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  1. Quantum random number generators

    Science.gov (United States)

    Herrero-Collantes, Miguel; Garcia-Escartin, Juan Carlos

    2017-01-01

    Random numbers are a fundamental resource in science and engineering with important applications in simulation and cryptography. The inherent randomness at the core of quantum mechanics makes quantum systems a perfect source of entropy. Quantum random number generation is one of the most mature quantum technologies with many alternative generation methods. This review discusses the different technologies in quantum random number generation from the early devices based on radioactive decay to the multiple ways to use the quantum states of light to gather entropy from a quantum origin. Randomness extraction and amplification and the notable possibility of generating trusted random numbers even with untrusted hardware using device-independent generation protocols are also discussed.

  2. Thermodynamics of random number generation

    Science.gov (United States)

    Aghamohammadi, Cina; Crutchfield, James P.

    2017-06-01

    We analyze the thermodynamic costs of the three main approaches to generating random numbers via the recently introduced Information Processing Second Law. Given access to a specified source of randomness, a random number generator (RNG) produces samples from a desired target probability distribution. This differs from pseudorandom number generators (PRNGs) that use wholly deterministic algorithms and from true random number generators (TRNGs) in which the randomness source is a physical system. For each class, we analyze the thermodynamics of generators based on algorithms implemented as finite-state machines, as these allow for direct bounds on the required physical resources. This establishes bounds on heat dissipation and work consumption during the operation of three main classes of RNG algorithms—including those of von Neumann, Knuth, and Yao and Roche and Hoshi—and for PRNG methods. We introduce a general TRNG and determine its thermodynamic costs exactly for arbitrary target distributions. The results highlight the significant differences between the three main approaches to random number generation: One is work producing, one is work consuming, and the other is potentially dissipation neutral. Notably, TRNGs can both generate random numbers and convert thermal energy to stored work. These thermodynamic costs on information creation complement Landauer's limit on the irreducible costs of information destruction.

  3. Random Process Generation.

    Science.gov (United States)

    1980-06-01

    Address: Professor Bruce W. Schmeiser School of Industrial Engineering Purdue University West Lafayette, IN 47907 UjDISTIUMUTIO" TTMJ Approved for...algorithms developed under this contract are about twice as fast as the best alternatives available today. Peter Lewis at the Naval Postgraduate School ...generating bivariate gazua vectors. These algorithms are the only methods available which are valid for an gaia marginal distributions and j 6 -. . 4

  4. Generating random networks and graphs

    CERN Document Server

    Coolen, Ton; Roberts, Ekaterina

    2017-01-01

    This book supports researchers who need to generate random networks, or who are interested in the theoretical study of random graphs. The coverage includes exponential random graphs (where the targeted probability of each network appearing in the ensemble is specified), growth algorithms (i.e. preferential attachment and the stub-joining configuration model), special constructions (e.g. geometric graphs and Watts Strogatz models) and graphs on structured spaces (e.g. multiplex networks). The presentation aims to be a complete starting point, including details of both theory and implementation, as well as discussions of the main strengths and weaknesses of each approach. It includes extensive references for readers wishing to go further. The material is carefully structured to be accessible to researchers from all disciplines while also containing rigorous mathematical analysis (largely based on the techniques of statistical mechanics) to support those wishing to further develop or implement the theory of rand...

  5. USER S GUIDE FOR THE RANDOM DRUG SCREENING SYSTEM

    Energy Technology Data Exchange (ETDEWEB)

    McNeany, Karen I [ORNL

    2013-12-01

    The Random Drug Screening System (RDSS) is a desktop computing application designed to assign nongameable drug testing dates to each member in a population of employees, within a specific time line. The program includes reporting capabilities, test form generation, unique test ID number assignment, and the ability to flag high-risk employees for a higher frequency of drug testing than the general population.

  6. Self-correcting random number generator

    Energy Technology Data Exchange (ETDEWEB)

    Humble, Travis S.; Pooser, Raphael C.

    2016-09-06

    A system and method for generating random numbers. The system may include a random number generator (RNG), such as a quantum random number generator (QRNG) configured to self-correct or adapt in order to substantially achieve randomness from the output of the RNG. By adapting, the RNG may generate a random number that may be considered random regardless of whether the random number itself is tested as such. As an example, the RNG may include components to monitor one or more characteristics of the RNG during operation, and may use the monitored characteristics as a basis for adapting, or self-correcting, to provide a random number according to one or more performance criteria.

  7. Analysis of android random number generator

    OpenAIRE

    Sarıtaş, Serkan

    2013-01-01

    Ankara : The Department of Computer Engineering and the Graduate School of Engineering and Science of Bilkent University, 2013. Thesis (Master's) -- Bilkent University, 2013. Includes bibliographical references leaves 61-65. Randomness is a crucial resource for cryptography, and random number generators are critical building blocks of almost all cryptographic systems. Therefore, random number generation is one of the key parts of secure communication. Random number generatio...

  8. Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized, double-blinded studies with eslicarbazepine acetate, lacosamide and oxcarbazepine.

    Science.gov (United States)

    Zaccara, Gaetano; Giovannelli, Fabio; Maratea, Dario; Fadda, Valeria; Verrotti, Alberto

    2013-09-01

    Analysis of overall tolerability and neurological adverse effects (AEs) of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from double-blind, placebo-controlled trials. Indirect comparisons of patients withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs between these three antiepileptic dugs (AEDs). We searched MEDLINE for all randomized, double-blind, placebo-controlled trials investigating therapeutic effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant epilepsy. Withdrawal rate due to AEs, percentages of patients with serious AEs, and the proportion of patients experiencing any neurological AE, nausea and vomiting were assessed for their association with the experimental drug. Analyses were performed between recommended daily doses of each AED according to the approved summary of product characteristics (SPC). Risk differences were used to evaluate the association of any AE [99% confidence intervals (CIs)] or study withdrawals because of AEs (95% CIs) with the experimental drug. Indirect comparisons between withdrawal rate and AEs dizziness, coordination abnormal/ataxia and diplopia were estimated according to network meta-analysis (Net-MA). Eight randomized, placebo-controlled, double-blind trials (4 with ESL, 3 with LCM, and 1 with OXC) were included in our analysis. At high doses (OXC 1200mg, ESL 1200mg and LCM 400mg) there was an increased risk of AE-related study withdrawals compared to placebo for all drugs. Several AEs were associated with the experimental drug. Both number and frequency of AEs were dose-related. At high recommended doses, patients treated with OXC withdrew from the experimental treatment significantly more frequently than patients treated with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia were significantly more frequently observed in patients treated with OXC compared to patients treated with LCM and ESL. The overall tolerability

  9. Source-Independent Quantum Random Number Generation

    Science.gov (United States)

    Cao, Zhu; Zhou, Hongyi; Yuan, Xiao; Ma, Xiongfeng

    2016-01-01

    Quantum random number generators can provide genuine randomness by appealing to the fundamental principles of quantum mechanics. In general, a physical generator contains two parts—a randomness source and its readout. The source is essential to the quality of the resulting random numbers; hence, it needs to be carefully calibrated and modeled to achieve information-theoretical provable randomness. However, in practice, the source is a complicated physical system, such as a light source or an atomic ensemble, and any deviations in the real-life implementation from the theoretical model may affect the randomness of the output. To close this gap, we propose a source-independent scheme for quantum random number generation in which output randomness can be certified, even when the source is uncharacterized and untrusted. In our randomness analysis, we make no assumptions about the dimension of the source. For instance, multiphoton emissions are allowed in optical implementations. Our analysis takes into account the finite-key effect with the composable security definition. In the limit of large data size, the length of the input random seed is exponentially small compared to that of the output random bit. In addition, by modifying a quantum key distribution system, we experimentally demonstrate our scheme and achieve a randomness generation rate of over 5 ×103 bit /s .

  10. Random Number Generators in Secure Disk Drives

    Directory of Open Access Journals (Sweden)

    Hars Laszlo

    2009-01-01

    Full Text Available Abstract Cryptographic random number generators seeded by physical entropy sources are employed in many embedded security systems, including self-encrypting disk drives, being manufactured by the millions every year. Random numbers are used for generating encryption keys and for facilitating secure communication, and they are also provided to users for their applications. We discuss common randomness requirements, techniques for estimating the entropy of physical sources, investigate specific nonrandom physical properties, estimate the autocorrelation, then mix reduce the data until all common randomness tests pass. This method is applied to a randomness source in disk drives: the always changing coefficients of an adaptive filter for the read channel equalization. These coefficients, affected by many kinds of physical noise, are used in the reseeding process of a cryptographic pseudorandom number generator in a family of self encrypting disk drives currently in the market.

  11. Generating Realistic Labelled, Weighted Random Graphs

    CERN Document Server

    Davis, Michael Charles; Liu, Weiru; Miller, Paul; Hunter, Ruth; Kee, Frank

    2015-01-01

    Generative algorithms for random graphs have yielded insights into the structure and evolution of real-world networks. Most networks exhibit a well-known set of properties, such as heavy-tailed degree distributions, clustering and community formation. Usually, random graph models consider only structural information, but many real-world networks also have labelled vertices and weighted edges. In this paper, we present a generative model for random graphs with discrete vertex labels and numeric edge weights. The weights are represented as a set of Beta Mixture Models (BMMs) with an arbitrary number of mixtures, which are learned from real-world networks. We propose a Bayesian Variational Inference (VI) approach, which yields an accurate estimation while keeping computation times tractable. We compare our approach to state-of-the-art random labelled graph generators and an earlier approach based on Gaussian Mixture Models (GMMs). Our results allow us to draw conclusions about the contribution of vertex labels a...

  12. A Hybrid Random Number Generator(HRNG

    Directory of Open Access Journals (Sweden)

    Osvaldo Skliar

    2011-07-01

    Full Text Available The purpose of this paper is to present a novel Hybrid Random Number Generator (HRNG. Here “hybrid” refers to the fact that to construct this generator it is necessary to use 1physical components – texts – and a physical process, and 2 a mathematical procedure. This HRNG makes it possible to generate genuine random numbers which may be used both for computer simulation of probabilistic systems and in the field of cryptography. The results of a comparative study of the binary strings generated by this HRNG and of those generated by two highly used implementations of a congruential algorithm designed to generate pseudorandom numbers are given here. One of the latter is the implementation incorporated into the Java 2 platform (version 1.6, and the other is the implementation incorporated into the runtime library of Microsoft’s Visual C++ 2008 compiler.

  13. Pseudo-random number generator based on asymptotic deterministic randomness

    Energy Technology Data Exchange (ETDEWEB)

    Wang Kai [Department of Radio Engineering, Southeast University, Nanjing (China)], E-mail: kaiwang@seu.edu.cn; Pei Wenjiang; Xia Haishan [Department of Radio Engineering, Southeast University, Nanjing (China); Cheung Yiuming [Department of Computer Science, Hong Kong Baptist University, Hong Kong (China)

    2008-06-09

    A novel approach to generate the pseudorandom-bit sequence from the asymptotic deterministic randomness system is proposed in this Letter. We study the characteristic of multi-value correspondence of the asymptotic deterministic randomness constructed by the piecewise linear map and the noninvertible nonlinearity transform, and then give the discretized systems in the finite digitized state space. The statistic characteristics of the asymptotic deterministic randomness are investigated numerically, such as stationary probability density function and random-like behavior. Furthermore, we analyze the dynamics of the symbolic sequence. Both theoretical and experimental results show that the symbolic sequence of the asymptotic deterministic randomness possesses very good cryptographic properties, which improve the security of chaos based PRBGs and increase the resistance against entropy attacks and symbolic dynamics attacks.

  14. Generating Realistic Labelled, Weighted Random Graphs

    Directory of Open Access Journals (Sweden)

    Michael Charles Davis

    2015-12-01

    Full Text Available Generative algorithms for random graphs have yielded insights into the structure and evolution of real-world networks. Most networks exhibit a well-known set of properties, such as heavy-tailed degree distributions, clustering and community formation. Usually, random graph models consider only structural information, but many real-world networks also have labelled vertices and weighted edges. In this paper, we present a generative model for random graphs with discrete vertex labels and numeric edge weights. The weights are represented as a set of Beta Mixture Models (BMMs with an arbitrary number of mixtures, which are learned from real-world networks. We propose a Bayesian Variational Inference (VI approach, which yields an accurate estimation while keeping computation times tractable. We compare our approach to state-of-the-art random labelled graph generators and an earlier approach based on Gaussian Mixture Models (GMMs. Our results allow us to draw conclusions about the contribution of vertex labels and edge weights to graph structure.

  15. Fast Generation of Discrete Random Variables

    Directory of Open Access Journals (Sweden)

    George Marsaglia

    2004-07-01

    Full Text Available We describe two methods and provide C programs for generating discrete random variables with functions that are simple and fast, averaging ten times as fast as published methods and more than five times as fast as the fastest of those. We provide general procedures for implementing the two methods, as well as specific procedures for three of the most important discrete distributions: Poisson, binomial and hypergeometric.

  16. Physical Principle for Generation of Randomness

    Science.gov (United States)

    Zak, Michail

    2009-01-01

    A physical principle (more precisely, a principle that incorporates mathematical models used in physics) has been conceived as the basis of a method of generating randomness in Monte Carlo simulations. The principle eliminates the need for conventional random-number generators. The Monte Carlo simulation method is among the most powerful computational methods for solving high-dimensional problems in physics, chemistry, economics, and information processing. The Monte Carlo simulation method is especially effective for solving problems in which computational complexity increases exponentially with dimensionality. The main advantage of the Monte Carlo simulation method over other methods is that the demand on computational resources becomes independent of dimensionality. As augmented by the present principle, the Monte Carlo simulation method becomes an even more powerful computational method that is especially useful for solving problems associated with dynamics of fluids, planning, scheduling, and combinatorial optimization. The present principle is based on coupling of dynamical equations with the corresponding Liouville equation. The randomness is generated by non-Lipschitz instability of dynamics triggered and controlled by feedback from the Liouville equation. (In non-Lipschitz dynamics, the derivatives of solutions of the dynamical equations are not required to be bounded.)

  17. Employing online quantum random number generators for generating truly random quantum states in Mathematica

    Science.gov (United States)

    Miszczak, Jarosław Adam

    2013-01-01

    The presented package for the Mathematica computing system allows the harnessing of quantum random number generators (QRNG) for investigating the statistical properties of quantum states. The described package implements a number of functions for generating random states. The new version of the package adds the ability to use the on-line quantum random number generator service and implements new functions for retrieving lists of random numbers. Thanks to the introduced improvements, the new version provides faster access to high-quality sources of random numbers and can be used in simulations requiring large amount of random data. New version program summaryProgram title: TRQS Catalogue identifier: AEKA_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKA_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 18 134 No. of bytes in distributed program, including test data, etc.: 2 520 49 Distribution format: tar.gz Programming language: Mathematica, C. Computer: Any supporting Mathematica in version 7 or higher. Operating system: Any platform supporting Mathematica; tested with GNU/Linux (32 and 64 bit). RAM: Case-dependent Supplementary material: Fig. 1 mentioned below can be downloaded. Classification: 4.15. External routines: Quantis software library (http://www.idquantique.com/support/quantis-trng.html) Catalogue identifier of previous version: AEKA_v1_0 Journal reference of previous version: Comput. Phys. Comm. 183(2012)118 Does the new version supersede the previous version?: Yes Nature of problem: Generation of random density matrices and utilization of high-quality random numbers for the purpose of computer simulation. Solution method: Use of a physical quantum random number generator and an on-line service providing access to the source of true random

  18. Short Duration vs Standard Duration of Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents - A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Wassef, Anthony W A; Khafaji, Hadi; Syed, Ishba; Yan, Andrew T; Udell, Jacob A; Goodman, Shaun G; Cheema, Asim N; Bagai, Akshay

    2016-12-01

    Current guidelines recommend 12 months of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. Whether the duration of DAPT can be safely shortened with use of second-generation DESs is unclear. We conducted a meta-analysis of randomized controlled trials comparing short duration (SD) (3-6 months) with standard longer duration (LD) (≥12 months) DAPT in patients treated with primarily second-generation DES implantation. Meta-regression was performed to explore the relationship between acute coronary syndrome (ACS) and the effect of DAPT duration. Six studies were included, with 12,752/13,928 (91.5%) patients receiving second-generation DESs. A total of 5367 patients (39%) had PCI in the setting of ACS. There was no difference in all-cause mortality (1.1% vs 1.2%; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.63-1.18; P=.36) or cardiac mortality (0.9% vs 1.0%; OR, 0.92; 95% CI, 0.61-1.39; P=.69) with SD-DAPT vs LD-DAPT, respectively. Definite/probable stent thrombosis (0.5% vs 0.3%; OR, 1.33; 95% CI, 0.75-2.34; P=.51), myocardial infarction (1.5% vs 1.3%; OR, 1.17; 95% CI, 0.88-1.56; P=.29), and stroke (0.4% vs 0.4%; OR, 1.04; 95% CI, 0.60-1.81; P=.88) were similar between the groups. Compared with LD-DAPT, SD-DAPT was associated with lower clinically significant bleeding (0.9% vs 1.4%; OR, 0.64; 95% CI, 0.46-0.89; P=.01). Meta-regression analysis showed no significant association between the proportion of ACS patients in trials and duration of DAPT for the outcomes of mortality (P=.95), myocardial infarction (P=.98), or stent thrombosis (P=.89). In low-risk patients treated with contemporary second-generation DES implantation, SD-DAPT has similar rates of mortality, myocardial infarction, and stent thrombosis, with lower rates of bleeding compared with LD-DAPT.

  19. Random Numbers Generated from Audio and Video Sources

    Directory of Open Access Journals (Sweden)

    I-Te Chen

    2013-01-01

    Full Text Available Random numbers are very useful in simulation, chaos theory, game theory, information theory, pattern recognition, probability theory, quantum mechanics, statistics, and statistical mechanics. The random numbers are especially helpful in cryptography. In this work, the proposed random number generators come from white noise of audio and video (A/V sources which are extracted from high-resolution IPCAM, WEBCAM, and MPEG-1 video files. The proposed generator applied on video sources from IPCAM and WEBCAM with microphone would be the true random number generator and the pseudorandom number generator when applied on video sources from MPEG-1 video file. In addition, when applying NIST SP 800-22 Rev.1a 15 statistics tests on the random numbers generated from the proposed generator, around 98% random numbers can pass 15 statistical tests. Furthermore, the audio and video sources can be found easily; hence, the proposed generator is a qualified, convenient, and efficient random number generator.

  20. Unbiased All-Optical Random-Number Generator

    OpenAIRE

    Tobias Steinle; Greiner, Johannes N.; Jörg Wrachtrup; Harald Giessen; Ilja Gerhardt

    2017-01-01

    The generation of random bits is of enormous importance in modern information science. Cryptographic security is based on random numbers which require a physical process for their generation. This is commonly performed by hardware random number generators. These exhibit often a number of problems, namely experimental bias, memory in the system, and other technical subtleties, which reduce the reliability in the entropy estimation. Further, the generated outcome has to be post-processed to "ir...

  1. Ternary jitter-based true random number generator

    Science.gov (United States)

    Latypov, Rustam; Stolov, Evgeni

    2017-01-01

    In this paper a novel family of generators producing true uniform random numbers in ternary logic is presented. The generator consists of a number of identical ternary logic combinational units connected into a ring. All the units are provided to have a random delay time, and this time is supposed to be distributed in accordance with an exponential distribution. All delays are supposed to be independent events. The theory of the generator is based on Erlang equations. The generator can be used for test production in various systems. Features of multidimensional random vectors, produced by the generator, are discussed.

  2. Random number datasets generated from statistical analysis of randomly sampled GSM recharge cards.

    Science.gov (United States)

    Okagbue, Hilary I; Opanuga, Abiodun A; Oguntunde, Pelumi E; Ugwoke, Paulinus O

    2017-02-01

    In this article, a random number of datasets was generated from random samples of used GSM (Global Systems for Mobile Communications) recharge cards. Statistical analyses were performed to refine the raw data to random number datasets arranged in table. A detailed description of the method and relevant tests of randomness were also discussed.

  3. Quantum Random Number Generation on a Mobile Phone

    Directory of Open Access Journals (Sweden)

    Bruno Sanguinetti

    2014-09-01

    Full Text Available Quantum random number generators (QRNGs can significantly improve the security of cryptographic protocols by ensuring that generated keys cannot be predicted. However, the cost, size, and power requirements of current Quantum random number generators have prevented them from becoming widespread. In the meantime, the quality of the cameras integrated in mobile telephones has improved significantly so that now they are sensitive to light at the few-photon level. We demonstrate how these can be used to generate random numbers of a quantum origin.

  4. SPRNG Scalable Parallel Random Number Generator LIbrary

    Energy Technology Data Exchange (ETDEWEB)

    2010-03-16

    This revision corrects some errors in SPRNG 1. Users of newer SPRNG versions can obtain the corrected files and build their version with it. This version also improves the scalability of some of the application-based tests in the SPRNG test suite. It also includes an interface to a parallel Mersenne Twister, so that if users install the Mersenne Twister, then they can test this generator with the SPRNG test suite and also use some SPRNG features with that generator.

  5. Humans cannot consciously generate random numbers sequences: Polemic study.

    Science.gov (United States)

    Figurska, Małgorzata; Stańczyk, Maciej; Kulesza, Kamil

    2008-01-01

    It is widely believed, that randomness exists in Nature. In fact such an assumption underlies many scientific theories and is embedded in the foundations of quantum mechanics. Assuming that this hypothesis is valid one can use natural phenomena, like radioactive decay, to generate random numbers. Today, computers are capable of generating the so-called pseudorandom numbers. Such series of numbers are only seemingly random (bias in the randomness quality can be observed). Question whether people can produce random numbers, has been investigated by many scientists in the recent years. The paper "Humans can consciously generate random numbers sequences..." published recently in Medical Hypotheses made claims that were in many ways contrary to state of art; it also stated far-reaching hypotheses. So, we decided to repeat the experiments reported, with special care being taken of proper laboratory procedures. Here, we present the results and discuss possible implications in computer and other sciences.

  6. Analysis of Additive Random Number Generators.

    Science.gov (United States)

    1977-03-01

    CLASSIFICATION OF THIS PAGE (When Data Entered; I .,.,•• n .„^iMl~^.-». H .,il~l.*...,...-•..,.,.., • 1 ——’"- •"•’ ANALYSIS OF ADDITIVE RANDOM...among my teachers two of the best: my parents, Bil and Marleen Reiser. - , i — - •- - J I " ii. .1 I l. Kl U...the period, we know that r(pa*z) * pr(pa) and k - • - ----• •--- - -— — ...., . H ..J 1-..11.111 ’ Introduction that r(pa *’) divides

  7. Experimental measurement-device-independent quantum random-number generation

    Science.gov (United States)

    Nie, You-Qi; Guan, Jian-Yu; Zhou, Hongyi; Zhang, Qiang; Ma, Xiongfeng; Zhang, Jun; Pan, Jian-Wei

    2016-12-01

    The randomness from a quantum random-number generator (QRNG) relies on the accurate characterization of its devices. However, device imperfections and inaccurate characterizations can result in wrong entropy estimation and bias in practice, which highly affects the genuine randomness generation and may even induce the disappearance of quantum randomness in an extreme case. Here we experimentally demonstrate a measurement-device-independent (MDI) QRNG based on time-bin encoding to achieve certified quantum randomness even when the measurement devices are uncharacterized and untrusted. The MDI-QRNG is randomly switched between the regular randomness generation mode and a test mode, in which four quantum states are randomly prepared to perform measurement tomography in real time. With a clock rate of 25 MHz, the MDI-QRNG generates a final random bit rate of 5.7 kbps. Such implementation with an all-fiber setup provides an approach to construct a fully integrated MDI-QRNG with trusted but error-prone devices in practice.

  8. Unbiased All-Optical Random-Number Generator

    Science.gov (United States)

    Steinle, Tobias; Greiner, Johannes N.; Wrachtrup, Jörg; Giessen, Harald; Gerhardt, Ilja

    2017-10-01

    The generation of random bits is of enormous importance in modern information science. Cryptographic security is based on random numbers which require a physical process for their generation. This is commonly performed by hardware random-number generators. These often exhibit a number of problems, namely experimental bias, memory in the system, and other technical subtleties, which reduce the reliability in the entropy estimation. Further, the generated outcome has to be postprocessed to "iron out" such spurious effects. Here, we present a purely optical randomness generator, based on the bistable output of an optical parametric oscillator. Detector noise plays no role and postprocessing is reduced to a minimum. Upon entering the bistable regime, initially the resulting output phase depends on vacuum fluctuations. Later, the phase is rigidly locked and can be well determined versus a pulse train, which is derived from the pump laser. This delivers an ambiguity-free output, which is reliably detected and associated with a binary outcome. The resulting random bit stream resembles a perfect coin toss and passes all relevant randomness measures. The random nature of the generated binary outcome is furthermore confirmed by an analysis of resulting conditional entropies.

  9. Unbiased All-Optical Random-Number Generator

    Directory of Open Access Journals (Sweden)

    Tobias Steinle

    2017-11-01

    Full Text Available The generation of random bits is of enormous importance in modern information science. Cryptographic security is based on random numbers which require a physical process for their generation. This is commonly performed by hardware random-number generators. These often exhibit a number of problems, namely experimental bias, memory in the system, and other technical subtleties, which reduce the reliability in the entropy estimation. Further, the generated outcome has to be postprocessed to “iron out” such spurious effects. Here, we present a purely optical randomness generator, based on the bistable output of an optical parametric oscillator. Detector noise plays no role and postprocessing is reduced to a minimum. Upon entering the bistable regime, initially the resulting output phase depends on vacuum fluctuations. Later, the phase is rigidly locked and can be well determined versus a pulse train, which is derived from the pump laser. This delivers an ambiguity-free output, which is reliably detected and associated with a binary outcome. The resulting random bit stream resembles a perfect coin toss and passes all relevant randomness measures. The random nature of the generated binary outcome is furthermore confirmed by an analysis of resulting conditional entropies.

  10. Streaming Algorithms for Optimal Generation of Random Bits

    OpenAIRE

    Zhou, Hongchao; Bruck, Jehoshua

    2012-01-01

    Generating random bits from a source of biased coins (the biased is unknown) is a classical question that was originally studied by von Neumann. There are a number of known algorithms that have asymptotically optimal information efficiency, namely, the expected number of generated random bits per input bit is asymptotically close to the entropy of the source. However, only the original von Neumann algorithm has a 'streaming property' - it operates on a single input bit at a time and it genera...

  11. Random Number Generation for Petascale Quantum Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Ashok Srinivasan

    2010-03-16

    The quality of random number generators can affect the results of Monte Carlo computations, especially when a large number of random numbers are consumed. Furthermore, correlations present between different random number streams in a parallel computation can further affect the results. The SPRNG software, which the author had developed earlier, has pseudo-random number generators (PRNGs) capable of producing large numbers of streams with large periods. However, they had been empirically tested on only thousand streams earlier. In the work summarized here, we tested the SPRNG generators with over a hundred thousand streams, involving over 10^14 random numbers per test, on some tests. We also tested the popular Mersenne Twister. We believe that these are the largest tests of PRNGs, both in terms of the numbers of streams tested and the number of random numbers tested. We observed defects in some of these generators, including the Mersenne Twister, while a few generators appeared to perform well. We also corrected an error in the implementation of one of the SPRNG generators.

  12. Long term outcomes of new generation drug eluting stents versus coronary artery bypass grafting for multivessel and/or left main coronary artery disease. A Bayesian network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mina, George S; Watti, Hussam; Soliman, Demiana; Shewale, Anand; Atkins, Jessica; Reddy, Pratap; Dominic, Paari

    2018-01-05

    Most data guiding revascularization of multivessel disease (MVD) and/or left main disease (LMD) favor coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). However, those data are based on trials comparing CABG to bare metal stents (BMS) or old generation drug eluting stents (OG-DES). Hence, it is essential to outcomes of CABG to those of new generation drug eluting stents (NG-DES). We searched PUBMED and Cochrane database for trials evaluating revascularization of MVD and/or LMD with CABG and/or PCI. A Bayesian network meta-analysis was performed to calculate odds ratios (OR) and 95% credible intervals (CrI). Primary outcome was major adverse cardiovascular events (MACE) at 3-5 years. Secondary outcomes were mortality, cerebrovascular accidents (CVA), myocardial infarction (MI) and repeat revascularization. We included 10 trials with a total of 9287 patients. CABG was associated with lower MACE when compared to BMS or OG-DES. However, MACE was not significantly different between CABG and NG-DES (OR 0.79, CrI 0.45-1.40). Moreover, there were no significant differences between CABG and NG-DES in mortality (OR 0.78, CrI 0.45-1.37), CVA (OR 0.93 CrI 0.35-2.2) or MI (OR 0.6, CrI 0.17-2.0). On the other hand, CABG was associated with lower repeat revascularization (OR 0.55, CrI 0.36-0.84). Our study suggests that NG-DES is an acceptable alternative to CABG in patients with MVD and/or LMD. However, repeat revascularization remains to be lower with CABG than with PCI. Copyright © 2018. Published by Elsevier Inc.

  13. The Reliability of Randomly Generated Math Curriculum-Based Measurements

    Science.gov (United States)

    Strait, Gerald G.; Smith, Bradley H.; Pender, Carolyn; Malone, Patrick S.; Roberts, Jarod; Hall, John D.

    2015-01-01

    "Curriculum-Based Measurement" (CBM) is a direct method of academic assessment used to screen and evaluate students' skills and monitor their responses to academic instruction and intervention. Interventioncentral.org offers a math worksheet generator at no cost that creates randomly generated "math curriculum-based measures"…

  14. Generation of Random Numbers and Parallel Random Number Streams for Monte Carlo Simulations

    Directory of Open Access Journals (Sweden)

    L. Yu. Barash

    2012-01-01

    Full Text Available Modern methods and libraries for high quality pseudorandom number generation and for generation of parallel random number streams for Monte Carlo simulations are considered. The probability equidistribution property and the parameters when the property holds at dimensions up to logarithm of mesh size are considered for Multiple Recursive Generators.

  15. Brain potentials index executive functions during random number generation.

    Science.gov (United States)

    Joppich, Gregor; Däuper, Jan; Dengler, Reinhard; Johannes, Sönke; Rodriguez-Fornells, Antoni; Münte, Thomas F

    2004-06-01

    The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation.

  16. Efficient Raman generation in a waveguide: A route to ultrafast quantum random number generation

    Energy Technology Data Exchange (ETDEWEB)

    England, D. G.; Bustard, P. J.; Moffatt, D. J.; Nunn, J.; Lausten, R.; Sussman, B. J., E-mail: ben.sussman@nrc.ca [National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6 (Canada)

    2014-02-03

    The inherent uncertainty in quantum mechanics offers a source of true randomness which can be used to produce unbreakable cryptographic keys. We discuss the development of a high-speed random number generator based on the quantum phase fluctuations in spontaneously initiated stimulated Raman scattering (SISRS). We utilize the tight confinement and long interaction length available in a Potassium Titanyl Phosphate waveguide to generate highly efficient SISRS using nanojoule pulse energies, reducing the high pump power requirements of the previous approaches. We measure the random phase of the Stokes output using a simple interferometric setup to yield quantum random numbers at 145 Mbps.

  17. Chaos-based Pseudo-random Number Generation

    KAUST Repository

    Barakat, Mohamed L.

    2014-04-10

    Various methods and systems related to chaos-based pseudo-random number generation are presented. In one example, among others, a system includes a pseudo-random number generator (PRNG) to generate a series of digital outputs and a nonlinear post processing circuit to perform an exclusive OR (XOR) operation on a first portion of a current digital output of the PRNG and a permutated version of a corresponding first portion of a previous post processed output to generate a corresponding first portion of a current post processed output. In another example, a method includes receiving at least a first portion of a current output from a PRNG and performing an XOR operation on the first portion of the current PRNG output with a permutated version of a corresponding first portion of a previous post processed output to generate a corresponding first portion of a current post processed output.

  18. Random generation of RNA secondary structures according to native distributions

    Directory of Open Access Journals (Sweden)

    Nebel Markus E

    2011-10-01

    Full Text Available Abstract Background Random biological sequences are a topic of great interest in genome analysis since, according to a powerful paradigm, they represent the background noise from which the actual biological information must differentiate. Accordingly, the generation of random sequences has been investigated for a long time. Similarly, random object of a more complicated structure like RNA molecules or proteins are of interest. Results In this article, we present a new general framework for deriving algorithms for the non-uniform random generation of combinatorial objects according to the encoding and probability distribution implied by a stochastic context-free grammar. Briefly, the framework extends on the well-known recursive method for (uniform random generation and uses the popular framework of admissible specifications of combinatorial classes, introducing weighted combinatorial classes to allow for the non-uniform generation by means of unranking. This framework is used to derive an algorithm for the generation of RNA secondary structures of a given fixed size. We address the random generation of these structures according to a realistic distribution obtained from real-life data by using a very detailed context-free grammar (that models the class of RNA secondary structures by distinguishing between all known motifs in RNA structure. Compared to well-known sampling approaches used in several structure prediction tools (such as SFold ours has two major advantages: Firstly, after a preprocessing step in time O(n2 for the computation of all weighted class sizes needed, with our approach a set of m random secondary structures of a given structure size n can be computed in worst-case time complexity Om⋅n⋅ log(n while other algorithms typically have a runtime in O(m⋅n2. Secondly, our approach works with integer arithmetic only which is faster and saves us from all the discomforting details of using floating point arithmetic with

  19. A Quickly Tested Pascal Random Number Generator for Microcomputers.

    Science.gov (United States)

    1985-05-01

    in any way at equal intervals spaced h units apart, the serial correlation of the series can be obtained for various lags and tested against...pass handily. The unit range between zero and unity was divided into 100 equally spaced frequencies, and the generated random numbers were...NSDTEST; (*MEAN AND SDEV TESTS*) FREQKOLTEST; (*CHISQ FREQ DISTR AND KOLMOGOROFF -SMIRNOV TESTS*) PAIRTEST; (*TEST DISTR OF RANDOM PAIRS*) TRIOTEST; (*TEST

  20. Canonical and new generation anticancer drugs also target energy metabolism.

    Science.gov (United States)

    Rodríguez-Enríquez, Sara; Gallardo-Pérez, Juan Carlos; Hernández-Reséndiz, Ileana; Marín-Hernández, Alvaro; Pacheco-Velázquez, Silvia C; López-Ramírez, Sayra Y; Rumjanek, Franklin D; Moreno-Sánchez, Rafael

    2014-07-01

    Significant efforts have been made for the development of new anticancer drugs (protein kinase or proteasome inhibitors, monoclonal humanized antibodies) with presumably low or negligible side effects and high specificity. However, an in-depth analysis of the side effects of several currently used canonical (platin-based drugs, taxanes, anthracyclines, etoposides, antimetabolites) and new generation anticancer drugs as the first line of clinical treatment reveals significant perturbation of glycolysis and oxidative phosphorylation. Canonical and new generation drug side effects include decreased (1) intracellular ATP levels, (2) glycolytic/mitochondrial enzyme/transporter activities and/or (3) mitochondrial electrical membrane potentials. Furthermore, the anti-proliferative effects of these drugs are markedly attenuated in tumor rho (0) cells, in which functional mitochondria are absent; in addition, several anticancer drugs directly interact with isolated mitochondria affecting their functions. Therefore, several anticancer drugs also target the energy metabolism, and hence, the documented inhibitory effect of anticancer drugs on cancer growth should also be linked to the blocking of ATP supply pathways. These often overlooked effects of canonical and new generation anticancer drugs emphasize the role of energy metabolism in maintaining cancer cells viable and its targeting as a complementary and successful strategy for cancer treatment.

  1. Analysis of entropy extraction efficiencies in random number generation systems

    Science.gov (United States)

    Wang, Chao; Wang, Shuang; Chen, Wei; Yin, Zhen-Qiang; Han, Zheng-Fu

    2016-05-01

    Random numbers (RNs) have applications in many areas: lottery games, gambling, computer simulation, and, most importantly, cryptography [N. Gisin et al., Rev. Mod. Phys. 74 (2002) 145]. In cryptography theory, the theoretical security of the system calls for high quality RNs. Therefore, developing methods for producing unpredictable RNs with adequate speed is an attractive topic. Early on, despite the lack of theoretical support, pseudo RNs generated by algorithmic methods performed well and satisfied reasonable statistical requirements. However, as implemented, those pseudorandom sequences were completely determined by mathematical formulas and initial seeds, which cannot introduce extra entropy or information. In these cases, “random” bits are generated that are not at all random. Physical random number generators (RNGs), which, in contrast to algorithmic methods, are based on unpredictable physical random phenomena, have attracted considerable research interest. However, the way that we extract random bits from those physical entropy sources has a large influence on the efficiency and performance of the system. In this manuscript, we will review and discuss several randomness extraction schemes that are based on radiation or photon arrival times. We analyze the robustness, post-processing requirements and, in particular, the extraction efficiency of those methods to aid in the construction of efficient, compact and robust physical RNG systems.

  2. Quantum random flip-flop and its applications in random frequency synthesis and true random number generation

    Energy Technology Data Exchange (ETDEWEB)

    Stipčević, Mario, E-mail: mario.stipcevic@irb.hr [Photonics and Quantum Optics Research Unit, Center of Excellence for Advanced Materials and Sensing Devices, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb (Croatia)

    2016-03-15

    In this work, a new type of elementary logic circuit, named random flip-flop (RFF), is proposed, experimentally realized, and studied. Unlike conventional Boolean logic circuits whose action is deterministic and highly reproducible, the action of a RFF is intentionally made maximally unpredictable and, in the proposed realization, derived from a fundamentally random process of emission and detection of light quanta. We demonstrate novel applications of RFF in randomness preserving frequency division, random frequency synthesis, and random number generation. Possible usages of these applications in the information and communication technology, cryptographic hardware, and testing equipment are discussed.

  3. Variability in response to albuminuria lowering drugs : true or random?

    NARCIS (Netherlands)

    Petrykiv, Sergei I.; de Zeeuw, Dick; Persson, Frederik; Rossing, Peter; Gansevoort, Ron T.; Laverman, Gozewijn D.; Heerspink, Hiddo J. L.

    AIMS Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day- to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random

  4. Solution-Processed Carbon Nanotube True Random Number Generator.

    Science.gov (United States)

    Gaviria Rojas, William A; McMorrow, Julian J; Geier, Michael L; Tang, Qianying; Kim, Chris H; Marks, Tobin J; Hersam, Mark C

    2017-08-09

    With the growing adoption of interconnected electronic devices in consumer and industrial applications, there is an increasing demand for robust security protocols when transmitting and receiving sensitive data. Toward this end, hardware true random number generators (TRNGs), commonly used to create encryption keys, offer significant advantages over software pseudorandom number generators. However, the vast network of devices and sensors envisioned for the "Internet of Things" will require small, low-cost, and mechanically flexible TRNGs with low computational complexity. These rigorous constraints position solution-processed semiconducting single-walled carbon nanotubes (SWCNTs) as leading candidates for next-generation security devices. Here, we demonstrate the first TRNG using static random access memory (SRAM) cells based on solution-processed SWCNTs that digitize thermal noise to generate random bits. This bit generation strategy can be readily implemented in hardware with minimal transistor and computational overhead, resulting in an output stream that passes standardized statistical tests for randomness. By using solution-processed semiconducting SWCNTs in a low-power, complementary architecture to achieve TRNG, we demonstrate a promising approach for improving the security of printable and flexible electronics.

  5. RNA nanomedicines: the next generation drugs?

    Science.gov (United States)

    Singh, Manu Smriti; Peer, Dan

    2016-06-01

    RNA therapeutics could represent the next generation personalized medicine. The variety of RNA molecules that can inhibit the expression of any mRNA using, for example, RNA interference (RNAi) strategies, or increase the expression of a given protein using modified mRNA together with new gene editing strategies open new avenues for manipulating the fate of diseased cells while leaving healthy cells untouched. In addition, these therapeutic RNA molecules can maximize the treatment of diseases and minimize its adverse effects. Yet, the promise of RNA therapeutics is hindered by the lack of efficient delivery strategies to selectively target these molecules into specific cells. Herein, we will focus on the challenges and opportunities of the delivery of therapeutic RNAi molecules into cancer cells with special emphasis on solid tumors. Solid tumors represent more than 80 percent of cancers and some are very challenging to treat, not merely due to physiological barriers but also since the tumor microenvironment (TME) is a complex milieu of accessory cells besides the cancerous cells. In this review, we will highlight various limiting factors to successful delivery, current clinical achievements and future outlook focusing on RNAi therapeutics to the TME. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Evolution of Random Number Generation in MUVES

    Science.gov (United States)

    2017-01-01

    3 2. Collins JC . Testing, selection, and implementation of random number genera- tors. Aberdeen Proving Ground (MD): Army Research Laboratory (US...261–269. 13, 16 5. L‘Ecuyer P. Tables of linear congruential generators of different sizes and good lattice structure. Mathematics of Computation

  7. Random Scenario Generation for a Multiple Target Tracking Environment Evaluation

    DEFF Research Database (Denmark)

    Hussain, Dil Muhammad Akbar

    2006-01-01

    The paper presents a simulation study on the generation of a random scenario for the performance of track splitting algorithm on a digital signal processor.  Much of the previous work [1] was done on specific (deterministic) scenarios. One of the reasons for considering the specific scenarios, wh...

  8. Simulations Using Random-Generated DNA and RNA Sequences

    Science.gov (United States)

    Bryce, C. F. A.

    1977-01-01

    Using a very simple computer program written in BASIC, a very large number of random-generated DNA or RNA sequences are obtained. Students use these sequences to predict complementary sequences and translational products, evaluate base compositions, determine frequencies of particular triplet codons, and suggest possible secondary structures.…

  9. REGAL: a library to randomly and exhaustively generate automata

    OpenAIRE

    Bassino, Frédérique; David, Julien; Nicaud, Cyril

    2007-01-01

    International audience; This paper presents a library devoted to the random and exhaustive generation of finite deterministic automata. This package provides a toolkit to experimentally study properties of automata, average complexities of algorithms dealing with automata or to compare different implementations of the same algorithm.

  10. Generation of genetically modified rodents using random ENU mutagenesis

    NARCIS (Netherlands)

    van Boxtel, R.; Cuppen, E.

    2011-01-01

    The generation of genetically modified animals using N-ethyl-N-nitrosourea (ENU) mutagenesis is a fast and highly effective method. The technique is based on treating male animals with the supermutagen ENU, which randomly introduces mutations in the spermatogonial stem cells. By breeding these

  11. Electrical generation of stationary light in random scattering media

    Science.gov (United States)

    Redmond, S. M.; Armstrong, G. L.; Chan, H.-Y.; Mattson, E.; Mock, A.; Li, B.; Potts, J. R.; Cui, M.; Rand, S. C.; Oliveira, S. L.; Marchal, J.; Hinklin, T.; Laine, R. M.

    2004-01-01

    In recent years there has been great interest in controlling the speed of propagation of electromagnetic waves. In gases and crystals, coherent techniques have been applied to alter the speed of light without changing the physical or chemical structure of the medium. Also, light transmitted by highly disordered solids has exhibited signatures of Anderson localization, indicating the existence of a regime of ``stopped'' light that is mediated by random elastic scattering. However, to date, light has not been generated in a random medium as a pointlike excitation that is fixed in space from the outset. Here we report experimental evidence for the electrical generation and confinement of light within nanosized volumes of a random dielectric scattering medium in which a population inversion has been established, and discuss the properties of these novel light sources.

  12. Source-Device-Independent Ultrafast Quantum Random Number Generation

    Science.gov (United States)

    Marangon, Davide G.; Vallone, Giuseppe; Villoresi, Paolo

    2017-02-01

    Secure random numbers are a fundamental element of many applications in science, statistics, cryptography and more in general in security protocols. We present a method that enables the generation of high-speed unpredictable random numbers from the quadratures of an electromagnetic field without any assumption on the input state. The method allows us to eliminate the numbers that can be predicted due to the presence of classical and quantum side information. In particular, we introduce a procedure to estimate a bound on the conditional min-entropy based on the entropic uncertainty principle for position and momentum observables of infinite dimensional quantum systems. By the above method, we experimentally demonstrated the generation of secure true random bits at a rate greater than 1.7 Gbit /s .

  13. Efficient biased random bit generation for parallel processing

    Energy Technology Data Exchange (ETDEWEB)

    Slone, Dale M. [Univ. of California, Davis, CA (United States)

    1994-09-28

    A lattice gas automaton was implemented on a massively parallel machine (the BBN TC2000) and a vector supercomputer (the CRAY C90). The automaton models Burgers equation ρt + ρρx = vρxx in 1 dimension. The lattice gas evolves by advecting and colliding pseudo-particles on a 1-dimensional, periodic grid. The specific rules for colliding particles are stochastic in nature and require the generation of many billions of random numbers to create the random bits necessary for the lattice gas. The goal of the thesis was to speed up the process of generating the random bits and thereby lessen the computational bottleneck of the automaton.

  14. The frequency of drugs in randomly selected drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Hels, Tove

    Introduction Driving under the influence of alcohol and drugs is a global problem. In Denmark as well as in other countries there is an increasing focus on impaired driving. Little is known about the occurrence of psychoactive drugs in the general traffic. Therefore the European commission...... initiated the DRUID project. This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Methods Oral fluid samples (n = 3002) were collected randomly from drivers using a sampling scheme...... stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Results Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53 g/l, which...

  15. Random number generation based on digital differential chaos

    KAUST Repository

    Zidan, Mohammed A.

    2012-07-29

    In this paper, we present a fully digital differential chaos based random number generator. The output of the digital circuit is proved to be chaotic by calculating the output time series maximum Lyapunov exponent. We introduce a new post processing technique to improve the distribution and statistical properties of the generated data. The post-processed output passes the NIST Sp. 800-22 statistical tests. The system is written in Verilog VHDL and realized on Xilinx Virtex® FPGA. The generator can fit into a very small area and have a maximum throughput of 2.1 Gb/s.

  16. DNA based random key generation and management for OTP encryption.

    Science.gov (United States)

    Zhang, Yunpeng; Liu, Xin; Sun, Manhui

    2017-09-01

    One-time pad (OTP) is a principle of key generation applied to the stream ciphering method which offers total privacy. The OTP encryption scheme has proved to be unbreakable in theory, but difficult to realize in practical applications. Because OTP encryption specially requires the absolute randomness of the key, its development has suffered from dense constraints. DNA cryptography is a new and promising technology in the field of information security. DNA chromosomes storing capabilities can be used as one-time pad structures with pseudo-random number generation and indexing in order to encrypt the plaintext messages. In this paper, we present a feasible solution to the OTP symmetric key generation and transmission problem with DNA at the molecular level. Through recombinant DNA technology, by using only sender-receiver known restriction enzymes to combine the secure key represented by DNA sequence and the T vector, we generate the DNA bio-hiding secure key and then place the recombinant plasmid in implanted bacteria for secure key transmission. The designed bio experiments and simulation results show that the security of the transmission of the key is further improved and the environmental requirements of key transmission are reduced. Analysis has demonstrated that the proposed DNA-based random key generation and management solutions are marked by high security and usability. Published by Elsevier B.V.

  17. GASPRNG: GPU accelerated scalable parallel random number generator library

    Science.gov (United States)

    Gao, Shuang; Peterson, Gregory D.

    2013-04-01

    Graphics processors represent a promising technology for accelerating computational science applications. Many computational science applications require fast and scalable random number generation with good statistical properties, so they use the Scalable Parallel Random Number Generators library (SPRNG). We present the GPU Accelerated SPRNG library (GASPRNG) to accelerate SPRNG in GPU-based high performance computing systems. GASPRNG includes code for a host CPU and CUDA code for execution on NVIDIA graphics processing units (GPUs) along with a programming interface to support various usage models for pseudorandom numbers and computational science applications executing on the CPU, GPU, or both. This paper describes the implementation approach used to produce high performance and also describes how to use the programming interface. The programming interface allows a user to be able to use GASPRNG the same way as SPRNG on traditional serial or parallel computers as well as to develop tightly coupled programs executing primarily on the GPU. We also describe how to install GASPRNG and use it. To help illustrate linking with GASPRNG, various demonstration codes are included for the different usage models. GASPRNG on a single GPU shows up to 280x speedup over SPRNG on a single CPU core and is able to scale for larger systems in the same manner as SPRNG. Because GASPRNG generates identical streams of pseudorandom numbers as SPRNG, users can be confident about the quality of GASPRNG for scalable computational science applications. Catalogue identifier: AEOI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOI_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: UTK license. No. of lines in distributed program, including test data, etc.: 167900 No. of bytes in distributed program, including test data, etc.: 1422058 Distribution format: tar.gz Programming language: C and CUDA. Computer: Any PC or

  18. Generation of correlated finite alphabet waveforms using gaussian random variables

    KAUST Repository

    Jardak, Seifallah

    2014-09-01

    Correlated waveforms have a number of applications in different fields, such as radar and communication. It is very easy to generate correlated waveforms using infinite alphabets, but for some of the applications, it is very challenging to use them in practice. Moreover, to generate infinite alphabet constant envelope correlated waveforms, the available research uses iterative algorithms, which are computationally very expensive. In this work, we propose simple novel methods to generate correlated waveforms using finite alphabet constant and non-constant-envelope symbols. To generate finite alphabet waveforms, the proposed method map the Gaussian random variables onto the phase-shift-keying, pulse-amplitude, and quadrature-amplitude modulation schemes. For such mapping, the probability-density-function of Gaussian random variables is divided into M regions, where M is the number of alphabets in the corresponding modulation scheme. By exploiting the mapping function, the relationship between the cross-correlation of Gaussian and finite alphabet symbols is derived. To generate equiprobable symbols, the area of each region is kept same. If the requirement is to have each symbol with its own unique probability, the proposed scheme allows us that as well. Although, the proposed scheme is general, the main focus of this paper is to generate finite alphabet waveforms for multiple-input multiple-output radar, where correlated waveforms are used to achieve desired beampatterns. © 2014 IEEE.

  19. New Design of Crypto-Based Pseudo random number generator (CBPRNG) using BLOW FISH cipher

    OpenAIRE

    T.Chalama Reddy; Dr.R.Seshadri

    2013-01-01

    Random Number Generators (RNGs) are an important building block for algorithms and protocols in cryptography. Random number generation is used in a wide variety of cryptographic operations, such as key generation and challenge/response protocols. A random number generator outputs a sequence of 0s and 1s such that at any position, the next bit cannot be expected on the previous bits. However, true random number produces non- deterministic output since if the same random generator is run twice,...

  20. PRIMITIVE MATRICES AND GENERATORS OF PSEUDO RANDOM SEQUENCES OF GALOIS

    Directory of Open Access Journals (Sweden)

    A. Beletsky

    2014-04-01

    Full Text Available In theory and practice of information cryptographic protection one of the key problems is the forming a binary pseudo-random sequences (PRS with a maximum length with acceptable statistical characteristics. PRS generators are usually implemented by linear shift register (LSR of maximum period with linear feedback [1]. In this paper we extend the concept of LSR, assuming that each of its rank (memory cell can be in one of the following condition. Let’s call such registers “generalized linear shift register.” The research goal is to develop algorithms for constructing Galois and Fibonacci generalized matrix of n-order over the field , which uniquely determined both the structure of corresponding generalized of n-order LSR maximal period, and formed on their basis Galois PRS generators of maximum length. Thus the article presents the questions of formation the primitive generalized Fibonacci and Galois arbitrary order matrix over the prime field . The synthesis of matrices is based on the use of irreducible polynomials of degree and primitive elements of the extended field generated by polynomial. The constructing methods of Galois and Fibonacci conjugated primitive matrices are suggested. The using possibilities of such matrices in solving the problem of constructing generalized generators of Galois pseudo-random sequences are discussed.

  1. At least some errors are randomly generated (Freud was wrong)

    Science.gov (United States)

    Sellen, A. J.; Senders, J. W.

    1986-01-01

    An experiment was carried out to expose something about human error generating mechanisms. In the context of the experiment, an error was made when a subject pressed the wrong key on a computer keyboard or pressed no key at all in the time allotted. These might be considered, respectively, errors of substitution and errors of omission. Each of seven subjects saw a sequence of three digital numbers, made an easily learned binary judgement about each, and was to press the appropriate one of two keys. Each session consisted of 1,000 presentations of randomly permuted, fixed numbers broken into 10 blocks of 100. One of two keys should have been pressed within one second of the onset of each stimulus. These data were subjected to statistical analyses in order to probe the nature of the error generating mechanisms. Goodness of fit tests for a Poisson distribution for the number of errors per 50 trial interval and for an exponential distribution of the length of the intervals between errors were carried out. There is evidence for an endogenous mechanism that may best be described as a random error generator. Furthermore, an item analysis of the number of errors produced per stimulus suggests the existence of a second mechanism operating on task driven factors producing exogenous errors. Some errors, at least, are the result of constant probability generating mechanisms with error rate idiosyncratically determined for each subject.

  2. Generating Correlated QPSK Waveforms By Exploiting Real Gaussian Random Variables

    KAUST Repository

    Jardak, Seifallah

    2012-11-01

    The design of waveforms with specified auto- and cross-correlation properties has a number of applications in multiple-input multiple-output (MIMO) radar, one of them is the desired transmit beampattern design. In this work, an algorithm is proposed to generate quadrature phase shift- keying (QPSK) waveforms with required cross-correlation properties using real Gaussian random-variables (RV’s). This work can be considered as the extension of what was presented in [1] to generate BPSK waveforms. This work will be extended for the generation of correlated higher-order phase shift-keying (PSK) and quadrature amplitude modulation (QAM) schemes that can better approximate the desired beampattern.

  3. Cellular Automata-Based Parallel Random Number Generators Using FPGAs

    Directory of Open Access Journals (Sweden)

    David H. K. Hoe

    2012-01-01

    Full Text Available Cellular computing represents a new paradigm for implementing high-speed massively parallel machines. Cellular automata (CA, which consist of an array of locally connected processing elements, are a basic form of a cellular-based architecture. The use of field programmable gate arrays (FPGAs for implementing CA accelerators has shown promising results. This paper investigates the design of CA-based pseudo-random number generators (PRNGs using an FPGA platform. To improve the quality of the random numbers that are generated, the basic CA structure is enhanced in two ways. First, the addition of a superrule to each CA cell is considered. The resulting self-programmable CA (SPCA uses the superrule to determine when to make a dynamic rule change in each CA cell. The superrule takes its inputs from neighboring cells and can be considered itself a second CA working in parallel with the main CA. When implemented on an FPGA, the use of lookup tables in each logic cell removes any restrictions on how the super-rules should be defined. Second, a hybrid configuration is formed by combining a CA with a linear feedback shift register (LFSR. This is advantageous for FPGA designs due to the compactness of the LFSR implementations. A standard software package for statistically evaluating the quality of random number sequences known as Diehard is used to validate the results. Both the SPCA and the hybrid CA/LFSR were found to pass all the Diehard tests.

  4. Random Sequence for Optimal Low-Power Laser Generated Ultrasound

    Science.gov (United States)

    Vangi, D.; Virga, A.; Gulino, M. S.

    2017-08-01

    Low-power laser generated ultrasounds are lately gaining importance in the research world, thanks to the possibility of investigating a mechanical component structural integrity through a non-contact and Non-Destructive Testing (NDT) procedure. The ultrasounds are, however, very low in amplitude, making it necessary to use pre-processing and post-processing operations on the signals to detect them. The cross-correlation technique is used in this work, meaning that a random signal must be used as laser input. For this purpose, a highly random and simple-to-create code called T sequence, capable of enhancing the ultrasound detectability, is introduced (not previously available at the state of the art). Several important parameters which characterize the T sequence can influence the process: the number of pulses Npulses , the pulse duration δ and the distance between pulses dpulses . A Finite Element FE model of a 3 mm steel disk has been initially developed to analytically study the longitudinal ultrasound generation mechanism and the obtainable outputs. Later, experimental tests have shown that the T sequence is highly flexible for ultrasound detection purposes, making it optimal to use high Npulses and δ but low dpulses . In the end, apart from describing all phenomena that arise in the low-power laser generation process, the results of this study are also important for setting up an effective NDT procedure using this technology.

  5. Generative Recurrent Networks for De Novo Drug Design.

    Science.gov (United States)

    Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

    2018-01-01

    Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  6. Random phase-free computer-generated hologram

    CERN Document Server

    Shimobaba, Tomoyoshi

    2015-01-01

    Addition of random phase to the object light is required in computer-generated holograms (CGHs) to widely diffuse the object light and to avoid its concentration on the CGH; however, this addition causes considerable speckle noise in the reconstructed image. For improving the speckle noise problem, techniques such as iterative phase retrieval algorithms and multi-random phase method are used; however, they are time consuming and are of limited effectiveness. Herein, we present a simple and computationally inexpensive method that drastically improves the image quality and reduces the speckle noise by multiplying the object light with the virtual convergence light. Feasibility of the proposed method is shown using simulations and optical reconstructions; moreover, we apply it to lens-less zoom-able holographic projection. The proposed method is useful for the speckle problems in holographic applications.

  7. Soliton generation from randomly modulated return-to-zero pulses

    Science.gov (United States)

    Derevyanko, Stanislav A.; Prilepsky, Jaroslaw E.

    2008-11-01

    We consider return-to-zero (RZ) pulses with random phase modulation propagating in a nonlinear channel (modelled by the integrable nonlinear Schrödinger equation, NLSE). We suggest two different models for the phase fluctuations of the optical field: (i) Gaussian short-correlated fluctuations and (ii) generalized telegraph process. Using the rectangular-shaped pulse form we demonstrate that the presence of phase fluctuations of both types strongly influences the number of solitons generated in the channel. It is also shown that increasing the correlation time for the random phase fluctuations affects the coherent content of a pulse in a non-trivial way. The result obtained has potential consequences for all-optical processing and design of optical decision elements.

  8. Generation of correlated finite alphabet waveforms using gaussian random variables

    KAUST Repository

    Ahmed, Sajid

    2016-01-13

    Various examples of methods and systems are provided for generation of correlated finite alphabet waveforms using Gaussian random variables in, e.g., radar and communication applications. In one example, a method includes mapping an input signal comprising Gaussian random variables (RVs) onto finite-alphabet non-constant-envelope (FANCE) symbols using a predetermined mapping function, and transmitting FANCE waveforms through a uniform linear array of antenna elements to obtain a corresponding beampattern. The FANCE waveforms can be based upon the mapping of the Gaussian RVs onto the FANCE symbols. In another example, a system includes a memory unit that can store a plurality of digital bit streams corresponding to FANCE symbols and a front end unit that can transmit FANCE waveforms through a uniform linear array of antenna elements to obtain a corresponding beampattern. The system can include a processing unit that can encode the input signal and/or determine the mapping function.

  9. Comparison of a quantum random number generator with pseudorandom number generators for their use in molecular Monte Carlo simulations.

    Science.gov (United States)

    Ghersi, Dario; Parakh, Abhishek; Mezei, Mihaly

    2017-12-05

    Four pseudorandom number generators were compared with a physical, quantum-based random number generator using the NIST suite of statistical tests, which only the quantum-based random number generator could successfully pass. We then measured the effect of the five random number generators on various calculated properties in different Markov-chain Monte Carlo simulations. Two types of systems were tested: conformational sampling of a small molecule in aqueous solution and liquid methanol under constant temperature and pressure. The results show that poor quality pseudorandom number generators produce results that deviate significantly from those obtained with the quantum-based random number generator, particularly in the case of the small molecule in aqueous solution setup. In contrast, the widely used Mersenne Twister pseudorandom generator and a 64-bit Linear Congruential Generator with a scrambler produce results that are statistically indistinguishable from those obtained with the quantum-based random number generator. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Quantum Statistical Testing of a Quantum Random Number Generator

    Energy Technology Data Exchange (ETDEWEB)

    Humble, Travis S [ORNL

    2014-01-01

    The unobservable elements in a quantum technology, e.g., the quantum state, complicate system verification against promised behavior. Using model-based system engineering, we present methods for verifying the opera- tion of a prototypical quantum random number generator. We begin with the algorithmic design of the QRNG followed by the synthesis of its physical design requirements. We next discuss how quantum statistical testing can be used to verify device behavior as well as detect device bias. We conclude by highlighting how system design and verification methods must influence effort to certify future quantum technologies.

  11. Drug resistance analysis by next generation sequencing in Leishmania

    Science.gov (United States)

    Leprohon, Philippe; Fernandez-Prada, Christopher; Gazanion, Élodie; Monte-Neto, Rubens; Ouellette, Marc

    2014-01-01

    The use of next generation sequencing has the power to expedite the identification of drug resistance determinants and biomarkers and was applied successfully to drug resistance studies in Leishmania. This allowed the identification of modulation in gene expression, gene dosage alterations, changes in chromosome copy numbers and single nucleotide polymorphisms that correlated with resistance in Leishmania strains derived from the laboratory and from the field. An impressive heterogeneity at the population level was also observed, individual clones within populations often differing in both genotypes and phenotypes, hence complicating the elucidation of resistance mechanisms. This review summarizes the most recent highlights that whole genome sequencing brought to our understanding of Leishmania drug resistance and likely new directions. PMID:25941624

  12. Fully Digital Chaotic Oscillators Applied to Pseudo Random Number Generation

    KAUST Repository

    Mansingka, Abhinav S.

    2012-05-01

    adapted for pseudo random number generation by truncating statistically defective bits. Finally, a novel post-processing technique using the Fibonacci series is proposed and implemented with a non-autonomous driven hyperchaotic system to provide pseudo random number generators with high nonlinear complexity and controllable period length that enables full utilization of all branches of the chaotic output as statistically secure pseudo random output.

  13. High-Quality Random Number Generation Software for High-Performance Computing Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Random number (RN) generation is the key software component that permits random sampling. Software for parallel RN generation (RNG) should be based on RNGs that are...

  14. 75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

    Science.gov (United States)

    2010-12-20

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random... rail industry random testing positive rates were .037 percent for drugs and .014 percent for alcohol... 25 percent of covered railroad employees. In addition, because the industry-wide random alcohol...

  15. Exploring potential anticoagulant drug formulations using thrombin generation test

    Directory of Open Access Journals (Sweden)

    Elena Zavyalova

    2016-03-01

    The thrombin generation test was used to assess the whole coagulation cascade in normal and factor-deficient human blood plasma. Potential therapeutic windows were estimated for coagulation factors, ranking them as targets for anticoagulant drugs. Thrombin and factor Xa have been revealed as the most promising targets, which fully agrees with the current drug development strategy. Inhibitors of factors Va and VIIa are expected to have narrow therapeutic windows. Inhibitors of factors VIIIa and IXa are expected to have a moderate anticoagulant effect. Factors XI and XII are poor targets for anticoagulant drugs. Compared with plasma that is deficient in factor II, the thrombin inhibitors bivalirudin and aptamer HD1 had increased activity. Both inhibitors were tested in deficient plasma providing a model of potential drug combination. The most promising combinations were anti-thrombin with anti-V/Va and also anti-thrombin with anti-IX/IXa. Each combination had an incremental dose-effect dependence that is promising from the standpoint of the therapeutic window.

  16. Generative Learning Objects Instantiated with Random Numbers Based Expressions

    Directory of Open Access Journals (Sweden)

    Ciprian Bogdan Chirila

    2015-12-01

    Full Text Available The development of interactive e-learning content requires special skills like programming techniques, web integration, graphic design etc. Generally, online educators do not possess such skills and their e-learning products tend to be static like presentation slides and textbooks. In this paper we propose a new interactive model of generative learning objects as a compromise betweenstatic, dull materials and dynamic, complex software e-learning materials developed by specialized teams. We find that random numbers based automatic initialization learning objects increases content diversity, interactivity thus enabling learners’ engagement. The resulted learning object model is at a limited level of complexity related to special e-learning software, intuitive and capable of increasing learners’ interactivity, engagement and motivation through dynamic content. The approach was applied successfully on several computer programing disciplines.

  17. Multi-bit quantum random number generation by measuring positions of arrival photons.

    Science.gov (United States)

    Yan, Qiurong; Zhao, Baosheng; Liao, Qinghong; Zhou, Nanrun

    2014-10-01

    We report upon the realization of a novel multi-bit optical quantum random number generator by continuously measuring the arrival positions of photon emitted from a LED using MCP-based WSA photon counting imaging detector. A spatial encoding method is proposed to extract multi-bits random number from the position coordinates of each detected photon. The randomness of bits sequence relies on the intrinsic randomness of the quantum physical processes of photonic emission and subsequent photoelectric conversion. A prototype has been built and the random bit generation rate could reach 8 Mbit/s, with random bit generation efficiency of 16 bits per detected photon. FPGA implementation of Huffman coding is proposed to reduce the bias of raw extracted random bits. The random numbers passed all tests for physical random number generator.

  18. Chimeric cytochromes P450 engineered by domain swapping and random mutagenesis for producing human metabolites of drugs.

    Science.gov (United States)

    Kang, Ji-Yeon; Ryu, Sang Hoon; Park, Sun-Ha; Cha, Gun Su; Kim, Dong-Hyun; Kim, Keon-Hee; Hong, Austin W; Ahn, Taeho; Pan, Jae-Gu; Joung, Young Hee; Kang, Hyung-Sik; Yun, Chul-Ho

    2014-07-01

    Human drug metabolites produced by cytochrome P450 enzymes are critical for safety testing and may themselves act as drugs or leads in the drug discovery and development process. Here, highly active chimeric fusion proteins (chimeras) were obtained by reductase domain swapping of mutants at key catalytic residues of the heme domain with that of a natural variant (CYP102A1.2) of P450 BM3 (CYP102A1.1) from Bacillus megaterium. Random mutagenesis at the heme domain of the chimera was also used to generate chimeric mutants that were more active and diverse than the chimeras themselves. To determine whether the chimeras and several mutants of the highly active chimera displayed enhanced catalytic activity and, more importantly, whether they acquired activities of biotechnological importance, we measured the oxidation activities of the chimeras and chimeric mutants toward human P450 substrates, mainly drugs. Some of the chimeric mutants showed high activity toward typical human P450 substrates including drugs. Statin leads, especially chiral products, with inhibitory effects toward HMG-CoA reductase could be obtained from metabolites of statin drugs generated using these chimeric mutants. This study reveals the critical role of the reductase domain for the activity of P450 BM3 and shows that chimeras generated by domain swapping can be used to develop industrial enzymes for the synthesis of human metabolites from drugs and drug leads. © 2014 Wiley Periodicals, Inc.

  19. Generation and Analysis of Constrained Random Sampling Patterns

    DEFF Research Database (Denmark)

    Pierzchlewski, Jacek; Arildsen, Thomas

    2016-01-01

    Random sampling is a technique for signal acquisition which is gaining popularity in practical signal processing systems. Nowadays, event-driven analog-to-digital converters make random sampling feasible in practical applications. A process of random sampling is defined by a sampling pattern, whi...

  20. Is the randomized controlled drug trial in Europe lagging behind the USA?

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; Knol, Mirjam J.; Tijssen, Robert J. W.; van Leeuwen, Thed N.; Grobbee, Diederick E.; de Zeeuw, Dick

    2008-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? center dot The USA, UK and Germany have a strong position in performance of drug and nondrug randomized controlled trials. center dot Europe's position in the quantitative and qualitative performance in drug randomized controlled trials in particular, and

  1. Drug Generations in the 2000s: An Analysis of Arrestee Data

    OpenAIRE

    Golub, Andrew; Brownstein, Henry H.

    2013-01-01

    Much empirical evidence indicates that the popularity of various drugs tends to increase and wane over time producing episodic epidemics of particular drugs. These epidemics mostly affect persons reaching their late teens at the time of the epidemic resulting in distinct drug generations. This article examines the drug generations present in the 2000s among arrestees in the 10 locations served by the Arrestee Drug Abuse Monitoring–II program. At all 10 locations, our findings show that crack ...

  2. Realization of a Quantum Random Generator Certified with the Kochen-Specker Theorem.

    Science.gov (United States)

    Kulikov, Anatoly; Jerger, Markus; Potočnik, Anton; Wallraff, Andreas; Fedorov, Arkady

    2017-12-15

    Random numbers are required for a variety of applications from secure communications to Monte Carlo simulation. Yet randomness is an asymptotic property, and no output string generated by a physical device can be strictly proven to be random. We report an experimental realization of a quantum random number generator (QRNG) with randomness certified by quantum contextuality and the Kochen-Specker theorem. The certification is not performed in a device-independent way but through a rigorous theoretical proof of each outcome being value indefinite even in the presence of experimental imperfections. The analysis of the generated data confirms the incomputable nature of our QRNG.

  3. Realization of a Quantum Random Generator Certified with the Kochen-Specker Theorem

    Science.gov (United States)

    Kulikov, Anatoly; Jerger, Markus; Potočnik, Anton; Wallraff, Andreas; Fedorov, Arkady

    2017-12-01

    Random numbers are required for a variety of applications from secure communications to Monte Carlo simulation. Yet randomness is an asymptotic property, and no output string generated by a physical device can be strictly proven to be random. We report an experimental realization of a quantum random number generator (QRNG) with randomness certified by quantum contextuality and the Kochen-Specker theorem. The certification is not performed in a device-independent way but through a rigorous theoretical proof of each outcome being value indefinite even in the presence of experimental imperfections. The analysis of the generated data confirms the incomputable nature of our QRNG.

  4. Drug-eluting stents for acute coronary syndrome: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Lishan Wang

    Full Text Available Drug-eluting stents (DES are increasingly used for treatment of acute coronary syndrome (ACS. However, clinical efficacy and safety of various types of DES is not well established in these subjects. We therefore evaluated clinical utility of second-generation and first-generation DES in patients with ACS by conducting a meta-analysis.A search of Medline, Embase, the Cochrane databases, and Web of Science was made. Randomized controlled trials (RCTs which compared second-generation DES (everolimus-eluting stents [EES] or zotarolimus-eluting stents [ZES] versus first-generation DES (sirolimus-eluting stents [SES] or paclitaxe-eluting stents [PES] in patients with ACS and provided data on clinical efficacy or safety endpoints were included. Pooled estimates were calculated using random-effects model.A total of 2,757 participants with ACS in 6 RCTs were included. Compared with first-generation one, second-generation DES trended to be associated with the decreased incidence of definite or probable stent thrombosis in ACS patients (risk ratio [RR]  = 0.60, 95% confidence intervals [CI] 0.33 to 1.07, p = 0.09. However, the rate of target lesion revascularization (TLR significantly increased in second-generation DES (RR = 2.08, 95%CI 1.25 to 3.47, p = 0.005. There were no significant differences in the incidence of major adverse cardiac events (MACEs, all-cause death, cardiac death, and recurrent myocardial infarction between the two arms (all p>0.10. The second-generation EES showed a tendency towards lower risk of MACEs (p = 0.06 and a beneficial effect on reducing stent thrombosis episodes (p = 0.009, while the second-generation ZES presented an increased occurrence of MACEs (p = 0.02 and TLR (p = 0.003.Second-generation DES, especially EES, appeared to present a lower risk of stent thrombosis, whereas second-generation ZES might increase the need for repeat revascularization in ACS patients. During coronary

  5. LOMA: A fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens

    Directory of Open Access Journals (Sweden)

    Lee Wah

    2008-09-01

    Full Text Available Abstract Background Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals. Results In this paper, we study how the efficiency of random PCR amplification affects hybridization signals. We describe a model that predicts the amplification efficiency of a given random primer on a target viral genome. The prediction allows us to filter false-negative probes of the genome that lie in regions of poor random PCR amplification and improves the accuracy of pathogen detection. Subsequently, we propose LOMA, an algorithm to generate random primers that have good amplification efficiency. Wet-lab validation showed that the generated random primers improve the amplification efficiency significantly. Conclusion The blind use of a random primer with attached universal tag (random-tagged primer in a PCR reaction on a pathogen sample may not lead to a successful amplification. Thus, the design of random-tagged primers is an important consideration when performing PCR.

  6. Effectiveness of second generation antipsychotics: A systematic review of randomized trials

    Directory of Open Access Journals (Sweden)

    Jørgensen Hugo A

    2008-04-01

    Full Text Available Abstract Background Systematic reviews based on efficacy trials are inconclusive about which second generation antipsychotic drug (SGA should be preferred in normal clinical practice, and studies with longer duration and more pragmatic designs are called for. Effectiveness studies, also known as naturalistic, pragmatic, practical or real life studies, adhere to these principles as they aim to mimic daily clinical practice and have longer follow-up. Objective To review the head-to-head effectiveness of SGAs in the domains of global outcomes, symptoms of disease, and tolerability. Methods Searches were made in Embase, PubMED, and the Cochrane central register of controlled trials for effectiveness studies published from 1980 to 2008, week 1. Different combinations of the keywords antipsychotic*, neuroleptic* AND open, pragmatic, practical, naturalistic, real life, effectiveness, side effect*, unwanted effect*, tolera* AND compar* AND random* were used. Results Sixteen different reports of randomized head-to-head comparisons of SGA effectiveness were located. There were differences regarding sample sizes, inclusion criteria and follow-up periods, as well as sources of financial sponsorship. In acute-phase and first-episode patients no differences between the SGAs were disclosed regarding alleviating symptoms of disease. Olanzapine was associated with more weight gain and adverse effects on serum lipids. In the chronic phase patients olanzapine groups had longer time to discontinuation of treatment and better treatment adherence compared to other SGAs. The majority of studies found no differences between the SGAs in alleviating symptoms of psychosis in chronically ill patients. Olanzapine was associated with more metabolic adverse effects compared to the others SGAs. There were surprisingly few between-drug differences regarding side effects. First generation antipsychotics were associated with lower total mental health care costs in 2 of 3 studies

  7. Algorithm for generation pseudo-random series with arbitrarily assigned distribution law

    Directory of Open Access Journals (Sweden)

    В.С. Єременко

    2005-04-01

    Full Text Available  Method for generation pseudo-random series with arbitrarily assigned distribution law has been proposed. The praxis of using proposed method for generation pseudo-random series with anti-modal and approximate to Gaussian distribution law has been investigated.

  8. Generating Variable and Random Schedules of Reinforcement Using Microsoft Excel Macros

    Science.gov (United States)

    Bancroft, Stacie L; Bourret, Jason C

    2008-01-01

    Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time. Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time. Generating schedule values for variable and random reinforcement schedules can be difficult. The present article describes the steps necessary to write macros in Microsoft Excel that will generate variable-ratio, variable-interval, variable-time, random-ratio, random-interval, and random-time reinforcement schedule values. PMID:18595286

  9. High-speed quantum-random number generation by continuous measurement of arrival time of photons.

    Science.gov (United States)

    Yan, Qiurong; Zhao, Baosheng; Hua, Zhang; Liao, Qinghong; Yang, Hao

    2015-07-01

    We demonstrate a novel high speed and multi-bit optical quantum random number generator by continuously measuring arrival time of photons with a common starting point. To obtain the unbiased and post-processing free random bits, the measured photon arrival time is converted into the sum of integral multiple of a fixed period and a phase time. Theoretical and experimental results show that the phase time is an independent and uniform random variable. A random bit extraction method by encoding the phase time is proposed. An experimental setup has been built and the unbiased random bit generation rate could reach 128 Mb/s, with random bit generation efficiency of 8 bits per detected photon. The random numbers passed all tests in the statistical test suite.

  10. Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules.

    Science.gov (United States)

    Gantt, Richard W; Peltier-Pain, Pauline; Thorson, Jon S

    2011-10-01

    Glyco (randomization/diversification) is a term that encompasses strategies to diversify a core drug scaffold via enzymatic glycosylation to provide sets of analogs wherein the sole diversity element is a carbohydrate. This review covers the influence of glycosylation upon various drug properties, the classes of glycosyl-conjugating enzymes amenable to glyco(randomization/diversification) schemes, approaches to the synthesis of required substrates and specific examples of glycorandomized libraries utilizing both wild-type and engineered enzymes.

  11. Generation and monitoring of a discrete stable random process

    CERN Document Server

    Hopcraft, K I; Matthews, J O

    2002-01-01

    A discrete stochastic process with stationary power law distribution is obtained from a death-multiple immigration population model. Emigrations from the population form a random series of events which are monitored by a counting process with finite-dynamic range and response time. It is shown that the power law behaviour of the population is manifested in the intermittent behaviour of the series of events. (letter to the editor)

  12. Communicating uncertainties about prescription drugs to the public: a national randomized trial.

    Science.gov (United States)

    Schwartz, Lisa M; Woloshin, Steven

    2011-09-12

    Many new drugs are aggressively promoted. The public may not realize that even with US Food and Drug Administration (FDA) approval, important uncertainties about the benefits and harms of these drugs remain. We assessed the US public's understanding of the meaning of FDA drug approval and tested how brief explanations communicating drug uncertainties affect consumer choices. We conducted an Internet-based randomized controlled trial using a national sample of US adults from a research panel of approximately 30,000 households. A total of 2944 participants were randomized to receive 1 of 3 explanations about a pair of cholesterol drugs (1 approved based only on a surrogate outcome [lower cholesterol] and 1 based on a patient outcome [reduced myocardial infarctions]). Participants were randomized a second time to receive 1 of 3 explanations about a pair of heartburn drugs (1 newly approved and 1 approved 8 years earlier). Controls received no explanation; the nondirective group received explanations (for the cholesterol drugs, surrogates do not always translate into patient outcomes; for the heartburn drugs, it takes time to establish the safety of new drugs); the directive group received explanations plus advice to "Ask for a drug shown to reduce heart attacks or ask for one with a longer track record." The primary outcomes were choice: the cholesterol drug reducing myocardial infarctions, and the older heartburn drug. Thirty-nine percent mistakenly believed that the FDA approves only "extremely effective" drugs; 25% mistakenly believed that the FDA approves only drugs without serious side effects. Explanations affected choices: 71% of those in the directive group, 71% in the nondirective group, and 59% of controls chose the cholesterol drug that reduced myocardial infarctions (absolute difference, 12% [95% confidence interval, 7%-18%] for each explanation vs control). For the heartburn drugs, 53% of the directive group, 53% of the nondirective group, and 34% of

  13. Recommendations and illustrations for the evaluation of photonic random number generators

    Science.gov (United States)

    Hart, Joseph D.; Terashima, Yuta; Uchida, Atsushi; Baumgartner, Gerald B.; Murphy, Thomas E.; Roy, Rajarshi

    2017-09-01

    The never-ending quest to improve the security of digital information combined with recent improvements in hardware technology has caused the field of random number generation to undergo a fundamental shift from relying solely on pseudo-random algorithms to employing optical entropy sources. Despite these significant advances on the hardware side, commonly used statistical measures and evaluation practices remain ill-suited to understand or quantify the optical entropy that underlies physical random number generation. We review the state of the art in the evaluation of optical random number generation and recommend a new paradigm: quantifying entropy generation and understanding the physical limits of the optical sources of randomness. In order to do this, we advocate for the separation of the physical entropy source from deterministic post-processing in the evaluation of random number generators and for the explicit consideration of the impact of the measurement and digitization process on the rate of entropy production. We present the Cohen-Procaccia estimate of the entropy rate h (𝜖 ,τ ) as one way to do this. In order to provide an illustration of our recommendations, we apply the Cohen-Procaccia estimate as well as the entropy estimates from the new NIST draft standards for physical random number generators to evaluate and compare three common optical entropy sources: single photon time-of-arrival detection, chaotic lasers, and amplified spontaneous emission.

  14. On random field Completely Automated Public Turing Test to Tell Computers and Humans Apart generation.

    Science.gov (United States)

    Kouritzin, Michael A; Newton, Fraser; Wu, Biao

    2013-04-01

    Herein, we propose generating CAPTCHAs through random field simulation and give a novel, effective and efficient algorithm to do so. Indeed, we demonstrate that sufficient information about word tests for easy human recognition is contained in the site marginal probabilities and the site-to-nearby-site covariances and that these quantities can be embedded directly into certain conditional probabilities, designed for effective simulation. The CAPTCHAs are then partial random realizations of the random CAPTCHA word. We start with an initial random field (e.g., randomly scattered letter pieces) and use Gibbs resampling to re-simulate portions of the field repeatedly using these conditional probabilities until the word becomes human-readable. The residual randomness from the initial random field together with the random implementation of the CAPTCHA word provide significant resistance to attack. This results in a CAPTCHA, which is unrecognizable to modern optical character recognition but is recognized about 95% of the time in a human readability study.

  15. Lightweight PUF-based Key and Random Number Generation

    OpenAIRE

    Van Herrewege, Anthony

    2015-01-01

    As embedded electronics continue to be integrated into our daily lives at such a pace that there are nowadays more cellphones than people on the planet, security is becoming ever more crucial. Unfortunately, this is all too often realized as an afterthought and thus the security implementations in many embedded devices offer little to no practical protection. Security does not require only cryptographic algorithms; two other critical modules in a secure system are a key generation module and ...

  16. Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity.

    Science.gov (United States)

    Shao, Naimin; Su, Yunzhang; Hu, Jingjing; Zhang, Jiahai; Zhang, Hongfeng; Cheng, Yiyun

    2011-01-01

    Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. The dendrimer-phenylbutazone complexes were characterized by (1)H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development.

  17. A Comparison of Three Random Number Generators for Aircraft Dynamic Modeling Applications

    Science.gov (United States)

    Grauer, Jared A.

    2017-01-01

    Three random number generators, which produce Gaussian white noise sequences, were compared to assess their suitability in aircraft dynamic modeling applications. The first generator considered was the MATLAB (registered) implementation of the Mersenne-Twister algorithm. The second generator was a website called Random.org, which processes atmospheric noise measured using radios to create the random numbers. The third generator was based on synthesis of the Fourier series, where the random number sequences are constructed from prescribed amplitude and phase spectra. A total of 200 sequences, each having 601 random numbers, for each generator were collected and analyzed in terms of the mean, variance, normality, autocorrelation, and power spectral density. These sequences were then applied to two problems in aircraft dynamic modeling, namely estimating stability and control derivatives from simulated onboard sensor data, and simulating flight in atmospheric turbulence. In general, each random number generator had good performance and is well-suited for aircraft dynamic modeling applications. Specific strengths and weaknesses of each generator are discussed. For Monte Carlo simulation, the Fourier synthesis method is recommended because it most accurately and consistently approximated Gaussian white noise and can be implemented with reasonable computational effort.

  18. Doing Better by Getting Worse: Posthypnotic Amnesia Improves Random Number Generation

    Science.gov (United States)

    Terhune, Devin Blair; Brugger, Peter

    2011-01-01

    Although forgetting is often regarded as a deficit that we need to control to optimize cognitive functioning, it can have beneficial effects in a number of contexts. We examined whether disrupting memory for previous numerical responses would attenuate repetition avoidance (the tendency to avoid repeating the same number) during random number generation and thereby improve the randomness of responses. Low suggestible and low dissociative and high dissociative highly suggestible individuals completed a random number generation task in a control condition, following a posthypnotic amnesia suggestion to forget previous numerical responses, and in a second control condition following the cancellation of the suggestion. High dissociative highly suggestible participants displayed a selective increase in repetitions during posthypnotic amnesia, with equivalent repetition frequency to a random system, whereas the other two groups exhibited repetition avoidance across conditions. Our results demonstrate that temporarily disrupting memory for previous numerical responses improves random number generation. PMID:22195022

  19. Doing better by getting worse: posthypnotic amnesia improves random number generation.

    Directory of Open Access Journals (Sweden)

    Devin Blair Terhune

    Full Text Available Although forgetting is often regarded as a deficit that we need to control to optimize cognitive functioning, it can have beneficial effects in a number of contexts. We examined whether disrupting memory for previous numerical responses would attenuate repetition avoidance (the tendency to avoid repeating the same number during random number generation and thereby improve the randomness of responses. Low suggestible and low dissociative and high dissociative highly suggestible individuals completed a random number generation task in a control condition, following a posthypnotic amnesia suggestion to forget previous numerical responses, and in a second control condition following the cancellation of the suggestion. High dissociative highly suggestible participants displayed a selective increase in repetitions during posthypnotic amnesia, with equivalent repetition frequency to a random system, whereas the other two groups exhibited repetition avoidance across conditions. Our results demonstrate that temporarily disrupting memory for previous numerical responses improves random number generation.

  20. High-speed true random number generation based on paired memristors for security electronics

    Science.gov (United States)

    Zhang, Teng; Yin, Minghui; Xu, Changmin; Lu, Xiayan; Sun, Xinhao; Yang, Yuchao; Huang, Ru

    2017-11-01

    True random number generator (TRNG) is a critical component in hardware security that is increasingly important in the era of mobile computing and internet of things. Here we demonstrate a TRNG using intrinsic variation of memristors as a natural source of entropy that is otherwise undesirable in most applications. The random bits were produced by cyclically switching a pair of tantalum oxide based memristors and comparing their resistance values in the off state, taking advantage of the more pronounced resistance variation compared with that in the on state. Using an alternating read scheme in the designed TRNG circuit, the unbiasedness of the random numbers was significantly improved, and the bitstream passed standard randomness tests. The Pt/TaO x /Ta memristors fabricated in this work have fast programming/erasing speeds of ∼30 ns, suggesting a high random number throughput. The approach proposed here thus holds great promise for physically-implemented random number generation.

  1. Note: A 10 Gbps real-time post-processing free physical random number generator chip

    Science.gov (United States)

    Qian, Yi; Liang, Futian; Wang, Xinzhe; Li, Feng; Chen, Lian; Jin, Ge

    2017-09-01

    A random number generator with high data rate, small size, and low power consumption is essential for a certain quantum key distribution (QKD) system. We designed a 10 Gbps random number generator ASIC, TRNG2016, for the QKD system. With a 6 mm × 6 mm QFN48 package, TRNG2016 has 10 independent physical random number generation channels, and each channel can work at a fixed frequency up to 1 Gbps. The random number generated by TRNG2016 can pass the NIST statistical tests without any post-processing. With 3.3 V IO power supply and 1.2 V core power supply, the typical power consumption of TRNG2016 is 773 mW with 10 channels on and running at 1 Gbps data rate.

  2. Note: Fully integrated 3.2 Gbps quantum random number generator with real-time extraction

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiao-Guang; Nie, You-Qi; Liang, Hao; Zhang, Jun, E-mail: zhangjun@ustc.edu.cn; Pan, Jian-Wei [Hefei National Laboratory for Physical Sciences at the Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); CAS Center for Excellence and Synergetic Innovation Center in Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhou, Hongyi; Ma, Xiongfeng [Center for Quantum Information, Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing 100084 (China)

    2016-07-15

    We present a real-time and fully integrated quantum random number generator (QRNG) by measuring laser phase fluctuations. The QRNG scheme based on laser phase fluctuations is featured for its capability of generating ultra-high-speed random numbers. However, the speed bottleneck of a practical QRNG lies on the limited speed of randomness extraction. To close the gap between the fast randomness generation and the slow post-processing, we propose a pipeline extraction algorithm based on Toeplitz matrix hashing and implement it in a high-speed field-programmable gate array. Further, all the QRNG components are integrated into a module, including a compact and actively stabilized interferometer, high-speed data acquisition, and real-time data post-processing and transmission. The final generation rate of the QRNG module with real-time extraction can reach 3.2 Gbps.

  3. GPCR-drug interactions prediction using random forest with drug-association-matrix-based post-processing procedure.

    Science.gov (United States)

    Hu, Jun; Li, Yang; Yang, Jing-Yu; Shen, Hong-Bin; Yu, Dong-Jun

    2016-02-01

    G-protein-coupled receptors (GPCRs) are important targets of modern medicinal drugs. The accurate identification of interactions between GPCRs and drugs is of significant importance for both protein function annotations and drug discovery. In this paper, a new sequence-based predictor called TargetGDrug is designed and implemented for predicting GPCR-drug interactions. In TargetGDrug, the evolutionary feature of GPCR sequence and the wavelet-based molecular fingerprint feature of drug are integrated to form the combined feature of a GPCR-drug pair; then, the combined feature is fed to a trained random forest (RF) classifier to perform initial prediction; finally, a novel drug-association-matrix-based post-processing procedure is applied to reduce potential false positive or false negative of the initial prediction. Experimental results on benchmark datasets demonstrate the efficacy of the proposed method, and an improvement of 15% in the Matthews correlation coefficient (MCC) was observed over independent validation tests when compared with the most recently released sequence-based GPCR-drug interactions predictor. The implemented webserver, together with the datasets used in this study, is freely available for academic use at http://csbio.njust.edu.cn/bioinf/TargetGDrug. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Conventional and novel approaches in generating and characterization of reactive intermediates from drugs/drug candidates

    NARCIS (Netherlands)

    Orhan, Hilmi; Vermeulen, Nico P E

    Despite several thousands of drugs are in use currently, research on new drug molecules is continuing. Because, there are diseases still without medication, successor/better drugs make the predecessor ones obsolete, and advancement in both life sciences and analytical technologies provide

  5. The impact of exposure to addictive drugs on future generations: Physiological and behavioral effects.

    Science.gov (United States)

    Vassoler, F M; Byrnes, E M; Pierce, R C

    2014-01-01

    It is clear that both genetic and environmental factors contribute to drug addiction. Recent evidence indicating trans-generational influences of drug abuse highlight potential epigenetic factors as well. Specifically, mounting evidence suggests that parental ingestion of abused drugs influence the physiology and behavior of future generations even in the absence of prenatal exposure. The goal of this review is to describe the trans-generational consequences of preconception exposure to drugs of abuse for five major classes of drugs: alcohol, nicotine, marijuana, opioids, and cocaine. The potential epigenetic mechanisms underlying the transmission of these phenotypes across generations also are detailed. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Beyond THC: the new generation of cannabinoid designer drugs

    Directory of Open Access Journals (Sweden)

    Liana eFattore

    2011-09-01

    Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

  7. Quantum cryptography using coherent states: Randomized encryption and key generation

    Science.gov (United States)

    Corndorf, Eric

    objectives of key generation and direct data-encryption, a new quantum cryptographic principle is demonstrated wherein keyed coherent-state signal sets are employed. Taking advantage of the fundamental and irreducible quantum-measurement noise of coherent states, these schemes do not require the users to measure the influence of an attacker. Experimental key-generation and data encryption schemes based on these techniques, which are compatible with today's WDM fiber-optic telecommunications infrastructure, are implemented and analyzed.

  8. Quantum random number generator based on quantum nature of vacuum fluctuations

    Science.gov (United States)

    Ivanova, A. E.; Chivilikhin, S. A.; Gleim, A. V.

    2017-11-01

    Quantum random number generator (QRNG) allows obtaining true random bit sequences. In QRNG based on quantum nature of vacuum, optical beam splitter with two inputs and two outputs is normally used. We compare mathematical descriptions of spatial beam splitter and fiber Y-splitter in the quantum model for QRNG, based on homodyne detection. These descriptions were identical, that allows to use fiber Y-splitters in practical QRNG schemes, simplifying the setup. Also we receive relations between the input radiation and the resulting differential current in homodyne detector. We experimentally demonstrate possibility of true random bits generation by using QRNG based on homodyne detection with Y-splitter.

  9. Modal generation of the design parameters of an elastic spacecraft by the random search method

    Science.gov (United States)

    Titov, B. A.

    A method for the modal generation of the dynamic properties of an elastic spacecraft is proposed which is based on algorithms of random search in the space of design parameters. A practical implementation of this approach is illustrated by an example. It is shown that the modal parameter generation procedure based on the random search solves the problem of parameter selection. However, as in any other method, the accuracy of the computation of matrix elements is largely determined by the initial set of permissible values and the number of random samples in determining the subgradient of the objective function.

  10. Parental and offspring assessment of driving capability under the influence of drugs or alcohol: gender and inter-generational differences.

    Science.gov (United States)

    Rosenbloom, Tova; Beigel, Ariela; Perlman, Amotz; Eldror, Ehud

    2010-11-01

    The current study set to examine whether there are inter-generational and gender-based differences between family members self-assessing their ability to drive under normal conditions and while under the influence of either alcohol or drugs. Participants were 135 young-adults and both their parents, consisting 45 family triads, who received self-assessment questionnaires relating to their driving skills in various road scenarios. Each family triad was randomly assigned to one of three groups: either requested to base the assessments on normal driving conditions, or under the influence of either drugs or alcohol, thus forming a control group, and two experimental groups (alcohol and drugs), respectively. The findings indicate the assessments of both the alcohol and drugs groups were more severe than those of the control group. The alcohol group assessments were less strict than the drug group assessment (non-significantly). Inter-generational differences indicated that the parents' driving-skills assessments were lower than those of their offspring, corresponding with previous findings (Elkind, 1967; Finn and Bragg, 1986). A significant within-subject interaction has been found between the respondent's gender and familial relations regarding the self-assessment of driving skills: male respondents assessed better driving skills compared to the self estimates of both parents (which did not significantly differ). In contrast, female respondents' estimates did not differ from their fathers' and both fathers' and daughters' estimates were significantly higher than that of the mothers in each family. 2010 Elsevier Ltd. All rights reserved.

  11. On the design of henon and logistic map-based random number generator

    Science.gov (United States)

    Magfirawaty; Suryadi, M. T.; Ramli, Kalamullah

    2017-10-01

    The key sequence is one of the main elements in the cryptosystem. True Random Number Generators (TRNG) method is one of the approaches to generating the key sequence. The randomness source of the TRNG divided into three main groups, i.e. electrical noise based, jitter based and chaos based. The chaos based utilizes a non-linear dynamic system (continuous time or discrete time) as an entropy source. In this study, a new design of TRNG based on discrete time chaotic system is proposed, which is then simulated in LabVIEW. The principle of the design consists of combining 2D and 1D chaotic systems. A mathematical model is implemented for numerical simulations. We used comparator process as a harvester method to obtain the series of random bits. Without any post processing, the proposed design generated random bit sequence with high entropy value and passed all NIST 800.22 statistical tests.

  12. 640-Gbit/s fast physical random number generation using a broadband chaotic semiconductor laser

    Science.gov (United States)

    Zhang, Limeng; Pan, Biwei; Chen, Guangcan; Guo, Lu; Lu, Dan; Zhao, Lingjuan; Wang, Wei

    2017-04-01

    An ultra-fast physical random number generator is demonstrated utilizing a photonic integrated device based broadband chaotic source with a simple post data processing method. The compact chaotic source is implemented by using a monolithic integrated dual-mode amplified feedback laser (AFL) with self-injection, where a robust chaotic signal with RF frequency coverage of above 50 GHz and flatness of ±3.6 dB is generated. By using 4-least significant bits (LSBs) retaining from the 8-bit digitization of the chaotic waveform, random sequences with a bit-rate up to 640 Gbit/s (160 GS/s × 4 bits) are realized. The generated random bits have passed each of the fifteen NIST statistics tests (NIST SP800-22), indicating its randomness for practical applications.

  13. Pseudo-Random Number Generators for Vector Processors and Multicore Processors

    DEFF Research Database (Denmark)

    Fog, Agner

    2015-01-01

    Large scale Monte Carlo applications need a good pseudo-random number generator capable of utilizing both the vector processing capabilities and multiprocessing capabilities of modern computers in order to get the maximum performance. The requirements for such a generator are discussed. New ways ...

  14. Delay line length selection in generating fast random numbers with a chaotic laser.

    Science.gov (United States)

    Zhang, Jianzhong; Wang, Yuncai; Xue, Lugang; Hou, Jiayin; Zhang, Beibei; Wang, Anbang; Zhang, Mingjiang

    2012-04-10

    The chaotic light signals generated by an external cavity semiconductor laser have been experimentally demonstrated to extract fast random numbers. However, the photon round-trip time in the external cavity can cause the occurrence of the periodicity in random sequences. To overcome it, the exclusive-or operation on corresponding random bits in samples of the chaotic signal and its time-delay signal from a chaotic laser is required. In this scheme, the proper selection of delay length is a key issue. By doing a large number of experiments and theoretically analyzing the interplay between the Runs test and the threshold value of the autocorrelation function, we find when the corresponding delay time of autocorrelation trace with the correlation coefficient of less than 0.007 is considered as the delay time between the chaotic signal and its time-delay signal, streams of random numbers can be generated with verified randomness.

  15. Randomized pharmacokinetic and drug-drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects.

    Science.gov (United States)

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-10-01

    We assessed pharmacokinetic and safety profiles of ceftazidime-avibactam administered ± metronidazole, and whether drug-drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime-avibactam (2000-500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime-avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime-avibactam over 4 days to assess drug-drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime-avibactam and metronidazole in subjects receiving ceftazidime-avibactam (2000-500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime-avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80-125%) indicating no drug-drug interaction between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug-drug interaction between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole.

  16. Concurrent Generation of Pseudo Random Numbers with LFSR of Fibonacci and Galois Type

    OpenAIRE

    Emina I. Milovanović; Stojčev, Mile K.; Igor Ž. Milovanović; Tatjana R. Nikolić; Zoran Stamenković

    2016-01-01

    We have considered implementation of parallel test pattern generator based on a linear feedback shift register (LFSR) with multiple outputs used as a building block in built-in-self-test (BIST) design within SoC. The proposed design can drive several circuits under test (CUT) simultaneously. The mathematical procedure for concurrent pseudo random number (PRN) generation is described. We have implemented LFSRs that generate two and three PRNs in FPGA and ASIC technology. The design was tested ...

  17. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    Directory of Open Access Journals (Sweden)

    Michael Guarnieri

    2014-01-01

    Full Text Available Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs.

  18. Random laser action with coherent feedback via second-harmonic generation

    CERN Document Server

    Qiao, Yanqi; Cai, Zengyan; Chen, Xianfeng

    2016-01-01

    The random laser action with coherent feedback by second-harmonic generation (SHG) was experimentally demonstrated in this paper. Compared with the conventional random laser action based on photoluminescence effect, which needs strong photoresponse in the active medium and has a fixed response waveband due to the inherent energy level structure of the material, this random SHG laser action indicates a possible confinement of the nonlinear signal with ring cavities and widens the response waveband due to the flexible frequency conversion in nonlinear process. The combination of coherent random laser and nonlinear optics will provide us another possible way to break phase-matching limitations, with fiber or feedback-based wavefront shaping method to transmit the emission signal directionally. This work suggests potential applications in band-tunable random laser, phase-matching-free nonlinear optics and even brings in new consideration about random nonlinear optics (RNO).

  19. Random Number Generation and Executive Functions in Parkinson's Disease: An Event-Related Brain Potential Study.

    Science.gov (United States)

    Münte, Thomas F; Joppich, Gregor; Däuper, Jan; Schrader, Christoph; Dengler, Reinhard; Heldmann, Marcus

    2015-01-01

    The generation of random sequences is considered to tax executive functions and has been reported to be impaired in Parkinson's disease (PD) previously. To assess the neurophysiological markers of random number generation in PD. Event-related potentials (ERP) were recorded in 12 PD patients and 12 age-matched normal controls (NC) while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus at a rate of 1 tone every 1800 ms. As a secondary task subjects had to monitor the tone-sequence for a particular target tone to which the number "0" key had to be pressed. This target tone occurred randomly and infrequently, thus creating a secondary oddball task. Behaviorally, PD patients showed an increased tendency to count in steps of one as well as a tendency towards repetition avoidance. Electrophysiologically, the amplitude of the P3 component of the ERP to the target tone of the secondary task was reduced during RNG in PD but not in NC. The behavioral findings indicate less random behavior in PD while the ERP findings suggest that this impairment comes about, because attentional resources are depleted in PD.

  20. Fractal generator for efficient production of random planar patterns and symbols in digital mapping

    Science.gov (United States)

    Chen, Qiyu; Liu, Gang; Ma, Xiaogang; Li, Xinchuan; He, Zhenwen

    2017-08-01

    In digital cartography, the automatic generation of random planar patterns and symbols is still an ongoing challenge. Those patterns and symbols of randomness have randomly variated configurations and boundaries, and their generating algorithms are constrained by the shape features, cartographic standards and many other conditions. The fractal geometry offers favorable solutions to simulate random boundaries and patterns. In the work presented in this paper, we used both fractal theory and random Iterated Function Systems (IFS) to develop a method for the automatic generation of random planar patterns and symbols. The marshland and the trough cross-bedding patterns were used as two case studies for the implementation of the method. We first analyzed the morphological characteristics of those two planar patterns. Then we designed algorithms and implementation schemes addressing the features of each pattern. Finally, we ran the algorithms to generate the patterns and symbols, and compared them with the requirements of a few digital cartographic standards. The method presented in this paper has already been deployed in a digital mapping system for practical uses. The flexibility of the method also allows it to be reused and/or adapted in various software platforms for digital mapping.

  1. Early stage hot spot analysis through standard cell base random pattern generation

    Science.gov (United States)

    Jeon, Joong-Won; Song, Jaewan; Kim, Jeong-Lim; Park, Seongyul; Yang, Seung-Hune; Lee, Sooryong; Kang, Hokyu; Madkour, Kareem; ElManhawy, Wael; Lee, SeungJo; Kwan, Joe

    2017-04-01

    Due to limited availability of DRC clean patterns during the process and RET recipe development, OPC recipes are not tested with high pattern coverage. Various kinds of pattern can help OPC engineer to detect sensitive patterns to lithographic effects. Random pattern generation is needed to secure robust OPC recipe. However, simple random patterns without considering real product layout style can't cover patterning hotspot in production levels. It is not effective to use them for OPC optimization thus it is important to generate random patterns similar to real product patterns. This paper presents a strategy for generating random patterns based on design architecture information and preventing hotspot in early process development stage through a tool called Layout Schema Generator (LSG). Using LSG, we generate standard cell based on random patterns reflecting real design cell structure - fin pitch, gate pitch and cell height. The output standard cells from LSG are applied to an analysis methodology to assess their hotspot severity by assigning a score according to their optical image parameters - NILS, MEEF, %PV band and thus potential hotspots can be defined by determining their ranking. This flow is demonstrated on Samsung 7nm technology optimizing OPC recipe and early enough in the process avoiding using problematic patterns.

  2. A revision of the subtract-with-borrow random number generators

    Science.gov (United States)

    Sibidanov, Alexei

    2017-12-01

    The most popular and widely used subtract-with-borrow generator, also known as RANLUX, is reimplemented as a linear congruential generator using large integer arithmetic with the modulus size of 576 bits. Modern computers, as well as the specific structure of the modulus inferred from RANLUX, allow for the development of a fast modular multiplication - the core of the procedure. This was previously believed to be slow and have too high cost in terms of computing resources. Our tests show a significant gain in generation speed which is comparable with other fast, high quality random number generators. An additional feature is the fast skipping of generator states leading to a seeding scheme which guarantees the uniqueness of random number sequences. Licensing provisions: GPLv3 Programming language: C++, C, Assembler

  3. Compact quantum random number generator based on superluminescent light-emitting diodes

    Science.gov (United States)

    Wei, Shihai; Yang, Jie; Fan, Fan; Huang, Wei; Li, Dashuang; Xu, Bingjie

    2017-12-01

    By measuring the amplified spontaneous emission (ASE) noise of the superluminescent light emitting diodes, we propose and realize a quantum random number generator (QRNG) featured with practicability. In the QRNG, after the detection and amplification of the ASE noise, the data acquisition and randomness extraction which is integrated in a field programmable gate array (FPGA) are both implemented in real-time, and the final random bit sequences are delivered to a host computer with a real-time generation rate of 1.2 Gbps. Further, to achieve compactness, all the components of the QRNG are integrated on three independent printed circuit boards with a compact design, and the QRNG is packed in a small enclosure sized 140 mm × 120 mm × 25 mm. The final random bit sequences can pass all the NIST-STS and DIEHARD tests.

  4. Quantum random number generation enhanced by weak-coherent states interference.

    Science.gov (United States)

    Ferreira da Silva, T; Xavier, G B; Amaral, G C; Temporão, G P; von der Weid, J P

    2016-08-22

    We propose and demonstrate a technique for quantum random number generation based on the random population of the output spatial modes of a beam splitter when both inputs are simultaneously fed with indistinguishable weak coherent states. We simulate and experimentally validate the probability of generation of random bits as a function of the average photon number per input, and compare it to the traditional approach of a single weak coherent state transmitted through a beam-splitter, showing an improvement of up to 32%. The ensuing interference phenomenon reduces the probability of coincident counts between the detectors associated with bits 0 and 1, thus increasing the probability of occurrence of a valid output. A long bit string is assessed by a standard randomness test suite with good confidence. Our proposal can be easily implemented and opens attractive performance gains without a significant trade-off.

  5. A Bidirectional Generalized Synchronization Theorem-Based Chaotic Pseudo-random Number Generator

    Directory of Open Access Journals (Sweden)

    Han Shuangshuang

    2013-07-01

    Full Text Available Based on a bidirectional generalized synchronization theorem for discrete chaos system, this paper introduces a new 5-dimensional bidirectional generalized chaos synchronization system (BGCSDS, whose prototype is a novel chaotic system introduced in [12]. Numerical simulation showed that two pair variables of the BGCSDS achieve generalized chaos synchronization via a transform H.A chaos-based pseudo-random number generator (CPNG was designed by the new BGCSDS. Using the FIPS-140-2 tests issued by the National Institute of Standard and Technology (NIST verified the randomness of the 1000 binary number sequences generated via the CPNG and the RC4 algorithm respectively. The results showed that all the tested sequences passed the FIPS-140-2 tests. The confidence interval analysis showed the statistical properties of the randomness of the sequences generated via the CPNG and the RC4 algorithm do not have significant differences.

  6. Generating Variable and Random Schedules of Reinforcement Using Microsoft Excel Macros

    OpenAIRE

    Bancroft, Stacie L; Bourret, Jason C

    2008-01-01

    Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time. Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time. Generating schedule values for variable and random reinforcement schedules can be difficult. The present article describes the steps necessary to writ...

  7. Theory of fast nondeterministic physical random-bit generation with chaotic lasers.

    Science.gov (United States)

    Harayama, Takahisa; Sunada, Satoshi; Yoshimura, Kazuyuki; Muramatsu, Jun; Arai, Ken-ichi; Uchida, Atsushi; Davis, Peter

    2012-04-01

    We theoretically show that completely stochastic fast physical random bit generation at a rate of more than one gigabit per second can be realized by using lasers with optical delayed feedback which creates high-dimensional chaos of laser light outputs. The theory is based on the mixing property of chaos, which transduces microscopic quantum noise of spontaneous emission in lasers into random transitions between discrete macroscopic states.

  8. A Randomized Trial of Probation Case Management for Drug-Involved Women Offenders

    Science.gov (United States)

    Guydish, Joseph; Chan, Monica; Bostrom, Alan; Jessup, Martha A.; Davis, Thomas B.; Marsh, Cheryl

    2011-01-01

    This article reports findings from a clinical trial of a probation case management (PCM) intervention for drug-involved women offenders. Participants were randomly assigned to PCM (n = 92) or standard probation (n = 91) and followed for 12 months using measures of substance abuse, psychiatric symptoms, social support, and service utilization.…

  9. Voluntary, Randomized, Student Drug-Testing: Impact in a Rural, Low-Income, Community

    Science.gov (United States)

    Barrington, Kyle D.

    2008-01-01

    Illegal drug use and abuse by the nation's secondary school students is a continuing public health issue and this is especially true for students living in rural, low-income areas where access to intervention and treatment services is often limited. To address this issue, some school districts have implemented voluntary, randomized, student …

  10. Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

    Science.gov (United States)

    Waffenschmidt, Siw; Guddat, Charlotte

    2015-01-01

    Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

  11. Graphene based widely-tunable and singly-polarized pulse generation with random fiber lasers

    Science.gov (United States)

    Yao, B. C.; Rao, Y. J.; Wang, Z. N.; Wu, Y.; Zhou, J. H.; Wu, H.; Fan, M. Q.; Cao, X. L.; Zhang, W. L.; Chen, Y. F.; Li, Y. R.; Churkin, D.; Turitsyn, S.; Wong, C. W.

    2015-12-01

    Pulse generation often requires a stabilized cavity and its corresponding mode structure for initial phase-locking. Contrastingly, modeless cavity-free random lasers provide new possibilities for high quantum efficiency lasing that could potentially be widely tunable spectrally and temporally. Pulse generation in random lasers, however, has remained elusive since the discovery of modeless gain lasing. Here we report coherent pulse generation with modeless random lasers based on the unique polarization selectivity and broadband saturable absorption of monolayer graphene. Simultaneous temporal compression of cavity-free pulses are observed with such a polarization modulation, along with a broadly-tunable pulsewidth across two orders of magnitude down to 900 ps, a broadly-tunable repetition rate across three orders of magnitude up to 3 MHz, and a singly-polarized pulse train at 41 dB extinction ratio, about an order of magnitude larger than conventional pulsed fiber lasers. Moreover, our graphene-based pulse formation also demonstrates robust pulse-to-pulse stability and wide-wavelength operation due to the cavity-less feature. Such a graphene-based architecture not only provides a tunable pulsed random laser for fiber-optic sensing, speckle-free imaging, and laser-material processing, but also a new way for the non-random CW fiber lasers to generate widely tunable and singly-polarized pulses.

  12. Random fields generation on the GPU with the spectral turning bands method

    Science.gov (United States)

    Hunger, L.; Cosenza, B.; Kimeswenger, S.; Fahringer, T.

    2014-08-01

    Random field (RF) generation algorithms are of paramount importance for many scientific domains, such as astrophysics, geostatistics, computer graphics and many others. Some examples are the generation of initial conditions for cosmological simulations or hydrodynamical turbulence driving. In the latter a new random field is needed every time-step. Current approaches commonly make use of 3D FFT (Fast Fourier Transform) and require the whole generated field to be stored in memory. Moreover, they are limited to regular rectilinear meshes and need an extra processing step to support non-regular meshes. In this paper, we introduce TBARF (Turning BAnd Random Fields), a RF generation algorithm based on the turning band method that is optimized for massively parallel hardware such as GPUs. Our algorithm replaces the 3D FFT with a lower order, one-dimensional FFT followed by a projection step, and is further optimized with loop unrolling and blocking. We show that TBARF can easily generate RF on non-regular (non uniform) meshes and can afford mesh sizes bigger than the available GPU memory by using a streaming, out-of-core approach. TBARF is 2 to 5 times faster than the traditional methods when generating RFs with more than 16M cells. It can also generate RF on non-regular meshes, and has been successfully applied to two real case scenarios: planetary nebulae and cosmological simulations.

  13. Random bit generation using an optically injected semiconductor laser in chaos with oversampling.

    Science.gov (United States)

    Li, Xiao-Zhou; Chan, Sze-Chun

    2012-06-01

    Random bit generation is experimentally demonstrated using a semiconductor laser driven into chaos by optical injection. The laser is not subject to any feedback so that the chaotic waveform possesses very little autocorrelation. Random bit generation is achieved at a sampling rate of 10 GHz even when only a fractional bandwidth of 1.5 GHz within a much broader chaotic bandwidth is digitized. By retaining only 3 least significant bits per sample, an output bit rate of 30 Gbps is attained. The approach requires no complicated postprocessing and has no stringent requirement on the electronics bandwidth.

  14. Fortran code for generating random probability vectors, unitaries, and quantum states

    Directory of Open Access Journals (Sweden)

    Jonas eMaziero

    2016-03-01

    Full Text Available The usefulness of generating random configurations is recognized in many areas of knowledge. Fortran was born for scientific computing and has been one of the main programming languages in this area since then. And several ongoing projects targeting towards its betterment indicate that it will keep this status in the decades to come. In this article, we describe Fortran codes produced, or organized, for the generation of the following random objects: numbers, probability vectors, unitary matrices, and quantum state vectors and density matrices. Some matrix functions are also included and may be of independent interest.

  15. Screening and brief intervention for drug use in primary care: the ASPIRE randomized clinical trial.

    Science.gov (United States)

    Saitz, Richard; Palfai, Tibor P A; Cheng, Debbie M; Alford, Daniel P; Bernstein, Judith A; Lloyd-Travaglini, Christine A; Meli, Seville M; Chaisson, Christine E; Samet, Jeffrey H

    2014-08-06

    The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse, based in part on evidence of efficacy for unhealthy alcohol use. However, it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy. To test the efficacy of 2 brief counseling interventions for unhealthy drug use (any illicit drug use or prescription drug misuse)-a brief negotiated interview (BNI) and an adaptation of motivational interviewing (MOTIV)-compared with no brief intervention. This 3-group randomized trial took place at an urban hospital-based primary care internal medicine practice; 528 adult primary care patients with drug use (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] substance-specific scores of ≥4) were identified by screening between June 2009 and January 2012 in Boston, Massachusetts. Two interventions were tested: the BNI is a 10- to 15-minute structured interview conducted by health educators; the MOTIV is a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by master's-level counselors. All study participants received a written list of substance use disorder treatment and mutual help resources. Primary outcome was number of days of use in the past 30 days of the self-identified main drug as determined by a validated calendar method at 6 months. Secondary outcomes included other self-reported measures of drug use, drug use according to hair testing, ASSIST scores (severity), drug use consequences, unsafe sex, mutual help meeting attendance, and health care utilization. At baseline, 63% of participants reported their main drug was marijuana, 19% cocaine, and 17% opioids. At 6 months, 98% completed follow-up. Mean adjusted number of days using the main drug at 6 months was 12 for no brief intervention vs 11 for the BNI group (incidence rate ratio [IRR], 0.97; 95% CI, 0.77-1.22) and 12

  16. Nonmedical prescription opioids and pathways of drug involvement in the US: Generational differences.

    Science.gov (United States)

    Wall, Melanie; Cheslack-Postava, Keely; Hu, Mei-Chen; Feng, Tianshu; Griesler, Pamela; Kandel, Denise B

    2018-01-01

    This study sought to specify (1) the position of nonmedical prescription opioids (NMPO) in drug initiation sequences among Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and racial/ethnic differences in sequences among Millennials. Data are from the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified statistically significant drug initiation sequences involving alcohol/cigarettes, marijuana, NMPO, cocaine, and heroin using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among drugs. Alcohol/cigarettes followed by marijuana was the most common sequence. NMPO or cocaine use after marijuana, and heroin use after NMPO or cocaine, differed by generation. Among successively younger generations, NMPO after marijuana and heroin after NMPO increased. Millennials were more likely to initiate NMPO than cocaine after marijuana; Generation X and Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more likely than Generation X and Baby Boomers to use heroin after NMPO (hazards ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to start heroin after both NMPO and cocaine than either alone. Sequences were similar by gender. Fewer paths were significant among African-Americans. NMPOs play a more prominent role in drug initiation sequences among Millennials than prior generations. Among Millennials, NMPO use is more likely than cocaine to follow marijuana use. In all generations, transition to heroin from NMPO significantly occurs only when both NMPO and cocaine have been used. Delineation of drug sequences suggests optimal points in development for prevention and treatment efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 75 FR 76069 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

    Science.gov (United States)

    2010-12-07

    ... aviation industry. If the reported random drug test positive rate is less than 1.00%, the Administrator may... Federal Aviation Administration Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of January 1, 2011, Through December 31, 2011 AGENCY: Federal Aviation...

  18. 78 FR 77196 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

    Science.gov (United States)

    2013-12-20

    ... testing rate is based on the reported random drug test positive rate for the entire aviation industry. If... TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of January 1, 2014, Through December 31, 2014 AGENCY: Federal Aviation...

  19. 77 FR 71669 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

    Science.gov (United States)

    2012-12-03

    ... testing rate is based on the reported random drug test positive rate for the entire aviation industry. If... Federal Aviation Administration Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of January 1, 2013, Through December 31, 2013 AGENCY: Federal Aviation...

  20. 76 FR 74843 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

    Science.gov (United States)

    2011-12-01

    ... testing rate is based on the reported random drug test positive rate for the entire aviation industry. If... Federal Aviation Administration Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of January 1, 2012, Through December 31, 2012 AGENCY: Federal Aviation...

  1. Maternal education and adolescent drug use: a longitudinal analysis of causation and selection over a generation.

    Science.gov (United States)

    Miech, Richard; Chilcoat, Howard

    2005-02-01

    Current evidence indicates that in the USA illegal drug use among adolescents between the 1980s and 1990s became significantly more prevalent in families with lower maternal education in comparison to families with higher maternal education. In this study, we examine whether this inter-generational change results from either (a) a changing influence of socioeconomic status on drug use, as predicted by the inter-generational social 'causation' hypothesis, or (b) a negative influence of drug use on socioeconomic status, as predicted by the inter-generational social 'selection/drift' hypothesis. The analyses are based on the US National Longitudinal Study of 1979, which includes information on drug use for both a nationally representative sample of respondents aged 19-27 in 1984, as well as drug use information for the children of these respondents, who were aged 18-27 in 1998. The results indicate that inter-generation change in cocaine and marijuana use resulted almost entirely from social causation. These findings support illegal drug use as a good candidate for analyses in the 'fundamental cause' tradition that seek to understand the social factors that concentrate poor health and health behaviors in the lower social strata over historical time.

  2. An On-Demand Optical Quantum Random Number Generator with In-Future Action and Ultra-Fast Response.

    Science.gov (United States)

    Stipčević, Mario; Ursin, Rupert

    2015-06-09

    Random numbers are essential for our modern information based society e.g. in cryptography. Unlike frequently used pseudo-random generators, physical random number generators do not depend on complex algorithms but rather on a physical process to provide true randomness. Quantum random number generators (QRNG) do rely on a process, which can be described by a probabilistic theory only, even in principle. Here we present a conceptually simple implementation, which offers a 100% efficiency of producing a random bit upon a request and simultaneously exhibits an ultra low latency. A careful technical and statistical analysis demonstrates its robustness against imperfections of the actual implemented technology and enables to quickly estimate randomness of very long sequences. Generated random numbers pass standard statistical tests without any post-processing. The setup described, as well as the theory presented here, demonstrate the maturity and overall understanding of the technology.

  3. Generation of sound by Alfven waves with random phases in the solar atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Petrukhin, N.S.; Fainshtein, S.M.

    1976-11-01

    The problem of the excitation of sound by Alfven waves meeting in the solar plasma is discussed. Kinetic equations for the interacting waves are derived and analyzed on the assumption that the Alfven waves have random phases. Estimates are given which show the possibility of the generation of LF-pulsations in the solar atmosphere.

  4. Examining Psychokinesis: The Interaction of Human Intention with Random Number Generators--A Meta-Analysis

    Science.gov (United States)

    Bosch, Holger; Steinkamp, Fiona; Boller, Emil

    2006-01-01

    Seance-room and other large-scale psychokinetic phenomena have fascinated humankind for decades. Experimental research has reduced these phenomena to attempts to influence (a) the fall of dice and, later, (b) the output of random number generators (RNGs). The meta-analysis combined 380 studies that assessed whether RNG output correlated with human…

  5. A time series approach to random number generation: Using recurrence quantification analysis to capture executive behavior

    NARCIS (Netherlands)

    Oomens, W.; Maes, J.H.R.; Hasselman, F.W.; Egger, J.I.M.

    2015-01-01

    The concept of executive functions plays a prominent role in contemporary experimental and clinical studies on cognition. One paradigm used in this framework is the random number generation (RNG) task, the execution of which demands aspects of executive functioning, specifically inhibition and

  6. Site-Specific Tandem Knoevenagel Condensation-Michael Addition To Generate Antibody-Drug Conjugates.

    Science.gov (United States)

    Kudirka, Romas A; Barfield, Robyn M; McFarland, Jesse M; Drake, Penelope M; Carlson, Adam; Bañas, Stefanie; Zmolek, Wes; Garofalo, Albert W; Rabuka, David

    2016-11-10

    Expanded ligation techniques are sorely needed to generate unique linkages for the growing field of functionally enhanced proteins. To address this need, we present a unique chemical ligation that involves the double addition of a pyrazolone moiety with an aldehyde-labeled protein. This ligation occurs via a tandem Knoevenagel condensation-Michael addition. A pyrazolone reacts with an aldehyde to generate an enone, which undergoes subsequent attack by a second pyrazolone to generate a bis-pyrazolone species. This rapid and facile ligation technique is performed under mild conditions in the absence of catalyst to generate new architectures that were previously inaccessible via conventional ligation reactions. Using this unique ligation, we generated three site-specifically labeled antibody-drug conjugates (ADCs) with an average of four drugs to one antibody. The in vitro and in vivo efficacies along with pharmacokinetic data of the site-specific ADCs are reported.

  7. A randomized controlled pilot study of motivational interviewing for patients with psychotic and drug use disorders.

    Science.gov (United States)

    Martino, Steve; Carroll, Kathleen M; Nich, Charla; Rounsaville, Bruce J

    2006-10-01

    This pilot study examined the efficacy of a two-session motivational interview adapted for dually diagnosed psychotic and drug-related disordered patients (DDMI) in comparison to a two-session standard psychiatric interview (SI). The study used a randomized controlled trial design. Participants received either DDMI or SI and were assessed at baseline, 4-, 8- and 12-week follow-up points. The principal analysis for examination of treatment effects across time was a random effects regression model. Both DDMI and SI interviews served as pre-admission intake interventions to an ambulatory specialty dual diagnosis intensive out-patient and partial hospital program. Forty-four treatment-seeking participants (DDMI = 24; SI = 20) who had co-occurring psychotic and drug-related disorders were assigned randomly to the treatment conditions. Measurements Primary outcomes were days of primary drug use, secondary drug use, alcohol use and psychotropic medication adherence, proportion of participants admitted into the program and days of attendance. DDMI and SI resulted in improved treatment outcomes, but there were no main effects for the sample as a whole. Separate examination of primary cocaine and primary marijuana using subsamples, however, suggested that DDMI resulted in significantly better primary drug treatment outcomes for the cocaine-using group, whereas SI resulted in significantly better primary drug treatment outcomes for the marijuana-using group. These findings indicate that MI may not work equally well for all types of psychotic disordered dually diagnosed patients and that alternative approaches may be as effective in fostering improved substance use treatment outcomes for subgroups of these individuals.

  8. Spectral turning bands for efficient Gaussian random fields generation on GPUs and accelerators

    Science.gov (United States)

    Hunger, L.; Cosenza, B.; Kimeswenger, S.; Fahringer, T.

    2015-11-01

    A random field (RF) is a set of correlated random variables associated with different spatial locations. RF generation algorithms are of crucial importance for many scientific areas, such as astrophysics, geostatistics, computer graphics, and many others. Current approaches commonly make use of 3D fast Fourier transform (FFT), which does not scale well for RF bigger than the available memory; they are also limited to regular rectilinear meshes. We introduce random field generation with the turning band method (RAFT), an RF generation algorithm based on the turning band method that is optimized for massively parallel hardware such as GPUs and accelerators. Our algorithm replaces the 3D FFT with a lower-order, one-dimensional FFT followed by a projection step and is further optimized with loop unrolling and blocking. RAFT can easily generate RF on non-regular (non-uniform) meshes and efficiently produce fields with mesh sizes bigger than the available device memory by using a streaming, out-of-core approach. Our algorithm generates RF with the correct statistical behavior and is tested on a variety of modern hardware, such as NVIDIA Tesla, AMD FirePro and Intel Phi. RAFT is faster than the traditional methods on regular meshes and has been successfully applied to two real case scenarios: planetary nebulae and cosmological simulations.

  9. Performance of university students on random number generation at different rates to evaluate executive functions

    Directory of Open Access Journals (Sweden)

    Hamdan Amer C.

    2004-01-01

    Full Text Available OBJECTIVE: To evaluate the performance of adult young subjects in a Random Number Generation (RNG task by controlling the response speed (RS. METHOD: Sixty-nine university students of both sexes took part in the experiment (25.05 ± 6.71 year-old. Participants were alloted into 3 groups which differed in RS rates to generate numbers: 1, 2 and 4 seconds to generate each number. A digital metronomer was used to control RS. Participants were asked to generate 100 numbers. The responses were mensured through Evans's RNG Index. RESULTS: There were statistically significant differences among the groups [F (3, 68 = 7.120; p < .05]. Differences were localized between 1 and 2 seconds (p = 0.004 and between 1 and 4 seconds (p = 0.006. No differences were observed between 2 and 4 seconds (p = 0.985. CONCLUSION: The present results suggest that the response speed in production of random numbers influences the performance of the Random Numbers Generation task.

  10. Identifying co-targets to fight drug resistance based on a random walk model

    Directory of Open Access Journals (Sweden)

    Chen Liang-Chun

    2012-01-01

    Full Text Available Abstract Background Drug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, wet-lab approaches alone to counter drug resistance have so far still achieved limited success due to less knowledge about the underlying mechanisms of drug resistance. Our approach apply a heuristic search algorithm in order to extract active network under drug treatment and use a random walk model to identify potential co-targets for effective antibacterial drugs. Results We use interactome network of Mycobacterium tuberculosis and gene expression data which are treated with two kinds of antibiotic, Isoniazid and Ethionamide as our test data. Our analysis shows that the active drug-treated networks are associated with the trigger of fatty acid metabolism and synthesis and nicotinamide adenine dinucleotide (NADH-related processes and those results are consistent with the recent experimental findings. Efflux pumps processes appear to be the major mechanisms of resistance but SOS response is significantly up-regulation under Isoniazid treatment. We also successfully identify the potential co-targets with literature confirmed evidences which are related to the glycine-rich membrane, adenosine triphosphate energy and cell wall processes. Conclusions With gene expression and interactome data supported, our study points out possible pathways leading to the emergence of drug resistance under drug treatment. We develop a computational workflow for giving new insights to bacterial drug resistance which can be gained by a systematic and global analysis of the bacterial regulation network. Our study also discovers the potential co-targets with good properties in biological and graph theory aspects to overcome the problem of drug resistance.

  11. Synchronization of random bit generators based on coupled chaotic lasers and application to cryptography.

    Science.gov (United States)

    Kanter, Ido; Butkovski, Maria; Peleg, Yitzhak; Zigzag, Meital; Aviad, Yaara; Reidler, Igor; Rosenbluh, Michael; Kinzel, Wolfgang

    2010-08-16

    Random bit generators (RBGs) constitute an important tool in cryptography, stochastic simulations and secure communications. The later in particular has some difficult requirements: high generation rate of unpredictable bit strings and secure key-exchange protocols over public channels. Deterministic algorithms generate pseudo-random number sequences at high rates, however, their unpredictability is limited by the very nature of their deterministic origin. Recently, physical RBGs based on chaotic semiconductor lasers were shown to exceed Gbit/s rates. Whether secure synchronization of two high rate physical RBGs is possible remains an open question. Here we propose a method, whereby two fast RBGs based on mutually coupled chaotic lasers, are synchronized. Using information theoretic analysis we demonstrate security against a powerful computational eavesdropper, capable of noiseless amplification, where all parameters are publicly known. The method is also extended to secure synchronization of a small network of three RBGs.

  12. Generating log-normally distributed random numbers by using the Ziggurat algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jong Soo [KINS, Daejeon (Korea, Republic of)

    2016-05-15

    Uncertainty analyses are usually based on the Monte Carlo method. Using an efficient random number generator(RNG) is a key element in success of Monte Carlo simulations. Log-normal distributed variates are very typical in NPP PSAs. This paper proposes an approach to generate log normally distributed variates based on the Ziggurat algorithm and evaluates the efficiency of the proposed Ziggurat RNG. The proposed RNG can be helpful to improve the uncertainty analysis of NPP PSAs. This paper focuses on evaluating the efficiency of the Ziggurat algorithm from a NPP PSA point of view. From this study, we can draw the following conclusions. - The Ziggurat algorithm is one of perfect random number generators to product normal distributed variates. - The Ziggurat algorithm is computationally much faster than the most commonly used method, Marsaglia polar method.

  13. Dynamics of a semiconductor laser with polarization-rotated feedback and its utilization for random bit generation.

    Science.gov (United States)

    Oliver, Neus; Soriano, Miguel C; Sukow, David W; Fischer, Ingo

    2011-12-01

    Chaotic semiconductor lasers have been proven attractive for fast random bit generation. To follow this strategy, simple robust systems and a systematic approach determining the required dynamical properties and most suitable conditions for this application are needed. We show that dynamics of a single mode laser with polarization-rotated feedback are optimal for random bit generation when characterized simultaneously by a broad power spectrum and low autocorrelation. We observe that successful random bit generation also is sensitive to digitization and postprocessing procedures. Applying the identified criteria, we achieve fast random bit generation rates (up to 4 Gbit/s) with minimal postprocessing. © 2011 Optical Society of America

  14. An adaptive random search for short term generation scheduling with network constraints.

    Directory of Open Access Journals (Sweden)

    J A Marmolejo

    Full Text Available This paper presents an adaptive random search approach to address a short term generation scheduling with network constraints, which determines the startup and shutdown schedules of thermal units over a given planning horizon. In this model, we consider the transmission network through capacity limits and line losses. The mathematical model is stated in the form of a Mixed Integer Non Linear Problem with binary variables. The proposed heuristic is a population-based method that generates a set of new potential solutions via a random search strategy. The random search is based on the Markov Chain Monte Carlo method. The main key of the proposed method is that the noise level of the random search is adaptively controlled in order to exploring and exploiting the entire search space. In order to improve the solutions, we consider coupling a local search into random search process. Several test systems are presented to evaluate the performance of the proposed heuristic. We use a commercial optimizer to compare the quality of the solutions provided by the proposed method. The solution of the proposed algorithm showed a significant reduction in computational effort with respect to the full-scale outer approximation commercial solver. Numerical results show the potential and robustness of our approach.

  15. PUFKEY: A High-Security and High-Throughput Hardware True Random Number Generator for Sensor Networks

    Directory of Open Access Journals (Sweden)

    Dongfang Li

    2015-10-01

    Full Text Available Random number generators (RNG play an important role in many sensor network systems and applications, such as those requiring secure and robust communications. In this paper, we develop a high-security and high-throughput hardware true random number generator, called PUFKEY, which consists of two kinds of physical unclonable function (PUF elements. Combined with a conditioning algorithm, true random seeds are extracted from the noise on the start-up pattern of SRAM memories. These true random seeds contain full entropy. Then, the true random seeds are used as the input for a non-deterministic hardware RNG to generate a stream of true random bits with a throughput as high as 803 Mbps. The experimental results show that the bitstream generated by the proposed PUFKEY can pass all standard national institute of standards and technology (NIST randomness tests and is resilient to a wide range of security attacks.

  16. PUFKEY: a high-security and high-throughput hardware true random number generator for sensor networks.

    Science.gov (United States)

    Li, Dongfang; Lu, Zhaojun; Zou, Xuecheng; Liu, Zhenglin

    2015-10-16

    Random number generators (RNG) play an important role in many sensor network systems and applications, such as those requiring secure and robust communications. In this paper, we develop a high-security and high-throughput hardware true random number generator, called PUFKEY, which consists of two kinds of physical unclonable function (PUF) elements. Combined with a conditioning algorithm, true random seeds are extracted from the noise on the start-up pattern of SRAM memories. These true random seeds contain full entropy. Then, the true random seeds are used as the input for a non-deterministic hardware RNG to generate a stream of true random bits with a throughput as high as 803 Mbps. The experimental results show that the bitstream generated by the proposed PUFKEY can pass all standard national institute of standards and technology (NIST) randomness tests and is resilient to a wide range of security attacks.

  17. An Architecturally Constrained Model of Random Number Generation and its Application to Modelling the Effect of Generation Rate

    Directory of Open Access Journals (Sweden)

    Nicholas J. Sexton

    2014-07-01

    Full Text Available Random number generation (RNG is a complex cognitive task for human subjects, requiring deliberative control to avoid production of habitual, stereotyped sequences. Under various manipulations (e.g., speeded responding, transcranial magnetic stimulation, or neurological damage the performance of human subjects deteriorates, as reflected in a number of qualitatively distinct, dissociable biases. For example, the intrusion of stereotyped behaviour (e.g., counting increases at faster rates of generation. Theoretical accounts of the task postulate that it requires the integrated operation of multiple, computationally heterogeneous cognitive control ('executive' processes. We present a computational model of RNG, within the framework of a novel, neuropsychologically-inspired cognitive architecture, ESPro. Manipulating the rate of sequence generation in the model reproduced a number of key effects observed in empirical studies, including increasing sequence stereotypy at faster rates. Within the model, this was due to time limitations on the interaction of supervisory control processes, namely, task setting, proposal of responses, monitoring, and response inhibition. The model thus supports the fractionation of executive function into multiple, computationally heterogeneous processes.

  18. Complexity and properties of a multidimensional Cat-Hadamard map for pseudo random number generation

    Science.gov (United States)

    Kim Hue, Ta Thi; Hoang, Thang Manh

    2017-07-01

    This paper presents a novel method to extend the Cat map from 2-dimension to higher dimension using the fast pseudo Hadamard Transform, and the resulted maps are called Cat-Hadamard maps. The complexity and properties of Cat-Hadamard maps are investigated under the point of view for cryptographic applications. In addition, we propose a method for constructing a pseudo random number generator using a novel design concept of the high dimensional Cat map. The simulation results show that the proposed generator fulfilled all the statistic tests of the NIST SP 800-90 A.

  19. Student Generated Solutions to the Alcohol/Drug Problem: A Wisconsin Profile.

    Science.gov (United States)

    Glassford, Darwin; And Others

    1991-01-01

    Surveyed junior and senior high school students (n=3,889) to generate their opinion of necessary "ingredients" for effective alcohol and drug abuse program. Resulting description was similar for junior and senior high levels, with little difference between sexes. Teachers and nurses were not considered likely candidates for providing counseling,…

  20. Generation of random numbers on graphics processors: forced indentation in silico of the bacteriophage HK97.

    Science.gov (United States)

    Zhmurov, A; Rybnikov, K; Kholodov, Y; Barsegov, V

    2011-05-12

    The use of graphics processing units (GPUs) in simulation applications offers a significant speed gain as compared to computations on central processing units (CPUs). Many simulation methods require a large number of independent random variables generated at each step. We present two approaches for implementation of random number generators (RNGs) on a GPU. In the one-RNG-per-thread approach, one RNG produces a stream of random numbers in each thread of execution, whereas the one-RNG-for-all-threads method builds on the ability of different threads to communicate, thus, sharing random seeds across an entire GPU device. We used these approaches to implement Ran2, Hybrid Taus, and Lagged Fibonacci algorithms on a GPU. We profiled the performance of these generators in terms of the computational time, memory usage, and the speedup factor (CPU time/GPU time). These generators have been incorporated into the program for Langevin simulations of biomolecules fully implemented on the GPU. The ∼250-fold computational speedup on the GPU allowed us to carry out single-molecule dynamic force measurements in silico to explore the mechanical properties of the bacteriophage HK97 in the experimental subsecond time scale. We found that the nanomechanical response of HK97 depends on the conditions of force application, including the rate of change and geometry of the mechanical perturbation. Hence, using the GPU-based implementation of RNGs, presented here, in conjunction with Langevin simulations, makes it possible to directly compare the results of dynamic force measurements in vitro and in silico.

  1. Analysis of a non-diffractive beam generated from an annular beam in random media

    Science.gov (United States)

    Peng, Ziqi; Shiina, Tatsuo

    2017-11-01

    An annular beam has the ability to self-transform into a non-diffractive beam when it propagates in air at a long distance. In our previous study, we propagated an annular beam in random media and obtained a non-diffractive beam at a short propagation distance of a few tens centimeters by adjusting the concentration of random media and narrowing the view angle of the receiver. In this paper, we aim to analyze the components and characteristics of a non-diffractive beam and elucidate how the non-diffractive beam is generated in random media. The intensity variation of the scattered waveform is examined when the distance between the receiver and the back plane of a medium tank is changed. The waveform scattered in random media is constructed from forward scattering light at the center and multiple scattering light in the surrounding part. The forward scattering light at the center generates the non-diffractive beam. In numerical analysis based on diffusion theory, the calculation result of the non-diffractive beam shows agreement with the experimental result.

  2. Leveraging Random Number Generation for Mastery of Learning in Teaching Quantitative Research Courses via an E-Learning Method

    Science.gov (United States)

    Boonsathorn, Wasita; Charoen, Danuvasin; Dryver, Arthur L.

    2014-01-01

    E-Learning brings access to a powerful but often overlooked teaching tool: random number generation. Using random number generation, a practically infinite number of quantitative problem-solution sets can be created. In addition, within the e-learning context, in the spirit of the mastery of learning, it is possible to assign online quantitative…

  3. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

  4. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study.

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients' engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants ( n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed.

  5. Treating adolescent drug abuse: a randomized trial comparing multidimensional family therapy and cognitive behavior therapy.

    Science.gov (United States)

    Liddle, Howard A; Dakof, Gayle A; Turner, Ralph M; Henderson, Craig E; Greenbaum, Paul E

    2008-10-01

    To examine the efficacy of two adolescent drug abuse treatments: individual cognitive behavioral therapy (CBT) and multidimensional family therapy (MDFT). A 2 (treatment condition) x 4 (time) repeated-measures intent-to-treat randomized design. Data were gathered at baseline, termination, 6 and 12 months post-termination. Analyses used latent growth curve modeling. Community-based drug abuse clinic in the northeastern United States. A total of 224 youth, primarily male (81%), African American (72%), from low-income single-parent homes (58%) with an average age of 15 years were recruited into the study. All youth were drug users, with 75% meeting DSM-IV criteria for cannabis dependence and 13% meeting criteria for abuse. Five outcomes were measured: (i) substance use problem severity; (ii) 30-day frequency of cannabis use; (iii) 30-day frequency of alcohol use; (iv) 30-day frequency of other drug use; and (v) 30-day abstinence. Both treatments produced significant decreases in cannabis consumption and slightly significant reductions in alcohol use, but there were no treatment differences in reducing frequency of cannabis and alcohol use. Significant treatment effects were found favoring MDFT on substance use problem severity, other drug use and minimal use (zero or one occasion of use) of all substances, and these effects continued to 12 months following treatment termination. Both interventions are promising treatments. Consistent with previous controlled trials, MDFT is distinguished by the sustainability of treatment effects.

  6. The cosmic microwave background radiation power spectrum as a random bit generator for symmetric- and asymmetric-key cryptography.

    Science.gov (United States)

    Lee, Jeffrey S; Cleaver, Gerald B

    2017-10-01

    In this note, the Cosmic Microwave Background (CMB) Radiation is shown to be capable of functioning as a Random Bit Generator, and constitutes an effectively infinite supply of truly random one-time pad values of arbitrary length. It is further argued that the CMB power spectrum potentially conforms to the FIPS 140-2 standard. Additionally, its applicability to the generation of a (n × n) random key matrix for a Vernam cipher is established.

  7. Randomized clinical trial on the use of antispasmodic drugs in barium enema: impact on radiological practice

    Energy Technology Data Exchange (ETDEWEB)

    Goei, Reginald; Kessels, Alphons H.; Nix, Maarten; Knipschild, Paul G

    2000-10-01

    Purpose: To assess the willingness of radiologists to change their practice when the results of a randomized clinical trial (RCT) on the use of antispasmodic drugs in barium enema are presented. Materials and Methods: During the years 1994 and 1995 two postal questionnaires were sent to 481 practicing radiologists who were all members of the Netherlands Society of Radiology. In the first questionnaire the respondents were asked to give the characteristics of their practices in performing daily barium enema. The data from this questionnaire was used as a reference. The second questionnaire was sent to the respondents together with an abstract on the randomized clinical trial supporting the use of antispasmodic drugs in barium enema. We also indicated a preference for Buscopan over Glucagon as the antispasmodic drug. The willingness to change prescription habits was measured by comparing the data of the two questionnaires. Results: Of 481 practicing radiologists, 312 responded to the first questionnaire and gave information of their prescription habits (response rate 64%). These 312 responders were sent an abstract of the RCT and were asked to fill out a second questionnaire to determine their willingness to change their practice. Two hundred and sixty-seven radiologists responded (response rate 86%). A significant number of 119 (51%) were willing to increase the use of antispasmodic drugs. A significant number of 128 (55%) chose to increase the use of Buscopan, while a significant number of 81 (32%) were willing to decrease the use of Glucagon. Conclusion: Direct exposure to the results of an RCT recommending the use of antispasmodic drugs in barium enema, especially Buscopan, is likely to increase its use by practicing radiologists.

  8. Application of random number generators in genetic algorithms to improve rainfall-runoff modelling

    Science.gov (United States)

    Chlumecký, Martin; Buchtele, Josef; Richta, Karel

    2017-10-01

    The efficient calibration of rainfall-runoff models is a difficult issue, even for experienced hydrologists. Therefore, fast and high-quality model calibration is a valuable improvement. This paper describes a novel methodology and software for the optimisation of a rainfall-runoff modelling using a genetic algorithm (GA) with a newly prepared concept of a random number generator (HRNG), which is the core of the optimisation. The GA estimates model parameters using evolutionary principles, which requires a quality number generator. The new HRNG generates random numbers based on hydrological information and it provides better numbers compared to pure software generators. The GA enhances the model calibration very well and the goal is to optimise the calibration of the model with a minimum of user interaction. This article focuses on improving the internal structure of the GA, which is shielded from the user. The results that we obtained indicate that the HRNG provides a stable trend in the output quality of the model, despite various configurations of the GA. In contrast to previous research, the HRNG speeds up the calibration of the model and offers an improvement of rainfall-runoff modelling.

  9. 77 FR 72905 - Pipeline Safety: Random Drug Testing Rate; Contractor MIS Reporting; and Obtaining DAMIS Sign-In...

    Science.gov (United States)

    2012-12-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate; Contractor MIS Reporting; and Obtaining DAMIS Sign-In Information AGENCY: Pipeline and Hazardous Materials...

  10. Neoclassic drug discovery: the case for lead generation using phenotypic and functional approaches.

    Science.gov (United States)

    Lee, Jonathan A; Berg, Ellen L

    2013-12-01

    Innovation and new molecular entity production by the pharmaceutical industry has been below expectations. Surprisingly, more first-in-class small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) between 1999 and 2008 were identified by functional phenotypic lead generation strategies reminiscent of pre-genomics pharmacology than contemporary molecular targeted strategies that encompass the vast majority of lead generation efforts. This observation, in conjunction with the difficulty in validating molecular targets for drug discovery, has diminished the impact of the "genomics revolution" and has led to a growing grassroots movement and now broader trend in pharma to reconsider the use of modern physiology-based or phenotypic drug discovery (PDD) strategies. This "From the Guest Editors" column provides an introduction and overview of the two-part special issues of Journal of Biomolecular Screening on PDD. Terminology and the business case for use of PDD are defined. Key issues such as assay performance, chemical optimization, target identification, and challenges to the organization and implementation of PDD are discussed. Possible solutions for these challenges and a new neoclassic vision for PDD that combines phenotypic and functional approaches with technology innovations resulting from the genomics-driven era of target-based drug discovery (TDD) are also described. Finally, an overview of the manuscripts in this special edition is provided.

  11. Engineering applications of fpgas chaotic systems, artificial neural networks, random number generators, and secure communication systems

    CERN Document Server

    Tlelo-Cuautle, Esteban; de la Fraga, Luis Gerardo

    2016-01-01

    This book offers readers a clear guide to implementing engineering applications with FPGAs, from the mathematical description to the hardware synthesis, including discussion of VHDL programming and co-simulation issues. Coverage includes FPGA realizations such as: chaos generators that are described from their mathematical models; artificial neural networks (ANNs) to predict chaotic time series, for which a discussion of different ANN topologies is included, with different learning techniques and activation functions; random number generators (RNGs) that are realized using different chaos generators, and discussions of their maximum Lyapunov exponent values and entropies. Finally, optimized chaotic oscillators are synchronized and realized to implement a secure communication system that processes black and white and grey-scale images. In each application, readers will find VHDL programming guidelines and computer arithmetic issues, along with co-simulation examples with Active-HDL and Simulink. Readers will b...

  12. Thermodynamic method for generating random stress distributions on an earthquake fault

    Science.gov (United States)

    Barall, Michael; Harris, Ruth A.

    2012-01-01

    This report presents a new method for generating random stress distributions on an earthquake fault, suitable for use as initial conditions in a dynamic rupture simulation. The method employs concepts from thermodynamics and statistical mechanics. A pattern of fault slip is considered to be analogous to a micro-state of a thermodynamic system. The energy of the micro-state is taken to be the elastic energy stored in the surrounding medium. Then, the Boltzmann distribution gives the probability of a given pattern of fault slip and stress. We show how to decompose the system into independent degrees of freedom, which makes it computationally feasible to select a random state. However, due to the equipartition theorem, straightforward application of the Boltzmann distribution leads to a divergence which predicts infinite stress. To avoid equipartition, we show that the finite strength of the fault acts to restrict the possible states of the system. By analyzing a set of earthquake scaling relations, we derive a new formula for the expected power spectral density of the stress distribution, which allows us to construct a computer algorithm free of infinities. We then present a new technique for controlling the extent of the rupture by generating a random stress distribution thousands of times larger than the fault surface, and selecting a portion which, by chance, has a positive stress perturbation of the desired size. Finally, we present a new two-stage nucleation method that combines a small zone of forced rupture with a larger zone of reduced fracture energy.

  13. Pragmatic randomized trials in drug development pose new ethical questions: a systematic review.

    Science.gov (United States)

    Kalkman, Shona; van Thiel, Ghislaine J M W; Grobbee, Diederick E; van Delden, Johannes J M

    2015-07-01

    Implementation of pragmatic design elements in drug development could bridge the evidence gap that currently exists between the knowledge we have regarding the efficacy of a drug versus its true, comparative effectiveness in real life. We performed a review of the literature to identify the ethical challenges thus far related to pragmatic trials. The three central ethical questions identified for pragmatic trials are: (i) what level of oversight should pragmatic trials require; (ii) do randomized patients face additional risks; and (iii) is a waiver of informed consent ethically defensible? Despite the fact all reviewed publications dealt with post-launch pragmatic trials, these results could serve as an important starting point for conceptualizing which challenges could potentially arise in the pre-launch setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Wheeze as an Adverse Event in Pediatric Vaccine and Drug Randomized Controlled Trials: A Systematic Review

    Science.gov (United States)

    Marangu, Diana; Kovacs, Stephanie; Walson, Judd; Bonhoeffer, Jan; Ortiz, Justin R.; John-Stewart, Grace; Horne, David J.

    2016-01-01

    Introduction Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs). Objective To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity. Conclusion Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as new vaccines and drugs are evaluated. PMID:26319071

  15. Use of an antiepileptic drug to control epileptic seizures associated with cranioplasty: A randomized controlled trial.

    Science.gov (United States)

    Chen, Fei; Duan, Yaqi; Li, Yongqin; Han, Wenjie; Shi, Weilei; Zhang, Weiwei; Huang, Yonghua

    2017-04-01

    Epilepsy is a common complication of cranioplasty. The present study was designed to explore the clinical effect of prophylactic anti-epilepsy drugs (AED) to control epileptic seizures associated with cranioplasty. and design: This trial was a prospective, randomized, open-label, single-centre, active controlled study designed to investigate the use of antiepileptic drug to control epileptic seizures associated with cranioplasty. We tested the necessity and methods of drug use. Three hundred twenty epilepsy patients who underwent cranioplasty were included in this study. The patients were randomly divided into the control group (160 cases) and the experimental group (160 cases). AED were administered to experimental group from 4 days before the surgery until 1 month after the surgery. The incidence of early and late epileptic seizures after cranioplasty was analyzed. The liver function, abnormal blood test 1 month after surgery were compared between these two groups. The incidence of seizures in the Control group was 28.6% (43 cases in 149 cases) while in the experimental group was only 5.9% (9 cases in 151 cases), which had statistical significance. The incidence of epileptic seizure was significantly higher in patients who received no AED treatment than in those who received AED treatment. Besides, the abnormal liver function and blood routine examination in both control and experimental group had no significant differences. The incidence of epilepsy associated with the cranioplasty is high and early use of anti-epileptic drugs can effectively reduce the occurrence of seizures. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  16. rMotifGen: random motif generator for DNA and protein sequences

    Directory of Open Access Journals (Sweden)

    Hardin C Timothy

    2007-08-01

    Full Text Available Abstract Background Detection of short, subtle conserved motif regions within a set of related DNA or amino acid sequences can lead to discoveries about important regulatory domains such as transcription factor and DNA binding sites as well as conserved protein domains. In order to help assess motif detection algorithms on motifs with varying properties and levels of conservation, we have developed a computational tool, rMotifGen, with the sole purpose of generating a number of random DNA or protein sequences containing short sequence motifs. Each motif consensus can be user-defined, randomly generated, or created from a position-specific scoring matrix (PSSM. Insertions and mutations within these motifs are created according to user-defined parameters and substitution matrices. The resulting sequences can be helpful in mutational simulations and in testing the limits of motif detection algorithms. Results Two implementations of rMotifGen have been created, one providing a graphical user interface (GUI for random motif construction, and the other serving as a command line interface. The second implementation has the added advantages of platform independence and being able to be called in a batch mode. rMotifGen was used to construct sample sets of sequences containing DNA motifs and amino acid motifs that were then tested against the Gibbs sampler and MEME packages. Conclusion rMotifGen provides an efficient and convenient method for creating random DNA or amino acid sequences with a variable number of motifs, where the instance of each motif can be incorporated using a position-specific scoring matrix (PSSM or by creating an instance mutated from its corresponding consensus using an evolutionary model based on substitution matrices. rMotifGen is freely available at: http://bioinformatics.louisville.edu/brg/rMotifGen/.

  17. Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

    Directory of Open Access Journals (Sweden)

    Jack Xie

    2010-08-01

    Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

  18. ADOLESCENT ALCOHOL- AND ILLICIT DRUG-USE IN FIRST AND SECOND GENERATION IMMIGRANTS IN SWEDEN

    OpenAIRE

    Svensson, Mikael; Hagquist, Curt

    2009-01-01

    In this paper adolescent alcohol- and illicit drug-use among 1st and 2nd generation immigrants from Nordic, non-Nordic European and non-European countries were compared with the Swedish majority population. Multilevel logistic regression analysis was performed based on survey data from three different Swedish regions including 24 municipalities sampled in 2005 including 13,070 adolescents. Immigrants from Nordic countries were more likely to use alcohol (OR: 1.10-1.37) while immigrants from n...

  19. Irrational use of antimalarial drugs in rural areas of eastern Pakistan: a random field study

    Directory of Open Access Journals (Sweden)

    Khan Shafaat Yar

    2012-11-01

    Full Text Available Abstract Background Prescription of antimalarial drugs in the absence of malarial disease is a common practice in countries where malaria is endemic. However, unwarranted use of such drugs can cause side effects in some people and is a financial drain on local economies. In this study, we surveyed the prevalence of malaria parasites in humans, and the prevalence of the malaria transmitting mosquito vectors in the study area. We also investigated the use of antimalarial drugs in the local people. We focused on randomly selected rural areas of eastern Pakistan where no malaria cases had been reported since May 2004. Methods Mass blood surveys, active case detection, passive case detection, and vector density surveys were carried out in selected areas of Sargodha district from September 2008 to August 2009. Data pertaining to the quantities and types of antimalarial drugs used in these areas were collected from health centers, pharmacies, and the district CDC program of the Health Department of the Government of the Punjab. Results Seven hundred and forty four blood samples were examined, resulting in a Blood Examination Rate (BER of 3.18; microscopic analysis of blood smears showed that none of the samples were positive for malaria parasites. Investigation of the mosquito vector density in 43 living rooms (bedrooms or rooms used for sleeping, 23 stores, and 32 animal sheds, revealed no vectors capable of transmitting malaria in these locations. In contrast, the density of Culex mosquitoes was high. Substantial consumption of a variety of antimalarial tablets, syrups, capsules and injections costing around 1000 US$, was documented for the region. Conclusion Use of antimalarial drugs in the absence of malarial infection or the vectors that transmit the disease was common in the study area. Continuous use of such drugs, not only in Pakistan, but in other parts of the world, may lead to drug-induced side effects amongst users. Better training of

  20. Emergence of deterministic Green's functions from noise generated by finite random sources.

    Science.gov (United States)

    Godin, Oleg A

    2009-12-01

    Two-point correlation functions of sufficiently diffuse wave fields generated by uncorrelated random sources are known to approximate deterministic Green's functions between the two points. This property is utilized increasingly for passive imaging and remote sensing of the environment. Here we show that the relation between the Green's functions and the noise cross-correlation function holds under much less restrictive conditions than previously thought. It can even hold when ambient noise sources have correlation ranges large compared to the wavelength. Admissible correlation ranges are limited from above by the size of the Fresnel zone at wave propagation between the points where noise cross correlation is evaluated.

  1. Random number generator based on an integrated laser with on-chip optical feedback

    Science.gov (United States)

    Verschaffelt, Guy; Khoder, Mulham; Van der Sande, Guy

    2017-11-01

    We discuss the design and testing of a laser integrated with a long on-chip optical feedback section. The device and feedback section have been fabricated on a generic photonic integration platform using only standard building blocks. We have been able to integrate a 10 cm feedback length on a footprint of 5.5 mm2. By controlling the amount of feedback, we achieve chaotic dynamics in the long-cavity regime and show that the resulting dynamics is sufficiently complex in order to generate random bits based on the chaotic intensity fluctuation at a rate of 500 Mbits/s.

  2. Application of random number generators in genetic algorithms to improve rainfall-runoff modelling

    Czech Academy of Sciences Publication Activity Database

    Chlumecký, M.; Buchtele, Josef; Richta, K.

    2017-01-01

    Roč. 553, October (2017), s. 350-355 ISSN 0022-1694 Institutional support: RVO:67985874 Keywords : genetic algorithm * optimisation * rainfall-runoff modeling * random generator Subject RIV: DA - Hydrology ; Limnology Impact factor: 3.483, year: 2016 https://ac.els-cdn.com/S0022169417305516/1-s2.0-S0022169417305516-main.pdf?_tid=fa1bad8a-bd6a-11e7-8567-00000aab0f27&acdnat=1509365462_a1335d3d997e9eab19e23b1eee977705

  3. A proposal for a drug information database and text templates for generating package inserts

    Directory of Open Access Journals (Sweden)

    Okuya R

    2013-07-01

    Full Text Available Ryo Okuya,1 Masaomi Kimura,2 Michiko Ohkura,2 Fumito Tsuchiya3 1Graduate School of Engineering and Science, 2Faculty of Engineering, Shibaura Institute of Technology, Tokyo, 3School of Pharmacy, International University of Health and Welfare, Tokyo, Japan Abstract: To prevent prescription errors caused by information systems, a database to store complete and accurate drug information in a user-friendly format is needed. In previous studies, the primary method for obtaining data stored in a database is to extract drug information from package inserts by employing pattern matching or more sophisticated methods such as text mining. However, it is difficult to obtain a complete database because there is no strict rule concerning expressions used to describe drug information in package inserts. The authors' strategy was to first build a database and then automatically generate package inserts by embedding data in the database using templates. To create this database, the support of pharmaceutical companies to input accurate data is required. It is expected that this system will work, because these companies can earn merit for newly developed drugs to decrease the effort to create package inserts from scratch. This study designed the table schemata for the database and text templates to generate the package inserts. To handle the variety of drug-specific information in the package inserts, this information in drug composition descriptions was replaced with labels and the replacement descriptions utilizing cluster analysis were analyzed. To improve the method by which frequently repeated ingredient information and/or supplementary information are stored, the method was modified by introducing repeat tags in the templates to indicate repetition and improving the insertion of data into the database. The validity of this method was confirmed by inputting the drug information described in existing package inserts and checking that the method could

  4. VITAMINE E IN THE MANAGEMENT OF DRUG INDUCED TARDIVE DYSKINESIA: A DOUBLE BLIND RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    M KAR AHMADI

    2002-12-01

    Full Text Available Introduction. Expresssion of tardive dyskinesia as one of the side effects of antipsychotic drugs causes various problems in psychotic patients. It is the main cause of patient"s drug incompliance.Vitamine E with it"s antioxidants properties might be an effective treatment for tardive dyskinesia. Methods. In a randomized double blind clinical trial, thirty inpatients of the psychiatric hospital in Isfahan were studied. Patients were stratified according to their age, psychiatric disorder and duration, intensity of tardive dyskinesia and antipsychotic dosage. Then they were asssigned randomly into two groups. Vitamine E (600 mg/day was administered to interventional group (15 patients. Another group received placebo (15 patients. Treatment durated for 6 weeks. Abnormal Involuntary Movment Scale (AIMS was used to measure tardive dyskinesia intensity. Results. Average of disorder intensity in those who received vit. E, dropped down from 8.33/10 (befor treatment to 6.13/10 (after treatment. It means 26.3 percent reduction of tardive dyskinesia intensity. This difference was only 7.3 percent in control group. There were no statistical diffrence between two groups after treatment (P>0.05. Discussion. There is no statistical efficacy for vitamine E in the management of tardive dyskinesia. But it is recommended to make another study with more samples.

  5. On Generating Optimal Signal Probabilities for Random Tests: A Genetic Approach

    Directory of Open Access Journals (Sweden)

    M. Srinivas

    1996-01-01

    Full Text Available Genetic Algorithms are robust search and optimization techniques. A Genetic Algorithm based approach for determining the optimal input distributions for generating random test vectors is proposed in the paper. A cost function based on the COP testability measure for determining the efficacy of the input distributions is discussed. A brief overview of Genetic Algorithms (GAs and the specific details of our implementation are described. Experimental results based on ISCAS-85 benchmark circuits are presented. The performance of our GAbased approach is compared with previous results. While the GA generates more efficient input distributions than the previous methods which are based on gradient descent search, the overheads of the GA in computing the input distributions are larger.

  6. A Chemical Reaction Network to Generate Random, Power-Law-Distributed Time Intervals.

    Science.gov (United States)

    Krauss, Patrick; Schulze, Holger; Metzner, Claus

    2017-10-06

    In Lévy walks (LWs), particles move with a fixed speed along straight line segments and turn in new directions after random time intervals that are distributed according to a power law. Such LWs are thought to be an advantageous foraging and search strategy for organisms. While complex nervous systems are certainly capable of producing such behavior, it is not clear at present how single-cell organisms can generate the long-term correlated control signals required for a LW. Here, we construct a biochemical reaction system that generates long-time correlated concentration fluctuations of a signaling substance, with a tunable fractional exponent of the autocorrelation function. The network is based on well-known modules, and its basic function is highly robust with respect to the parameter settings.

  7. A Hardware Efficient Random Number Generator for Nonuniform Distributions with Arbitrary Precision

    Directory of Open Access Journals (Sweden)

    Christian de Schryver

    2012-01-01

    number generators is a very active research field. However, most state-of-the-art architectures are either tailored to specific distributions or use up a lot of hardware resources. At ReConFig 2010, we have presented a new design that saves up to 48% of area compared to state-of-the-art inversion-based implementation, usable for arbitrary distributions and precision. In this paper, we introduce a more flexible version together with a refined segmentation scheme that allows to further reduce the approximation error significantly. We provide a free software tool allowing users to implement their own distributions easily, and we have tested our random number generator thoroughly by statistic analysis and two application tests.

  8. Pulsed magnetic field induced fast drug release from magneto liposomes via ultrasound generation.

    Science.gov (United States)

    Podaru, George; Ogden, Saralyn; Baxter, Amanda; Shrestha, Tej; Ren, Shenqiang; Thapa, Prem; Dani, Raj Kumar; Wang, Hongwang; Basel, Matthew T; Prakash, Punit; Bossmann, Stefan H; Chikan, Viktor

    2014-10-09

    Fast drug delivery is very important to utilize drug molecules that are short-lived under physiological conditions. Techniques that can release model molecules under physiological conditions could play an important role to discover the pharmacokinetics of short-lived substances in the body. Here an experimental method is developed for the fast release of the liposomes' payload without a significant increase in (local) temperatures. This goal is achieved by using short magnetic pulses to disrupt the lipid bilayer of liposomes loaded with magnetic nanoparticles. The drug release has been tested by two independent assays. The first assay relies on the AC impedance measurements of MgSO4 released from the magnetic liposomes. The second standard release assay is based on the increase of the fluorescence signal from 5(6)-carboxyfluorescein dye when the dye is released from the magneto liposomes. The efficiency of drug release ranges from a few percent to up to 40% in the case of the MgSO4. The experiments also indicate that the magnetic nanoparticles generate ultrasound, which is assumed to have a role in the release of the model drugs from the magneto liposomes.

  9. Sentiment Analysis of User-Generated Content on Drug Review Websites

    Directory of Open Access Journals (Sweden)

    Na, Jin-Cheon

    2015-03-01

    Full Text Available This study develops an effective method for sentiment analysis of user-generated content on drug review websites, which has not been investigated extensively compared to other general domains, such as product reviews. A clause-level sentiment analysis algorithm is developed since each sentence can contain multiple clauses discussing multiple aspects of a drug. The method adopts a pure linguistic approach of computing the sentiment orientation (positive, negative, or neutral of a clause from the prior sentiment scores assigned to words, taking into consideration the grammatical relations and semantic annotation (such as disorder terms of words in the clause. Experiment results with 2,700 clauses show the effectiveness of the proposed approach, and it performed significantly better than the baseline approaches using a machine learning approach. Various challenging issues were identified and discussed through error analysis. The application of the proposed sentiment analysis approach will be useful not only for patients, but also for drug makers and clinicians to obtain valuable summaries of public opinion. Since sentiment analysis is domain specific, domain knowledge in drug reviews is incorporated into the sentiment analysis algorithm to provide more accurate analysis. In particular, MetaMap is used to map various health and medical terms (such as disease and drug names to semantic types in the Unified Medical Language System (UMLS Semantic Network.

  10. Randomized response estimates for the 12-month prevalence of cognitive-enhancing drug use in university students.

    Science.gov (United States)

    Dietz, Pavel; Striegel, Heiko; Franke, Andreas G; Lieb, Klaus; Simon, Perikles; Ulrich, Rolf

    2013-01-01

    To estimate the 12-month prevalence of cognitive-enhancing drug use. Paper-and-pencil questionnaire that used the randomized response technique. University in Mainz, Germany. A total of 2569 university students who completed the questionnaire. An anonymous, specialized questionnaire that used the randomized response technique was distributed to students at the beginning of classes and was collected afterward. From the responses, we calculated the prevalence of students taking drugs only to improve their cognitive performance and not to treat underlying mental disorders such as attention-deficit-hyperactivity disorder, depression, and sleep disorders. The estimated 12-month prevalence of using cognitive-enhancing drugs was 20%. Prevalence varied by sex (male 23.7%, female 17.0%), field of study (highest in students studying sports-related fields, 25.4%), and semester (first semester 24.3%, beyond first semester 16.7%). To our knowledge, this is the first time that the randomized response technique has been used to survey students about cognitive-enhancing drug use. Using the randomized response technique, our questionnaire provided data that showed a high 12-month prevalence of cognitive-enhancing drug use in German university students. Our study suggests that other direct survey techniques have underestimated the use of these drugs. Drug prevention programs need to be established at universities to address this issue. © 2013 Pharmacotherapy Publications, Inc.

  11. Voriconazole therapeutic drug monitoring: results of a prematurely discontinued randomized multicenter trial.

    Science.gov (United States)

    Neofytos, D; Ostrander, D; Shoham, S; Laverdiere, M; Hiemenz, J; Nguyen, H; Clarke, W; Brass, L; Lu, N; Marr, K A

    2015-12-01

    Voriconazole (VOR) levels are highly variable, with potential implications to both efficacy and safety. We hypothesized that VOR therapeutic drug monitoring (TDM) will decrease the incidence of treatment failures and adverse events (AEs). We initiated a prospective, randomized, non-blinded multicenter study to compare clinical outcomes in adult patients randomized to standard dosing (clinician-driven) vs. TDM (doses adjusted based on levels). VOR trough levels were obtained on day 5, 14, 28, and 42 (or at completion of drug; ± 3 days). Real-time dose adjustments were made to maintain a range between 1-5 μg/mL on the TDM-arm, while levels were assessed retrospectively in the standard-arm. Patient questionnaires were administered to assess subjective AEs. The study was discontinued prematurely, after 29 patients were enrolled. Seventeen (58.6%) patients experienced 38 AEs: visual changes (22/38, 57.9%), neurological symptoms (13/38, 34.2%), and liver abnormalities (3/38, 7.9%). VOR was discontinued in 7 (25%) patients because of an AE (4 standard-arm, 3 TDM-arm). VOR levels were frequently out of range in the standard-arm (8 tests >5 μg/mL; 9 tests <1 μg/mL). Three dose changes occurred in the TDM-arm for VOR levels <1 μg/mL. Levels decreased over time in the standard-arm, with mean VOR levels lower at end of therapy compared to TDM (1.3 vs. 4.6 μg/mL, P = 0.008). VOR TDM has become widespread clinical practice, based on known variability in drug levels, which impaired accrual in this study. Although comparative conclusions are limited, observations of variability and waning levels over time support TDM. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. [Clinical randomized controlled study on acupuncture for treatment of peripheral neuropathy induced by chemotherapeutic drugs].

    Science.gov (United States)

    Xu, Wei-Ru; Hua, Bao-Jin; Hou, Wei; Bao, Yan-Ju

    2010-06-01

    To seek the effective treatment for peripheral neuropathy induced by chemotherapeutic drugs. Sixty-four cases of peripheral neuropathy induced by Paclitaxel or Oxaliplatin were randomly divided into an acupuncture group and a medication group, 32 cases in each group. The acupuncture group was treated with therapeutic principle of dredging meridians and collaterals, tonifying qi and eliminating blood stasis, supplementing liver and kidney, nourishing blood and tendon. Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36), Qihai (CV 6) and Quchi (LI 11) etc. were selected. The medication group was treated with intramuscular injection of Cobamamide. The neurotoxicity of two groups was compared with questionnaire of peripheral neuropathy induced by chemotherapeutic drugs before and after treatment. The total effective rate for sensory nerve disorder of acupuncture group was 66.7% (20/30), which was superior to that of 40.0% (12/30) in medication group (P Cobamamide for treatment of peripheral neuropathy induced by chemotherapeutic drugs, especially for moderate and severe sensory nerve disorder induced by paclitaxel.

  13. Generation mechanism of nonlinear ultrasonic Lamb waves in thin plates with randomly distributed micro-cracks.

    Science.gov (United States)

    Zhao, Youxuan; Li, Feilong; Cao, Peng; Liu, Yaolu; Zhang, Jianyu; Fu, Shaoyun; Zhang, Jun; Hu, Ning

    2017-08-01

    Since the identification of micro-cracks in engineering materials is very valuable in understanding the initial and slight changes in mechanical properties of materials under complex working environments, numerical simulations on the propagation of the low frequency S 0 Lamb wave in thin plates with randomly distributed micro-cracks were performed to study the behavior of nonlinear Lamb waves. The results showed that while the influence of the randomly distributed micro-cracks on the phase velocity of the low frequency S 0 fundamental waves could be neglected, significant ultrasonic nonlinear effects caused by the randomly distributed micro-cracks was discovered, which mainly presented as a second harmonic generation. By using a Monte Carlo simulation method, we found that the acoustic nonlinear parameter increased linearly with the micro-crack density and the size of micro-crack zone, and it was also related to the excitation frequency and friction coefficient of the micro-crack surfaces. In addition, it was found that the nonlinear effect of waves reflected by the micro-cracks was more noticeable than that of the transmitted waves. This study theoretically reveals that the low frequency S 0 mode of Lamb waves can be used as the fundamental waves to quantitatively identify micro-cracks in thin plates. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 1.2 GBit/s Pseudo Random Pulse Generator Using Multiplexing with GaAs Mesfet Gates

    DEFF Research Database (Denmark)

    Hede, Carsten

    1978-01-01

    A l.2 Gbit/s RZ pseudo random bit generator using multiplexing of six 200 Mbit/s channels, and a GaAs-MESFET gate circuit which exhibits both high speed and simplicity are presented. As a new contribution to the treatment of pseudo random sequences it is shown how the autocorrelation function and...

  15. Chronic care management for dependence on alcohol and other drugs: the AHEAD randomized trial.

    Science.gov (United States)

    Saitz, Richard; Cheng, Debbie M; Winter, Michael; Kim, Theresa W; Meli, Seville M; Allensworth-Davies, Don; Lloyd-Travaglini, Christine A; Samet, Jeffrey H

    2013-09-18

    People with substance dependence have health consequences, high health care utilization, and frequent comorbidity but often receive poor-quality care. Chronic care management (CCM) has been proposed as an approach to improve care and outcomes. To determine whether CCM for alcohol and other drug dependence improves substance use outcomes compared with usual primary care. The AHEAD study, a randomized trial conducted among 563 people with alcohol and other drug dependence at a Boston, Massachusetts, hospital-based primary care practice. Participants were recruited from September 2006 to September 2008 from a freestanding residential detoxification unit and referrals from an urban teaching hospital and advertisements; 95% completed 12-month follow-up. Participants were randomized to receive CCM (n=282) or no CCM (n=281). Chronic care management included longitudinal care coordinated with a primary care clinician; motivational enhancement therapy; relapse prevention counseling; and on-site medical, addiction, and psychiatric treatment, social work assistance, and referrals (including mutual help). The no CCM (control) group received a primary care appointment and a list of treatment resources including a telephone number to arrange counseling. The primary outcome was self-reported abstinence from opioids, stimulants, or heavy drinking. Biomarkers were secondary outcomes. There was no significant difference in abstinence from opioids, stimulants, or heavy drinking between the CCM (44%) and control (42%) groups (adjusted odds ratio, 0.84; 95% CI, 0.65-1.10; P=.21). No significant differences were found for secondary outcomes of addiction severity, health-related quality of life, or drug problems. No subgroup effects were found except among those with alcohol dependence, in whom CCM was associated with fewer alcohol problems (mean score, 10 vs 13; incidence rate ratio, 0.85; 95% CI, 0.72-1.00; P=.048). Among persons with alcohol and other drug dependence, CCM compared

  16. The cosmic microwave background radiation power spectrum as a random bit generator for symmetric- and asymmetric-key cryptography

    Directory of Open Access Journals (Sweden)

    Jeffrey S. Lee

    2017-10-01

    Full Text Available In this note, the Cosmic Microwave Background (CMB Radiation is shown to be capable of functioning as a Random Bit Generator, and constitutes an effectively infinite supply of truly random one-time pad values of arbitrary length. It is further argued that the CMB power spectrum potentially conforms to the FIPS 140-2 standard. Additionally, its applicability to the generation of a (n × n random key matrix for a Vernam cipher is established. Keywords: Particle physics, Computer science, Mathematics, Astrophysics

  17. Next-Generation Human Immunodeficiency Virus Sequencing for Patient Management and Drug Resistance Surveillance.

    Science.gov (United States)

    Noguera-Julian, Marc; Edgil, Dianna; Harrigan, P Richard; Sandstrom, Paul; Godfrey, Catherine; Paredes, Roger

    2017-12-01

    High-quality, simplified, and low-cost human immunodeficiency virus (HIV) drug resistance tests that are able to provide timely actionable HIV resistance data at individual, population, and programmatic levels are needed to confront the emerging drug-resistant HIV epidemic. Next-generation sequencing technologies embedded in automated cloud-computing analysis environments are ideally suited for such endeavor. Whereas NGS can reduce costs over Sanger sequencing, automated analysis pipelines make NGS accessible to molecular laboratories regardless of the available bioinformatic skills. They can also produce highly structured, high-quality data that could be examined by healthcare officials and program managers on a real-time basis to allow timely public health action. Here we discuss the opportunities and challenges of such an approach. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Evaluation of dysprosia aerogels as drug delivery systems: a comparative study with random and ordered mesoporous silicas.

    Science.gov (United States)

    Bang, Abhishek; Sadekar, Anand G; Buback, Clayton; Curtin, Brice; Acar, Selin; Kolasinac, Damir; Yin, Wei; Rubenstein, David A; Lu, Hongbing; Leventis, Nicholas; Sotiriou-Leventis, Chariklia

    2014-04-09

    Biocompatible dysprosia aerogels were synthesized from DyCl3·6H2O and were reinforced mechanically with a conformal nano-thin-polyurea coating applied over their skeletal framework. The random mesoporous space of dysprosia aerogels was filled up to about 30% v/v with paracetamol, indomethacin, or insulin, and the drug release rate was monitored spectrophotometrically in phosphate buffer (pH = 7.4) or 0.1 M aqueous HCl. The drug uptake and release study was conducted comparatively with polyurea-crosslinked random silica aerogels, as well as with as-prepared (native) and polyurea-crosslinked mesoporous silica perforated with ordered 7 nm tubes in hexagonal packing. Drug uptake from random nanostructures (silica or dysprosia) was higher (30-35% w/w) and the release rate was slower (typically >20 h) relative to ordered silica (19-21% w/w, Drug release data from dysprosia aerogels were fitted with a flux equation consisting of three additive terms that correspond to drug stored successively in three hierarchical pore sites on the skeletal framework. The high drug uptake and slow release from dysprosia aerogels, in combination with their low toxicity, strong paramagnetism, and the possibility for neutron activation render those materials attractive multifunctional vehicles for site-specific drug delivery.

  19. Underutilization of prescribed drugs use among first generation elderly immigrants in the Netherlands

    Directory of Open Access Journals (Sweden)

    Birnie Erwin

    2010-06-01

    Full Text Available Abstract Background In developed countries, health care utilization among immigrant groups differs where the dominant interpretation is unjustified overutilization due to lack of acculturation. We investigated utilization of prescribed drugs in native Dutch and various groups of immigrant elderly. Methods Cross-sectional study using data from the survey "Social Position, Health and Well-being of Elderly Immigrants" (the Netherlands, 2003. Ethnicity-matched interviewers conducted the survey among first generation immigrants aged 55 years and older. Outcome measure is self-reported use of prescribed drugs. Utilization is explained by need, and by enabling and predisposing factors, in particular acculturation; analysis is conducted by multiple logistic regression. Results The study population consisted of immigrants from Turkey (n = 307, Morocco (n = 284, Surinam (n = 308 and the Netherlands Antilles (n = 300, and a native Dutch reference group (n = 304. Prevalence of diabetes mellitus (DM, COPD and musculoskeletal disorders was relatively high among immigrant elderly. Drug utilization in especially Turkish and Moroccan elderly with DM and COPD was relatively low. Drugs use for non-mental chronic diseases was explained by more chronic conditions (OR 2.64, higher age (OR 1.03, and modern attitudes on male-female roles (OR 0.74 and religiosity (OR 0.89. Ethnicity specific effects remained only among Turkish elderly (OR 0.42. Drugs use for mental health problems was explained by more chronic conditions (OR 1.43, better mental health (OR 0.95 and modern attitudes on family values (OR 0.59. Ethnicity specific effects remained only among Moroccan (OR 0.19 and Antillean elderly (OR 0.31. Explanation of underutilization of drugs among diseased with diabetes and musculoskeletal disorders are found in number of chronic diseases (OR 0.74 and OR 0.78 and regarding diabetes also in language proficiency (OR 0.66 and modern attitudes on male-female roles (OR 1

  20. Underutilization of prescribed drugs use among first generation elderly immigrants in the Netherlands.

    Science.gov (United States)

    Denktaş, Semiha; Koopmans, Gerrit; Birnie, Erwin; Foets, Marleen; Bonsel, Gouke

    2010-06-22

    In developed countries, health care utilization among immigrant groups differs where the dominant interpretation is unjustified overutilization due to lack of acculturation. We investigated utilization of prescribed drugs in native Dutch and various groups of immigrant elderly. Cross-sectional study using data from the survey "Social Position, Health and Well-being of Elderly Immigrants" (the Netherlands, 2003). Ethnicity-matched interviewers conducted the survey among first generation immigrants aged 55 years and older. Outcome measure is self-reported use of prescribed drugs. Utilization is explained by need, and by enabling and predisposing factors, in particular acculturation; analysis is conducted by multiple logistic regression. The study population consisted of immigrants from Turkey (n = 307), Morocco (n = 284), Surinam (n = 308) and the Netherlands Antilles (n = 300), and a native Dutch reference group (n = 304). Prevalence of diabetes mellitus (DM), COPD and musculoskeletal disorders was relatively high among immigrant elderly. Drug utilization in especially Turkish and Moroccan elderly with DM and COPD was relatively low. Drugs use for non-mental chronic diseases was explained by more chronic conditions (OR 2.64), higher age (OR 1.03), and modern attitudes on male-female roles (OR 0.74) and religiosity (OR 0.89). Ethnicity specific effects remained only among Turkish elderly (OR 0.42). Drugs use for mental health problems was explained by more chronic conditions (OR 1.43), better mental health (OR 0.95) and modern attitudes on family values (OR 0.59). Ethnicity specific effects remained only among Moroccan (OR 0.19) and Antillean elderly (OR 0.31). Explanation of underutilization of drugs among diseased with diabetes and musculoskeletal disorders are found in number of chronic diseases (OR 0.74 and OR 0.78) and regarding diabetes also in language proficiency (OR 0.66) and modern attitudes on male-female roles (OR 1.69). Need and predisposing factors

  1. Comparison of HIV-1 drug resistance profiles generated from novel software applications for routine patient care

    Directory of Open Access Journals (Sweden)

    Dimitri Gonzalez

    2014-11-01

    Full Text Available Introduction: Clinical laboratories performing routine HIV-1 genotyping antiviral drug resistance (DR testing need reliable and up-to-date information systems to provide accurate and timely test results to optimize antiretroviral treatment in HIV-1-infected patients. Materials and Methods: Three software applications were used to compare DR profiles generated from the analysis of HIV-1 protease (PR and reverse transcriptase (RT gene sequences obtained by Sanger sequencing assay in 100 selected clinical plasma samples from March 2013 through May 2014. Interpretative results obtained from the Trugene HIV-1 Genotyping assay (TG; Guidelines v17.0 were compared with a newly FDA-registered data processing module (DPM v1.0 and the research-use-only ViroScore-HIV (VS software, both of which use the latest versions of Stanford HIVdb (SD v7.0 and geno2pheno (G2P v3.3 interpretive algorithms (IA. Differences among the DR interpretive algorithms were compared according to drug class (NRTI, NNRTI, PI and each drug. HIV-1 tropism and integrase inhibitor resistance were not evaluated (not available in TG. Results: Overall, only 17 of the 100 TG sequences obtained yielded equivalent DR profiles among all 3 software applications for every IA and for all drug classes. DPM and VS generated equivalent results with >99.9% agreement. Excluding AZT, DDI, D4T and rilpivirine (not available in G2P, ranges of agreement in DR profiles among the three IA (using the DPM are shown in Table 1. Conclusions: Substantial discrepancies (<75% agreement exist among the three interpretive algorithms for ETR, while G2P differed from TG and SD for resistance to TDF and TPV/r. Use of more than one DR interpretive algorithm using well-validated software applications, such as DPM v1.0 and VS, would enable clinical laboratories to provide clinically useful and accurate DR results for patient care needs.

  2. In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

    Science.gov (United States)

    Zhang, J; Wang, Q; Wang, A

    2010-02-01

    In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

  3. K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology.

    Science.gov (United States)

    Sakamoto, Kotaro; Kamada, Yusuke; Sameshima, Tomoya; Yaguchi, Masahiro; Niida, Ayumu; Sasaki, Shigekazu; Miwa, Masanori; Ohkubo, Shoichi; Sakamoto, Jun-Ichi; Kamaura, Masahiro; Cho, Nobuo; Tani, Akiyoshi

    2017-03-11

    Amino-acid mutations of Gly 12 (e.g. G12D, G12V, G12C) of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras), the most promising drug target in cancer therapy, are major growth drivers in various cancers. Although over 30 years have passed since the discovery of these mutations in most cancer patients, effective mutated K-Ras inhibitors have not been marketed. Here, we report novel and selective inhibitory peptides to K-Ras(G12D). We screened random peptide libraries displayed on T7 phage against purified recombinant K-Ras(G12D), with thorough subtraction of phages bound to wild-type K-Ras, and obtained KRpep-2 (Ac-RRCPLYISYDPVCRR-NH 2 ) as a consensus sequence. KRpep-2 showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. K D and IC 50 values were 51 and 8.9 nM, respectively. After subsequent sequence optimization, we successfully generated KRpep-2d (Ac-RRRRCPLYISYDPVCRRRR-NH 2 ) that inhibited enzyme activity of K-Ras(G12D) with IC 50  = 1.6 nM and significantly suppressed ERK-phosphorylation, downstream of K-Ras(G12D), along with A427 cancer cell proliferation at 30 μM peptide concentration. To our knowledge, this is the first report of a K-Ras(G12D)-selective inhibitor, contributing to the development and study of K-Ras(G12D)-targeting drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Harvesting Entropy for Random Number Generation for Internet of Things Constrained Devices Using On-Board Sensors

    Science.gov (United States)

    Pawlowski, Marcin Piotr; Jara, Antonio; Ogorzalek, Maciej

    2015-01-01

    Entropy in computer security is associated with the unpredictability of a source of randomness. The random source with high entropy tends to achieve a uniform distribution of random values. Random number generators are one of the most important building blocks of cryptosystems. In constrained devices of the Internet of Things ecosystem, high entropy random number generators are hard to achieve due to hardware limitations. For the purpose of the random number generation in constrained devices, this work proposes a solution based on the least-significant bits concatenation entropy harvesting method. As a potential source of entropy, on-board integrated sensors (i.e., temperature, humidity and two different light sensors) have been analyzed. Additionally, the costs (i.e., time and memory consumption) of the presented approach have been measured. The results obtained from the proposed method with statistical fine tuning achieved a Shannon entropy of around 7.9 bits per byte of data for temperature and humidity sensors. The results showed that sensor-based random number generators are a valuable source of entropy with very small RAM and Flash memory requirements for constrained devices of the Internet of Things. PMID:26506357

  5. Harvesting entropy for random number generation for internet of things constrained devices using on-board sensors.

    Science.gov (United States)

    Pawlowski, Marcin Piotr; Jara, Antonio; Ogorzalek, Maciej

    2015-10-22

    Entropy in computer security is associated with the unpredictability of a source of randomness. The random source with high entropy tends to achieve a uniform distribution of random values. Random number generators are one of the most important building blocks of cryptosystems. In constrained devices of the Internet of Things ecosystem, high entropy random number generators are hard to achieve due to hardware limitations. For the purpose of the random number generation in constrained devices, this work proposes a solution based on the least-significant bits concatenation entropy harvesting method. As a potential source of entropy, on-board integrated sensors (i.e., temperature, humidity and two different light sensors) have been analyzed. Additionally, the costs (i.e., time and memory consumption) of the presented approach have been measured. The results obtained from the proposed method with statistical fine tuning achieved a Shannon entropy of around 7.9 bits per byte of data for temperature and humidity sensors. The results showed that sensor-based random number generators are a valuable source of entropy with very small RAM and Flash memory requirements for constrained devices of the Internet of Things.

  6. Harvesting Entropy for Random Number Generation for Internet of Things Constrained Devices Using On-Board Sensors

    Directory of Open Access Journals (Sweden)

    Marcin Piotr Pawlowski

    2015-10-01

    Full Text Available Entropy in computer security is associated with the unpredictability of a source of randomness. The random source with high entropy tends to achieve a uniform distribution of random values. Random number generators are one of the most important building blocks of cryptosystems. In constrained devices of the Internet of Things ecosystem, high entropy random number generators are hard to achieve due to hardware limitations. For the purpose of the random number generation in constrained devices, this work proposes a solution based on the least-significant bits concatenation entropy harvesting method. As a potential source of entropy, on-board integrated sensors (i.e., temperature, humidity and two different light sensors have been analyzed. Additionally, the costs (i.e., time and memory consumption of the presented approach have been measured. The results obtained from the proposed method with statistical fine tuning achieved a Shannon entropy of around 7.9 bits per byte of data for temperature and humidity sensors. The results showed that sensor-based random number generators are a valuable source of entropy with very small RAM and Flash memory requirements for constrained devices of the Internet of Things.

  7. Optical key distribution system using atmospheric turbulence as the randomness generating function: classical optical protocol for information assurance

    Science.gov (United States)

    Drake, Marvin D.; Bas, Christophe F.; Gervais, David; Renda, Priscilla F.; Townsend, Daniel; Rushanan, Joseph J.; Francoeur, Joe; Donnangelo, Nick; Stenner, Michael D.

    2013-05-01

    We describe an experimental laboratory system that generates and distributes random binary sequence bit streams between two optical terminals (labeled Alice and Bob). The random binary sequence is generated through probing the optical channel of a turbulent atmosphere between the two terminals with coincident laser beams. The two laser beams experience differential phase delays while propagating through the atmospheric optical channel. The differential phase delays are detected and sampled at each terminal to yield raw random bit streams. The random bit streams are processed to remove bit errors and, through privacy amplification, to yield a bit stream known only to Alice and Bob. The same chaotic physical mechanism that provides randomness also provides confidentiality. The laboratory system yielded secret key bit rates of a few bits/second. For external optical channels over longer channel lengths with atmospheric turbulence levels, secret bit rates of 10 s of bits/second are predicted.

  8. A comparison of alcohol and drug use by random motor vehicle drivers in Brazil and Norway.

    Science.gov (United States)

    Gjerde, Hallvard; Sousa, Tanara R; De Boni, Raquel; Christophersen, Asbjørg S; Limberger, Renata P; Zancanaro, Ivomar; Oiestad, Elisabeth L; Normann, Per T; Mørland, Jørg; Pechansky, Flavio

    2014-05-01

    A large proportion of road traffic crashes are related to driving under the influence (DUI) of alcohol or drugs. The aim of this study was to compare the use of alcohol, illegal drugs and psychoactive medicinal drugs among random drivers in Brazil and Norway, two countries with the same legal limit for drunk driving, but with marked differences in legislation history, enforcement and penalties for DUI, and to discuss any differences found. Roadside surveys were conducted on Fridays and Saturdays between noon and midnight. Samples of oral fluid were collected for analysis of drugs, whereas alcohol was determined by breath testing or by analysis of oral fluid. High participation rates of 94-97% were obtained in both countries. The weighted prevalence of driving with alcohol concentrations in breath or oral fluid equivalent to blood alcohol concentrations (BAC) above 0.2g/L was 2.7% (95% CI 2.2-3.3) in Brazil and 0.2% (95% CI 0.0-0.5) in Norway. Stimulants (amphetamines or cocaine) were found in samples from 1.0% (95% CI 0.7-1.4) of drivers in Brazil and 0.3% (95% CI 0.1-0.7) in Norway. The prevalence of amphetamines was highest among Brazilian truck drivers (3.6%; 95% CI 2.0-6.4). Tetrahydrocannabinol was found in samples from 0.5% (95% CI 0.3-0.8) of drivers in Brazil and 1.0% (95% CI 0.6-1.5) in Norway, whereas benzodiazepines or zopiclone were found in 1.0% (95% CI 0.7-1.4) and 1.7% (95% CI 1.2-2.4) of the samples from Brazil and Norway, respectively. The difference in the prevalence of alcohol may be related to the fact that Norway has implemented steps to reduce drunk driving since 1936, whereas Brazil has attempted to do the same for only a few years. Differences for drugs may be related to different patterns in the use of stimulants, cannabis and medicines. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. An advanced monolithic digitalized random carrier frequency spread-spectrum clock generator for EMI suppression

    Energy Technology Data Exchange (ETDEWEB)

    Guo Haiyan; Chen Zao; Zhang Bo; Li Zhaoji, E-mail: guohy5@sina.co [State Key Laboratory of Electronic Thin Films and Integrated devices, University of Electronic Science and Technology of China, Chengdu 610054 (China)

    2010-06-15

    A novel monolithic digitalized random carrier frequency modulation spread-spectrum clock generator (RCF-SSCG) is proposed. In this design, the output frequency of the proposed RCF-SSCG changes with the intensity of the capacitive charge and discharge current. Its analytical model is induced and the effect of the modulation parameters on the spread spectrum is numerically simulated and discussed. Compared with other works, this design has the advantages of small size, low power consumption and good robustness. The circuit has been fabricated in a 0.5 {mu}m CMOS process and applied to a class D amplifier in which the proposed RCF-SSCG occupies an area of 0.112 mm{sup 2} and consumes 9 mW. The experimental results confirm the theoretical analyses. (semiconductor integrated circuits)

  10. Generation of Random Wind Speed Profiles for Evaluation of Stress in WT Power Converters

    DEFF Research Database (Denmark)

    Pigazo, Alberto; Qin, Zian; Liserre, Marco

    2013-01-01

    Wind turbines are subjected to wind speed variations that cause a power profile that will stress the overall system. This stress is tranfered to the power converter, resulting in temperature variations of the power devices and, hence, causing the reduction of the lifetime. The lifetime expectation...... changes depending on the real wind speed once the wind turbine is operating. Usually, the real wind speed profiles are employed to evaluate this stress but they do not consider all possible operation conditions and require intensive computations. To solve these issues, this paper proposes the generation...... of random wind speed profiles, based on the measured ones, in order to evaluate the thermal stress of the power devices based on a simplified statistical approach....

  11. Recursive Random Lasso (RRLasso for Identifying Anti-Cancer Drug Targets.

    Directory of Open Access Journals (Sweden)

    Heewon Park

    Full Text Available Uncovering driver genes is crucial for understanding heterogeneity in cancer. L1-type regularization approaches have been widely used for uncovering cancer driver genes based on genome-scale data. Although the existing methods have been widely applied in the field of bioinformatics, they possess several drawbacks: subset size limitations, erroneous estimation results, multicollinearity, and heavy time consumption. We introduce a novel statistical strategy, called a Recursive Random Lasso (RRLasso, for high dimensional genomic data analysis and investigation of driver genes. For time-effective analysis, we consider a recursive bootstrap procedure in line with the random lasso. Furthermore, we introduce a parametric statistical test for driver gene selection based on bootstrap regression modeling results. The proposed RRLasso is not only rapid but performs well for high dimensional genomic data analysis. Monte Carlo simulations and analysis of the "Sanger Genomics of Drug Sensitivity in Cancer dataset from the Cancer Genome Project" show that the proposed RRLasso is an effective tool for high dimensional genomic data analysis. The proposed methods provide reliable and biologically relevant results for cancer driver gene selection.

  12. Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Gao XF

    2017-05-01

    Full Text Available Xiao-Fei Gao,1 Jun-Jie Zhang,1,2 Xiao-Min Jiang,1 Zhen Ge,1,2 Zhi-Mei Wang,1 Bing Li,1 Wen-Xing Mao,1 Shao-Liang Chen1,2 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China Background: Pulmonary arterial hypertension (PAH is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs, phosphodiesterase 5 inhibitors (PDE-5Is, and soluble guanylate cyclase stimulator (sGCS, have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.Methods: Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD.Results: Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003 vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008 vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028 vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001 vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001 vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023 vs

  13. Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial.

    Science.gov (United States)

    Helft, Gérard; Steg, Philippe Gabriel; Le Feuvre, Claude; Georges, Jean-Louis; Carrie, Didier; Dreyfus, Xavier; Furber, Alain; Leclercq, Florence; Eltchaninoff, Hélène; Falquier, Jean-François; Henry, Patrick; Cattan, Simon; Sebagh, Laurent; Michel, Pierre-Louis; Tuambilangana, Albert; Hammoudi, Nadjib; Boccara, Franck; Cayla, Guillaume; Douard, Hervé; Diallo, Abdourahmane; Berman, Emmanuel; Komajda, Michel; Metzger, Jean-Philippe; Vicaut, Eric

    2016-01-21

    This open-label, randomized, and multicentre trial tested the hypothesis that, on a background of aspirin, continuing clopidogrel would be superior to stopping clopidogrel at 12 months following drug-eluting stent (DES) implantation. Patients (N = 1799) who had undergone placement of ≥1 DES for stable coronary artery disease or acute coronary syndrome were included in 58 French sites (January 2009-January 2013). Patients (N = 1385) free of major cardiovascular/cerebrovascular events or major bleeding and on aspirin and clopidogrel 12 months after stenting were eligible for randomization (1:1) between continuing clopidogrel 75 mg daily (extended-dual antiplatelet therapy, DAPT, group) or discontinuing clopidogrel (aspirin group). The primary outcome was net adverse clinical events defined as the composite of death, myocardial infarction, stroke, or major bleeding. Follow-up was planned from a minimum of 6 to a maximum of 36 months after randomization. Owing to slow recruitment, the study was stopped after enrolment of 1385 of a planned 1966 patients. Median follow-up after stenting was 33.4 months. The primary outcome occurred in 40 patients (5.8%) in the extended-DAPT group and 52 in the aspirin group (7.5%; hazard ratio 0.75, 95% confidence interval 0.50-1.28; P = 0.17). Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (HR 0.65, 95% CI 0.34-1.22; P = 0.18). Rates of major bleeding were identical (2.0%, P = 0.95). Extended DAPT did not achieve superiority in reducing net adverse clinical events compared to 12 months of DAPT after DES placement. The power of the OPTIDUAL trial was however low and reduced by premature termination of enrolment. NCT00822536. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  14. Drug reimbursement and GPs' prescribing decisions: a randomized case-vignette study about the pharmacotherapy of obesity associated with type 2 diabetes: how GPs react to drug reimbursement.

    Science.gov (United States)

    Verger, Pierre; Rolland, Sophie; Paraponaris, Alain; Bouvenot, Julien; Ventelou, Bruno

    2010-08-01

    This study sought to identify the effect of drug reimbursability--a decision made in France by the National Authority for Health--on physicians' prescribing practices for a diet drug such as rimonabant, approved for obese or overweight patients with type-2 diabetes. A cross-sectional survey of French general practitioners (GPs) presented a case-vignette about a patient for whom this drug is indicated in two alternative versions, differing only in its reimbursability, to two separate randomized subsamples of GPs in early 2007, before any decision was made about reimbursement. The results indicate that (i) more than 20% of GPs in private practice would be willing to prescribe a non-reimbursed diet drug for patients with obesity complicated by type 2 diabetes; (ii) the number of GPs willing to prescribe it would increase by 47.6% if the drug were reimbursed, and (iii) such a drug would be adopted at a higher rate by GPs who have regular contacts with pharmaceutical sales representatives. In France, unlike most other countries, drug reimbursement status is a signal of quality. However, our results suggest that a significant proportion of GPs would spontaneously adopt anti-obesity drugs even if they were not reimbursed. Decisions about reimbursement of pharmaceutical products should be made taking into account that reimbursement is likely to intensify prescription.

  15. The Road from Host-Defense Peptides to a New Generation of Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Alicia Boto

    2018-02-01

    Full Text Available Host-defense peptides, also called antimicrobial peptides (AMPs, whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1 broad spectrum of activity; (2 unlike classic antibiotics, they induce very little resistance; (3 they act synergically with conventional antibiotics; (4 they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.

  16. Novel nano-cellulose excipient for generating non-Newtonian droplets for targeted nasal drug delivery.

    Science.gov (United States)

    Young, Paul M; Traini, Daniela; Ong, Hui Xin; Granieri, Angelo; Zhu, Bing; Scalia, Santo; Song, Jie; Spicer, Patrick T

    2017-10-01

    Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips. Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive's potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient. The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray. Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners.

  17. A random generation approach to pattern library creation for full chip lithographic simulation

    Science.gov (United States)

    Zou, Elain; Hong, Sid; Liu, Limei; Huang, Lucas; Yang, Legender; Kabeel, Aliaa; Madkour, Kareem; ElManhawy, Wael; Kwan, Joe; Du, Chunshan; Hu, Xinyi; Wan, Qijian; Zhang, Recoo

    2017-04-01

    As technology advances, the need for running lithographic (litho) checking for early detection of hotspots before tapeout has become essential. This process is important at all levels—from designing standard cells and small blocks to large intellectual property (IP) and full chip layouts. Litho simulation provides high accuracy for detecting printability issues due to problematic geometries, but it has the disadvantage of slow performance on large designs and blocks [1]. Foundries have found a good compromise solution for running litho simulation on full chips by filtering out potential candidate hotspot patterns using pattern matching (PM), and then performing simulation on the matched locations. The challenge has always been how to easily create a PM library of candidate patterns that provides both comprehensive coverage for litho problems and fast runtime performance. This paper presents a new strategy for generating candidate real design patterns through a random generation approach using a layout schema generator (LSG) utility. The output patterns from the LSG are simulated, and then classified by a scoring mechanism that categorizes patterns according to the severity of the hotspots, probability of their presence in the design, and the likelihood of the pattern causing a hotspot. The scoring output helps to filter out the yield problematic patterns that should be removed from any standard cell design, and also to define potential problematic patterns that must be simulated within a bigger context to decide whether or not they represent an actual hotspot. This flow is demonstrated on SMIC 14nm technology, creating a candidate hotspot pattern library that can be used in full chip simulation with very high coverage and robust performance.

  18. Stabilizing ability of surfactant on physicochemical properties of drug nanoparticles generated from solid dispersions.

    Science.gov (United States)

    Thongnopkoon, Thanu; Puttipipatkhachorn, Satit

    2017-07-01

    This study was aimed to examine the nanoparticle formation from redispersion of binary and ternary solid dispersions. Binary systems are composed of various ratios of glibenclamide (GBM) and polyvinylpyrrolidone K30 (PVP-K30), whereas a constant amount at 2.5%w/w of a surfactant, sodium lauryl sulfate (SLS) or Gelucire44/14 (GLC), was added to create ternary systems. GBM nanoparticles were collected after the systems were dispersed in water for 15 min. The obtained nanoparticles were characterized for size distribution, crystallinity, thermal behavior, molecular structure, and dissolution properties. The results indicated that GBM nanoparticles could be formed when the drug content of the systems was lower than 30%w/w in binary systems and ternary systems containing SLS. The particle size ranged from 200 to 500 nm in diameter with narrow size distribution. The particle size was increased with increasing drug content in the systems. The obtained nanoparticles were spherical and showed the amorphous state. Furthermore, because of being amorphous form and reduced particle size, the dissolution of the generated nanoparticles was markedly improved compared with the GBM powder. In contrast, all the ternary solid dispersions prepared with GLC anomalously provided the crystalline particles with the size ranging over 5 µm and irregular shape. Interestingly, this was irrelevant to the drug content in the systems. These results indicated the ability of GLC to destabilize the polymer network surrounding the particles during particle precipitation. Therefore, this study suggested that drug content, quantity, and type of surfactant incorporated in solid dispersions drastically affected the physicochemical properties of the precipitated particles.

  19. Assessment of the suitability of different random number generators for Monte Carlo simulations in gamma-ray spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo Diaz, N.; Vergara Gil, A. [Centre for Radiological Protection and Higiene, P.O. Box 6195, Habana (Cuba); Jurado Vargas, M. [Physics Department, University of Extremadura, 06071 Badajoz (Spain)], E-mail: mjv@unex.es

    2010-03-15

    The Monte Carlo method has become a valuable numerical laboratory framework in which to simulate complex physical systems. It is based on the generation of pseudo-random number sequences by numerical algorithms called random generators. In this work we assessed the suitability of different well-known random number generators for the simulation of gamma-ray spectrometry systems during efficiency calibrations. The assessment was carried out in two stages. The generators considered (Delphi's linear congruential, mersenne twister, XorShift, multiplier with carry, universal virtual array, and non-periodic logistic map based generator) were first evaluated with different statistical empirical tests, including moments, correlations, uniformity, independence of terms and the DIEHARD battery of tests. In a second step, an application-specific test was conducted by implementing the generators in our Monte Carlo program DETEFF and comparing the results obtained with them. The calculations were performed with two different CPUs, for a typical HpGe detector and a water sample in Marinelli geometry, with gamma-rays between 59 and 1800 keV. For the Non-periodic Logistic Map based generator, dependence of the most significant bits was evident. This explains the bias, in excess of 5%, of the efficiency values obtained with this generator. The results of the application-specific assessment and the statistical performance of the other algorithms studied indicate their suitability for the Monte Carlo simulation of gamma-ray spectrometry systems for efficiency calculations.

  20. Insights into Integrated Lead Generation and Target Identification in Malaria and Tuberculosis Drug Discovery.

    Science.gov (United States)

    Okombo, John; Chibale, Kelly

    2017-07-18

    New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery. This Account recaps the existing challenges facing antimalarial and antituberculosis drug discovery, including limitations associated with experimental animal models as well as biological complexities intrinsic to the causative pathogens. We enlist various highlights from a body of work within our research group aimed at identifying and characterizing new chemical leads, and navigating these challenges to contribute toward the global drug discovery and development pipeline in malaria and tuberculosis. We describe a catalogue of in-house efforts toward deriving safe and efficacious preclinical drug development candidates via cell-based medicinal chemistry optimization of phenotypic whole-cell medium and high throughput screening hits sourced from various small molecule chemical libraries. We also provide an appraisal of target-based screening, as invoked in our laboratory for mechanistic evaluation of the hits generated, with particular focus on the enzymes within the de novo pyrimidine biosynthetic and hemoglobin degradation pathways, the latter constituting a heme detoxification process and an associated cysteine

  1. Research of the method of pseudo-random number generation based on asynchronous cellular automata with several active cells

    Directory of Open Access Journals (Sweden)

    Bilan Stepan

    2017-01-01

    Full Text Available To date, there are many tasks that are aimed at studying the dynamic changes in physical processes. These tasks do not give advance known result. The solution of such problems is based on the construction of a dynamic model of the object. Successful structural and functional implementation of the object model can give a positive result in time. This approach uses the task of constructing artificial biological objects. To solve such problems, pseudo-random number generators are used, which also find wide application for information protection tasks. Such generators should have good statistical properties and give a long repetition period of the generated pseudo-random bit sequence. This work is aimed at improving these characteristics. The paper considers the method of forming pseudo-random sequences of numbers on the basis of aperiodic cellular automata with two active cells. A pseudo-random number generator is proposed that generates three bit sequences. The first two bit sequences are formed by the corresponding two active cells in the cellular automaton. The third bit sequence is the result of executing the XOR function over the bits of the first two sequences and it has better characteristics compared to them. The use of cellular automata with two active cells allowed to improve the statistical properties of the formed bit sequence, as well as its repetition period. This is proved by using graphical tests for generators built based on cellular automata using the neighborhoods of von Neumann and Moore. The tests showed high efficiency of the generator based on an asynchronous cellular automaton with the neighborhood of Moore. The proposed pseudo-random number generators have good statistical properties, which makes it possible to use them in information security systems, as well as for simulation tasks of various dynamic processes.

  2. Visual presentations of efficacy data in direct-to-consumer prescription drug print and television advertisements: A randomized study.

    Science.gov (United States)

    Sullivan, Helen W; O'Donoghue, Amie C; Aikin, Kathryn J; Chowdhury, Dhuly; Moultrie, Rebecca R; Rupert, Douglas J

    2016-05-01

    To determine whether visual aids help people recall quantitative efficacy information in direct-to-consumer (DTC) prescription drug advertisements, and if so, which types of visual aids are most helpful. Individuals diagnosed with high cholesterol (n=2504) were randomized to view a fictional DTC print or television advertisement with no visual aid or one of four visual aids (pie chart, bar chart, table, or pictograph) depicting drug efficacy. We measured drug efficacy and risk recall, drug perceptions and attitudes, and behavioral intentions. For print advertisements, a bar chart or table, compared with no visual aid, elicited more accurate drug efficacy recall. The bar chart was better at this than the pictograph and the table was better than the pie chart. For television advertisements, any visual aid, compared with no visual aid, elicited more accurate drug efficacy recall. The bar chart was better at this than the pictograph or the table. Visual aids depicting quantitative efficacy information in DTC print and television advertisements increased drug efficacy recall, which may help people make informed decisions about prescription drugs. Adding visual aids to DTC advertising may increase the public's knowledge of how well prescription drugs work. Published by Elsevier Ireland Ltd.

  3. Randomized Trial to Reduce Club Drug Use and HIV Risk Behaviors among Men Who Have Sex with Men

    Science.gov (United States)

    Morgenstern, Jon; Bux, Donald A., Jr.; Parsons, Jeffrey; Hagman, Brett T.; Wainberg, Milton; Irwin, Thomas

    2009-01-01

    The authors examined the effectiveness of motivational interviewing (MI) on club drug use and risky sex in non-treatment-seeking men who have sex with men (MSM). MSM (N = 150) were assessed and randomly assigned to 4 sessions of MI or an educational control intervention. Follow-up occurred at quarterly intervals for 1 year. Primary outcomes were…

  4. Effectiveness of the 'Healthy School and Drugs' prevention programme on adolescents' substance use: a randomized clustered trial

    NARCIS (Netherlands)

    Malmberg, M.; Kleinjan, M.; Overbeek, G.J.; Vermulst, A.A.; Monshouwer, K.; Lammers, J.; Vollebergh, W.A.M.; Engels, R.C.M.E.

    2014-01-01

    Aim To evaluate the effectiveness of the Healthy School and Drugs programme on alcohol, tobacco and marijuana use among Dutch early adolescents. Design Randomized clustered trial with two intervention conditions (i.e. e-learning and integral). Setting General population of 11-15-year-old adolescents

  5. Effectiveness of the 'Healthy School and Drugs' prevention programme on adolescents' substance use : A randomized clustered trial

    NARCIS (Netherlands)

    Malmberg, Monique; Kleinjan, Marloes; Overbeek, Geertjan; Vermulst, Ad; Monshouwer, Karin; Lammers, Jeroen; Vollebergh, Wilma A M; Engels, Rutger C M E

    2014-01-01

    Aim: To evaluate the effectiveness of the Healthy School and Drugs programme on alcohol, tobacco and marijuana use among Dutch early adolescents. Design: Randomized clustered trial with two intervention conditions (i.e. e-learning and integral). Setting: General population of 11-15-year-old

  6. Effectiveness of the 'Healthy School and Drugs' prevention programme on adolescents' substance use: a randomized clustered trial

    NARCIS (Netherlands)

    Malmberg, M.; Kleinjan, M.; Overbeek, G.; Vermulst, A.; Monshouwer, K.; Lammers, J.; Vollebergh, W.A.M.; Engels, R.C.M.E.

    2014-01-01

    Aim: To evaluate the effectiveness of the Healthy School and Drugs programme on alcohol, tobacco and marijuana use among Dutch early adolescents. Design: Randomized clustered trial with two intervention conditions (i.e. e-learning and integral). Setting: General population of 11-15-year-old

  7. Embedded Platform for Automatic Testing and Optimizing of FPGA Based Cryptographic True Random Number Generators

    Directory of Open Access Journals (Sweden)

    M. Varchola

    2009-12-01

    Full Text Available This paper deals with an evaluation platform for cryptographic True Random Number Generators (TRNGs based on the hardware implementation of statistical tests for FPGAs. It was developed in order to provide an automatic tool that helps to speed up the TRNG design process and can provide new insights on the TRNG behavior as it will be shown on a particular example in the paper. It enables to test sufficient statistical properties of various TRNG designs under various working conditions on the fly. Moreover, the tests are suitable to be embedded into cryptographic hardware products in order to recognize TRNG output of weak quality and thus increase its robustness and reliability. Tests are fully compatible with the FIPS 140 standard and are implemented by the VHDL language as an IP-Core for vendor independent FPGAs. A recent Flash based Actel Fusion FPGA was chosen for preliminary experiments. The Actel version of the tests possesses an interface to the Actel’s CoreMP7 softcore processor that is fully compatible with the industry standard ARM7TDMI. Moreover, identical tests suite was implemented to the Xilinx Virtex 2 and 5 in order to compare the performance of the proposed solution with the performance of already published one based on the same FPGAs. It was achieved 25% and 65% greater clock frequency respectively while consuming almost equal resources of the Xilinx FPGAs. On the top of it, the proposed FIPS 140 architecture is capable of processing one random bit per one clock cycle which results in 311.5 Mbps throughput for Virtex 5 FPGA.

  8. HIV incidence among people who inject drugs (PWID) in Ukraine: results from a clustered randomized trial

    Science.gov (United States)

    Davis, Jonathan M.; Dvoryak, Sergey; Brewster, John T.; Lisovska, Oksana; Strathdee, Steffanie A.; Latkin, Carl A.

    2016-01-01

    Summary Background In this study, we sought to assess whether a social network intervention was superior to HIV testing and counseling in impacting HIV incidence among PWID. Although this was not a primary study aim, it is associated with reducing drug and sex risk behaviors, which were primary aims. Methods PWID were recruited from street settings in Odessa, Donetsk, and Nikolayev, Ukraine for a clustered randomized clinical trial (RCT). “Index” or peer leaders, along with two of their network members, were randomly assigned to testing and counseling block (N=589) or testing and counseling plus a social network intervention block (N=611). Participants in the network intervention received 5-sessions to train their network members in risk reduction. Those assigned testing and counseling received no further intervention following counseling. Employing an intent to treat analyses, the primary outcome was HIV sero-conversion using Cox regression and incorporating a gamma frailty term to account for clustering. No stratification or minimization was utilized. The trail was registered with ClinicalTrial.gov, NCT01159704. Findings Between July 12, 2010 and November 23, 2012, 2,304 PWID were recruited, 1,200 of whom were HIV negative and included in the present study. At baseline, there were no significant differences between groups. Of the 1,200 HIV negative participants, 1,085 (90.4%) were retained at 12 months. Incidence density revealed 18.45 (95% CI 14.87 – 22.03, 102 events in 553.0 py) per 100 person years (py) for those in the intervention group and 31.78 (95% CI 26.83–36.74, 158 events in 497.1 py) per 100 py among control arm participants. This corresponded to a reduced hazard in the intervention group, HR= 0.53 (95% CI 0.38, 0.76, p =0.0003). There were no study-related adverse events. Interpretation These data provide strong support for integrating peer education into comprehensive HIV prevention programs for PWID and suggest the value in developing and

  9. Incidence of periprocedural myocardial infarction following stent implantation: Comparison between first- and second-generation drug-eluting stents

    NARCIS (Netherlands)

    Tandjung, Kenneth; Basalus, Mounir W.Z.; Muurman, Esther; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Jansen, Hanneke; Huisman, Jennifer; Linssen, Gerard C.M.; Droste, Herman T.; Nienhuis, Mark B.; von Birgelen, Clemens

    2012-01-01

    Background: First- and second-generation drug-eluting stents (DES) differ in coating materials, which may influence the incidence of periprocedural myocardial infarction (PMI). Objective: To compare the incidence of PMI between first- and second-generation DES, using the current Academic Research

  10. NullSeq: A Tool for Generating Random Coding Sequences with Desired Amino Acid and GC Contents.

    Directory of Open Access Journals (Sweden)

    Sophia S Liu

    2016-11-01

    Full Text Available The existence of over- and under-represented sequence motifs in genomes provides evidence of selective evolutionary pressures on biological mechanisms such as transcription, translation, ligand-substrate binding, and host immunity. In order to accurately identify motifs and other genome-scale patterns of interest, it is essential to be able to generate accurate null models that are appropriate for the sequences under study. While many tools have been developed to create random nucleotide sequences, protein coding sequences are subject to a unique set of constraints that complicates the process of generating appropriate null models. There are currently no tools available that allow users to create random coding sequences with specified amino acid composition and GC content for the purpose of hypothesis testing. Using the principle of maximum entropy, we developed a method that generates unbiased random sequences with pre-specified amino acid and GC content, which we have developed into a python package. Our method is the simplest way to obtain maximally unbiased random sequences that are subject to GC usage and primary amino acid sequence constraints. Furthermore, this approach can easily be expanded to create unbiased random sequences that incorporate more complicated constraints such as individual nucleotide usage or even di-nucleotide frequencies. The ability to generate correctly specified null models will allow researchers to accurately identify sequence motifs which will lead to a better understanding of biological processes as well as more effective engineering of biological systems.

  11. The effect of hypnotic drug type on anesthetic depth and amnesia: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Amiri HR

    2009-06-01

    Full Text Available "n Normal 0 false false false EN-GB X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Bispectral index (BIS index shows the depth of anesthesia. The effects of drugs on BIS and amnesia are different. This study was performed to evaluate the association between two different sedative regimens on BIS and amnesia."n"nMethods: In this clinical trial, 60 patients who needed elective orthopedic surgery under regional anesthesia with intravenous sedation were elected. Patients divided in two equal groups based on sedation protocol by block randomization method: midazolam plus fentanyl group (MF group or propofol group (P group. Dose of sedative drugs were adjusted according to clinical findings of sedation. Depth of sedation in all patients, preserved in four based on modified Ramsey Sedation Score. Patients questioned about spontaneous recall after full awakening in recovery room. Recall of any event during operation considered as failed amnesia. Correlation of BIS index with recall was measured in two different groups separately."n"nResults: The frequency of recall was 2 (6.7% in P group and 10 (33.3% in MF group (p=0.01. The mean± SD of BIS in P group was 76±5 (68-91 and in MF group was 93.4±5 (77-98 (p<0.001. The difference of BIS in patients without amnesia (p=0.019 and with amnesia (p<0

  12. Goal-independent mechanisms for free response generation: creative and pseudo-random performance share neural substrates.

    Science.gov (United States)

    de Manzano, Örjan; Ullén, Fredrik

    2012-01-02

    To what extent free response generation in different tasks uses common and task-specific neurocognitive processes has remained unclear. Here, we investigated overlap and differences in neural activity during musical improvisation and pseudo-random response generation. Brain activity was measured using fMRI in a group of professional classical pianists, who performed musical improvisation of melodies, pseudo-random key-presses and a baseline condition (sight-reading), on either two, six or twelve keys on a piano keyboard. The results revealed an extensive overlap in neural activity between the two generative conditions. Active regions included the dorsolateral and dorsomedial prefrontal cortices, inferior frontal gyrus, anterior cingulate cortex and pre-SMA. No regions showed higher activity in improvisation than in pseudo-random generation. These findings suggest that the activated regions fulfill generic functions that are utilized in different types of free generation tasks, independent of overall goal. In contrast, pseudo-random generation was accompanied by higher activity than improvisation in several regions. This presumably reflects the participants' musical expertise as well as the pseudo-random generation task's high load on attention, working memory, and executive control. The results highlight the significance of using naturalistic tasks to study human behavior and cognition. No brain activity was related to the size of the response set. We discuss that this may reflect that the musicians were able to use specific strategies for improvisation, by which there was no simple relationship between response set size and neural activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Aging effect on Executive Control in the Random Number Generation Test

    Directory of Open Access Journals (Sweden)

    Amer Cavalheiro Hamdan

    2006-12-01

    Full Text Available The decline of abilities related to Executive Control –EC with aging has been related with the Pre-Frontal System neurobiological aging. This study compared the score obtained in the Random Number Generation Test (RNG by two groups: 30 college students (older than 18 and 36 elderly (older than 60. This last group was divided according to the criteria of schooling in up to 8 years of schooling and over 8 years of schooling. The results show that the younger participants scored 0,344 ± 0,04 in the RNG test; the elderly with up to 8 years of schooling punctuated 0,432 ± 0,10 and that those who studied for 9 years or more reached a mean of 0,393 ± 0,05. The statistical analysis of these data suggest that the elderly performance in the RNG test (0,420 ± 0,09 was significantly worse when compared to the performance of the younger participants (t (64 = -3,9927; p = 0,0001, which confirms that the manipulation and inhibitory control abilities of information are decreased in older people, probably due to the natural aging process of the Frontal Cortex. Keywords: neuropsychology; aging; executive functions.

  14. Shocking Behavior: Random Wealth in Antebellum Georgia and Human Capital Across Generations.

    Science.gov (United States)

    Bleakley, Hoyt; Ferrie, Joseph

    2016-08-01

    Does the lack of wealth constrain parents' investments in the human capital of their descendants? We conduct a nearly fifty-year followup of an episode in which such constraints would have been plausibly relaxed by a random allocation of substantial wealth to families. We track descendants of participants in Georgia's Cherokee Land Lottery of 1832, in which nearly every adult white male in Georgia took part. Winners received close to the median level of wealth - a large financial windfall orthogonal to participants' underlying characteristics that might have also affected their children's human capital. Although winners had slightly more children than non-winners, they did not send them to school more. Sons of winners have no better adult outcomes (wealth, income, literacy) than the sons of non-winners, and winners' grandchildren do not have higher literacy or school attendance than non-winners' grandchildren. This suggests only a limited role for family financial resources in the formation of human capital in the next generations in this environment and a potentially more important role for other factors that persist through family lines.

  15. Turbulence generation by a shock wave interacting with a random density inhomogeneity field

    Science.gov (United States)

    Huete Ruiz de Lira, C.

    2010-12-01

    When a planar shock wave interacts with a random pattern of pre-shock density non-uniformities, it generates an anisotropic turbulent velocity/vorticity field. This turbulence plays an important role in the early stages of the mixing process in a compressed fluid. This situation emerges naturally in a shock interaction with weakly inhomogeneous deuterium-wicked foam targets in inertial confinement fusion and with density clumps/clouds in astrophysics. We present an exact small-amplitude linear theory describing such an interaction. It is based on the exact theory of time and space evolution of the perturbed quantities behind a corrugated shock front for a single-mode pre-shock non-uniformity. Appropriate mode averaging in two dimensions results in closed analytical expressions for the turbulent kinetic energy, degree of anisotropy of velocity and vorticity fields in the shocked fluid, shock amplification of the density non-uniformity and sonic energy flux radiated downstream. These explicit formulae are further simplified in the important asymptotic limits of weak/strong shocks and highly compressible fluids. A comparison with the related problem of a shock interacting with a pre-shock isotropic vorticity field is also presented.

  16. Shocking Behavior: Random Wealth in Antebellum Georgia and Human Capital Across Generations

    Science.gov (United States)

    Bleakley, Hoyt; Ferrie, Joseph

    2017-01-01

    Does the lack of wealth constrain parents’ investments in the human capital of their descendants? We conduct a nearly fifty-year followup of an episode in which such constraints would have been plausibly relaxed by a random allocation of substantial wealth to families. We track descendants of participants in Georgia’s Cherokee Land Lottery of 1832, in which nearly every adult white male in Georgia took part. Winners received close to the median level of wealth – a large financial windfall orthogonal to participants’ underlying characteristics that might have also affected their children’s human capital. Although winners had slightly more children than non-winners, they did not send them to school more. Sons of winners have no better adult outcomes (wealth, income, literacy) than the sons of non-winners, and winners’ grandchildren do not have higher literacy or school attendance than non-winners’ grandchildren. This suggests only a limited role for family financial resources in the formation of human capital in the next generations in this environment and a potentially more important role for other factors that persist through family lines. PMID:28529385

  17. A bibliometric study of scientific research conducted on second-generation antipsychotic drugs in Singapore

    Science.gov (United States)

    López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Ángel Miguel, Pérez-Nieto; Álamo, Cecilio

    2014-01-01

    INTRODUCTION A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. METHODS A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors ‘atypic* antipsychotic*’, ‘second-generation antipsychotic*’, ‘clozapine’, ‘risperidone’, ‘olanzapine’, ‘ziprasidone’, ‘quetiapine’, ‘sertindole’, ‘aripiprazole’, ‘paliperidone’, ‘amisulpride’, ‘zotepine’, ‘asenapine’, ‘iloperidone’, ‘lurasidone’, ‘perospirone’ and ‘blonanserin’ in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. RESULTS From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal (4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. CONCLUSION Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature. PMID:24452974

  18. Generating Charged Pharmaceutical Aerosols Intended to Improve Targeted Drug Delivery in Ventilated Infants.

    Science.gov (United States)

    Holbrook, Landon; Hindle, Michael; Longest, P Worth

    2015-10-01

    The delivery of pharmaceutical aerosols to infants receiving mechanical ventilation is extremely challenging due to small diameter flow passages, low tidal volumes, and frequent exhalation of the aerosol. The use of small charged particles is proposed as a novel method to prevent deposition in ventilator components and foster deposition in the lower infant airways. The objective of this study was to compare the performance of multiple new devices for generating small charged particles that are expected to maximize respiratory drug delivery in ventilated infants. Criteria used to select a leading device included production of a charged aerosol with a mass median aerodynamic diameter (MMAD) ≤ approximately 1.8 μm; low device depositional loss of the aerosol (MMAD of 0.14 μm and a drug delivery rate of 25 μg/min. However, the device was excluded because it failed to produce a charged aerosol. In contrast, the LF-IC produced a 1.6 μm aerosol with high net charge, low device depositional loss (MMAD, the LF-IC produced >100 elementary charges per particle, which was an order of magnitude increase compared to the case of zero charging voltage. In conclusion, the LF-IC was selected as a leading system that is expected to improve aerosol delivery efficiency in ventilated infants through the use of small charged particles.

  19. Mechanism of generation of drug nanocrystals in celecoxib: mannitol nanocrystalline solid dispersion.

    Science.gov (United States)

    Bhatt, Varun; Shete, Ganesh; Bansal, Arvind Kumar

    2015-11-10

    Objective of this work was to understand the mechanism of formation of celecoxib nanocrystals in celecoxib: mannitol nanocrystalline solid dispersion (NSD). Solution of celecoxib and mannitol was spray dried in 1:1 (g:g) proportion to obtain NSD, with average crystallite size of 214.07 ± 45.27 nm. Solubility parameters of celecoxib and mannitol were 23.1 MPa(1/2) and 38.5 MPa(1/2), respectively, hinting their immiscibility. Formation of nanocrystals during NanoCrySP proceeds via intermediate amorphous form of the drug. Earlier work from our lab on hesperetin-mannitol system, had underlined the role of plasticization of amorphous drug by excipient in the formation of nanocrystals. However, in present case, mannitol failed to plasticize amorphous celecoxib and Tg of amorphous celecoxib (56.8°C) showed a negligible change (54.8°C) in presence of mannitol. However, DSC data also suggested crystallization inducing potential of mannitol on amorphous celecoxib. Polarized light microscopy provided evidence that, mannitol facilitated heterogeneous nucleation of amorphous celecoxib at their interface. Transmission electron microscopy analysis suggested that, mannitol acted as a physical barrier to crystal growth of celecoxib crystallites. Thus, though mannitol did not plasticize amorphous celecoxib, it aided in nanocrystal generation by heterogeneous nucleation and providing physical barrier to crystal growth. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. A generator for unique quantum random numbers based on vacuum states

    DEFF Research Database (Denmark)

    Gabriel, C.; Wittmann, C.; Sych, D.

    2010-01-01

    Random numbers are a valuable component in diverse applications that range from simulations(1) over gambling to cryptography(2,3). The quest for true randomness in these applications has engendered a large variety of different proposals for producing random numbers based on the foundational unpre...

  1. Outcomes of a prospective trial of student-athlete drug testing: the Student Athlete Testing Using Random Notification (SATURN) study.

    Science.gov (United States)

    Goldberg, Linn; Elliot, Diane L; MacKinnon, David P; Moe, Esther L; Kuehl, Kerry S; Yoon, Myeongsun; Taylor, Aaron; Williams, Jason

    2007-11-01

    To assess the effects of random drug and alcohol testing (DAT) among high school athletes. This was a 2-year prospective randomized controlled study of a single cohort among five intervention high schools with a DAT policy and six schools with a deferred policy, serially assessed by voluntary, confidential questionnaires. DAT school athletes were at risk for random testing during the full academic year. Positive test results were reported to parents or guardians, with mandatory counseling. Indices of illicit drug use, with and without alcohol use, were assessed at the beginning and end of each school year for the past month and prior year. Potential mediating variables were evaluated. Student-athletes from intervention and control schools did not differ in past 1-month use of illicit drug or a combination of drug and alcohol use at any of the four follow-up periods. At the end of the initial school year and after 2 full school years, student-athletes at DAT schools reported less drug use during the past year (p < .01) compared to athletes at the deferred policy schools. Combining past year drug and alcohol use together, student-athletes at DAT schools reported less use at the second and third follow-up assessments (p < .05). Paradoxically, DAT athletes across all assessments reported less athletic competence (p < .001), less belief authorities were opposed to drug use (p < .01), and indicated greater risk-taking (p < .05). At the final assessment, DAT athletes believed less in testing benefits (p < .05) and less that testing was a reason not to use drugs (p < .01). No DAT deterrent effects were evident for past month use during any of four follow-up periods. Prior-year drug use was reduced in two of four follow-up self-reports, and a combination of drug and alcohol use was reduced at two assessments as well. Overall, drug testing was accompanied by an increase in some risk factors for future substance use. More research is needed before DAT is considered an

  2. Analyzing user-generated online content for drug discovery: development and use of MedCrawler.

    Science.gov (United States)

    Helfenstein, Andreas; Tammela, Päivi

    2017-04-15

    Ethnopharmacology, or the scientific validation of traditional medicine, is a respected starting point in drug discovery. Home remedies and traditional use of plants are still widespread, also in Western societies. Instead of perusing ancient pharmacopeias, we developed MedCrawler, which we used to analyze blog posts for mentions of home remedies and their applications. This method is free and accessible from the office computer. We developed MedCrawler, a data mining tool for analyzing user-generated blog posts aiming to find modern 'traditional' medicine or home remedies. It searches user-generated blog posts and analyzes them for correlations between medically relevant terms. We also present examples and show that this method is capable of delivering both scientifically validated uses as well as not so well documented applications, which might serve as a starting point for follow-up research. Source code is available on GitHub at {{ https://github.com/a-hel/medcrawler }}. paivi.tammela@helsinki.fi. Supplementary data are available at Bioinformatics online.

  3. Generation of Aptamers from A Primer-Free Randomized ssDNA Library Using Magnetic-Assisted Rapid Aptamer Selection

    Science.gov (United States)

    Tsao, Shih-Ming; Lai, Ji-Ching; Horng, Horng-Er; Liu, Tu-Chen; Hong, Chin-Yih

    2017-04-01

    Aptamers are oligonucleotides that can bind to specific target molecules. Most aptamers are generated using random libraries in the standard systematic evolution of ligands by exponential enrichment (SELEX). Each random library contains oligonucleotides with a randomized central region and two fixed primer regions at both ends. The fixed primer regions are necessary for amplifying target-bound sequences by PCR. However, these extra-sequences may cause non-specific bindings, which potentially interfere with good binding for random sequences. The Magnetic-Assisted Rapid Aptamer Selection (MARAS) is a newly developed protocol for generating single-strand DNA aptamers. No repeat selection cycle is required in the protocol. This study proposes and demonstrates a method to isolate aptamers for C-reactive proteins (CRP) from a randomized ssDNA library containing no fixed sequences at 5‧ and 3‧ termini using the MARAS platform. Furthermore, the isolated primer-free aptamer was sequenced and binding affinity for CRP was analyzed. The specificity of the obtained aptamer was validated using blind serum samples. The result was consistent with monoclonal antibody-based nephelometry analysis, which indicated that a primer-free aptamer has high specificity toward targets. MARAS is a feasible platform for efficiently generating primer-free aptamers for clinical diagnoses.

  4. Some Bounds on the Deviation Probability for Sums of Nonnegative Random Variables Using Upper Polynomials, Moment and Probability Generating Functions

    OpenAIRE

    From, Steven G.

    2010-01-01

    We present several new bounds for certain sums of deviation probabilities involving sums of nonnegative random variables. These are based upon upper bounds for the moment generating functions of the sums. We compare these new bounds to those of Maurer [2], Bernstein [4], Pinelis [16], and Bentkus [3]. We also briefly discuss the infinitely divisible distributions case.

  5. Randomized controlled trial of motivational interviewing compared with drug information and advice for early intervention among young cannabis users.

    Science.gov (United States)

    McCambridge, Jim; Slym, Renee L; Strang, John

    2008-11-01

    To test the effectiveness of motivational interviewing (MI) in comparison with drug information and advice in opportunistically securing reductions in drug-related risk among young cannabis users not seeking help. Randomized controlled trial. Eleven London Further Education colleges. A total of 326 students aged 16-19 years who smoked cannabis weekly or more frequently. Participants were randomized to a single-session intervention of MI or drug information and advice-giving. Cannabis use, cigarette smoking and alcohol consumption and harm outcomes were assessed after both 3 and 6 months. No differences were found between MI and drug information and advice, although MI fidelity was not high. There were wide-ranging individual practitioner effects on observed outcomes and a practitioner-intervention interaction was detected in relation to cannabis cessation after 3 months. Change over time was more pronounced for cannabis use than for other drug use. Further study of the nature and consequences of MI fidelity, and individual practitioner effects more generally, is needed. Advice may be an effective brief intervention with young cannabis users in its own right and should be evaluated further in trials.

  6. Random walks with long-range steps generated by functions of Laplacian matrices

    OpenAIRE

    Riascos, A. P.; Michelitsch, T. M.; Collet, B. A.; Nowakowski, A. F.; Nicolleau, F. C. G. A

    2017-01-01

    In this paper, we explore different Markovian random walk strategies on networks with transition probabilities between nodes defined in terms of functions of the Laplacian matrix. We generalize random walk strategies with local information in the Laplacian matrix, that describes the connections of a network, to a dynamics determined by functions of this matrix. The resulting processes is non-local allowing transitions of the random walker from one node to nodes beyond its nearest neighbors. I...

  7. Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Pitkala Kaisu H

    2012-06-01

    Full Text Available Abstract Background Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people’s drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents’ quality of life and use of health services. Methods and design During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212 will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months. The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially

  8. Random number generation in bilingual Balinese and German students: preliminary findings from an exploratory cross-cultural study.

    Science.gov (United States)

    Strenge, Hans; Lesmana, Cokorda Bagus Jaya; Suryani, Luh Ketut

    2009-08-01

    Verbal random number generation is a procedurally simple task to assess executive function and appears ideally suited for the use under diverse settings in cross-cultural research. The objective of this study was to examine ethnic group differences between young adults in Bali (Indonesia) and Kiel (Germany): 50 bilingual healthy students, 30 Balinese and 20 Germans, attempted to generate a random sequence of the digits 1 to 9. In Balinese participants, randomization was done in Balinese (native language L1) and Indonesian (first foreign language L2), in German subjects in the German (L1) and English (L2) languages. 10 of 30 Balinese (33%), but no Germans, were unable to inhibit habitual counting in more than half of the responses. The Balinese produced significantly more nonrandom responses than the Germans with higher rates of counting and significantly less occurrence of the digits 2 and 3 in L1 compared with L2. Repetition and cycling behavior did not differ between the four languages. The findings highlight the importance of taking into account culture-bound psychosocial factors for Balinese individuals when administering and interpreting a random number generation test.

  9. Portraying mental illness and drug addiction as treatable health conditions: effects of a randomized experiment on stigma and discrimination.

    Science.gov (United States)

    McGinty, Emma E; Goldman, Howard H; Pescosolido, Bernice; Barry, Colleen L

    2015-02-01

    Despite significant advances in treatment, stigma and discrimination toward persons with mental illness and drug addiction have remained constant in past decades. Prior work suggests that portraying other stigmatized health conditions (i.e., HIV/AIDS) as treatable can improve public attitudes toward those affected. Our study compared the effects of vignettes portraying persons with untreated and symptomatic versus successfully treated and asymptomatic mental illness and drug addiction on several dimensions of public attitudes about these conditions. We conducted a survey-embedded randomized experiment using a national sample (N = 3940) from an online panel. Respondents were randomly assigned to read one of ten vignettes. Vignette one was a control vignette, vignettes 2-5 portrayed individuals with untreated schizophrenia, depression, prescription pain medication addiction and heroin addiction, and vignettes 6-10 portrayed successfully treated individuals with the same conditions. After reading the randomly assigned vignette, respondents answered questions about their attitudes related to mental illness or drug addiction. Portrayals of untreated and symptomatic schizophrenia, depression, and heroin addiction heightened negative public attitudes toward persons with mental illness and drug addiction. In contrast, portrayals of successfully treated schizophrenia, prescription painkiller addiction, and heroin addiction led to less desire for social distance, greater belief in the effectiveness of treatment, and less willingness to discriminate against persons with these conditions. Portrayal of persons with successfully treated mental illness and drug addiction is a promising strategy for reducing stigma and discrimination toward persons with these conditions and improving public perceptions of treatment effectiveness. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Antiepileptic Drug Treatment in Community-Dwelling Older Patients with Epilepsy: A Retrospective Observational Study of Old- Versus New-Generation Antiepileptic Drugs.

    Science.gov (United States)

    Theitler, Jacques; Brik, Anna; Shaniv, Dotan; Berkovitch, Matitiahu; Gandelman-Marton, Revital

    2017-06-01

    The use of antiepileptic drugs (AEDs) in older patients with epilepsy is challenged by polypharmacy and decreased drug elimination. Newer AEDs have a lower potential for drug interactions and are reported to be better tolerated by the elderly than old-generation AEDs. The objective of this study was to evaluate AED use and the related adverse event rate in an outpatient cohort of older patients with epilepsy. We retrospectively reviewed the computerized database and medical records of all the patients aged ≥60 years who visited our epilepsy outpatient clinic (Assaf Harofeh Medical Center, Zerifin, Israel) during a 4-year period from February 2012 to February 2016. In this study, phenytoin, valproic acid, carbamazepine, phenobarbital, clobazam, and clonazepam were defined as old-generation AEDs. Gabapentin, levetiracetam, lamotrigine, topiramate, oxcarbazepine, lacosamide, and perampanel were defined as new-generation AEDs. The study group included 115 patients aged 60-90 years (mean 70.5 ± 7.8 years), 70 (61%) of whom were men. Co-morbidities were present in 98.3% of the patients, including neuropsychiatric illnesses in 21.2%. Present medical treatment included new-generation AEDs in 49 (44.5%) and both old- and new-generation AEDs in 20 (18.2%) patients. The most commonly used current AEDs were phenytoin, gabapentin, levetiracetam, and lamotrigine. Adverse reactions mainly included fatigue and CNS-related symptoms, and were more frequent among patients treated with new-generation AEDs than in those treated with old-generation AEDs or a combination of old- and new-generation AEDs; however, these reactions were mostly related to levetiracetam treatment. The likelihood of levetiracetam-related adverse events was increased by slow levetiracetam titration [defined as a weekly dose increase of ≤250 mg/day in this study; odds ratio (OR) 16.35, 95% confidence interval (CI) 2.94-90.98], and by low- (OR 5.68, 95% CI 1.40-22.95) and high (OR 4.24, 95% CI 1

  11. Biological treatment of steroidal drug industrial effluent and electricity generation in the microbial fuel cells.

    Science.gov (United States)

    Liu, Ru; Gao, Chongyang; Zhao, Yang-Guo; Wang, Aijie; Lu, Shanshan; Wang, Min; Maqbool, Farhana; Huang, Qing

    2012-11-01

    The single chamber microbial fuel cells (MFCs) were used to treat steroidal drug production wastewater (SPW) and generate electricity simultaneously. The results indicated that the maximum COD removal efficiency reached 82%, total nitrogen and sulfate removal rate approached 62.47% and 26.46%, respectively. The maximum power density and the Coulombic efficiency reached to 22.3Wm(-3) and 30%, respectively. The scanning electron microscope showed that the dominant microbial populations were remarkably different in morphology on the surface of SPW and acetate-fed anodes. PCR-denaturing gradient gel electrophoresis profiles revealed that the microbial community structure fed with different concentrations of SPW presented a gradual succession and unique bacterial sequences were detected on the SPW and acetate-fed anodes. This research demonstrates that MFCs fed with SPW achieved a high efficiency of power density and simultaneous nutrient removal, and the dominant microorganisms on the anode were related to the types and the concentrations of substrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. A Mobile Device App to Reduce Medication Errors and Time to Drug Delivery During Pediatric Cardiopulmonary Resuscitation: Study Protocol of a Multicenter Randomized Controlled Crossover Trial.

    Science.gov (United States)

    Siebert, Johan N; Ehrler, Frederic; Lovis, Christian; Combescure, Christophe; Haddad, Kevin; Gervaix, Alain; Manzano, Sergio

    2017-08-22

    prescription by the physician to drug delivery by the nurse in each allocation group. TDD includes TDP. Stress level during the resuscitation scenario will be assessed for each participant by questionnaire and recorded by the heart rate monitor of a fitness watch. The study is formatted according to the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of Electronic and Mobile Health Applications and Online TeleHealth (CONSORT-EHEALTH) and the Reporting Guidelines for Health Care Simulation Research. Enrollment and data analysis started in March 2017. We anticipate the intervention will be completed in late 2017, and study results will be submitted in early 2018 for publication expected in mid-2018. Results will be reported in line with recommendations from CONSORT-EHEALTH and the Reporting Guidelines for Health Care Simulation Research . This paper describes the protocol used for a clinical trial assessing the impact of a mobile device app to reduce the rate of medication errors, time to drug preparation, and time to drug delivery during pediatric resuscitation. As research in this area is scarce, results generated from this study will be of great importance and might be sufficient to change and improve the pediatric emergency care practice. ClinicalTrials.gov NCT03021122; https://clinicaltrials.gov/ct2/show/NCT03021122 (Archived by WebCite at http://www.webcitation.org/6nfVJ5b4R).

  13. Combination of Deep Recurrent Neural Networks and Conditional Random Fields for Extracting Adverse Drug Reactions from User Reviews

    Directory of Open Access Journals (Sweden)

    Elena Tutubalina

    2017-01-01

    Full Text Available Adverse drug reactions (ADRs are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.

  14. Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

    Energy Technology Data Exchange (ETDEWEB)

    Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Spiliopoulos, Stavros [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece); Diamantopoulos, Athanasios [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Karnabatidis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece); Sabharwal, Tarun [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Siablis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece)

    2013-06-15

    IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absence of {>=}50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall

  15. Practical Guidelines for the Use of New Generation Antipsychotic Drugs (except Clozapine) in Adult Individuals with Intellectual Disabilities

    Science.gov (United States)

    de Leon, Jose; Greenlee, Brian; Barber, Jack; Sabaawi, Mohamed; Singh, Nirbhay N.

    2009-01-01

    New generation antipsychotic (NGA) drugs introduced to the US market after clozapine (aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) are frequently used in individuals with intellectual disabilities (ID). However, there is very limited research to fully establish evidence-based or personalized medicine approaches…

  16. Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B

    2017-01-01

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Drug*placebo interaction effect may bias clinical trials interpretation: hybrid balanced placebo and randomized placebo-controlled design.

    Science.gov (United States)

    Hammami, Muhammad M; Hammami, Safa; Al-Swayeh, Reem; Al-Gaai, Eman; Farah, Faduma Abdi; De Padua, Sophia J S

    2016-11-29

    Conventional randomized placebo-controlled study design assumes the absence of drug*placebo interaction. We hypothesized the presence of such an interaction and that conventionally estimated drug effect might be biased. The objectives of the study were to determine the drug*placebo interaction effect (main) and compare conventionally estimated and interaction model-estimated drug effects (secondary). We used a hybrid of balanced placebo and randomized placebo-controlled designs. Four hundred eighty healthy volunteers were randomized to three groups. The first received hydroxyzine (25 mg) described as hydroxyzine or placebo, the second received placebo described as hydroxyzine or placebo, and the third received hydroxyzine and placebo described as unknown; each in a randomized crossover design. Seven participants failed to crossover. Group assignment was concealed from participants and study coordinators. Coordinators were blinded to group and intervention assignment. Participants and coordinators were deceived as to study objectives. Main outcomes were mean area-under-the-curve of drowsiness (therapeutic outcome) and mouth-dryness (adverse outcome), self-reported on 100 mm visual analog scale over 7 h. Drug, placebo, placebo + interaction, and total effects were estimated using analysis of covariance by comparing received hydroxyzine/told placebo to received placebo/told placebo, received placebo/told hydroxyzine to received placebo/told placebo, received hydroxyzine/told hydroxyzine to received hydroxyzine/told placebo, and received hydroxyzine/told hydroxyzine to received placebo/told placebo, respectively. Drug effect was also conventionally estimated in the third group. Mean (SD) age was 31.4 (6.6) years, 65% were males. There was significant difference between placebo + interaction effect and placebo effect for both drowsiness and mouth-dryness with a mean difference (95% confidence interval) of 35.1 (5.6 to 64.6) and 23.8 (2.4 to 45.2) mm

  18. First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry.

    Directory of Open Access Journals (Sweden)

    Jong-Hwa Ahn

    Full Text Available Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES versus first-generation DES in patients with coronary chronic total occlusion (CTO who undergo percutaneous coronary intervention (PCI. The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557 or second-generation DES (n = 449 were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72 or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99. After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86 and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71 were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.

  19. Theory and implementation of a very high throughput true random number generator in field programmable gate array.

    Science.gov (United States)

    Wang, Yonggang; Hui, Cong; Liu, Chong; Xu, Chao

    2016-04-01

    The contribution of this paper is proposing a new entropy extraction mechanism based on sampling phase jitter in ring oscillators to make a high throughput true random number generator in a field programmable gate array (FPGA) practical. Starting from experimental observation and analysis of the entropy source in FPGA, a multi-phase sampling method is exploited to harvest the clock jitter with a maximum entropy and fast sampling speed. This parametrized design is implemented in a Xilinx Artix-7 FPGA, where the carry chains in the FPGA are explored to realize the precise phase shifting. The generator circuit is simple and resource-saving, so that multiple generation channels can run in parallel to scale the output throughput for specific applications. The prototype integrates 64 circuit units in the FPGA to provide a total output throughput of 7.68 Gbps, which meets the requirement of current high-speed quantum key distribution systems. The randomness evaluation, as well as its robustness to ambient temperature, confirms that the new method in a purely digital fashion can provide high-speed high-quality random bit sequences for a variety of embedded applications.

  20. Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

    Directory of Open Access Journals (Sweden)

    R.-D. Hofheinz

    2016-01-01

    Full Text Available Background. In metastatic colorectal cancer (mCRC, continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS and progression-free survival (PFS. Secondary endpoints were the impact of continuing antiangiogenic drugs (i in subgroups, (ii in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors, and (iii on remission rates and prevention of progression. Results. Eight studies (3,668 patients were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75 and OS (HR 0.83; 95%-CI, 0.76–0.89. PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58. Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

  1. Collaborative behavioral management among parolees: drug use, crime and re-arrest in the Step'n Out randomized trial.

    Science.gov (United States)

    Friedmann, Peter D; Green, Traci C; Taxman, Faye S; Harrington, Magdalena; Rhodes, Anne G; Katz, Elizabeth; O'Connell, Daniel; Martin, Steven S; Frisman, Linda K; Litt, Mark; Burdon, William; Clarke, Jennifer G; Fletcher, Bennett W

    2012-06-01

    To determine whether collaborative behavioral management (CBM) reduces substance use, crime and re-arrest among drug-involved parolees. Step'n Out was a randomized behavioral trial of CBM versus standard parole (SP) during 2004-08. CBM adapted evidence-based role induction, behavioral contracting and contingent reinforcement to provide parole officer/treatment counselor dyads with positive tools in addition to sanctions to manage parolees' behavior over 12 weeks. Six parole offices in five states in the USA. Parolee volunteers with a mandate for addiction treatment and a minimum of 3 months of parole (n = 476). Follow-up was 94% at 3 months and 86% at 9 months. Drug use and crime in a given month from calendar interviews 3 and 9 months after parole initiation, and re-arrests from criminal justice administrative data. The CBM group had fewer months in which they used their primary drug [adjusted risk ratio (ARR) 0.20, 95% confidence interval (CI): 0.05, 0.78, P = 0.02] and alcohol (ARR 0.38, 95% CI: 0.22, 0.66, P = 0.006) over follow-up. CBM had its greatest effects among parolees who reported marijuana or another 'non-hard' drug as their primary drug; parolees who preferred stimulants or opiates did not benefit. No differences were seen in total crime, re-arrests or parole revocations. Collaborative behavioral management may reduce substance use among primary marijuana or other 'non-hard' drug-using parolees without increasing revocations. Because the majority of drug violation arrests in the United States are for marijuana, these findings have important implications for the management of a substantial proportion of the US community correctional population. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

  2. Using histograms to introduce randomization in the generation of ensembles of decision trees

    Science.gov (United States)

    Kamath, Chandrika; Cantu-Paz, Erick; Littau, David

    2005-02-22

    A system for decision tree ensembles that includes a module to read the data, a module to create a histogram, a module to evaluate a potential split according to some criterion using the histogram, a module to select a split point randomly in an interval around the best split, a module to split the data, and a module to combine multiple decision trees in ensembles. The decision tree method includes the steps of reading the data; creating a histogram; evaluating a potential split according to some criterion using the histogram, selecting a split point randomly in an interval around the best split, splitting the data, and combining multiple decision trees in ensembles.

  3. Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Xiaojie; Zheng, Hong; Shou, Tao; Tang, Chunming; Miao, Kun; Wang, Ping

    2017-03-29

    Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. We searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords "osteosarcoma", "osteogenic sarcoma", "chemotherapy", and "random*" without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons. We included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen. We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine

  4. Impact of drug reconciliation at discharge and communication between hospital and community pharmacists on drug-related problems: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Pourrat, Xavier; Roux, Clarisse; Bouzige, Brigitte; Garnier, Valérie; Develay, Armelle; Allenet, Benoit; Fraysse, Martial; Halimi, Jean-Michel; Grassin, Jacqueline; Giraudeau, Bruno

    2014-06-30

    Patients are at risk of drug-related problems (DRPs) at transition points during hospitalization. The community pharmacist (CP) is often the first healthcare professional patients visit after discharge. CPs lack sufficient information about the patient and so they may be unable to identify problems in medications, which may lead to dispensing the wrong drugs or dosage, and/or giving wrong information. We aim to assess the impact of a complex intervention comprising of medication reconciliation performed at discharge by a hospital pharmacist (HP) with communication between the HP and CP on DRPs during the seven days following discharge. The study is a cluster randomized crossover trial involving 46 care units (each unit corresponding to a cluster) in 22 French hospitals during two consecutive 14-day periods, randomly assigned as 'experimental' or 'control' (usual care) periods. We will recruit patients older than 18 years of age and visiting the same CP for at least three months. We will exclude patients with a hospital length of stay of more than 21 days, who do not return home or those in palliative care. During the experimental period, the HP will perform a medications reconciliation that will be communicated to the patient. The HP will inform the patient's CP about the patient's drug therapy (modification in home medication, acute drugs prescribed, nonprescription treatments, and/or lab results). The primary outcome will be a composite outcome of any kind of drug misuse during the seven days following discharge assessed at day seven (±2) post-discharge by a pharmacist in charge of the study who will contact both patients and CPs by phone. The secondary outcome will be unplanned hospitalizations assessed by phone contact at day 35 (±5) after discharge. We plan to recruit 1,176 patients. This study will assess the impact of a reconciliation of medications performed at patient discharge followed by communication between the HP and the patient's CP. It will allow

  5. BLEEDING PEPTIC ULCER, NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND HELICOBACTER PYLORI INFECTION – A PROSPECTIVE, CONTROLLED, RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    Pavel Skok

    2002-06-01

    Full Text Available Background. The explanation of peptic ulcer etiology has changed significantly in the past decade after the clarification of the significance of Helicobacter pylori infection.Aim. To evaluate the effectiveness of Helicobacter pylori eradication in patients with hemorrhaging peptic ulcer and patients with peptic ulcer without complications.Study ethics. The study was approved in 1998 by the Medical Ethics Committee of the Republic of Slovenia (No. 90/09/98.Type of study. Prospective, controlled and randomized study, carried out between 1998–2000.Patients and methods. The study included 80 patients (50 male and 30 female, av.age 57.5 years, SD ± 17.1, range 22– 80 in which endoscopy confirmed hemorrhage from peptic ulcer of stomach or duodenum and Helicobacter pylori infection. In all cases endoscopic hemostasis was performed: injection sclerotherapy with diluted adrenalin 1:10,000 and 1% polidocanol or argon plasma coagulation. The control group was made up of 80 patients (50 male and 30 female, av.age 56.8 years, SD ± 16.8, range 19–80 with peptic ulcer of stomach or duodenum and Helicobacter pylori infection. Infection was confirmed by a rapid urease test and histologic investigation of the gastric mucosa. In all cases the recommended drug combinations were used in the treatment of the infection: a proton pump inhibitor, omeprazol (4 weeks, and combination of antibiotics, claritromycin and metronidazole or with regard to the antibiogram (1 week. The therapeutic success was ascertained endoscopically four weeks after inclusion in the study. Infection eradication was confirmed by the rapid urease test and histologic investigation of the gastric mucosa.Results. Four weeks after inclusion in the study the success of infection eradication was 92.5% in the study group, in the control group it was 91.3% (p > 0.05. In 6 patients (7.5%, 6/ 80 from the study group and in 7 (8.8%, 7/80 from the control group we introduced a replacement treatment

  6. Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.

    Science.gov (United States)

    Goulding, Rebecca; Dawes, Diana; Price, Morgan; Wilkie, Sabrina; Dawes, Martin

    2015-10-01

    Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing. Three electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-genetic informed prescribing, reported drug specific adverse drug events and clinical effectiveness outcomes. Two reviewers independently screened titles and abstracts, extracted data and assessed study quality. Meta-analyses of specific outcomes were conducted where data allowed. Fifteen studies, involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria. Eight studies had statistically significant results for their primary outcome in favour of genotype-guided prescribing. Nine studies evaluated genotype-guided warfarin dosing. Analysis of percentage of time in therapeutic international normalized ratio range (1952 individuals) showed a statistically significant benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95% CI 1.34, 12.0, I(2) = 80%). There was a statistically significant reduction in numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33, 0.99; I(2) = 60%). It was not possible to meta-analyze genotype-guided dosing for other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a statistically significant benefit for their primary outcome, odds ratio 0.03 (95% CI 0.00, 0.62, P genotype-guided warfarin dosing. © 2014 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

  7. Generating Variable and Random Schedules of Reinforcement Using Microsoft Excel Macros

    Science.gov (United States)

    Bancroft, Stacie L.; Bourret, Jason C.

    2008-01-01

    Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time. Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time.…

  8. Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls.

    Science.gov (United States)

    Nakamura, Hideaki; Fang, Jun; Jun, Fang; Maeda, Hiroshi

    2015-01-01

    A major problem with conventional antitumor therapeutics is nonselective delivery of cytotoxic drugs to normal vital organs and tissues but little delivery to tumor tissues. Here, the authors describe the tumor selective delivery of antitumor drugs by taking advantage of nano-sized drugs and the means to augment it further. Based on the enhanced permeability and retention (EPR) effect, the mechanism for more efficient universal tumor delivery using macromolecular drugs to cover wider tumor types than single molecular target is discussed. Unique properties of solid tumor vasculature in the tumor tissue are discussed, especially leakiness of the blood vessels and factors involved and impaired clearance of macromolecular drugs from the tumor interstitium via the lymphatic system. The criteria for such macromolecular drugs or nanomedicines for effective accumulation at tumor sites is commented on as well as the importance of long plasma retention time of such drugs and a need to release active principles from nanoparticles at target sites. Methods to augment the EPR effect and tumor delivery (2 - 3 times) and its application to photodynamic therapy are also discussed. Tumor selective delivery of antitumor drugs based on the EPR effect can be accomplished and augmented by modulating the tumor environment. This methodology is favorable not only for tumor therapy but also for tumor imaging.

  9. Effect of an educational intervention to improve adverse drug reaction reporting in physicians: a cluster randomized controlled trial.

    Science.gov (United States)

    Lopez-Gonzalez, Elena; Herdeiro, Maria T; Piñeiro-Lamas, María; Figueiras, Adolfo

    2015-02-01

    The yellow-card scheme continues to be one of the principal methods for signal generation in pharmacovigilance. Nevertheless, under-reporting, one of its disadvantages, delays alert signals and has a negative influence on public health. Educational interventions in pharmacovigilance may have a positive impact on the spontaneous reporting of adverse drug reactions (ADRs). To assess the duration of the effect and effectiveness of an educational intervention in pharmacovigilance designed to improve ADR reporting in a robust pharmacovigilance system. A spatial, cluster randomized controlled trial was conducted covering all National Health System physicians in the northwest of Spain and targeting those who were actively engaged in clinical practice (n = 7,498). Of these, 2,120 were assigned in three spatial clusters to the intervention group (six hospitals and 138 primary care centers) and 3,614 in four clusters to the control group (seven hospitals and 267 primary care centers). The educational intervention consisted of two complementary approaches--one active (group sessions), the other passive (educational material, reporting form)-implemented from November 2007 to December 2008, with a follow-up period of 8 months. Intervention participation was 53.7 % in a hospital setting and 60.5 % in primary care settings. ADR reporting in the intervention group increased by 65.4 % (95 % confidence interval [CI]: 8.2-153.4) across the follow-up. The ADR reporting rate per 1,000 physicians/year in the intervention group rose from 28.1 to 39.6 following the intervention (51.7 and 27.4 in the first and second 4-month period, respectively). For the intervention group, relative risk (RR) was 2.31 (95 % CI: 1.46-3.68) and 1.04 (95 % CI: 0.61-1.77) in the first and second 4-month period, respectively adjusted to baseline values. There was an increase in unexpected ADR reporting (RR 2.06, 95 % CI 1.19-3.55). Pharmacovigilance educational interventions that have proved effective can be

  10. A randomized controlled trial of an inference generation strategy intervention for adults with high-functioning autism spectrum disorder.

    Science.gov (United States)

    Murza, Kimberly A; Nye, Chad; Schwartz, Jamie B; Ehren, Barbara J; Hahs-Vaughn, Debbie L

    2014-08-01

    The present intervention study investigated the efficacy of the ACT & Check Strategy intervention to improve inference generation when reading, metacognitive ability, general reading comprehension, and social inference ability in adults with high-functioning autism spectrum disorder (HF-ASD). Twenty-five adults with HF-ASD were randomly assigned to either a treatment or a control group. Treatment sessions were conducted in 1-hr sessions, twice a week, for a total of 6 weeks. Treatment focused on explicit instruction of components of inference generation, categories of inferences, and increasingly independent strategy use. The treatment group demonstrated significantly superior performance on 1 of 2 measures of inference generation in reading and 1 measure of metacognitive ability compared with the control group. Significant differences between groups were not found on measures of reading comprehension or social inference ability. These findings suggest that the ACT & Check Strategy was effective in improving participants' ability to generate inferences in reading and certain metacognitive abilities, but the skills do not appear to generalize to other social communication contexts, such as social inference generation. This research provides a measure of support for explicitly teaching inference generation to address a reading inference deficit in adults with HF-ASD.

  11. Mersenne Twister: A 623-Dimensionally Equidistributed Uniform Pseudo-Random Number Generator

    OpenAIRE

    Matsumoto, Makoto; Nishimura, Takuji

    1998-01-01

    A new algorithm called Mersenne Twister (MT) is proposed for generating uniform pseudorandom numbers. For a particular choice of parameters, the algorithm provides a super astronomical period of 219937 - 1 and 623-dimensional equidistribution up to 32-bit accuracy, while using a working area of only 624 words. This is a new variant of the previously proposed generators, TGFSR, modified so as to admit a Mersenne-prime period. The characteristic polynomial has many terms. The distribution up to...

  12. The NARCONON drug education curriculum for high school students: a non-randomized, controlled prevention trial.

    Science.gov (United States)

    Lennox, Richard D; Cecchini, Marie A

    2008-03-19

    An estimated 13 million youths aged 12 to 17 become involved with alcohol, tobacco and other drugs annually. The number of 12- to 17-year olds abusing controlled prescription drugs increased an alarming 212 percent between 1992 and 2003. For many youths, substance abuse precedes academic and health problems including lower grades, higher truancy, drop out decisions, delayed or damaged physical, cognitive, and emotional development, or a variety of other costly consequences. For thirty years the Narconon program has worked with schools and community groups providing single educational modules aimed at supplementing existing classroom-based prevention activities. In 2004, Narconon International developed a multi-module, universal prevention curriculum for high school ages based on drug abuse etiology, program quality management data, prevention theory and best practices. We review the curriculum and its rationale and test its ability to change drug use behavior, perceptions of risk/benefits, and general knowledge. After informed parental consent, approximately 1000 Oklahoma and Hawai'i high school students completed a modified Center for Substance Abuse Prevention (CSAP) Participant Outcome Measures for Discretionary Programs survey at three testing points: baseline, one month later, and six month follow-up. Schools assigned to experimental conditions scheduled the Narconon curriculum between the baseline and one-month follow-up test; schools in control conditions received drug education after the six-month follow-up. Student responses were analyzed controlling for baseline differences using analysis of covariance. At six month follow-up, youths who received the Narconon drug education curriculum showed reduced drug use compared with controls across all drug categories tested. The strongest effects were seen in all tobacco products and cigarette frequency followed by marijuana. There were also significant reductions measured for alcohol and amphetamines. The program

  13. The NARCONON™ drug education curriculum for high school students: A non-randomized, controlled prevention trial

    Directory of Open Access Journals (Sweden)

    Cecchini Marie A

    2008-03-01

    Full Text Available Abstract Background An estimated 13 million youths aged 12 to 17 become involved with alcohol, tobacco and other drugs annually. The number of 12- to 17-year olds abusing controlled prescription drugs increased an alarming 212 percent between 1992 and 2003. For many youths, substance abuse precedes academic and health problems including lower grades, higher truancy, drop out decisions, delayed or damaged physical, cognitive, and emotional development, or a variety of other costly consequences. For thirty years the Narconon program has worked with schools and community groups providing single educational modules aimed at supplementing existing classroom-based prevention activities. In 2004, Narconon International developed a multi-module, universal prevention curriculum for high school ages based on drug abuse etiology, program quality management data, prevention theory and best practices. We review the curriculum and its rationale and test its ability to change drug use behavior, perceptions of risk/benefits, and general knowledge. Methods After informed parental consent, approximately 1000 Oklahoma and Hawai'i high school students completed a modified Center for Substance Abuse Prevention (CSAP Participant Outcome Measures for Discretionary Programs survey at three testing points: baseline, one month later, and six month follow-up. Schools assigned to experimental conditions scheduled the Narconon curriculum between the baseline and one-month follow-up test; schools in control conditions received drug education after the six-month follow-up. Student responses were analyzed controlling for baseline differences using analysis of covariance. Results At six month follow-up, youths who received the Narconon drug education curriculum showed reduced drug use compared with controls across all drug categories tested. The strongest effects were seen in all tobacco products and cigarette frequency followed by marijuana. There were also significant

  14. Pseudorandom Number Generators for Mobile Devices: An Examination and Attempt to Improve Randomness

    Science.gov (United States)

    2013-09-01

    what if the tickets are not properly mixed and instead are just put in a jar as they are being sold? What if the lottery tickets have different sizes...winner of the raffle randomly, and the lottery would not be considered fair. In the situation described in the previous paragraph, the raffle...official drawing the winning ticket is clearly a great risk to biasing the outcome. Therefore, mechanical raffle and lottery machines are widely used in

  15. Pseudo-Random Modulation of a Laser Diode for Generating Ultrasonic Longitudinal Waves

    Science.gov (United States)

    Madaras, Eric I.; Anatasi, Robert F.

    2004-01-01

    Laser generated ultrasound systems have historically been more complicated and expensive than conventional piezoelectric based systems, and this fact has relegated the acceptance of laser based systems to niche applications for which piezoelectric based systems are less suitable. Lowering system costs, while improving throughput, increasing ultrasound signal levels, and improving signal-to-noise are goals which will help increase the general acceptance of laser based ultrasound. One current limitation with conventional laser generated ultrasound is a material s damage threshold limit. Increasing the optical power to generate more signal eventually damages the material being tested due to rapid, high heating. Generation limitations for laser based ultrasound suggests the use of pulse modulation techniques as an alternate generation method. Pulse modulation techniques can spread the laser energy over time or space, thus reducing laser power densities and minimizing damage. Previous experiments by various organizations using spatial or temporal pulse modulation have been shown to generate detectable surface, plate, and bulk ultrasonic waves with narrow frequency bandwidths . Using narrow frequency bandwidths improved signal detectability, but required the use of expensive and powerful lasers and opto-electronic systems. The use of a laser diode to generate ultrasound is attractive because of its low cost, small size, light weight, simple optics and modulation capability. The use of pulse compression techniques should allow certain types of laser diodes to produce usable ultrasonic signals. The method also does not need to be limited to narrow frequency bandwidths. The method demonstrated here uses a low power laser diode (approximately 150 mW) that is modulated by controlling the diode s drive current and the resulting signal is recovered by cross correlation. A potential application for this system which is briefly demonstrated is in detecting signals in thick

  16. [Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes].

    Science.gov (United States)

    Ma, Li-xin; Wang, Yu-yi; Li, Xin-xue; Liu, Jian-ping

    2012-03-01

    Randomized controlled trial (RCT) is considered as the gold standard for the efficacy assessment of medicines. With the increasing number of Chinese patent drugs for treatment of type 2 diabetes, the methodology of post-marketing RCTs evaluating the efficacy and specific effect has become more important. To investigate post-marketing Chinese patent drugs for treatment of type 2 diabetes, as well as the methodological quality of post-marketing RCTs. Literature was searched from the books of Newly Compiled Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the State Food and Drug Administration and the Ministry of Human Resources and Social Security of the People's Republic of China, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period for searching ran from the commencement of each database to August 2011. RCTs of post-marketing Chinese patent drugs for treatment of type 2 diabetes with intervention course no less than 3 months. Two authors independently evaluated the research quality of the RCTs by the checklist of risk bias assessment and the data collection forms based on the CONSORT Statement. Independent double data-extraction was performed. The authors identified a total of 149 Chinese patent drugs for treatment of type 2 diabetes. According to different indicative syndromes, the Chinese patent drugs can be divided into the following types, namely, yin deficiency and interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41 RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor endpoint outcome reports were found. Risk bias analysis showed that 81% of the included studies reported randomization for grouping without sequence generation, 98% of these studies did not report

  17. Underutilization of prescribed drugs use among first generation elderly immigrants in the Netherlands

    NARCIS (Netherlands)

    S. Denktaş (Semiha); G. Koopmans (Gerrit); E. Birnie (Erwin); M.M.E. Foets (Marleen); G.J. Bonsel (Gouke)

    2010-01-01

    textabstractBackground. In developed countries, health care utilization among immigrant groups differs where the dominant interpretation is unjustified overutilization due to lack of acculturation. We investigated utilization of prescribed drugs in native Dutch and various groups of immigrant

  18. Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes.

    Science.gov (United States)

    Zhelev, Zhivko; Ivanova, Donika; Bakalova, Rumiana; Aoki, Ichio; Higashi, Tatsuya

    2017-01-01

    The present study demonstrates specific sensitization of leukemia lymphocytes towards anticancer drugs using melatonin and clarifies the role of reactive oxygen species (ROS) for induction of apoptosis. The study covers four conventional and 11 new-generation anticancer drugs. Four parameters were analyzed simultaneously in leukemia and normal lymphocytes treated with drug, melatonin, or their combination: cell viability, induction of apoptosis, level of reactive oxygen species (ROS), and level of protein-carbonyl products. Almost all investigated combinations of melatonin with new-generation anticancer drugs were characterized by synergistic cytotoxicity towards leukemia lymphocytes, while the combinations with conventional drugs exhibited additive or antagonistic effects on cell viability. In leukemia lymphocytes, the additive cytotoxicity of doxorubicin plus melatonin was accompanied by low levels of ROS and protein-carbonyl products, as well as by suppression of apoptosis. In normal lymphocytes, none of the studied parameters changed significantly compared to cells treated with doxorubicin only. The combinations of everolimus plus melatonin and barasertib plus melatonin exhibited impressive synergistic cytotoxic effects on leukemia lymphocytes but did not affect the viability of normal lymphocytes. In leukemia cells, the synergistic cytotoxicity was accompanied by strong induction of apoptosis but a decrease of ROS to a level below that of the control. In normal lymphocytes, these combinations did not affect the level of ROS nor of protein-carbonyl products, and did not induce apoptosis. The data suggest that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. 78 FR 71036 - Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting...

    Science.gov (United States)

    2013-11-27

    ...; Contractor Management Information System Reporting; and Obtaining Drug and Alcohol Management Information System Sign-In Information AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT... Operators to Report Contractor Management Information System (MIS) Data; and New Method for Operators to...

  20. Impact of Paclitaxel-Eluting Balloons Compared to Second-Generation Drug-Eluting Stents for of In-Stent Restenosis in a Primarily Acute Coronary Syndrome Population

    Directory of Open Access Journals (Sweden)

    Guillaume Marquis-Gravel

    2017-09-01

    Full Text Available Abstract Background: The place of drug-eluting balloons (DEB in the treatment of in-stent restenosis (ISR is not well-defined, particularly in a population of all-comers with acute coronary syndromes (ACS. Objective: Compare the clinical outcomes of DEB with second-generation drug-eluting stents (DES for the treatment of ISR in a real-world population with a high proportion of ACS. Methods: A retrospective analysis of consecutive patients with ISR treated with a DEB compared to patients treated with a second-generation DES was performed. The primary endpoint was a composite of major adverse cardiovascular events (MACE: all-cause death, non-fatal myocardial infarction, and target lesion revascularization. Comparisons were performed using Cox proportional hazards multivariate adjustment and Kaplan-Meier analysis with log-rank. Results: The cohort included 91 patients treated with a DEB and 89 patients treated with a DES (74% ACS. Median follow-up was 26 months. MACE occurred in 33 patients (36% in the DEB group, compared to 17 patients (19% in the DES group (p log-rank = 0.02. After multivariate adjustment, there was no significant difference between the groups (HR for DEB = 1.45 [95%CI: 0.75-2.83]; p = 0.27. Mortality rates at 1 year were 11% with DEB, and 3% with DES (p = 0.04; adjusted HR = 2.85 [95%CI: 0.98-8.32]; p = 0.06. Conclusion: In a population with a high proportion of ACS, a non-significant numerical signal towards increased rates of MACE with DEB compared to second-generation DES for the treatment of ISR was observed, mainly driven by a higher mortality rate. An adequately-powered randomized controlled trial is necessary to confirm these findings.

  1. Experimental observation of second-harmonic generation and diffusion inside random media

    NARCIS (Netherlands)

    Faez, Sanli; Johnson, P. M.; Mazurenko, D. A.; Lagendijk, Ad

    We have experimentally measured the distribution of the second-harmonic intensity that is generated inside a highly scattering slab of porous gallium phosphide. Two complementary techniques for determining the distribution are used. First, the spatial distribution of second-harmonic light intensity

  2. Simulated Performance Evaluation of a Selective Tracker Through Random Scenario Generation

    DEFF Research Database (Denmark)

    Hussain, Dil Muhammad Akbar

    2006-01-01

      The paper presents a simulation study on the performance of a target tracker using selective track splitting filter algorithm through a random scenario implemented on a digital signal processor.  In a typical track splitting filter all the observation which fall inside a likelihood ellipse...... are used for update, however, in our proposed selective track splitting filter less number of observations are used for track update.  Much of the previous performance work [1] has been done on specific (deterministic) scenarios. One of the reasons for considering the specific scenarios, which were...

  3. The isector: a simple and direct method for generating isotropic, uniform random sections from small specimens

    DEFF Research Database (Denmark)

    Nyengaard, Jens Randel; Gundersen, Hans Jørgen Gottlieb

    1992-01-01

    The very simple and strong principle of vertical sections devised by Baddeley et al. has been a major advance in stereology when any kind of anisotropy is present in the specimen under study. On the other hand, some important stereological estimators still require isotropic, uniform random sectio....... This paper deals with a simple technique for embedding specimens in rubber moulds with spherical cavities. After the embedding, any handling or the resulting sphere independent of the specimen will induce isotropy of the final histological sections....

  4. Randomized pharmacokinetic and drug–drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects

    Science.gov (United States)

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-01-01

    We assessed pharmacokinetic and safety profiles of ceftazidime–avibactam administered ± metronidazole, and whether drug–drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime–avibactam (2000–500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime–avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime–avibactam over 4 days to assess drug–drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime–avibactam and metronidazole in subjects receiving ceftazidime–avibactam (2000–500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime–avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80–125%) indicating no drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. PMID:26516584

  5. Can Targeted Intervention Mitigate Early Emotional and Behavioral Problems?: Generating Robust Evidence within Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Orla Doyle

    Full Text Available This study examined the impact of a targeted Irish early intervention program on children's emotional and behavioral development using multiple methods to test the robustness of the results. Data on 164 Preparing for Life participants who were randomly assigned into an intervention group, involving home visits from pregnancy onwards, or a control group, was used to test the impact of the intervention on Child Behavior Checklist scores at 24-months. Using inverse probability weighting to account for differential attrition, permutation testing to address small sample size, and quantile regression to characterize the distributional impact of the intervention, we found that the few treatment effects were largely concentrated among boys most at risk of developing emotional and behavioral problems. The average treatment effect identified a 13% reduction in the likelihood of falling into the borderline clinical threshold for Total Problems. The interaction and subgroup analysis found that this main effect was driven by boys. The distributional analysis identified a 10-point reduction in the Externalizing Problems score for boys at the 90th percentile. No effects were observed for girls or for the continuous measures of Total, Internalizing, and Externalizing problems. These findings suggest that the impact of this prenatally commencing home visiting program may be limited to boys experiencing the most difficulties. Further adoption of the statistical methods applied here may help to improve the internal validity of randomized controlled trials and contribute to the field of evaluation science more generally.ISRCTN Registry ISRCTN04631728.

  6. Internal wave generation by tidal flow over periodically and randomly distributed seamounts

    Science.gov (United States)

    Zhang, Likun; Buijsman, Maarten C.; Comino, Eva; Swinney, Harry L.

    2017-06-01

    We examine numerically the conversion of barotropic tidal energy into internal waves by flow over an isolated seamount and over systems of periodically and randomly distributed 1100 m tall seamounts with Gaussian profiles. The simulations use the Massachusetts Institute of Technology general circulation model (MITgcm) to calculate for an infinitely deep ocean the dependence of the energy conversion on seamount slope, seamount separation, tidal direction, and the size and aspect ratio of the simulation domain. For neighboring seamounts with a slope greater than the internal wave beam slope, wave interference reduces the conversion relative to that calculated for an isolated seamount, and relative to that predicted by linear theory for a seamount of slope less than the beam slope. The conversion by an individual seamount in a system of random seamounts separated by an average distance of 18 km is found to be suppressed by 16% relative to the conversion by an isolated seamount. This study provides insight into tidal conversion by ocean seamounts modeled as Gaussian mountains with slopes both smaller and larger than the beam slope. We conclude that the total energy conversion by all seamounts (peak height ≥1000 m) and knolls (peak height 500-1000 m), taking into account interference affects, is of the order of 1% of the total barotropic to baroclinic energy conversion in the oceans, which is about twice as large as previous estimates.

  7. Synaptic signal streams generated by ex vivo neuronal networks contain non-random, complex patterns.

    Science.gov (United States)

    Lee, Sangmook; Zemianek, Jill M; Shultz, Abraham; Vo, Anh; Maron, Ben Y; Therrien, Mikaela; Courtright, Christina; Guaraldi, Mary; Yanco, Holly A; Shea, Thomas B

    2014-11-01

    Cultured embryonic neurons develop functional networks that transmit synaptic signals over multiple sequentially connected neurons as revealed by multi-electrode arrays (MEAs) embedded within the culture dish. Signal streams of ex vivo networks contain spikes and bursts of varying amplitude and duration. Despite the random interactions inherent in dissociated cultures, neurons are capable of establishing functional ex vivo networks that transmit signals among synaptically connected neurons, undergo developmental maturation, and respond to exogenous stimulation by alterations in signal patterns. These characteristics indicate that a considerable degree of organization is an inherent property of neurons. We demonstrate herein that (1) certain signal types occur more frequently than others, (2) the predominant signal types change during and following maturation, (3) signal predominance is dependent upon inhibitory activity, and (4) certain signals preferentially follow others in a non-reciprocal manner. These findings indicate that the elaboration of complex signal streams comprised of a non-random distribution of signal patterns is an emergent property of ex vivo neuronal networks. Copyright © 2014. Published by Elsevier Ltd.

  8. New generation nanomedicines constructed from self-assembling small molecule prodrugs alleviate cancer drug toxicity.

    Science.gov (United States)

    Wang, Hangxiang; Lu, Zhongjie; Wang, Lijiang; Guo, Tingting; Wu, Jiaping; Wan, Jianqin; Zhou, Liqian; Li, Hui; Li, Zhen; Jiang, Donghai; Song, Penghong; Xie, Haiyang; Zhou, Lin; Xu, Xiao; Zheng, Shusen

    2017-10-20

    The therapeutic index for chemotherapeutic drugs is determined in part by systemic toxicity, so strategies for dose intensification to improve efficacy must also address tolerability. In addressing this issue, we have investigated a novel combinatorial strategy of reconstructing a drug molecule and using sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines (SNM). Using cabazitaxel (CTX) as a target agent, we established that individual synthetic prodrugs tethered with polyunsaturated fatty acids were capable of recapitulating self-assembly behavior independent of exogenous excipients. The resulting SNM could be further refined by PEGylation with amphiphilic copolymers suitable for preclinical studies. Among these CTX derivatives, docosahexaenoic acid-derived compound 1 retained high anti-proliferative activity. SNM assembled with compound 1 displayed an unexpected enhancement of tolerability in animals along with effective therapeutic efficacy in a mouse xenograft model of human cancer, compared to free drug administered in its clinical formulation. Overall, our studies showed how attaching flexible lipid chains to a hydrophobic and highly toxic anticancer drug can convert it to a systemic self-deliverable nanotherapy, preserving its pharmacological efficacy while improving its safety profile. Copyright ©2017, American Association for Cancer Research.

  9. Highly efficient hybrid energy generator: coupled organic photovoltaic device and randomly oriented electrospun poly(vinylidene fluoride) nanofiber.

    Science.gov (United States)

    Park, Boongik; Lee, Kihwan; Park, Jongjin; Kim, Jongmin; Kim, Ohyun

    2013-03-01

    A hybrid architecture consisting of an inverted organic photovoltaic device and a randomly-oriented electrospun PVDF piezoelectric device was fabricated as a highly-efficient energy generator. It uses the inverted photovoltaic device with coupled electrospun PVDF nanofibers as tandem structure to convert solar and mechanical vibrations energy to electricity simultaneously or individually. The power conversion efficiency of the photovoltaic device was also significantly improved up to 4.72% by optimized processes such as intrinsic ZnO, MoO3 and active layer. A simple electrospinning method with the two electrode technique was adopted to achieve a high voltage of - 300 mV in PVDF piezoelectric fibers. Highly-efficient HEG using voltage adder circuit provides the conceptual possibility of realizing multi-functional energy generator whenever and wherever various energy sources are available.

  10. Probabilistic Approach to Generating MPOs and Its Application as a Scoring Function for CNS Drugs.

    Science.gov (United States)

    Gunaydin, Hakan

    2016-01-14

    Multiparameter optimization (MPO) scoring functions are popular tools for providing guidance on how to design desired molecules in medicinal chemistry. The utility of a new probabilistic MPO (pMPO) scoring function method and its application as a scoring function for CNS drugs are described in this letter. In this new approach, a minimal number of statistically determined empirical boundaries is combined with the probability distribution of the desired molecules to define desirability functions. This approach attempts to minimize the number of parameters that define MPO scores while maintaining a high level of predictive power. Results obtained from a test-set of orally approved drugs show that the pMPO approach described here can be used to separate desired molecules from undesired ones with accuracy comparable to a Bayesian model with the advantage of better human interpretability. The application of this pMPO approach for blood-brain barrier penetrant drugs is also described.

  11. Generation of Multicellular Tumor Spheroids with Microwell-Based Agarose Scaffolds for Drug Testing.

    Directory of Open Access Journals (Sweden)

    Xue Gong

    Full Text Available Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold prepared with the template containing uniform-sized micro-wells in commercially available cell culture plates. The agarose scaffold allows for good adjustment of MCTS size and large-scale production of MCTS. Transparent agarose scaffold also allows for monitoring of spheroid formation under an optical microscopy. The formation of MCTS from MCF-7 cells was prepared using different-size-well templates and systematically investigated in terms of spheroid growth curve, circularity, and cell viability. The doxorubicin cytotoxicity against MCF-7 spheroid and MCF-7 monolayer cells was compared. The drug penetration behavior, cell cycle distribution, cell apoptosis, and gene expression were also evaluated in MCF-7 spheroid. The findings of this study indicate that, compared with cellular monolayer, MCTS provides a valuable platform for the assessment of therapeutic candidates in an in vivo-mimic microenvironment, and thus has great potential for use in drug discovery and tumor biology research.

  12. Random Assignment of Schools to Groups in the Drug Resistance Strategies Rural Project: Some New Methodological Twists

    Science.gov (United States)

    Pettigrew, Jonathan; Miller-Day, Michelle; Krieger, Janice L.; Zhou, Jiangxiu; Hecht, Michael L.

    2014-01-01

    Random assignment to groups is the foundation for scientifically rigorous clinical trials. But assignment is challenging in group randomized trials when only a few units (schools) are assigned to each condition. In the DRSR project, we assigned 39 rural Pennsylvania and Ohio schools to three conditions (rural, classic, control). But even with 13 schools per condition, achieving pretest equivalence on important variables is not guaranteed. We collected data on six important school-level variables: rurality, number of grades in the school, enrollment per grade, percent white, percent receiving free/assisted lunch, and test scores. Key to our procedure was the inclusion of school-level drug use data, available for a subset of the schools. Also, key was that we handled the partial data with modern missing data techniques. We chose to create one composite stratifying variable based on the seven school-level variables available. Principal components analysis with the seven variables yielded two factors, which were averaged to form the composite inflate-suppress (CIS) score which was the basis of stratification. The CIS score was broken into three strata within each state; schools were assigned at random to the three program conditions from within each stratum, within each state. Results showed that program group membership was unrelated to the CIS score, the two factors making up the CIS score, and the seven items making up the factors. Program group membership was not significantly related to pretest measures of drug use (alcohol, cigarettes, marijuana, chewing tobacco; smallest p>.15), thus verifying that pretest equivalence was achieved. PMID:23722619

  13. Generation of drugs coated iron nanoparticles through high energy ball milling

    Energy Technology Data Exchange (ETDEWEB)

    Radhika Devi, A.; Murty, B. S. [Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai 600036 (India); Chelvane, J. A. [Defence Metallurgical Research Laboratory, Hyderabad 500058 (India); Prabhakar, P. K.; Padma Priya, P. V.; Doble, Mukesh [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036 (India)

    2014-03-28

    The iron nanoparticles coated with oleic acid and drugs such as folic acid/Amoxicillin were synthesized by high energy ball milling and characterized by X-ray diffraction, Transmission electron microscope, zeta potential, dynamic light scattering, Fourier Transform Infra red (FT-IR) measurements, and thermo gravimetric analysis (TGA). FT-IR and TGA measurements show good adsorption of drugs on oleic acid coated nanoparticles. Magnetic measurements indicate that saturation magnetization is larger for amoxicillin coated particles compared to folic acid coated particles. The biocompatibility of the magnetic nanoparticles prepared was evaluated by in vitro cytotoxicity assay using L929 cells as model cells.

  14. A randomized clinical trial of behavioral couples therapy versus individually-based treatment for drug-abusing women.

    Science.gov (United States)

    O'Farrell, Timothy J; Schumm, Jeremiah A; Murphy, Marie M; Muchowski, Patrice M

    2017-04-01

    Behavioral couples therapy (BCT) is more efficacious than individually-based therapy (IBT) for substance and relationship outcomes among substance use disorder patients. This study compared BCT with IBT for drug-abusing women. Sixty-one women, mostly White, late 30s, with primary substance use disorder other than alcohol (74% opioid), and male partners were randomized to 26 sessions over 13 weeks of BCT plus 12-step-oriented IBT (i.e., BCT + IBT) or IBT. Substance-related outcomes were percentage days abstinent (PDA), percentage days drug use (PDDU), Inventory of Drug Use Consequences. Relationship outcomes were Dyadic Adjustment Scale (DAS), days separated. Data were collected at baseline, posttreatment, and quarterly for 1-year follow-up. On PDA, PDDU, and substance-related problems, both BCT + IBT and IBT patients showed significant (p .8 for most time periods). BCT + IBT showed a significant (p .47). On relationship outcomes, compared to IBT, BCT + IBT had significantly higher male-reported Dyadic Adjustment Scale (p women was more efficacious than IBT in improving relationship satisfaction and preventing relationship breakup. On substance use and substance-related problems, women receiving both treatments substantially improved, and women receiving BCT + IBT had fewer substance-related problems than IBT. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. ANALYSIS AND VALIDATION OF GRID DEM GENERATION BASED ON GAUSSIAN MARKOV RANDOM FIELD

    Directory of Open Access Journals (Sweden)

    F. J. Aguilar

    2016-06-01

    Full Text Available Digital Elevation Models (DEMs are considered as one of the most relevant geospatial data to carry out land-cover and land-use classification. This work deals with the application of a mathematical framework based on a Gaussian Markov Random Field (GMRF to interpolate grid DEMs from scattered elevation data. The performance of the GMRF interpolation model was tested on a set of LiDAR data (0.87 points/m2 provided by the Spanish Government (PNOA Programme over a complex working area mainly covered by greenhouses in Almería, Spain. The original LiDAR data was decimated by randomly removing different fractions of the original points (from 10% to up to 99% of points removed. In every case, the remaining points (scattered observed points were used to obtain a 1 m grid spacing GMRF-interpolated Digital Surface Model (DSM whose accuracy was assessed by means of the set of previously extracted checkpoints. The GMRF accuracy results were compared with those provided by the widely known Triangulation with Linear Interpolation (TLI. Finally, the GMRF method was applied to a real-world case consisting of filling the LiDAR-derived DSM gaps after manually filtering out non-ground points to obtain a Digital Terrain Model (DTM. Regarding accuracy, both GMRF and TLI produced visually pleasing and similar results in terms of vertical accuracy. As an added bonus, the GMRF mathematical framework makes possible to both retrieve the estimated uncertainty for every interpolated elevation point (the DEM uncertainty and include break lines or terrain discontinuities between adjacent cells to produce higher quality DTMs.

  16. W-Band Millimeter-Wave Vector Signal Generation Based on Precoding-Assisted Random Photonic Frequency Tripling Scheme Enabled by Phase Modulator

    National Research Council Canada - National Science Library

    Li, Xinying; Xu, Yuming; Xiao, Jiangnan; Yu, Jianjun

    2016-01-01

    We propose W-band photonic millimeter-wave (mm-wave) vector signal generation employing a precoding-assisted random frequency tripling scheme enabled by a single phase modulator cascaded with a wavelength selective switch (WSS...

  17. Quantum random number generator based on ‘Fermi–Dirac’ statistics of photocounts of faint laser pulses with a 75 Mbit s‑1 rate

    Science.gov (United States)

    Balygin, K. A.; Zaitsev, V. I.; Klimov, A. N.; Kulik, S. P.; Molotkov, S. N.; Popova, E.; Vinogradov, S.

    2017-12-01

    We implemented experimentally a quantum random number generator, based on the registration of quasi-single-photon light by a silicon photo-multiplier, which allows one to reliably achieve the Poisson statistics of photocounts. The use of the optimal grouping of photocounts and a polynomial-length sequence of the method for extracting the random sequence 0 and 1 made it possible to achieve the output rate of a provably random sequence up to 75 Mbit s-1 .

  18. Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity

    Science.gov (United States)

    Raghavan, Shreya; Rowley, Katelyn R.; Mehta, Geeta

    2016-01-01

    Multicellular tumor spheroids are powerful in vitro models to perform preclinical chemosensitivity assays. We compare different methodologies to generate tumor spheroids in terms of resultant spheroid morphology, cellular arrangement and chemosensitivity. We used two cancer cell lines (MCF7 and OVCAR8) to generate spheroids using i) hanging drop array plates; ii) liquid overlay on ultra-low attachment plates; iii) liquid overlay on ultra-low attachment plates with rotating mixing (nutator plates). Analysis of spheroid morphometry indicated that cellular compaction was increased in spheroids generated on nutator and hanging drop array plates. Collagen staining also indicated higher compaction and remodeling in tumor spheroids on nutator and hanging drop arrays compared to conventional liquid overlay. Consequently, spheroids generated on nutator or hanging drop plates had increased chemoresistance to cisplatin treatment (20-60% viability) compared to spheroids on ultra low attachment plates (10-20% viability). Lastly, we used a mathematical model to demonstrate minimal changes in oxygen and cisplatin diffusion within experimentally generated spheroids. Our results demonstrate that in vitro methods of tumor spheroid generation result in varied cellular arrangement and chemosensitivity. PMID:26918944

  19. Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

    Directory of Open Access Journals (Sweden)

    Jayavel Arumugam

    Full Text Available Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve. In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

  20. Introducing rapid diagnostic tests for malaria into drug shops in Uganda: design and implementation of a cluster randomized trial.

    Science.gov (United States)

    Mbonye, Anthony K; Magnussen, Pascal; Chandler, Clare I R; Hansen, Kristian S; Lal, Sham; Cundill, Bonnie; Lynch, Caroline A; Clarke, Siân E

    2014-07-29

    An intervention was designed to introduce rapid diagnostics tests for malaria (mRDTs) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy (ACT). We conducted participatory training of drug shop vendors and implemented supporting interventions to orientate local communities (patients) and the public sector (health facility staff and district officials) to the behavioral changes in diagnosis, treatment and referral being introduced in drug shops. The intervention was designed to be evaluated through a cluster randomized trial. In this paper, we present detailed design, implementation and evaluation experiences in order to help inform future studies of a complex nature. Three preparatory studies (formative, baseline and willingness-to-pay) were conducted to explore perceptions on diagnosis and treatment of malaria at drug shops, and affordable prices for mRDTs and ACTs in order to inform the design of the intervention and implementation modalities. The intervention required careful design with the intention to be acceptable, sustainable and effective. Critical components of intervention were: community sensitization and creating awareness, training of drug shop vendors to diagnose malaria with mRDTs, treat and refer customers to formal health facilities, giving pre-referral rectal artesunate and improved record-keeping. The primary outcome was the proportion of patients receiving appropriately-targeted treatment with ACT, evaluated against microscopy on a research blood slide. Introducing mRDTs in drug shops may seem simple, but our experience of intervention design, conduct and evaluation showed this to be a complex process requiring multiple interventions and evaluation components drawing from a combination of epidemiological, social science and health economics methodologies. The trial was conducted in phases sequenced such that each benefited from the other. The main challenges

  1. Acupuncture Antiarrhythmic Effects on Drug Refractory Persistent Atrial Fibrillation: Study Protocol for a Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Jimin Park

    2015-01-01

    Full Text Available Background. Atrial fibrillation (AF is the most common form of arrhythmia. Several trials have suggested that acupuncture may prevent AF. However, the efficacy of acupuncture for AF prevention has not been well investigated. Therefore, we designed a prospective, two-parallel-armed, participant and assessor blinded, randomized, sham-controlled clinical trial to investigate acupuncture in persistent AF (ACU-AF. Methods. A total of 80 participants will be randomly assigned to active acupuncture or sham acupuncture groups in a 1 : 1 ratio. Both groups will take the same antiarrhythmic medication during the study period. Patients will receive 10 sessions of acupuncture treatment once a week for 10 weeks. The primary endpoint is AF recurrence rate. Secondary endpoints are left atrium (LA and left atrial appendage (LAA changes in function and volume, and inflammatory biomarker changes. Ethics. This study protocol was approved by the institutional review boards (IRBs of Kyung Hee University Hospital (number 1335-04. This trial is registered with clinicaltrials.gov NCT02110537.

  2. Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry.

    Science.gov (United States)

    Lee, Joo Myung; Kang, Jeehoon; Lee, Euijae; Hwang, Doyeon; Rhee, Tae-Min; Park, Jonghanne; Kim, Hack-Lyoung; Lee, Sang Eun; Han, Jung-Kyu; Yang, Han-Mo; Park, Kyung Woo; Na, Sang-Hoon; Kang, Hyun-Jae; Koo, Bon-Kwon; Kim, Hyo-Soo

    2016-10-24

    The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited. We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM). A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HR adjust ]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HR adjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HR adjust 2.44; 95% CI: 1.54 to 3.86; HR adjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m 2 . Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HR adjust : 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events. In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All

  3. Description of the Protocols for Randomized Controlled Trials on Cancer Drugs Conducted in Spain (1999–2003)

    Science.gov (United States)

    Bonfill, Xavier; Ballesteros, Mónica; Gich, Ignasi; Serrano, María Antonia; García López, Fernando; Urrútia, Gerard

    2013-01-01

    Objective To describe the characteristics of randomized controlled clinical trials (RCT) on cancer drugs conducted in Spain between 1999 and 2003 based on their protocols. Methods We conducted an observational retrospective cohort study to identify the protocols of RCTs on cancer drugs authorized by the Agencia Española del Medicamento y Productos Sanitarios (AEMPS) (Spanish Agency for Medicines and Medical Devices) during 1999-2003. A descriptive analysis was completed and the association between variables based on the study setting and sponsorship were assessed. Results We identified a total of 303 protocols, which included 176,835 potentially eligible patients. Three-quarter of the studies were internationally-based, 61.7% were phase III, and 76.2% were sponsored by pharmaceutical companies. The most frequently assessed outcomes were response rate (24.7%), overall survival (20.7%), and progression-free survival (14.5%). Of all protocols, 10.6% intended to include more than 1000 patients (mean: 2442, SD: 2724). Compared with their national counterparts, internationally-based studies were significantly larger (p<0.001) and were more likely to implement centralized randomization (p<0.001), blinding of the intervention (p<0.001), and survival as primary outcome (p<0.001). Additionally, most internationally-based studies were sponsored by pharmaceutical companies (p<0.01). In a high percentage of protocols, the available information was not explicit enough to assess the validity of each trial. Compared to other European countries, the proportion of Spanish cancer drugs protocols registered at www.clinicaltrials.gov (7%) was lower. Conclusion RCTs on cancer drugs conducted in Spain between 1999 and 2003 were more likely to be promoted by pharmaceutical companies rather than by non-profit national groups. The former were more often part of international studies, which generally had better methodological quality than national ones. There are some worldwide on

  4. Description of the protocols for randomized controlled trials on cancer drugs conducted in Spain (1999-2003.

    Directory of Open Access Journals (Sweden)

    Xavier Bonfill

    Full Text Available OBJECTIVE: To describe the characteristics of randomized controlled clinical trials (RCT on cancer drugs conducted in Spain between 1999 and 2003 based on their protocols. METHODS: We conducted an observational retrospective cohort study to identify the protocols of RCTs on cancer drugs authorized by the Agencia Española del Medicamento y Productos Sanitarios (AEMPS (Spanish Agency for Medicines and Medical Devices during 1999-2003. A descriptive analysis was completed and the association between variables based on the study setting and sponsorship were assessed. RESULTS: We identified a total of 303 protocols, which included 176,835 potentially eligible patients. Three-quarter of the studies were internationally-based, 61.7% were phase III, and 76.2% were sponsored by pharmaceutical companies. The most frequently assessed outcomes were response rate (24.7%, overall survival (20.7%, and progression-free survival (14.5%. Of all protocols, 10.6% intended to include more than 1000 patients (mean: 2442, SD: 2724. Compared with their national counterparts, internationally-based studies were significantly larger (p<0.001 and were more likely to implement centralized randomization (p<0.001, blinding of the intervention (p<0.001, and survival as primary outcome (p<0.001. Additionally, most internationally-based studies were sponsored by pharmaceutical companies (p<0.01. In a high percentage of protocols, the available information was not explicit enough to assess the validity of each trial. Compared to other European countries, the proportion of Spanish cancer drugs protocols registered at www.clinicaltrials.gov (7% was lower. CONCLUSION: RCTs on cancer drugs conducted in Spain between 1999 and 2003 were more likely to be promoted by pharmaceutical companies rather than by non-profit national groups. The former were more often part of international studies, which generally had better methodological quality than national ones. There are some worldwide

  5. Generation of pharmacophores and classification of drugs using protein-ligand complexes

    Directory of Open Access Journals (Sweden)

    Eliana Velasquez

    2014-04-01

    Full Text Available Pharmacophore identification is a veryimportant step in de novo design, leadoptimization, chemogenomics, and virtualscreening of drugs. Unfortunately,the high cost of comercial software forpharmacophore detection is a commonlimiting factor for researchers with limitedfunding. This paper presents a set offreely available perl routines that weredesigned to help in the process of 3Dpharmacophore identification and QSARstudies. These routines also allowed theclassification of ligands based on theirtridimensional similarity and bindingmechanism. The family of phosphodiesterasesand their inhibitors were used astest model.

  6. Drug-eluting balloon versus bare-mental stent and drug-eluting stent for de novo coronary artery disease: A systematic review and meta-analysis of 14 randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Kongyong Cui

    Full Text Available Drug-eluting balloon (DEB has become an alternative option to drug-eluting stent (DES for the treatment of in-stent restenosis (ISR. However, the effect of drug-eluting balloon with regular bare-mental stent (BMS in de novo coronary artery disease (CAD is unclear. This meta-analysis aimed to evaluate the efficacy of DEB with regular BMS compared to BMS or DES in de novo CAD.Randomized controlled trials (RCTs assessing the efficacy of DEB+BMS in comparison with BMS or DES were obtained by searching the PubMed, EMBASE, and Cochrane Library databases through January 2016. Primary endpoints were major adverse cardiac events (MACEs and late lumen loss (LLL. Secondary endpoints included death, myocardial infarction (MI, target lesion revascularization (TLR, stent thrombosis (ST, binary restenosis, and minimum lumen diameter (MLD. Dichotomous and continuous data were presented as odds ratios (ORs and mean differences (MDs with 95% confidence intervals (CIs, respectively, and analyzed using a random-effects model.A total of 14 RCTs involving 2281 patients were included in this meta-analysis. DEB+BMS showed significantly less MACEs (OR: 0.67, 95%CI 0.45 to 0.99, P = 0.04 and reduced LLL (MD: -0.30 mm, 95%CI: -0.48 mm to -0.11 mm, P = 0.001 compared with BMS. Meanwhile, treatment with DEB+BMS had disadvantages over DES in terms of MACEs (OR: 1.94, 95%CI 1.24 to 3.05, P = 0.004, LLL (MD: 0.20 mm, 95%CI: 0.07 mm to 0.33 mm, P = 0.003, TLR (OR: 2.53, 95% CI 1.36 to 4.72, P = 0.003, and MLD (MD: -0.25 mm, 95%CI: -0.42 mm to -0.09 mm, P = 0.003.This limited evidence demonstrated that treatment with DEB+BMS appears to be effective in de novo CAD. In addition, DEB+ BMS clearly showed superiority to BMS, but is inferior to DES in the treatment of patients with de novo CAD. Hence, DES (especially new generation DES should be recommended for patients with de novo CAD.

  7. Homogeneous generation of iDA neurons with high similarity to bona fide DA neurons using a drug inducible system.

    Science.gov (United States)

    Park, Hanseul; Kim, Hongwon; Yoo, Junsang; Lee, Jaekwang; Choi, Hwan; Baek, Soonbong; Lee, C Justin; Kim, Janghwan; Lengner, Christopher J; Sung, Jung-Suk; Kim, Jongpil

    2015-12-01

    Recent work generating induced dopaminergic (iDA) neurons using direct lineage reprogramming potentially provides a novel platform for the study and treatment Parkinson's disease (PD). However, one of the most important issues for iDA-based applications is the degree to which iDA neurons resemble the molecular and functional properties of their endogenous DA neuron counterparts. Here we report that the homogeneity of the reprogramming gene expression system is critical for the generation of iDA neuron cultures that are highly similar to endogenous DA neurons. We employed an inducible system that carries iDA-inducing factors as defined transgenes for direct lineage reprogramming to iDA neurons. This system circumvents the need for viral transduction, enabling a more efficient and reproducible reprogramming process for the generation of genetically homogenous iDA neurons. We showed that this inducible system generates iDA neurons with high similarity to their bona fide in vivo counterparts in comparison to direct infection methods. Thus, our results suggest that homogenous expression of exogenous genes in direct lineage reprogramming is critical for the generation of high quality iDA neuron cultures, making such culture systems a valuable resource for iDA-based drug screening and, ultimately, potential therapeutic intervention in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Cromoglycate drugs suppress eicosanoid generation in U937 cells by promoting the release of Anx-A1

    Science.gov (United States)

    Yazid, Samia; Solito, Egle; Christian, Helen; McArthur, Simon; Goulding, Nicolas; Flower, Roderick

    2009-01-01

    Using biochemical, epifluorescence and electron microscopic techniques in a U937 model system, we investigated the effect of anti-allergic drugs di-sodium cromoglycate and sodium nedocromil on the trafficking and release of the anti-inflammatory protein Annexin-A1 (Anx-A1) when this was triggered by glucocorticoid (GC) treatment. GCs alone produced a rapid (within 5 min) concentration-dependent activation of PKCα/β (Protein Kinase C; EC 2.7.11.13) and phosphorylation of Anx-A1 on Ser27. Both phosphoproteins accumulated at the plasma membrane and Anx-A1 was subsequently externalised thereby inhibiting thromboxane (Tx) B2 generation. When administered alone, cromoglycate or nedocromil had little effect on this pathway however, in the presence of a fixed sub-maximal concentration of GCs, increasing amounts of the cromoglycate-like drugs caused a striking concentration-dependent enhancement of Anx-A1 and PKCα/β phosphorylation, membrane recruitment and Anx-A1 release from cells resulting in greatly enhanced inhibition of TxB2 generation. GCs also stimulated phosphatase accumulation at the plasma membrane of U937 cells. Both cromoglycate and nedocromil inhibited this enzymatic activity as well as that of a highly purified PP2A phosphatase preparation. We conclude that stimulation by the cromoglycate-like drugs of intracellular Anx-A1 trafficking and release (hence inhibition of eicosanoid release) is secondary to inhibition of a phosphatase PP2A (phosphoprotein phosphatase; EC 3.1.3.16), which probably forms part of a control loop to limit Anx-A1 release. These experiments provide a basis for a novel mechanism of action for the cromolyns, a group of drugs that have long puzzled investigators. PMID:19428336

  9. Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Gøtzsche, P C; Hansen, M; Stoltenberg, M

    1996-01-01

    Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe...... between the observers' evaluations of the joints. The effect of slow-acting antirheumatic drugs was unequivocal and no observer bias occurred....... received placebo (p = 0.000,001). There was no difference in the severity of side effects (p = 0.91). The patients guessed their treatment correctly more often than expected (p = 0.02) because of the perceived effect. None of the two observers guessed better than chance, and there were no differences...

  10. Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Gøtzsche, P C; Hansen, M; Stoltenberg, M

    1996-01-01

    Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe...... disease than the others. The patients felt worse on placebo than on active drug (p = 0.002). The mean differences in number of tender, painful and swollen joints after one month were 2.4 (p = 0.08), 3.0 (p = 0.12) and 2.2 (p = 0.03), respectively. Treatment failure occurred for 42 patients of whom 33...... received placebo (p = 0.000,001). There was no difference in the severity of side effects (p = 0.91). The patients guessed their treatment correctly more often than expected (p = 0.02) because of the perceived effect. None of the two observers guessed better than chance, and there were no differences...

  11. Effects of interactive patient smartphone support app on drug adherence and lifestyle changes in myocardial infarction patients: A randomized study.

    Science.gov (United States)

    Johnston, Nina; Bodegard, Johan; Jerström, Susanna; Åkesson, Johanna; Brorsson, Hilja; Alfredsson, Joakim; Albertsson, Per A; Karlsson, Jan-Erik; Varenhorst, Christoph

    2016-08-01

    Patients with myocardial infarction (MI) seldom reach recommended targets for secondary prevention. This study evaluated a smartphone application ("app") aimed at improving treatment adherence and cardiovascular lifestyle in MI patients. Multicenter, randomized trial. A total of 174 ticagrelor-treated MI patients were randomized to either an interactive patient support tool (active group) or a simplified tool (control group) in addition to usual post-MI care. Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence, defined as a combination of adherence failure events (2 missed doses registered in 7-day cycles) and treatment gaps (4 consecutive missed doses). Secondary end points included change in cardiovascular risk factors, quality of life (European Quality of Life-5 Dimensions), and patient device satisfaction (System Usability Scale). Patient mean age was 58 years, 81% were men, and 21% were current smokers. At 6 months, greater patient-registered drug adherence was achieved in the active vs the control group (nonadherence score: 16.6 vs 22.8 [P = .025]). Numerically, the active group was associated with higher degree of smoking cessation, increased physical activity, and change in quality of life; however, this did not reach statistical significance. Patient satisfaction was significantly higher in the active vs the control group (system usability score: 87.3 vs 78.1 [P = .001]). In MI patients, use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life. Use of a disease-specific interactive patient support tool may be an appreciated, simple, and promising complement to standard secondary prevention. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment

    DEFF Research Database (Denmark)

    Sjo, Christina Power; Stenstrøm, Anne Dorte; Bojesen, Anders Bo

    2017-01-01

    OBJECTIVES: Mental illness is often accompanied by poor physical health and shorter life expectancy. Second-generation antipsychotics (SGAs) are suspected of increasing cardiovascular risk, possibly through development of metabolic syndrome (MetS), and the risk of adverse outcome is even higher...... if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG...

  13. A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the "DAPT-STEMI trial".

    Science.gov (United States)

    Kedhi, Elvin; Fabris, Enrico; van der Ent, Martin; Kennedy, Mark W; Buszman, Pawel; von Birgelen, Clemens; Cook, Stéphane; Wedel, Hans; Zijlstra, Felix

    2017-06-01

    The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. In vitro bactericidal activity of aminoglycosides, including the next-generation drug plazomicin, against Brucella spp.

    Science.gov (United States)

    Plazomicin is a next-generation aminoglycoside with a potentially improved safety profile compared to other aminoglycosides. This study assessed plazomicin MICs and MBCs in four Brucella spp. reference strains. Like other aminoglycosides and aminocyclitols, plazomicin MBC values equaled MIC values ...

  15. Cross-generational transmission from drug abuse in parents to attention-deficit/hyperactivity disorder in children.

    Science.gov (United States)

    Kendler, K S; Ohlsson, H; Sundquist, K; Sundquist, J

    2016-04-01

    Attention-deficit/hyperactivity disorder (ADHD) predisposes to drug abuse (DA) and twin studies suggest shared genetic effects. We here seek to determine, using adoption and adoption-like samples, the magnitude of the cross-generational transmission from DA in parents to ADHD in their children and clarify the degree to which this arises from genetic v. rearing effects. We ascertained ADHD and DA from multiple Swedish registries. Statistical analysis was performed by Cox and path models. Risk for ADHD was significantly and similarly increased in the offspring of biological mothers and fathers with DA who did v. did not rear their offspring. Risk for ADHD was not elevated in the offspring of adoptive or step-parents with DA. Cross-generational transmission was observed from DA in parents to ADHD in their children. An analysis of adoptive and adoptive-like parent-offspring relationships suggested that this transmission results from genetic and not from rearing effects.

  16. Assessment of abuse liability of Tramadol among experienced drug users: Double-blind crossover randomized controlled trial.

    Science.gov (United States)

    Das, Mrinmay; Jain, Raka; Dhawan, Anju; Kaur, Amandeep

    Tramadol is a widely used opioid analgesic. Different preclinical, clinical, and postmarketing surveillance studies show conflicting results regarding abuse potential of this drug. A randomized double-blind complete crossover study was conducted at National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi. Total subjects were 10, comprising total 120 observations (each subject assessed at baseline, 5, 45, and 240 minutes). Subjects with history of substance abuse were included after detoxification and informed consent. Assessment was done using modified single dose opiate questionnaire, morphine benzedrine group (MBG), pentobarbital chlorpromazine alcohol group (PCAG), and two bipolar visual analogue scales (VAS) after administration of three drugs-Tramadol (100 mg), Buprenorphine (0.6 mg), and Placebo (Normal Saline) intramuscularly, at 5-day interval. In intra-group analysis, there was statistically significant increase in scores of all four scales from baseline to all three time points after Tramadol and Buprenorphine administration. In inter-group analysis, statistically higher scores were seen for Buprenorphine in comparison to Tramadol at 5, 45, and 240 minutes for MBG scale; the score was significantly higher for Buprenorphine in VAS for pleasurable effect at 45 and 240 minutes, but not at baseline and 5 minutes. There was no significant difference in score at any point of time between Tramadol and Buprenorphine in PCAG scale and VAS for sedative/alertness effect. The scores were statistically insignificant in case of Placebo. All the subjects liked Buprenorphine most and then Tramadol followed by Placebo. Tramadol has abuse potential (even in therapeutic doses) more than Placebo but less than or comparable to Buprenorphine.

  17. Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Martin Boegsted

    Full Text Available BACKGROUND: Recent reports indicate that in vitro drug screens combined with gene expression profiles (GEP of cancer cell lines may generate informative signatures predicting the clinical outcome of chemotherapy. In multiple myeloma (MM a range of new drugs have been introduced and now challenge conventional therapy including high dose melphalan. Consequently, the generation of predictive signatures for response to melphalan may have a clinical impact. The hypothesis is that melphalan screens and GEPs of B-cell cancer cell lines combined with multivariate statistics may provide predictive clinical information. MATERIALS AND METHODS: Microarray based GEPs and a melphalan growth inhibition screen of 59 cancer cell lines were downloaded from the National Cancer Institute database. Equivalent data were generated for 18 B-cell cancer cell lines. Linear discriminant analyses (LDA, sparse partial least squares (SPLS and pairwise comparisons of cell line data were used to build resistance signatures from both cell line panels. A melphalan resistance index was defined and estimated for each MM patient in a publicly available clinical data set and evaluated retrospectively by Cox proportional hazards and Kaplan-Meier survival analysis. PRINCIPAL FINDINGS: Both cell line panels performed well with respect to internal validation of the SPLS approach but only the B-cell panel was able to predict a significantly higher risk of relapse and death with increasing resistance index in the clinical data sets. The most sensitive and resistant cell lines, MOLP-2 and RPMI-8226 LR5, respectively, had high leverage, which suggests their differentially expressed genes to possess important predictive value. CONCLUSION: The present study presents a melphalan resistance index generated by analysis of a B-cell panel of cancer cell lines. However, the resistance index needs to be functionally validated and correlated to known MM biomarkers in independent data sets in order to

  18. Next generation drug-eluting stents: focus on bioabsorbable platforms and polymers

    Directory of Open Access Journals (Sweden)

    Brendan Doyle

    2009-11-01

    Full Text Available Brendan Doyle, David R Holmes JrDivision of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USAAbstract: The success of drug-eluting stents in preventing restenosis has shifted the focus of new stent development toward enhancing long term safety and efficacy of these devices, while simultaneously eliminating the need for indefinite dual antiplatelet therapy. A technical advance fulfilling these aims would hold tremendous potential to reduce morbidity, mortality and economic costs associated with the percutaneous treatment of coronary artery disease. An attractive approach is the use of bioabsorbable stent designs. These may include stents with different bioabsorbable drugs, bioabsorbable polymers or even bioabsorbable metallic backbones. A device that could achieve excellent acute and long-term results, but disappear completely within months (thereby avoiding the need for prolonged dual antiplatelet therapy, would be a tremendous advance. Too good to be true? We explore here the scientific rationale and prospects for success with this exciting concept.Keywords: percutaneous coronary intervention, biodegradable, bioabsorbable, polymer, stent

  19. Next-generation ion torrent sequencing of drug resistance mutations in Mycobacterium tuberculosis strains.

    Science.gov (United States)

    Daum, Luke T; Rodriguez, John D; Worthy, Sue A; Ismail, Nazir A; Omar, Shaheed V; Dreyer, Andries W; Fourie, P Bernard; Hoosen, Anwar A; Chambers, James P; Fischer, Gerald W

    2012-12-01

    A novel protocol for full-length Mycobacterium tuberculosis gene analysis of first- and second-line drug resistance was developed using the Ion Torrent Personal Genome Machine (PGM). Five genes-rpoB (rifampin), katG (isoniazid), pncA (pyrazinamide), gyrA (ofloxacin/fluoroquinolone), and rrs (aminoglycosides)-were amplified and sequenced, and results were compared to those obtained by genotypic Hain line probe assay (LPA) and phenotypic Bactec MGIT 960 analysis using 26 geographically diverse South African clinical isolates collected between July and November 2011. Ion Torrent sequencing exhibited 100% (26/26) concordance to phenotypic resistance obtained by MGIT 960 culture and genotypic rpoB and katG results by LPA. In several rifampin-resistant isolates, Ion Torrent sequencing revealed uncommon substitutions (H526R and D516G) that did not have a defined mutation by LPA. Importantly, previously uncharacterized mutations in rpoB (V194I), rrs (G878A), and pncA (Q122Stop) genes were observed. Ion Torrent sequencing may facilitate tracking and monitoring geographically diverse multidrug-resistant and extensively drug-resistant strains and could potentially be integrated into selected regional and reference settings throughout Africa, India, and China.

  20. Benefits of Reiki therapy for a severely neutropenic patient with associated influences on a true random number generator.

    Science.gov (United States)

    Morse, Melvin L; Beem, Lance W

    2011-12-01

    Reiki therapy is documented for relief of pain and stress. Energetic healing has been documented to alter biologic markers of illness such as hematocrit. True random number generators are reported to be affected by energy healers and spiritually oriented conscious awareness. The patient was a then 54-year-old severely ill man who had hepatitis C types 1 and 2 and who did not improve with conventional therapy. He also suffered from obesity, the metabolic syndrome, asthma, and hypertension. He was treated with experimental high-dose interferon/riboviron therapy with resultant profound anemia and neutropenia. Energetic healing and Reiki therapy was administered initially to enhance the patient's sense of well-being and to relieve anxiety. Possible effects on the patient's absolute neutrophil count and hematocrit were incidentally noted. Reiki therapy was then initiated at times of profound neutropenia to assess its possible effect on the patient's absolute neutrophil count (ANC). Reiki and other energetic healing sessions were monitored with a true random number generator (RNG). Statistically significant relationships were documented between Reiki therapy, a quieting of the electronically created white noise of the RNG during healing sessions, and improvement in the patient's ANC. The immediate clinical result was that the patient could tolerate the high-dose interferon regimen without missing doses because of absolute neutropenia. The patient was initially a late responder to interferon and had been given a 5% chance of clearing the virus. He remains clear of the virus 1 year after treatment. The association between changes in the RNG, Reiki therapy, and a patient's ANC is the first to the authors' knowledge in the medical literature. Future studies assessing the effects of energetic healing on specific biologic markers of disease are anticipated. Concurrent use of a true RNG may prove to correlate with the effectiveness of energetic therapy.

  1. A time-series approach to random number generation: Using recurrence quantification analysis to capture executive behavior

    Directory of Open Access Journals (Sweden)

    Wouter eOomens

    2015-06-01

    Full Text Available The concept of executive functions plays a prominent role in contemporary experimental and clinical studies on cognition. One paradigm used in this framework is the random number generation (RNG task, the execution of which demands aspects of executive functioning, specifically inhibition and working memory. Data from the RNG task are best seen as a series of successive events. However, traditional RNG measures that are used to quantify executive functioning are mostly summary statistics referring to deviations from mathematical randomness. In the current study, we explore the utility of recurrence quantification analysis (RQA, a nonlinear method that keeps the entire sequence intact, as a better way to describe executive functioning compared to traditional measures. To this aim, 242 first- and second-year students completed a non-paced RNG task. Principal component analysis of their data showed that traditional and RQA measures convey more or less the same information. However, RQA measures do so more parsimoniously and have a better interpretation.

  2. Safety concerns and hidden agenda behind HPV vaccines: another generation of drug-dependent society?

    OpenAIRE

    Khatami, Mahin

    2016-01-01

    Analyses of data and hidden agenda behind repeated failed outcomes of cancer research and therapy, status of American health, safety concerns for HPV vaccines and future research considerations are summarized in this commentary. A closer look at cancer science reveals that highly power structure (system) in medical establishment vs. anti-system and chaos in cancer research (?medical/scientific ponzi schemes?) is potent recipe for failed therapeutics that kills patients but generates huge corp...

  3. Last generation of amino-bisphosphonates (N-BPs) and cancer angio-genesis: a new role for these drugs?

    Science.gov (United States)

    Santini, Daniele; Schiavon, Gaia; Angeletti, Silvia; Vincenzi, Bruno; Gasparro, Simona; Grilli, Claudia; La Cesa, Annalisa; Virzí, Vladimir; Leoni, Valentina; Budillon, Alfredo; Addeo, Santolo R; Caraglia, Michele; Dicuonzo, Giordano; Tonini, Giuseppe

    2006-11-01

    Bisphosphonate (BPs) therapy has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that BPs exert their direct or indirect antitumoral effects on cancer growth factor release, on cancer cell adhesion, invasion and viability, on cancer angiogenesis and on cancer cell apoptosis. Here, after a brief analysis on clinical indications, on the last generation amino-bisphosphonates (N-BP) and on biochemical pathways as molecular targets of BPs, we will discuss the molecular mechanisms of these antitumor effects. Recent evidence suggests that part of the antitumor activity of bisphosphonates may be attributed to an antiangiogenic effect. For this reason, we will analyse all the in vitro and in vivo preclinical reports and the first clinical evidence of anti-angiogenic activity exerted by this class of drugs. Several patents have been reported in the review, considering the recents activities observed for these drugs. Taking together all the major results obtained in the described studies, it is possible to affirm that BPs, particularly zoledronic acid and pamidronate, could potentially represent a very powerful tool for angiogenesis inhibition leading to a better control of cancer growth and progression. The translation into the clinical setting of the preclinical evidence of an antiangiogenic power of these drugs is becoming an imperative need and should represent the objective of future clinical trials.

  4. Rapid generation of drug-resistance alleles at endogenous loci using CRISPR-Cas9 indel mutagenesis.

    Directory of Open Access Journals (Sweden)

    Jonathan J Ipsaro

    Full Text Available Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors. We used this approach to identify novel resistance alleles of two lysine methyltransferases, DOT1L and EZH2, which are each essential for the growth of MLL-fusion leukemia cells. We biochemically characterized the DOT1L mutation, showing that it is significantly more active than the wild-type enzyme. These findings validate the on-target anti-leukemia activities of existing DOT1L and EZH2 inhibitors and reveal a simple method for deriving drug-resistance alleles for novel targets, which may have utility during early stages of drug development.

  5. Next generation sequencing for profiling expression of miRNAs: technical progress and applications in drug development.

    Science.gov (United States)

    Liu, Jie; Jennings, Steven F; Tong, Weida; Hong, Huixiao

    2011-10-01

    miRNAs are non-coding RNAs that play a regulatory role in expression of genes and are associated with diseases. Quantitatively measuring expression levels of miRNAs can help in understanding the mechanisms of human diseases and discovering new drug targets. There are three major methods that have been used to measure the expression levels of miRNAs: real-time reverse transcription PCR (qRT-PCR), microarray, and the newly introduced next-generation sequencing (NGS). NGS is not only suitable for profiling of known miRNAs as qRT-PCR and microarray can do too but it also is able to detect unknown miRNAs which the other two methods are incapable of doing. Profiling of miRNAs by NGS has progressed rapidly and is a promising field for applications in drug development. This paper reviews the technical advancement of NGS for profiling miRNAs, including comparative analyses between different platforms and software packages for analyzing NGS data. Examples and future perspectives of applications of NGS profiling miRNAs in drug development will be discussed.

  6. Social cognition and visual perception in schizophrenia inpatients treated with first-and second-generation antipsychotic drugs.

    Science.gov (United States)

    Kucharska-Pietura, Katarzyna; Mortimer, Ann; Tylec, Aneta; Czernikiewicz, Andrzej

    2012-04-01

    Social cognition captures affect recognition, social cue perception, "theory of mind," empathy, and attributional style. The aim of our study was to assess social cognition in schizophrenia inpatients being treated with first-generation antipsychotic drugs (FGAs), n=28 (perphenazine and haloperidol, FGAs) or with second-generation antipsychotic drugs (SGAs), n=56 (olanzapine and clozapine, SGAs). Eighty-four patients completed the Facial Expression Recognition Test, the Voice Emotion Recognition Test, the Short Recognition Memory Test for Faces, and the Reading the Mind in the Eyes Test. Patients also completed the Visual Object and Space Perception Test (VOSP) as a control task, which would not engage social cognition. The patients were compared with fifty healthy controls matched for age and gender. There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups. Nor was olanzapine superior to clozapine, FGAs or both. However, patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs, a 10% difference. We cannot conclude that SGAs were associated with better social cognition than FGAs. However, there were small but significant advantages for SGAs in non-social visual processing function, as evaluated with the VOSP.

  7. Specificity and sensitivity of 3rd generation EIA for detection of HCV antibodies among intravenous drug-users.

    Science.gov (United States)

    Filice, G; Patruno, S; Campisi, D; Chiesa, A; Orsolini, P; Debiaggi, M; Bruno, R; Tinelli, M

    1993-01-01

    Serum samples from 487 ambulatory I.V. drug users were screened for HIV and HCV antibodies to determine the prevalence of coinfection in this high risk group for AIDS. For anti-HCV antibody screening we first used a 3rd generation EIA using, as antigen synthetic peptides which were not subjected to false positive results due to antibodies against superoxide dismutase or against yeast proteins (which may copurify with the recombinant proteins employed in the first and second generation test). The specimens that were positive in the screening test were confirmed by a more specific EIA system that detect antibodies to proteins encoded by structural (HCV-st EIA) and non structural (HCV-nst-EIA) regions of the HCV genome. A second confirmation assay was also performed: sera were run in presence or absence of blocking reagents which inhibits antibodies to C200 and C22 HCV epitopes for binding to the solid phase. The sensitivity of the HCV EIA screening for human HCV antibody detection revealed a 100% positivity for HCV infection. The confirmatory strategy presented in this paper revealed an HCV EIA specificity of 98.6%. In this work we demonstrated a significantly higher prevalence (p HIV infected individuals compared to the general population. Our experimental data also confirmed that HBV infection in drug-users at high risk for HIV infection was significantly associated with HCV infection (p HIV by sexual contact was not a statistically significant risk factor for HCV coinfection.

  8. Virtual population generator for human cardiomyocytes parameters: in silico drug cardiotoxicity assessment.

    Science.gov (United States)

    Polak, Sebastian; Fijorek, Kamil; Glinka, Anna; Wisniowska, Barbara; Mendyk, Aleksander

    2012-01-01

    The anatomical and histological parameters of the human ventricle depend on many factors including age and sex. Myocyte volume and electric capacitance are significant physiological parameters of left ventricle cardiomyocyte mathematical models. They allow the assessment of inter-individual variability during in vitro-in vivo extrapolation of the drug cardiotoxic effect. The current research was carried out to analyze the relationship between age, human left ventricle cardiomyocyte volume, and electric capacitance in a healthy population. In order to collect data describing cardiomyocyte volume and membrane area, literature searches were performed. It was assumed that the cardiomyocyte volume (VOL) and area (AREA) distribution have non-negative support and are skewed to the right. A log-linear model with constant variance was used. A simulation study was run to assess the influence of physiological parameters on action potential duration. The coefficient of determination for the proposed model R(2) = 0.95, that is, 95% of the variability observed in log cardiomyocyte volume can be explained by the estimated regression equation. To allow simple calculation and model performance validation, a simple Excel file was developed (Supplementary material). To the best of our knowledge, there is no other model available, combining age, cardiomyocyte volume, and area. The main limitations of the proposed models result from the assumptions made at the data analysis stage. The limited amount of information available in the literature and the lack of differentiation between sexes results in one common equation. The developed model is a part of the computational system for drug cardiotoxicity assessment.

  9. Modified-Release Formulations of Second-Generation Antiepileptic Drugs: Pharmacokinetic and Clinical Aspects.

    Science.gov (United States)

    Anderson, Gail D; Saneto, Russell P

    2015-08-01

    Modified-release or extended-release (XR) formulations are used to decrease the frequency of dosing for drugs with rapid elimination, to improve convenience and adherence. Use of a modified-release formulation can decrease the peak to trough fluctuations in serum concentrations and theoretically improve the therapeutic benefit of the drug, by decreasing adverse events associated with the higher peak concentrations. Once-daily formulations of lamotrigine (Lamictal XR(®)), levetiracetam (Keppra XR(®)), oxcarbazepine (Oxtellar XR(®), Apydan(®) extent) and topiramate (Qudexy XR™, Trokendi XR™) are approved for the treatment of focal and/or generalized onset seizures. Other seizure medications have been approved for non-epileptic symptoms. Gabapentin XR (Gralise(®)) is approved for the treatment of post-herpetic neuralgias. Gabapentin enacarbil XR (Horizant(®)) is a prodrug of gabapentin and is indicated for treatment of post-herpetic neuralgia and restless leg syndrome, a novel indication. For all but Qudexy XR™, the tablets/capsules must be swallowed whole, without cutting, crushing or chewing, in order to maintain the XR properties of the formulation. Qudexy XR™ can be swallowed intact or the capsules can be opened and sprinkled onto soft food for those with swallowing difficulties, for example, children and the elderly. The bioavailability of Gralise(®) and Horizant(®) is significantly affected by food, specifically fat content, and should be taken with a meal to maximize absorption. Overall, the primary advantage of the newly released XR formulations is the once-daily dosing to improve convenience and adherence, with very limited data suggesting improved tolerability.

  10. 6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial.

    Science.gov (United States)

    Gilard, Martine; Barragan, Paul; Noryani, Arif A L; Noor, Hussam A; Majwal, Talib; Hovasse, Thomas; Castellant, Philippe; Schneeberger, Michel; Maillard, Luc; Bressolette, Erwan; Wojcik, Jaroslaw; Delarche, Nicolas; Blanchard, Didier; Jouve, Bernard; Ormezzano, Olivier; Paganelli, Franck; Levy, Gilles; Sainsous, Joël; Carrie, Didier; Furber, Alain; Berland, Jacques; Darremont, Oliver; Le Breton, Hervé; Lyuycx-Bore, Anne; Gommeaux, Antoine; Cassat, Claude; Kermarrec, Alain; Cazaux, Pierre; Druelles, Philippe; Dauphin, Raphael; Armengaud, Jean; Dupouy, Patrick; Champagnac, Didier; Ohlmann, Patrick; Endresen, Knut; Benamer, Hakim; Kiss, Robert Gabor; Ungi, Imre; Boschat, Jacques; Morice, Marie-Claude

    2015-03-03

    The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS). This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients. A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting. A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]). Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Second harmonic generation in gallium phosphide microdisks on silicon: from strict \\bar{4} to random quasi-phase matching

    Science.gov (United States)

    Guillemé, P.; Dumeige, Y.; Stodolna, J.; Vallet, M.; Rohel, T.; Létoublon, A.; Cornet, C.; Ponchet, A.; Durand, O.; Léger, Y.

    2017-06-01

    The convergence of nonlinear optical devices and silicon photonics is a key milestone for the practical development of photonic integrated circuits. The associated technological issues often stem from material incompatibility. This is the case of second order nonlinear processes in monolithically integrated III-V semiconductor devices on silicon, where structural defects called antiphase domains strongly impact the optical properties of the material. We theoretically investigate the influence of antiphase domains on second harmonic generation in III-V whispering gallery mode microresonators on silicon and focus on the effects of the antiphase domains’ mean size (i.e. the correlation length of the distribution). We demonstrate that the domain distributions can have opposite effects depending on the nonlinear process under consideration: while antiphase domains negatively impact second harmonic generation under \\bar{4} quasi-phase matching conditions (independent of the correlation length), large conversion efficiencies can arise far from \\bar{4}-quasi-phase matching provided that the APD correlation length remains within an appropriate range, and is still compatible with the spontaneous emergence of such defects in the usual III-V on Si epilayers. Such a build-up can be explained by the occurrence of random quasi-phase matching in the system.

  12. Effect of Chronic Kidney Disease in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: A Patient-Level Pooled Analysis of Randomized Controlled Trials

    NARCIS (Netherlands)

    Baber, Usman; Giustino, Gennaro; Sartori, Samantha; Aquino, Melissa; Stefanini, Giulio G.; Steg, Gabriel; Windecker, Stephan; Leon, Martin B.; Wijns, William; Serruys, Patrick W.; Valgimigli, Marco; Stone, Gregg W.; Dangas, George D.; Morice, Marie-Claude; Camenzind, Edoardo; Weisz, Giora; Smits, Pieter C.; Kandzari, David E.; von Birgelen, Clemens; Mastoris, Ioannis; Galatius, Soren; Jeger, Raban V.; Kimura, Takeshi; Mikhail, Ghada W.; Itchhaporia, Dipti; Mehta, Laxmi; Ortega, Rebecca; Kim, Hyo-Soo; Kastrati, Adnan; Chieffo, Alaide; Mehran, Roxana

    2016-01-01

    Objectives This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women

  13. Can Online Consumers Contribute to Drug Knowledge? A Mixed-Methods Comparison of Consumer-Generated and Professionally Controlled Psychotropic Medication Information on the Internet

    Science.gov (United States)

    Cohen, David

    2011-01-01

    Background Ongoing initiatives to filter online health searches exclude consumer-generated content from search returns, though its inferiority compared with professionally controlled content is not demonstrated. The antidepressant escitalopram and the antipsychotic quetiapine have ranked over the last 5 years as top-selling agents in their respective drug classes. Both drugs have various off-label mental health and non–mental health uses, ranging from the relief of insomnia and migraines to the treatment of severe developmental disorders. Objective Our objective was to describe the most frequently reported effects of escitalopram and quetiapine in online consumer reviews, to compare them with effects described in professionally controlled commercial health websites, and to gauge the usability of online consumer medication reviews. Methods A stratified simple random sample of 960 consumer reviews was selected from all 6998 consumer reviews of the two drugs in 2 consumer-generated (www.askapatient.com and www.crazymeds.us) and 2 professionally controlled (www.webmd.com and www.revolutionhealth.com) health websites. Professional medication descriptions included all standard information on the medications from the latter 2 websites. All textual data were inductively coded for medication effects, and intercoder agreement was assessed. Chi-square was used to test for associations between consumer-reported effects and website origination. Results Consumers taking either escitalopram (n = 480) or quetiapine (n = 480) most frequently reported symptom improvement (30.4% or 146/480, 24.8% or 119/480) or symptom worsening (15.8% or 76/480, 10.2% or 49/480), changes in sleep (36% or 173/480, 60.6% or 291/480) and changes in weight and appetite (22.5% or 108/480, 30.8% or 148/480). More consumers posting reviews on consumer-generated rather than professionally controlled websites reported symptom worsening on quetiapine (17.3% or 38/220 versus 5% or 11/220, P consumers posting

  14. Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial.

    Science.gov (United States)

    Stingl, Julia Carolin; Kaumanns, Katharina Luise; Claus, Katrin; Lehmann, Marie-Louise; Kastenmüller, Kathrin; Bleckwenn, Markus; Hartmann, Gunther; Steffens, Michael; Wirtz, Dorothee; Leuchs, Ann-Kristin; Benda, Norbert; Meier, Florian; Schöffski, Oliver; Holdenrieder, Stefan; Coch, Christoph; Weckbecker, Klaus

    2016-04-26

    Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects. The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk "index drugs" oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients' adherence to medication regimen as well as health related quality of life

  15. The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

    Science.gov (United States)

    Eldin, Essam Eldin Mohamed Nour; Elshebiny, Hosam Abdel-Fattah; Mohamed, Tarek Mostafa; Abdel-Aziz, Mohamed Abdel-Azim; El-Readi, Mahmoud Zaki

    2016-01-01

    Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

  16. First-generation versus second-generation drug-eluting stents in current clinical practice: updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients

    NARCIS (Netherlands)

    Navarese, E.P.; Kowalewski, M.; Kandzari, D.; Lansky, A.; Gorny, B.; Koltowski, L.; Waksman, R.; Berti, S.; Musumeci, G.; Limbruno, U.; Schaaf, R.J. van der; Kelm, M.; Kubica, J.; Suryapranata, H.

    2014-01-01

    BACKGROUND: First-generation drug-eluting stents (DES) have become the most widely used devices worldwide for management of coronary artery disease. As remote follow-up data were becoming available, concerns emerged in regard to their long-term safety. Second-generation DES were designed to overcome

  17. An empirical test of pseudo random number generators by means of an exponential decaying process; Una prueba empirica de generadores de numeros pseudoaleatorios mediante un proceso de decaimiento exponencial

    Energy Technology Data Exchange (ETDEWEB)

    Coronel B, H.F.; Hernandez M, A.R.; Jimenez M, M.A. [Facultad de Fisica e Inteligencia Artificial, Universidad Veracruzana, A.P. 475, Xalapa, Veracruz (Mexico); Mora F, L.E. [CIMAT, A.P. 402, 36000 Guanajuato (Mexico)]. e-mail: hcoronel@uv.mx

    2007-07-01

    Empirical tests for pseudo random number generators based on the use of processes or physical models have been successfully used and are considered as complementary to theoretical tests of randomness. In this work a statistical methodology for evaluating the quality of pseudo random number generators is presented. The method is illustrated in the context of the so-called exponential decay process, using some pseudo random number generators commonly used in physics. (Author)

  18. Expecting innovation: psychoactive drug primes and the generation of creative solutions.

    Science.gov (United States)

    Hicks, Joshua A; Pedersen, Sarah L; Pederson, Sarah L; Friedman, Ronald S; McCarthy, Denis M

    2011-08-01

    Many individuals expect that alcohol and drug consumption will enhance creativity. The present studies tested whether substance related primes would influence creative performance for individuals who possessed creativity-related substance expectancies. Participants (n = 566) were briefly exposed to stimuli related to psychoactive substances (alcohol, for Study 1, Sample 1, and Study 2; and marijuana, for Study 1, Sample 2) or neutral stimuli. Participants in Study 1 then completed a creative problem-solving task, while participants in Study 2 completed a divergent thinking task or a task unrelated to creative problem solving. The results of Study 1 revealed that exposure to the experimental stimuli enhanced performance on the creative problem-solving task for those who expected the corresponding substance would trigger creative functioning. In a conceptual replication, Study 2 showed that participants exposed to alcohol cues performed better on a divergent thinking task if they expected alcohol to enhance creativity. It is important to note that this same interaction did not influence performance on measures unrelated to creative problem solving, suggesting that the activation of creativity-related expectancies influenced creative performance, specifically. These findings highlight the importance of assessing expectancies when examining pharmacological effects of alcohol and marijuana. Future directions and implications for substance-related interventions are discussed. (c) 2011 APA, all rights reserved.

  19. Creating novel activated factor XI inhibitors through fragment based lead generation and structure aided drug design.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Activated factor XI (FXIa inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1'-S2' FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1'-S2' binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1'-S2' binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.

  20. The Effectiveness of Family Interventions in Preventing Adolescent Illicit Drug Use: A Systematic Review and Meta-analysis of Randomized Controlled Trials

    NARCIS (Netherlands)

    Smit, E.; Verdurmen, J.E.E.; Engels, R.C.M.E.

    2015-01-01

    In order to quantify the effectiveness of family interventions in preventing and reducing adolescent illicit drug use, we conducted a systematic review and meta-analysis of randomized controlled trials. We searched the Cochrane Database of Systematic Reviews, Educational Research Information Centre

  1. WWC Quick Review of the Article "Outcomes of a Prospective Trial of Student-Athlete Drug Testing: The Student Athlete Testing Using Random Notification ('SATURN') Study"

    Science.gov (United States)

    What Works Clearinghouse, 2008

    2008-01-01

    This study examines whether the Student Athlete Testing Using Random Notification ("SATURN") program affects illicit drug and alcohol use among student athletes. The study experienced high rates of sample attrition. Seven of the 18 study schools (39%) left the study and were not included in the analysis. Some students at the remaining…

  2. Intimal disruption affects drug-eluting cobalt-chromium stent expansion: A randomized trial comparing scoring and conventional balloon predilation.

    Science.gov (United States)

    Jujo, Kentaro; Saito, Katsumi; Ishida, Issei; Kim, Ahsung; Suzuki, Yuki; Furuki, Yuho; Ouchi, Taisuke; Ishii, Yasuhiro; Sekiguchi, Haruki; Yamaguchi, Junichi; Ogawa, Hiroshi; Hagiwara, Nobuhisa

    2016-10-15

    Stent expansion remains one of the most important predictors of restenosis and subacute thrombosis, even with the use of drug-eluting stents. This study was designed to clarify the impact of lesion preparation on final stent expansion. Sixty-six consecutive patients were included in this trial, and ultimately 52 enrolled non-calcified de novo lesions were randomly assigned to undergo single predilation with either a semi-compliant scoring balloon or a semi-compliant conventional balloon. Lesions were treated with a single 2.5- to 3.0-mm cobalt-chromium everolimus-eluting stent under optical coherence tomography (OCT) guidance without post-stenting dilation. Stent expansion was defined as the ratio of OCT-measured minimum stent area to the predicted stent area. Stent expansion was significantly higher after predilation by a scoring balloon (68.0% vs. 62.1%, p=0.017) with similar stent lumen eccentricity (0.84 vs. 0.80, p=0.18). Intimal disruption was induced significantly more frequently (68.0% vs. 38.4%, p=0.035) and was more extensive in the scoring group (122° vs. 65°, p=0.038). Lesions with intimal disruption after predilation achieved significantly higher stent expansion than that without it (67.7% vs. 61.6%, p=0.023). One case in the conventional group required target lesion revascularization; however, any other adverse clinical events including death, myocardial infarction, and stent thrombosis were not observed up to 9months after PCI in both groups. In this randomized study, pretreatment with a scoring balloon enhanced stent expansion partly through induction of intimal disruption. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014176. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Safety concerns and hidden agenda behind HPV vaccines: another generation of drug-dependent society?

    Science.gov (United States)

    Khatami, Mahin

    2016-12-01

    Analyses of data and hidden agenda behind repeated failed outcomes of cancer research and therapy, status of American health, safety concerns for HPV vaccines and future research considerations are summarized in this commentary. A closer look at cancer science reveals that highly power structure (system) in medical establishment vs. anti-system and chaos in cancer research ('medical/scientific ponzi schemes') is potent recipe for failed therapeutics that kills patients but generates huge corporate profit. American health status ranks last among other developed nations despite the highest amount that USA invests in healthcare. This is a wake-up call to make sure that the evil part of human being does not prevent the health services that the public deserves. Otherwise, 'it does not matter how many resources you have, if you don't know, or don't want to know, how to use them, they will never be enough'. Answer to cancer and improved public health is possible only by switching the current corruptive and abusive culture of 'who you know' to a culture of 'what you know'. Policy makers and professionals in decision making roles are urged to return to common sense and logics that our Forefathers used to serve the public.

  4. Metal complexes of the fourth generation quinolone antimicrobial drug gatifloxacin: Synthesis, structure and biological evaluation

    Science.gov (United States)

    Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

    2010-08-01

    Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(ΙΙΙ), Zr(ΙV) and U(VΙ) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, gatifloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylato oxygen. The complexes are six-coordinated with distorted octahedral geometry. The kinetic parameters for gatifloxacin and the three prepared complexes have been evaluated from TGA curves by using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The calculated bond length and force constant, F(U dbnd O), for the UO 2 bond in uranyl complex are 1.7522 Å and 639.46 N m -1. The antimicrobial activity of the complexes has been tested against microorganisms, three bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) and two fungi species, penicillium ( P. rotatum) and trichoderma ( T. sp.), showing that they exhibit higher activity than free ligand.

  5. Effectiveness of the universal prevention program 'Healthy School and Drugs': Study protocol of a randomized clustered trial

    Directory of Open Access Journals (Sweden)

    Malmberg Monique

    2010-09-01

    Full Text Available Abstract Background Substance use is highly prevalent among Dutch adolescents. The Healthy School and Drugs program is a nationally implemented school-based prevention program aimed at reducing early and excessive substance use among adolescents. Although the program's effectiveness was tested in a quasi-experimental design before, many program changes were made afterwards. The present study, therefore, aims to test the effects of this widely used, renewed universal prevention program. Methods/Design A randomized clustered trial will be conducted among 3,784 adolescents of 23 secondary schools in The Netherlands. The trial has three conditions; two intervention conditions (i.e., e-learning and integral and a control condition. The e-learning condition consists of three digital learning modules (i.e., about alcohol, tobacco, and marijuana that are sequentially offered over the course of three school years (i.e., grade 1, grade 2, and grade 3. The integral condition consists of parental participation in a parental meeting on substance use, regulation of substance use, and monitoring and counseling of students' substance use at school, over and above the three digital modules. The control condition is characterized as business as usual. Participating schools were randomly assigned to either an intervention or control condition. Participants filled out a digital questionnaire at baseline and will fill out the same questionnaire three more times at follow-up measurements (8, 20, and 32 months after baseline. Outcome variables included in the questionnaire are the percentage of binge drinking (more than five drinks per occasion, the average weekly number of drinks, and the percentage of adolescents who ever drunk a glass of alcohol and the percentage of adolescents who ever smoked a cigarette or a joint respectively for tobacco and marijuana. Discussion This study protocol describes the design of a randomized clustered trial that evaluates the

  6. Assessing the quality of evidence from randomized, controlled drug and nutritional supplement trials conducted among nursing home residents between 1968 and 2004: what can we learn?

    Science.gov (United States)

    Cheng, Huai Yong

    2009-01-01

    An estimated 1.5 million residents of nursing homes (NH) in the United States were prescribed an average of 7 to 8 medications each month. However, it is unknown which of these prescribed drugs and nutritional supplements have been tested for use among NH residents who often have distinct and complex needs compared with other geriatric patients. This pilot study addresses the quantity and quality of randomized, controlled drug and nutritional supplement trials that have been conducted among NH residents. Using multiple search strategies and review protocol, I assessed the quality of evidence from randomized, controlled drug and nutritional supplement trials that had a parallel-group design, were conducted among NH residents, and were published in English between 1968 and October 2004. Internal validity of the trials was examined by assessing adequately reporting power calculation, drop-outs (completion fraction), randomization and allocation concealment, blind status, and intention-to-treat analysis. External validity of the trials was examined by assessing adequately reporting the sample description, the inclusion and exclusion criteria, the recruitment process, and comorbidities and harm. Relatively few drug and nutritional supplements have been tested among NH residents by well-designed and executed randomized controlled trials (N = 42). The total number of participants (N = 7941) is small. The quality of many trials is poor. Given the limited number and poor quality of existing trials conducted among NH residents in this pilot study, I conclude that there is a limited body of evidence that could be used to establish quality of care standards or pay for performance criteria for drug therapy and nutritional supplements in NH. Long-term care providers face a great challenge in practicing evidence-based medicine in prescribing drugs and nutritional supplements.

  7. Critical side channel effects in random bit generation with multiple semiconductor lasers in a polarization-based quantum key distribution system.

    Science.gov (United States)

    Ko, Heasin; Choi, Byung-Seok; Choe, Joong-Seon; Kim, Kap-Joong; Kim, Jong-Hoi; Youn, Chun Ju

    2017-08-21

    Most polarization-based BB84 quantum key distribution (QKD) systems utilize multiple lasers to generate one of four polarization quantum states randomly. However, random bit generation with multiple lasers can potentially open critical side channels that significantly endangers the security of QKD systems. In this paper, we show unnoticed side channels of temporal disparity and intensity fluctuation, which possibly exist in the operation of multiple semiconductor laser diodes. Experimental results show that the side channels can enormously degrade security performance of QKD systems. An important system issue for the improvement of quantum bit error rate (QBER) related with laser driving condition is further addressed with experimental results.

  8. New-Generation, non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs

    Science.gov (United States)

    Mandrioli, Roberto; Protti, Michele; Mercolini, Laura

    2017-07-12

    New-generation antidepressants (NGAs) are the latest additions to the clinician's arsenal in the fight against depression. After the introduction of selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups followed, identified by their main mechanisms of activity: serotonin and norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators (SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and selective serotonergic antidepressants (NaSSA); norepinephrine reuptake inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors (SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists (MaSA). Although SSRIs are still the most widely used and well known NGAs, the other groups are increasingly being used in the current therapeutic settings obtaining comparable clinical results, and with tolerability and safety profiles that can often provide significant advantages over those of SSRIs. Scopus and PubMed databases were searched for the most significant papers centered on the medicinal chemistry, pharmacodynamics, pharmacokinetics and analysis in human biological fluids of the following antidepressants: venlafaxine, duloxetine, milnacipran, trazodone, vortioxetine, vilazodone. The main characteristics of commercially available non-SSRI NGAs (belonging to the SNRI, SARI and SMS classes) are described, focusing on the role of analytical methods that can be applied to perform therapeutic drug monitoring (TDM), but also including drug pharmacokinetics, metabolism and interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Ikeda H

    2015-10-01

    Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

  10. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

    DEFF Research Database (Denmark)

    Macdonald, Thomas M; Hawkey, Chris J; Ford, Ian

    2017-01-01

    BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting....... METHOD: Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established CV disease and taking chronic prescribed nsNSAIDs, were randomized to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalization for non-fatal myocardial...... expected developed an on-treatment (OT) primary CV event and the rate was similar for celecoxib, 0.95 per 100 patient-years, and nsNSAIDs, 0.86 per 100 patient-years (HR = 1.12, 95% confidence interval, 0.81-1.55; P = 0.50). Comparable intention-to-treat (ITT) rates were 1.14 per 100 patient...

  11. Antivertiginous drug therapy does not hinder the efficacy of individualized vibrotactile neurofeedback training for vestibular rehabilitation - a randomized trial.

    Science.gov (United States)

    Basta, Dietmar; Borsellino, Liliana; Ernst, Arne

    2017-12-01

    Vestibular rehabilitation using individualized vibrotactile neurofeedback training (IVNT) can lead to significant improvement in the postural stability of patients with vestibular symptoms of different origins. However, some of these patients have complex, severe dizziness, meaning that a pharmacological pretreatment or parallel (to vestibular rehabilitation) treatment can help them perform the rehabilitation exercises. Hence, the present study investigated the influence of a pharmacological treatment on the efficacy of vibrotactile neurofeedback training in patients with chronic, noncompensated vestibulopathies. All participants performed IVNT for ∼10 min each day for 2 weeks. In addition, every second participant was selected randomly to receive oral medication (20 mg cinnarizine and 40 mg dimenhydrinate per tablet), taking three tables per day. Trunk and ankle sway and postural stability were measured. In addition, the dizziness handicap inventory was evaluated immediately before training on the last day of training and 6 months after training. After the 10-day period of IVNT, both groups showed a statistically significant improvement in all parameters tested. A follow-up analysis after 6 months showed a long-term efficacy for the IVNT, that is, the patients remained significantly improved in their postural stability. The antivertiginous therapy did not hinder the efficacy of the IVNT. The present results indicate that IVNT even in combination with an antivertiginous drug therapy is an effective treatment regime for patients with disabling vertigo of different origins.

  12. Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method.

    Science.gov (United States)

    Hamanaka, Sanae; Ooehara, Jun; Morita, Yohei; Ema, Hideo; Takahashi, Satoru; Miyawaki, Atsushi; Otsu, Makoto; Yamaguchi, Tomoyuki; Onodera, Masafumi; Nakauchi, Hiromitsu

    2013-06-14

    Fluorescent-protein transgenic mice are useful for obtaining marked somatic cells to study kinetics of development or differentiation. Fluorescence-marked hematopoietic stem cells in particular are commonly used for studying hematopoiesis. However, as far as we know, no transgenic mouse line is described in which a fluorescent protein is stably and constitutively expressed in all hematopoietic cells, including erythrocytes and platelets. Using the random segregation of provirus (RSP) method, we generated from retrovirally transduced mouse embryonic stem cells a transgenic mouse line expressing a red/orange fluorescent protein, Kusabira Orange (KuO). KuO transgenic mouse line cells carry only one proviral integration site and stably express KuO in all hematopoietic-lineage elements, including erythrocytes and platelets. Moreover, bone-marrow transplantation in KuO transgenic mice demonstrated normal hematopoieisis. KuO transgenic mice likely will prove useful for study of hematopoiesis that includes erythropoiesis and megakaryopoiesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Use of Hot Rolling for Generating Low Deviation Twins and a Disconnected Random Boundary Network in Inconel 600 Alloy

    Science.gov (United States)

    Sahu, Sandeep; Yadav, Prabhat Chand; Shekhar, Shashank

    2018-02-01

    In this investigation, Inconel 600 alloy was thermomechanically processed to different strains via hot rolling followed by a short-time annealing treatment to determine an appropriate thermomechanical process to achieve a high fraction of low-Σ CSL boundaries. Experimental results demonstrate that a certain level of deformation is necessary to obtain effective "grain boundary engineering"; i.e., the deformation must be sufficiently high to provide the required driving force for postdeformation static recrystallization, yet it should be low enough to retain a large fraction of original twin boundaries. Samples processed in such a fashion exhibited 77 pct length fraction of low-Σ CSL boundaries, a dominant fraction of which was from Σ3 ( 64 pct), the latter with very low deviation from its theoretical misorientation. The application of hot rolling also resulted in a very low fraction of Σ1 ( 1 pct) boundaries, as desired. The process also leads to so-called "triple junction engineering" with the generation of special triple junctions, which are very effective in disrupting the connectivity of the random grain boundary network.

  14. Use of Hot Rolling for Generating Low Deviation Twins and a Disconnected Random Boundary Network in Inconel 600 Alloy

    Science.gov (United States)

    Sahu, Sandeep; Yadav, Prabhat Chand; Shekhar, Shashank

    2017-12-01

    In this investigation, Inconel 600 alloy was thermomechanically processed to different strains via hot rolling followed by a short-time annealing treatment to determine an appropriate thermomechanical process to achieve a high fraction of low-Σ CSL boundaries. Experimental results demonstrate that a certain level of deformation is necessary to obtain effective "grain boundary engineering"; i.e., the deformation must be sufficiently high to provide the required driving force for postdeformation static recrystallization, yet it should be low enough to retain a large fraction of original twin boundaries. Samples processed in such a fashion exhibited 77 pct length fraction of low-Σ CSL boundaries, a dominant fraction of which was from Σ3 ( 64 pct), the latter with very low deviation from its theoretical misorientation. The application of hot rolling also resulted in a very low fraction of Σ1 ( 1 pct) boundaries, as desired. The process also leads to so-called "triple junction engineering" with the generation of special triple junctions, which are very effective in disrupting the connectivity of the random grain boundary network.

  15. Letter to the editor: Generation of self organized critical connectivity network map (SOCCNM of randomly situated water bodies during flooding process

    Directory of Open Access Journals (Sweden)

    B. S. Daya Sagar

    2001-01-01

    Full Text Available This letter presents a brief framework based on nonlinear morphological transformations to generate a self organized critical connectivity network map (SOCCNM in 2-dimensional space. This simple and elegant framework is implemented on a section that contains a few simulated water bodies to generate SOCCNM. This is based on a postulate that the randomly situated surface water bodies of various sizes and shapes self organize during flooding process.

  16. Next-generation drug-eluting stents in coronary artery disease: focus on everolimus-eluting stent (Xience V).

    Science.gov (United States)

    Sheiban, Imad; Villata, Gianluca; Bollati, Mario; Sillano, Dario; Lotrionte, Marzia; Biondi-Zoccai, Giuseppe

    2008-01-01

    Percutaneous coronary revascularization has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stents and, more recently, first-generation drug-eluting stents (DES), such as sirolimus-eluting (Cypher) and paclitaxel-eluting stents (Taxus), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. There is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. There are well known caveats on the performance of their respective metallic stent platforms, delivery, and dilation systems, and polymer coatings. Second-generation DES, such as zotarolimus-eluting (Endeavor) and everolimus-eluting stents (Xience V), have recently become available in the USA and/or Europe. The Xience V stent holds the promise of superior anti-restenotic efficacy as well as long-term safety. In addition, this stent is based on the Multi-link platform and delivery system. Recently available data already suggest the superiority of the Xience V stent in comparison to the Taxus stent in terms of prevention of restenosis, without significant untoward events. Nonetheless, the number of patients studied and the follow-up duration are still too limited to enable definitive conclusions. Only indirect meta-analyses can be used to date to compare the Xience V with the Cypher. This systematic review tries to provide a concise and critical appraisal of the data in support of the Xience V everolimus-eluting stent.

  17. Next-generation drug-eluting stents in coronary artery disease: focus on everolimus-eluting stent (Xience V®

    Directory of Open Access Journals (Sweden)

    Imad Sheiban

    2008-02-01

    Full Text Available Imad Sheiban1, Gianluca Villata1, Mario Bollati1, Dario Sillano1, Marzia Lotrionte2, Giuseppe Biondi-Zoccai11Interventional Cardiology, Division of Cardiology, University of Turin, Turin, Italy; 2Institute of Cardiology, Catholic University, Rome, ItalyAbstract: Percutaneous coronary revascularization has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stents and, more recently, first-generation drug-eluting stents (DES, such as sirolimus-eluting (Cypher® and paclitaxel-eluting stents (Taxus®, have further improved results of percutaneous coronary intervention (PCI by improving early results and reducing the risk of restenosis. There is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. There are well known caveats on the performance of their respective metallic stent platforms, delivery, and dilation systems, and polymer coatings. Second-generation DES, such as zotarolimus-eluting (Endeavor® and everolimus-eluting stents (Xience V®, have recently become available in the USA and/or Europe. The Xience V stent holds the promise of superior anti-restenotic efficacy as well as long-term safety. In addition, this stent is based on the Multi-link platform and delivery system. Recently available data already suggest the superiority of the Xience V stent in comparison to the Taxus stent in terms of prevention of restenosis, without significant untoward events. Nonetheless, the number of patients studied and the follow-up duration are still too limited to enable definitive conclusions. Only indirect meta-analyses can be used to date to compare the Xience V with the Cypher. This systematic review tries to provide a concise and critical appraisal of the data in support of the Xience V everolimus-eluting stent.Keywords: coronary artery disease, everolimus, percutaneous

  18. Next-generation drug-eluting stents in coronary artery disease: focus on everolimus-eluting stent (Xience V®)

    Science.gov (United States)

    Sheiban, Imad; Villata, Gianluca; Bollati, Mario; Sillano, Dario; Lotrionte, Marzia; Biondi-Zoccai, Giuseppe

    2008-01-01

    Percutaneous coronary revascularization has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stents and, more recently, first-generation drug-eluting stents (DES), such as sirolimus-eluting (Cypher®) and paclitaxel-eluting stents (Taxus®), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. There is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. There are well known caveats on the performance of their respective metallic stent platforms, delivery, and dilation systems, and polymer coatings. Second-generation DES, such as zotarolimus-eluting (Endeavor®) and everolimus-eluting stents (Xience V®), have recently become available in the USA and/or Europe. The Xience V stent holds the promise of superior anti-restenotic efficacy as well as long-term safety. In addition, this stent is based on the Multi-link platform and delivery system. Recently available data already suggest the superiority of the Xience V stent in comparison to the Taxus stent in terms of prevention of restenosis, without significant untoward events. Nonetheless, the number of patients studied and the follow-up duration are still too limited to enable definitive conclusions. Only indirect meta-analyses can be used to date to compare the Xience V with the Cypher. This systematic review tries to provide a concise and critical appraisal of the data in support of the Xience V everolimus-eluting stent. PMID:18629361

  19. Improving psychotropic drug prescription in nursing home patients with dementia: design of a cluster randomized controlled trial

    NARCIS (Netherlands)

    Smeets, C.H.; Smalbrugge, M.; Gerritsen, D.L.; Nelissen-Vrancken, M.H.; Wetzels, R.B.; van der Spek, K.; Zuidema, S.U.; Koopmans, R.T.

    2013-01-01

    Background: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are

  20. Improving psychotropic drug prescription in nursing home patients with dementia : design of a cluster randomized controlled trial

    NARCIS (Netherlands)

    Smeets, Claudia H. W.; Smalbrugge, Martin; Gerritsen, Debby L.; Nelissen-Vrancken, Marjorie H. J. M. G.; Wetzels, Roland B.; van der Spek, Klaas; Zuidema, Sytse U.; Koopmans, Raymond T. C. M.

    2013-01-01

    Background: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are

  1. Exact distribution of a pattern in a set of random sequences generated by a Markov source: applications to biological data

    Directory of Open Access Journals (Sweden)

    Regad Leslie

    2010-01-01

    Full Text Available Abstract Background In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.. Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. Results The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Conclusions Our algorithms prove to be effective and able to handle real data sets with

  2. Exact distribution of a pattern in a set of random sequences generated by a Markov source: applications to biological data

    Science.gov (United States)

    2010-01-01

    Background In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.). Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. Results The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Conclusions Our algorithms prove to be effective and able to handle real data sets with multiple sequences, as well

  3. Deep tissue massage and nonsteroidal anti-inflammatory drugs for low back pain: a prospective randomized trial.

    Science.gov (United States)

    Majchrzycki, Marian; Kocur, Piotr; Kotwicki, Tomasz

    2014-01-01

    To investigate whether chronic low back pain therapy with deep tissue massage (DTM) gives similar results to combined therapy consisting of DTM and non-steroid anti-inflammatory drugs (NSAID). Prospective controlled randomized single blinded trial. Ambulatory care of rehabilitation. 59 patients, age 51.8 ± 9.0 years, with chronic low back pain. Interventions. 2 weeks of DTM in the treatment group (TG) versus 2 weeks of DTM combined with NSAID in the control group (CG). Visual analogue scale, Oswestry disability index (ODI), and Roland-Morris questionnaire (RM). In both the TG and the CG, a significant pain reduction and function improvement were observed. VAS decreased from 58.3 ± 18.2 to 42.2 ± 21.1 (TG) and from 51.8 ± 18.8 to 30.6 ± 21.9 (CG). RM value decreased from 9.8 ± 5.1 to 6.4 ± 4.4 (TG), and from 9.3 ± 5.5 to 6.1 ± 4.6 (CG). ODI value decreased from 29.2 ± 17.3 to 21.4 ± 15.1 (TG) and from 21.4 ± 9.4 to 16.6 ± 9.4 (CG). All pre-post-treatment differences were significant; however, there was no significant difference between the TG and the CG. DTM had a positive effect on reducing pain in patients with chronic low back pain. Concurrent use of DTM and NSAID contributed to low back pain reduction in a similar degree that the DTM did.

  4. Short-term Antiarrhythmic Drugs After Catheter Ablation for Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Xu, Buyun; Peng, Fang; Tang, Weiliang; Du, Ye; Guo, Hangyuan

    2016-09-01

    The incidence of recurrent arrhythmia after catheter ablation (CA) for atrial fibrillation (AF) is unacceptable. Short-term antiarrhythmic drug (AAD) treatment following CA was presumed to be effective in reducing recurrent arrhythmia. To fully evaluate the efficacy of short-term use of AADs following CA for AF in preventing recurrence of atrial tachyarrhythmias. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched up until May 1, 2016. We enrolled randomized controlled trials (RCTs) that evaluated the efficacy of short-term use of AADs following CA for AF in preventing early and/or late recurrence of atrial tachyarrhythmias. The statistical analyses were performed using Review Manager Version 5.3. Six RCTs were included in this analysis, involving a total of 2764 patients. The frequency of early recurrence of atrial tachyarrhythmias was 39.5% in the AAD group (556 of 1407) and 47.2% (640 of 1357) in the control group. The pooled risk ratio of the AAD group to the control group was 0.78 (95% CI = 0.62-0.98). Regarding late recurrence of AF (LRAF), the incidence in the AAD group and the control group was 32.5% (420 of 1293) and 34.6% (450 of 1300), respectively. No significant difference was identified between the 2 groups (relative risk = 0.94, 95% CI = 0.85-1.05). Short-term use of AADs following CA for AF reduced the incidence of early recurrent atrial tachyarrhythmias but did not prevent LRAF. © The Author(s) 2016.

  5. Casting epPCR (cepPCR): A simple random mutagenesis method to generate high quality mutant libraries.

    Science.gov (United States)

    Yang, Jianhua; Ruff, Anna J; Arlt, Marcus; Schwaneberg, Ulrich

    2017-09-01

    During the last decade, directed evolution has become a standard protein engineering strategy to reengineer proteins for industrial applications under high stress conditions (e.g., high temperature, extreme pH, ionic liquids, or organic solvents). The most commonly employed method for diversity generation to improve biocatalysts for these properties is random mutagenesis by error-prone polymerase chain reaction (epPCR). However, recent reports show that epPCR often fails to produce >70% of beneficial positions/amino acid exchanges which improve enzyme properties such as organic solvent or ionic liquid resistance. In this report, bsla (543 bp, small lipase gene from Bacillus subtilis) was divided into three fragments (147, 192, 204 bp). Each fragment was subjected to an epPCR with a high mutation load (22, 31, and 33 mutations per kb) in order to increase the number of identified beneficial positions while maintaining a fraction of active population which can efficiently be screened in agar plate or microtiter plate format. The use of this "casting epPCR" process termed as (cepPCR), doubles the number of identified beneficial positions (from 14% to 29%), when compared to standard epPCR for the BSLA enzyme model. A further increase to 39% of beneficial positions is obtainable through combination of cepPCR with the transversion biased sequence saturation mutagenesis (SeSaM) method. Furthermore, sequencing of up to 600 mutations per fragment provided valuable insights into the correlation of total throughput and number of identified beneficial positions as well as how an efficient balance of screening efforts to obtainable results can be achieved in directed evolution campaigns. Biotechnol. Bioeng. 2017;114: 1921-1927. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. pH-Responsive drug release and NIR-triggered singlet oxygen generation based on a multifunctional core-shell-shell structure.

    Science.gov (United States)

    Han, Renlu; Yi, Haopeng; Shi, Junhui; Liu, Zongjun; Wang, Hao; Hou, Yafei; Wang, You

    2016-09-14

    A multifunctional platform with pH-responsive drug release and near-infrared (NIR) light-triggered photodynamic therapy (PDT) was designed and prepared using the novel core-shell-shell structure. The multifunctional platform consists of an upconversion nanoparticle (UCNP) emission core, a photosensitizer methylene blue (MB) embedded dense silica sandwich shell, and a polyethyleneimine conjugated folic acid (PEI-FA) gated mesoporous silica (MS) outmost shell with doxorubicin hydrochloride (DOX) loaded inside. The simulated drug release experiments revealed that DOX will release from the nanoparticles because of the distortion in the PEI-FA layer under acidic conditions. Moreover, under 980 nm NIR irradiation, a 660 nm red light emission was excited, activating MB to generate a singlet oxygen (1O2), which acts as the PDT drug. The multifunctional platform integrated pH-responsive drug release and UCNP-based PDT drug together show promising potential in nanomedicine for future chemotherapy and NIR-triggered PDT.

  7. Transitions in drug use in a new generation of problem drug users in Amsterdam: a 6-year follow-up study

    NARCIS (Netherlands)

    Buster, Marcel C. A.; Witteveen, Ewald; Prins, Maria; van Ameijden, Erik J. C.; Schippers, Gerard; Krol, Anneke

    2009-01-01

    This study describes the transitions in drug use in Amsterdam among young drug users (YDUs) who are inhaling or injecting cocaine or using illicitly obtained opiates. From 2000 until 2003, 187 YDUs (

  8. Next-generation sequencing of dried blood spot specimens: a novel approach to HIV drug-resistance surveillance.

    Science.gov (United States)

    Ji, Hezhao; Li, Yang; Graham, Morag; Liang, Ben Binhua; Pilon, Richard; Tyson, Shari; Peters, Geoff; Tyler, Shaun; Merks, Harriet; Bertagnolio, Silvia; Soto-Ramirez, Luis; Sandstrom, Paul; Brooks, James

    2011-01-01

    HIV drug-resistance (DR) surveillance in resource-limited settings can be performed using dried blood spots (DBS) because of ease of collection, transportation and storage. Analysis of pooled specimens on next-generation sequencing (NGS)-based platforms, such as the 454 pyrosequencing, is an efficient sequencing method for determining HIV DR rates. In this study, we conducted HIV DR surveillance on DBS using NGS and identified minority variants in individual patients. A total of 48 extracts of DBS from an HIV DR surveillance study in Mexico City were re-amplified using primers tagged with multiplex identifiers, pooled and pyrosequenced. Consensus sequences were generated for each specimen with mixtures identified at positions where >20% of the reads contained a variant. Individual consensus sequences were then analysed for DR mutations and compared with those derived from Sanger sequencing. DBS analysed with tagged pooled pyrosequencing (TPP) were highly concordant with Sanger sequencing genotypes from matching plasma and DBS (99.21% and 99.51%, respectively). An exception was an M184I mutation only detected with TPP of DBS at a frequency of 20.4%. Multiple specimens had minority variant reads below the 20% mixture threshold. TPP using DBS is an effective method for HIV DR surveillance. TPP for genotyping results in cost savings of 40% over conventional in-house methods. The effect of low-abundance DR mutations, undetectable by conventional methods, remains to be determined. This technology might be applied to any HIV specimen (plasma/serum) and can also be used for other diagnostic assays where DNA sequencing is required. © 2011 International Medical Press

  9. Randomized, community-based pharmacy intervention to expand services beyond sale of sterile syringes to injection drug users in pharmacies in New York City.

    Science.gov (United States)

    Crawford, Natalie D; Amesty, Silvia; Rivera, Alexis V; Harripersaud, Katherine; Turner, Alezandria; Fuller, Crystal M

    2013-09-01

    Structural interventions may help reduce racial/ethnic disparities in HIV. In 2009 to 2011, we randomized pharmacies participating in a nonprescription syringe access program in minority communities to intervention (pharmacy enrolled and delivered HIV risk reduction information to injection drug users [IDUs]), primary control (pharmacy only enrolled IDUs), and secondary control (pharmacy did not engage IDUs). Intervention pharmacy staff reported more support for syringe sales than did control staff. An expanded pharmacy role in HIV risk reduction may be helpful.

  10. A non-commercial approach for the generation of transgenic Leishmania tarentolae and its application in antileishmanial drug discovery.

    Science.gov (United States)

    Pineda, Tatiana; Valencia, Yesenia; Flórez, María F; Pulido, Sergio A; Vélez, Iván D; Robledo, Sara M

    2016-08-01

    Leishmaniasis is a parasitic infection caused by several species of the genus Leishmania that is considered as a neglected disease. Drug development process requires a robust and updated high-throughput technology to the evaluation of candidate compounds that imply the manipulation of the pathogenic species of the parasite in the laboratory. Therefore, it is restricted to trained personal and level II biosafety environments. However, it has been established the utility of Leishmania tarentolae as a model for in vitro screening of antileishmanial agents without the necessity of level II biosafety setups. In parallel the transfection of Leishmania parasites with reporter genes as the eGFP using non-commercial integration vectors like the pIRmcs3(-) has proved to be a powerful tool for the implementation of semi automatized high-throughput platforms for the evaluation of antileishmanial compounds. Here we report the generation of a new L. tarentolae strain overexpressing the eGFP gene harboured by the non-commercial vector pIR3(-). We also demonstrate its utility for the semi-automatized screening of antileshmanial compounds in intracellular forms of the L. tarentolae parasite.

  11. A group intervention to reduce intimate partner violence among female drug users. Results from a randomized controlled pilot trial in a community substance-abuse center.

    Science.gov (United States)

    Tirado-Muñoz, Judit; Gilchrist, Gail; Lligoña, Eva; Gilbert, Louisa; Torrens, Marta

    2015-09-15

    A greater proportion of drug dependent women are victims of intimate partner violence (IPV) than women in the general population; however, few interventions have been developed to reduce IPV among drug dependent women. An adapted version of the Women's Wellness Treatment, to address IPV and depressive symptoms, was piloted in a randomized controlled trial conducted in outpatient treatment program in Barcelona, Spain among 14 women receiving outpatient treatment for a drug use disorder who screened positive for IPV in the previous month. Participants were randomly assigned to receive the 10 session cognitive behavioral therapy (IPaViT-CBT) group intervention or treatment as usual. The frequency of IPV, depressive symptoms, substance use, quality of life and health status were assessed at baseline and 1, 3 and 12 months post intervention. Intention to treat analysis was performed. Moderate effects for the intervention were found in reducing psychological maltreatment, increasing assertiveness of IPV and reducing aggressiveness in the partner relationship, and in reducing the frequency of drinking up to 3 months post intervention. The intervention did not significantly reduce the likelihood of any IPV, depressive symptoms, quality of life or self-reported health status, up to 12-months post intervention. This pilot trial suggests some initial support for the 10-session CBT group intervention among IPV victims who received treatment for drug use. Study findings indicate that it is feasible to deliver the intervention in a community substance abuse center. An adequately powered trial is required to replicate these results.

  12. Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

    Science.gov (United States)

    Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

    2017-06-03

    Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

  13. Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

    Directory of Open Access Journals (Sweden)

    Heiner K Berthold

    Full Text Available CONTEXT AND OBJECTIVE: Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. DESIGN AND PARTICIPANTS: A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l. They were treated with ezetimibe (10 mg/day, n = 24, simvastatin (40 mg/day, n = 24 or their combination (n = 24 for 14 days. Blood was drawn before and after the treatment period. HDL subclasses were determined using polyacrylamide gel-tube electrophoresis. Multivariate regression models were used to determine the influence of treatment and covariates on changes in HDL subclass composition. RESULTS: Baseline HDL subclasses consisted of 33±10% large, 48±6% intermediate and 19±8% small HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL-C and the ratio triglycerides/HDL-C, there was a significant increase in large HDL by about 3.9 percentage points (P<0.05 and a decrease in intermediate HDL by about 3.5 percentage points (P<0.01 in both simvastatin-containing treatment arms in comparison to ezetimibe. The parameters obtained after additional adjustment for the decrease in LDL-C indicated that about one third to one half of these effects could be explained by the extent of LDL-C-lowering. CONCLUSIONS: In healthy men, treatment with simvastatin leads to favorable effects on HDL subclass composition, which was not be observed with ezetimibe. Part of these differential effects may be due to the stronger LDL-C-lowering effects of simvastatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00317993.

  14. Necessary, sufficient and contributory factors generating illegal economic activity, and specifically drug-related activity, in Colombia

    Directory of Open Access Journals (Sweden)

    Francisco E. Thoumi

    2014-06-01

    Full Text Available The international drug control regime is formulated under a basic paradigm: all drugs included in the convention schedules I, II and IV can only have medical and research uses. The policies derived from these conventions forbid all recreational, ritual, experimental, or self-medicating consumption of coca, cocaine, opium, heroin, marijuana and many other drugs. The conventions allow the production of controlled drugs for medical and research uses and criminalize all other production. Where consumption is concerned they are less rigid, as users of illegal drugs do not have to be arrested or jailed. Anti-drug policies seek to suppress both illicit drug supply and demand but are formulated without clearly spelling out the reasons why there is a demand and a supply for illegal drugs. To understand illegal drug demand and supply it is necessary to have clear answers to fundamental criminological questions such as: Why do people commit crimes? Or why some individuals contravene formal or informal norms while others do not? Policymakers, however, do not hesitate to formulate and implement anti-drug policies without having first considered those questions. They proceed as if their answers were obvious or known. Yet, when asked about the reasons why the illegal drugs industry develops in a location, most answers are highly questionable and at best partially right. The aim of this essay is to show this using Colombia as an example.

  15. A randomized, double-blind, placebo-controlled, cross-over pilot study to assess the effects of long-term opioid drug consumption and subsequent abstinence in chronic noncancer pain patients receiving controlled-release morphine.

    Science.gov (United States)

    Cowan, David T; Wilson-Barnett, Jenifer; Griffiths, Peter; Vaughan, David J A; Gondhia, Anjalee; Allan, Laurie G

    2005-01-01

    The long-term use of strong opioid analgesics among chronic noncancer pain (CNCP) patients remains controversial because of concerns over problematic drug use. However, previous surveys suggest that this is not necessarily the case. Therefore, we designed a controlled study to generate evidence in support of these findings. Ten CNCP patients attending the pain clinic in a district general hospital had been taking an average daily dose of 40 mg controlled-release morphine sulphate (mean 40, range 10-90, SD 21 mg), for an average of 2 years (mean 2.175, range 2-2.25, SD 0.2 years). Randomized, double-blind, placebo controlled cross-over study. The study was based on the premise that abrupt cessation of opioid drugs is most likely to highlight problematic use and the consequent inability to stop using opioids. Morphine was substituted with placebo for 60-hour periods to compare the effects of abstinence with those of continued use. Assessment of morphine cessation and abstinence effects was through direct observation, physiological measurements, questionnaire responses, and Brief Pain Inventory scores. Following cessation and abstinence, there were no indications of psychological dependence or drug craving, but there was evidence of the detrimental effects of pain intensity on activity, mood, relationships, sleep, and enjoyment of life. Three patients (30%) reported opioid drug withdrawal symptoms. Pharmacokinetic data demonstrated compliance with abstinence by all patients. The results suggest the existence of a group of CNCP patients whose long-term opioid consumption can be beneficial and remain moderate without them suffering from the consequences of problematic opioid drug use.

  16. Parenting Practices and Problem Behavior across Three Generations: Monitoring, Harsh Discipline, and Drug Use in the Intergenerational Transmission of Externalizing Behavior

    Science.gov (United States)

    Bailey, Jennifer A.; Hill, Karl G.; Oesterle, Sabrina; Hawkins, J. David

    2009-01-01

    Using data from grandparents (G1), parents (G2), and children (G3), this study examined continuity in parental monitoring, harsh discipline, and child externalizing behavior across generations, and the contribution of parenting practices and parental drug use to intergenerational continuity in child externalizing behavior. Structural equation and…

  17. Parental Influences on Adolescent Marijuana Use and the Baby Boom Generation: Findings from the 1979-1996 National Household Surveys on Drug Abuse. Analytic Series.

    Science.gov (United States)

    Kandel, Denise B.; Griesler, Pamela C.; Lee, Gang; Davies, Mark; Schaffsan, Christine

    This report uses the 1979-1996 National Household Surveys on Drug Abuse to investigate the role of parents, especially members of the baby boom generation, on the marijuana use of children. The association of marijuana use between parents and children, the differences among parental birth cohorts, and the determinants of child marijuana use are…

  18. Predicting the velocity and azimuth of fragments generated by the range destruction or random failure of rocket casings and tankage

    Science.gov (United States)

    Eck, M.; Mukunda, M.

    The proliferation of space vehicle launch sites and the projected utilization of these facilities portends an increase in the number of on-pad, ascent, and on-orbit solid-rocket motor (SRM) casings and liquid-rocket tanks which will randomly fail or will fail from range destruct actions. Beyond the obvious safety implications, these failures may have serious resource implications for mission system and facility planners. SRM-casing failures and liquid-rocket tankage failures result in the generation of large, high velocity fragments which may be serious threats to the safety of launch support personnel if proper bunkers and exclusion areas are not provided. In addition, these fragments may be indirect threats to the general public's safety if they encounter hazardous spacecraft payloads which have not been designed to withstand shrapnel of this caliber. They may also become threats to other spacecraft if, by failing on-orbit, they add to the ever increasing space-junk collision cross-section. Most prior attempts to assess the velocity of fragments from failed SRM casings have simply assigned the available chamber impulse to available casing and fuel mass and solved the resulting momentum balance for velocity. This method may predict a fragment velocity which is high or low by a factor of two depending on the ratio of fuel to casing mass extant at the time of failure. Recognizing the limitations of existing methods, the authors devised an analytical approach which properly partitions the available impulse to each major system-mass component. This approach uses the Physics International developed PISCES code to couple the forces generated by an Eulerian modeled gas flow field to a Lagrangian modeled fuel and casing system. The details of a predictive analytical modeling process as well as the development of normalized relations for momentum partition as a function of SRM burn time and initial geometry are discussed in this paper. Methods for applying similar modeling

  19. Drug testing athletes to prevent substance abuse: background and pilot study results of the SATURN (Student Athlete Testing Using Random Notification) study.

    Science.gov (United States)

    Goldberg, Linn; Elliot, Diane L; MacKinnon, David P; Moe, Esther; Kuehl, Kerry S; Nohre, Liva; Lockwood, Chondra M

    2003-01-01

    To assess the deterrent effect of mandatory, random drug testing among high school (HS) athletes in a controlled setting. Two high schools, one with mandatory drug testing (DT) consent before sports participation, and a control school (C), without DT, were assessed during the 1999-2000 school year. Athletes (A) and nonathletes (NA) in each school completed confidential (A) or anonymous (NA) questionnaires developed for this study, respectively, at the beginning and end of the school year. Positive alcohol or drug tests required parent notification and mandatory counseling without team or school suspension. Thirty percent of the DT athletes were tested. Data were analyzed using the end of the school year measure, adjusted for the initial questionnaire results. Demographics of the athlete sample revealed that mean age was 15.5 years with 81.5% white, 9.6% Hispanic, 4.5% Asian, 2.6% American Indian/Native Alaskan, 1.3% African-American, and 1.3% Native Hawaiian/Pacific Islander. A (n = 276) and NA (n = 507) were assessed at the beginning (baseline) and at the end of the school year (A, n = 159; NA, n = 338). The past 30-day index of illicit drugs (4-fold difference) and athletic enhancing substances (3-fold difference) were lower (p athletes at follow-up without difference in alcohol use. However, most drug use risk factors, including norms of use, belief in lower risk of drugs, and poorer attitudes toward the school, increased among DT athletes (p drug use index was present among nonathletes at the DT school, at the end of the school year, it did not achieve statistical significance (p athletes. However, worsening of risk factors and small sample size suggests caution to this drug prevention approach. A larger long-term study to confirm these findings is necessary. Copyright Society for Adolescent Medicine, 2003

  20. Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain.

    Directory of Open Access Journals (Sweden)

    David A Barrière

    activation of bulbospinal pathways. Our findings demonstrate that it is possible to construct novel antinociceptive drugs based on fatty acid conjugation as a metabolic pathway for the generation of TRPV1 modulators in the CNS.

  1. Newest-generation drug-eluting and bare-metal stents combined with prasugrel-based antiplatelet therapy in large coronary arteries

    DEFF Research Database (Denmark)

    Jeger, Raban; Pfisterer, Matthias; Alber, Hannes

    2012-01-01

    In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal sten...... (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known....

  2. Protocol of the impact of alternative social assistance disbursement on drug-related harm (TASA study: a randomized controlled trial to evaluate changes to payment timing and frequency among people who use illicit drugs

    Directory of Open Access Journals (Sweden)

    Lindsey Richardson

    2016-07-01

    Full Text Available Abstract Background Government social assistance payments seek to alleviate poverty and address survival needs, but their monthly disbursement may cue increases in illicit drug use. This cue may be magnified when assistance is disbursed simultaneously across the population. Synchronized payments have been linked to escalations in drug use and unintended but severe drug-related harms, including overdose, as well as spikes in demand for health, social, financial and police services. Methods/design The TASA study examines whether changing payment timing and frequency can mitigate drug-related harm associated with synchronized social assistance disbursement. The study is a parallel arm multi-group randomized controlled trial in which 273 participants are randomly allocated for six assistance cycles to a control or one of two intervention arms on a 1:1:1 basis. Intervention arm participants receive their payments: (1 monthly; or (2 semi-monthly, in each case on days that are not during the week when cheques are normally issued. The study partners with a community-based credit union that has developed a system to vary social assistance payment timing. The primary outcome is a 40 % increase in drug use during the 3 days beginning with cheque issue day compared to other days of the month. Bi-weekly follow-up interviews collect participant information on this and secondary outcomes of interest, including drug-related harm (e.g. non-fatal overdose, exposure to violence and health service utilization. Self-reported data will be supplemented with participant information from health, financial, police and government administrative databases. A longitudinal, nested, qualitative parallel process evaluation explores participant experiences, and a cost-effectiveness evaluation of different disbursement scenarios will be undertaken. Outcomes will be compared between control and intervention arms to identify the impacts of alternative disbursement schedules on

  3. Design of high-throughput and low-power true random number generator utilizing perpendicularly magnetized voltage-controlled magnetic tunnel junction

    Directory of Open Access Journals (Sweden)

    Hochul Lee

    2017-05-01

    Full Text Available A true random number generator based on perpendicularly magnetized voltage-controlled magnetic tunnel junction devices (MRNG is presented. Unlike MTJs used in memory applications where a stable bit is needed to store information, in this work, the MTJ is intentionally designed with small perpendicular magnetic anisotropy (PMA. This allows one to take advantage of the thermally activated fluctuations of its free layer as a stochastic noise source. Furthermore, we take advantage of the voltage dependence of anisotropy to temporarily change the MTJ state into an unstable state when a voltage is applied. Since the MTJ has two energetically stable states, the final state is randomly chosen by thermal fluctuation. The voltage controlled magnetic anisotropy (VCMA effect is used to generate the metastable state of the MTJ by lowering its energy barrier. The proposed MRNG achieves a high throughput (32 Gbps by implementing a 64×64 MTJ array into CMOS circuits and executing operations in a parallel manner. Furthermore, the circuit consumes very low energy to generate a random bit (31.5 fJ/bit due to the high energy efficiency of the voltage-controlled MTJ switching.

  4. Design of high-throughput and low-power true random number generator utilizing perpendicularly magnetized voltage-controlled magnetic tunnel junction

    Science.gov (United States)

    Lee, Hochul; Ebrahimi, Farbod; Amiri, Pedram Khalili; Wang, Kang L.

    2017-05-01

    A true random number generator based on perpendicularly magnetized voltage-controlled magnetic tunnel junction devices (MRNG) is presented. Unlike MTJs used in memory applications where a stable bit is needed to store information, in this work, the MTJ is intentionally designed with small perpendicular magnetic anisotropy (PMA). This allows one to take advantage of the thermally activated fluctuations of its free layer as a stochastic noise source. Furthermore, we take advantage of the voltage dependence of anisotropy to temporarily change the MTJ state into an unstable state when a voltage is applied. Since the MTJ has two energetically stable states, the final state is randomly chosen by thermal fluctuation. The voltage controlled magnetic anisotropy (VCMA) effect is used to generate the metastable state of the MTJ by lowering its energy barrier. The proposed MRNG achieves a high throughput (32 Gbps) by implementing a 64 ×64 MTJ array into CMOS circuits and executing operations in a parallel manner. Furthermore, the circuit consumes very low energy to generate a random bit (31.5 fJ/bit) due to the high energy efficiency of the voltage-controlled MTJ switching.

  5. New-generation drug-eluting stents reduce stent thrombosis and myocardial infarction: a propensity-score-adjusted analysis from the multicenter REAL registry (REgistro Regionale AngiopLastiche Dell'Emilia-Romagna).

    Science.gov (United States)

    Vignali, Luigi; Saia, Francesco; Belotti, Laura Maria Beatrice; Solinas, Emilia; Guastaroba, Paolo; Rubboli, Andrea; Manari, Antonio; Mehran, Roxana; Ardissino, Diego; De Palma, Rossana

    2015-04-01

    The aim of this study was to compare long-term clinical outcomes in patients treated with new-generation drug-eluting stent (DES) or early-generation DES in a real-world registry. New-generation DESs have proved to be more effective and safer than early-generation DES in randomized trials. However, the effects of new-generation DES versus early-generation DES in everyday clinical practice deserve further verification. A propensity-score and inverse-probability weighted analysis of 5,332 patients undergoing DES implantation (2,557 new-generation and 2,775 early-generation) between January 1, 2007 and June 30, 2011 was performed, with a median follow-up of 3 years. We assessed the incidence of major adverse cardiovascular events (MACE: all-cause death, nonfatal myocardial infarction [MI], and target vessel revascularization [TVR]), and angiographic stent thrombosis (ST) during follow-up. At 3-years, new-generation DES in comparison with early-generation DES were associated with a reduced risk of MI (5% versus 7.4%, hazard ratio [HR]=0.65, 95% confidence interval [CI]=0.51-0.82, P=0.0004) and angiographic ST (0.5% vs. 1.1%, HR=0.35, 95% CI 0.17-0.72, P=0.004), whereas, the risk of TVR (10.9% vs. 13.5%; HR 0.99, 95% CI 0.84-1.16, P=0.99) and overall MACE was not significantly different (19.2% vs. 22.4%, HR=0.94, 95% CI=0.83-1.07, P=0.35). Our data from a large all-comers multicenter registry confirm that, in comparison with early-generation DES, the use of new-generation DES is associated with similar efficacy and increased long-term safety, because of a reduced risk of ST and MI. © 2014 Wiley Periodicals, Inc.

  6. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  7. Effects of music therapy on drug avoidance self-efficacy in patients on a detoxification unit: a three-group randomized effectiveness study.

    Science.gov (United States)

    Silverman, Michael J

    2014-01-01

    Self-efficacy is a component of Bandura's social cognitive theory and can lead to abstinence and a reduction of relapse potential for people who have substance abuse disorders. To date, no music therapy researcher has utilized this theoretical model to address abstinence and reduce the likelihood of relapse in people who have addictions. The purpose of this study was to determine the effects of music therapy on drug avoidance self-efficacy in a randomized three-group wait-list control design with patients on a detoxification unit. Participants (N = 131) were cluster randomized to one of three single-session conditions: music therapy, verbal therapy, or wait-list control. Music therapy participants received a group lyric analysis intervention, verbal therapy participants received a group talk therapy session, and wait-list control participants eventually received a group recreational music therapy intervention. Although there was no significant between-group difference in drug avoidance self-efficacy, participants in the music therapy condition tended to have the highest mean drug avoidance self-efficacy scores. Posttest written comments supported the use of both music therapy and verbal therapy sessions. Two music therapy participants specifically noted that their initial skepticism had dissipated after receiving music therapy. Despite a lack of significant differences, the theoretical support of self-efficacy for substance abuse rehabilitation suggests that this may be an area of continued clinical focus and empirical investigation. Clinical anecdotes, limitations of the study, and suggestions for future research are provided.

  8. Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials.

    Science.gov (United States)

    Thomopoulos, Costas; Parati, Gianfranco; Zanchetti, Alberto

    2016-10-01

    Choice of antihypertensive drugs is also based on the expected burden of adverse events associated with each class of agents, and we have recently identified treatment discontinuation for adverse events as a measure of treatment tolerability frequently reported in randomized controlled trials (RCTs). To investigate whether all classes of blood pressure (BP) lowering drugs increase discontinuations for adverse events when compared with placebo and whether risk of discontinuation is similar for all classes when compared in head-to-head RCTs. RCTs of BP-lowering treatment were subdivided in groups according to class of drug compared with placebo or with other classes. Risk ratios and 95% confidence intervals of major cardiovascular events and of treatment discontinuations for adverse events were calculated (random-effects model). Thirty-eight placebo-controlled RCTs (147 788 patients) and 37 head-to-head RCTs (242 481 patients) provided comparative information on discontinuations for adverse events. All classes of drugs significantly increased discontinuations for adverse events over those occurring on placebo: risk ratio diuretics 2.23 (1.32-3.76), beta-blockers 2.88 (1.58-5.28), calcium antagonists 2.03 (1.17-3.56), angiotensin-converting enzyme inhibitors 2.78 (1.37-5.47), central agents 1.74 (1.24-2.45), with the single exception of angiotensin receptor blockers, which did not significantly increase adverse events over placebo [risk ratio 1.13 (0.78-1.62)]. Similarly, in head-to-head comparison RCTs with other classes, angiotensin receptor blockers were the only class associated with a significantly lower risk of adverse events [risk ratio 0.71 (0.58-0.87)] when head-to-head compared with other classes. Regression analysis also shows that incidence of discontinuations for adverse events is proportional to the number of antihypertensive and other cardiovascular drugs, which accounts for the high incidence of this outcome often found in groups randomized to

  9. Does Multimodal Analgesia with Acetaminophen, Nonsteroidal Antiinflammatory Drugs, or Selective Cyclooxygenase-2 Inhibitors and Patient-controlled Analgesia Morphine Offer Advantages over Morphine Alone?: Meta-analyses of Randomized Trials

    National Research Council Canada - National Science Library

    Elia, Nadia; Lysakowski, Christopher; Tramèr, Martin R

    2005-01-01

    The authors analyzed data from 52 randomized placebo-controlled trials (4,893 adults) testing acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors given in conjunction with morphine after surgery...

  10. Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management

    Directory of Open Access Journals (Sweden)

    Feng XQ

    2017-05-01

    Full Text Available Xiu-qin Feng,1 Ling-ling Zhu,2 Quan Zhou3 1Nursing Administration Office, Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs. Method: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results: Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8% were conducted in healthy volunteers, whereas 10 RCTs (19.2% enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone, quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone, antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol, protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine, grapefruit juice–opioids (oxycodone, fentanyl, methadone, antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol, metoclopramide–morphine, amantadine–morphine, sumatriptan

  11. A Randomized Trial Among Compression Plus Nonsteroidal Antiinflammatory Drugs, Aspiration, and Aspiration With Steroid Injection for Nonseptic Olecranon Bursitis.

    Science.gov (United States)

    Kim, Joon Yub; Chung, Seok Won; Kim, Joo Hak; Jung, Jae Hong; Sung, Gwang Young; Oh, Kyung-Soo; Lee, Jong Soo

    2016-03-01

    Olecranon bursitis might be a minor problem in the outpatient clinic but relatively be common to occur. However, there are few well-designed studies comparing approaches to treatment. (1) Which treatment (compression bandaging with nonsteroidal antiinflammatory drugs [NSAIDs], aspiration, or aspiration with steroid injections) is associated with the highest likelihood of resolution of nonseptic olecranon bursitis? (2) Which treatment is associated with earliest resolution of symptoms? (3) What factors are associated with treatment failure by 4 weeks? We enrolled 133 patients from two centers; after applying prespecified exclusions (septic bursitis or concomitant inflammatory arthritis, intraarticular elbow pathology, recent aspiration or steroid injection done elsewhere, and refusal to participate), 90 patients were randomly allocated to receive compression bandaging with NSAIDs (C), aspiration (A), or aspiration with steroid injection (AS) groups (30 patients in each). The groups were similar at baseline in terms of age and gender. Seven patients (four from Group A and three from Group AS) were lost to followup. All patients were followed up weekly for 4 weeks, and the same treatment procedure was repeated if the bursitis recurred with any substantial fluid collection. At 4 weeks, the state of resolution and pain visual analog scale (VAS) were evaluated. Failed resolution was defined as presence of persistent olecranon bursal fluid collection at Week 4 after the initiation of the treatment; on the contrary, if bursal fluid collection was clinically reduced or completely disappeared by the end of Week 4, the treatment was considered successful. We compared the proportion of resolution by Week 4 and the median times to resolution among the treatment groups. In addition, we evaluated whether the resolution affected pain VAS and what factors were associated with the resolution. There were no differences in the proportion of patients whose bursitis resolved by Week 4

  12. Age and Individual Differences in Controlled Force Exertion Measured by a Computer-Generated Sinusoidal and Quasi-Random Display

    Science.gov (United States)

    Nagasawa, Yoshinori; Demura, Shinichi

    2010-01-01

    This study examined age group and individual differences in controlled force exertion by emulating sinusoidal and quasi-random waveforms in 222 right-handed female adults aged 20 to 86 years. The subjects matched their submaximal grip strength by the dominant hand to changing demand values displayed as either a sinusoidal or a quasi-random…

  13. Long-term effectiveness of computer-generated tailored patient education on benzodiazepines : a randomized controlled trial

    NARCIS (Netherlands)

    Ten Wolde, Geeske Brecht; Dijkstra, Arie; Van Empelen, Pepijn; van den Hout, Wilbert; Neven, Arie Knuistingh; Zitman, Frans

    Aims Chronic benzodiazepine use is highly prevalent and is associated with a variety of negative health consequences. The present study examined the long-term effectiveness of a tailored patient education intervention on benzodiazepine use. Participants A randomized controlled trial was conducted

  14. Moderate consumption of wine, through both its phenolic compounds and alcohol content, promotes hydroxytyrosol endogenous generation in humans. A randomized controlled trial.

    Science.gov (United States)

    Pérez-Mañá, Clara; Farré, Magí; Rodríguez-Morató, Jose; Papaseit, Esther; Pujadas, Mitona; Fitó, Montserrat; Robledo, Patricia; Covas, Maria-Isabel; Cheynier, Véronique; Meudec, Emmanuelle; Escudier, Jean-Louis; de la Torre, Rafael

    2015-06-01

    In humans, urinary hydroxytyrosol (OHTyr) concentrations have been associated to alcohol and wine consumption. To explore the role of wine components on promoting an endogenous OHTyr generation we performed a cross-over, double-blind, randomized controlled clinical trial (n = 28 healthy volunteers). Ethanol (wine and vodka), dealcoholized wine, and placebo were administered. Alcohol, dealcoholized wine, and particularly wine promoted a de novo OHTyr generation in vivo in humans. Potential OHTyr precursors (tyrosine, tyrosol, tyramine) were investigated in rats. Tyrosol was metabolized to OHTyr. Collating both studies, it is postulated that an increased Tyr bioavailability, a shift to a reductive pathway in dopamine and tyramine oxidative metabolism, and the biotransformation of Tyr to OHTyr were mechanisms involved in the OHTyr endogenous generation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. A Mobile Device App to Reduce Time to Drug Delivery and Medication Errors During Simulated Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial.

    Science.gov (United States)

    Siebert, Johan N; Ehrler, Frederic; Combescure, Christophe; Lacroix, Laurence; Haddad, Kevin; Sanchez, Oliver; Gervaix, Alain; Lovis, Christian; Manzano, Sergio

    2017-02-01

    During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusion is both complex and time-consuming, placing children at higher risk than adults for medication errors. Following an evidence-based ergonomic-driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. The aim of our study was to determine whether the use of PedAMINES reduces drug preparation time (TDP) and time to delivery (TDD; primary outcome), as well as medication errors (secondary outcomes) when compared with conventional preparation methods. The study was a randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drugs infusion rate table in the preparation of continuous drug infusion. We used a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin in the shock room of a tertiary care pediatric emergency department. After epinephrine-induced return of spontaneous circulation, pediatric emergency nurses were first asked to prepare a continuous infusion of dopamine, using either PedAMINES (intervention group) or the infusion table (control group), and second, a continuous infusion of norepinephrine by crossing the procedure. The primary outcome was the elapsed time in seconds, in each allocation group, from the oral prescription by the physician to TDD by the nurse. TDD included TDP. The secondary outcome was the medication dosage error rate during the sequence from drug preparation to drug injection. A total of 20 nurses were randomized into 2 groups. During the first study period, mean TDP while using PedAMINES and conventional preparation methods was 128.1 s (95% CI 102-154) and 308.1 s (95% CI 216-400), respectively (180 s reduction, P=.002). Mean TDD was 214 s (95% CI 171-256) and

  16. Drug use, health and social outcomes of hard-to-treat heroin addicts receiving supervised injectable opiate treatment: secondary outcomes from the Randomized Injectable Opioid Treatment Trial (RIOTT).

    Science.gov (United States)

    Metrebian, Nicola; Groshkova, Teodora; Hellier, Jennifer; Charles, Vikki; Martin, Anthea; Forzisi, Luciana; Lintzeris, Nicholas; Zador, Deborah; Williams, Hugh; Carnwath, Tom; Mayet, Soraya; Strang, John

    2015-03-01

    The Randomized Injectable Opioid Treatment Trial (RIOTT) compared supervised injectable heroin (SIH) and supervised injectable methadone (SIM) with optimized oral methadone (OOM) (ISRCTN0133807). Heroin addicts (previously unresponsive to treatment) made significant reductions in street heroin use at 6 months when treated with SIH. We now examine secondary outcomes. Multi-site randomized controlled trial (RCT) comparing SIH versus OOM and SIM versus OOM. Three supervised injectable opiate clinics in England. Chronic refractory heroin addicts continuing to inject street heroin virtually daily despite oral substitution treatment (n = 127), randomized to either SIH(n = 43), SIM(n = 42) or OOM(n = 42). All received high levels of medical and psychosocial support. wider drug use, crime, health and social functioning at 6 months. At 6 months, no significant differences were found between treatment groups in wider drug use (crack/cocaine, benzodiazepines, alcohol), physical and mental health (SF-36) or social functioning. Within each treatment group, significant reductions were observed in crime [SIH = odds ratio (OR) 0.05; P health for SIH and SIM (SIH = mean change 3.97; P = 0.008; SIM = mean change 4.73; P = 0.002) and mental health for OOM (mean change 6.04; P = 0.013). Supervised injectable heroin treatment and supervised injectable methadone treatment showed no clearly identified benefit over optimized oral methadone in terms of wider drug use, crime, physical and mental health within a 6-month period, despite reducing street heroin use to a greater extent. However, all interventions were associated with improvements in these outcomes. © 2014 Society for the Study of Addiction.

  17. Evaluation of the methodologies used to generate random pavement profiles based on the power spectral density: An approach based on the International Roughness Index

    Directory of Open Access Journals (Sweden)

    Boris Jesús Goenaga

    2017-01-01

    Full Text Available The pavement roughness is the main variable that produces the vertical excitation in vehicles. Pavement profiles are the main determinant of (i discomfort perception on users and (ii dynamic loads generated at the tire-pavement interface, hence its evaluation constitutes an essential step on a Pavement Management System. The present document evaluates two specific techniques used to simulate pavement profiles; these are the shaping filter and the sinusoidal approach, both based on the Power Spectral Density. Pavement roughness was evaluated using the International Roughness Index (IRI, which represents the most used index to characterize longitudinal road profiles. Appropriate parameters were defined in the simulation process to obtain pavement profiles with specific ranges of IRI values using both simulation techniques. The results suggest that using a sinusoidal approach one can generate random profiles with IRI values that are representative of different road types, therefore, one could generate a profile for a paved or an unpaved road, representing all the proposed categories defined by ISO 8608 standard. On the other hand, to obtain similar results using the shaping filter approximation a modification in the simulation parameters is necessary. The new proposed values allow one to generate pavement profiles with high levels of roughness, covering a wider range of surface types. Finally, the results of the current investigation could be used to further improve our understanding on the effect of pavement roughness on tire pavement interaction. The evaluated methodologies could be used to generate random profiles with specific levels of roughness to assess its effect on dynamic loads generated at the tire-pavement interface and user’s perception of road condition.

  18. Generator. Generator

    Energy Technology Data Exchange (ETDEWEB)

    Knoedler, R.; Bossmann, H.P.

    1992-03-12

    The invention refers to a thermo-electric generator, whose main part is a sodium concentration cell. In conventional thermo-electric generators of this kind, the sodium moving from a hot space to a colder space must be transported back to the hot space via a circulation pipe and a pump. The purpose of the invention is to avoid the disadvantages of this return transport. According to the invention, the thermo-electric generator is supported so that it can rotate, so that the position of each space relative to its propinquity to the heat source can be changed at any time.

  19. Anticonvulsant profile and teratogenicity of 3,3-dimethylbutanoylurea: a potential for a second generation drug to valproic acid.

    Science.gov (United States)

    Shimshoni, Jakob Avi; Yagen, Boris; Pessah, Neta; Wlodarczyk, Bogdan; Finnell, Richard H; Bialer, Meir

    2008-07-01

    The purpose of this study was to evaluate the anticonvulsant activity and teratogenic potential of branched aliphatic acylureas represented by isovaleroylurea (IVU), pivaloylurea (PVU) and 3,3-dimethylbutanoylurea (DBU), as potential second-generation drugs to valproic acid (VPA). The anticonvulsant activity of IVU, PVU, and DBU was determined in mice and rats utilizing the maximal electroshock seizure (MES) and the pentylenetetrazole (scMet) tests. The ability of DBU to block electrical-, or chemical-induced seizures was further examined in three acute seizure models: the psychomotor 6 Hz model, the bicuculline and picrotoxin models and one model of chronic epilepsy (i.e., the hippocampal kindled rat model). The induction of neural tube defects (NTDs) by IVU, PVU, and DBU was evaluated after i.p. administration at day 8.5 of gestation to a mouse strain highly susceptible to VPA-induced teratogenicity. The pharmacokinetics of DBU was studied following i.v. administration to rats. DBU emerged as the most potent compound having an MES-ED(50)of 186 mg/kg (mice) and 64 mg/kg (rats) and an scMet-ED(50)of 66 mg/kg (mice) and 26 mg/kg (rats). DBU underwent further evaluation in the hippocampal kindled rat (ED(50)= 35 mg/kg), the psychomotor 6 Hz mouse model (ED(50)= 80 mg/kg at 32 mA and ED(50)= 133 mg/kg at 44 mA), the bicuculline- and picrotoxin-induced seizure mouse model (ED(50)= 205 mg/kg and 167 mg/kg, respectively). In contrast to VPA, DBU, IVU, and PVU did not induce a significant increase in NTDs as compared to control. DBU was eliminated by metabolism with a half-life of 4.5 h. DBU's broad spectrum and potent anticonvulsant activity, along with its high safety margin and favorable pharmacokinetic profile, make it an attractive candidate to become a new, potent, and safe AED.

  20. Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

    Science.gov (United States)

    Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

    2016-09-10

    The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Randomized Controlled Trials of Technology-Based HIV/STI and Drug Abuse Preventive Interventions for African American and Hispanic Youth: Systematic Review.

    Science.gov (United States)

    Córdova, David; Mendoza Lua, Frania; Ovadje, Lauretta; Hong, Ethan; Castillo, Berenice; Salas-Wright, Christopher P

    2017-12-13

    HIV/sexually transmitted infections (STIs) and drug abuse remain significant public health concerns in the United States, and African American and Hispanic youth are disproportionately affected. Although technology-based interventions are efficacious in preventing and reducing HIV/STI and licit/illicit drug use behaviors, relatively little is known regarding the state of the science of these interventions among African American and Hispanic youth. The aim of this review is to identify and examine randomized controlled trials (RCTs) of technology-based HIV/STI and/or drug abuse preventive interventions for African American and Hispanic youth. We searched electronic databases (ie, PubMed, Proquest, PsycINFO, Ebscohost, Google Scholar) to identify studies between January 2006 and October 2016. RCTs of technology-based interventions targeting African American and Hispanic youth HIV/STI risk behaviors, including sexual risk, licit and illicit drug use, and HIV/STI testing were included. Our search revealed a total of three studies that used an RCT design and included samples comprised of >50% African American and/or Hispanic youth. The follow-up assessments ranged from two weeks to six months and the number of participants in each trial ranged from 72 to 141. The three interventions were theory-driven, interactive, and tailored. The long-term effects of the interventions were mixed, and outcomes included reductions in sex partners, licit drug use, and condomless anal sex acts. Although technology-based interventions seem promising in the prevention of HIV/STI and drug abuse among African American and Hispanic youth, more research is needed.

  2. Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial.

    Science.gov (United States)

    Schneider, Peter A; Laird, John R; Tepe, Gunnar; Brodmann, Marianne; Zeller, Thomas; Scheinert, Dierk; Metzger, Christopher; Micari, Antonio; Sachar, Ravish; Jaff, Michael R; Wang, Hong; Hasenbank, Melissa S; Krishnan, Prakash

    2018-01-01

    Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2-4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank PURL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States. © 2018 The Authors.

  3. [Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study

    Directory of Open Access Journals (Sweden)

    Mattace-Raso Francesco US

    2011-08-01

    Full Text Available Background Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. Methods/Design A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged ≥65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D, costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. Discussion The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. Trial Registration The trial is registered in the Netherlands Trial Register (NTR1593

  4. Community Pharmacist Training-and-Communication Network and Drug-Related Problems in Patients With CKD: A Multicenter, Cluster-Randomized, Controlled Trial.

    Science.gov (United States)

    Lalonde, Lyne; Quintana-Bárcena, Patricia; Lord, Anne; Bell, Robert; Clément, Valérie; Daigneault, Anne-Marie; Legris, Marie-Ève; Letendre, Sara; Mouchbahani, Marie; Jouini, Ghaya; Azar, Joëlle; Martin, Élisabeth; Berbiche, Djamal; Beaulieu, Stephanie; Beaunoyer, Sébastien; Bertin, Émilie; Bouvrette, Marianne; Charbonneau-Séguin, Noémie; Desrochers, Jean-François; Desforges, Katherine; Dumoulin-Charette, Ariane; Dupuis, Sébastien; El Bouchikhi, Maryame; Forget, Roxanne; Guay, Marianne; Lemieux, Jean-Phillippe; Morin-Bélanger, Claudia; Noël, Isabelle; Ricard, Stephanie; Sauvé, Patricia; Ste-Marie Paradis, François

    2017-09-01

    Appropriate training for community pharmacists may improve the quality of medication use. Few studies have reported the impact of such programs on medication management for patients with chronic kidney disease (CKD). Multicenter, cluster-randomized, controlled trial. Patients with CKD stage 3a, 3b, or 4 from 6 CKD clinics (Quebec, Canada) and their community pharmacies. Each cluster (a pharmacy and its patients) was randomly assigned to either ProFiL, a training-and-communication network program, or the control group. ProFiL pharmacists completed a 90-minute interactive web-based training program on use of medications in CKD and received a clinical guide, patients' clinical summaries, and facilitated access to the CKD clinic. Drug-related problems (primary outcome), pharmacists' knowledge and clinical skills, and patients' clinical attributes (eg, blood pressure and glycated hemoglobin concentration). Drug-related problems were evaluated the year before and after the recruitment of patients using a validated set of significant drug-related problems, the Pharmacotherapy Assessment in Chronic Renal Disease (PAIR) criteria. Pharmacists' questionnaires were completed at baseline and after 1 year. Clinical attributes were documented at baseline and after 1 year using available information in medical charts. 207 community pharmacies, 494 pharmacists, and 442 patients with CKD participated. After 1 year, the mean number of drug-related problems per patient decreased from 2.16 to 1.60 and from 1.70 to 1.62 in the ProFiL and control groups, respectively. The difference in reduction of drug-related problems per patient between the ProFiL and control groups was -0.32 (95% CI, -0.63 to -0.01). Improvements in knowledge (difference, 4.5%; 95% CI, 1.6%-7.4%) and clinical competencies (difference, 7.4%; 95% CI, 3.5%-11.3%) were observed among ProFiL pharmacists. No significant differences in clinical attributes were observed across the groups. High proportion of missing data

  5. Comparison of 2 lumbar total disc replacements: results of a prospective, randomized, controlled, multicenter Food and Drug Administration trial with 24-month follow-up.

    Science.gov (United States)

    Guyer, Richard D; Pettine, Kenneth; Roh, Jeffrey S; Dimmig, Thomas A; Coric, Domagoj; McAfee, Paul C; Ohnmeiss, Donna D

    2014-05-20

    This was a prospective, randomized, controlled multicenter study with 24-month follow-up. The purpose of this study was to evaluate the safety and efficacy in a Food and Drug Administration Investigation Device Exemption of a new lumbar total disc replacement (TDR) by comparing it to an earlier TDR approved for sale. Randomized trials have reported TDR to produce results similar or superior to lumbar fusion. Results for various TDRs seem to be similar, but differences in study design and outcome measures pose challenges in definitively comparing devices. The purpose of this study was to perform a direct comparison of 2 lumbar TDRs in a prospective, randomized trial. TDR was performed in 457 patients from 21 sites (261 patients in the investigational group (Kineflex-L Disc; metal-on-metal design anchored with keels, 204 randomized and 57 nonrandomized training cases), and 196 in the control group (CHARITE artificial disc; metal with polyethylene core with teeth for anchoring; 190 randomized and 6 nonrandomized training cases). All patients were treated nonoperatively for single-level symptomatic disc degeneration for at least 6 months prior to surgery. Perioperative data were collected. Clinical outcome data were collected prospectively, as approved by the Food and Drug Administration, through 24-month follow-up. Primary outcome measures used were the Oswestry Disability Index, visual analogue scales assessing pain, patient satisfaction, and reoperations. Success was defined to be at least 15-point improvements in Oswestry Disability Index scores, no reoperation, and no major adverse events. Radiographical measures included range of motion, disc space height, and assessment for device migration, subsidence, and fusion at the TDR level. There were no significant differences between the groups when comparing operative time, blood loss, or length of hospital stay. Both groups improved significantly on Oswestry Disability Index and visual analogue scale scores (P < 0

  6. Cognitive consequences of early versus late antiepileptic drug withdrawal after pediatric epilepsy surgery, the TimeToStop (TTS) trial: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Boshuisen, Kim; Lamberink, Herm J; van Schooneveld, Monique Mj; Cross, J Helen; Arzimanoglou, Alexis; van der Tweel, Ingeborg; Geleijns, Karin; Uiterwaal, Cuno Spm; Braun, Kees Pj

    2015-10-26

    The goals of intentional curative pediatric epilepsy surgery are to achieve seizure-freedom and antiepileptic drug (AED) freedom. Retrospective cohort studies have indicated that early postoperative AED withdrawal unmasks incomplete surgical success and AED dependency sooner, but not at the cost of long-term seizure outcome. Moreover, AED withdrawal seemed to improve cognitive outcome. A randomized trial is needed to confirm these findings. We hypothesized that early AED withdrawal in children is not only safe, but also beneficial with respect to cognitive functioning. This is a multi-center pragmatic randomized clinical trial to investigate whether early AED withdrawal improves cognitive function, in terms of attention, executive function and intelligence, quality of life and behavior, and to confirm safety in terms of eventual seizure freedom, seizure recurrences and "seizure and AED freedom." Patients will be randomly allocated in parallel groups (1:1) to either early or late AED withdrawal. Randomization will be concealed and stratified for preoperative IQ and medical center. In the early withdrawal arm reduction of AEDs will start 4 months after surgery, while in the late withdrawal arm reduction starts 12 months after surgery, with intended complete cessation of drugs after 12 and 20 months respectively. Cognitive outcome measurements will be performed preoperatively, and at 1 and 2 years following surgery, and consist of assessment of attention and executive functioning using the EpiTrack Junior test and intelligence expressed as IQ (Wechsler Intelligence Scales). Seizure outcomes will be assessed at 24 months after surgery, and at 20 months following start of AED reduction. We aim to randomize 180 patients who underwent anticipated curative epilepsy surgery below 16 years of age, were able to perform the EpiTrack Junior test preoperatively, and have no predictors of poor postoperative seizure prognosis (multifocal magnetic resonance imaging (MRI

  7. The Cedar Project WelTel mHealth intervention for HIV prevention in young Indigenous people who use illicit drugs: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Jongbloed, Kate; Friedman, Anton J; Pearce, Margo E; Van Der Kop, Mia L; Thomas, Vicky; Demerais, Lou; Pooyak, Sherri; Schechter, Martin T; Lester, Richard T; Spittal, Patricia M

    2016-03-09

    Despite successes in preventing and treating HIV, Indigenous people in Canada continue to face disproportionately high rates of HIV infection. Programs that support healing from lifetime trauma, support connection to culture, and reduce drug-related harms are critical to preventing HIV among young Indigenous people who use drugs. The Cedar Project WelTel mHealth intervention proposed here is a structured mobile-phone initiative to connect young Indigenous people who use drugs with Cedar Case Managers in a community-based setting. The intervention consists of a package of supports, including a mobile phone and cellular plan, weekly two-way text messaging, and support from Cedar Case Managers. The Cedar Project WelTel mHealth study is a multi-site Zelen pre-randomized trial to measure the effect of a two-way supportive text-message intervention to reduce HIV vulnerability among young Indigenous people who use illicit drugs in two Canadian cities. The trial is nested within the Cedar Project, an ongoing cohort study addressing HIV and hepatitis C vulnerability among young Indigenous people who use drugs in Vancouver and Prince George, British Columbia. The Cedar Project Partnership, an independent body of Indigenous Elders, leaders, and health/social service experts, governs all aspects of the study. Two hundred participants will be followed over a 16-month period, with HIV propensity score at 6 months as the primary outcome. Secondary outcomes include HIV propensity at 1 year, HIV risk, resilience, psychological distress, access to drug-related services, and connection to culture measured at 6 months and 1 year. Primary analysis is by intention to treat. Culturally safe interventions that address barriers to HIV prevention while supporting the strength of young Indigenous people who use drugs are urgently needed. Despite presenting a tremendous opportunity to connect young, highly transient Indigenous people who use drugs to prevention services, supportive two-way m

  8. Community Impact of Pharmacy-Randomized Intervention to Improve Access to Syringes and Services for Injection Drug Users

    Science.gov (United States)

    Crawford, Natalie D.; Amesty, Silvia; Rivera, Alexis V.; Harripersaud, Katherine; Turner, Alezandria; Fuller, Crystal M.

    2014-01-01

    Objectives: In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural, pharmacy-based…

  9. HIV-1 Drug Resistance and Second-Line Treatment in Children Randomized to Switch at Low Versus Higher RNA Thresholds

    NARCIS (Netherlands)

    Harrison, L.; Melvin, A.; Fiscus, S.; Saidi, Y.; Nastouli, E.; Harper, L.; Compagnucci, A.; Babiker, A.; McKinney, R.; Gibb, D.; Tudor-Williams, G.; Burger, D.M.

    2015-01-01

    BACKGROUND: The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. METHODS: PENPACT-1 had a 2 x 2 factorial

  10. Effectiveness of the universal prevention program 'Healthy School and Drugs': Study protocol of a randomized clustered trial

    NARCIS (Netherlands)

    Malmberg, M.; Overbeek, G.J.; Kleinjan, M.; Vermulst, A.A.; Monshouwer, K.; Lammers, J.; Vollebergh, W.A.M.; Engels, R.C.M.E.

    2010-01-01

    Background: Substance use is highly prevalent among Dutch adolescents. The Healthy School and Drugs program is a nationally implemented school-based prevention program aimed at reducing early and excessive substance use among adolescents. Although the program's effectiveness was tested in a

  11. Effectiveness of the universal prevention program 'Healthy School and Drugs': study protocol of a randomized clustered trial

    NARCIS (Netherlands)

    Malmberg, M.; Overbeek, G.J.; Kleinjan, M.; Vermulst, A.; Monshouwer, K.; Lammers, J.; Vollebergh, W.A.M.; Engels, R.C.M.E.

    2010-01-01

    Background: Substance use is highly prevalent among Dutch adolescents. The Healthy School and Drugs program is a nationally implemented school-based prevention program aimed at reducing early and excessive substance use among adolescents. Although the program's effectiveness was tested in a

  12. Drug-Eluting Balloon versus New-Generation Drug-Eluting Stent for the Treatment of In-Stent Restenosis: An Updated Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Kong-Yong Cui

    2018-01-01

    Conclusions: The current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies.

  13. Generator. Generator

    Energy Technology Data Exchange (ETDEWEB)

    Bossmann, H.P.; Knoedler, R.

    1992-03-12

    The invention refers to a thermo-electric generator, which contains sodium as the means of heat transport. The sodium moves from the space of higher temperature through a space into the space of lower temperature. One can do without a pump for transporting the sodium back from the space of lower temperature to the space of higher temperature, as the thermo-electric generator can rotate around an axis. It is therefore possible to interchange the position of the two spaces relative to the heat source.

  14. Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhou, Yu-Hao; Ma, Xiu-Qiang; Wu, Cheng; Lu, Jian; Zhang, Shan-Shan; Guo, Jia; Wu, Shun-Quan; Ye, Xiao-Fei; Xu, Jin-Fang; He, Jia

    2012-01-01

    Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45) for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17) for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12) for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04) for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40) for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58) for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors.

  15. A Peer-Educator Network HIV Prevention Intervention Among Injection Drug Users: Results of a Randomized Controlled Trial in St. Petersburg, Russia

    Science.gov (United States)

    Latkin, Carl A.; Kukhareva, Polina V.; Malov, Sergey V.; Batluk, Julia V.; Shaboltas, Alla V.; Skochilov, Roman V.; Sokolov, Nicolay V.; Verevochkin, Sergei V.; Hudgens, Michael G.; Kozlov, Andrei P.

    2014-01-01

    We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74–35.65) and 7.76 (95 % CI 3.51–17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15–1.08) without a statistically significant difference between the two groups (log rank test statistic X2 = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs. PMID:23881187

  16. Randomized Clinical Trial of Periarticular Drug Injection used in combination Patient-Controlled Analgesia versus Patient-Controlled Analgesia Alone in Total Knee Arthroplasty

    Directory of Open Access Journals (Sweden)

    MN Sabran

    2008-11-01

    Full Text Available This is a prospective randomized clinical trial to compare use of a combination of periarticular drug injection with patient- controlled analgesia (PCA to PCA alone in post-total knee arthroplasty (TKA. Thirty patients who were admitted for unilateral total knee arthroplasty were selected randomly into an Injection group or a Standard group. The periarticular injection contained Ropivacaine, Ketorolac and Adrenaline, given intra-operatively. The mean amount of opioid used was 22.87 mmol/L in the Injection group as compared to 39.78 mmol/L in the Standard group (p = 0.026. The Injection group had lower pain score at rest and during exercise (p=0.021, p=0.041, respectively, as well as better return to function (p=0.026 and shorter hospital stay (6.1 days, Injection; 7.5 days, Standard, p=0.027. Overall, the group receiving periarticular drugs injection had less pain, less narcotic usage, earlier return to function, similar experience of adverse effects and shorter hospital stays.

  17. Effectiveness of the Strengthening Families Programme 10–14 in Poland for the prevention of alcohol and drug misuse: protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Okulicz-Kozaryn Katarzyna

    2012-06-01

    Full Text Available Abstract Background Alcohol and other drug use and misuse is a significant problem amongst Polish youth. The SFP10-14 is a family-based prevention intervention that has positive results in US trials, but questions remain about the generalizability of these results to other countries and settings. Methods/Design A cluster randomized controlled trial in community settings across Poland. Communities will be randomized to a SFP10-14 trial arm or to a control arm. Recruitment and consent of families, and delivery of the SFP10-14, will be undertaken by community workers. The primary outcomes are alcohol and other drug use and misuse. Secondary (or intermediate outcomes include parenting practices, parent–child relations, and child problem behaviour. Interview-based questionnaires will be administered at baseline, 12 and 24 months. Discussion The trial will provide information about the effectiveness of the SFP10-14 in Poland. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN89673828

  18. Reducing risky relationships: a multisite randomized trial of a prison-based intervention for reducing HIV sexual risk behaviors among women with a history of drug use.

    Science.gov (United States)

    Knudsen, Hannah K; Staton-Tindall, Michele; Oser, Carrie B; Havens, Jennifer R; Leukefeld, Carl G

    2014-01-01

    Women involved in the criminal justice system, particularly those with a history of drug use, are at elevated risk of HIV infection, yet few HIV prevention interventions have been tailored for delivery to incarcerated women. Drawing on the Relational Model, the Reducing Risky Relationships for HIV (RRR-HIV) intervention was developed and evaluated in a multisite randomized clinical trial. Women with weekly drug use prior to incarceration (n = 444) who were incarcerated within correctional institutions in four states were randomized to (1) the RRR-HIV intervention consisting of an HIV educational video, five group sessions, and one postrelease booster session or (2) a control condition consisting of the HIV educational video. The RRR-HIV intervention combined didactic and interactive content regarding seven "thinking myths" about intimate relationships that may result in decisions to engage in risky sexual behaviors. Data were collected while women were still incarcerated and approximately 90 days following release from prison by trained interviewers. A negative binomial regression (NBR) model of unprotected sexual behaviors at the 90-day follow-up indicated that RRR-HIV participants reported fewer unprotected sexual behaviors than women in the control condition once the analysis was adjusted for study site. Future studies should examine the sustainability of the RRR-HIV intervention's effect on risk reduction. Implementation research is needed to determine whether delivery of this intervention by correctional staff or peers, rather than research staff, yields similar reductions in unprotected sexual behaviors.

  19. Web-based screening and brief intervention for poly-drug use among teenagers: study protocol of a multicentre two-arm randomized controlled trial.

    Science.gov (United States)

    Arnaud, Nicolas; Bröning, Sonja; Drechsel, Magdalena; Thomasius, Rainer; Baldus, Christiane

    2012-09-26

    Mid to late adolescence is characterised by a vulnerability to problematic substance use since the consumption of alcohol and illicit drugs is frequently initiated and increased in this life period. While the detrimental long- and short-term effects of problematic consumption patterns in adolescence pose a major public health concern, current prevention programs targeting alcohol- and other substance-using adolescents are scarce. The study described in this protocol will test the effectiveness of a web-based brief intervention aimed at reducing problematic alcohol use and promoting abstinence from illegal drugs in adolescents with risky substance use aged 16 to 18 years old in four EU-countries. To determine the effectiveness of our web-BI, we apply a two-arm randomized controlled trial (RCT) study design, with baseline assessment at study entry and a three month follow-up assessment. Adolescents aged 16 to 18 years from Belgium, the Czech Republic, Germany, and Sweden will be randomly assigned to either the fully electronically delivered brief intervention group (N = 400) or an assessment only control group (N = 400) depending on their screening for risky substance use (using the CRAFFT). Recruitment, informed consent, randomization, intervention and follow-up will be implemented online. Primary outcomes are reductions in frequency and quantity of use of alcohol and drugs other than alcohol over a 30 day period, as well as consumption per typical occasion. Secondary outcomes concern changes in substance use related cognitions including the constructs of the Theory of Planned Behaviour, implementation intentions, and stages of change. Moreover the study addresses a number of moderator variables, including age of first use, general psychopathology and quality of parent-child relationship. The trial is expected to contribute to the growing literature on theory- and web-based brief interventions for adolescents. We will explore the potential of using web

  20. Web-based screening and brief intervention for poly-drug use among teenagers: study protocol of a multicentre two-arm randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Arnaud Nicolas

    2012-09-01

    Full Text Available Abstract Background Mid to late adolescence is characterised by a vulnerability to problematic substance use since the consumption of alcohol and illicit drugs is frequently initiated and increased in this life period. While the detrimental long- and short-term effects of problematic consumption patterns in adolescence pose a major public health concern, current prevention programs targeting alcohol- and other substance-using adolescents are scarce. The study described in this protocol will test the effectiveness of a web-based brief intervention aimed at reducing problematic alcohol use and promoting abstinence from illegal drugs in adolescents with risky substance use aged 16 to 18 years old in four EU-countries. Methods/design To determine the effectiveness of our web-BI, we apply a two-arm randomized controlled trial (RCT study design, with baseline assessment at study entry and a three month follow-up assessment. Adolescents aged 16 to 18 years from Belgium, the Czech Republic, Germany, and Sweden will be randomly assigned to either the fully electronically delivered brief intervention group (N = 400 or an assessment only control group (N = 400 depending on their screening for risky substance use (using the CRAFFT. Recruitment, informed consent, randomization, intervention and follow-up will be implemented online. Primary outcomes are reductions in frequency and quantity of use of alcohol and drugs other than alcohol over a 30 day period, as well as consumption per typical occasion. Secondary outcomes concern changes in substance use related cognitions including the constructs of the Theory of Planned Behaviour, implementation intentions, and stages of change. Moreover the study addresses a number of moderator variables, including age of first use, general psychopathology and quality of parent–child relationship. Discussion The trial is expected to contribute to the growing literature on theory- and web-based brief interventions

  1. Fully digital jerk-based chaotic oscillators for high throughput pseudo-random number generators up to 8.77Gbits/s

    KAUST Repository

    Mansingka, Abhinav S.

    2014-06-18

    This paper introduces fully digital implementations of four di erent systems in the 3rd order jerk-equation based chaotic family using the Euler approximation. The digitization approach enables controllable chaotic systems that reliably provide sinusoidal or chaotic output based on a selection input. New systems are introduced, derived using logical and arithmetic operations between two system implementations of different bus widths, with up to 100x higher maximum Lyapunov exponent than the original jerkequation based chaotic systems. The resulting chaotic output is shown to pass the NIST sp. 800-22 statistical test suite for pseudorandom number generators without post-processing by only eliminating the statistically defective bits. The systems are designed in Verilog HDL and experimentally verified on a Xilinx Virtex 4 FPGA for a maximum throughput of 15.59 Gbits/s for the native chaotic output and 8.77 Gbits/s for the resulting pseudo-random number generators.

  2. Comparative Effectiveness of Acupuncture and Antiarrhythmic Drugs for the Prevention of Cardiac Arrhythmias: A Systematic Review and Meta-analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Yanda Li

    2017-06-01

    Full Text Available Introduction and Objectives: This study was designed to systematically evaluate the effectiveness of acupuncture treatment for arrhythmia compared to existing drug therapy.Methods: Randomized controlled trials (RCTs were identified through searches of the MEDLINE, CNKI, Embase, and Cochrane databases (1970 through 2016 and hand searches of cross-references from original articles and reviews. Clinical trials that randomized arrhythmia patients to acupuncture therapy vs. conventional drugs, sham acupuncture, or bed rest were included for analysis.Results: A total of 13 trials with 797 patients met the criteria for analysis. The results of the meta-analysis showed no statistically significant difference between acupuncture and conventional treatment for paroxysmal supraventricular tachycardia (PSVT (n = 203; RR, 1.18; 95% CI 0.78–1.79; I2 = 80%; P = 0.44. However, in the ventricular premature beat (VPB group, it showed a significant benefit of acupuncture plus oral administration of anti-arrhythmic drug (AAD on response rates compared with the oral administration of AAD (n = 286; RR, 1.15; 95% CI 1.05–1.27; I2 = 0%; P = 0.002. Finally, when compared with the sinus tachycardia (ST cases without any treatment, acupuncture has benefited these patients (n = 120; MD, 18.80, 95% CI 12.68–24.92; I2 = 81%; P < 0.00001.Conclusions: In summary, our meta-analysis demonstrates that clinical efficacy of acupuncture is not less than AAD for PSVT. Furthermore, in sub-group analysis, acupuncture with or without AAD, shows a clear benefit in treating VPB and ST. However, more definitive RCTs are warranted to guide clinical practice.

  3. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH).

    Science.gov (United States)

    Kuck, K H; Cappato, R; Siebels, J; Rüppel, R

    2000-08-15

    We conducted a prospective, multicenter, randomized comparison of implantable cardioverter-defibrillator (ICD) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias. From 1987, eligible patients were randomized to an ICD, amiodarone, propafenone, or metoprolol (ICD versus antiarrhythmic agents randomization ratio 1:3). Assignment to propafenone was discontinued in March 1992, after an interim analysis conducted in 58 patients showed a 61% higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months. The study continued to recruit 288 patients in the remaining 3 study groups; of these, 99 were assigned to ICDs, 92 to amiodarone, and 97 to metoprolol. The primary end point was all-cause mortality. The study was terminated in March 1998, when all patients had concluded a minimum 2-year follow-up. Over a mean follow-up of 57+/-34 months, the crude death rates were 36.4% (95% CI 26.9% to 46.6%) in the ICD and 44.4% (95% CI 37.2% to 51.8%) in the amiodarone/metoprolol arm. Overall survival was higher, though not significantly, in patients assigned to ICD than in those assigned to drug therapy (1-sided P=0.081, hazard ratio 0.766, [97.5% CI upper bound 1.112]). In ICD patients, the percent reductions in all-cause mortality were 41.9%, 39.3%, 28. 4%, 27.7%, 22.8%, 11.4%, 9.1%, 10.6%, and 24.7% at years 1 to 9 of follow-up. During long-term follow-up of cardiac arrest survivors, therapy with an ICD is associated with a 23% (nonsignificant) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol. The benefit of ICD therapy is more evident during the first 5 years after the index event.

  4. The explanatory role of stroke as a mediator of the mortality risk difference between older adults who initiate first- versus second-generation antipsychotic drugs.

    Science.gov (United States)

    Jackson, John W; VanderWeele, Tyler J; Viswanathan, Anand; Blacker, Deborah; Schneeweiss, Sebastian

    2014-10-15

    Antipsychotic drugs are used to treat dementia-related symptoms in older adults, and observational studies show higher risks of death and stroke associated with the use of first-generation antipsychotic drugs (FGAs) compared with second-generation antipsychotic drugs (SGAs). However, the extent to which stroke explains the differential mortality risk between FGA use and SGA use in older adults is unclear. We followed those who initiated use of antipsychotic drugs (9,777 FGA users and 21,164 SGA users) aged 65 years or older, and who were enrolled in Medicare and either the New Jersey or Pennsylvania pharmacy assistance program during 1994 to 2005, over 180 days for the outcomes of stroke and death. We estimated direct and indirect effects by comparing 180-day mortality risks associated with the use of FGAs versus SGAs as mediated by stroke on the risk ratio scale, as well as the proportion mediated on the risk difference scale. FGA use was associated with marginally higher risks of stroke (risk ratio =1.24, 95% confidence interval (CI): 1.01, 1.53) and death (risk ratio = 1.15, 95% CI: 1.08, 1.22) compared with SGA use, but stroke explained little (2.7%) of the observed difference in mortality risk. The indirect effect was null (risk ratio = 1.004, 95% CI: 1.000, 1.008), and the direct effect was equal to the total effect of antipsychotic drug type (FGA vs. SGA) on mortality risk (risk ratio = 1.15, 95% CI: 1.08, 1.22). These results suggest that the difference in mortality risk between users of FGAs and SGAs may develop mostly through pathways that do not involve stroke. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Adding ofloxacin to standard triple-drug regimens increased the Helicobacter pylori eradication rate: Data from randomized clinical trial

    OpenAIRE

    Sadeghi-Hadad-Zavareh, Mahmoud; Mohammadi, Seyyedsaeid; Hajiahmadi, Mahmoud; Javanian, Mostafa; Habibian, Masoomeh

    2017-01-01

    Background: The rate of Helicobacter pylori (H.pylori) eradication in dyspeptic patients using bismuth- based triple therapy is low due to bacterial that are resistant to antibiotics. The results of recent studies regarding levofloxacin have been encouraging, but the high cost of treatment prevents its routine administration. We, therefore, performed the present double-blind clinical trial to compare the efficiency of quadruple-drug regimen containing ofloxacin, clarithromycin, amoxicillin, a...

  6. Efficacy of Immunobiologic and Small Molecule Inhibitor Drugs for Psoriasis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

    Science.gov (United States)

    de Carvalho, André Vicente Esteves; Duquia, Rodrigo Pereira; Horta, Bernardo Lessa; Bonamigo, Renan Rangel

    2017-03-01

    Psoriasis is an immune-mediated inflammatory disease for which treatment has evolved over the past few years due to the introduction of immunobiologic and small molecule inhibitor medications. A better understanding of the comparative efficacies of drugs may help doctors to choose the most appropriate treatment for patients. The aim of this study was to conduct a systematic review and meta-analysis to assess the efficacy of immunobiologic and small molecule inhibitor drugs for patients with moderate to severe psoriasis. The EMBASE, PUBMED, LILACS, Web of Science and ClinicalTrials.org databases were searched for trials published to 21 July 2016. Only randomized, double-blind, placebo-controlled clinical trials that evaluated the efficacy of immunobiologics or small molecule inhibitors for moderate to severe plaque-type psoriasis were selected by two independent authors. No restrictions were used. Two authors independently extracted the data and a random-effects model meta-analysis was performed. The Psoriasis Area and Severity Index (PASI) 75 was considered the primary outcome, measured at the primary endpoint of each study. Thirty-eight studies were included in our analysis. The overall pooled effect favored biologics and small molecule inhibitors over placebo (risk difference [RD] 0.59, 95% confidence interval [CI] 0.58-0.60). Ixekizumab at a dose of 160 mg on week 0 and then every 2 weeks (RD 0.84, 95% CI 0.81-0.88), brodalumab 210 mg (RD 0.79, 95% CI 0.76-0.82), infliximab 5 mg/kg (RD 0.76, 95% CI 0.73-0.79), and secukinumab 300 mg (RD 0.76, 95% CI 0.71-0.81) showed a greater chance of response (PASI 75) when compared with placebo. The methodology of a traditional meta-analysis does not allow for drugs to be ranked. Included studies used short-term endpoints (10-16 weeks) to evaluate the primary outcome, therefore long-term efficacy could not be determined. The anti-IL-17 drugs brodalumab, ixekizumab and secukinumab showed an equal or greater chance of

  7. Pooled analysis of two randomized trials comparing titanium-nitride-oxide-coated stent versus drug-eluting stent in STEMI.

    Science.gov (United States)

    Tuomainen, Petri O; Sia, Jussi; Nammas, Wail; Niemelä, Matti; Airaksinen, Juhani K E; Biancari, Fausto; Karjalainen, Pasi P

    2014-07-01

    We performed a pooled analysis based on patient-level data from the TITAX-AMI and BASE-ACS trials to evaluate the outcome of titanium-nitride-oxide-coated bioactive stents vs drug-eluting stents in patients with ST-segment elevation myocardial infarction at 2-year follow-up. The TITAX-AMI trial compared bioactive stents with paclitaxel-eluting stents in 425 patients with acute myocardial infarction. The BASE-ACS trial compared bioactive stents with everolimus-eluting stents in 827 patients with acute coronary syndrome. The primary endpoint for the pooled analysis was major adverse cardiac events: a composite of cardiac death, recurrent myocardial infarction, or ischemia-driven target lesion revascularization at 2-year follow-up. The pooled analysis included 501 patients; 245 received bioactive stents, and 256 received drug-eluting stents. The pooled bioactive stent group was associated with a risk ratio of 0.85 for major adverse cardiac events (95% confidence interval, 0.53-1.35; P=.49) compared to the pooled drug-eluting stent group. Similarly, the pooled bioactive stent group was associated with a risk ratio of 0.71 for cardiac death (95% confidence interval, 0.26-1.95; P=.51), 0.44 for recurrent myocardial infarction (95% confidence interval, 0.20-0.97; P=.04), and 1.39 for ischemia-driven target lesion revascularization (95% confidence interval, 0.74-2.59; P=.30), compared to the pooled drug-eluting stent group. These results were confirmed by propensity-score adjusted analysis of the combined datasets. In patients with ST-segment elevation myocardial infarction, bioactive stents were associated with lower rates of recurrent myocardial infarction compared to drug-eluting stents at 2-year follow-up; yet, the rates of cardiac death and ischemia-driven target lesion revascularization were similar. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  8. Impact of drug-eluting stent generation on patient- and stent-related adverse events of diabetic patients treated by percutaneous coronary intervention.

    Science.gov (United States)

    D'Amico, G; Fabris, T; Mojoli, M; Napodano, M; Frigo, A C; Buja, P; Hoxha, B; Lunardon, A; Zanetti, C; Isabella, G; Iliceto, S; Tarantini, G

    2014-02-01

    Aim of the present study was to assess stent- and patient-related outcomes of the first- vs. second-generation drug-eluting stents (DES) in diabetics, according to the insulin requirement status. Data were obtained from a prospective, single-center registry of 816 consecutive patients with diabetes mellitus (23% insulin-requiring) who underwent percutaneous coronary intervention (PCI) between April 2003 and May 2012 with first- (N.=534) or second-generation DES (N.=282) at our Institution, with at least 12 months of follow-up. We assessed the occurrence of stent-related outcome, including cardiac death, target vessel-related myocardial infarction and target lesion revascularization, versus patient-related outcome, including any cause death, any myocardial infarction and any coronary revascularization. Patients treated with second-generation DES were older and had more complex lesions than patients treated with first-generation DES. Both among patients treated with first-generation DES and those treated with second generation DES, patient-related events were almost double than stent-related events. No interactions were observed between the DES generation type and insulin requirement status. In this observational study, first- and second-generation DES were equally safe and efficacious in diabetic patients undergoing PCI, regardless of insulin requirements. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasizes that the optimization of secondary prevention is at least as important as the selection of which new generation DES to implant in a specific lesion.

  9. Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery.

    Science.gov (United States)

    Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu

    2010-02-02

    Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.

  10. Antisepsis regimen in the surgical treatment of HPV generated cervical lesions: polyhexamethylene biguanide vs chlorhexidine. A randomized, double blind study.

    Science.gov (United States)

    Gerli, S; Bavetta, F; Di Renzo, G C

    2012-12-01

    To reduce the risk of local infections after surgical treatments for HPV infected cervical lesions, the post-operative regimen is generally based on the use of vaginal antimicrobial agents. The efficacy and safety of polyhexamethylene biguanide-based vaginal suppositories was compared to a similar chlorhexidine-based treatment, in the post recovery regimen after surgical treatment of cervical lesions. 50 women who underwent to CO2 laser therapy for cervical lesions were randomly assigned to receive 10 days of antiseptic treatment with chlorhexidine digluconate vaginal suppositories, or polyhexamethylene biguanide vaginal suppositories (Monogin®/Biguanelle® ovuli, Lo.Li. Pharma, Italy). A weekly follow-up check was performed for 6 weeks. Polyhexamethylene biguanide-based treatment showed improved efficacy compared to chlorhexidine, in terms of healing process and prevention of bacterial infections. Due to its safety and effectiveness, the vaginal treatment with polyhexamethylene biguanide is preferred to chlorexidine, in accordance with previously reported in vitro evidences.

  11. The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Park Kyung

    2012-03-01

    Full Text Available Abstract Background Second-generation drug-eluting stents (DES have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES. In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI. A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES and antiplatelet regimen (TAT vs DDAT. The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734.

  12. The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

    Science.gov (United States)

    2012-01-01

    Background Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734. PMID:22463698

  13. SPARSE: Seed Point Auto-Generation for Random Walks Segmentation Enhancement in medical inhomogeneous targets delineation of morphological MR and CT images.

    Science.gov (United States)

    Chen, Haibin; Zhen, Xin; Gu, Xuejun; Yan, Hao; Cervino, Laura; Xiao, Yang; Zhou, Linghong

    2015-03-08

    In medical image processing, robust segmentation of inhomogeneous targets is a challenging problem. Because of the complexity and diversity in medical images, the commonly used semiautomatic segmentation algorithms usually fail in the segmentation of inhomogeneous objects. In this study, we propose a novel algorithm imbedded with a seed point autogeneration for random walks segmentation enhancement, namely SPARSE, for better segmentation of inhomogeneous objects. With a few user-labeled points, SPARSE is able to generate extended seed points by estimating the probability of each voxel with respect to the labels. The random walks algorithm is then applied upon the extended seed points to achieve improved segmentation result. SPARSE is implemented under the compute unified device architecture (CUDA) programming environment on graphic processing unit (GPU) hardware platform. Quantitative evaluations are performed using clinical homogeneous and inhomogeneous cases. It is found that the SPARSE can greatly decrease the sensitiveness to initial seed points in terms of location and quantity, as well as the freedom of selecting parameters in edge weighting function. The evaluation results of SPARSE also demonstrate substantial improvements in accuracy and robustness to inhomogeneous target segmentation over the original random walks algorithm.

  14. On the short-term predictability of fully digital chaotic oscillators for pseudo-random number generation

    KAUST Repository

    Radwan, Ahmed Gomaa

    2014-06-18

    This paper presents a digital implementation of a 3rd order chaotic system using the Euler approximation. Short-term predictability is studied in relation to system precision, Euler step size and attractor size and optimal parameters for maximum performance are derived. Defective bits from the native chaotic output are neglected and the remaining pass the NIST SP. 800-22 tests without post-processing. The resulting optimized pseudorandom number generator has throughput up to 17.60 Gbits/s for a 64-bit design experimentally verified on a Xilinx Virtex 4 FPGA with logic utilization less than 1.85%.

  15. Development and comparison of algorithms for generating a scan sequence for a random access scanner. [ZAP (and flow charts for ZIP and SCAN), in FORTRAN for DEC-10

    Energy Technology Data Exchange (ETDEWEB)

    Eason, R. O.

    1980-09-01

    Many data acquisition systems incorporate high-speed scanners to convert analog signals into digital format for further processing. Some systems multiplex many channels into a single scanner. A random access scanner whose scan sequence is specified by a table in random access memory will permit different scan rates on different channels. Generation of this scan table can be a tedious manual task when there are many channels (e.g. 50), when there are more than a few scan rates (e.g. 5), and/or when the ratio of the highest scan rate to the lowest scan rate becomes large (e.g. 100:1). An algorithm is developed which will generate these scan sequences for the random access scanner and implements the algorithm on a digital computer. Application of number theory to the mathematical statement of the problem led to development of several algorithms which were implemented in FORTRAN. The most efficient of these algorithms operates by partitioning the problem into a set of subproblems. Through recursion they solve each subproblem by partitioning it repeatedly into even smaller parts, continuing until a set of simple problems is created. From this process, a pictorial representation or wheel diagram of the problem can be constructed. From the wheel diagram and a description of the original problem, a scan table can be constructed. In addition, the wheel diagram can be used as a method of storing the scan sequence in a smaller amount of memory. The most efficient partitioning algorithm solved most scan table problems in less than a second of CPU time. Some types of problems, however, required as much as a few minutes of CPU time. 26 figures, 2 tables.

  16. Ethical complexities in standard of care randomized trials: A case study of morning versus nighttime dosing of blood pressure drugs.

    Science.gov (United States)

    Kim, Scott Y H; Miller, Franklin G

    2015-12-01

    Pragmatic trials comparing "standard of care" treatments provide comparative effectiveness data to make practice of medicine more evidence-based. With electronic health records, recruiting and conducting such trials can be relatively inexpensive. But some worry that the traditional research ethics framework poses unnecessary obstacles and is not appropriate for evaluating such clinical trials. This concern is based on the view (which we call the "Standard of Care Principle") that such research is similar to usual clinical practice and therefore does not raise significant ethical issues since everyone in the research study will receive an accepted standard of care treatment. A case study of a pragmatic randomized clinical trial (Blood Pressure Medication Timing study) comparing morning versus nighttime dosing of antihypertensive medications. The Blood Pressure Medication Timing study has been proposed as a paradigm example of why the Standard of Care Principle obviates the need for traditional levels of ethical scrutiny and how the current regulatory framework poses unnecessary obstacles to research. We provide an ethical analysis of the Blood Pressure Medication Timing study, drawing on the empirical literature as well as on normative analysis. The Standard of Care Principle is the main ethical rationale given by commentators for asserting that the Blood Pressure Medication Timing study does not require "significant ethical debate" and by investigators for the assertion that the Blood Pressure Medication Timing study is minimal risk and thus eligible for lessened regulatory requirements. However, the Blood Pressure Medication Timing study raises important ethical issues, including whether it is even necessary, given the considerable randomized clinical trial evidence in support of nighttime dosing, a much larger (N≈17,000) confirmatory randomized clinical trial already in progress, evidence for safety of nighttime dosing, and the cost-free availability of the

  17. SARAPAN—A Simulated-Annealing-Based Tool to Generate Random Patterned-Channel-Age in CANDU Fuel Management Analyses

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    Doddy Kastanya

    2017-02-01

    Full Text Available In any reactor physics analysis, the instantaneous power distribution in the core can be calculated when the actual bundle-wise burnup distribution is known. Considering the fact that CANDU (Canada Deuterium Uranium utilizes on-power refueling to compensate for the reduction of reactivity due to fuel burnup, in the CANDU fuel management analysis, snapshots of power and burnup distributions can be obtained by simulating and tracking the reactor operation over an extended period using various tools such as the *SIMULATE module of the Reactor Fueling Simulation Program (RFSP code. However, for some studies, such as an evaluation of a conceptual design of a next-generation CANDU reactor, the preferred approach to obtain a snapshot of the power distribution in the core is based on the patterned-channel-age model implemented in the *INSTANTAN module of the RFSP code. The objective of this approach is to obtain a representative snapshot of core conditions quickly. At present, such patterns could be generated by using a program called RANDIS, which is implemented within the *INSTANTAN module. In this work, we present an alternative approach to derive the patterned-channel-age model where a simulated-annealing-based algorithm is used to find such patterns, which produce reasonable power distributions.

  18. Generation of random mutants to improve light-use efficiency of Nannochloropsis gaditana cultures for biofuel production.

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    Perin, Giorgio; Bellan, Alessandra; Segalla, Anna; Meneghesso, Andrea; Alboresi, Alessandro; Morosinotto, Tomas

    2015-01-01

    The productivity of an algal culture depends on how efficiently it converts sunlight into biomass and lipids. Wild-type algae in their natural environment evolved to compete for light energy and maximize individual cell growth; however, in a photobioreactor, global productivity should be maximized. Improving light use efficiency is one of the primary aims of algae biotechnological research, and genetic engineering can play a major role in attaining this goal. In this work, we generated a collection of Nannochloropsis gaditana mutant strains and screened them for alterations in the photosynthetic apparatus. The selected mutant strains exhibited diverse phenotypes, some of which are potentially beneficial under the specific artificial conditions of a photobioreactor. Particular attention was given to strains showing reduced cellular pigment contents, and further characterization revealed that some of the selected strains exhibited improved photosynthetic activity; in at least one case, this trait corresponded to improved biomass productivity in lab-scale cultures. This work demonstrates that genetic modification of N. gaditana has the potential to generate strains with improved biomass productivity when cultivated under the artificial conditions of a photobioreactor.

  19. Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs.

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    Hammami, Muhammad M; De Padua, Sophia J S; Hussein, Rajaa; Al Gaai, Eman; Khodr, Nesrine A; Al-Swayeh, Reem; Alvi, Syed N; Binhashim, Nada

    2017-12-08

    The extents of generic-reference and generic-generic average bioequivalence and intra-subject variation of on-market drug products have not been prospectively studied on a large scale. We assessed bioequivalence of 42 generic products of 14 immediate-release oral drugs with the highest number of generic products on the Saudi market. We conducted 14 four-sequence, randomized, crossover studies on the reference and three randomly-selected generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin, clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole, paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum concentration (Cmax) and area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to Cmax time of reference product (AUCReftmax) were calculated using non-compartmental method and their 90% confidence intervals (CI) were compared to the 80.00%-125.00% bioequivalence range. Percentages of individual ratios falling outside the ±25% range were also determined. Mean (SD) age and body-mass-index of 700 healthy volunteers (28-80/study) were 32.2 (6.2) years and 24.4 (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs failed to show bioequivalence. Average geometric mean ratio deviation from 100% was ≤3.2 and ≤5.4 percentage points for AUCI and Cmax, respectively, in both generic

  20. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.

    Science.gov (United States)

    Ventura, Andréa M C; Shieh, Huei Hsin; Bousso, Albert; Góes, Patrícia F; de Cássia F O Fernandes, Iracema; de Souza, Daniela C; Paulo, Rodrigo Locatelli Pedro; Chagas, Fabiana; Gilio, Alfredo E

    2015-11-01

    The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. PICU, Hospital Universitário da Universidade de São Paulo, Brazil. Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders. Patients were randomly assigned to receive either dopamine (5-10 μg/kg/min) or epinephrine (0.1-0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine. Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p=0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p=0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p=0.001). The use of epinephrine was associated with a survival odds ratio of 6.49. Dopamine was associated with an increased risk of death and healthcare

  1. Antibacterial activity of chensinin-1b, a peptide with a random coil conformation, against multiple-drug-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Shang, Dejing; Meng, Xin; Zhang, Dongdong; Kou, Zhiru

    2017-11-01

    Nosocomial infections caused by Pseudomonas aeruginosa are difficult to treat due to the low permeability of its outer membrane as well as to its remarkable ability to acquire further resistance to antibiotics. Chensinin-1b exhibited antibacterial activity against the tested multiple-drug-resistant bacteria with a MIC ranging between 1.56 and 50μM, except E. cloacae strain 0320 (MREC0320), P. fluorescens strain 0322 (MRPF0322) and E. aerogenes strain 0320 (MREA0320). However, the MIC (25μM) of chensinin-1b to multiple-drug-resistant P. aeruginosa strain (MRPA 0108) was 16-fold higher than that observed to P. aeruginosa susceptible strain CGMCC 1.860 (PA1860). Chensinin-1b was able to disturb the integration of the cytoplasmic membrane of PA1860 and MRPA0108 cells similarly, but the outer membrane permeability of MRPA0108 cells was significantly lower. This low permeability was associated with increased expression of lipopolysaccharide (LPS) in the outer membrane and a decrease in negatively charged phospholipids in the outer membrane leaflet. In addition, the biofilm of MRPA0108 was responsible for the reduced susceptibility to chensinin-1b. A higher concentration of chensinin-1b (12.5µM) was required to maximally inhibit the formation of MRPA0108 biofilm. Notably, chensinin-1b inhibited the formation of MRPA0108 biofilm at concentrations below its MIC value by down-regulating the level of PelA, algD, and PslA gene transcription. Importantly, chensinin-1b had a significant antibacterial effect against MRPA0108 in vivo. Administration of chensinin-1b to mice infected with MRPA 0108 significantly increased survival by 50-70%. Moreover, chensinin-1b reduced the production of pro-inflammatory mediators and correspondingly reduced lung and liver tissue damage in the mouse model of septic shock induced by MRPA 0108. Collectively, these results suggest that chensinin-1b could be an effective antibiotic against multiple-drug-resistant bacterial strains. Copyright

  2. High-throughput expression of animal venom toxins in Escherichia coli to generate a large library of oxidized disulphide-reticulated peptides for drug discovery.

    Science.gov (United States)

    Turchetto, Jeremy; Sequeira, Ana Filipa; Ramond, Laurie; Peysson, Fanny; Brás, Joana L A; Saez, Natalie J; Duhoo, Yoan; Blémont, Marilyne; Guerreiro, Catarina I P D; Quinton, Loic; De Pauw, Edwin; Gilles, Nicolas; Darbon, Hervé; Fontes, Carlos M G A; Vincentelli, Renaud

    2017-01-17

    Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, a variety of membrane receptors. Disulphide-reticulated peptides have evolved to display improved specificity, low immunogenicity and to show much higher resistance to degradation than linear peptides. These properties make venom peptides attractive candidates for drug development. However, recombinant expression of reticulated peptides containing disulphide bonds is challenging, especially when associated with the production of large libraries of bioactive molecules for drug screening. To date, as an alternative to artificial synthetic chemical libraries, no comprehensive recombinant libraries of natural venom peptides are accessible for high-throughput screening to identify novel therapeutics. In the accompanying paper an efficient system for the expression and purification of oxidized disulphide-reticulated venom peptides in Escherichia coli is described. Here we report the development of a high-throughput automated platform, that could be adapted to the production of other families, to generate the largest ever library of recombinant venom peptides. The peptides were produced in the periplasm of E. coli using redox-active DsbC as a fusion tag, thus allowing the efficient formation of correctly folded disulphide bridges. TEV protease was used to remove fusion tags and recover the animal venom peptides in the native state. Globally, within nine months, out of a total of 4992 synthetic genes encoding a representative diversity of venom peptides, a library containing 2736 recombinant disulphide-reticulated peptides was generated. The data revealed that the animal venom peptides produced in the bacterial host were natively folded and, thus, are putatively biologically active. Overall this study reveals that high-throughput expression of animal venom peptides in E. coli can generate large

  3. Priming psychic and conjuring abilities of a magic demonstration influences event interpretation and random number generation biases

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    Christine eMohr

    2015-01-01

    Full Text Available Magical ideation and belief in the paranormal is considered to represent a trait-like character; people either believe in it or not. Yet, anecdotes indicate that exposure to an anomalous event can turn sceptics into believers. This transformation is likely to be accompanied by altered cognitive functioning such as impaired judgements of event likelihood. Here, we investigated whether the exposure to an anomalous event changes individuals’ explicit traditional (religious and non-traditional (e.g. paranormal beliefs as well as cognitive biases that have previously been associated with non-traditional beliefs, e.g. repetition avoidance when producing random numbers in a mental dice task. In a classroom, 91 students saw a magic demonstration after their psychology lecture. Before the demonstration, half of the students were told that the performance was done respectively by a conjuror (magician group or a psychic (psychic group. The instruction influenced participants’ explanations of the anomalous event. Participants in the magician, as compared to the psychic group, were more likely to explain the event through conjuring abilities while the reverse was true for psychic abilities. Moreover, these explanations correlated positively with their prior traditional and non-traditional beliefs. Finally, we observed that the psychic group showed more repetition avoidance than the magician group, and this effect remained the same regardless of whether assessed before or after the magic demonstration. We conclude that pre-existing beliefs and contextual suggestions both influence people’s interpretations of anomalous events and associated cognitive biases. Beliefs and associated cognitive biases are likely flexible well into adulthood and change with actual life events.

  4. How to improve drug dosing for patients with renal impairment in primary care - a cluster-randomized controlled trial

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    Erler Antje

    2012-09-01

    Full Text Available Abstract Background Patients with chronic kidney disease (CKD are at increased risk for inappropriate or potentially harmful prescribing. The aim of this study was to examine whether a multifaceted intervention including the use of a software programme for the estimation of creatinine clearance and recommendation of individual dosage requirements may improve correct dosage adjustment of relevant medications for patients with CKD in primary care. Methods A cluster-randomized controlled trial was conducted between January and December 2007 in small primary care practices in Germany. Practices were randomly allocated to intervention or control groups. In each practice, we included patients with known CKD and elderly patients (≥70 years suffering from hypertension. The practices in the intervention group received interactive training and were provided a software programme to assist with individual dose adjustment. The control group performed usual care. Data were collected at baseline and at 6 months. The outcome measures, analyzed across individual patients, included prescriptions exceeding recommended maximum daily doses, with the primary outcome being prescriptions exceeding recommended standard daily doses by more than 30%. Results Data from 44 general practitioners and 404 patients are included. The intervention was effective in reducing prescriptions exceeding the maximum daily dose per patients, with a trend in reducing prescriptions exceeding the standard daily dose by more than 30%. Conclusions A multifaceted intervention including the use of a software program effectively reduced inappropriately high doses of renally excreted medications in patients with CKD in the setting of small primary care practices. Trial registration Current Controlled Trials ISRCTN02900734

  5. Rationale and design of a randomized trial to evaluate an evidence-based prescription drug label on actual medication use.

    Science.gov (United States)

    Shrank, William H; Parker, Ruth; Davis, Terry; Pandit, Anjali U; Knox, Joann P; Moraras, Pear; Rademaker, Alfred; Wolf, Michael S

    2010-11-01

    Medication errors are an important public health concern, and poor understanding of medication labels are a root cause. Research shows that labels are variable, of poor quality, and not patient-centered. No real-world trials have evaluated whether improved medication labels can affect appropriate medication use, adherence or health outcomes. We developed an evidence-based prescription label that addresses both content and format. The enhanced label includes a universal medication schedule (UMS) that standardizes the directions for use incorporating 1) standard time periods for administration (morning, noon, evening, and bedtime), 2) numeric vs. alpha characters, 3) 'carriage returns' to separate daily dose and 4) a graphic aid to visually depict dose and frequency. We will evaluate the effect of providing this label to randomly sampled patients who receive their care from free clinics, mobile vans and federally qualified health centers (FQHCs) in Northern Virginia. We will recruit patients with diabetes or hypertension; these patients will be randomly assigned to receive all of their medications with improved labels or to receive prescriptions with standard labels. The primary outcome will be the patient's ability to correctly demonstrate dosing instructions. Other outcomes include adherence, error rates and health outcomes. To our knowledge, this trial is the first to evaluate the effect of prescription label improvement on understanding, medication use and outcomes in a clinical setting. If successful, these findings could be implemented broadly to promote safe and appropriate medication use and to support evidence-based standards in the development of labels. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. High throughput screening for small molecule enhancers of the interferon signaling pathway to drive next-generation antiviral drug discovery.

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    Dhara A Patel

    Full Text Available Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses. Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN signaling system might better protect against viral infection. Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense. Accordingly, we developed a cell-based high-throughput screening (HTS assay to identify small molecules that enhance the IFN signaling pathway components. The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE activity in a fully automated and robust format (Z'>0.7. Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs led to the identification of 64 compounds with significant ISRE activity. From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range. We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production. We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV. The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity. Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify

  7. Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management.

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    Feng, Xiu-Qin; Zhu, Ling-Ling; Zhou, Quan

    2017-01-01

    Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs). A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8%) were conducted in healthy volunteers, whereas 10 RCTs (19.2%) enrolled true patients. None of the opioid-drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine-P2Y12 inhibitors, morphine-gabapentin, and methadone-zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin-opioids (morphine, tramadol, oxycodone, methadone), quinidine-opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone), antimycotics-opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol), protease inhibitors-opioids (ritonavir, ritonavir/lopinavir-oxycodone, ritonavir-fentanyl, ritonavir-tilidine), grapefruit juice-opioids (oxycodone, fentanyl, methadone), antidepressants-opioids (paroxetine-tramadol, paroxetine-hydrocodone, paroxetine-oxycodone, escitalopram-tramadol), metoclopramide-morphine, amantadine-morphine, sumatriptan-butorphanol nasal sprays, ticlopidine-tramadol, St John's wort-oxycodone, macrolides/ketolides-oxycodone, and levomepromazine-codeine. RCTs investigating the same combination, almost unanimously, drew consistent conclusions, except two RCTs on amantadine-intravenous morphine combination where a different amantadine dose was used and two RCTs on morphine

  8. Fixed herbal drug combination with and without butterbur (Ze 185) for the treatment of patients with somatoform disorders: randomized, placebo-controlled pharmaco-clinical trial.

    Science.gov (United States)

    Melzer, Jörg; Schrader, Ewald; Brattström, Axel; Schellenberg, Rüdiger; Saller, Reinhard

    2009-09-01

    Herbal drugs are often used in patients with somatoform disorders yet, the available evidence is limited. The aim of the present short-term study was to evaluate in a pharmaco-clinical trial the additional benefit of butterbur in a fixed herbal drug combination (Ze 185 = 4-combination versus 3-combination without butterbur and placebo) in patients with somatoform disorders.For a 2-week treatment in patients with somatization disorder (F45.0) and undifferentiated somatoform disorder (F45.1), 182 patients were randomized for a 3-arm trial (butterbur root, valerian root, passionflower herb, lemon balm leaf versus valerian root, passionflower herb, lemon balm leaf versus placebo). Anxiety (visual analogue scale - VAS) and depression (Beck's Depression Inventory - BDI) served as primary parameters, Clinical Global Impression (CGI) was a secondary parameter.The 4-combination was significantly superior to the 3-combination and placebo (4-combination > 3-combination > placebo) in all the primary and secondary parameters (PP-population). Analysis of the ITT population confirmed these results. As to safety, no serious adverse events occurred. In total 9 non-serious adverse events were documented but the distribution did not differ significantly between the treatment groups.This herbal preparation (Ze185) showed to be an efficacious and safe short-term treatment in patients with somatoform disorders.

  9. Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimulation on the treatment of rheumatoid arthritis with peptic ulcer: a randomized controlled study.

    Science.gov (United States)

    Liu, Defang; Guo, Mingyang; Hu, Yonghe; Liu, Taihua; Yan, Jiao; Luo, Yong; Yun, Mingdong; Yang, Min; Zhang, Jun; Guo, Linglin

    2015-06-01

    To observe the efficacy and safety of oral sanhuangwuji powder, anti-rheumatic drugs (ARDs), and ginger-partitioned acupoint stimulation at zusanli (ST 36) on the treatment of rheumatoid arthritis (RA) complicated by peptic ulcer. This prospective randomized controlled study included 180 eligible inpatients and outpatients randomly assigned to an ARD treatment (n.= 60), ginger-partitioned stimulation (n = 60), or combination treatment (n = 60). Patients assigned to the ARD group were given oral celecoxib, methotrexate, and esomeprazole. Patients assigned to the ginger-partitioned stimulation group were given ginger-partitioned acupoint stimulation at zusanli (ST 36) in addition to the ARDs. Patients in the combination treatment group were given oral sanhuangwuji powder, ginger-partitioned acupoint stimulation at susanli (ST 36), and ARDs. All patients were followed up for 2 months to evaluate clinical effects and safety. The study was registered in the World Health Organization database at the General Hospital of Chengdu Military Area Command Chinese People's Liberation Army (ChiCTR-TCC12002824). The combination treatment group had significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal symptom scores, compared with the other groups (P ginger-partitioned stimulation group (χ2= 6.171, P ginger-partitioned acupoint stimulation at zusanli (ST 36), oral sanhuangwuji powder, and ARDs had a better clinical effect for RA with complicated peptic ulcer, compared with ARD treatmentalone or in combination with ginger-partitioned acupoint stimulation.

  10. Comparison of the Effects on Rib Fracture between the Traditional Japanese Medicine Jidabokuippo and Nonsteroidal Anti-Inflammatory Drugs: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hajime Nakae

    2012-01-01

    Full Text Available Jidabokuippo is a traditional Japanese medicine used for contusion-induced swelling and pain. This open multicenter randomized study was designed to compare the efficacies of jidabokuippo and nonsteroidal anti-inflammatory drugs (NSAIDs in patients with rib fracture by analyzing the treatment duration. Our study involved 170 rib fracture patients capable of oral ingestion divided randomly into 2 groups: the jidabokuippo and NSAID groups. We compared the duration of treatment and healthcare expenditure between these 2 groups. Medication was continued in both groups until the visual analogue scale score decreased to less than 50% of the pretreatment score. We excluded the patients in whom medication was prematurely discontinued. We analyzed 81 patients belonging to the jidabokuippo and NSAIDs groups. No significant intergroup differences were observed in age, gender, severity (injury severity score, and presence/absence of underlying disease. The treatment duration was significantly shorter in the jidabokuippo group than in the NSAIDs group (P=0.0003. Healthcare expenditure was significantly lower in the jidabokuippo group than in the NSAIDs group (P<0.0001. Our results suggest that compared to NSAIDs, jidabokuippo can shorten the duration of treatment in patients with rib fracture and is a promising analgesic agent based on the medical economic viewpoint.

  11. Cluster randomized trial of text message reminders to retail staff in tanzanian drug shops dispensing artemether-lumefantrine: effect on dispenser knowledge and patient adherence.

    Science.gov (United States)

    Bruxvoort, Katia; Festo, Charles; Kalolella, Admirabilis; Cairns, Matthew; Lyaruu, Peter; Kenani, Mitya; Kachur, S Patrick; Goodman, Catherine; Schellenberg, David

    2014-10-01

    Artemisinin combination therapies are available in private outlets, but patient adherence might be compromised by poor advice from dispensers. In this cluster randomized trial in drug shops in Tanzania, 42 of 82 selected shops were randomized to receive text message reminders about what advice to provide when dispensing artemether-lumefantrine (AL). Eligible patients purchasing AL at shops in both arms were followed up at home and questioned about each dose taken. Dispensers were interviewed regarding knowledge of AL dispensing practices and receipt of the malaria-related text messages. We interviewed 904 patients and 110 dispensers from 77 shops. Although there was some improvement in dispenser knowledge, there was no difference between arms in adherence measured as completion of all doses (intervention 68.3%, control 69.8%, p [adjusted] = 0.6), or as completion of each dose at the correct time (intervention 33.1%, control 32.6%, p [adjusted] = 0.9). Further studies on the potential of text messages to improve adherence are needed. © The American Society of Tropical Medicine and Hygiene.

  12. No Wrong Doors: Findings from a Critical Review of Behavioral Randomized Clinical Trials for Individuals with Co-Occurring Alcohol/Drug Problems and Posttraumatic Stress Disorder.

    Science.gov (United States)

    Simpson, Tracy L; Lehavot, Keren; Petrakis, Ismene L

    2017-04-01

    Prior reviews of behavioral treatments for individuals with comorbid alcohol and drug use disorders (substance use disorder SUD) and posttraumatic stress disorder (PTSD) have not systematically considered whether comparison conditions are matched to target treatments on time and attention. A systematic literature search using PubMed MESH terms for alcohol and substance use disorders, PTSD, and treatment identified relevant behavioral randomized clinical trials (RCTs) that evaluated PTSD-oriented exposure-based treatments, addiction-focused treatments, and coping-based treatments that do not involve exposure to trauma memories. Information pertaining to within-subject changes over time and between-subject differences, quality of control condition, recruitment efficiency, and assessment and treatment retention was synthesized. Alcohol and drug outcomes were described separately when possible. Twenty-four behavioral RCTs were identified: 7 exposure based, 6 addiction focused, and 11 coping based. Seven studies included SUD intervention comparison conditions matched to the target intervention on time and attention. Most of the 24 studies found that participants in both the experimental and control conditions improved significantly over time on SUD and PTSD outcomes. No study found significant between-group differences in both SUD and PTSD outcomes favoring the experimental treatment. Despite greater treatment dropout, there was greater improvement in some PTSD outcomes for exposure-based interventions than the control conditions, including when the control conditions were matched for time and attention. Addiction-focused and coping-based interventions did not generally show an advantage over comparably robust controls, although some coping-based interventions yielded better drug use outcomes than control conditions. When available, interventions that integrate exposure-based PTSD treatment and behavioral SUD treatment are recommended as they are associated with better

  13. Patient-reported functional health and well-being outcomes with drug therapy: a systematic review of randomized trials using the SF-36 health survey.

    Science.gov (United States)

    Frendl, Daniel M; Ware, John E

    2014-05-01

    To evaluate the responsiveness of the SF-36 Health Survey in drug trials and to determine how often clinically efficacious treatments produce meaningful functional health changes across medical conditions. We conducted a systematic review of randomized, double-blind, placebo-controlled drug trials published from 1995 to 2011 that documented results for primary clinical endpoints and SF-36 outcomes. PubMed and a database of SF-36 publications were searched. We evaluated responsiveness as concordance (both statistically significant or both nonsignificant) between primary clinical and SF-36 outcomes. To determine how often SF-36 physical and mental component summary (PCS, MCS) score changes were of meaningful magnitude, mean net of placebo changes with treatment were compared against the developer's recommended 3-point threshold for a minimal important difference (MID) across groups of medical conditions. Of 805 screened trials, 185 met eligibility criteria. Primary clinical and SF-36 outcomes were concordant in 151 trials (82%). Among clinically efficacious trials, 58% reported net mean SF-36 improvements ≥MID threshold; however, SF-36 changes were often modest (PCS IQR, 1.6-4.1; MCS IQR, 0.8-3.5). Variations in treatment impact were apparent across conditions. Clinically efficacious therapies for rheumatoid arthritis, psoriatic arthritis, and psoriasis consistently achieved the largest SF-36 improvements, with 87% exceeding MID, whereas no efficacious therapies for peripheral arterial disease or chronic obstructive pulmonary disease achieved MID threshold. The SF-36 responds to treatment impact, distinguishing drug therapies that, on average, produce meaningful functional health benefits. Overall, just over half of clinically efficacious trials report meaningful functional health improvements, and results vary widely by medical condition.

  14. Auricular acupuncture for substance use: a randomized controlled trial of effects on anxiety, sleep, drug use and use of addiction treatment services.

    Science.gov (United States)

    Ahlberg, Rickard; Skårberg, Kurt; Brus, Ole; Kjellin, Lars

    2016-07-25

    A common alternative treatment for substance abuse is auricular acupuncture. The aim of the study was to evaluate the short and long-term effect of auricular acupuncture on anxiety, sleep, drug use and addiction treatment utilization in adults with substance abuse. Of the patients included, 280 adults with substance abuse and psychiatric comorbidity, 80 were randomly assigned to auricular acupuncture according to the NADA protocol, 80 to auricular acupuncture according to a local protocol (LP), and 120 to relaxation (controls). The primary outcomes anxiety (Beck Anxiety Inventory; BAI) and insomnia (Insomnia Severity Index; ISI) were measured at baseline and at follow-ups 5 weeks and 3 months after the baseline assessment. Secondary outcomes were drug use and addiction service utilization. Complete datasets regarding BAI/ISI were obtained from 37/34 subjects in the NADA group, 28/28 in the LP group and 36/35 controls. Data were analyzed using Chi-square, Analysis of Variance, Kruskal Wallis, Repeated Measures Analysis of Variance, Eta square (η(2)), and Wilcoxon Signed Ranks tests. Participants in NADA, LP and control group improved significantly on the ISI and BAI. There was no significant difference in change over time between the three groups in any of the primary (effect size: BAI, η(2) = 0.03, ISI, η(2) = 0.05) or secondary outcomes. Neither of the two acupuncture treatments resulted in differences in sleep, anxiety or drug use from the control group at 5 weeks or 3 months. No evidence was found that acupuncture as delivered in this study is more effective than relaxation for problems with anxiety, sleep or substance use or in reducing the need for further addiction treatment in patients with substance use problems and comorbid psychiatric disorders. The substantial attrition at follow-up is a main limitation of the study. Clinical Trials NCT02604706 (retrospectively registered).

  15. Study protocol for a group randomized controlled trial of a classroom-based intervention aimed at preventing early risk factors for drug abuse: integrating effectiveness and implementation research

    Directory of Open Access Journals (Sweden)

    Keegan Natalie

    2009-09-01

    Full Text Available Abstract Background While a number of preventive interventions delivered within schools have shown both short-term and long-term impact in epidemiologically based randomized field trials, programs are not often sustained with high-quality implementation over time. This study was designed to support two purposes. The first purpose was to test the effectiveness of a universal classroom-based intervention, the Whole Day First Grade Program (WD, aimed at two early antecedents to drug abuse and other problem behaviors, namely, aggressive, disruptive behavior and poor academic achievement. The second purpose--the focus of this paper--was to examine the utility of a multilevel structure to support high levels of implementation during the effectiveness trial, to sustain WD practices across additional years, and to train additional teachers in WD practices. Methods The WD intervention integrated three components, each previously tested separately: classroom behavior management; instruction, specifically reading; and family-classroom partnerships around behavior and learning. Teachers and students in 12 schools were randomly assigned to receive either the WD intervention or the standard first-grade program of the school system (SC. Three consecutive cohorts of first graders were randomized within schools to WD or SC classrooms and followed through the end of third grade to test the effectiveness of the WD intervention. Teacher practices were assessed over three years to examine the utility of the multilevel structure to support sustainability and scaling-up. Discussion The design employed in this trial appears to have considerable utility to provide data on WD effectiveness and to inform the field with regard to structures required to move evidence-based programs into practice. Trial Registration Clinical Trials Registration Number: NCT00257088

  16. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.

    Science.gov (United States)

    Durante-Mangoni, Emanuele; Signoriello, Giuseppe; Andini, Roberto; Mattei, Annunziata; De Cristoforo, Maria; Murino, Patrizia; Bassetti, Matteo; Malacarne, Paolo; Petrosillo, Nicola; Galdieri, Nicola; Mocavero, Paola; Corcione, Antonio; Viscoli, Claudio; Zarrilli, Raffaele; Gallo, Ciro; Utili, Riccardo

    2013-08-01

    Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. NCT01577862.

  17. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

    DEFF Research Database (Denmark)

    Macdonald, Thomas M; Hawkey, Chris J; Ford, Ian

    2017-01-01

    infarction or other biomarker positive acute coronary syndrome, non-fatal stroke or CV death analysed using a Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio (HR). RESULTS: In total, 7297 participants were randomized. During a median 3-year follow-up, fewer subjects than......-years with celecoxib and 1.10 per 100 patient-years with nsNSAIDs (HR = 1.04; 95% confidence interval, 0.81-1.33; P = 0.75). Pre-specified non-inferiority was achieved in the ITT analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was two......NSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. This study excluded an increased risk of the primary endpoint of more than two events per 1000 patient-years associated with switching to prescribed celecoxib....

  18. Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for Liver Cancer Therapy

    Science.gov (United States)

    2017-09-01

    unexplored therapeutic targets. While most normal tissues use HK1 for glycolysis , HK4 is the only HK isoform in hepatocytes. The transition from hepatocyte to...HCC is frequently accompanied by a complete switch from HK4 to the highly active HK2 isoform, and increased glycolysis (the “Warburg effect”). HK2...energy generation triangle” ( glycolysis , oxidative phosphorylation, and FAO) as a translational, effective and safe therapy for HCC. 15. SUBJECT

  19. Adding ofloxacin to standard triple-drug regimens increased the Helicobacter pylori eradication rate: Data from randomized clinical trial.

    Science.gov (United States)

    Sadeghi-Hadad-Zavareh, Mahmoud; Mohammadi, Seyyedsaeid; Hajiahmadi, Mahmoud; Javanian, Mostafa; Habibian, Masoomeh

    2017-01-01

    The rate of Helicobacter pylori (H.pylori) eradication in dyspeptic patients using bismuth- based triple therapy is low due to bacterial that are resistant to antibiotics. The results of recent studies regarding levofloxacin have been encouraging, but the high cost of treatment prevents its routine administration. We, therefore, performed the present double-blind clinical trial to compare the efficiency of quadruple-drug regimen containing ofloxacin, clarithromycin, amoxicillin, and omeprazole and the same standard triple-therapy regimen minus ofloxacin in H. pylori positive dyspepsia. The study patients were recruited among dyspeptic patients requiring gastroscopy. Patients with the history of H.pylori treatment, renal failure and pregnancy were excluded. Diagnosis of H.pylori infection was confirmed by rapid urease test and response to treatment was confirmed via negative urease breath test (UBT) 20 days after completion of treatment. Patients were allocated intermittently to standard triple therapy containing amoxicillin, clarithromycin, omeprazole alone or plus ofloxacin for ten days. Response to treatment was compared between the two groups. A total of 140 patients entered the study (70 patients in each group). At endpoint 30 (42.9%) patients of group 1 and 39 (55.7%) patients of group 2 became asymptomatic. Furthermore, 55 (78.6%) patients of group 1 and 66 (94.3%) patients of group 2 revealed negative urea breath test (P= 0.01). This study indicates adding ofloxacin to standard triple-therapy for H.pylorri infection significantly increases the rate of eradication. These findings highlight ofloxacin as empiric treatment of H. pylori infection.

  20. Flow analysis-hydride generation-gas phase derivative molecular absorption spectrophotometric determination of antimony in antileishmanial drugs

    Directory of Open Access Journals (Sweden)

    Máximo Gallignani

    2009-01-01

    Full Text Available In the present work, the development of a method based on the coupling of flow analysis (FA, hydride generation (HG, and derivative molecular absorption spectrophotometry (D-EAM in gas phase (GP, is described in order to determine total antimony in antileishmanial products. Second derivative order (D²224nm of the absorption spectrum (190 - 300 nm is utilized as measurement criterion. Each one of the parameters involved in the development of the proposed method was examined and optimized. The utilization of the EAM in GP as detection system in a continuous mode instead of atomic absorption spectrometry represents the great potential of the analytic proposal.

  1. Generation of multi-channel high-speed physical random numbers originated from two chaotic signals of mutually coupled semiconductor lasers

    Science.gov (United States)

    Tang, X.; Wu, Z. M.; Wu, J. G.; Deng, T.; Fan, L.; Zhong, Z. Q.; Chen, J. J.; Xia, G. Q.

    2015-01-01

    We propose and experimentally demonstrate a novel technique to generate multi-channel high-speed physical random numbers (PRNs) by taking two chaotic signal outputs from mutually coupled semiconductor lasers (MC-SLs) as entropy sources. First, through controlling the operation parameters of the MC-SL system, two time-delay signature (TDS) suppressed chaotic signals can be obtained. Next, each of these two chaotic signals is sampled by an 8 bit analog-to-digital converter (ADC) with a sampling rate of 10 GHz, and then a bitwise exclusive-OR (XOR) operation on the corresponding bits in samples of the chaotic signal and its time delayed signal is implemented to obtain 8 bit XOR data. Furthermore, through selecting the five least significant bits (LSBs) of 8 bit XOR data to form 5 bit Boolean sequences, two sets of PRN streams with a rate up to 50 Gbits s-1 are generated and successfully pass the NIST statistical tests. Finally, merging these two sets of 50 Gbits s-1 PRN streams by an interleaving operation, another set of the 100 Gbits s-1 PRN stream, which meets all the quality criteria of NIST statistical tests, is also acquired.

  2. Random thoughts

    Science.gov (United States)

    ajansen; kwhitefoot; panteltje1; edprochak; sudhakar, the

    2014-07-01

    In reply to the physicsworld.com news story “How to make a quantum random-number generator from a mobile phone” (16 May, http://ow.ly/xFiYc, see also p5), which describes a way of delivering random numbers by counting the number of photons that impinge on each of the individual pixels in the camera of a Nokia N9 smartphone.

  3. Influence of trans fat and omega-3 on the preference of psychostimulant drugs in the first generation of young rats.

    Science.gov (United States)

    Kuhn, Fábio T; Roversi, Karine; Antoniazzi, Caren T D; Pase, Camila S; Trevizol, Fabíola; Barcelos, Raquel C S; Dias, Verônica T; Roversi, Katiane; Boufleur, Nardeli; Benvegnú, Dalila M; Piccolo, Jaqueline; Emanuelli, Tatiana; Bürger, Marilise E

    2013-09-01

    The current Western diet often provides considerable amounts of saturated and trans fatty acids (TFA), whose incorporation into neuronal membranes has been implicated in changes of brain neurochemical functions. Such influence has caused concerns due to precipitation of neuropsychiatric disorders, whose data are still unclear. Here we evaluated the influence of different fats on preference parameters for amphetamine (AMPH): adolescent rats were orally supplemented with soybean oil (SO, rich in n-6 FA, which was considered an isocaloric control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in saturated and trans FA) from weaning, which were born of dams supplemented with the same fat from pregnancy and lactation. AMPH preference, anxiety-like symptoms and locomotor index were evaluated in conditioned place preference (CPP), elevated plus maze (EPM) and open-field (OF), respectively, while brain oxidative status was determined in cortex, striatum and hippocampus. HVF increased AMPH-CPP and was associated with withdrawal signs, as observed by increased anxiety-like symptoms. Moreover, SO and FO were not associated with AMPH preference, but only FO-supplemented rats did not show any anxiety-like symptoms or increased locomotion. FO supplementation was related to lower oxidative damages to proteins and increased CAT activity in striatum and hippocampus, as well as increased GSH levels in blood, while HVF was related to increased oxidative status. In conclusion, our study showed the harmful influence of TFA on AMPH-CPP and drug craving symptoms, which can be related to dopaminergic neurotransmission. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial

    Science.gov (United States)

    Jiang, Yan; Zhang, Zhen-Lin; Zhang, Zhong-Lan; Zhu, Han-Min; Wu, Yi-Yong; Cheng, Qun; Wu, Feng-Li; Xing, Xiao-Ping; Liu, Jian-Li; Yu, Wei; Meng, Xun-Wu

    2014-01-01

    Objective To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. Method This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. Results A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. Conclusion Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women. PMID:24426779

  5. Next-generation sequencing-based user-friendly platforms for drug-resistant tuberculosis diagnosis: A promise for the near future.

    Science.gov (United States)

    Dolinger, David L; Colman, Rebecca E; Engelthaler, David M; Rodwell, Timothy C

    2016-12-01

    Since 2002, there has been a gradual worldwide 1.3% annual decrease in the incidence of tuberculosis (TB). This is an encouraging statistic; however, it will not achieve the World Health Organization's goal of eliminating TB by 2050, and it is being compounded by the persistent global incidence of drug-resistant tuberculosis (DR-TB) acquired by transmission and by treatment pressure. One key to effectively control tuberculosis and the spread of multiresistant strains is accurate information pertaining to drug resistance and susceptibility. Next-generation sequencing (NGS) has the potential to effectively change global health and the management of TB. Industry has focused primarily on using NGS for oncology diagnostics and human genomics, but the area in which NGS can rapidly impact health care is in the area of infectious disease diagnostics in low- and middle-income countries. To date, there has been a failure as a community to capitalize on the potential of NGS, especially at the reference laboratory level where it can provide actionable information pertaining to treatment options for patients. The rapid evolution of knowledge about the genetic foundations of tuberculosis drug resistance makes sequencing a versatile technology platform for providing rapid, accurate, and actionable results for treating this disease. No "plug-and-play" and "end-to-end" NGS solutions exist that provide clinically relevant sequence data from the Mycobacterium tuberculosis complex genome from primary clinical samples (e.g., sputum) in high-burden country reference laboratories, which is where they are most needed. However, such a system-based solution is underdeveloped by Foundation for Innovative Diagnostics (FIND), in collaboration with partners from academia, nongovernmental organizations, and industry. The solution is modular and is designed and developed to perform targeted amplicon sequencing directly from a patient's primary sputum sample. This solution will initially allow

  6. Next-generation sequencing-based user-friendly platforms for drug-resistant tuberculosis diagnosis: A promise for the near future

    Directory of Open Access Journals (Sweden)

    David L Dolinger

    2016-01-01

    Full Text Available Since 2002, there has been a gradual worldwide 1.3% annual decrease in the incidence of tuberculosis (TB. This is an encouraging statistic; however, it will not achieve the World Health Organization's goal of eliminating TB by 2050, and it is being compounded by the persistent global incidence of drug-resistant tuberculosis (DR-TB acquired by transmission and by treatment pressure. One key to effectively control tuberculosis and the spread of multiresistant strains is accurate information pertaining to drug resistance and susceptibility. Next-generation sequencing (NGS has the potential to effectively change global health and the management of TB. Industry has focused primarily on using NGS for oncology diagnostics and human genomics, but the area in which NGS can rapidly impact health care is in the area of infectious disease diagnostics in low- and middle-income countries. To date, there has been a failure as a community to capitalize on the potential of NGS, especially at the reference laboratory level where it can provide actionable information pertaining to treatment options for patients. The rapid evolution of knowledge about the genetic foundations of tuberculosis drug resistance makes sequencing a versatile technology platform for providing rapid, accurate, and actionable results for treating this disease. No “plug-and-play” and “end-to-end” NGS solutions exist that provide clinically relevant sequence data from the Mycobacterium tuberculosis complex genome from primary clinical samples (e.g., sputum in high-burden country reference laboratories, which is where they are most needed. However, such a system-based solution is underdeveloped by Foundation for Innovative Diagnostics (FIND, in collaboration with partners from academia, nongovernmental organizations, and industry. The solution is modular and is designed and developed to perform targeted amplicon sequencing directly from a patient's primary sputum sample. This solution

  7. Generating genius: how an Alzheimer’s drug became considered a ‘cognitive enhancer’ for healthy individuals

    Science.gov (United States)

    2014-01-01

    Background Donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer’s disease, has been widely cited in media and bioethics literature on cognitive enhancement (CE) as having the potential to improve the cognitive ability of healthy individuals. In both literatures, this claim has been repeatedly supported by the results of a small study published by Yesavage et al. in 2002 on non-demented pilots (30–70 years old). The factors contributing to this specific interpretation of this study’s results are unclear. Methods We examined print media and interdisciplinary bioethics coverage of this small study, aiming to provide insight into how evidence from research may be shaped within different discourses, potentially influencing important policy, ethics, and clinical decisions. Systematic qualitative content analysis was used to examine how this study was reported in 27 media and 22 bioethics articles. Articles were analyzed for content related to: (1) headlines and titles; (2) colloquialisms; and, (3) accuracy of reporting of the characteristics and results of the study. Results In media and bioethics articles referencing this small study, strong claims were made about donepezil as a CE drug. The majority of headlines, titles, and colloquialisms used enhancement language and the majority of these suggest that donepezil could be used to enhance intellectual ability. Further, both literatures moved between reporting the results of the primary study and magnifying the perceived connection between these results and the CE debate that was alluded to in the primary study. Specific descriptions of the results overwhelmingly reported an improvement in performance on a flight simulator, while more general statements claimed donepezil enhanced cognitive performance. Further, a high level of reporting accuracy was found regarding study characteristics of the original study, but variable levels of accuracy surrounded the presentation of complex

  8. Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens.

    Science.gov (United States)

    Nguyen, Anh To; Tran, Thanh Tan; Hoang, Van Minh Tu; Nghiem, Ngoc My; Le, Nhu Nguyen Truc; Le, Thanh Thi My; Phan, Qui Tu; Truong, Khanh Huu; Le, Nhan Nguyen Thanh; Ho, Viet Lu; Do, Viet Chau; Ha, Tuan Manh; Nguyen, Hung Thanh; Nguyen, Chau Van Vinh; Thwaites, Guy; van Doorn, H Rogier; Le, Tan Van

    2016-07-07

    Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole-genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV-A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. In conclusion, we have successfully developed a non-ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples.

  9. The Additional Value of an E-Mail to Inform Healthcare Professionals of a Drug Safety Issue: A Randomized Controlled Trial in the Netherlands.

    Science.gov (United States)

    Piening, Sigrid; de Graeff, Pieter A; Straus, Sabine M J M; Haaijer-Ruskamp, Flora M; Mol, Peter G M

    2013-09-01

    The usefulness and the impact of Direct Healthcare Professional Communications (DHPCs, or 'Dear Doctor letters') in changing the clinical behaviour of physicians have been debated. Changes in the current risk communication methods should preferably be based on the preferences of the healthcare professionals, to optimize the uptake of the message. The aim of this study was to assess whether safety issues are communicated more effectively with an additional e-mail sent by the Dutch Medicines Evaluation Board (MEB) than with the DHPC only. A randomized controlled trial was conducted amongst ophthalmologists and hospital pharmacists in the Netherlands, who were the target group of a DHPC that was issued for pegaptanib, a drug that is administered intra-ocularly in patients with macular degeneration. The intervention group (N = 110) received the pegaptanib DHPC, as well as the MEB e-mail. The control group (N = 105) received the traditional paper-based DHPC only. Two weeks later, the study population received an invitation to fill out an online questionnaire. Questions were asked about the respondents' knowledge and attitude regarding the pegaptanib issue, and any action they had consequently taken. Additional questions were asked about their satisfaction with the DHPC and the e-mail, and their preferred source of such information. Forty respondents (18.6%) completed the questionnaire. Eighty-one percent of the respondents in the intervention group (N = 21) and 47% of the control group (N = 19) correctly indicated that a serious increase in intra-ocular pressure could be caused by pegaptanib injections (Fishers' exact test, p = 0.046). Nine respondents in the intervention group versus none of the control group respondents indicated that they had taken action in response to the pegaptanib safety issue (Fishers' exact test, p = 0.01). The majority of both the intervention group and the control group confirmed that they would like to receive an MEB e-mail with safety

  10. Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing.

    Science.gov (United States)

    Gilbert, Ashley N; Shevin, Rachael S; Anderson, Joshua C; Langford, Catherine P; Eustace, Nicholas; Gillespie, G Yancey; Singh, Raj; Willey, Christopher D

    2016-06-09

    The use of patient-derived xenografts for modeling cancers has provided important insight into cancer biology and drug responsiveness. However, they are time consuming, expensive, and labor intensive. To overcome these obstacles, many research groups have turned to spheroid cultures of cancer cells. While useful, tumor spheroids or aggregates do not replicate cell-matrix interactions as found in vivo. As such, three-dimensional (3D) culture approaches utilizing an extracellular matrix scaffold provide a more realistic model system for investigation. Starting from subcutaneous or intracranial xenografts, tumor tissue is dissociated into a single cell suspension akin to cancer stem cell neurospheres. These cells are then embedded into a human-derived extracellular matrix, 3D human biogel, to generate a large number of microtumors. Interestingly, microtumors can be cultured for about a month with high viability and can be used for drug response testing using standard cytotoxicity assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live cell imaging using Calcein-AM. Moreover, they can be analyzed via immunohistochemistry or harvested for molecular profiling, such as array-based high-throughput kinomic profiling, which is detailed here as well. 3D microtumors, thus, represent a versatile high-throughput model system that can more closely replicate in vivo tumor biology than traditional approaches.

  11. Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial.

    Science.gov (United States)

    Eisele, Thomas P; Bennett, Adam; Silumbe, Kafula; Finn, Timothy P; Chalwe, Victor; Kamuliwo, Mulakwa; Hamainza, Busiku; Moonga, Hawela; Kooma, Emmanuel; Chizema Kawesha, Elizabeth; Yukich, Joshua; Keating, Joseph; Porter, Travis; Conner, Ruben O; Earle, Duncan; Steketee, Richard W; Miller, John M

    2016-12-15

     Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir.  A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence.  All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02-.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06-1.49; P = .14) and 58% lower (0.42; .18-.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point.  Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas.  NCT02329301. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. The Cobalt chromium STent with Antiproliferative for Restenosis II (COSTAR II) trial study design: advancing the active-control evaluation of second-generation drug-eluting stents.

    Science.gov (United States)

    Wang, Tracy Y; Hasselblad, Vic; Peterson, John L; Wijns, William; Parhizgar, Azin; Kereiakes, Dean J; Krucoff, Mitchell W

    2007-05-01

    Randomized clinical trials have demonstrated the superiority of drug-eluting stents (DESs) compared with bare-metal stents in reducing the need for revascularization and major adverse cardiac events (MACEs) in low-risk patients with single-vessel lesions. Rapid DES uptake has necessitated shifting the paradigm to active DES-controlled noninferiority study models with most studies using surrogate angiographic measurements to attain adequate statistical power. No previous prospective trial has specifically compared a new DES with an active-control DES in a high-risk patient population using primary clinical end points. COSTAR II is designed to compare use of the investigational Costar stent (Conor MedSystems, Palo Alto, CA) with the Taxus (Boston Scientific, Maple Grove, MN) stent in single- and multivessel percutaneous coronary intervention. The primary end point is the clinical composite of MACE at 8 months supported by consistent results in the evaluation of 8-month MACE rates in the single- and multivessel cohorts and of in-segment late loss in a small angiographic substudy at 9 months. A total of 1700 patients, 50% with single-vessel and 50% with multivessel disease, are randomized in a 3:2 ratio to receive either Costar or Taxus stent(s) in this prospective, multicenter, noninferiority study design. Because no prior data were available to determine control multivessel MACE rates, an imputed placebo statistical analysis plan incorporating a variable delta based on actually observed control DES MACE rates will be implemented. The results of COSTAR II will provide information about a novel coronary stent device as well as unique data regarding both control and test DES use in more complex "real-world" patients.

  13. Randomized clinical study for comparative evaluation of fourth-generation fluoroquinolones with the combination of fortified antibiotics in the treatment of bacterial corneal ulcers.

    Science.gov (United States)

    Shah, Vinit Mahendra; Tandon, Radhika; Satpathy, Gita; Nayak, Niranjan; Chawla, Bhavna; Agarwal, Tushar; Sharma, Namrata; Titiyal, Jeewan S; Vajpayee, Rasik B

    2010-07-01

    Comparative evaluation of efficacy of monotherapy with moxifloxacin (0.5%) or gatifloxacin (0.3%) with combination therapy of cefazolin (5%) and tobramycin (1.3%) in treatment of bacterial corneal ulcers. Patients diagnosed with bacterial keratitis (ulcer diameter 2-8 mm) were randomized to 1 of the 3 treatment groups (tobramycin 1.3% and cefazolin 5%, gatifloxacin 0.3%, or moxifloxacin 0.5%). After obtaining corneal scrapings, assigned study medication was instilled hourly for 48 hours and tapered as per clinical response. Healing of ulcer, duration to cure, adverse reactions, antibiogram profile, treatment failures, final visual acuity, and corneal opacity size were evaluated. A total of 61 patients were enrolled [cefazolin and tobramycin (n = 20), gatifloxacin (n = 21), and moxifloxacin (n = 20)]. Overall, 57 patients (93%) healed on treatment. On comparison of the mean time taken to heal, no statistically significant difference was found among all the 3 treatment groups (P = 0.98). Positive bacterial culture was obtained in only 38 patients (62%). There was no significant difference in the bacterial isolates in each treatment group. There were 4 (7%) treatment failures (perforation or nonhealing ulcer): 1 (5%) each in moxifloxacin and gatifloxacin group and 2 (10%) in fortified antibiotics group. All regimens were well tolerated. The study failed to find a difference in the efficacy of monotherapy with fourth-generation fluoroquinolones in the treatment of bacterial corneal ulcers of 2-8 mm size when compared with combination therapy of fortified antibiotics.

  14. The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study.

    Science.gov (United States)

    Borgatta, Myriam; Decosterd, Laurent-Arthur; Waridel, Patrice; Buclin, Thierry; Chèvre, Nathalie

    2015-07-01

    Although pharmaceutical metabolites are found in the aquatic environment, their toxicity on living organisms is poorly studied in general. Endoxifen and 4-hydroxy-tamoxifen (4OHTam) are two metabolites of the widely used anticancer drug tamoxifen for the prevention and treatment of breast cancers. Both metabolites have a high pharmacological potency in vertebrates, attributing prodrug characteristics to tamoxifen. Tamoxifen and its metabolites are body-excreted by patients, and the parent compound is found in sewage treatment plan effluents and natural waters. The toxicity of these potent metabolites on non-target aquatic species is unknown, which forces environmental risk assessors to predict their toxicity on aquatic species using knowledge on the parent compounds. Therefore, the aim of this study was to assess the sensitivity of two generations of the freshwater microcrustacean Daphnia pulex towards 4OHTam and endoxifen. Two chronic tests of 4OHTam and endoxifen were run in parallel and several endpoints were assessed. The results show that the metabolites 4OHTam and endoxifen induced reproductive and survival effects. For both metabolites, the sensitivity of D. pulex increased in the second generation. The intrinsic rate of natural increase (r) decreased with increasing 4OHTam and endoxifen concentrations. The No-Observed Effect Concentrations (NOECs) calculated for the reproduction of the second generation exposed to 4OHTam and endoxifen were <1.8 and 4.3 μg/L, respectively, whereas the NOECs that were calculated for the intrinsic rate of natural increase were <1.8 and 0.4 μg/L, respectively. Our study raises questions about prodrug and active metabolites in environmental toxicology assessments of pharmaceuticals. Our findings also emphasize the importance of performing long-term experiments and considering multi-endpoints instead of the standard reproduction outcome. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Impact of PCI Appropriateness in the Long-Term Outcomes of Consecutive Patients Treated With Second-Generation Drug-Eluting Stents.

    Science.gov (United States)

    Seixas, Ana Cristina; Sousa, Amanda; de Ribamar Costa, Jose; Costa Moreira, Adriana; Costa, Ricardo; Damiani, Lucas; Campos Neto, Cantídio; Maldonado, Galo; Cano, Manuel; Sousa, J Eduardo

    2017-09-01

    Appropriate use criteria (AUC) for coronary revascularization were developed to deliver high-quality care; however, the prognostic impact of these criteria remains unclear. We sought to assess the outcomes of patients treated with second-generation drug-eluting stent (DES) classified according to the updated American College of Cardiology Foundation/American Heart Association/Society for Cardiac Angiography and Intervention AUC for percutaneous coronary intervention (PCI). Between January 2012 and December 2013, a total of 1108 consecutive patients treated only with second-generation DES were categorized according to the AUC in three groups, using the new proposed terminology: appropriate ("A"); uncertain ("U"); and inappropriate ("I"). Major adverse cardiac event (MACE, defined as cardiac death, non-fatal myocardial infarction, and ischemia-driven target-lesion revascularization) and stent thrombosis up to 3 years were compared. PCI was categorized as A in 33.8%, U in 46.8%, and I in 19.4% of all cases. PCI-A patients had a higher prevalence of acute coronary syndromes, while PCI-I involved the treatment of more diabetics and patients with stable coronary disease. There were no differences in procedural complications among the three groups, with comparable rates of in-hospital MACE (9.3% for A vs 9.0% for U vs 7.0% for I; P=.70) and 2-year MACE (13.9% for A vs 9.0% for U vs 8.6% for I; P=.40). In the multivariable analysis, AUC classification was not associated with adverse outcomes. In this contemporary cohort of patients treated with second-generation DES implantation, AUC did not impact 3-year clinical follow-up.

  16. A new risk of bias checklist applicable to randomized trials, observational studies, and systematic reviews was developed and validated to be used for systematic reviews focusing on drug adverse events.

    Science.gov (United States)

    Faillie, Jean-Luc; Ferrer, Pili; Gouverneur, Amandine; Driot, Damien; Berkemeyer, Shoma; Vidal, Xavier; Martínez-Zapata, Maria José; Huerta, Consuelo; Castells, Xavier; Rottenkolber, Marietta; Schmiedl, Sven; Sabaté, Mònica; Ballarín, Elena; Ibáñez, Luisa

    2017-06-01

    The objective of the study was to develop and validate an adequate tool to evaluate the risk of bias of randomized controlled trials, observational studies, and systematic reviews assessing drug adverse events. We developed a structured risk of bias checklist applicable to randomized trials, cohort, case-control and nested case-control studies, and systematic reviews focusing on drug safety. Face and content validity was judged by three experienced reviewers. Interrater and intrarater reliability were determined using 20 randomly selected studies, assessed by three other independent reviewers including one performing a 3-week retest. The developed checklist examines eight domains: study design and objectives, selection bias, attrition, adverse events information bias, other information bias, statistical methods to control confounding, other statistical methods, and conflicts of interest. The total number of questions varied from 10 to 32 depending on the study design. Interrater and intrarater agreements were fair with Kendall's W of 0.70 and 0.74, respectively. Median time to complete the checklist was 8.5 minutes. The developed checklist showed face and content validity and acceptable reliability to assess the risk of bias for studies analyzing drug adverse events. Hence, it might be considered as a novel useful tool for systematic reviews and meta-analyses focusing on drug safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Prevalence and Management of Drug-Related Problems in Chronic Kidney Disease Patients by Severity Level: A Subanalysis of a Cluster Randomized Controlled Trial in Community Pharmacies.

    Science.gov (United States)

    Quintana-Bárcena, Patricia; Lord, Anne; Lizotte, Annie; Berbiche, Djamal; Lalonde, Lyne

    2018-02-01

    Drug-related problems (DRPs) are prevalent among chronic kidney disease (CKD) patients. However, little is known about their severity and management by community pharmacists. To (a) describe the prevalence of DRPs by severity level in CKD patients and (b) assess the effect of a training-and-communication network program in nephrology (ProFiL) on these DRPs. This is a secondary analysis of a cluster randomized controlled trial evaluating the effect of the ProFiL-program. In 6 CKD clinics, patients at CKD stage 3 or 4 and their community pharmacists were recruited and assigned to the ProFiL group or a usual care (UC) group. Using validated criteria, 2 pharmacists identified DRPs and assessed their severity at baseline and after 12 months. The mean annual change in the number of DRPs per patient by severity level was assessed using a 2-level multivariable linear mixed-effects model. A total of 494 pharmacists and 442 patients participated. At baseline, the prevalence (mean number of DRPs per patient [SD]) of mild DRPs (e.g., requiring dosage adjustment) and moderate DRPs (e.g., drug adherence requiring a monitoring plan) were 0.55 (0.98) and 1.04 (1.51), respectively. After 12 months, an unadjusted incremental annual reduction of 0.34 moderate DRPs (95% CI = -0.66 to -0.01) was observed in the ProFiL group compared with the UC group. After adjustment, no between-group differences were observed. Among patients followed in CKD clinics, most DRPs have a moderate severity requiring specific monitoring by pharmacists. The benefit of continuing education programs, such as ProFiL, to reduce moderate DRPs remains to be determined. This study was supported by the Canadian Institutes of Health Research (grant number: MOP-230207). Part of the study was also funded by Pfizer Canada, Leo Pharma, and Amgen. The authors declare that they have no relevant financial interests. Study concept and design were contributed by Quintana-Bárcena, Lord, and Lalonde. Quintana-Bárcena, Lord

  18. Reductions in HIV/STI Incidence and Sharing of Injection Equipment among Female Sex Workers Who Inject Drugs: Results from a Randomized Controlled Trial

    Science.gov (United States)

    Strathdee, Steffanie A.; Abramovitz, Daniela; Lozada, Remedios; Martinez, Gustavo; Rangel, Maria Gudelia; Vera, Alicia; Staines, Hugo; Magis-Rodriguez, Carlos; Patterson, Thomas L.

    2013-01-01

    Background We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs (FSW-IDUs) in Tijuana and Ciudad Juarez, Mexico during 2008–2010, when harm reduction coverage was expanding rapidly in Tijuana, but less so in Juarez. Methods FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a randomized factorial trial comparing four brief, single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use, and an injection risk intervention to reduce sharing of needles/injection paraphernalia. Women underwent quarterly interviews and testing for HIV, syphilis, gonorrhea, Chlamydia and Trichomonas, blinding interviewers and assessors to assignment. Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency. Findings Of 584 initially HIV-negative FSW-IDUs, retention was ≥90%. After 12 months, HIV/STI incidence decreased >50% in the interactive vs. didactic sex intervention (Tijuana:AdjRR:0.38,95% CI:0.16–0.89; Juarez: AdjRR:0.44,95% CI:0.19–0.99). In Juarez, women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85% vs. 71%, respectively (p = 0.04); in Tijuana, receptive needle sharing declined by 95%, but was similar in active versus didactic groups. Tijuana women reported significant increases in access to syringes and condoms, but Juarez women did not. Interpretation After 12 months in both cities, the interactive sexual risk intervention significantly reduced HIV/STI incidence. Expanding free access to sterile syringes coupled with brief, didactic education on safer injection was necessary and sufficient for achieving robust, sustained

  19. A systematic literature review on the efficacy–effectiveness gap: comparison of randomized controlled trials and observational studies of glucose-lowering drugs