acute responses to both WBV and SWBV were compared with repeated measures analysis of variance and repeated contrasts. Small changes in dyspnoea and oxygen saturation lacked subjective and clinical meaningfulness. One session of WBV and SWBV significantly increased heart rate (p ≤ 0.02), although there was no difference among WBV and SWBV (p = 0.67). This community-based proof-of-concept trial showed that a session of WBV can be completed with the absence of dyspnoea for people with COPD. Furthermore, there were no meaningful differences among WBV and SWBV for heart rate and oxygen saturation. There is scope for long-term community-based intervention research using WBV given the known effects of WBV on peripheral muscle function and functional independence.

  4. 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.)

  5. Coupling HPLC-SPE-NMR with a microplate-based high-resolution antioxidant assay for efficient analysis of antioxidants in food--validation and proof-of-concept study with caper buds.

    Science.gov (United States)

    Wiese, Stefanie; Wubshet, Sileshi G; Nielsen, John; Staerk, Dan

    2013-12-15

    This work describes the coupling of a microplate-based antioxidant assay with a hyphenated system consisting of high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HPLC-SPE-NMR/high-resolution antioxidant assay, for the analysis of complex food extracts. The applicability of the microplate-based antioxidant assay for high-resolution screening of common food phenolics as well as parameters related to their trapping efficiency, elution behavior, and recovery on/from SPE cartridges are described. It was found that the microplate-based high-resolution antioxidant assay is an attractive and easy implementable alternative to direct on-line screening methods. Furthermore, it was shown that Resin SH and Resin GP SPE material are superior to RP C18HD for trapping of phenolic compounds. Proof-of-concept study was performed with caper bud extract, revealing the most important antioxidants to be quercetin, kaempferol, rutin, kaempferol-3-O-β-rutinoside and N(1),N(5),N(10)-triphenylpropenoyl spermidine amides. Targeted isolation of the latter, and comprehensive NMR experiments showed them to be N(1),N(10)-di-(E)-caffeoyl-N(5)-p-(E)-coumaroyl spermidine, N(1)-(E)-caffeoyl-N(5),N(10)-di-p-(E)-coumaroyl spermidine, N(10)-(E)-caffeoyl-N(1),N(5)-di-p-(E)-coumaroyl spermidine, and N(1),N(5),N(10)-tri-p-(E)-coumaroyl spermidine amides. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. 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

  7. Proof of Concept Integration of a Single-Level Service-Oriented Architecture into a Multi-Domain Secure Environment

    National Research Council Canada - National Science Library

    Gilkey, Craig M

    2008-01-01

    .... A SOA software platform integrates independent, unrelated applications into a common architecture, thereby introducing data reuse, interoperability, and loose coupling between the services involved. The U.S...

  8. 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). © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.

  9. 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

  10. 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

  11. 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

  12. Mobile phone-based evaluation of latent tuberculosis infection: Proof of concept for an integrated image capture and analysis system.

    Science.gov (United States)

    Naraghi, Safa; Mutsvangwa, Tinashe; Goliath, René; Rangaka, Molebogeng X; Douglas, Tania S

    2018-05-08

    The tuberculin skin test is the most widely used method for detecting latent tuberculosis infection in adults and active tuberculosis in children. We present the development of a mobile-phone based screening tool for measuring the tuberculin skin test induration. The tool makes use of a mobile application developed on the Android platform to capture images of an induration, and photogrammetric reconstruction using Agisoft PhotoScan to reconstruct the induration in 3D, followed by 3D measurement of the induration with the aid of functions from the Python programming language. The system enables capture of images by the person being screened for latent tuberculosis infection. Measurement precision was tested using a 3D printed induration. Real-world use of the tool was simulated by application to a set of mock skin indurations, created by a make-up artist, and the performance of the tool was evaluated. The usability of the application was assessed with the aid of a questionnaire completed by participants. The tool was found to measure the 3D printed induration with greater precision than the current ruler and pen method, as indicated by the lower standard deviation produced (0.3 mm versus 1.1 mm in the literature). There was high correlation between manual and algorithm measurement of mock skin indurations. The height of the skin induration and the definition of its margins were found to influence the accuracy of 3D reconstruction and therefore the measurement error, under simulated real-world conditions. Based on assessment of the user experience in capturing images, a simplified user interface would benefit wide-spread implementation. The mobile application shows good agreement with direct measurement. It provides an alternative method for measuring tuberculin skin test indurations and may remove the need for an in-person follow-up visit after test administration, thus improving latent tuberculosis infection screening throughput. Copyright © 2018 Elsevier Ltd

  13. List-Mode PET Motion Correction Using Markerless Head Tracking: Proof-of-Concept With Scans of Human Subject

    DEFF Research Database (Denmark)

    Olesen, Oline Vinter; Sullivan, Jenna M.; Mulnix, Tim

    2013-01-01

    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 $^{11}{\\rm C}$-racolopride on the high resolution research tomograph (HRRT) PET...... in contrast recovery of small structures....

  14. Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid: A proof-of-concept study.

    Science.gov (United States)

    Hirschfield, Gideon M; Gershwin, M Eric; Strauss, Richard; Mayo, Marlyn J; Levy, Cynthia; Zou, Bin; Johanns, Jewel; Nnane, Ivo P; Dasgupta, Bidisha; Li, Katherine; Selmi, Carlo; Marschall, Hanns-Ulrich; Jones, David; Lindor, Keith

    2016-07-01

    The interleukin (IL)-12 signaling cascade has been associated with primary biliary cholangitis (PBC). This multicenter, open-label, proof-of-concept study evaluated the anti-IL12/23 monoclonal antibody, ustekinumab (90 mg subcutaneous at weeks 0 and 4, then every 8 weeks through week 20), in adults with PBC and an inadequate response to ursodeoxycholic acid therapy (i.e., alkaline phosphatase [ALP] >1.67× upper limit of normal [ULN] after ≥6 months). ALP response was defined as a >40% decrease from baseline and ALP remission as ALP normalization (if baseline ALP 1.67×-2.8× ULN) or 2.8× ULN). Changes in Enhanced Liver Fibrosis (ELF) scores and serum bile acids were also assessed. At baseline, patients had median disease duration of 3.2 years, median ELF score of 9.8, and highly elevated total bile acid concentration (median, 43.3 μmol/L); 13 of 20 (65%) patients had baseline ALP >3× ULN. Although steady-state serum ustekinumab concentrations were reached by week 12, no patient achieved ALP response or remission. Median percent ALP reduction from baseline to week 28 was 12.1%. ELF score decreased slightly from baseline to week 28 (median reduction: 0.173), and total serum bile acid concentrations decreased from baseline to week 28 (median reduction: 8.8 μmol/L). No serious infections or discontinuations resulting from adverse events were reported through week 28. One patient had a serious upper gastrointestinal hemorrhage considered unrelated to test agent by the investigator. Open-label ustekinumab therapy, though associated with a modest decrease in ALP after 28 weeks of therapy, did not otherwise appreciably change ALP and overt proof-of-concept was not established as per prespecified primary endpoint of proposed efficacy. No new ustekinumab safety signals were observed. (Hepatology 2016;64:189-199). © 2015 by the American Association for the Study of Liver Diseases.

  15. Software and hardware developments for remote participation in TJ-II operation. Proof of concept using the NPA diagnostic

    International Nuclear Information System (INIS)

    Lopez, A.; Vega, J.; Montoro, A.; Sanchez, E.; Encabo, J.; Portas, A.; Balbin, R.; Fontdecaba, J.M.; Jimenez, J.A.; Dies, J.

    2002-01-01

    The operation protocols for the TJ-II require that all diagnostics be controlled remotely during machine operation. For this reason, most diagnostics have control systems that permit remote actions to be performed on their various subsystems. An Internet browser, which connects to a server where the human machine interfaces (HMIs) for all diagnostics are situated, is used for this. Real time control has been resolved using programmable automates for each diagnostic. Dedicated application software is in operation to provide a user interface for programming digitisers, for signal visualisation and for data processing during TJ-II discharges. This software is an event-based application that can be remotely launched from any X terminal. Other resources provided to users are graphical and computational tools for data analysis, data compression, off-line access to databases, reception of data and its integration in the databases at any moment. Two neutral particle analysers (NPAs) are operating on TJ-II to measure the energy spectra of charge exchange (CX) neutral particles. Protocols require remote control over several actions and subsystems of this diagnostic. With all these tools a proof of the concept of remote participation has being performed during the present experimental campaign. The NPA diagnostic has been operated from UPC-ETSEIB in Barcelona, 600 km of distance from the machine

  16. Proof of concept for continuous enantioselective liquid-liquid extraction in capillary microreactors using 1-octanol as a sustainable solvent

    NARCIS (Netherlands)

    Susanti, S.; Meinds, Tim G.; Pinxterhuis, Erik B.; Schuur, Boelo; De Vries, Johannes G.; Feringa, Ben L.; Winkelman, Jozef G.M.; Yue, Jun; Heeres, Hero J.

    2017-01-01

    The use of capillary microreactors for enantioselective liquid-liquid extraction (ELLE) was successfully demonstrated using a model system consisting of a buffered aqueous amino acid derivative (3,5-dinitrobenzoyl-(R,S)-leucine) solution (phosphate buffer, pH 6.58) and a chiral cinchona alkaloid

  17. Genome-wide prediction methods in highly diverse and heterozygous species: proof-of-concept through simulation in grapevine.

    Directory of Open Access Journals (Sweden)

    Agota Fodor

    Full Text Available Nowadays, genome-wide association studies (GWAS and genomic selection (GS methods which use genome-wide marker data for phenotype prediction are of much potential interest in plant breeding. However, to our knowledge, no studies have been performed yet on the predictive ability of these methods for structured traits when using training populations with high levels of genetic diversity. Such an example of a highly heterozygous, perennial species is grapevine. The present study compares the accuracy of models based on GWAS or GS alone, or in combination, for predicting simple or complex traits, linked or not with population structure. In order to explore the relevance of these methods in this context, we performed simulations using approx 90,000 SNPs on a population of 3,000 individuals structured into three groups and corresponding to published diversity grapevine data. To estimate the parameters of the prediction models, we defined four training populations of 1,000 individuals, corresponding to these three groups and a core collection. Finally, to estimate the accuracy of the models, we also simulated four breeding populations of 200 individuals. Although prediction accuracy was low when breeding populations were too distant from the training populations, high accuracy levels were obtained using the sole core-collection as training population. The highest prediction accuracy was obtained (up to 0.9 using the combined GWAS-GS model. We thus recommend using the combined prediction model and a core-collection as training population for grapevine breeding or for other important economic crops with the same characteristics.

  18. Applying advanced analytics to guide emergency department operational decisions: A proof-of-concept study examining the effects of boarding.

    Science.gov (United States)

    Andrew Taylor, R; Venkatesh, Arjun; Parwani, Vivek; Chekijian, Sharon; Shapiro, Marc; Oh, Andrew; Harriman, David; Tarabar, Asim; Ulrich, Andrew

    2018-01-04

    Emergency Department (ED) leaders are increasingly confronted with large amounts of data with the potential to inform and guide operational decisions. Routine use of advanced analytic methods may provide additional insights. To examine the practical application of available advanced analytic methods to guide operational decision making around patient boarding. Retrospective analysis of the effect of boarding on ED operational metrics from a single site between 1/2015 and 1/2017. Times series were visualized through decompositional techniques accounting for seasonal trends, to determine the effect of boarding on ED performance metrics and to determine the impact of boarding "shocks" to the system on operational metrics over several days. There were 226,461 visits with the mean (IQR) number of visits per day was 273 (258-291). Decomposition of the boarding count time series illustrated an upward trend in the last 2-3 quarters as well as clear seasonal components. All performance metrics were significantly impacted (pstudy regarding the use of advanced analytics in daily ED operations, time series analysis provided multiple useful insights into boarding and its impact on performance metrics. Copyright © 2018. Published by Elsevier Inc.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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. Published by Elsevier B.V.

  8. 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.

  9. Coordinating water conservation efforts through tradable credits: A proof of concept for drought response in the San Francisco Bay area

    Science.gov (United States)

    Gonzales, Patricia; Ajami, Newsha; Sun, Yujie

    2017-09-01

    Water utilities are increasingly relying on water efficiency and conservation to extend the availability of supplies. Despite spatial and institutional interdependency of many utilities, these demand-side management initiatives have traditionally been tackled by individual utilities operating in isolation. In this study, we introduce a policy framework for water conservation credits that enables collaboration at the regional scale. Under the proposed approach, utilities have the flexibility to invest in water conservation measures that are appropriate for their specific service area. When utilities have insufficient capacity for local cost-effective measures, they may opt to purchase credits, contributing to fund subsidies for utilities that do have that capacity and can provide the credits, while the region as a whole benefits from more reliable water supplies. This work aims to provide insights on the potential impacts of a water conservation credit policy framework when utilities are given the option to collaborate in their efforts. We model utility decisions as rational cost-minimizing actors subject to different decision-making dynamics and water demand scenarios, and demonstrate the institutional characteristics needed for the proposed policy to be effective. We apply this model to a counterfactual case study of water utility members of the Bay Area Water Supply and Conservation Agency in California during the drought period of June 2015 to May 2016. Our scenario analysis indicates that when the institutional structure and incentives are appropriately defined, water agencies can achieve economic benefits from collaborating in their conservation efforts, especially if they coordinate more closely in their decision-making.

  10. Integration of on-line imaging, plan adaptation and radiation delivery: proof of concept using digital tomosynthesis

    International Nuclear Information System (INIS)

    Mestrovic, Ante; Otto, Karl; Nichol, Alan; Clark, Brenda G

    2009-01-01

    The main objective of this manuscript is to propose a new approach to on-line adaptive radiation therapy (ART) in which daily image acquisition, plan adaptation and radiation delivery are integrated together and performed concurrently. A method is described in which on-line ART is performed based on intra-fractional digital tomosynthesis (DTS) images. Intra-fractional DTS images were reconstructed as the gantry rotated between treatment positions. An edge detection algorithm was used to automatically segment the DTS images as the gantry arrived at each treatment position. At each treatment position, radiation was delivered based on the treatment plan re-optimized for the most recent DTS image contours. To investigate the feasibility of this method, a model representing a typical prostate, bladder and rectum was used. To simulate prostate deformations, three clinically relevant, non-rigid deformations (small, medium and large) were modeled by systematically deforming the original anatomy. Using our approach to on-line ART, the original treatment plan was successfully adapted to arrive at a clinically acceptable plan for all three non-rigid deformations. In conclusion, we have proposed a new approach to on-line ART in which plan adaptation is performed based on intra-fractional DTS images. The study findings indicate that this approach can be used to re-optimize the original treatment plan to account for non-rigid anatomical deformations. The advantages of this approach are 1) image acquisition and radiation delivery are integrated in a single gantry rotation around the patient, reducing the treatment time, and 2) intra-fractional DTS images can be used to detect and correct for patient motion prior to the delivery of each beam (intra-fractional patient motion).

  11. 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.

  12. A health record integrated clinical decision support system to support prescriptions of pharmaceutical drugs in patients with reduced renal function: design, development and proof of concept.

    Science.gov (United States)

    Shemeikka, Tero; Bastholm-Rahmner, Pia; Elinder, Carl-Gustaf; Vég, Anikó; Törnqvist, Elisabeth; Cornelius, Birgitta; Korkmaz, Seher

    2015-06-01

    To develop and verify proof of concept for a clinical decision support system (CDSS) to support prescriptions of pharmaceutical drugs in patients with reduced renal function, integrated in an electronic health record system (EHR) used in both hospitals and primary care. A pilot study in one geriatric clinic, one internal medicine admission ward and two outpatient healthcare centers was evaluated with a questionnaire focusing on the usefulness of the CDSS. The usage of the system was followed in a log. The CDSS is considered to increase the attention on patients with impaired renal function, provides a better understanding of dosing and is time saving. The calculated glomerular filtration rate (eGFR) and the dosing recommendation classification were perceived useful while the recommendation texts and background had been used to a lesser extent. Few previous systems are used in primary care and cover this number of drugs. The global assessment of the CDSS scored high but some elements were used to a limited extent possibly due to accessibility or that texts were considered difficult to absorb. Choosing a formula for the calculation of eGFR in a CDSS may be problematic. A real-time CDSS to support kidney-related drug prescribing in both hospital and outpatient settings is valuable to the physicians. It has the potential to improve quality of drug prescribing by increasing the attention on patients with renal insufficiency and the knowledge of their drug dosing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. 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 (pbrain stress systems that are dysregulated in drug dependence and withdrawal. PMID:22373942

  14. 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. © 2014, The American College of Clinical Pharmacology.

  15. 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.

  16. Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

    Directory of Open Access Journals (Sweden)

    Wüthrich Rudolf P

    2007-09-01

    Full Text Available Abstract Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD. Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune® in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918

  17. Promoting the inclusion of Afghan women and men in research: reflections from research and community partners involved in implementing a 'proof of concept' project.

    Science.gov (United States)

    Riggs, Elisha; Yelland, Jane; Szwarc, Josef; Casey, Sue; Chesters, Donna; Duell-Piening, Philippa; Wahidi, Sayed; Fouladi, Fatema; Brown, Stephanie

    2015-01-31

    With mounting evidence that poor maternal and child health outcomes are related to the social determinants of health, researchers need to engage with vulnerable and isolated communities to gather the evidence that is essential to determine appropriate solutions. Conventional research methods may not ensure the degree and quality of participation that is necessary for meaningful study findings. Participatory methods provide reciprocal opportunities for often excluded communities to both take part in, and guide the conduct of research. The Having a baby in a new country research project was undertaken to provide evidence about how women and men of refugee background experience health services at the time of having a baby. This two year, multifaceted proof of concept study comprised: 1) an organisational partnership to oversee the project; 2) a community engagement framework including: female and male Afghan community researchers, community and sector stakeholder advisory groups and community consultation and engagement. Inclusive research strategies that address power imbalances in research, and diversity of and within communities, are necessary to obtain the evidence required to address health inequalities in vulnerable populations. Such an approach involves mindfully adapting research processes to ensure that studies have regard for the advice of community members about the issues that affect them. Researchers have much to gain by committing time and resources to engaging communities in reciprocal ways in research processes.

  18. A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF

    Directory of Open Access Journals (Sweden)

    Laëtitia Théron

    2016-10-01

    Full Text Available 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.

  19. 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.

  20. Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof-of-concept randomized trial.

    Science.gov (United States)

    Anguera, Joaquin A; Gunning, Faith M; Areán, Patricia A

    2017-06-01

    Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. In this proof-of-concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. EVO participants demonstrated similar improvements in mood and self-reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

  1. Understanding Social Situations (USS): A proof-of-concept social-cognitive intervention targeting theory of mind and attributional bias in individuals with psychosis.

    Science.gov (United States)

    Fiszdon, Joanna M; Roberts, David L; Penn, David L; Choi, Kee-Hong; Tek, Cenk; Choi, Jimmy; Bell, Morris D

    2017-03-01

    In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social-cognitive intervention that targets higher level social-cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social-cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social-cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social-cognitive measures. USS shows promise as a treatment for higher level social-cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. 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

    2012-06-01

    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 (pcannabis 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.

  3. Volumetric MR-Guided High-Intensity Focused Ultrasound with Direct Skin Cooling for the Treatment of Symptomatic Uterine Fibroids: Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Marlijne E. Ikink

    2015-01-01

    Full Text Available Objective. To prospectively assess the safety and technical feasibility of volumetric magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU ablation with direct skin cooling (DISC during treatment of uterine fibroids. Methods. In this proof-of-concept study, eight patients were consecutively selected for clinical MR-HIFU ablation of uterine fibroids with the use of an additional DISC device to maintain a constant temperature (T≈20°C at the interface between the HIFU table top and the skin. Technical feasibility was verified by successful completion of MR-HIFU ablation. Contrast-enhanced T1-weighted MRI was used to measure the treatment effect (nonperfused volume (NPV ratio. Safety was evaluated by recording of adverse events (AEs within 30 days’ follow-up. Results. All MR-HIFU treatments were successfully completed in an outpatient setting. The median NPV ratio was 0.56 (IQR [0.27–0.72]. Immediately after treatment, two patients experienced coldness related discomfort which resolved at the same day. No serious (device-related AEs were reported. Specifically, no skin burns, cold injuries, or subcutaneous edema were observed. Conclusion. This study showed that it is safe and technically feasible to complete a volumetric MR-HIFU ablation with DISC. This technique may reduce the risk of thermal injury to the abdominal wall during MR-HIFU ablation of uterine fibroids. This trial is registered with NTR4189.

  4. Music Recommendation System for Human Attention Modulation by Facial Recognition on a driving task: A Proof of Concept

    Directory of Open Access Journals (Sweden)

    Avila-Vázquez Roberto

    2017-01-01

    Full Text Available The role of music on driving process had been discussed in the context of driver assistance as an element of security and comfort. Throughout this document, we present the development of an audio recommender system for the use by drivers, based on facial expression analysis. This recommendation system has the objective of increasing the attention of the driver by the election of specific music pieces. For this pilot study, we start presenting an introduction to audio recommender systems and a brief explanation of the function of our facial expression analysis system. During the driving course the subjects (seven participants between 19 and 25 years old are stimulated with a chosen group of audio compositions and their facial expressions are captured via a camera mounted in the car's dashboard. Once the videos were captured and recollected, we proceeded to analyse them using the FACET™ module of the biometric capture platform iMotions™. This software provides us with the expression analysis of the subjects. Analysed data is postprocessed and the data obtained were modelled on a quadratic surface that was optimized based on the known cestrum and tempo of the songs and the average evidence of emotion. The results showed very different optimal points for each subject, that indicates different type of music for optimizing driving attention. This work is a first step for obtaining a music recommendation system capable to modulate subject attention while driving.

  5. Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof of Concept Study using Computational Fluid Dynamics

    Science.gov (United States)

    Rygg, Alex; Hindle, Michael; Longest, P. Worth

    2016-01-01

    The objective of this study is to link regional nasal spray deposition patterns of suspension formulations, predicted with computational fluid dynamics (CFD), to in vivo human pharmacokinetic (PK) plasma concentration profiles. This is accomplished through the use of CFD simulations coupled with compartmental PK modeling. Results showed a rapid initial rise in plasma concentration that is due to the absorption of drug particles deposited in the nasal middle passages, followed by a slower increase in plasma concentration that is governed by the transport of drug particles from the nasal vestibule to the middle passages. Although drug deposition locations in the nasal cavity had a significant effect on the shape of the concentration profile, the absolute bioavailability remained constant provided that all of the drug remained in the nose over the course of the simulation. Loss of drug through the nostrils even after long time periods resulted in a significant decrease in bioavailability and increased variability. The results of this study quantify how differences in nasal drug deposition affect transient plasma concentrations and overall bioavailability. These findings are potentially useful for establishing bioequivalence for nasal spray devices and reducing the burden of in vitro testing, pharmacodynamics and clinical studies. PMID:27238495

  6. The Longitudinal Force Measurement of CWR Tracks with Hetero-Cladding FBG Sensors: A Proof of Concept

    Directory of Open Access Journals (Sweden)

    Li-Yang Shao

    2016-12-01

    Full Text Available A new method has been proposed to accurately determine longitudinal additional force in continuous welded rail (CWR on bridges via hetero-cladding fiber Bragg grating (HC-FBG sensors. The HC-FBG sensor consists of two FBGs written in the same type of fiber but with different cladding diameters. The HC-FBGs have the same temperature sensitivity but different strain sensitivity because of the different areas of the cross section. The differential strain coefficient is defined as the relative wavelength differences of two FBGs with the change of applied longitudinal force. In the verification experiment in the lab, the HC-FBGs were attached on a section of rail model of which the material property is the same as that of rail on line. The temperature and differential strain sensitivity were calibrated using a universal testing machine. As shown by the test results, the linearity between the relative wavelength difference and the longitudinal additional force is greater than 0.9999. The differential strain sensitivity is 4.85 × 10−6/N. Moreover, the relative wavelength difference is not affected by the temperature change. Compared to the theoretical results, the accumulated error is controlled within 5.0%.

  7. Critical consideration of the multiplicity of experimental and organismic determinants of pyrethroid neurotoxicity: a proof of concept.

    Science.gov (United States)

    Wolansky, M J; Tornero-Velez, R

    2013-01-01

    Pyrethroids (PYR) are pesticides with high insecticidal activity that may disrupt neuronal excitability in target and nontarget species. The accumulated evidence consistently showed that this neurophysiologic action is followed by alterations in motor, sensorimotor, neuromuscular, and thermoregulatory responses. Nevertheless, there are some equivocal results regarding the potency of PYR in lab animals. The estimation of potency is an important step in pesticide chemical risk assessment. In order to identify the variables influencing neurobehavioral findings across PYR studies, evidence on experimental and organismic determinants of acute PYR-induced neurotoxicity was reviewed in rodents. A comprehensive analysis of these studies was conducted focusing on test material and dosing conditions, testing conditions, animal models, and other determinants such as testing room temperature. Variations in the severity of the neurotoxicity, under lab-controlled conditions, was explained based upon factors including influence of animal species and age, test material features such as chemical structure and stereochemistry, and dosing conditions such as vehicle, route of exposure, and dose volume. If not controlled, the interplay of these factors may lead to large variance in potency estimation. This review examined the scope of acute toxicological data required to determine the safety of pesticide products, and factors and covariates that need to be controlled in order to ensure that predictivity and precaution are balanced in a risk assessment process within a reasonable time-frame, using acute PYR-induced neurotoxicity in rodents as an exemplar.

  8. Evaluation of a flexible bronchoscope prototype designed for bronchoscopy during mechanical ventilation: a proof-of-concept study.

    Science.gov (United States)

    Nay, M-A; Auvet, A; Mankikian, J; Herve, V; Dequin, P-F; Guillon, A

    2017-06-01

    Bronchoscopy during mechanical ventilation of patients' lungs significantly affects ventilation because of partial obstruction of the tracheal tube, and may thus be omitted in the most severely ill patients. It has not previously been possible to reduce the external diameter of the bronchoscope without reducing the diameter of the suction channel, thus reducing the suctioning capacity of the device. We believed that a better-designed bronchoscope could improve the safety of bronchoscopy in patients whose lungs were ventilated. We designed a flexible bronchoscope prototype with a drumstick-shaped head consisting of a long, thin proximal portion; a short and large distal portion for camera docking; and a large suction channel throughout the length of the device. The aims of our study were to test the impact of our prototype on mechanical ventilation when inserted into the tracheal tube, and to assess suctioning capacity. We first tested the efficiency of the suction channel, and demonstrated that the suction flow of the prototype was similar to that of conventional adult bronchoscopes. We next evaluated the consequences of bronchoscopy when using the prototype on minute ventilation and intrathoracic pressures during mechanical ventilation: firstly, in vitro using a breathing simulator; and secondly, in vivo using a porcine model of pulmonary ventilation. The insertion of adult bronchoscopes into the tracheal tube immediately impaired the protective ventilation strategy employed, whereas the prototype preserved it. For the first time, we have developed an innovative flexible bronchoscope designed for bronchoscopy during invasive mechanical ventilation, that both preserved the protective ventilation strategy, and enabled efficient suction flow. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  9. Intracorporeal Heat Distribution from Fully Implantable Energy Sources for Mechanical Circulatory Support: A Computational Proof-of-Concept Study

    Directory of Open Access Journals (Sweden)

    Jacopo Biasetti

    2017-10-01

    Full Text Available Mechanical circulatory support devices, such as total artificial hearts and left ventricular assist devices, rely on external energy sources for their continuous operation. Clinically approved power supplies rely on percutaneous cables connecting an external energy source to the implanted device with the associated risk of infections. One alternative, investigated in the 70s and 80s, employs a fully implanted nuclear power source. The heat generated by the nuclear decay can be converted into electricity to power circulatory support devices. Due to the low conversion efficiencies, substantial levels of waste heat are generated and must be dissipated to avoid tissue damage, heat stroke, and death. The present work computationally evaluates the ability of the blood flow in the descending aorta to remove the locally generated waste heat for subsequent full-body distribution and dissipation, with the specific aim of investigating methods for containment of local peak temperatures within physiologically acceptable limits. To this aim, coupled fluid–solid heat transfer computational models of the blood flow in the human aorta and different heat exchanger architectures are developed. Particle tracking is used to evaluate temperature histories of cells passing through the heat exchanger region. The use of the blood flow in the descending aorta as a heat sink proves to be a viable approach for the removal of waste heat loads. With the basic heat exchanger design, blood thermal boundary layer temperatures exceed 50°C, possibly damaging blood cells and proteins. Improved designs of the heat exchanger, with the addition of fins and heat guides, allow for drastically lower blood temperatures, possibly leading to a more biocompatible implant. The ability to maintain blood temperatures at biologically compatible levels will ultimately allow for the body-wise distribution, and subsequent dissipation, of heat loads with minimum effects on the human physiology.

  10. Intracorporeal Heat Distribution from Fully Implantable Energy Sources for Mechanical Circulatory Support: A Computational Proof-of-Concept Study.

    Science.gov (United States)

    Biasetti, Jacopo; Pustavoitau, Aliaksei; Spazzini, Pier Giorgio

    2017-01-01

    Mechanical circulatory support devices, such as total artificial hearts and left ventricular assist devices, rely on external energy sources for their continuous operation. Clinically approved power supplies rely on percutaneous cables connecting an external energy source to the implanted device with the associated risk of infections. One alternative, investigated in the 70s and 80s, employs a fully implanted nuclear power source. The heat generated by the nuclear decay can be converted into electricity to power circulatory support devices. Due to the low conversion efficiencies, substantial levels of waste heat are generated and must be dissipated to avoid tissue damage, heat stroke, and death. The present work computationally evaluates the ability of the blood flow in the descending aorta to remove the locally generated waste heat for subsequent full-body distribution and dissipation, with the specific aim of investigating methods for containment of local peak temperatures within physiologically acceptable limits. To this aim, coupled fluid-solid heat transfer computational models of the blood flow in the human aorta and different heat exchanger architectures are developed. Particle tracking is used to evaluate temperature histories of cells passing through the heat exchanger region. The use of the blood flow in the descending aorta as a heat sink proves to be a viable approach for the removal of waste heat loads. With the basic heat exchanger design, blood thermal boundary layer temperatures exceed 50°C, possibly damaging blood cells and proteins. Improved designs of the heat exchanger, with the addition of fins and heat guides, allow for drastically lower blood temperatures, possibly leading to a more biocompatible implant. The ability to maintain blood temperatures at biologically compatible levels will ultimately allow for the body-wise distribution, and subsequent dissipation, of heat loads with minimum effects on the human physiology.

  11. Biological anoxic treatment of O2-free VOC emissions from the petrochemical industry: A proof of concept study

    International Nuclear Information System (INIS)

    Muñoz, Raúl; Souza, Theo S.O.; Glittmann, Lina; Pérez, Rebeca; Quijano, Guillermo

    2013-01-01

    Highlights: • The treatment of O 2 -free VOC emissions can be done by means of denitrifying processes. •Toluene vapors were successfully removed under anoxic denitrifying conditions. • A high bacterial diversity was observed. • Actinobacteria and Proteobacteria were the predominant phyla. • The nature and number of metabolites accumulated varied with the toluene load -- Abstract: An innovative biofiltration technology based on anoxic biodegradation was proposed in this work for the treatment of inert VOC-laden emissions from the petrochemical industry. Anoxic biofiltration does not require conventional O 2 supply to mineralize VOCs, which increases process safety and allows for the reuse of the residual gas for inertization purposes in plant. The potential of this technology was evaluated in a biotrickling filter using toluene as a model VOC at loads of 3, 5, 12 and 34 g m −3 h −1 (corresponding to empty bed residence times of 16, 8, 4 and 1.3 min) with a maximum elimination capacity of ∼3 g m −3 h −1 . However, significant differences in the nature and number of metabolites accumulated at each toluene load tested were observed, o- and p-cresol being detected only at 34 g m −3 h −1 , while benzyl alcohol, benzaldehyde and phenol were detected at lower loads. A complete toluene removal was maintained after increasing the inlet toluene concentration from 0.5 to 1 g m −3 (which entailed a loading rate increase from 3 to 6 g m −3 h −1 ), indicating that the system was limited by mass transfer rather than by biological activity. A high bacterial diversity was observed, the predominant phyla being Actinobacteria and Proteobacteria

  12. Biological anoxic treatment of O{sub 2}-free VOC emissions from the petrochemical industry: A proof of concept study

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Raúl; Souza, Theo S.O. [Department of Chemical Engineering and Environmental Technology, University of Valladolid, Dr Mergelina s/n, 47011 Valladolid (Spain); Glittmann, Lina [Ostfalia University of Applied Sciences, Department of Supply Engineering, Wolfenbüttel (Germany); Pérez, Rebeca [Department of Chemical Engineering and Environmental Technology, University of Valladolid, Dr Mergelina s/n, 47011 Valladolid (Spain); Quijano, Guillermo [Department of Chemical Engineering and Environmental Technology, University of Valladolid, Dr Mergelina s/n, 47011 Valladolid (Spain)

    2013-09-15

    Highlights: • The treatment of O{sub 2}-free VOC emissions can be done by means of denitrifying processes. •Toluene vapors were successfully removed under anoxic denitrifying conditions. • A high bacterial diversity was observed. • Actinobacteria and Proteobacteria were the predominant phyla. • The nature and number of metabolites accumulated varied with the toluene load -- Abstract: An innovative biofiltration technology based on anoxic biodegradation was proposed in this work for the treatment of inert VOC-laden emissions from the petrochemical industry. Anoxic biofiltration does not require conventional O{sub 2} supply to mineralize VOCs, which increases process safety and allows for the reuse of the residual gas for inertization purposes in plant. The potential of this technology was evaluated in a biotrickling filter using toluene as a model VOC at loads of 3, 5, 12 and 34 g m{sup −3} h{sup −1} (corresponding to empty bed residence times of 16, 8, 4 and 1.3 min) with a maximum elimination capacity of ∼3 g m{sup −3} h{sup −1}. However, significant differences in the nature and number of metabolites accumulated at each toluene load tested were observed, o- and p-cresol being detected only at 34 g m{sup −3} h{sup −1}, while benzyl alcohol, benzaldehyde and phenol were detected at lower loads. A complete toluene removal was maintained after increasing the inlet toluene concentration from 0.5 to 1 g m{sup −3} (which entailed a loading rate increase from 3 to 6 g m{sup −3} h{sup −1}), indicating that the system was limited by mass transfer rather than by biological activity. A high bacterial diversity was observed, the predominant phyla being Actinobacteria and Proteobacteria.

  13. Augmented reality fluoroscopy simulation of the guide-wire insertion in DHS surgery: A proof of concept study.

    Science.gov (United States)

    van Duren, B H; Sugand, K; Wescott, R; Carrington, R; Hart, A

    2018-05-01

    workshop bone models. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

  14. Strengthening Government Leadership in Family Planning Programming in Senegal: From Proof of Concept to Proof of Implementation in 2 Districts.

    Science.gov (United States)

    Aichatou, Barry; Seck, Cheikh; Baal Anne, Thierno Souleymane; Deguenovo, Gabrielle Clémentine; Ntabona, Alexis; Simmons, Ruth

    2016-12-23

    Given Senegal's limited resources, the country receives substantial support from externally funded partner organizations to provide family planning and maternal and child health services. These organizations often take a strong and sometimes independent role in implementing interventions with their own structures and personnel, thereby bypassing the government district health system. This article presents findings from the Initiative Sénégalaise de Santé Urbaine (ISSU) (Senegal Urban Health Initiative) that assessed in 2 districts, Diamniadio and Rufisque, the extent to which it was feasible to create stronger government ownership and leadership in implementing a simplified package of family planning interventions from among those previously tested in other districts. The simplified package consisted of both supply- and demand-side interventions, introduced in October 2014 and concluding at the end of 2015. The interventions included ensuring adequate human resources and contraceptive supplies, contraceptive technology updates for providers, special free family planning service days to bring services closer to where people live, family planning integration into other routine services, household visits for family planning education, religious sermons to clarify Islam's position on family planning, and radio broadcasts. District leadership in Diamniadio and Rufisque were actively involved in guiding and implementing interventions, and they also contributed some of their own resources to the project. However, reliance on external funding continued because district budgets were extremely limited. Monitoring data on the number of contraceptive methods provided by district facilities supported by a sister project, the Informed Push Model project, indicate overall improvement in contraceptive provision during the intervention period. In Diamniadio, contraceptive provision increased by 43% between the 6-month period prior to the ISSU interventions (November 2013 through

  15. Noninvasive calculation of the aortic blood pressure waveform from the flow velocity waveform: a proof of concept.

    Science.gov (United States)

    Vennin, Samuel; Mayer, Alexia; Li, Ye; Fok, Henry; Clapp, Brian; Alastruey, Jordi; Chowienczyk, Phil

    2015-09-01

    Estimation of aortic and left ventricular (LV) pressure usually requires measurements that are difficult to acquire during the imaging required to obtain concurrent LV dimensions essential for determination of LV mechanical properties. We describe a novel method for deriving aortic pressure from the aortic flow velocity. The target pressure waveform is divided into an early systolic upstroke, determined by the water hammer equation, and a diastolic decay equal to that in the peripheral arterial tree, interposed by a late systolic portion described by a second-order polynomial constrained by conditions of continuity and conservation of mean arterial pressure. Pulse wave velocity (PWV, which can be obtained through imaging), mean arterial pressure, diastolic pressure, and diastolic decay are required inputs for the algorithm. The algorithm was tested using 1) pressure data derived theoretically from prespecified flow waveforms and properties of the arterial tree using a single-tube 1-D model of the arterial tree, and 2) experimental data acquired from a pressure/Doppler flow velocity transducer placed in the ascending aorta in 18 patients (mean ± SD: age 63 ± 11 yr, aortic BP 136 ± 23/73 ± 13 mmHg) at the time of cardiac catheterization. For experimental data, PWV was calculated from measured pressures/flows, and mean and diastolic pressures and diastolic decay were taken from measured pressure (i.e., were assumed to be known). Pressure reconstructed from measured flow agreed well with theoretical pressure: mean ± SD root mean square (RMS) error 0.7 ± 0.1 mmHg. Similarly, for experimental data, pressure reconstructed from measured flow agreed well with measured pressure (mean RMS error 2.4 ± 1.0 mmHg). First systolic shoulder and systolic peak pressures were also accurately rendered (mean ± SD difference 1.4 ± 2.0 mmHg for peak systolic pressure). This is the first noninvasive derivation of aortic pressure based on fluid dynamics (flow and wave speed) in the

  16. Detection and characterisation of deep-sea benthopelagic animals from an autonomous underwater vehicle with a multibeam echosounder: A proof of concept and description of data-processing methods

    Science.gov (United States)

    Dunlop, Katherine M.; Jarvis, Toby; Benoit-Bird, Kelly J.; Waluk, Chad M.; Caress, David W.; Thomas, Hans; Smith, Kenneth L.

    2018-04-01

    Benthopelagic animals are an important component of the deep-sea ecosystem, yet are notoriously difficult to study. Multibeam echosounders (MBES) deployed on autonomous underwater vehicles (AUVs) represent a promising technology for monitoring this elusive fauna at relatively high spatial and temporal resolution. However, application of this remote-sensing technology to the study of small (relative to the sampling resolution), dispersed and mobile animals at depth does not come without significant challenges with respect to data collection, data processing and vessel avoidance. As a proof of concept, we used data from a downward-looking RESON SeaBat 7125 MBES mounted on a Dorado-class AUV to detect and characterise the location and movement of backscattering targets (which were likely to have been individual fish or squid) within 50 m of the seafloor at 800 m depth in Monterey Bay, California. The targets were detected and tracked, enabling their numerical density and movement to be characterised. The results revealed a consistent movement of targets downwards away from the AUV that we interpreted as an avoidance response. The large volume and complexity of the data presented a computational challenge, while reverberation and noise, spatial confounding and a marginal sampling resolution relative to the size of the targets caused difficulties for reliable and comprehensive target detection and tracking. Nevertheless, the results demonstrate that an AUV-mounted MBES has the potential to provide unique and detailed information on the in situ abundance, distribution, size and behaviour of both individual and aggregated deep-sea benthopelagic animals. We provide detailed data-processing information for those interested in working with MBES water-column data, and a critical appraisal of the data in the context of aquatic ecosystem research. We consider future directions for deep-sea water-column echosounding, and reinforce the importance of measures to mitigate vessel

  17. The efficacy and tolerability of 5-aminolevulinic acid 5% thermosetting gel photodynamic therapy (PDT) in the treatment of mild-to-moderate acne vulgaris. A two-center, prospective assessor-blinded, proof-of-concept study.

    Science.gov (United States)

    Serini, Stefano Maria; Cannizzaro, Maria Vittoria; Dattola, Annunziata; Garofalo, Virginia; Del Duca, Esther; Ventura, Alessandra; Milani, Massimo; Campione, Elena; Bianchi, Luca

    2018-05-22

    Acne vulgaris is a chronic inflammatory skin disease, commonly treated with topical or systemic drugs, according to the severity of the condition. Retinoids and antibiotic compounds are considered cornerstone approaches in this condition. However, low adherence to the therapy and the issue of bacterial resistance undermine the efficacy in the long term. Photodynamic therapy (PDT) with 20% aminolevulinic acid (ALA) has shown to be effective in the treatment of inflammatory acne. Skin tolerability, however, could be a limiting factor for a widespread use of this approach. A new formulation of 5% ALA in thermosetting gel has been recently available. This formulation allows a more convenient application procedure without occlusion and better and more efficient release of the active compound in comparison with traditional ALA formulations like creams or ointments. To evaluate in a two-center, assessor-blinded, prospective, proof-of-concept study, the efficacy, and tolerability of red-light (630 nm) PDT with a new 5-ALA "low-dose" topical gel formulation (5%) in the treatment of inflammatory mild-to-moderate acne vulgaris (AV). A total of 35 subjects with moderate AV of the face (mean age: 24 ± 8 years, 13 men and 22 women) were enrolled, after their written informed consent. The primary outcome was the evolution of GAG (Global Acne Grade System) score at baseline and after an average of three, 630-nm, 15-minute, PDT sessions, performed every 2 weeks. GAG score was also calculated in a follow-up visit 6 months after the last PDT session. Skin tolerability was assessed during PDT sessions with a patient-reported discomfort level evaluation score from 0 (no discomfort at all) to 3 (severe discomfort). At baseline, the GAG score was 21 ± 6. After the last PDT session, the GAG score evaluated in a blinded fashion (digital photographs) was significantly reduced to 6.5 ± 5.7, representing a 70% reduction (P = .0001, Wilcoxon test; mean difference 14.9; 95% CI of

  18. Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Satlin, Andrew; Wang, Jinping; Logovinsky, Veronika; Berry, Scott; Swanson, Chad; Dhadda, Shobha; Berry, Donald A

    2016-01-01

    Recent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly. We designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics. The study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. Bayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.

  19. First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment

    Science.gov (United States)

    Raaymakers, B. W.; Jürgenliemk-Schulz, I. M.; Bol, G. H.; Glitzner, M.; Kotte, A. N. T. J.; van Asselen, B.; de Boer, J. C. J.; Bluemink, J. J.; Hackett, S. L.; Moerland, M. A.; Woodings, S. J.; Wolthaus, J. W. H.; van Zijp, H. M.; Philippens, M. E. P.; Tijssen, R.; Kok, J. G. M.; de Groot-van Breugel, E. N.; Kiekebosch, I.; Meijers, L. T. C.; Nomden, C. N.; Sikkes, G. G.; Doornaert, P. A. H.; Eppinga, W. S. C.; Kasperts, N.; Kerkmeijer, L. G. W.; Tersteeg, J. H. A.; Brown, K. J.; Pais, B.; Woodhead, P.; Lagendijk, J. J. W.

    2017-12-01

    The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

  20. A randomized, double-blind, placebo-controlled proof of concept study to evaluate samidorphan in the prevention of olanzapine-induced weight gain in healthy volunteers.

    Science.gov (United States)

    Silverman, Bernard L; Martin, William; Memisoglu, Asli; DiPetrillo, Lauren; Correll, Christoph U; Kane, John M

    2017-11-17

    Antipsychotic medications are associated with weight gain and adverse metabolic effects that complicate the treatment and management of schizophrenia. Olanzapine (OLZ) in particular is associated with significant weight gain and adverse metabolic effects. The present Phase 1, proof of concept, multicenter, randomized, double-blind, placebo-controlled study investigated the safety and effect on weight of a combination of OLZ (10mg) and the opioid modulator samidorphan (SAM; 5mg) in comparison to OLZ alone in healthy, male normal weight volunteers. Altogether, 106 male subjects with stable body weight and BMI 18-25kg/m 2 were randomized to OLZ alone, OLZ+SAM, SAM alone, or placebo in a 2:2:1:1 ratio. The primary efficacy endpoint, mean (SD) body weight change from baseline to last assessment in the 3-week treatment period, was significantly less for OLZ+SAM vs. OLZ alone subjects [+2.2 (1.4) kg vs. +3.1 (1.9) kg; respectively; p=0.02]. In contrast, there was no significant difference in weight from baseline for either SAM or placebo [+0.1 (1.0) kg and +0.8 (1.4) kg, respectively]; p=0.09. Overall, OLZ+SAM compared to OLZ alone had similar safety and tolerability. In addition, less nausea was observed in subjects given OLZ+SAM compared to SAM alone. Thus, OLZ+SAM may offer effective treatment of schizophrenia with less weight gain and metabolic risk. Additional research exploring additional doses over longer durations in psychiatric populations is warranted. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Pulmonary hyperpolarized (129) Xe morphometry for mapping xenon gas concentrations and alveolar oxygen partial pressure: Proof-of-concept demonstration in healthy and COPD subjects.

    Science.gov (United States)

    Ouriadov, A; Farag, A; Kirby, M; McCormack, D G; Parraga, G; Santyr, G E

    2015-12-01

    Diffusion-weighted (DW) hyperpolarized (129) Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pA O2 ) maps by extracting the unrestricted diffusion coefficient (D0 ) of xenon as a morphometric parameter. In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm(2) ) DW hyperpolarized (129) Xe images obtained in four never-smokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pA O2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. Xenon D0 was significantly increased (P = 0.035) in COPD (0.14 ± 0.03 cm(2) /s) compared with never-smokers (0.12 ± 0.02 cm(2) /s). COPD ex-smokers also had significantly decreased [Xe] (COPD = 8 ± 7% versus never-smokers = 13 ± 8%, P = 0.012) and increased pA O2 (COPD = 18 ± 3% versus never-smokers = 15 ± 3%, P = 0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. DW hyperpolarized (129) Xe MRI morphometry can be used to simultaneously map [Xe] and pA O2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0 ([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity. © 2014 Wiley Periodicals, Inc.

  2. Hybrid Assistive Limb Exoskeleton HAL in the Rehabilitation of Chronic Spinal Cord Injury: Proof of Concept; the Results in 21 Patients.

    Science.gov (United States)

    Jansen, Oliver; Grasmuecke, Dennis; Meindl, Renate C; Tegenthoff, Martin; Schwenkreis, Peter; Sczesny-Kaiser, Matthias; Wessling, Martin; Schildhauer, Thomas A; Fisahn, Christian; Aach, Mirko

    2018-02-01

    The use of mobile exoskeletons is becoming more and more common in the field of spinal cord injury (SCI) rehabilitation. The hybrid assistive limb (HAL) exoskeleton provides a tailored support depending on the patient's voluntary drive. After a pilot study in 2014 that included 8 patients with chronic SCI, this study of 21 patients with chronic SCI serves as a proof of concept. It was conducted to provide further evidence regarding the efficacy of exoskeletal-based rehabilitation. Functional assessment included walking speed, distance, and time on a treadmill, with additional analysis of functional mobility using the following tests: 10-meter walk test (10MWT), timed up and go (TUG) test, 6-minute walk test (6MWT), and the walking index for SCI II (WISCI-II) score. After a training period of 90 days, all 21 patients significantly improved their functional and ambulatory mobility without the exoskeleton. Patients were assessed by the 6MWT, the TUG test, and the 10MWT, which also indicated an increase in the WISCI-II score along with significant improvements in HAL-associated walking speed, distance, and time. Although, exoskeletons are not yet an established treatment in the rehabilitation of spinal cord injuries, the devices will play a more important role in the future. The HAL exoskeleton training enables effective, body weight-supported treadmill training and is capable of improving ambulatory mobility. Future controlled studies are required to enable a comparison of the new advances in the field of SCI rehabilitation with traditional over-ground training. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Novel Automated Slide-Based Technology for Visualization, Counting, and Characterization of the Formed Elements of Blood: A Proof of Concept Study.

    Science.gov (United States)

    Winkelman, James W; Tanasijevic, Milenko J; Zahniser, David J

    2017-08-01

    - A novel automated slide-based approach to the complete blood count and white blood cell differential count is introduced. - To present proof of concept for an image-based approach to complete blood count, based on a new slide preparation technique. A preliminary data comparison with the current flow-based technology is shown. - A prototype instrument uses a proprietary method and technology to deposit a precise volume of undiluted peripheral whole blood in a monolayer onto a glass microscope slide so that every cell can be distinguished, counted, and imaged. The slide is stained, and then multispectral image analysis is used to measure the complete blood count parameters. Images from a 600-cell white blood cell differential count, as well as 5000 red blood cells and a variable number of platelets, that are present in 600 high-power fields are made available for a technologist to view on a computer screen. An initial comparison of the basic complete blood count parameters was performed, comparing 1857 specimens on both the new instrument and a flow-based hematology analyzer. - Excellent correlations were obtained between the prototype instrument and a flow-based system. The primary parameters of white blood cell, red blood cell, and platelet counts resulted in correlation coefficients (r) of 0.99, 0.99, and 0.98, respectively. Other indices included hemoglobin (r = 0.99), hematocrit (r = 0.99), mean cellular volume (r = 0.90), mean corpuscular hemoglobin (r = 0.97), and mean platelet volume (r = 0.87). For the automated white blood cell differential counts, r values were calculated for neutrophils (r = 0.98), lymphocytes (r = 0.97), monocytes (r = 0.76), eosinophils (r = 0.96), and basophils (r = 0.63). - Quantitative results for components of the complete blood count and automated white blood cell differential count can be developed by image analysis of a monolayer preparation of a known volume of peripheral blood.

  4. Breath-print analysis by e-nose for classifying and monitoring chronic liver disease: a proof-of-concept study.

    Science.gov (United States)

    De Vincentis, Antonio; Pennazza, Giorgio; Santonico, Marco; Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; Vernile, Chiara; Pedone, Claudio; Antonelli Incalzi, Raffaele; Picardi, Antonio

    2016-05-05

    Since the liver plays a key metabolic role, volatile organic compounds in the exhaled breath might change with type and severity of chronic liver disease (CLD). In this study we analysed breath-prints (BPs) of 65 patients with liver cirrhosis (LC), 39 with non-cirrhotic CLD (NC-CLD) and 56 healthy controls by the e-nose. Distinctive BPs characterized LC, NC-CLD and healthy controls, and, among LC patients, the different Child-Pugh classes (sensitivity 86.2% and specificity 98.2% for CLD vs healthy controls, and 87.5% and 69.2% for LC vs NC-CLD). Moreover, the area under the BP profile, derived from radar-plot representation of BPs, showed an area under the ROC curve of 0.84 (95% CI 0.76-0.91) for CLD, of 0.76 (95% CI 0.66-0.85) for LC, and of 0.70 (95% CI 0.55-0.81) for decompensated LC. By applying the cut-off values of 862 and 812, LC and decompensated LC could be predicted with high accuracy (PPV 96.6% and 88.5%, respectively). These results are proof-of-concept that the e-nose could be a valid non-invasive instrument for characterizing CLD and monitoring hepatic function over time. The observed classificatory properties might be further improved by refining stage-specific breath-prints and considering the impact of comorbidities in a larger series of patients.

  5. Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study.

    Science.gov (United States)

    Smits, Loek P; Coolen, Bram F; Panno, Maria D; Runge, Jurgen H; Nijhof, Wouter H; Verheij, Joanne; Nieuwdorp, Max; Stoker, Jaap; Beuers, Ulrich H; Nederveen, Aart J; Stroes, Erik S

    2016-03-01

    To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis. This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve. Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P steatosis was 0.87 (95% confidence interval: 0.72, 1.00). This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis.

  6. Skin conductance biofeedback training in adults with drug-resistant temporal lobe epilepsy and stress-triggered seizures: a proof-of-concept study.

    Science.gov (United States)

    Micoulaud-Franchi, Jean-Arthur; Kotwas, Iliana; Lanteaume, Laura; Berthet, Christelle; Bastien, Mireille; Vion-Dury, Jean; McGonigal, Aileen; Bartolomei, Fabrice

    2014-12-01

    The present proof-of-concept study investigated the feasibility of skin conductance biofeedback training in reducing seizures in adults with drug-resistant temporal lobe epilepsy (TLE), whose seizures are triggered by stress. Skin conductance biofeedback aims to increase levels of peripheral sympathetic arousal in order to reduce cortical excitability. This might seem somewhat counterintuitive, since such autonomic arousal may also be associated with increased stress and anxiety. Thus, this sought to verify that patients with TLE and stress-triggered seizures are not worsened in terms of stress, anxiety, and negative emotional response to this nonpharmacological treatment. Eleven patients with drug-resistant TLE with seizures triggered by stress were treated with 12 sessions of biofeedback. Patients did not worsen on cognitive evaluation of attentional biases towards negative emotional stimuli (P>.05) or on psychometric evaluation with state anxiety inventory (P = .059); in addition, a significant improvement was found in the Negative Affect Schedule (P = .014) and in the Beck Depression Inventory (P = .009). Biofeedback training significantly reduced seizure frequency with a mean reduction of -48.61% (SD = 27.79) (P = .005). There was a correlation between the mean change in skin conductance activity over the biofeedback treatment and the reduction of seizure frequency (r(11) = .62, P = .042). Thus, the skin conductance biofeedback used in the present study, which teaches patients to achieve an increased level of peripheral sympathetic arousal, was a well-tolerated nonpharmacological treatment. Further, well-controlled studies are needed to confirm the therapeutic value of this nonpharmacological treatment in reducing seizures in adults with drug-resistant TLE with seizures triggered by stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study.

    Science.gov (United States)

    Yu, Lilei; Huang, Bing; Po, Sunny S; Tan, Tuantuan; Wang, Menglong; Zhou, Liping; Meng, Guannan; Yuan, Shenxu; Zhou, Xiaoya; Li, Xuefei; Wang, Zhuo; Wang, Songyun; Jiang, Hong

    2017-08-14

    The aim of this study was to investigate whether low-level tragus stimulation (LL-TS) treatment could reduce myocardial ischemia-reperfusion injury in patients with ST-segment elevation myocardial infarction (STEMI). The authors' previous studies suggested that LL-TS could reduce the size of myocardial injury induced by ischemia. Patients who presented with STEMI within 12 h of symptom onset, treated with primary percutaneous coronary intervention, were randomized to the LL-TS group (n = 47) or the control group (with sham stimulation [n = 48]). LL-TS, 50% lower than the electric current that slowed the sinus rate, was delivered to the right tragus once the patients arrived in the catheterization room and lasted for 2 h after balloon dilatation (reperfusion). All patients were followed for 7 days. The occurrence of reperfusion-related arrhythmia, blood levels of creatine kinase-MB, myoglobin, N-terminal pro-B-type natriuretic peptide and inflammatory markers, and echocardiographic characteristics were evaluated. The incidence of reperfusion-related ventricular arrhythmia during the first 24 h was significantly attenuated by LL-TS. In addition, the area under the curve for creatine kinase-MB and myoglobin over 72 h was smaller in the LL-TS group than the control group. Furthermore, blood levels of inflammatory markers were decreased by LL-TS. Cardiac function, as demonstrated by the level of N-terminal pro-B-type natriuretic peptide, the left ventricular ejection fraction, and the wall motion index, was markedly improved by LL-TS. LL-TS reduces myocardial ischemia-reperfusion injury in patients with STEMI. This proof-of-concept study raises the possibility that this noninvasive strategy may be used to treat patients with STEMI undergoing primary percutaneous coronary intervention. Copyright © 2017. Published by Elsevier Inc.

  8. A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control

    OpenAIRE

    Shannon, R; Nelson, A

    2017-01-01

    To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, cont...

  9. A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.

    Science.gov (United States)

    Toniolo, Ricardo Alexandre; Silva, Michelle; Fernandes, Francy de Brito Ferreira; Amaral, José Antonio de Mello Siqueira; Dias, Rodrigo da Silva; Lafer, Beny

    2018-02-01

    Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression. We conducted a double-blind trial in which 35 patients with bipolar disorder type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17) or placebo (N = 18). Primary efficacy was assessed by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS). We did not find a statistically significant difference in the comparison between groups for the change in score on the MADRS after 6 weeks in an intention-to-treat (ITT) analysis (p = 0.560; Cohen's d = 0.231). However, we found significant superiority of creatine add-on vs. placebo when we considered the remission criterion of a MADRS score ≤ 12 at week 6 analyzing the outcome of the 35 randomized patients on ITT (52.9% remission in the creatine group vs. 11.1% remission in the placebo group) and of the 23 completers (66.7% remission in the creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched to hypomania/mania early in the trial. No clinically relevant physical side-effects were reported or observed. This proof-of-concept study, aiming to restore brain bioenergetics using an adjunctive mitochondrial modulator, is not conclusive on the efficacy of creatine add-on for bipolar

  10. Carbohydrate restricted diet in conjunction with metformin and liraglutide is an effective treatment in patients with deteriorated type 2 diabetes mellitus: Proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Müller Jürgen E

    2011-12-01

    Full Text Available Abstract Background Type 2 diabetes mellitus is a chronic progressive disease. During the course of the disease intensive treatment is often necessary resulting in multiple interventions including administration of insulin. Although dietary intervention is highly recommended, the clinical results of the widely prescribed diets with low fat content and high carbohydrates are disappointing. In this proof-of-concept study, we tested the effect of dietary carbohydrate-restriction in conjunction with metformin and liraglutide on metabolic control in patients with type 2 diabetes. Methods Forty patients with type 2 diabetes already being treated with two oral anti-diabetic drugs or insulin treatment and who showed deterioration of their glucose metabolism (i.e. HbA1c >7.5, were treated. A carbohydrate-restricted diet and a combination of metformin and liraglutide were instituted, after stopping either insulin or oral anti-diabetic drugs (excluding metformin. After enrollment, the study patients were scheduled for follow-up visits at one, two, three and six months. Primary outcome was glycemic control, measured by HbA1c at six months. Secondary outcomes were body weight, lipid-profile and treatment satisfaction. Results Thirty-five (88% participants completed the study. Nearly all participating patients experienced a drop in HbA1c and body weight during the first three months, an effect which was maintained until the end of the study at six months. Seventy-one percent of the patients reached HbA1c values below 7.0%. The range of body weight at enrollment was extreme, reaching 165 kg as the highest initial value. The average weight loss after 6 months was 10%. Most patients were satisfied with this treatment. During the intervention no significant change of lipids was observed. Most patients who were on insulin could maintain the treatment without insulin with far better metabolic control. Conclusions Carbohydrate restriction in conjunction with

  11. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial.

    Science.gov (United States)

    Roberts, Jason D; Wells, George A; Le May, Michel R; Labinaz, Marino; Glover, Chris; Froeschl, Michael; Dick, Alexander; Marquis, Jean-Francois; O'Brien, Edward; Goncalves, Sandro; Druce, Irena; Stewart, Alexandre; Gollob, Michael H; So, Derek Y F

    2012-05-05

    Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI. Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300. After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3-100) and a specificity of 99·3% (96·3-100). Point-of-care genetic testing after

  12. Developing professional caregivers' empathy and emotional competencies through mindfulness-based stress reduction (MBSR): results of two proof-of-concept studies.

    Science.gov (United States)

    Lamothe, Martin; McDuff, Pierre; Pastore, Yves D; Duval, Michel; Sultan, Serge

    2018-01-05

    To assess the feasibility and acceptability of a mindfulness-based stress reduction (MBSR)-based intervention and determine if the intervention is associated with a significant signal on empathy and emotional competencies. Two pre-post proof-of-concept studies. Participants were recruited at the University of Montreal's Psychology Department (Study 1) and the CHU Sainte-Justine Department of Hematology-Oncology (Study 2). Study 1: 12 students completed the 8-week programme (mean age 24, range 18-34). Study 2: 25 professionals completed the 8-week programme (mean age 48, range 27-63). Standard MBSR programme including 8-week mindfulness programme consisting of 8 consecutive weekly 2-hour sessions and a full-day silent retreat. Mindfulness as measured by the Mindful Attention Awareness Scale; empathy as measured by the Interpersonal Reactivity Index (IRI)'s Perspective Taking and Empathic Concern subscales; identification of one's own emotions and those of others as measured by the Profile of Emotional Competence (PEC)'s Identify my Emotions and Identify Others' Emotions subscales; emotional acceptance as measured by the Acceptance and Action Questionnaire-II (AAQ-II) and the Emotion Regulation Scale (ERQ)'s Expressive Suppression subscale; and recognition of emotions in others as measured by the Geneva Emotion Recognition Test (GERT). In both studies, retention rates (80%-81%) were acceptable. Participants who completed the programme improved on all measures except the PEC's Identify Others' Emotions and the IRI's Empathic Concern (Cohen's d median=0.92, range 45-1.72). In Study 2, favourable effects associated with the programme were maintained over 3 months on the PEC's Identify my Emotions, the AAQ-II, the ERQ's Expressive Suppression and the GERT. The programme was feasible and acceptable. It was associated with a significant signal on the following outcomes: perspective taking, the identification of one's own emotions and emotional acceptance, thus, justifying

  13. Developing professional caregivers’ empathy and emotional competencies through mindfulness-based stress reduction (MBSR): results of two proof-of-concept studies

    Science.gov (United States)

    Lamothe, Martin; McDuff, Pierre; Pastore, Yves D; Duval, Michel; Sultan, Serge

    2018-01-01

    Objectives To assess the feasibility and acceptability of a mindfulness-based stress reduction (MBSR)-based intervention and determine if the intervention is associated with a significant signal on empathy and emotional competencies. Design Two pre–post proof-of-concept studies. Setting Participants were recruited at the University of Montreal’s Psychology Department (Study 1) and the CHU Sainte-Justine Department of Hematology-Oncology (Study 2). Participants Study 1: 12 students completed the 8-week programme (mean age 24, range 18–34). Study 2: 25 professionals completed the 8-week programme (mean age 48, range 27–63). Intervention Standard MBSR programme including 8-week mindfulness programme consisting of 8 consecutive weekly 2-hour sessions and a full-day silent retreat. Outcomes measures Mindfulness as measured by the Mindful Attention Awareness Scale; empathy as measured by the Interpersonal Reactivity Index (IRI)’s Perspective Taking and Empathic Concern subscales; identification of one’s own emotions and those of others as measured by the Profile of Emotional Competence (PEC)’s Identify my Emotions and Identify Others’ Emotions subscales; emotional acceptance as measured by the Acceptance and Action Questionnaire-II (AAQ-II) and the Emotion Regulation Scale (ERQ)’s Expressive Suppression subscale; and recognition of emotions in others as measured by the Geneva Emotion Recognition Test (GERT). Results In both studies, retention rates (80%–81%) were acceptable. Participants who completed the programme improved on all measures except the PEC’s Identify Others’ Emotions and the IRI’s Empathic Concern (Cohen’s d median=0.92, range 45–1.72). In Study 2, favourable effects associated with the programme were maintained over 3 months on the PEC’s Identify my Emotions, the AAQ-II, the ERQ’s Expressive Suppression and the GERT. Conclusions The programme was feasible and acceptable. It was associated with a significant signal on the

  14. Mindful2Work: Effects of Combined Physical Exercise, Yoga, and Mindfulness Meditations for Stress Relieve in Employees. A Proof of Concept Study.

    Science.gov (United States)

    de Bruin, Esther I; Formsma, Anne R; Frijstein, Gerard; Bögels, Susan M

    2017-01-01

    Work-related stress and associated illness and burnout is rising in western society, with now as much as almost a quarter of European and half of USA's employees estimated to be at the point of burnout. Mindfulness meditation, yoga, and physical exercise have all shown beneficial effects for work-related stress and illness. This proof of concept study assessed the feasibility, acceptability, and preliminary effects of the newly developed Mindful2Work training, a combination of physical exercise, restorative yoga, and mindfulness meditations, delivered in six weekly group sessions plus a follow-up session. Participants ( n  = 26, four males), referred by company doctors with (work-related) stress and burnout complaints, completed measurements pre and post the intervention, as well as at 6-week (FU1) and 6-month (FU2) follow-up. Results showed very high feasibility and acceptability of the Mindful2Work training. The training and trainers were rated with an 8.1 and 8.4 on a 1-10 scale, respectively, and training dropout rate was zero. Significant improvements with (very) large effect sizes were demonstrated for the primary outcome measures of physical and mental workability, and for anxiety, depression, stress, sleep quality, positive and negative affect, which remained (very) large and mostly increased further over time. Risk for long-term dropout from work (checklist individual strength [CIS]) was 92 % at pre-test, reduced to 67 % at post-test, to 44 % at FU1, and 35 % at FU2, whereas employees worked (RTWI) 65 % of their contract hours per week at pre-test, which increased to 73 % at post-test, 81 % at FU1 and 93 % at FU2. Intensity of home practice or number of attended sessions were not related to training effects. To conclude, the newly developed Mindful2Work training seems very feasible, and acceptable, and although no control group was included, the large effects of Mindful2Work are highly promising.

  15. Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undifferentiated arthritis: a proof-of-concept clinical and imaging study.

    Science.gov (United States)

    Buch, Maya H; Hensor, Elizabeth M A; Rakieh, Chadi; Freeston, Jane E; Middleton, Edward; Horton, Sarah; Das, Sudipto; Peterfy, Charles; Tan, Ai Lyn; Wakefield, Richard J; Emery, Paul

    2017-01-01

    No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS). A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months). Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively. This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Can Seeding in the Clinic Reach a Wide Audience? A Proof of Concept Study on Spreading a Health Message About Juvenile Idiopathic Arthritis Using a Shareable Online Video

    Science.gov (United States)

    Fay, Michaela; Rapley, Tim; Foster, Helen; Pain, Clare

    2016-01-01

    Background Shareable online video offers the potential for spreading a health message across online and real world social networks. Seeding a message in a clinical setting may be advantageous. Objective To investigate the potential of an online video to spread a health message about juvenile idiopathic arthritis (JIA) when delivered or seeded in a clinical setting and investigate factors that influence sharing behavior. Methods Multimethod proof of concept study. Concepts for two different styles of video were developed using focus groups and interviews and reviewed by an online market research panel. We compared dissemination of the two videos from two specialist pediatric rheumatology clinics in NHS Hospitals. Participants were 15 patients, family members, and clinical staff with knowledge of JIA at concept stage; 300 market research panel members in development stage; and 38 patients and their parents or guardians in the seeding stage. Newly diagnosed patients with JIA and/or parents or guardians were invited to view and share an online video with a health message about JIA across real-life and electronic social networks. Main outcome measures were viewing statistics, sharing behavior and patterns, and participant feedback. Results Of 38 patients and/or their parents or guardians given links, 26 visited the video webpage and shared the link, 2 visited and did not share, and 10 did not visit. Most links were viewed and shared within a few days. A total of 3314 pageviews were recorded with a mean of 89.6 pageviews per link (range 0-1245). Links were accessed from 26 countries, with most viewers in the United Kingdom (82.5%). Mothers were the most active group of sharers. Conclusions Distribution of a video link in a clinical setting may be an effective way to spread a health message. Parents or guardians of children with JIA are more likely to share a link than young people. Dissemination depends on a small number of active sharers, the content of the video, and

  17. SU-E-J-12: An Image-Guided Soft Robotic Patient Positioning System for Maskless Head-And-Neck Cancer Radiotherapy: A Proof-Of-Concept Study

    International Nuclear Information System (INIS)

    Ogunmolu, O; Gans, N; Jiang, S; Gu, X

    2015-01-01

    Purpose: We propose a surface-image-guided soft robotic patient positioning system for maskless head-and-neck radiotherapy. The ultimate goal of this project is to utilize a soft robot to realize non-rigid patient positioning and real-time motion compensation. In this proof-of-concept study, we design a position-based visual servoing control system for an air-bladder-based soft robot and investigate its performance in controlling the flexion/extension cranial motion on a mannequin head phantom. Methods: The current system consists of Microsoft Kinect depth camera, an inflatable air bladder (IAB), pressured air source, pneumatic valve actuators, custom-built current regulators, and a National Instruments myRIO microcontroller. The performance of the designed system was evaluated on a mannequin head, with a ball joint fixed below its neck to simulate torso-induced head motion along flexion/extension direction. The IAB is placed beneath the mannequin head. The Kinect camera captures images of the mannequin head, extracts the face, and measures the position of the head relative to the camera. This distance is sent to the myRIO, which runs control algorithms and sends actuation commands to the valves, inflating and deflating the IAB to induce head motion. Results: For a step input, i.e. regulation of the head to a constant displacement, the maximum error was a 6% overshoot, which the system then reduces to 0% steady-state error. In this initial investigation, the settling time to reach the regulated position was approximately 8 seconds, with 2 seconds of delay between the command start of motion due to capacitance of the pneumatics, for a total of 10 seconds to regulate the error. Conclusion: The surface image-guided soft robotic patient positioning system can achieve accurate mannequin head flexion/extension motion. Given this promising initial Result, the extension of the current one-dimensional soft robot control to multiple IABs for non-rigid positioning control

  18. Can Seeding in the Clinic Reach a Wide Audience? A Proof of Concept Study on Spreading a Health Message About Juvenile Idiopathic Arthritis Using a Shareable Online Video.

    Science.gov (United States)

    Fay, Michaela; Rapley, Tim; Foster, Helen; Pain, Clare; Gerrand, Craig

    2016-02-22

    Shareable online video offers the potential for spreading a health message across online and real world social networks. Seeding a message in a clinical setting may be advantageous. To investigate the potential of an online video to spread a health message about juvenile idiopathic arthritis (JIA) when delivered or seeded in a clinical setting and investigate factors that influence sharing behavior. Multimethod proof of concept study. Concepts for two different styles of video were developed using focus groups and interviews and reviewed by an online market research panel. We compared dissemination of the two videos from two specialist pediatric rheumatology clinics in NHS Hospitals. Participants were 15 patients, family members, and clinical staff with knowledge of JIA at concept stage; 300 market research panel members in development stage; and 38 patients and their parents or guardians in the seeding stage. Newly diagnosed patients with JIA and/or parents or guardians were invited to view and share an online video with a health message about JIA across real-life and electronic social networks. Main outcome measures were viewing statistics, sharing behavior and patterns, and participant feedback. Of 38 patients and/or their parents or guardians given links, 26 visited the video webpage and shared the link, 2 visited and did not share, and 10 did not visit. Most links were viewed and shared within a few days. A total of 3314 pageviews were recorded with a mean of 89.6 pageviews per link (range 0-1245). Links were accessed from 26 countries, with most viewers in the United Kingdom (82.5%). Mothers were the most active group of sharers. Distribution of a video link in a clinical setting may be an effective way to spread a health message. Parents or guardians of children with JIA are more likely to share a link than young people. Dissemination depends on a small number of active sharers, the content of the video, and the willingness of participants to share health

  19. Fasinumab (REGN475, an antinerve growth factor monoclonal antibody, for the treatment of acute sciatic pain: results of a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Tiseo PJ

    2014-08-01

    Full Text Available Paul J Tiseo,1 Haobo Ren,2 Scott Mellis3 1Pharmacovigilance Operations and Risk Management, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 2Biostatitics, Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA; 3Translational Medicine and Predictive Medicine, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Objective: To evaluate the efficacy and safety of subcutaneously administered fasinumab (REGN475, a nerve growth factor-neutralizing antibody, in patients with acute sciatic pain receiving standard of care therapy. Methods: This was a double-blind, parallel-group, proof-of-concept study. Patients with unilateral, moderate-to-severe sciatic pain of 2–16 weeks' duration were randomized to a subcutaneous dose of placebo (n=51, fasinumab 0.1 mg/kg (n=53, or 0.3 mg/kg (n=53; follow-up was 12 weeks. Pain was assessed in a daily diary using a numerical rating scale (NRS (0= no pain, 10= worst pain for average and worst leg and back pain. The primary efficacy end point was the area under the curve of NRS scores for average leg pain from baseline to week 4. Key secondary end points included changes in average and worst leg and back pain from baseline to the end of week 4 and to each weekly study visit. Patient functioning (Oswestry Disability Index and concomitant analgesic use were also assessed. Safety and tolerability were evaluated by treatment-emergent adverse events (TEAEs. Results: Demographic and clinical characteristics were similar among the treatment groups; 141 (88.7% patients completed the study. For the primary end point, mean ± standard deviation area under the curve values from baseline to week 4 were not significantly different between placebo (96.8±6.0 and fasinumab 0.1 mg/kg (112.7±58.3; P=0.0610 or fasinumab 0.3 mg/kg (112.4±55.8; P=0.0923. All secondary efficacy end points of changes in pain and function demonstrated responses that were similar between placebo and fasinumab groups. Incidence of TEAEs was 45.1%, 50

  20. SU-E-J-12: An Image-Guided Soft Robotic Patient Positioning System for Maskless Head-And-Neck Cancer Radiotherapy: A Proof-Of-Concept Study

    Energy Technology Data Exchange (ETDEWEB)

    Ogunmolu, O; Gans, N [The University of Texas at Dallas, Richardson, TX (United States); Jiang, S; Gu, X [UT Southwestern Medical Center, Dallas, TX (United States)

    2015-06-15

    Purpose: We propose a surface-image-guided soft robotic patient positioning system for maskless head-and-neck radiotherapy. The ultimate goal of this project is to utilize a soft robot to realize non-rigid patient positioning and real-time motion compensation. In this proof-of-concept study, we design a position-based visual servoing control system for an air-bladder-based soft robot and investigate its performance in controlling the flexion/extension cranial motion on a mannequin head phantom. Methods: The current system consists of Microsoft Kinect depth camera, an inflatable air bladder (IAB), pressured air source, pneumatic valve actuators, custom-built current regulators, and a National Instruments myRIO microcontroller. The performance of the designed system was evaluated on a mannequin head, with a ball joint fixed below its neck to simulate torso-induced head motion along flexion/extension direction. The IAB is placed beneath the mannequin head. The Kinect camera captures images of the mannequin head, extracts the face, and measures the position of the head relative to the camera. This distance is sent to the myRIO, which runs control algorithms and sends actuation commands to the valves, inflating and deflating the IAB to induce head motion. Results: For a step input, i.e. regulation of the head to a constant displacement, the maximum error was a 6% overshoot, which the system then reduces to 0% steady-state error. In this initial investigation, the settling time to reach the regulated position was approximately 8 seconds, with 2 seconds of delay between the command start of motion due to capacitance of the pneumatics, for a total of 10 seconds to regulate the error. Conclusion: The surface image-guided soft robotic patient positioning system can achieve accurate mannequin head flexion/extension motion. Given this promising initial Result, the extension of the current one-dimensional soft robot control to multiple IABs for non-rigid positioning control

  1. Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

    Science.gov (United States)

    Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

    2017-04-01

    The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks

  2. Safety and efficacy of at-home robotic locomotion therapy in individuals with chronic incomplete spinal cord injury: a prospective, pre-post intervention, proof-of-concept study.

    Directory of Open Access Journals (Sweden)

    Rüdiger Rupp

    Full Text Available The compact Motorized orthosis for home rehabilitation of Gait (MoreGait was developed for continuation of locomotion training at home. MoreGait generates afferent stimuli of walking with the user in a semi-supine position and provides feedback about deviations from the reference walking pattern.Prospective, pre-post intervention, proof-of-concept study to test the feasibility of an unsupervised home-based application of five MoreGait prototypes in subjects with incomplete spinal cord injury (iSCI.Twenty-five (5 tetraplegia, 20 paraplegia participants with chronic (mean time since injury: 5.8 ± 5.4 (standard deviation, SD years sensorimotor iSCI (7 ASIA Impairment Scale (AIS C, 18 AIS D; Walking Index for Spinal Cord Injury (WISCI II: Interquartile range 9 to 16 completed the training (45 minutes / day, at least 4 days / week, 8 weeks. Baseline status was documented 4 and 2 weeks before and at training onset. Training effects were assessed after 4 and 8 weeks of therapy.After therapy, 9 of 25 study participants improved with respect to the dependency on walking aids assessed by the WISCI II. For all individuals, the short-distance walking velocity measured by the 10-Meter Walk Test showed significant improvements compared to baseline (100% for both self-selected (Mean 139.4% ± 35.5% (SD and maximum (Mean 143.1% ± 40.6% (SD speed conditions as well as the endurance estimated with the six-minute walk test (Mean 166.6% ± 72.1% (SD. One device-related adverse event (pressure sore on the big toe occurred in over 800 training sessions.Home-based robotic locomotion training with MoreGait is feasible and safe. The magnitude of functional improvements achieved by MoreGait in individuals with iSCI is well within the range of complex locomotion robots used in hospitals. Thus, unsupervised MoreGait training potentially represents an option to prolong effective training aiming at recovery of locomotor function beyond in-patient rehabilitation

  3. Can Fire and Rescue Services and the National Health Service work together to improve the safety and wellbeing of vulnerable older people? Design of a proof of concept study

    Directory of Open Access Journals (Sweden)

    Whiting David G

    2010-12-01

    Full Text Available Abstract Background Older adults are at increased risk both of falling and of experiencing accidental domestic fire. In addition to advanced age, these adverse events share the risk factors of balance or mobility problems, cognitive impairment and socioeconomic deprivation. For both events, the consequences include significant injury and death, and considerable socioeconomic costs for the individual and informal carers, as well as for emergency services, health and social care agencies. Secondary prevention services for older people who have fallen or who are identifiable as being at high risk of falling include NHS Falls clinics, where a multidisciplinary team offers an individualised multifactorial targeted intervention including strength and balance exercise programmes, medication changes and home hazard modification. A similar preventative approach is employed by most Fire and Rescue Services who conduct Home Fire Safety Visits to assess and, if necessary, remedy domestic fire risk, fit free smoke alarms with instruction for use and maintenance, and plan an escape route. We propose that the similarity of population at risk, location, specific risk factors and the commonality of preventative approaches employed could offer net gains in terms of feasibility, effectiveness and acceptability if activities within these two preventative approaches were to be combined. Methods/Design This prospective proof of concept study, currently being conducted in two London boroughs, (Southwark and Lambeth aims to reduce the incidence of both fires and falls in community-dwelling older adults. It comprises two concurrent 12-month interventions: the integration of 1 fall risk assessments into the Brigade's Home Fire Safety Visit and 2 fire risk assessments into Falls services by inviting older clinic attendees to book a Visit. Our primary objective is to examine the feasibility and effectiveness of these interventions. Furthermore, we are evaluating their

  4. Three-dimensional structure discrepancy between HLA alleles for effective prediction of aGVHD severity and optimal selection of recipient-donor pairs: a proof-of-concept study.

    Science.gov (United States)

    Han, Hongxing; Yuan, Fang; Sun, Yuying; Liu, Jinfeng; Liu, Shuguang; Luo, Yuan; Liang, Fei; Liu, Nan; Long, Juan; Zhao, Xiao; Kong, Fanhua; Xi, Yongzhi

    2015-11-24

    The optimal selection of recipient-donor pair and accurate prediction of acute graft-versus-host disease (aGVHD) severity are always the two most crucial works in allogeneic hematopoietic stem cell transplantation (allo-HSCT), which currently rests mostly with HLA compatibility, the most polymorphic loci in the human genome, in clinic. Thus, there is an urgent need for a rapid and reliable quantitative system for optimal recipient-donor pairs selection and accurate prediction of aGVHD severity prior to allo-HSCT. For these reasons, we have developed a new selection/prediction system for optimal recipient-donor selection and effective prediction of aGVHD severity based on HLA three-dimensional (3D) structure modeling (HLA-TDSM) discrepancy, and applied this system in a pilot randomized clinical allo-HSCT study. The 37 patient-donor pairs in the study were typed at low- and high-resolution levels for HLA-A/-B/-DRB1/-DQB1 loci. HLA-TDSM system covering the 10000 alleles in HLA class I and II consists of the revised local and coordinate root-mean-square deviation (RMSD) values for each locus. Its accuracy and reliability were confirmed using stably transfected Hmy2.CIR-HLA-B cells, TCR Vβ gene scan, and antigen-specific alloreactive cytotoxic lymphocytes. Based on the preliminary results, we theoretically defined all HLA acceptable versus unacceptable mismatched alleles. More importantly, HLA-TDSM enabled a successful retrospective verification and prospective prediction for aGVHD severity in a pilot randomized clinical allo-HSCT study of 32 recipient-donor transplant pairs. There was a strong direct correlation between single/total revised RMSD and aGVHD severity (92% in retrospective group vs 95% in prospective group). These results seem to be closely related to the 3D structure discrepancy of mismatched HLA-alleles, but not the number or loci of mismatched HLA-alleles. Our data first provide the proof-of-concept that HLA-TDSM is essential for optimal selection of

  5. Efficacy of a Community-Based Technology-Enabled Physical Activity Counseling Program for People With Knee Osteoarthritis: Proof-of-Concept Study.

    Science.gov (United States)

    Li, Linda C; Sayre, Eric C; Xie, Hui; Falck, Ryan S; Best, John R; Liu-Ambrose, Teresa; Grewal, Navi; Hoens, Alison M; Noonan, Greg; Feehan, Lynne M

    2018-04-30

    Current practice guidelines emphasize the use of physical activity as the first-line treatment of knee osteoarthritis; however, up to 90% of people with osteoarthritis are inactive. We aimed to assess the efficacy of a technology-enabled counseling intervention for improving physical activity in people with either a physician-confirmed diagnosis of knee osteoarthritis or having passed two validated criteria for early osteoarthritis. We conducted a proof-of-concept randomized controlled trial. The immediate group received a brief education session by a physical therapist, a Fitbit Flex, and four biweekly phone calls for activity counseling. The delayed group received the same intervention 2 months later. Participants were assessed at baseline (T0) and at the end of 2 months (T1), 4 months (T2), and 6 months (T3). Outcomes included (1) mean time on moderate-to-vigorous physical activity (MVPA ≥3 metabolic equivalents [METs], primary outcome), (2) mean time on MVPA ≥4 METs, (3) mean daily steps, (4) mean time on sedentary activities, (5) Knee Injury and Osteoarthritis Outcome Score (KOOS), and (6) Partners in Health scale. Mixed-effects repeated measures analysis of variance was used to assess five planned contrasts of changes in outcome measures over measurement periods. The five contrasts were (1) immediate T1-T0 vs delayed T1-T0, (2) delayed T2-T1 vs delayed T1-T0, (3) mean of contrast 1 and contrast 2, (4) immediate T1-T0 vs delayed T2-T1, and (5) mean of immediate T2-T1 and delayed T3-T2. The first three contrasts estimate the between-group effects. The latter two contrasts estimate the effect of the 2-month intervention delay on outcomes. We recruited 61 participants (immediate: n=30; delayed: n=31). Both groups were similar in age (immediate: mean 61.3, SD 9.4 years; delayed: mean 62.1, SD 8.5 years) and body mass index (immediate: mean 29.2, SD 5.5 kg/m 2 ; delayed: mean 29.2, SD 4.8 kg/m 2 ). Contrast analyses revealed significant between-group effects in

  6. Application of digital mapping technology to the display of hydrologic information; a proof-of-concept test in the Fox-Wolf River Basin, Wisconsin

    Science.gov (United States)

    Moore, G.K.; Baten, L.G.; Allord, G.J.; Robinove, C.J.

    1983-01-01

    The Fox-Wolf River basin in east-central Wisconsin was selected to test concepts for a water-resources information system using digital mapping technology. This basin of 16,800 sq km is typical of many areas in the country. Fifty digital data sets were included in the Fox-Wolf information system. Many data sets were digitized from 1:500,000 scale maps and overlays. Some thematic data were acquired from WATSTORE and other digital data files. All data were geometrically transformed into a Lambert Conformal Conic map projection and converted to a raster format with a 1-km resolution. The result of this preliminary processing was a group of spatially registered, digital data sets in map form. Parameter evaluation, areal stratification, data merging, and data integration were used to achieve the processing objectives and to obtain analysis results for the Fox-Wolf basin. Parameter evaluation includes the visual interpretation of single data sets and digital processing to obtain new derived data sets. In the areal stratification stage, masks were used to extract from one data set all features that are within a selected area on another data set. Most processing results were obtained by data merging. Merging is the combination of two or more data sets into a composite product, in which the contribution of each original data set is apparent and can be extracted from the composite. One processing result was also obtained by data integration. Integration is the combination of two or more data sets into a single new product, from which the original data cannot be separated or calculated. (USGS)

  7. Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing In Vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Krishna Deepika

    2017-01-01

    Full Text Available Objective: Is a single dose of gonadotropin-releasing hormone agonist (GnRHa trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS undergoing in vitro fertilization (IVF cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity? Design: This is a prospective, randomized, double-blind, proof-of-concept study. Setting: This study was carried out at a tertiary care center. Material and Methods: A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003 undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH, progesterone (P4, and follicle-stimulating hormone (FSH values were estimated. Statistical Analysis: Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR with 95% confidence intervals (CIs was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity. Main Outcome Measures: Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L, FSH (IU/L, and P4 (ng/mL levels implantation rate and clinical pregnancy rate. Results: A higher number of mature (metaphase II oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0

  8. Analysis of the Effect of Environmental Conditions in Conducting Amphibious Assaults Using a Ship Simulator/Vessel-Response Model Proof-of-Concept Study

    Science.gov (United States)

    2017-05-01

    maximum water depth is about 7.3 m (24 ft) at slack high water. ERDC/CHL TR-17-4 34 Figure 26. Amphibious operations area. Figure 27. Landing... operational risk by testing the feasibility of the navigability of an area; 2) determining the capacity and timing of that operation ; 3) defining the...amphibious operations and their use in a virtual amphibious assault near the Port of Anchorage, Alaska. This site was chosen because the environmental

  9. Establishing the subcellular localization of photodynamically-induced ROS using 3,3′-diaminobenzidine: A methodological proposal, with a proof-of-concept demonstration

    DEFF Research Database (Denmark)

    Stockert, Juan Carlos; Blazquez-Castro, Alfonso

    2016-01-01

    The critical involvement of reactive oxygen species (ROS) in both physiological and pathological processes in cell biology makes their detection and assessment a fundamental topic in biomedical research. Established methodologies to study ROS in cell biology take advantage of oxidation reactions...... is proved in a photodynamic model of ROS generation, the principle is applicable to many different scenarios of intracellular ROS production. As a consequence this proposed methodology should greatly complement other techniques aiming at establishing a precise subcellular localization of ROS generation....... between the ROS and a reduced probe. After reacting the probe reveals the presence of ROS either by the appearance of colour (chromogenic reaction) or fluorescence (fluorogenic reaction). However current methodologies rarely allow for a site-specific detection of ROS production. Here we propose...

  10. Thiazide diuretic-caused hyponatremia in the elderly hypertensive: will a bottle of Nepro a day keep hyponatremia and the doctor away? Study protocol for a proof-of-concept feasibility trial.

    Science.gov (United States)

    Ruzicka, Marcel; McCormick, Brendan; Magner, Peter; Ramsay, Tim; Edwards, Cedric; Bugeja, Ann; Hiremath, Swapnil

    2018-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, with an increasing prevalence with age, but with easily available medications to control it. Adverse effects of these medications do limit their use, in particular hyponatremia due to thiazide and thiazide-like diuretics. This is more common in the elderly patients due to a combination of inadequate protein intake and impaired urinary dilution capability, made worse by additional thiazide use. Limiting free water intake and increasing protein intake are often not successful resulting in thiazide avoidance. Daily protein supplement is a potential option in this clinical scenario. We describe the protocol for a feasibility study to explore this option. This is a single-arm, prospective, open-label proof-of-concept trial, including elderly patients with thiazide diuretic-induced hyponatremia. Forty patients will be enrolled and receive a bottle of a protein supplement daily, providing 120 mmol of solutes and permitting an extra 163 mL free water loss, for 4 weeks. The main outcome measures will be (1) feasibility for enrollment, (2) safety of the intervention, and (3) potential efficacy of the intervention in improving hyponatremia. Secondary outcome measures will include changes in urine osmolality, body weight, and urea measurements. Thiazide diuretic-induced hyponatremia is an important adverse effect, with significant clinical impact, such as delirium and falls, and limits the use of these potent antihypertensive agents. There are little data on the effect or safety of protein supplementation and also on whether a trial of this is feasible. The results of this proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test protein supplementation as an effective strategy in this condition. The trial is registered with Clinical trials, registration identifier: NCT02614807.

  11. Potential of EPR spin-trapping to investigate in situ free radicals generation from skin allergens in reconstructed human epidermis: cumene hydroperoxide as proof of concept.

    Science.gov (United States)

    Kuresepi, Salen; Vileno, Bertrand; Turek, Philippe; Lepoittevin, Jean-Pierre; Giménez-Arnau, Elena

    2018-02-01

    The first step in the development of skin sensitisation to a chemical, and in the elicitation of further allergic contact dermatitis (ACD), is the binding of the allergen to skin proteins after penetrating into the epidermis. The so-formed antigenic adduct is then recognised by the immune system as foreign to the body. Sensitising organic hydroperoxides derived from autoxidation of natural terpenes are believed to form antigens through radical-mediated mechanisms, although this has not yet been established. So far, in vitro investigations on reactive radical intermediates derived from these skin sensitisers have been conducted in solution, yet with experimental conditions being far away from real-life sensitisation. Herein, we report for the first time, the potential use of EPR spin-trapping to study the in situ generation of free radicals derived from cumene hydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model, thus much closer to what may happen in vivo. Among the undesirable effects associated with dermal exposure to CumOOH, it is described to cause allergic and irritant dermatitis, being reported as a significant sensitiser. We considered exploiting the usage of spin-trap DEPMPO as an extensive view of all sort of radicals derived from CumOOH were observed all at once in solution. We showed that in the Episkin TM RHE model, both by incubating in the assay medium and by topical application, carbon radicals are mainly formed by redox reactions suggesting the key role of CumOOH-derived carbon radicals in the antigen formation process.

  12. A novel magnet based 3D printed marker wand as basis for repeated in-shoe multi segment foot analysis: a proof of concept.

    Science.gov (United States)

    Eerdekens, Maarten; Staes, Filip; Pilkington, Thomas; Deschamps, Kevin

    2017-01-01

    Application of in-shoe multi-segment foot kinematic analyses currently faces a number of challenges, including: (i) the difficulty to apply regular markers onto the skin, (ii) the necessity for an adequate shoe which fits various foot morphologies and (iii) the need for adequate repeatability throughout a repeated measure condition. The aim of this study therefore was to design novel magnet based 3D printed markers for repeated in-shoe measurements while using accordingly adapted modified shoes for a specific multi-segment foot model. Multi-segment foot kinematics of ten participants were recorded and kinematics of hindfoot, midfoot and forefoot were calculated. Dynamic trials were conducted to check for intra and inter-session repeatability when combining novel markers and modified shoes in a repeated measures design. Intraclass correlation coefficients were calculated to determine reliability. Both repeatability and reliability were proven to be good to excellent with maximum joint angle deviations of 1.11° for intra-session variability and 1.29° for same-day inter-session variability respectively and ICC values of >0.91. The novel markers can be reliably used in future research settings using in-shoe multi-segment foot kinematic analyses with multiple shod conditions.

  13. Calibration-free technique for the measurement of oxygen saturation changes in muscles of marine mammals and its proof of concept

    Science.gov (United States)

    Ortega-Martinez, Antonio; Goenka, Chhavi; Booker, Marloes; Grange, Robert M. H.; Hindle, Allyson G.; Franco, Walfre

    2018-02-01

    Marine mammals possess impressive breath-holding capabilities made possible by physiological adjustments during dives. Studying marine mammals in their natural environment unravels vital information about these physiological adjustments particularly when we can monitor altered dive behavior in response to stressful situations such as human-induced oceanic disturbances, presence of predators and altered prey distributions. An important indicator of physiological status during submergence is the change in oxygen saturation in the muscles and blood of these mammals. In this work, we aim to investigate oxygen storage and consumption in the muscles of free-diving elephant seals when exposed to disturbances such as sonar or predator sounds while they are at sea. Optical oxygen sensors are a mature technology with multiple medical applications that provide a way to measure oxygenation changes in biological tissues in a minimally invasive manner. While these sensors are well calibrated and readily available for humans, they are still inadequate for marine mammals primarily due to a very small number of test candidates and therefore little data is available for validation and calibration. We propose a probe geometry and associated mathematical model for measuring muscle oxygenation in seals based on near infrared diffuse transport with no need for calibration. A prototype based on this concept has been designed and tested on humans and rats. We use the test results to discuss the advantages and limitations of the approach. We also detail the constraints on size, sensor location, electronics, light source properties and detector characteristics posed by the unique biology of seals.

  14. Atlantis Modeled Output Data for the Coral Reef Ecosystems of Guam

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A proof-of-concept Guam Atlantis Coral Reef Ecosystem Model has been developed and an added coral module to the Atlantis framework has been validated. The model is...

  15. Proof of concept of a "greener" protein purification/enrichment method based on carboxylate-terminated carbosilane dendrimer-protein interactions.

    Science.gov (United States)

    González-García, Estefanía; Maly, Marek; de la Mata, Francisco Javier; Gómez, Rafael; Marina, María Luisa; García, María Concepción

    2016-11-01

    Protein sample preparation is a critical and an unsustainable step since it involves the use of tedious methods that usually require high amount of solvents. The development of new materials offers additional opportunities in protein sample preparation. This work explores, for the first time, the potential application of carboxylate-terminated carbosilane dendrimers to the purification/enrichment of proteins. Studies on dendrimer binding to proteins, based on protein fluorescence intensity and emission wavelengths measurements, demonstrated the interaction between carboxylate-terminated carbosilane dendrimers and proteins at all tested pH levels. Interactions were greatly affected by the protein itself, pH, and dendrimer concentration and generation. Especially interesting was the interaction at acidic pH since it resulted in a significant protein precipitation. Dendrimer-protein interactions were modeled observing stable complexes for all proteins. Carboxylate-terminated carbosilane dendrimers at acidic pH were successfully used in the purification/enrichment of proteins extracted from a complex sample. Graphical Abstract Images showing the growing turbidity of solutions containing a mixture of proteins (lysozyme, myoglobin, and BSA) at different protein:dendrimer ratios (1:0, 1:1, 1:8, and 1:20) at acidic pH and SDS-PAGE profiles of the corresponsing supernatants. Comparison of SDS-PAGE profiles for the pellets obtained during the purification of proteins present in a complex sample using a conventional "no-clean" method based on acetone precipitation and the proposed "greener" method using carboxylate-terminated carbosilane dendrimer at a 1:20 protein:dendrimer ratio.

  16. Aviation Proof of Concept: The Transition of Marine Corps Aviation Maintenance Computer Assets and Systems into the Navy Marine Corps Intranet

    Science.gov (United States)

    2010-03-01

    Player & Windows Media Player  WinZip  Antivirus Protection  PDF Viewer  TN3270 Client & VT100 Emulation  Remote Management Software ...33 2. Aviation Software Applications ........................................................37 3. Seat Transition...application OT Operational Test PUK Pack Up Kit RAP Tool Requirements To Award Process Tool RCP Remote Copy Protocol ( Cisco ) Seat A NMCI desktop

  17. Modelling Imprecise Arguments in Description Logic

    Directory of Open Access Journals (Sweden)

    LETIA, I. A.

    2009-10-01

    Full Text Available Real arguments are a mixture of fuzzy linguistic variables and ontological knowledge. This paper focuses on modelling imprecise arguments in order to obtain a better interleaving of human and software agents argumentation, which might be proved useful for extending the number of real life argumentative-based applications. We propose Fuzzy Description Logic as the adequate technical instrumentation for filling the gap between human arguments and software agents arguments. A proof of concept scenario has been tested with the fuzzyDL reasoner.

  18. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

    2017-01-01

    Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

  19. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  20. Analysis, Design and Implementation of a Networking Proof-of-Concept Prototype to Support Maritime Visit, Board, Search and Seizure Teams

    Science.gov (United States)

    2014-03-01

    information base MIO maritime interdiction operations MPU man portable unit NLOS non-line-of-site NMS network management system NOC...administrator. For smaller networks, the economic feasibility for a comprehensive NMS might not be worth the investment. Instead, an application designed to... MPU -4s with Samsung devices attached to host a variety of IP-based applications. These nodes were utilized by the BTs to sweep the vessel in a