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Sample records for non-negative drug test

  1. Drugs of Abuse Testing

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Drug Abuse Testing Share this page: Was this page helpful? Also ... of Abuse Screen Related tests: Emergency and Overdose Drug Testing ; Ethanol ; Nicotine ; Phenobarbital ; Testosterone ; Growth Hormone ; Erythropoietin ; IGF- ...

  2. 49 CFR 40.129 - What are the MRO's functions in reviewing laboratory confirmed non-negative drug test results?

    Science.gov (United States)

    2010-10-01

    ... CCF copy containing the employee's signature; and (2) A legible copy (fax, photocopy, image) of Copy 1... directly by a company, you must not tell anyone on the company's staff or management that you have...

  3. On affine non-negative matrix factorization

    DEFF Research Database (Denmark)

    Laurberg, Hans; Hansen, Lars Kai

    2007-01-01

    We generalize the non-negative matrix factorization (NMF) generative model to incorporate an explicit offset. Multiplicative estimation algorithms are provided for the resulting sparse affine NMF model. We show that the affine model has improved uniqueness properties and leads to more accurate...

  4. Drug testing in American schools

    Directory of Open Access Journals (Sweden)

    C.J. Russo

    2003-08-01

    Full Text Available As the use of illegal drugs has reached epidemic proportions in schools, educational leaders in the United States have turned to drug testing in attempting to maintain learner discipline. To this end, the United States Supreme Court has addressed the issue twice in the past eight years. In 1995, the Court permitted drug testing in Acton v. Vernonia School District 47J. More recently, in Board of Education of Independent School District No. 92 of Pottawatomie v. Earls (2002, the Court upheld suspicionless drug testing of learners who wished to participate in extracurricular activities. Even though drug testing has yet to emerge as an issue in South Africa, Earls is significant for educational leaders and policy makers in South Africa since it involves concerns under the National Policy on Privacy. More specifically, under Items 20 and 21 of the South African National Policy on the Management of Drug Abuse (SA, 1996b searches and drug testing should only be used where there is reasonable suspicion, the same standard applied by American courts. However, unlike the United States, the South African policy prohibits random searches and/or drug testing. Thus, due to constitutional and educational issues that drug testing raises, a timely discussion of this matter should be of interest to educational leaders and policy makers in South Africa.

  5. Adulterants in Urine Drug Testing.

    Science.gov (United States)

    Fu, S

    Urine drug testing plays an important role in monitoring licit and illicit drug use for both medico-legal and clinical purposes. One of the major challenges of urine drug testing is adulteration, a practice involving manipulation of a urine specimen with chemical adulterants to produce a false negative test result. This problem is compounded by the number of easily obtained chemicals that can effectively adulterate a urine specimen. Common adulterants include some household chemicals such as hypochlorite bleach, laundry detergent, table salt, and toilet bowl cleaner and many commercial products such as UrinAid (glutaraldehyde), Stealth® (containing peroxidase and peroxide), Urine Luck (pyridinium chlorochromate, PCC), and Klear® (potassium nitrite) available through the Internet. These adulterants can invalidate a screening test result, a confirmatory test result, or both. To counteract urine adulteration, drug testing laboratories have developed a number of analytical methods to detect adulterants in a urine specimen. While these methods are useful in detecting urine adulteration when such activities are suspected, they do not reveal what types of drugs are being concealed. This is particularly the case when oxidizing urine adulterants are involved as these oxidants are capable of destroying drugs and their metabolites in urine, rendering the drug analytes undetectable by any testing technology. One promising approach to address this current limitation has been the use of unique oxidation products formed from reaction of drug analytes with oxidizing adulterants as markers for monitoring drug misuse and urine adulteration. This novel approach will ultimately improve the effectiveness of the current urine drug testing programs. © 2016 Elsevier Inc. All rights reserved.

  6. Health care organization drug testing.

    Science.gov (United States)

    Brooks, J P; Dempsey, J

    1992-09-01

    Health care managers are being required to respond to the growing concerns of the public about alcohol and drug use in the health care workplace. To this end, the following recommendations are offered. A drug testing policy should be developed with input from and support of employees and unions. "For cause" testing should be used because it results in more definitive results and better employee acceptance. Unless there are compelling reasons for random testing, "for cause" testing is the preferable method. All levels of employees and the medical staff should be subject to the drug-testing policy. Rehabilitation rather than punishment should be emphasized in dealing with employees with alcohol and drug problems.

  7. How quantum are non-negative wavefunctions?

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, M. B. [Station Q, Microsoft Research, Santa Barbara, California 93106-6105, USA and Quantum Architectures and Computation Group, Microsoft Research, Redmond, Washington 98052 (United States)

    2016-01-15

    We consider wavefunctions which are non-negative in some tensor product basis. We study what possible teleportation can occur in such wavefunctions, giving a complete answer in some cases (when one system is a qubit) and partial answers elsewhere. We use this to show that a one-dimensional wavefunction which is non-negative and has zero correlation length can be written in a “coherent Gibbs state” form, as explained later. We conjecture that such holds in higher dimensions. Additionally, some results are provided on possible teleportation in general wavefunctions, explaining how Schmidt coefficients before measurement limit the possible Schmidt coefficients after measurement, and on the absence of a “generalized area law” [D. Aharonov et al., in Proceedings of Foundations of Computer Science (FOCS) (IEEE, 2014), p. 246; e-print arXiv.org:1410.0951] even for Hamiltonians with no sign problem. One of the motivations for this work is an attempt to prove a conjecture about ground state wavefunctions which have an “intrinsic” sign problem that cannot be removed by any quantum circuit. We show a weaker version of this, showing that the sign problem is intrinsic for commuting Hamiltonians in the same phase as the double semion model under the technical assumption that TQO-2 holds [S. Bravyi et al., J. Math. Phys. 51, 093512 (2010)].

  8. Implications of Drug Testing Cheerleaders

    Science.gov (United States)

    Trachsler, Tracy A.; Birren, Genevieve

    2016-01-01

    With the untimely death of a University of Louisville cheerleader due to an accidental drug overdose in the summer of 2014, the athletic department representatives took steps to prevent future incidents by adding cheerleaders to the randomized drug testing protocols conducted at the university for the student-athletes involved in National…

  9. Common Interferences in Drug Testing.

    Science.gov (United States)

    Smith, Michael P; Bluth, Martin H

    2016-12-01

    Interferences relating to laboratory toxicology testing refer to results which differ from their true value and are often encountered in the setting of a drug screen compared with confirmatory testing. Such interferences fall into two general categories; those that cause false positive results (when a drug screen is positive but confirmatory testing is negative) and those that cause false negative results (when a drug screen is negative when in reality the sample donor has ingested the tested substance). Such interferences can result from differences in laboratory testing methodology, reagent and analyte cross reactivity, limits of analyte detection, instrument resolution, reporting cutoff, sample processing, tissue type and sample adulteration among others. Awareness of the possible causes of such interferences are integral to proper laboratory result interpretation and patient management. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Non-negative Matrix Factorization for Binary Data

    DEFF Research Database (Denmark)

    Larsen, Jacob Søgaard; Clemmensen, Line Katrine Harder

    We propose the Logistic Non-negative Matrix Factorization for decomposition of binary data. Binary data are frequently generated in e.g. text analysis, sensory data, market basket data etc. A common method for analysing non-negative data is the Non-negative Matrix Factorization, though this is in......We propose the Logistic Non-negative Matrix Factorization for decomposition of binary data. Binary data are frequently generated in e.g. text analysis, sensory data, market basket data etc. A common method for analysing non-negative data is the Non-negative Matrix Factorization, though...

  11. 49 CFR 655.21 - Drug testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Drug testing. 655.21 Section 655.21 Transportation... TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Drug Use § 655.21 Drug testing. (a) An employer shall establish a program that provides testing for prohibited...

  12. 78 FR 22209 - Additional Synthetic Drug Testing

    Science.gov (United States)

    2013-04-15

    ... COMMISSION 10 CFR Part 26 Additional Synthetic Drug Testing AGENCY: Nuclear Regulatory Commission. ACTION... NRC amend its Fitness for Duty program regulations to amend drug testing requirements to test for... raised in the PRM are appropriate for consideration in an ongoing rulemaking on Drug and Alcohol Testing...

  13. 76 FR 59574 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs: Federal Drug Testing...

    Science.gov (United States)

    2011-09-27

    ... Alcohol Testing Programs: Federal Drug Testing Custody and Control Form; Technical Amendment AGENCY... of a new Federal Drug Testing Custody and Control Form (CCF) in its drug testing program. Use of the... amendment to its drug testing procedures by amending a provision of the rule which was inadvertently omitted...

  14. Multiplicative algorithms for constrained non-negative matrix factorization

    KAUST Repository

    Peng, Chengbin

    2012-12-01

    Non-negative matrix factorization (NMF) provides the advantage of parts-based data representation through additive only combinations. It has been widely adopted in areas like item recommending, text mining, data clustering, speech denoising, etc. In this paper, we provide an algorithm that allows the factorization to have linear or approximatly linear constraints with respect to each factor. We prove that if the constraint function is linear, algorithms within our multiplicative framework will converge. This theory supports a large variety of equality and inequality constraints, and can facilitate application of NMF to a much larger domain. Taking the recommender system as an example, we demonstrate how a specialized weighted and constrained NMF algorithm can be developed to fit exactly for the problem, and the tests justify that our constraints improve the performance for both weighted and unweighted NMF algorithms under several different metrics. In particular, on the Movielens data with 94% of items, the Constrained NMF improves recall rate 3% compared to SVD50 and 45% compared to SVD150, which were reported as the best two in the top-N metric. © 2012 IEEE.

  15. A Model for Random Student Drug Testing

    Science.gov (United States)

    Nelson, Judith A.; Rose, Nancy L.; Lutz, Danielle

    2011-01-01

    The purpose of this case study was to examine random student drug testing in one school district relevant to: (a) the perceptions of students participating in competitive extracurricular activities regarding drug use and abuse; (b) the attitudes and perceptions of parents, school staff, and community members regarding student drug involvement; (c)…

  16. Patch testing for adverse drug reactions.

    Science.gov (United States)

    Sekhon, Sahil; Nedorost, Susan T

    2017-01-01

    Adverse drug reactions result in a substantial number of hospital admissions and inpatient events. Diagnosis usually is made with clinical judgment and circumstantiality without diagnostic testing. Furthermore, even in situations where diagnostic testing is performed, no safe gold standard tests exist. Oral rechallenge is currently the gold standard but carries the risk of recrudescence of severe allergic symptoms. Other tests include skin prick tests, the lymphocyte transformation test, immunohistochemistry, and patch testing. This article provides a review of patch testing in cases of adverse drug reactions and presents new data on this topic.

  17. Sparse Non-negative Matrix Factor 2-D Deconvolution

    DEFF Research Database (Denmark)

    Mørup, Morten; Schmidt, Mikkel N.

    2006-01-01

    We introduce the non-negative matrix factor 2-D deconvolution (NMF2D) model, which decomposes a matrix into a 2-dimensional convolution of two factor matrices. This model is an extension of the non-negative matrix factor deconvolution (NMFD) recently introduced by Smaragdis (2004). We derive...... and prove the convergence of two algorithms for NMF2D based on minimizing the squared error and the Kullback-Leibler divergence respectively. Next, we introduce a sparse non-negative matrix factor 2-D deconvolution model that gives easy interpretable decompositions and devise two algorithms for computing...... this form of factorization. The developed algorithms have been used for source separation and music transcription....

  18. Drug susceptibility testing of nontuberculous mycobacteria

    NARCIS (Netherlands)

    Ingen, J. van; Kuijper, E.J.

    2014-01-01

    Diseases caused by nontuberculous mycobacteria are emerging in many settings. With an increased number of patients needing treatment, the role of drug susceptibility testing is again in the spotlight. This articles covers the history and methodology of drug susceptibility tests for nontuberculous

  19. Learning Hidden Markov Models using Non-Negative Matrix Factorization

    CERN Document Server

    Cybenko, George

    2008-01-01

    The Baum-Welsh algorithm together with its derivatives and variations has been the main technique for learning Hidden Markov Models (HMM) from observational data. We present an HMM learning algorithm based on the non-negative matrix factorization (NMF) of higher order Markovian statistics that is structurally different from the Baum-Welsh and its associated approaches. The described algorithm supports estimation of the number of recurrent states of an HMM and iterates the non-negative matrix factorization (NMF) algorithm to improve the learned HMM parameters. Numerical examples are provided as well.

  20. NON-NEGATIVE RADIAL SOLUTION FOR AN ELLIPTIC EQUATION

    Institute of Scientific and Technical Information of China (English)

    Yang Guoying; Guo Zongming

    2005-01-01

    We study the structure and behavior of non-negative radial solution for the following elliptic equation △u = uv, x ∈ Rn with 0 < v < 1. We also obtain the detailed asymptotic expansion of u near infinity.

  1. Algorithms for Sparse Non-negative Tucker Decompositions

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai

    2008-01-01

    for Tucker decompositions when indeed the data and interactions can be considered non-negative. We further illustrate how sparse coding can help identify what model (PARAFAC or Tucker) is the most appropriate for the data as well as to select the number of components by turning off excess components...

  2. Society of Hair Testing guidelines for drug testing in hair.

    Science.gov (United States)

    Cooper, Gail A A; Kronstrand, Robert; Kintz, Pascal

    2012-05-10

    The Society of Hair Testing (SoHT) Guidelines for Drug Testing in Hair provide laboratories with recommended best practice guidelines whether they are currently offering drug testing in hair, or plan to offer a hair testing service in the future. The guidelines include reference to recommended sample collection and storage procedures, through sample preparation, pre-treatment and analysis and the use of cut-offs.

  3. Workplace drug testing in Italy - critical considerations.

    Science.gov (United States)

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; Pozzi, Fulvia; Collo, Giancarlo; Groppi, Angelo

    2013-04-01

    Workplace drug testing (WDT) was established in Italy on 30 October 2007. Two tiers of survey are required: the first tier concerns drug testing on urine samples, the second involves both urine and hair analysis. Between July 2008 and December 2011, 10 598 workers' urine samples and 72 hair samples for opiates, cocaine, cannabinoids, amphetamines, methylenedioxyamphetamines, methadone, and buprenorphine were tested in our laboratory. Urine analyses were performed by immunological screening (EMIT); hair analysis and confirmation tests in urine were performed by gas chromatography-mass spectrometry (GC-MS). Employees tested positive in urine for drugs of abuse numbered 2.8% in 2008, 2.03% in 2009, 1.62% in 2010, and 1.43% in 2011. As regards the second level of analysis, we observed that only one-third of the workers who had been tested positive for drugs of abuse were referred to an Addiction Treatment Unit in order to verify drug addiction. Our experience shows that, four years after approval of the law on WDT, the percentage of workers positive for drugs of abuse in urine has reduced in comparison to the first year. Moreover, our data show that most of the times employees who tested positive are tardily referred or not referred at all to a Public Addiction Treatment Unit to verify drug addiction. This makes us believe that the legal provisions are widely disregarded not paying the right tribute to the fact that Italy is one of few European countries with legislation on WDT.

  4. Hair Testing for Drugs of Abuse

    OpenAIRE

    Karačić, Višnja; Skender, Ljiljana

    2003-01-01

    Hair testing for drugs of abuse is a developing technology, which offers the possibility of longer detection times than is commonly obtained with urine analysis. It is the main method for evaluation of an individual’s drugs of abuse history. In many countries hair analysis is routinely used to detect drug abuse in forensic cases, occupational and traffic medicine and clinical toxicology. Hair analysis in pregnant women, neonates and infants is a useful tool for the detection of...

  5. Efficient non-negative constrained model-based inversion in optoacoustic tomography

    Science.gov (United States)

    Ding, Lu; Luís Deán-Ben, X.; Lutzweiler, Christian; Razansky, Daniel; Ntziachristos, Vasilis

    2015-09-01

    The inversion accuracy in optoacoustic tomography depends on a number of parameters, including the number of detectors employed, discrete sampling issues or imperfectness of the forward model. These parameters result in ambiguities on the reconstructed image. A common ambiguity is the appearance of negative values, which have no physical meaning since optical absorption can only be higher or equal than zero. We investigate herein algorithms that impose non-negative constraints in model-based optoacoustic inversion. Several state-of-the-art non-negative constrained algorithms are analyzed. Furthermore, an algorithm based on the conjugate gradient method is introduced in this work. We are particularly interested in investigating whether positive restrictions lead to accurate solutions or drive the appearance of errors and artifacts. It is shown that the computational performance of non-negative constrained inversion is higher for the introduced algorithm than for the other algorithms, while yielding equivalent results. The experimental performance of this inversion procedure is then tested in phantoms and small animals, showing an improvement in image quality and quantitativeness with respect to the unconstrained approach. The study performed validates the use of non-negative constraints for improving image accuracy compared to unconstrained methods, while maintaining computational efficiency.

  6. Algorithms for Sparse Non-negative Tucker Decompositions

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai

    2008-01-01

    There is a increasing interest in analysis of large scale multi-way data. The concept of multi-way data refers to arrays of data with more than two dimensions, i.e., taking the form of tensors. To analyze such data, decomposition techniques are widely used. The two most common decompositions...... decompositions). To reduce ambiguities of this type of decomposition we develop updates that can impose sparseness in any combination of modalities, hence, proposed algorithms for sparse non-negative Tucker decompositions (SN-TUCKER). We demonstrate how the proposed algorithms are superior to existing algorithms...... for Tucker decompositions when indeed the data and interactions can be considered non-negative. We further illustrate how sparse coding can help identify what model (PARAFAC or Tucker) is the most appropriate for the data as well as to select the number of components by turning off excess components...

  7. 49 CFR 199.105 - Drug tests required.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing... a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any... likely that a drug test would reveal whether the performance was affected by drug use. (c) Random testing...

  8. Testing drug additivity based on monotherapies.

    Science.gov (United States)

    Yang, Harry; Novick, Steven J; Zhao, Wei

    2015-01-01

    Under the Loewe additivity, constant relative potency between two drugs is a sufficient condition for the two drugs to be additive. Implicit in this condition is that one drug acts like a dilution of the other. Geometrically, it means that the dose-response curve of one drug is a copy of another that is shifted horizontally by a constant over the log-dose axis. Such phenomenon is often referred to as parallelism. Thus, testing drug additivity is equivalent to the demonstration of parallelism between two dose-response curves. Current methods used for testing parallelism are usually based on significance tests for differences between parameters in the dose-response curves of the monotherapies. A p-value of less than 0.05 is indicative of non-parallelism. The p-value-based methods, however, may be fundamentally flawed because an increase in either sample size or precision of the assay used to measure drug effect may result in more frequent rejection of parallel lines for a trivial difference. Moreover, similarity (difference) between model parameters does not necessarily translate into the similarity (difference) between the two response curves. As a result, a test may conclude that the model parameters are similar (different), yet there is little assurance on the similarity between the two dose-response curves. In this paper, we introduce a Bayesian approach to directly test the hypothesis that the two drugs have a constant relative potency. An important utility of our proposed method is in aiding go/no-go decisions concerning two drug combination studies. It is illustrated with both a simulated example and a real-life example. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Results of workplace drug testing in Norway

    Directory of Open Access Journals (Sweden)

    Hilde Marie Erøy Lund

    2011-12-01

    Full Text Available Workplace drug testing is less common in Norway than in many other countries. During the period from 2000-2006, 13469 urine or blood samples from employees in the offshore industry, shipping companies and aviation industry were submitted to the Norwegian Institute of Public Health for drug testing. The samples were analysed for benzodiazepines, illicit drugs, muscle relaxants with sedating properties, opioids and z-hypnotics. In total, 2.9% of the samples were positive for one or more substances. During the study period the prevalence decreased for morphine (from 1.9% to 1.1% and increased for amphetamine (from 0.04% to 0.6%, clonazepam (from 0% to 0.1%, methamphetamine (from 0.04% to 0.6%, nitrazepam (from 0% to 0.4% and oxazepam (from 0.5% to 1.3% (p<0.05. There was no significant change in prevalence for the other substances included in the analytical programme. Illicit drugs were significantly associated with lower age (OR: 0.93, p<0.05. This study found low prevalence of drugs among employees in companies with workplace drug testing programmes in Norway.

  10. An elementary proof of the Harnack inequality for non-negative infinity-superharmonic functions

    Directory of Open Access Journals (Sweden)

    Tilak Bhattacharya

    2001-06-01

    Full Text Available We present an elementary proof of the Harnack inequality for non-negative viscosity supersolutions of $Delta_{infty}u=0$. This was originally proven by Lindqvist and Manfredi using sequences of solutions of the $p$-Laplacian. We work directly with the $Delta_{infty}$ operator using the distance function as a test function. We also provide simple proofs of the Liouville property, Hopf boundary point lemma and Lipschitz continuity.

  11. Drug Testing. ERIC Digest Series Number EA 35.

    Science.gov (United States)

    Klauke, Amy

    The issue of drug testing is the focus of this ERIC Digest. Several aspects of drug testing discussed in question-and-answer format: (1) What is the current status of drug use in the schools? (2) What legal questions arise when schools consider drug testing? (3) How might drug testing be applied in a fair, economical, and legally safe manner? (4)…

  12. Wind Noise Reduction using Non-negative Sparse Coding

    DEFF Research Database (Denmark)

    Schmidt, Mikkel N.; Larsen, Jan; Hsiao, Fu-Tien

    2007-01-01

    We introduce a new speaker independent method for reducing wind noise in single-channel recordings of noisy speech. The method is based on non-negative sparse coding and relies on a wind noise dictionary which is estimated from an isolated noise recording. We estimate the parameters of the model...... and discuss their sensitivity. We then compare the algorithm with the classical spectral subtraction method and the Qualcomm-ICSI-OGI noise reduction method. We optimize the sound quality in terms of signal-to-noise ratio and provide results on a noisy speech recognition task....

  13. Hierarchical subtask discovery with non-negative matrix factorization

    CSIR Research Space (South Africa)

    Earle, AC

    2017-08-01

    Full Text Available . Donoho, D. and Stodden, V. When does non-negative matrix factorization give a correct decomposition into parts? Proc. Advances in Neural Information Processing Systems 16, pp. 1141–1148, 2004. Hennequin, R., David, B., and Badeau, R. Beta-divergence as a... with Linearly Solvable Markov Decision Processes. arXiv, 2016. S¸ims¸ek, Ö. and Barto, A.S. Skill Characterization Based on Be- tweenness. Advances in Neural Information Processing Systems, pp. 1497–1504, 2009. Solway, A., Diuk, C., Córdova, N., Yee, D., Barto...

  14. Representations of non-negative polynomials via critical ideals

    CERN Document Server

    Hiep, Dang Tuan

    2011-01-01

    This paper studies the representations of a non-negative polynomial $f$ on a non-compact semi-algebraic set $K$ modulo its critical ideal. Under the assumptions that the semi-algebraic set $K$ is regular and $f$ satisfies the boundary Hessian conditions (BHC) at each zero of $f$ in $K$, we show that $f$ can be represented as a sum of squares (SOS) of real polynomials modulo its critical ideal if $f\\ge 0$ on $K$. In particular, we focus on the polynomial ring $\\mathbb R[x]$.

  15. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  16. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  17. Human sports drug testing by mass spectrometry.

    Science.gov (United States)

    Schänzer, Wilhelm; Thevis, Mario

    2017-01-01

    Since the installation of anti-doping rules and regulations and their international enforcement in the mid-1960s, mass spectrometry has been an integral part of doping control procedures. Although its utility was limited in the first decade, instrumental improvements and method optimizations have made mass spectrometry, in all its facets, an indispensable tool in modern sports drug testing. In this review, milestones in doping control analysis accomplished in Germany and reaching from the early developments to the current use of hyphenated mass spectrometric techniques concerning low- and high molecular mass analytes are presented. The considered drug classes include anabolic agents, peptidic drugs, nucleotide-derived therapeutics, approved and non-approved organic as well as inorganic analytes, and particular focus is put on drug class- and instrument-driven strategies. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:16-46, 2017.

  18. 14 CFR 120.117 - Implementing a drug testing program.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Implementing a drug testing program. 120... AND ALCOHOL TESTING PROGRAM Drug Testing Program Requirements § 120.117 Implementing a drug testing.... (4) A part 145 certificate holder who has your own drug testing program Obtain an Antidrug and...

  19. 46 CFR 16.113 - Chemical drug testing.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... testing programs required by this part must use only drug testing laboratories certified by the Department...

  20. HIV-1 drug resistance and resistance testing.

    Science.gov (United States)

    Clutter, Dana S; Jordan, Michael R; Bertagnolio, Silvia; Shafer, Robert W

    2016-12-01

    The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases. Copyright © 2016 Elsevier B

  1. Ethical considerations in urine drug testing.

    Science.gov (United States)

    Passik, Steven D; Kirsh, Kenneth L

    2011-01-01

    Recent passage of a House Bill in the state of Washington led to a commentary on whether mandates for urine drug testing of pain patients represented a breach of the Fourth and Fourteenth Amendment rights of patients. Issues over true consent to such tests and potential view of warrantless searches were discussed. The authors address these concerns in a broader context of risk management and stratification efforts, along with discussion about the need for a tailored approach in this arena and consideration of cost burden for such tests. Finally, the argument is made that social justice issues need to be considered (along with issues of autonomy, beneficence, and nonmaleficence).

  2. 49 CFR 199.109 - Review of drug testing results.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  3. 75 FR 76078 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-12-07

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY... percentage rate for random drug testing. SUMMARY: PHMSA has determined that the minimum random drug testing... percentage of covered employees for random drug testing. Pursuant to 49 CFR 199.105(c)(2), (3), and (4), the...

  4. 77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2012-01-18

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY... Percentage Rate for Random Drug Testing. SUMMARY: PHMSA has determined that the minimum random drug testing... percentage of covered employees for random drug testing. Pursuant to 49 CFR 199.105(c)(2), (3), and (4), the...

  5. 75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-02-26

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY... Percentage Rate for Random Drug Testing. SUMMARY: PHMSA has determined that the minimum random drug testing... percentage of covered employees for random drug testing. Pursuant to 49 CFR 199.105(c)(2), (3), and (4), the...

  6. 49 CFR 199.107 - Drug testing laboratory.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Drug testing laboratory. 199.107 Section 199.107... § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this part only drug testing laboratories certified by the Department of Health and Human Services under...

  7. 10 CFR 707.10 - Drug testing for reasonable suspicion of illegal drug use.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Drug testing for reasonable suspicion of illegal drug use... Procedures § 707.10 Drug testing for reasonable suspicion of illegal drug use. (a)(1) It may be necessary to... relating to the testing for the use of illegal drugs are not intended to prohibit the contractor from...

  8. [Thyroid function tests in acute drug intoxication].

    Science.gov (United States)

    Tseng, F Y; Chen, C S

    1992-03-01

    It is well known that thyroid function tests may be changed in non-thyroidal illnesses. To understand the influence of acute drug intoxication on thyroid function tests, 31 drug intoxicated patients without previous thyroid disorders and systemic diseases were included in our study. T3, T4, TSH, and resin T3 uptake were checked as soon as they arrived at our emergency service and were compared to that of 58 healthy volunteers. Within 31 patients, 14 were intoxicated by organophosphorous compounds, 6 by sedatives and hypnotics, 3 by strong acid, 2 by paraquet, 2 by rodenticides (warfarin), 2 by lysol and the other 2 were intoxicated by acetaminophen. The mean T3 and TSH levels were significantly lower in the drug intoxicated group. Among the 31 patients, 14 (45.2%) had a low T3, 2 (6.5%) had a low T3 and T4, and 6 (19.3%) had an elevated T4. All of the patients with an elevated T4 were intoxicated by organophosphates. If we divided the 31 patients into 2 subgroups: organophosphate intoxicated group and non-organophosphate intoxicated group, T4 and FT4I were significantly higher in the former group. Thyroid function tests became normal after treatment in 27 patients, discharged in good general condition. T3 and T4 became extremely low in 4 patients before they expired. The present study confirms that acute drug intoxication, like other non-thyroidal illnesses, affects thyroid function tests. Acute organophosphate intoxication may cause transient hyperthyroxinemia.

  9. Does Drug Testing Deter Drug Court Participants from Using Drugs or Alcohol?

    Science.gov (United States)

    Kleinpeter, Christine B.; Brocato, Jo; Koob, Jeffrey J.

    2010-01-01

    This study evaluates 3 drug-testing strategies implemented in 5 different jurisdictions with drug courts in Orange County, California. The purpose of the study was to determine whether the sweat patch acts as a deterrent and under what conditions it can be used to improve outcomes. Results indicated that although the use of the sweat patch did not…

  10. 49 CFR 219.601 - Railroad random drug testing programs.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Railroad random drug testing programs. 219.601... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.601 Railroad random drug testing programs. (a) Submission. Each railroad must submit for FRA...

  11. 76 FR 79204 - Random Drug Testing Rate for Covered Crewmembers

    Science.gov (United States)

    2011-12-21

    ... SECURITY Coast Guard Random Drug Testing Rate for Covered Crewmembers AGENCY: Coast Guard, DHS. ACTION: Notice of minimum random drug testing rate. SUMMARY: The Coast Guard has set the calendar year 2012 minimum random drug testing rate at 50 percent of covered crewmembers. DATES: The minimum random drug...

  12. 49 CFR 219.603 - Participation in drug testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Participation in drug testing. 219.603 Section 219... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.603 Participation in drug testing. A railroad shall, under the conditions specified in this...

  13. 76 FR 1448 - Random Drug Testing Rate for Covered Crewmembers

    Science.gov (United States)

    2011-01-10

    ... SECURITY Coast Guard Random Drug Testing Rate for Covered Crewmembers AGENCY: Coast Guard, DHS. ACTION: Notice of minimum random drug testing rate. SUMMARY: The Coast Guard has set the calendar year 2011 minimum random drug testing rate at 50 percent of covered crewmembers. DATES: The minimum random drug...

  14. 49 CFR 219.605 - Positive drug test results; procedures.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2010-10-01 2010-10-01 false Positive drug test results; procedures. 219.605...

  15. 10 CFR 707.8 - Applicant drug testing.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy... testing. An applicant for a testing designated position will be tested for the use of illegal drugs before... contractors from conducting drug testing on applicants for employment in any position. ...

  16. Aspect-Aided Dynamic Non-Negative Sparse Representation-Based Microwave Image Classification

    Directory of Open Access Journals (Sweden)

    Xinzheng Zhang

    2016-09-01

    Full Text Available Classification of target microwave images is an important application in much areas such as security, surveillance, etc. With respect to the task of microwave image classification, a recognition algorithm based on aspect-aided dynamic non-negative least square (ADNNLS sparse representation is proposed. Firstly, an aspect sector is determined, the center of which is the estimated aspect angle of the testing sample. The training samples in the aspect sector are divided into active atoms and inactive atoms by smooth self-representative learning. Secondly, for each testing sample, the corresponding active atoms are selected dynamically, thereby establishing dynamic dictionary. Thirdly, the testing sample is represented with ℓ 1 -regularized non-negative sparse representation under the corresponding dynamic dictionary. Finally, the class label of the testing sample is identified by use of the minimum reconstruction error. Verification of the proposed algorithm was conducted using the Moving and Stationary Target Acquisition and Recognition (MSTAR database which was acquired by synthetic aperture radar. Experiment results validated that the proposed approach was able to capture the local aspect characteristics of microwave images effectively, thereby improving the classification performance.

  17. Medication monitoring and drug testing ethics project.

    Science.gov (United States)

    Payne, Richard; Moe, Jeffrey L; Sevier, Catherine Harvey; Sevier, David; Waitzkin, Michael

    2015-01-01

    In 2012, Duke University initiated a research project, funded by an unrestricted research grant from Millennium Laboratories, a drug testing company. The project focused on assessing the frequency and nature of questionable, unethical, and illegal business practices in the clinical drug testing industry and assessing the potential for establishing a business code of ethics. Laboratory leaders, clinicians, industry attorneys, ethicists, and consultants participated in the survey, were interviewed, and attended two face-to-face meetings to discuss a way forward. The study demonstrated broad acknowledgment of variations in the legal and regulatory environment, resulting in inconsistent enforcement of industry practices. Study participants expressed agreement that overtly illegal practices sometimes exist, particularly when laboratory representatives and clinicians discuss reimbursement, extent of testing, and potential business incentives with medical practitioners. Most respondents reported directly observing probable violations involving marketing materials, contracts, or, in the case of some individuals, directly soliciting people with offers of clinical supplies and other "freebies." While many study respondents were skeptical that voluntary standards alone would eliminate questionable business practices, most viewed ethics codes and credentialing as an important first step that could potentially mitigate uneven enforcement, while improving quality of care and facilitating preferred payment options for credentialed parties. Many were willing to participate in future discussions and industry-wide initiatives to improve the environment.

  18. The Relationship between Student Illicit Drug Use and School Drug-Testing Policies.

    Science.gov (United States)

    Yamaguchi, Ryoko; Johnston, Lloyd D.; O'Malley, Patrick M.

    This report provides information about drug testing by American secondary schools, based on results from national surveys. The purposes of this study are (1) to provide descriptive information on drug testing practices by schools from 1998 to 2001, and (2) to examine the association between drug testing by schools and reported drug use by…

  19. Drug Testing and Searches in Public Schools: A Legal Analysis.

    Science.gov (United States)

    Minnesota House of Representatives, St. Paul. Research Dept.

    This document examines the Fourth Amendment as the source of search and seizure law; drug testing of school employees; and drug testing searches of students. The United States Supreme Court case that established the two-part test to determine the legality of a student search is discussed, three separate student drug testing programs that have been…

  20. To Test or Not to Test? Drug Testing Teachers: The View of the Superintendent

    Science.gov (United States)

    DeMitchell, Todd A.; Kossakoski, Stephen; Baldasaro, Tony

    2008-01-01

    Purpose: School superintendents are charged with maintaining the safety and security of the schools in their district. One major recognized threat to the security and safety of students and staff is the use of illegal drugs. Superintendents are responding to the constitutionality of student drug-testing policies by implementing drug-testing…

  1. 78 FR 4855 - Random Drug Testing Rate for Covered Crewmembers

    Science.gov (United States)

    2013-01-23

    ... SECURITY Coast Guard Random Drug Testing Rate for Covered Crewmembers AGENCY: Coast Guard, DHS. ACTION: Notice of minimum random drug testing rate. SUMMARY: The Coast Guard has set the calendar year 2013 minimum random drug testing rate at 25 percent of covered crewmembers. The Coast Guard will continue to...

  2. 49 CFR 219.501 - Pre-employment drug testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Pre-employment drug testing. 219.501 Section 219...-employment drug testing. (a) Prior to the first time a covered employee performs covered service for a railroad, the employee must undergo testing for drugs. No railroad may allow a covered employee to perform...

  3. Proposed Policy: Drug Testing of Hawaii's Public School Teachers

    Science.gov (United States)

    Davis, Bebi

    2007-01-01

    Because of a proposed policy, public school teachers in Hawaii are facing the possibility of being randomly tested for illegal drugs. Random drug testing has many implications and its impact is questionable. In this article, the author scrutinizes the controversial drug-testing policy for both troubling and promising aspects and how educators may…

  4. 21 CFR 343.90 - Dissolution and drug release testing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Dissolution and drug release testing. 343.90...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) [Reserved] (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in...

  5. 78 FR 37231 - Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-06-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry; Guidance on Abbreviated New Drug... the availability of a guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and... generic drug review, FDA is recommending that the generic drug industry follow the approach in...

  6. 77 FR 58999 - Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2012-09-25

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug... availability of a draft guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and... of a draft guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and...

  7. Non-negative constraint for image-based breathing gating in ultrasound hepatic perfusion data

    Science.gov (United States)

    Wu, Kaizhi; Ding, Mingyue; Chen, Xi; Deng, Wenjie; Zhang, Zhijun

    2015-12-01

    Images acquired during free breathing using contrast enhanced ultrasound hepatic perfusion imaging exhibits a periodic motion pattern. It needs to be compensated for if a further accurate quantification of the hepatic perfusion analysis is to be executed. To reduce the impact of respiratory motion, image-based breathing gating algorithm was used to compensate the respiratory motion in contrast enhanced ultrasound. The algorithm contains three steps of which respiratory kinetics extracted, image subsequences determined and image subsequences registered. The basic performance of the algorithm was to extract the respiratory kinetics of the ultrasound hepatic perfusion image sequences accurately. In this paper, we treated the kinetics extracted model as a non-negative matrix factorization (NMF) problem. We extracted the respiratory kinetics of the ultrasound hepatic perfusion image sequences by non-negative matrix factorization (NMF). The technique involves using the NMF objective function to accurately extract respiratory kinetics. It was tested on simulative phantom and used to analyze 6 liver CEUS hepatic perfusion image sequences. The experimental results show the effectiveness of our proposed method in quantitative and qualitative.

  8. What You Need To Know about Drug Testing in Schools.

    Science.gov (United States)

    Office of National Drug Control Policy, Washington, DC.

    The Office of National Drug Control policy has put together this guide to assist educators, parents, and community leaders in determining whether student drug testing is appropriate for their schools. The aim is to provide anyone considering a drug-testing program in his or her community with a broad understanding of the issue and solid,…

  9. 14 CFR 120.35 - Testing for prohibited drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Testing for prohibited drugs. 120.35... (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS DRUG AND... for prohibited drugs. (a) Each certificate holder or operator shall test each of its employees...

  10. 75 FR 1547 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2010

    Science.gov (United States)

    2010-01-12

    ... Federal Railroad Administration 49 CFR Part 219 RIN 2130-AA81 Alcohol and Drug Testing: Determination of... percent for drugs and 0.15 percent for alcohol. Because the industry-wide random drug testing positive... (Administrator) has determined that the minimum annual random drug testing rate for the period January 1, 2010...

  11. European guidelines for workplace drug and alcohol testing in hair.

    Science.gov (United States)

    Salomone, A; Tsanaclis, L; Agius, R; Kintz, P; Baumgartner, M R

    2016-10-01

    Guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). They are based on the 2010 version published by Pascal Kintz and Ronald Agius (Guidelines for European workplace drug and alcohol testing in hair. Drug Test. Anal. 2010, 2, 367) and in concordance with the Society of Hair Testing guidelines (Society of Hair Testing guidelines for drug testing in hair. Forensic Sci. Int. 2012, 218, 20-24). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing use these guidelines as a template for accreditation. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Scientific issues in drug testing: council on scientific affairs

    Energy Technology Data Exchange (ETDEWEB)

    1987-06-12

    Testing for drugs in biologic fluids, especially urine, is a practice that has become widespread. The technology of testing for drugs in urine has greatly improved in recent years. Inexpensive screening techniques are not sufficiently accurate for forensic testing standards, which must be met wihen a person's employment or reputation may be affected by results. This is particularly a concern during screening of a population in which the prevalence of drug use is very low, in which the predictive value of a positive result would be quite low. Physicians should be aware that results from drug testing can yield accurate evidence of prior exposure to drugs, but they do not provide information about patterns of drug use, about abuse of or dependence on drugs, or about mental or physical impairments that may result from drug use.

  13. Analytical evaluation of five oral fluid drug testing devices

    OpenAIRE

    Isalberti, Cristina; Van Stechelman, Sylvie; Legrand, Sara-Ann; Van der Linden, Gertrude; Verstraete, Alain

    2010-01-01

    Introduction: The correlation with blood drug presence and the easiness of sample collection make oral fluid an ideal matrix for roadside drug tests targeting impaired drivers. Aim: To evaluate the reliability of five oral fluid testing devices: Varian OraLab®6, Dräger DrugTest® 5000, Cozart® DDS 806, Mavand RapidSTAT® and Innovacon OrAlert. Method: More than 760 samples were collected from volunteers either at drug addiction treatment centres or during roadside sessions. Target drug ...

  14. Information comparison of the effects of drugs on laboratory tests in drug labels and Young's book

    NARCIS (Netherlands)

    Geerts, A.F.; Koning, F.H. de; Egberts, T.C.; Smet, P.A. de; Solinge, W.W. van

    2012-01-01

    Abstract Background: The effects of drugs on laboratory tests may lead to misinterpretation of laboratory data, unnecessary tests, higher costs and missed diagnoses. This study compared the information on drug-laboratory effects (DLE) described in 200 drug labels with that in Young's book. Methods:

  15. 78 FR 52931 - Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-08-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug Substances and Products, Questions and Answers; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``ANDAs: Stability Testing of...

  16. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

  17. Drug Combinations: Tests and Analysis with Isoboles.

    Science.gov (United States)

    Tallarida, Ronald J

    2016-03-18

    Described in this unit are experimental and computational methods to detect and classify drug interactions. In most cases, this relates to two drugs or compounds with overtly similar effects, e.g., two analgesics or two anti-hypertensives. From the dose-response data of the individual drugs, it is possible to generate a curve, the isobole, which defines all dose combinations that are expected to yield a specified effect. The theory underlying the isobole involves the calculation of doses of drug A that are effectively equivalent to doses of drug B with that equivalence determining whether the isobole is linear or nonlinear. In either case, the isobole allows for a comparison with actual combination effects making it possible to determine whether the interaction is synergistic, additive, or sub-additive. Actual as well as illustrative data are employed to demonstrate experimental design and data analysis.

  18. Overview on drug and alcohol testing in the workplace.

    Science.gov (United States)

    Hanson, M

    1993-01-01

    A flashpoint in the debate over workplace responses to alcohol and drug use by members of the workforce centres on the chemical testing of current employees and job applicants for alcohol and drug use. Drug testing may be the most contentious issue faced by enterprises struggling to develop fair and effective programmes to deal with the consequences of substance use in the workplace. The present paper examines scientific evidence on the nature and extent of alcohol and drug use by members of the workforce, evidence linking alcohol and drug use to workplace problems, workplace strategies for managing alcohol- and drug-related difficulties, and arguments for and against drug and alcohol testing. To date, the evidence supportive of alcohol and drug testing is inconclusive. Testing programmes may be useful in identifying drug users in the workforce. Their deterrent value is uncertain, however, and they are not efficient tools for linking drug users to assistance programmes. Enterprises that are contemplating establishing testing programmes should consider: (a) whether substance use is a problem in their setting; (b) whether testing will respond to the problem; (c) the costs and benefits of testing; and (d) any ethical and legal questions raised by the programmes.

  19. Testing for drugs of abuse in children and adolescents.

    Science.gov (United States)

    Levy, Sharon; Siqueira, Lorena M; Ammerman, Seth D; Gonzalez, Pamela K; Ryan, Sheryl A; Siqueira, Lorena M; Smith, Vincent C

    2014-06-01

    Drug testing is often used as part of an assessment for substance use in children and adolescents. However, the indications for drug testing and guidance on how to use this procedure effectively are not clear. The complexity and invasiveness of the procedure and limitations to the information derived from drug testing all affect its utility. The objective of this clinical report is to provide guidance to pediatricians and other clinicians on the efficacy and efficient use of drug testing on the basis of a review of the nascent scientific literature, policy guidelines, and published clinical recommendations.

  20. 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. Because the industry-wide random drug testing positive rate has remained below 1.0 percent for the last...

  1. 77 FR 75896 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2013

    Science.gov (United States)

    2012-12-26

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random.... According to data from FRA's Management Information System, the rail industry's random drug testing positive... (Administrator) has therefore determined that the minimum annual random drug testing rate for the period January...

  2. 76 FR 80781 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2012

    Science.gov (United States)

    2011-12-27

    ... Federal Railroad Administration 49 CFR Part 219 RIN 2130-AA81 Alcohol and Drug Testing: Determination of... random drug testing ] positive rate has remained below 1.0 percent for the last two years. The Federal Railroad Administrator (Administrator) has therefore determined that the minimum annual random drug testing...

  3. Effects of antiepileptic drugs in electrophysiological tests.

    Science.gov (United States)

    Rump, S; Kowalczyk, M

    1987-01-01

    Methods of the study of antiepileptic drugs activity by means of analysis of their effects on bioelectrical ictal phenomena in the animal brain are described. The paper deals especially with EEG signal processing methods. Application of various nonparametric models (e.g. interval-amplitude scatter plots, power spectra analysis) as well as parametric models (e.g. autoregressive model, segmentation analysis) is discussed. A discriminative approach to some of these methods (especially to autoregressive model) is also presented. Special attention is stressed on the value of these methods for the study of anticonvulsant drugs activity.

  4. Experiences with urine drug testing by police among people who inject drugs in Bangkok, Thailand.

    Science.gov (United States)

    Hayashi, Kanna; Ti, Lianping; Buxton, Jane A; Kaplan, Karyn; Suwannawong, Paisan; Wood, Evan; Kerr, Thomas

    2014-03-01

    Thailand has relied on drug law enforcement in an effort to curb illicit drug use. While anecdotal reports suggest that Thai police frequently use urine toxicology to identify drug users, little is known about the prevalence or impacts of this practice among people who inject drugs (IDU). Therefore, we sought to examine experiences with urine drug testing by police among IDU in Bangkok. Data were derived from a community-recruited sample of IDU in Bangkok participating in the Mitsampan Community Research Project between July and October 2011. We assessed the prevalence and correlates of being subjected to urine toxicology testing by police using multivariate Poisson regression. In total, 438 IDU participated in this study, with 293 (66.9%) participants reporting having been tested for illicit drugs by police. In multivariate analyses, reports of drug testing by police were independently and positively associated with younger age (adjusted prevalence ratio [APR]: 1.28), a history of methamphetamine injection (APR: 1.22), a history of incarceration (APR: 1.21), having been in compulsory drug detention (APR: 1.43), avoiding healthcare (APR: 1.15), and HIV seropositivity (APR: 1.19), and negatively associated with access to voluntary drug treatment (APR: 0.82) (all p<0.05). A high proportion of IDU in Bangkok were subjected to drug testing by police. Young people and methamphetamine injectors were more likely to have been tested. The findings indicate that drug testing by police is associated with the compulsory drug detention system and may be interfering with IDU's access to healthcare and voluntary drug treatment. These findings raise concern about the widespread practice of drug testing by police and its associated impacts. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. The Effectiveness of Mandatory-Random Student Drug Testing

    Science.gov (United States)

    James-Burdumy, Susanne; Goesling, Brian; Deke, John; Einspruch, Eric

    2011-01-01

    One approach some U.S. schools now use to combat high rates of adolescent substance use is school-based mandatory-random student drug testing (MRSDT). Under MRSDT, students and their parents sign consent forms agreeing to the students' participation in random drug testing as a condition of participating in athletics and other school-sponsored…

  6. Towards a pragmatic human migraine model for drug testing

    DEFF Research Database (Denmark)

    Hansen, Emma Katrine; Olesen, Jes

    2017-01-01

    BACKGROUND: A model for the testing of novel anti-migraine drugs should preferably use healthy volunteers for ease of recruiting. Isosorbide-5-mononitrate (5-ISMN) provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity...... drug testing....

  7. 78 FR 41999 - Combined Drug and Alcohol Testing Programs

    Science.gov (United States)

    2013-07-15

    ... or on-demand operators that also conduct commercial air tour operations to combine the drug and... operators to conduct separate testing programs for their commercial air tour operations. This results in an..., an operator's drug and alcohol testing program covered its commercial air tour operations. In...

  8. 77 FR 39194 - Combined Drug and Alcohol Testing Programs

    Science.gov (United States)

    2012-07-02

    ... 135 flight-for-hire and on-demand operators also conduct commercial air tours. Parts 121 and 135 each contain requirements for drug and alcohol testing and, until 2007, commercial air tour operators were... commercial air tour operators. That rule contained requirements for drug and alcohol testing for...

  9. An Assessment of Drug Testing within the Construction Industry.

    Science.gov (United States)

    Gerber, Jonathan K.; Yacoubian, George S., Jr.

    2002-01-01

    Investigates the efficacy of workplace drug-testing programs in reducing injury incident rates and workers' compensation experience-rating modification factors within the construction industry. Analyses indicate that companies with drug-testing programs experienced a 51 percent reduction in incident rates within two years of implementation.…

  10. Approximate L0 constrained Non-negative Matrix and Tensor Factorization

    DEFF Research Database (Denmark)

    Mørup, Morten; Madsen, Kristoffer Hougaard; Hansen, Lars Kai

    2008-01-01

    Non-negative matrix factorization (NMF), i.e. V = WH where both V, W and H are non-negative has become a widely used blind source separation technique due to its part based representation. The NMF decomposition is not in general unique and a part based representation not guaranteed. However...... path for the L1 norm regularized least squares NMF for fixed W can be calculated at the cost of an ordinary least squares solution based on a modification of the Least Angle Regression and Selection (LARS) algorithm forming a non-negativity constrained LARS (NLARS). With the full regularization path...

  11. Guidelines for European workplace drug testing in oral fluid.

    Science.gov (United States)

    Cooper, Gail; Moore, Christine; George, Claire; Pichini, Simona

    2011-05-01

    Over the past decade, oral fluid has established itself as a robust testing matrix for monitoring drug use or misuse. Commercially available collection devices provide opportunities to collect and test oral fluid by the roadside and near-patient testing with both clinical and criminal justice applications. One of the main advantages of oral fluid relates to the collection of the matrix which is non-invasive, simple, and can be carried out under direct observation making it ideal for workplace drug testing. Laboratories offering legally defensible oral fluid workplace drug testing must adhere to national and international quality standards (ISO/IEC 17025); however, these standards do not address issues specific to oral fluid testing. The European Workplace Drug Testing Society (EWDTS) recognizes the importance of providing best practice guidelines to organizations offering testing and those choosing to use oral fluid drug testing to test their employees. The aim of this paper is to present the EWDTS guidelines for oral fluid workplace drug testing. Copyright © 2011 John Wiley & Sons, Ltd.

  12. European Guidelines for Workplace Drug Testing in Oral Fluid.

    Science.gov (United States)

    Brcak, Michaela; Beck, Olof; Bosch, Tessa; Carmichael, Duncan; Fucci, Nadia; George, Claire; Piper, Mark; Salomone, Alberto; Schielen, Wim; Steinmeyer, Stefan; Taskinen, Sanna; Weinmann, Wolfgang

    2017-06-28

    These guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. These guidelines are relevant to laboratory-based testing only. These guidelines follow current best practices and are constantly under review. This article is protected by copyright. All rights reserved.

  13. Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project.

    Science.gov (United States)

    Brunt, Tibor M; Nagy, Constanze; Bücheli, Alexander; Martins, Daniel; Ugarte, Miren; Beduwe, Cécile; Ventura Vilamala, Mireia

    2017-02-01

    Drug testing is a harm reduction strategy that has been adopted by certain countries in Europe. Drug users are able to hand in their drugs voluntarily for chemical analysis of composition and dose. Drug users will be alerted about dangerous test results by the drug testing systems directly and through warning campaigns. An international collaborative effort was launched to combine data of drug testing systems, called the Trans European Drug Information (TEDI) project. Drug testing systems of Spain, Switzerland, Belgium, Austria, Portugal, and the Netherlands participated in this project. This study presents results of some of the main illicit drugs encountered: cocaine, ecstasy and amphetamine and also comments on new psychoactive substances (NPS) detected between 2008 and 2013. A total of 45 859 different drug samples were analyzed by TEDI. The drug markets of the distinct European areas showed similarities, but also some interesting differences. For instance, purity of cocaine and amphetamine powders was generally low in Austria, whilst high in Spain and the Netherlands. And the market for ecstasy showed a contrast: whereas in the Netherlands and Switzerland there was predominantly a market for ecstasy tablets, in Portugal and Spain MDMA (3,4-methylenedioxymethamphetamine) crystals were much more prevalent. Also, some NPS appearing in ecstasy seemed more specific for one country than another. In general, prevalence of NPS clearly increased between 2008 and 2013. Drug testing can be used to generate a global picture of drug markets and provides information about the pharmacological contents of drugs for the population at risk. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Urine drug testing of chronic pain patients: licit and illicit drug patterns.

    Science.gov (United States)

    Cone, Edward J; Caplan, Yale H; Black, David L; Robert, Timothy; Moser, Frank

    2008-10-01

    Chronic pain patients are frequently maintained on one or more powerful opioid medications in combination with other psychoactive medications. Urine tests provide objective information regarding patient compliance status. Little information is available on testing this unique population. The goal of this study was to characterize drug disposition patterns in urine specimens collected from a large population of pain patients. Confirmation data for 10,922 positive specimens were collated into 11 drug Classes. The number of drug/metabolites tested (#) and number of confirmed positive specimens were as follows: amphetamines (7), 160; barbiturates (5), 308; benzodiazepines (6), 2397; cannabinoids (1), 967; carisoprodol (2), 611; cocaine (1), 310; fentanyl (1), 458; meperidine (2), 58; methadone (2), 1209; opiates (7), 8996; and propoxyphene (2), 385. Subdivision into 19 distinct drug Groups allowed characterization of drug use patterns. Of the 10,922 positive specimens, 15,859 results were reported as positive in various drug Classes, and 27,197 drug/metabolites were measured by gas chromatography-mass spectrometry. The frequency of illicit drug use (cannabis, cocaine, ecstasy) was 10.8%. Being the first study of this type, these data present a large array of information on licit and illicit drug use, drug detection frequencies, drug/metabolite patterns, and multi-drug use combinations in pain patients.

  15. Non-negative matrix factorization and term structure of interest rates

    Science.gov (United States)

    Takada, Hellinton H.; Stern, Julio M.

    2015-01-01

    Non-Negative Matrix Factorization (NNMF) is a technique for dimensionality reduction with a wide variety of applications from text mining to identification of concentrations in chemistry. NNMF deals with non-negative data and results in non-negative factors and factor loadings. Consequently, it is a natural choice when studying the term structure of interest rates. In this paper, NNMF is applied to obtain factors from the term structure of interest rates and the procedure is compared with other very popular techniques: principal component analysis and Nelson-Siegel model. The NNMF approximation for the term structure of interest rates is better in terms of fitting. From a practitioner point of view, the NNMF factors and factor loadings obtained possess straightforward financial interpretations due to their non-negativeness.

  16. Monte Carlo Algorithm for Least Dependent Non-Negative Mixture Decomposition

    CERN Document Server

    Astakhov, S A; Kraskov, A; Grassberger, P; Astakhov, Sergey A.; St\\"ogbauer, Harald; Kraskov, Alexander; Grassberger, Peter

    2006-01-01

    We propose a simulated annealing algorithm (called SNICA for "stochastic non-negative independent component analysis") for blind decomposition of linear mixtures of non-negative sources with non-negative coefficients. The de-mixing is based on a Metropolis type Monte Carlo search for least dependent components, with the mutual information between recovered components as a cost function and their non-negativity as a hard constraint. Elementary moves are shears in two-dimensional subspaces and rotations in three-dimensional subspaces. The algorithm is geared at decomposing signals whose probability densities peak at zero, the case typical in analytical spectroscopy and multivariate curve resolution. The decomposition performance on large samples of synthetic mixtures and experimental data is much better than that of traditional blind source separation methods based on principal component analysis (MILCA, FastICA, RADICAL) and chemometrics techniques (SIMPLISMA, ALS, BTEM) The source codes of SNICA, MILCA and th...

  17. Drug Testing of Student-Athletes: Another Weapon in the War against Drugs.

    Science.gov (United States)

    Russo, Charles J.; Morse, Timothy E.

    1995-01-01

    In "Acton," the Supreme Court upheld a local school board policy calling for the random, suspicionless drug testing of interscholastic student-athletes. Reviews the Court's holdings. Concludes that a drug-testing policy that is consistent with "Acton" and enjoys broad-based community support probably would be worth its expense.…

  18. Drug Testing of Student-Athletes: Another Weapon in the War against Drugs.

    Science.gov (United States)

    Russo, Charles J.; Morse, Timothy E.

    1995-01-01

    In "Acton," the Supreme Court upheld a local school board policy calling for the random, suspicionless drug testing of interscholastic student-athletes. Reviews the Court's holdings. Concludes that a drug-testing policy that is consistent with "Acton" and enjoys broad-based community support probably would be worth its expense.…

  19. School Drug Testing: A Critical Review of the Literature

    Directory of Open Access Journals (Sweden)

    Daniel T.L. Shek

    2010-01-01

    Full Text Available This paper explores the question of whether school drug testing is an effective solution to tackle adolescent substance abuse problems. Research studies in major academic databases and Internet websites are reviewed. Several observations are highlighted from the review: (1 there are few research studies in this area, particularly in different Chinese contexts; (2 the quality of the existing studies was generally low; and (3 research findings supporting the effectiveness of school drug testing were mixed. Methodological issues underlying quantitative and qualitative evaluation studies of the effectiveness of school drug testing are also discussed.

  20. 14 CFR 120.109 - Types of drug testing required.

    Science.gov (United States)

    2010-01-01

    ... the employer's Substance Abuse Professional conducted in accordance with the provisions of 49 CFR part... CFR part 40). (a) Pre-employment drug testing. (1) No employer may hire any individual for a safety..., cocaine, opiates, phencyclidine (PCP), and amphetamines, or a metabolite of those drugs in the...

  1. Validity of Integrity Tests for Predicting Drug and Alcohol Abuse

    Science.gov (United States)

    1993-08-31

    drug-testing programs. Personnel Psvcholo-a, , 745-763. Gough, H. G. (1948). A Sociological theory of psychopathy . American Journal of Sociology, 5a...Personal Outlook Inventory. Parkridge, IL: Author. Simpson, D. D., Curtis, B., & Butler, M. C. ý1975,. Description of drug users in treatment : 1971-1972

  2. European guidelines for workplace drug testing in urine.

    Science.gov (United States)

    Taskinen, Sanna; Beck, Olof; Bosch, Tessa; Brcak, Michaela; Carmichael, Duncan; Fucci, Nadia; George, Claire; Piper, Mark; Salomone, Alberto; Schielen, Wim; Steinmeyer, Stefan; Weinmann, Wolfgang

    2017-06-01

    These European Guidelines for Workplace Drug Testing in Urine have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The first version of these urine guidelines was published in 2002. Since then, the guidelines have been followed by many laboratories in different European countries and their role has been essential particularly in countries lacking legislation for workplace drug testing. In 2014, the EWDTS started a guidelines updating project and published a new version of the urine guidelines in 2015. Here we represent this updated version of the urine guidelines. The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. 75 FR 3153 - Drug and Alcohol Testing Program; Correction

    Science.gov (United States)

    2010-01-20

    ... flights, Commercial air tour operators, Drug testing, Operators, Safety, Safety-sensitive, Transportation... applicable regulations; and added wording when describing an operator. This rule corrects those inadvertent... requirements on operators affected by these regulations. DATES: Effective January 20, 2010. FOR...

  4. 78 FR 78275 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014

    Science.gov (United States)

    2013-12-26

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014 AGENCY: Federal Railroad Administration (FRA), DOT. ACTION: Notice of determination... therefore determined that the minimum annual random drug testing rate for the period January 1, 2014...

  5. Drug testing for multiemployer plans: choosing the proper legal structure.

    Science.gov (United States)

    Barlament, John L

    2004-03-01

    If drug testing of employees in a multiemployer fund must be performed, how should it be funded? This article illustrates the legal issues associated with several entities often used to fund a drug-testing program, such as health and welfare funds, apprenticeship and training funds, and labor-management cooperation committees. Without such a structure, the plan administrator and others could face unnecessary risks.

  6. Direct-to-Consumer Genetic Testing and Orphan Drug Development.

    Science.gov (United States)

    Mason, Matthew; Levenson, James; Quillin, John

    2017-08-01

    Since the introduction of the Orphan Drug Act (ODA) in 1983, orphan drug approvals in the United States have jumped from testing companies. This emerging trend is the subject of this article, which begins by considering how rare-disease drugs are regulated and the rising interest in nonclinical genetic testing. It then outlines how DTC companies analyze DNA and how their techniques benefit researchers and drug developers. Then, after an overview of the current partnerships between DTCs and drug developers, it examines concerns about privacy and cost brought up by these partnerships. The article concludes by contrasting the enormous positive potential of DTC-pharma relationships and their concomitant dangers, especially to consumer privacy and cost to the healthcare system.

  7. A study of drug eruptions by provocative tests

    Directory of Open Access Journals (Sweden)

    Das J

    2001-09-01

    Full Text Available Sixty cases of drug eruptions were observed during the period of one year. The incidence of drug eruption was 0.47% amongst all Dermatology O.P.D. attendances. Male to female ratio was 7:3. The highest number of cases were seen in the age group of 21-30 years. Fixed drug eruptions were the most frequent (58.3%, followed by urticaria and angioedema (20%. The drug sulphonamides (including co-trimoxazole accounted for the highest number of eruptions (35%. The other drugs which were responsible for the eruptions, in order of frequency, were oxyphenbutazone, ampicillin, analgin, penicillin, tetracycline, ibuprofen, paracetamol, phenylbutazone, acetaminophen and phenobarbitone. The causative drug (s were confirmed by provocation tests in 42 (70% cases.

  8. Drug Testing in Schools: Policies, Practices, and Association with Student Drug Use. YES Occasional Papers. Paper 2

    Science.gov (United States)

    Yamaguchi, Ryoko; Johnston, Lloyd D.; O'Malley, Patrick M.

    2003-01-01

    Despite considerable recent public and judicial attention to the issue of drug testing, little empirical research has focused on the relationship between drug testing in schools and the actual use of illicit drugs by students. To explore this issue, we use school-level survey data about drug testing from the Youth, Education, and Society study and…

  9. 49 CFR 40.81 - What laboratories may be used for DOT drug testing?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What laboratories may be used for DOT drug testing... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Drug Testing Laboratories § 40.81 What laboratories may be used for DOT drug testing? (a) As a drug testing laboratory located in the U.S., you are...

  10. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Science.gov (United States)

    2010-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2010-10-01 2010-10-01 false Use of persons who fail or refuse a drug test. 199...

  11. Appropriate Use of Drug Testing in Clinical Addiction Medicine.

    Science.gov (United States)

    Jarvis, Margaret; Williams, Jessica; Hurford, Matthew; Lindsay, Dawn; Lincoln, Piper; Giles, Leila; Luongo, Peter; Safarian, Taleen

    : Biological drug testing is a tool that provides information about an individual's recent substance use. Like any tool, its value depends on using it correctly; that is, on selecting the right test for the right person at the right time. This document is intended to clarify appropriate clinical use of drug testing in addiction medicine and aid providers in their decisions about drug testing for the identification, diagnosis, treatment, and recovery of patients with, or at risk for, addiction. The RAND Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) process for combining scientific evidence with the collective judgment of experts was used to identify appropriate clinical practices and highlight areas where research is needed. Although consensus panels and expert groups have offered guidance on the use of drug testing for patients with addiction, very few addressed considerations for patients across settings and in different levels of care. This document will focus primarily on patients in addiction treatment and recovery, where drug testing is used to assess patients for a substance use disorder, monitor the effectiveness of a treatment plan, and support recovery. Inasmuch as the scope includes the recognition of addiction, which often occurs in general healthcare settings, selected special populations at risk for addiction visiting these settings are briefly included.

  12. Rat gingival model for testing drugs influencing inflammation

    Directory of Open Access Journals (Sweden)

    Shaju P Jacob

    2013-07-01

    Full Text Available Preclinical drug testing is an important areain new drug development where animals are used.An ideal animal model for this is one which is simple,reliable and can be extrapolated to humans. Topicaldrugs for inflammation are conventionally tested onthe skin of animals after induction of inflammation.A gingival model would be simple as inflammation canbe induced naturally by the action of plaque. Rats area popular animal model for testing drugs as well as tostudy various diseases of the periodontium. Periodontaldisease including gingival inflammation develops inrats in relation to indigenous plaque or experimentallyinduced bacterial products. A number of features ofrats ranging from anatomy, histology and response tobacterial insult can be seen mirrored to a great extentin humans. There is a lot similarity in the developmentand resolution of inflammation as well as the gingivalwound healing of rats and humans. This paper tries toexplore the feasibility of using the rat gingival modelfor preclinical testing of drugs acting on or influencinginflammation and concludes by identifying potentialareas of research using this model. The addition of sucha simple and inexpensive model for preclinical testing ofdrugs will be welcomed by the drug developers.

  13. Army Drug Development Program. Phase 1. Clinical Testing

    Science.gov (United States)

    1981-02-01

    done as clinically indicated. * Part III of Experiment 114 was cancelled. 35 ( H+r rDrug Assay: The schedule of blood sampling will be de...Indicated. * Part III of Experiment #14 was cancelled. 79 ■■— ’( mmmm ■H-K. rDrug Assay: The schedule of blood sampling will be de...reading of phototoxicity tests. 89 tDrug Assay? 10 ml of venous blood were taXen from each sub- ject for each of 20

  14. Fixed drug eruption by etoricoxib confirmed by patch test*

    Science.gov (United States)

    de Sousa, Aline Soares; Cardoso, José Carlos; Gouveia, Miguel Pinto; Gameiro, Ana Rita; Teixeira, Vera Barreto; Gonçalo, Maria

    2016-01-01

    Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction. PMID:27828643

  15. Gene Ranking of RNA-Seq Data via Discriminant Non-Negative Matrix Factorization.

    Science.gov (United States)

    Jia, Zhilong; Zhang, Xiang; Guan, Naiyang; Bo, Xiaochen; Barnes, Michael R; Luo, Zhigang

    2015-01-01

    RNA-sequencing is rapidly becoming the method of choice for studying the full complexity of transcriptomes, however with increasing dimensionality, accurate gene ranking is becoming increasingly challenging. This paper proposes an accurate and sensitive gene ranking method that implements discriminant non-negative matrix factorization (DNMF) for RNA-seq data. To the best of our knowledge, this is the first work to explore the utility of DNMF for gene ranking. When incorporating Fisher's discriminant criteria and setting the reduced dimension as two, DNMF learns two factors to approximate the original gene expression data, abstracting the up-regulated or down-regulated metagene by using the sample label information. The first factor denotes all the genes' weights of two metagenes as the additive combination of all genes, while the second learned factor represents the expression values of two metagenes. In the gene ranking stage, all the genes are ranked as a descending sequence according to the differential values of the metagene weights. Leveraging the nature of NMF and Fisher's criterion, DNMF can robustly boost the gene ranking performance. The Area Under the Curve analysis of differential expression analysis on two benchmarking tests of four RNA-seq data sets with similar phenotypes showed that our proposed DNMF-based gene ranking method outperforms other widely used methods. Moreover, the Gene Set Enrichment Analysis also showed DNMF outweighs others. DNMF is also computationally efficient, substantially outperforming all other benchmarked methods. Consequently, we suggest DNMF is an effective method for the analysis of differential gene expression and gene ranking for RNA-seq data.

  16. 49 CFR 219.701 - Standards for drug and alcohol testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

  17. Non-negative matrix analysis in x-ray spectromicroscopy: choosing regularizers

    Science.gov (United States)

    Mak, Rachel; Wild, Stefan M.; Jacobsen, Chris

    2016-01-01

    In x-ray spectromicroscopy, a set of images can be acquired across an absorption edge to reveal chemical speciation. We previously described the use of non-negative matrix approximation methods for improved classification and analysis of these types of data. We present here an approach to find appropriate values of regularization parameters for this optimization approach. PMID:27041779

  18. Existence of non-negative solutions for nonlinear equations in the semi-positone case

    Directory of Open Access Journals (Sweden)

    Naji Yebari

    2006-09-01

    Full Text Available Using the fibring method we prove the existence of non-negative solution of the p-Laplacian boundary value problem $-Delta_pu=lambda f(u$, for any $lambda >0$ on any regular bounded domain of $mathbb{R}^N$, in the special case $f(t=t^q-1$.

  19. Non-negatively curved 5-manifolds with almost maximal symmetry rank

    CERN Document Server

    Galaz-Garcia, Fernando

    2011-01-01

    We show that a closed, simply-connected, non-negatively curved 5-manifold admitting an effective, isometric $T^2$ action is diffeomorphic to one of $S^5$, $S^3\\times S^2$, $S^3\\tilde{\\times} S^2$ (the non-trivial $S^3$-bundle over $S^2$) or the Wu manifold $SU(3)/SO(3)$.

  20. Reduction of Non-stationary Noise using a Non-negative Latent Variable Decomposition

    DEFF Research Database (Denmark)

    Schmidt, Mikkel Nørgaard; Larsen, Jan

    2008-01-01

    We present a method for suppression of non-stationary noise in single channel recordings of speech. The method is based on a non-negative latent variable decomposition model for the speech and noise signals, learned directly from a noisy mixture. In non-speech regions an over complete basis...

  1. Road-Side Drug Testing: An Evaluation of the Alere DDS®2 Mobile Test System.

    Science.gov (United States)

    Rohrig, Timothy P; Moore, Christine M; Stephens, Kimberly; Cooper, Kelsey; Coulter, Cynthia; Baird, Tyson; Garnier, Margaux; Miller, Samuel; Tuyay, James; Osawa, Kei; Chou, Joshua; Nuss, Carson; Collier, Jeff; Wittman, Karen Cudlin

    2017-09-06

    The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however there are insufficient numbers of these highly trained drug recognition experts (DRE's) who are available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages particularly as it pertains to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory based analysis and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing; both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of a driver should still be considered the most important aspect for arrest and further action. This article is protected by copyright. All rights reserved.

  2. Dissolution testing for generic drugs: an FDA perspective.

    Science.gov (United States)

    Anand, Om; Yu, Lawrence X; Conner, Dale P; Davit, Barbara M

    2011-09-01

    In vitro dissolution testing is an important tool used for development and approval of generic dosage forms. The objective of this article is to summarize how dissolution testing is used for the approval of safe and effective generic drug products in the United States (US). Dissolution testing is routinely used for stability and quality control purposes for both oral and non-oral dosage forms. The dissolution method should be developed using an appropriate validated method depending on the dosage form. There are several ways in which dissolution testing plays a pivotal role in regulatory decision-making. It may be used to waive in vivo bioequivalence (BE) study requirements, as BE documentation for Scale Up and Post Approval Changes (SUPAC), and to predict the potential for a modified-release (MR) drug product to dose-dump if co-administered with alcoholic beverages. Thus, in vitro dissolution testing plays a major role in FDA's efforts to reduce the regulatory burden and unnecessary human studies in generic drug development without sacrificing the quality of the drug products.

  3. 14 CFR 120.123 - Drug testing outside the territory of the United States.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Drug testing outside the territory of the... OPERATIONS DRUG AND ALCOHOL TESTING PROGRAM Drug Testing Program Requirements § 120.123 Drug testing outside the territory of the United States. (a) No part of the testing process (including specimen collection...

  4. 21 CFR 355.70 - Testing procedures for fluoride dentifrice drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Testing procedures for fluoride dentifrice drug... Procedures § 355.70 Testing procedures for fluoride dentifrice drug products. (a) A fluoride dentifrice drug... biological tests are labeled Biological Testing Procedures for Fluoride Dentifrices; these testing procedures...

  5. Toward a pragmatic migraine model for drug testing

    DEFF Research Database (Denmark)

    Hansen, Emma Katrine; Guo, Song; Ashina, Messoud

    2016-01-01

    BACKGROUND: A model for the testing of novel antimigraine drugs should ideally use healthy volunteers for ease of recruiting. Cilostazol provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity. Therefore, this headache...

  6. NCAA Drug-Testing Program 2010-11

    Science.gov (United States)

    National Collegiate Athletic Association (NJ1), 2010

    2010-01-01

    The National Collegiate Athletic Association (NCAA) Drug-Testing Program was created to protect the health and safety of student-athletes and to ensure that no one participant might have an artificially induced advantage or be pressured to use chemical substances. This publication describes this program in the following chapters: (1) NCAA…

  7. Oral fluid for workplace drug testing: laboratory implementation.

    Science.gov (United States)

    Moore, Christine

    2012-02-01

    As oral fluid increases in popularity for workplace testing, due to its easy and observed collection, the ability to adapt existing laboratory instrumentation without further capital investment will allow more facilities to test oral fluid. The European Workplace Drug Testing Society (EWDTS) guidelines for oral fluid testing outline the maximum cut-off concentrations acceptable under the workplace drug testing programme. The recommended cut-off values may be subject to change as advances in technology or other considerations warrant identification of these substances at different concentrations; however, the instrumentation currently exists for routine screening using immunoassay and confirmation by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectral detection (LC-MS/MS) so laboratories can easily implement oral fluid analysis in their current systems. Immunoassays for the detection of the drug classes at recommended levels have been developed using various collection devices and different formats: liquid reagent chemistries and enzyme-linked immunosorbent assay (ELISA) platforms. Immunoassays provide faster turnaround than mass spectral methods particularly when the number of specimens increases. Since the guidelines state that positive immunoassay results should not be reported without confirmation, fully validated methods using LC-MS/MS and/or GC-MS for all drugs are also widely available. All proposed concentrations are easily achievable using MS instruments currently in testing laboratories; however, the likelihood of a low number of positive specimens in workplace populations allows the test facility to screen specimens in a cost-effective manner using immunoassay, while ensuring scientific credibility and defensibility by confirming the positive results with a second test. Copyright © 2011 John Wiley & Sons, Ltd.

  8. 21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

    Science.gov (United States)

    2010-04-01

    ... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

  9. Testing a fall risk model for injection drug users.

    Science.gov (United States)

    Pieper, Barbara; Templin, Thomas N; Goldberg, Allon

    2012-01-01

    Fall risk is a critical component of clinical assessment and has not been examined for persons who have injected illicit drugs and are aging. The aim of this study was to test and develop the Fall Risk Model for Injection Drug Users by examining the relationships among injection drug use, chronic venous insufficiency, lower extremity impairments (i.e., decreased ankle range of motion, reduced calf muscle endurance, and leg pain), age and other covariates, and the Tinetti balance and gait total score as a measure of fall risk. A cross-sectional comparative design was used with four crossed factors. Standardized instruments were used to assess the variables. Moderated multiple regression with linear and quadratic trends in age was used to examine the nature of the relationship between the Tinetti balance and gait total and age and the potential moderating role of injection drug use. A prespecified series of models was tested. Participants (n = 713) were men (46.9%) and women with a mean age of 46.26 years and primarily African American (61.7%) in methadone treatment centers. The fall risk of a 48-year-old leg injector was comparable with the fall risk of a 69-year-old who had not injected drugs. Variables were added to the model sequentially, resulting in some lost significance of some when they were explained by subsequent variables. Final significant variables in the model were employment status, number of comorbidities, ankle range of motion, leg pain, and calf muscle endurance. Fall risk was associated with route of drug use. Lower extremity impairments accounted for the effects of injection drug use and chronic venous insufficiency on risk for falls. Further understanding of fall risk in injection users is necessary as they age, attempt to work, and participate in activities.

  10. Comparison of Urine and Oral Fluid for Workplace Drug Testing.

    Science.gov (United States)

    Casolin, Armand

    2016-09-01

    To determine the relative detection rates of urine versus oral fluid testing in a safety sensitive industry and the correlation with diagnosed substance use disorders and possible impairment at work. The trial involved 1,500 paired urine and oral fluid tests performed in accordance with Australian Standard/New Zealand Standard (AS/NZS) 4308:2008 and AS 4760:2006. Workers who returned a positive test were screened for substance use disorders, as defined by DSM-5, and for possible impairment at work following that particular episode of substance use. Substances were detected in 3.7% (n = 56) of urine samples and 0.5% (n = 8) of oral fluid samples (p drug or a controlled substance without a clinical indication and prescription. Nine workers tested positive on urine alone, one on oral fluid alone and two on both (p = 0.0114). Of note, 6/11 workers who tested positive on urine had possible impairment at work and 2/11 had a substance use disorder versus 2/3 and 0/3, respectively, who tested positive on oral fluid. Urine drug testing performed in accordance with AS/NZS 4308:2008 is more likely to detect overall substance use and illicit drug use than oral fluid testing conducted in accordance with AS 4760:2006. Urine testing performed in accordance with AS/NZS 4308:2008 may also be more likely to detect workers with possible impairment at work and substance use disorders than oral fluid testing performed in accordance with AS 4760:2006. © The Author 2016. Published by Oxford University Press.

  11. Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

    Science.gov (United States)

    Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

    2016-07-01

    Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Testing for diabetes in hospitalised patients prescribed antipsychotic drugs.

    Science.gov (United States)

    Taylor, David; Young, Corina; Esop, Raadiyya; Paton, Carol; Walwyn, Rebecca

    2004-08-01

    Studies using computer databases suggest that atypical antipsychotic agents are more likely to be associated with diabetes than are conventional drugs. To discover the extent of testing for diabetes mellitus in hospital in-patients prescribed antipsychotics. Prescription charts were screened to identify patients prescribed antipsychotics. Case notes were then searched for evidence of testing for diabetes. In all, 606 patients were prescribed antipsychotics, of whom 250 (41.3%) had evidence of prior testing for diabetes. Patients prescribed atypicals were 40% more likely to have been tested than those prescribed conventional drugs (RR =1.4,95% CI1.1-1.9). Adjusted odds ratios v. conventional antipsychotics for conventional antipsychotics for testing were significantly higher for clozapine (OR=4.64,95% CI 2.42-8.90), olanzapine (OR=1.85,95% CI1.04-3.30) and antipsychotic polypharmacy (OR=2.96,95% CI1.59-5.52). Testing for diabetes was undertaken in less than half of the patients studied. Testing was more common in those receiving atypical antipsychotics. Apparent differences in claimed causal association of the use of some antipsychotics with diabetes may in part reflect different rates of testing.

  13. Technique for computing the PDFs and CDFs of non-negative infinitely divisible random variables

    CERN Document Server

    Veillette, Mark S

    2010-01-01

    We present a method for computing the PDF and CDF of a non-negative infinitely divisible random variable $X$. Our method uses the L\\'{e}vy-Khintchine representation of the Laplace transform $\\mathbb{E} e^{-\\lambda X} = e^{-\\phi(\\lambda)}$, where $\\phi$ is the Laplace exponent. We apply the Post-Widder method for Laplace transform inversion combined with a sequence convergence accelerator to obtain accurate results. We demonstrate this technique on several examples including the stable distribution, mixtures thereof, and integrals with respect to non-negative L\\'{e}vy processes. Software to implement this method is available from the authors and we illustrate its use at the end of the paper.

  14. Single-channel source separation using non-negative matrix factorization

    DEFF Research Database (Denmark)

    Schmidt, Mikkel Nørgaard

    , in which a number of methods for single-channel source separation based on non-negative matrix factorization are presented. In the papers, the methods are applied to separating audio signals such as speech and musical instruments and separating different types of tissue in chemical shift imaging.......Single-channel source separation problems occur when a number of sources emit signals that are mixed and recorded by a single sensor, and we are interested in estimating the original source signals based on the recorded mixture. This problem, which occurs in many sciences, is inherently under......-determined and its solution relies on making appropriate assumptions concerning the sources. This dissertation is concerned with model-based probabilistic single-channel source separation based on non-negative matrix factorization, and consists of two parts: i) three introductory chapters and ii) five published...

  15. Instability of elliptic equations on compact Riemannian manifolds with non-negative Ricci curvature

    Directory of Open Access Journals (Sweden)

    Arnaldo S. Nascimento

    2010-05-01

    Full Text Available We prove the nonexistence of nonconstant local minimizers for a class of functionals, which typically appear in scalar two-phase field models, over smooth N-dimensional Riemannian manifolds without boundary and non-negative Ricci curvature. Conversely, for a class of surfaces possessing a simple closed geodesic along which the Gauss curvature is negative, we prove the existence of nonconstant local minimizers for the same class of functionals.

  16. Expanding solitons with non-negative curvature operator coming out of cones

    CERN Document Server

    Schulze, Felix

    2010-01-01

    We show that a Ricci flow of any complete Riemannian manifold without boundary with bounded non-negative curvature operator and non-zero asymptotic volume ratio exists for all time and has constant asymptotic volume ratio. We show that there is a limit solution, obtained by scaling down this solution at a fixed point in space, which is an expanding soliton coming out of the asymptotic cone at infinity.

  17. Non-negative submodular stochastic probing via stochastic contention resolution schemes

    OpenAIRE

    Adamczyk, Marek

    2015-01-01

    The abstract model of stochastic probing was presented by Gupta and Nagarajan (IPCO'13), and provides a unified view of a number of problems. Adamczyk, Sviridenko, Ward (STACS'14) gave better approximation for matroid environments and linear objectives. At the same time this method was easily extendable to settings, where the objective function was monotone submodular. However, the case of non-negative submodular function could not be handled by previous techniques. In this paper we address t...

  18. Real-time detection of overlapping sound events with non-negative matrix factorization

    OpenAIRE

    Dessein, Arnaud; Cont, Arshia; Lemaitre, Guillaume

    2013-01-01

    International audience; In this paper, we investigate the problem of real-time detection of overlapping sound events by employing non-negative matrix factorization techniques. We consider a setup where audio streams arrive in real-time to the system and are decomposed onto a dictionary of event templates learned off-line prior to the decomposition. An important drawback of existing approaches in this context is the lack of controls on the decomposition. We propose and compare two provably con...

  19. Supervised non-negative matrix factorization based latent semantic image indexing

    Institute of Scientific and Technical Information of China (English)

    Dong Liang; Jie Yang; Yuchou Chang

    2006-01-01

    @@ A novel latent semantic indexing (LSI) approach for content-based image retrieval is presented in this paper. Firstly, an extension of non-negative matrix factorization (NMF) to supervised initialization isdiscussed. Then, supervised NMF is used in LSI to find the relationships between low-level features and high-level semantics. The retrieved results are compared with other approaches and a good performance is obtained.

  20. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  1. 49 CFR 40.87 - What are the cutoff concentrations for drug tests?

    Science.gov (United States)

    2010-10-01

    ... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Drug Testing Laboratories § 40.87 What are the cutoff concentrations for drug tests? (a) As a laboratory, you must use the cutoff concentrations displayed in the... 49 Transportation 1 2010-10-01 2010-10-01 false What are the cutoff concentrations for drug tests...

  2. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  3. 75 FR 59105 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs: Federal Drug Testing...

    Science.gov (United States)

    2010-09-27

    ... modifications. As a reminder to MROs, the ``Test Cancelled'' box should only be used when the split fails to....187(f) rule text on how MROs are to document split specimen results. It is our understanding that...

  4. Mouse models for pre-clinical drug testing in leukemia.

    Science.gov (United States)

    Bhatia, Sanil; Daschkey, Svenja; Lang, Franziska; Borkhardt, Arndt; Hauer, Julia

    2016-11-01

    The development of novel drugs which specifically target leukemic cells, with the overall aim to increase complete remission and to reduce toxicity and morbidity, is the most important prerequisite for modern leukemia treatment. In this regard, the current transition rate of potential novel drugs from bench to bedside is remarkably low. Although many novel drugs show promising data in vitro and in vivo, testing of these medications in clinical phase I trials is often sobering with intolerable toxic side effects leading to failure in FDA approval. Areas covered: In this review, the authors discuss the development of murine model generation in the context of targeted therapy development for the treatment of childhood leukemia, aiming to decrease the attrition rate of progressively complex targeted therapies ranging from small molecules to cell therapy. As more complex therapeutic approaches develop, more complex murine models are needed, to recapitulate closely the human phenotype. Expert opinion: Combining xenograft models for efficacy testing and GEMMs for toxicity testing will be a global approach for pre-clinical testing of complex therapeutics and will contribute to the clinical approval of novel compounds. Finally, this approach is likely to increase clinical approval of novel compounds.

  5. Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

    Science.gov (United States)

    Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

    2015-02-01

    Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

  6. [Interventional neuroradiology. Drug treatment, monitoring and function tests].

    Science.gov (United States)

    Laurent, A; Gobin, Y P; Launay, F; Aymard, A; Casasco, A; Merland, J J

    1994-04-23

    Specialized monitoring as well as function tests and drug therapy play an ever growing role in neuroradiological procedures. The particular route of administration and the territories involved in neuroradiology require special precautions. Anaesthesia must enable the operators to monitor the central nervous system since the patients must remain totally immobilized for several hours. Catheterization is made safe by careful asepsia and antibiotic prophylaxis and by preventing embolic events, particularly in neuro-cervico-facial interventions where an anticoagulant protocol is important. Arterial spasms can be prevented or cured with calcium inhibitors. The safety of the procedure itself is guaranteed by various function tests including sensitivity to ischaemia using anaesthetic barbiturates, controlled clampings or the lidocaine test. Undesirable effects of both emboli (e.g. toxicity of cyanoacrylate glue) and embolization (e.g. subsequent venous thrombosis) can be prevented by adapted anti-inflammatory drugs. Herein, we describe the routine monitoring conditions, drugs prescribed and function tests performed at the Therapeutic Angiography Department of the Lariboisière Hospital, Paris.

  7. Decomposing the time-frequency representation of EEG using non-negative matrix and multi-way factorization

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai; Parnas, Josef;

    2006-01-01

    generalized to a parallel factor (PARAFAC) model to form a non-negative multi-way factorization (NMWF). While the NMF can examine subject specific activities the NMWF can effectively extract the most similar activities across subjects and or conditions. The methods are tested on a proprioceptive stimulus...... consisting of a weight change in a handheld load. While somatosensory gamma oscillations have previously only been evoked by electrical stimuli we hypothesized that a natural proprioceptive stimulus also would be able to evoke gamma oscillations. ITPC maxima were determined by visual inspection...... contralateral to stimulus side and additionally an unexpected 20Hz activity slightly lateralized in the frontal central region. Consequently, also proprioceptive stimuli are able to elicit evoked gamma activity....

  8. Olodaterol and vilanterol detection in sport drug testing.

    Science.gov (United States)

    Chundela, Zdenek; Große, Joachim

    2015-01-01

    The possibility of the detection of olodaterol and vilanterol, two novel β2 -agonists, in human urine for the purpose of sport drug testing was investigated. Compounds of interest were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) employing methods commonly used in the World Anti-Doping Agency (WADA) accredited laboratories. For both substances, the respective parent compound was found to be a suitable target analyte for monitoring therapeutic dose administration.

  9. Template synthesized chitosan nano test tubes for drug delivery applications

    Science.gov (United States)

    Perry, Jillian L. Moulton

    There is tremendous current interest in developing nanoscale drug delivery vehicles. Though intensive efforts have focused on developing spherical drug delivery vehicles, cylindrically shaped vehicles such as nanotubes offer many advantages. Typically, nanotubes can carry a larger inner payload than nanoparticles of the same diameter. Also, we can prepare nanotubes in templates whose geometries can be controlled, in turn allowing precise control over the length and diameter of the tubes. In addition, template synthesized nanotubes can be differentially functionalized on the inner and outer surfaces. Furthermore, templates that are closed on one end can be used to fabricate nano test tubes (closed on one end). The geometry of these nano test tubes allows them to be easily filled with a payload, the open end sealed with a nanoparticle to protect the payload from leaking out, and then the exterior of the tube can be functionalized with a targeting moiety. In an effort to develop such a system, we explored the fabrication of chitosan nano test tubes. Defect-free, chitosan nano test tubes of uniform size were synthesized within the pores of a nanoporous alumina template membrane. While the nano test tubes remained within the template membrane, their inner cavities were filled with a model payload. The payload was then trapped inside the nano test tubes by sealing the open ends of the tubes with latex nanoparticle caps. For proof-of-principle studies, imine linkages were used to attach the caps to the nano test tubes. To create a self-disassembling system, disulfide chemistry was used to covalently cap the nano test tubes. Once removed from the template, the exterior of the nano test tubes were modified with a targeting moiety, allowing them to be targeted to pathological sites. We have also shown that the chitosan nano test tubes are biodegradable by two systems: enzymatic cleavage by lysozymes and disulfide cleavage of the crosslinker by reducing environments

  10. The role of drug susceptibility testing in controlling drug resistant tuberculosis: Challenges and possibilities

    Directory of Open Access Journals (Sweden)

    Sven Hoffner

    2015-01-01

    Conclusions: Reliable and timely detection of drug-resistant TB is needed, which is best achieved with molecular assays. In this author's opinion, rapid detection of resistance to isoniazid should be included with rifampicin resistance examination. In MDR, timely detection of the XDR defining agents and PZA is urgently needed. Development and validation of such tests should be a priority, as well as establishing QMS for the implementation and routine use of molecular rapid diagnostics. Each country should develop national diagnostic algorithms for how, when and where rapid molecular assays should be used for early detection of drug-resistant TB.

  11. Workplace drug testing in Italy: findings about second-stage testing.

    Science.gov (United States)

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; San Bartolomeo, Paolo; Groppi, Angelo

    2015-03-01

    Workplace Drug Testing (WDT) in Italy includes two levels of monitoring: a first stage concerning drug testing on urine samples and a second involving both urine and hair analysis. The second stage is performed only on workers who tested positive at the first level. We analyzed urine and hair specimens from 120 workers undergoing second-level testing between 2009 and 2012. Eighty percent of them had tested positive for cannabinoids during the first level analysis, and 15.8% for cocaine. Both urine and hair samples were analyzed in order to find the following drugs of abuse: amphetamines, buprenorphine, cannabinoids, cocaine, ecstasy, methadone, and opiates. Urine analyses were performed by immunological screening (EMIT); urine confirmatory tests and hair analyses were performed by gas chromatography-mass spectrometry (GC-MS). As regards second-stage testing on urine samples, 71.2% of workers were always negative, whereas 23.9% tested positive at least once for cannabinoids and 2.5% for cocaine. Hair analyses produced surprising results: 61.9% of hair samples tested negative, only 6.2% tested positive for cannabinoids, whereas 28.8% tested positive for cocaine. These findings confirm that second-level surveillance of WDT, which includes hair analysis, is very effective because it highlights drug intake - sometimes heavy - that cannot be revealed only through urine analyses. The employees for whom drug addiction is proved can begin rehabilitation, while keeping their job. Eventually, our results confirmed the widespread and undeclared use of cocaine in Italy. Copyright © 2014 John Wiley & Sons, Ltd.

  12. 49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

    Science.gov (United States)

    2010-10-01

    ... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

  13. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-06-15

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

  14. Application of drug testing using exhaled breath for compliance monitoring of drug addicts in treatment.

    Science.gov (United States)

    Carlsson, Sten; Olsson, Robert; Lindkvist, Irene; Beck, Olof

    2015-04-01

    Exhaled breath has recently been identified as a possible matrix for drug testing. This study explored the potential of this new method for compliance monitoring of patients being treated for dependence disorders. Outpatients in treatment programs were recruited for this study. Urine was collected as part of clinical routine and a breath sample was collected in parallel together with a questionnaire about their views of the testing procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis, cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical screening and mass spectrometry confirmation. The exhaled breath was collected using the SensAbues device and analyzed by mass spectrometry for amphetamine, methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine, benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6-acetylmorphine. A total of 122 cases with parallel urine and breath samples were collected; 34 of these were negative both in urine and breath. Out of 88 cases with positive urine samples 51 (58%) were also positive in breath. Among the patients on methadone treatment, all were positive for methadone in urine and 83% were positive in breath. Among patients in treatment with buprenorphine, 92% were positive in urine and among those 80% were also positive in breath. The questionnaire response documented that in general, patients accepted drug testing well and that the breath sampling procedure was preferred. Compliance testing for the intake of prescribed and unprescribed drugs among patients in treatment for dependence disorders using the exhaled breath sampling technique is a viable method and deserves future attention.

  15. Animal models for testing anti-prion drugs.

    Science.gov (United States)

    Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

    2013-01-01

    Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

  16. Exploring syndrome differentiation using non-negative matrix factorization and cluster analysis in patients with atopic dermatitis.

    Science.gov (United States)

    Yun, Younghee; Jung, Wonmo; Kim, Hyunho; Jang, Bo-Hyoung; Kim, Min-Hee; Noh, Jiseong; Ko, Seong-Gyu; Choi, Inhwa

    2017-08-01

    Syndrome differentiation (SD) results in a diagnostic conclusion based on a cluster of concurrent symptoms and signs, including pulse form and tongue color. In Korea, there is a strong interest in the standardization of Traditional Medicine (TM). In order to standardize TM treatment, standardization of SD should be given priority. The aim of this study was to explore the SD, or symptom clusters, of patients with atopic dermatitis (AD) using non-negative factorization methods and k-means clustering analysis. We screened 80 patients and enrolled 73 eligible patients. One TM dermatologist evaluated the symptoms/signs using an existing clinical dataset from patients with AD. This dataset was designed to collect 15 dermatologic and 18 systemic symptoms/signs associated with AD. Non-negative matrix factorization was used to decompose the original data into a matrix with three features and a weight matrix. The point of intersection of the three coordinates from each patient was placed in three-dimensional space. With five clusters, the silhouette score reached 0.484, and this was the best silhouette score obtained from two to nine clusters. Patients were clustered according to the varying severity of concurrent symptoms/signs. Through the distribution of the null hypothesis generated by 10,000 permutation tests, we found significant cluster-specific symptoms/signs from the confidence intervals in the upper and lower 2.5% of the distribution. Patients in each cluster showed differences in symptoms/signs and severity. In a clinical situation, SD and treatment are based on the practitioners' observations and clinical experience. SD, identified through informatics, can contribute to development of standardized, objective, and consistent SD for each disease. Copyright © 2017. Published by Elsevier Ltd.

  17. The Influence of Drug Testing and Benefit-Based Distribution of Opioid Substitution Therapy on Drug Abstinence.

    Science.gov (United States)

    Gabrovec, Branko

    2015-01-01

    The objective of our research was to discover whether the new approach to urine drug testing has a positive effect on users' abstinence, users' treatment, and their cooperation, while remaining user-friendly, and whether this approach is more cost-effective. The centers are focused on providing high-quality treatment within a cost-efficient program. In this study, we focus on the influence of drug testing and benefit-based distribution of opioid substitution therapy (BBDOST) on drug abstinence. The purpose of this study was to find any possible positive effect of modified distribution of the therapy and illicit drug testing on the number of users who are abstinent from illicit drugs and users who are not abstinent from illicit drugs as well as the users' opinion on BBDOST and testing. We are also interested in a difference in abstinence rates between those on BBDOST and those not receiving BBDOST. In 2010, the method of drug testing at the center was changed (less frequent and random drug testing) to enable its users faster access to BBDOST (take-home therapy). It was found that the number of drug-abstinent program participants has increased from initial 44.5% (2010) to 54.1% (2014). According to the program participants, the new method allows them to achieve and maintain abstinence from drugs more easily. In addition, they are also satisfied with the modified way of drug testing. This opinion does not change with age, gender, and acquired benefits.

  18. Ascent sequences and upper triangular matrices containing non-negative integers

    CERN Document Server

    Dukes, Mark

    2009-01-01

    This paper presents a bijection between ascent sequences and upper triangular matrices whose non-negative entries are such that all rows and columns contain at least one non-zero entry. We show the equivalence of several natural statistics on these structures under this bijection and prove that some of these statistics are equidistributed. Several special classes of matrices are shown to have simple formulations in terms of ascent sequences. Binary matrices are shown to correspond to ascent sequences with no two adjacent entries the same. Bidiagonal matrices are shown to be related to order-consecutive set partitions and a simple condition on the ascent sequences generate this class.

  19. Non-negative matrix factorization with Log Gabor wavelets for image representation and classification

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhonglong; Yang Jie

    2005-01-01

    Many problems in image representation and classification involve some form of dimensionality reduction. Non-negative matrix factorization (NMF) is a recently proposed unsupervised procedure for learning spatially localized, parts-based subspace representation of objects. An improvement of the classical NMF by combining with Log-Gabor wavelets to enhance its part-based learning ability is presented. The new method with principal component analysis (PCA) and locally linear embedding (LLE) proposed recently in Science are compared. Finally, the new method to several real world datasets and achieve good performance in representation and classification is applied.

  20. Fast Bayesian Non-Negative Matrix Factorisation and Tri-Factorisation

    DEFF Research Database (Denmark)

    Brouwer, Thomas; Frellsen, Jes; Liò, Pietro

    We present a fast variational Bayesian algorithm for performing non-negative matrix factorisation and tri-factorisation. We show that our approach achieves faster convergence per iteration and timestep (wall-clock) than Gibbs sampling and non-probabilistic approaches, and do not require additional...... samples to estimate the posterior. We show that in particular for matrix tri-factorisation convergence is difficult, but our variational Bayesian approach offers a fast solution, allowing the tri-factorisation approach to be used more effectively....

  1. Non-negative Ricci curvature on closed manifolds under Ricci flow

    CERN Document Server

    Maximo, Davi

    2009-01-01

    In this short note we show that non-negative Ricci curvature is not preserved under Ricci flow for closed manifolds of dimensions four and above, strengthening a previous result of Knopf in \\cite{K} for complete non-compact manifolds of bounded curvature. This brings down to four dimensions a similar result B\\"ohm and Wilking have for dimensions twelve and above, \\cite{BW}. Moreover, the manifolds constructed here are \\Kahler manifolds and relate to a question raised by Xiuxiong Chen in \\cite{XC}, \\cite{XCL}.

  2. Single-Channel Speech Separation using Sparse Non-Negative Matrix Factorization

    DEFF Research Database (Denmark)

    Schmidt, Mikkel N.; Olsson, Rasmus Kongsgaard

    2007-01-01

    We apply machine learning techniques to the problem of separating multiple speech sources from a single microphone recording. The method of choice is a sparse non-negative matrix factorization algorithm, which in an unsupervised manner can learn sparse representations of the data. This is applied...... to the learning of personalized dictionaries from a speech corpus, which in turn are used to separate the audio stream into its components. We show that computational savings can be achieved by segmenting the training data on a phoneme level. To split the data, a conventional speech recognizer is used...

  3. Online multi-modal robust non-negative dictionary learning for visual tracking.

    Science.gov (United States)

    Zhang, Xiang; Guan, Naiyang; Tao, Dacheng; Qiu, Xiaogang; Luo, Zhigang

    2015-01-01

    Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality.

  4. Online multi-modal robust non-negative dictionary learning for visual tracking.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    Full Text Available Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality.

  5. Hyperspectral Image Super-Resolution via Non-Negative Structured Sparse Representation.

    Science.gov (United States)

    Dong, Weisheng; Fu, Fazuo; Shi, Guangming; Cao, Xun; Wu, Jinjian; Li, Guangyu; Li, Guangyu

    2016-05-01

    Hyperspectral imaging has many applications from agriculture and astronomy to surveillance and mineralogy. However, it is often challenging to obtain high-resolution (HR) hyperspectral images using existing hyperspectral imaging techniques due to various hardware limitations. In this paper, we propose a new hyperspectral image super-resolution method from a low-resolution (LR) image and a HR reference image of the same scene. The estimation of the HR hyperspectral image is formulated as a joint estimation of the hyperspectral dictionary and the sparse codes based on the prior knowledge of the spatial-spectral sparsity of the hyperspectral image. The hyperspectral dictionary representing prototype reflectance spectra vectors of the scene is first learned from the input LR image. Specifically, an efficient non-negative dictionary learning algorithm using the block-coordinate descent optimization technique is proposed. Then, the sparse codes of the desired HR hyperspectral image with respect to learned hyperspectral basis are estimated from the pair of LR and HR reference images. To improve the accuracy of non-negative sparse coding, a clustering-based structured sparse coding method is proposed to exploit the spatial correlation among the learned sparse codes. The experimental results on both public datasets and real LR hypspectral images suggest that the proposed method substantially outperforms several existing HR hyperspectral image recovery techniques in the literature in terms of both objective quality metrics and computational efficiency.

  6. Online Multi-Modal Robust Non-Negative Dictionary Learning for Visual Tracking

    Science.gov (United States)

    Zhang, Xiang; Guan, Naiyang; Tao, Dacheng; Qiu, Xiaogang; Luo, Zhigang

    2015-01-01

    Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality. PMID:25961715

  7. Pavement crack detection combining non-negative feature with fast LoG in complex scene

    Science.gov (United States)

    Wang, Wanli; Zhang, Xiuhua; Hong, Hanyu

    2015-12-01

    Pavement crack detection is affected by much interference in the realistic situation, such as the shadow, road sign, oil stain, salt and pepper noise etc. Due to these unfavorable factors, the exist crack detection methods are difficult to distinguish the crack from background correctly. How to extract crack information effectively is the key problem to the road crack detection system. To solve this problem, a novel method for pavement crack detection based on combining non-negative feature with fast LoG is proposed. The two key novelties and benefits of this new approach are that 1) using image pixel gray value compensation to acquisit uniform image, and 2) combining non-negative feature with fast LoG to extract crack information. The image preprocessing results demonstrate that the method is indeed able to homogenize the crack image with more accurately compared to existing methods. A large number of experimental results demonstrate the proposed approach can detect the crack regions more correctly compared with traditional methods.

  8. Bayesian non-negative factor analysis for reconstructing transcription factor mediated regulatory networks

    Directory of Open Access Journals (Sweden)

    Chen Yidong

    2011-10-01

    Full Text Available Abstract Background Transcriptional regulation by transcription factor (TF controls the time and abundance of mRNA transcription. Due to the limitation of current proteomics technologies, large scale measurements of protein level activities of TFs is usually infeasible, making computational reconstruction of transcriptional regulatory network a difficult task. Results We proposed here a novel Bayesian non-negative factor model for TF mediated regulatory networks. Particularly, the non-negative TF activities and sample clustering effect are modeled as the factors from a Dirichlet process mixture of rectified Gaussian distributions, and the sparse regulatory coefficients are modeled as the loadings from a sparse distribution that constrains its sparsity using knowledge from database; meantime, a Gibbs sampling solution was developed to infer the underlying network structure and the unknown TF activities simultaneously. The developed approach has been applied to simulated system and breast cancer gene expression data. Result shows that, the proposed method was able to systematically uncover TF mediated transcriptional regulatory network structure, the regulatory coefficients, the TF protein level activities and the sample clustering effect. The regulation target prediction result is highly coordinated with the prior knowledge, and sample clustering result shows superior performance over previous molecular based clustering method. Conclusions The results demonstrated the validity and effectiveness of the proposed approach in reconstructing transcriptional networks mediated by TFs through simulated systems and real data.

  9. Sharp maximal inequalities for the moments of martingales and non-negative submartingales

    CERN Document Server

    Osȩkowski, Adam

    2012-01-01

    In the paper we study sharp maximal inequalities for martingales and non-negative submartingales: if $f$, $g$ are martingales satisfying \\[|\\mathrm{d}g_n|\\leq|\\mathrm{d}f_n|,\\qquad n=0,1,2,...,\\] almost surely, then \\[\\Bigl\\|\\sup_{n\\geq0}|g_n|\\Bigr\\|_p\\leq p\\|f\\|_p,\\qquad p\\geq2,\\] and the inequality is sharp. Furthermore, if $\\alpha\\in[0,1]$, $f$ is a non-negative submartingale and $g$ satisfies \\[|\\mathrm{d}g_n|\\leq|\\mathrm{d}f_n|\\quad and\\quad |\\mathbb{E}(\\mathrm{d}g_{n+1}|\\mathcal {F}_n)|\\leq\\alpha\\mathbb{E}(\\mathrm{d}f_{n+1}|\\mathcal{F}_n),\\qquad n=0,1,2,...,\\] almost surely, then \\[\\Bigl\\|\\sup_{n\\geq0}|g_n|\\Bigr\\|_p\\leq(\\alpha+1)p\\|f\\|_p,\\qquad p\\geq2,\\] and the inequality is sharp. As an application, we establish related estimates for stochastic integrals and It\\^{o} processes. The inequalities strengthen the earlier classical results of Burkholder and Choi.

  10. Non-negative matrix factorization by maximizing correntropy for cancer clustering

    KAUST Repository

    Wang, Jim Jing-Yan

    2013-03-24

    Background: Non-negative matrix factorization (NMF) has been shown to be a powerful tool for clustering gene expression data, which are widely used to classify cancers. NMF aims to find two non-negative matrices whose product closely approximates the original matrix. Traditional NMF methods minimize either the l2 norm or the Kullback-Leibler distance between the product of the two matrices and the original matrix. Correntropy was recently shown to be an effective similarity measurement due to its stability to outliers or noise.Results: We propose a maximum correntropy criterion (MCC)-based NMF method (NMF-MCC) for gene expression data-based cancer clustering. Instead of minimizing the l2 norm or the Kullback-Leibler distance, NMF-MCC maximizes the correntropy between the product of the two matrices and the original matrix. The optimization problem can be solved by an expectation conditional maximization algorithm.Conclusions: Extensive experiments on six cancer benchmark sets demonstrate that the proposed method is significantly more accurate than the state-of-the-art methods in cancer clustering. 2013 Wang et al.; licensee BioMed Central Ltd.

  11. Semi-Supervised Projective Non-Negative Matrix Factorization for Cancer Classification.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    Full Text Available Advances in DNA microarray technologies have made gene expression profiles a significant candidate in identifying different types of cancers. Traditional learning-based cancer identification methods utilize labeled samples to train a classifier, but they are inconvenient for practical application because labels are quite expensive in the clinical cancer research community. This paper proposes a semi-supervised projective non-negative matrix factorization method (Semi-PNMF to learn an effective classifier from both labeled and unlabeled samples, thus boosting subsequent cancer classification performance. In particular, Semi-PNMF jointly learns a non-negative subspace from concatenated labeled and unlabeled samples and indicates classes by the positions of the maximum entries of their coefficients. Because Semi-PNMF incorporates statistical information from the large volume of unlabeled samples in the learned subspace, it can learn more representative subspaces and boost classification performance. We developed a multiplicative update rule (MUR to optimize Semi-PNMF and proved its convergence. The experimental results of cancer classification for two multiclass cancer gene expression profile datasets show that Semi-PNMF outperforms the representative methods.

  12. Galactosylated cellulosic sponge for multi-well drug safety testing.

    Science.gov (United States)

    Nugraha, Bramasta; Hong, Xin; Mo, Xuejun; Tan, Looling; Zhang, Wenxia; Chan, Po-Mak; Kang, Chiang Huen; Wang, Yan; Beng, Lu Thong; Sun, Wanxin; Choudhury, Deepak; Robens, Jeffrey M; McMillian, Michael; Silva, Jose; Dallas, Shannon; Tan, Choon-Hong; Yue, Zhilian; Yu, Hanry

    2011-10-01

    Hepatocyte spheroids can maintain mature differentiated functions, but collide to form bulkier structures when in extended culture. When the spheroid diameter exceeds 200 μm, cells in the inner core experience hypoxia and limited access to nutrients and drugs. Here we report the development of a thin galactosylated cellulosic sponge to culture hepatocytes in multi-well plates as 3D spheroids, and constrain them within a macroporous scaffold network to maintain spheroid size and prevent detachment. The hydrogel-based soft sponge conjugated with galactose provided suitable mechanical and chemical cues to support rapid formation of hepatocyte spheroids with a mature hepatocyte phenotype. The spheroids tethered in the sponge showed excellent maintenance of 3D cell morphology, cell-cell interaction, polarity, metabolic and transporter function and/or expression. For example, cytochrome P450 (CYP1A2, CYP2B2 and CYP3A2) activities were significantly elevated in spheroids exposed to β-naphthoflavone, phenobarbital, or pregnenolone-16α-carbonitrile, respectively. The sponge also exhibits minimal drug absorption compared to other commercially available scaffolds. As the cell seeding and culture protocols are similar to various high-throughput 2D cell-based assays, this platform is readily scalable and provides an alternative to current hepatocyte platforms used in drug safety testing applications.

  13. Pumpless microfluidic platform for drug testing on human skin equivalents.

    Science.gov (United States)

    Abaci, Hasan Erbil; Gledhill, Karl; Guo, Zongyou; Christiano, Angela M; Shuler, Michael L

    2015-02-07

    Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies. In this study, we designed and developed a microfluidic platform that allows for long-term maintenance of full thickness human skin equivalents (HSE) which are comprised of both the epidermal and dermal compartments. The design is based on the physiologically relevant blood residence times in human skin tissue and allows for the establishment of an air-epidermal interface which is crucial for maturation and terminal differentiation of HSEs. The small scale of the design reduces the amount of culture medium and the number of cells required by 36 fold compared to conventional transwell cultures. Our HSE-on-a-chip platform has the capability to recirculate the medium at desired flow rates without the need for pump or external tube connections. We demonstrate that the platform can be used to maintain HSEs for three weeks with proliferating keratinocytes similar to conventional HSE cultures. Immunohistochemistry analyses show that the differentiation and localization of keratinocytes was successfully achieved, establishing all sub-layers of the epidermis after one week. Basal keratinocytes located at the epidermal-dermal interface remain in a proliferative state for three weeks. We use a transdermal transport model to show that the skin barrier function is maintained for three weeks. We also validate the capability of the HSE-on-a-chip platform to be used for drug testing purposes by examining the toxic effects of doxorubucin on skin cells and structure. Overall, the HSE-on-a-chip is a user-friendly and cost-effective in vitro platform for drug testing of candidate molecules for skin disorders.

  14. In vitro tests for drug hypersensitivity reactions : an ENDA/EAACI Drug Allergy Interest Group position paper

    NARCIS (Netherlands)

    Mayorga, C.; Celik, G.; Rouzaire, P.; Whitaker, P.; Bonadonna, P.; Rodrigues-Cernadas, J.; Vultaggio, A.; Brockow, K.; Caubet, J. C.; Makowska, J.; Nakonechna, A.; Romano, A.; Montanez, M. I.; Laguna, J. J.; Zanoni, G.; Gueant, J. L.; Oude Elberink, H.; Fernandez, J.; Viel, S.; Demoly, P.; Torres, M. J.

    2016-01-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because invivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation test

  15. Detecting cells using non-negative matrix factorization on calcium imaging data.

    Science.gov (United States)

    Maruyama, Ryuichi; Maeda, Kazuma; Moroda, Hajime; Kato, Ichiro; Inoue, Masashi; Miyakawa, Hiroyoshi; Aonishi, Toru

    2014-07-01

    We propose a cell detection algorithm using non-negative matrix factorization (NMF) on Ca2+ imaging data. To apply NMF to Ca2+ imaging data, we use the bleaching line of the background fluorescence intensity as an a priori background constraint to make the NMF uniquely dissociate the background component from the image data. This constraint helps us to incorporate the effect of dye-bleaching and reduce the non-uniqueness of the solution. We demonstrate that in the case of noisy data, the NMF algorithm can detect cells more accurately than Mukamel's independent component analysis algorithm, a state-of-art method. We then apply the NMF algorithm to Ca2+ imaging data recorded on the local activities of subcellular structures of multiple cells in a wide area. We show that our method can decompose rapid transient components corresponding to somas and dendrites of many neurons, and furthermore, that it can decompose slow transient components probably corresponding to glial cells.

  16. Convergence, Non-negativity and Stability of a New Milstein Scheme with Applications to Finance

    CERN Document Server

    Higham, Desmond J; Szpruch, Lukasz

    2012-01-01

    We propose and analyse a new Milstein type scheme for simulating stochastic differential equations (SDEs) with highly nonlinear coefficients. Our work is motivated by the need to justify multi-level Monte Carlo simulations for mean-reverting financial models with polynomial growth in the diffusion term. We introduce a double implicit Milstein scheme and show that it possesses desirable properties. It converges strongly and preserves non-negativity for a rich family of financial models and can reproduce linear and nonlinear stability behaviour of the underlying SDE without severe restriction on the time step. Although the scheme is implicit, we point out examples of financial models where an explicit formula for the solution to the scheme can be found.

  17. Facial Expression Recognition via Non-Negative Least-Squares Sparse Coding

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2014-05-01

    Full Text Available Sparse coding is an active research subject in signal processing, computer vision, and pattern recognition. A novel method of facial expression recognition via non-negative least squares (NNLS sparse coding is presented in this paper. The NNLS sparse coding is used to form a facial expression classifier. To testify the performance of the presented method, local binary patterns (LBP and the raw pixels are extracted for facial feature representation. Facial expression recognition experiments are conducted on the Japanese Female Facial Expression (JAFFE database. Compared with other widely used methods such as linear support vector machines (SVM, sparse representation-based classifier (SRC, nearest subspace classifier (NSC, K-nearest neighbor (KNN and radial basis function neural networks (RBFNN, the experiment results indicate that the presented NNLS method performs better than other used methods on facial expression recognition tasks.

  18. Song Recommendation with Non-Negative Matrix Factorization and Graph Total Variation

    CERN Document Server

    Benzi, Kirell; Bresson, Xavier; Vandergheynst, Pierre

    2016-01-01

    This work formulates a novel song recommender system as a matrix completion problem that benefits from collaborative filtering through Non-negative Matrix Factorization (NMF) and content-based filtering via total variation (TV) on graphs. The graphs encode both playlist proximity information and song similarity, using a rich combination of audio, meta-data and social features. As we demonstrate, our hybrid recommendation system is very versatile and incorporates several well-known methods while outperforming them. Particularly, we show on real-world data that our model overcomes w.r.t. two evaluation metrics the recommendation of models solely based on low-rank information, graph-based information or a combination of both.

  19. Joint cluster and non-negative least squares analysis for aerosol mass spectrum data

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, T; Zhu, W [Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-3600 (United States); McGraw, R [Environmental Sciences Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States)], E-mail: zhu@ams.sunysb.edu

    2008-07-15

    Aerosol mass spectrum (AMS) data contain hundreds of mass to charge ratios and their corresponding intensities from air collected through the mass spectrometer. The observations are usually taken sequentially in time to monitor the air composition, quality and temporal change in an area of interest. An important goal of AMS data analysis is to reduce the dimensionality of the original data yielding a small set of representing tracers for various atmospheric and climatic models. In this work, we present an approach to jointly apply the cluster analysis and the non-negative least squares method towards this goal. Application to a relevant study demonstrates the effectiveness of this new approach. Comparisons are made to other relevant multivariate statistical techniques including the principal component analysis and the positive matrix factorization method, and guidelines are provided.

  20. Infinity Behavior of Bounded Subharmonic Functions on Ricci Non-negative Manifolds

    Institute of Scientific and Technical Information of China (English)

    Bao Qiang WU

    2004-01-01

    In this paper, we study the infinity behavior of the bounded subharmonic functions on a Ricci non-negative Riemannian manifold M. We first show that limr→∞r2/V(r) ∫B(r)△hdv = 0 if h is a bounded subharmonic function. If we further assume that the Laplacian decays pointwisely faster than quadratically we show that h approaches its supremun pointwisely at infinity, under certain auxiliary conditions on the volume growth of M. In particular, our result applies to the case when the Riemannian manifold has maximum volume growth. We also derive a representation formula in our paper, from which one can easily derive Yau's Liouville theorem on bounded harmonic functions.

  1. Categorical dimensions of human odor descriptor space revealed by non-negative matrix factorization

    Energy Technology Data Exchange (ETDEWEB)

    Chennubhotla, Chakra [University of Pittsburgh School of Medicine, Pittsburgh PA; Castro, Jason [Bates College

    2013-01-01

    In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain un- clear. Here, we use non-negative matrix factorization (NMF) - a dimensionality reduction technique - to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor di- mensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures.

  2. Clustering Algorithm for Unsupervised Monaural Musical Sound Separation Based on Non-negative Matrix Factorization

    Science.gov (United States)

    Park, Sang Ha; Lee, Seokjin; Sung, Koeng-Mo

    Non-negative matrix factorization (NMF) is widely used for monaural musical sound source separation because of its efficiency and good performance. However, an additional clustering process is required because the musical sound mixture is separated into more signals than the number of musical tracks during NMF separation. In the conventional method, manual clustering or training-based clustering is performed with an additional learning process. Recently, a clustering algorithm based on the mel-frequency cepstrum coefficient (MFCC) was proposed for unsupervised clustering. However, MFCC clustering supplies limited information for clustering. In this paper, we propose various timbre features for unsupervised clustering and a clustering algorithm with these features. Simulation experiments are carried out using various musical sound mixtures. The results indicate that the proposed method improves clustering performance, as compared to conventional MFCC-based clustering.

  3. Drug Testing. ERIC Digest Series Number EA35 (Revised).

    Science.gov (United States)

    Klauke, Amy; Hadderman, Margaret

    Despite privacy concerns, school administrators are feeling pressure to adopt urgent measures to keep drugs and alcohol from further endangering our youth's well-being and undermining staff performance. This urgency is reinforced by a national anti-drug campaign and Congressional passage of the Drug-Free Workplace Act (1988) and the Drug-Free…

  4. 76 FR 34086 - Mandatory Guidelines for Federal Workplace Drug Testing Programs; Request for Information...

    Science.gov (United States)

    2011-06-10

    ... Federal Workplace Drug Testing Programs; Request for Information Regarding Specific Issues Related to the Use of the Oral Fluid Specimen for Drug Testing AGENCY: Substance Abuse and Mental Health Services... Mandatory Guidelines for Federal Workplace Drug Testing Programs (oral fluid specimen). DATES: Comment Close...

  5. 49 CFR 40.123 - What are the MRO's responsibilities in the DOT drug testing program?

    Science.gov (United States)

    2010-10-01

    ... drug testing program? 40.123 Section 40.123 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the Verification Process § 40.123 What are the MRO's responsibilities in the DOT drug testing program? As an MRO...

  6. Drug Testing Guidelines and Practices for Juvenile Probation and Parole Agencies.

    Science.gov (United States)

    American Probation and Parole Association, Lexington, KY.

    This document, intended as a resource manual, provides guidelines on drug testing. These topics are covered: (1) National Institute on Drug Abuse guidelines applicability; (2) introduction to legal issues, drug testing in juvenile probation and parole, and juvenile law; (3) mission of a juvenile parole agency; (4) purpose of testing; (5) drug…

  7. 78 FR 39190 - Revisions to Fitness for Duty Programs' Drug Testing Requirements

    Science.gov (United States)

    2013-07-01

    ...-2009-0225] RIN 3150-AI67 Revisions to Fitness for Duty Programs' Drug Testing Requirements AGENCY... regulations regarding drug testing requirements in NRC licensees' fitness for duty programs. The regulatory... select drug testing provisions in the U.S. Department of Health and Human Services' ``Mandatory...

  8. 75 FR 76478 - Mandatory Guidelines for Federal Workplace Drug Testing Programs

    Science.gov (United States)

    2010-12-08

    ... HUMAN SERVICES Mandatory Guidelines for Federal Workplace Drug Testing Programs AGENCY: Substance Abuse... Department of Health and Human Services (HHS) Mandatory Guidelines for Federal Workplace Drug Testing... drug testing results that seek approval by the Secretary must submit their qualifications and a sample...

  9. 49 CFR 40.31 - Who may collect urine specimens for DOT drug testing?

    Science.gov (United States)

    2010-10-01

    ... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Urine Collection Personnel § 40.31 Who may collect urine specimens for DOT drug testing? (a) Collectors meeting the requirements of this subpart are the only persons authorized to collect urine specimens for DOT drug testing. (b) A collector must meet...

  10. 10 CFR 26.65 - Pre-access drug and alcohol testing.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Pre-access drug and alcohol testing. 26.65 Section 26.65... § 26.65 Pre-access drug and alcohol testing. (a) Purpose. This section contains pre-access testing... rely on the results of those drug and alcohol tests to meet the requirements for pre-access testing in...

  11. An Analysis of the Effectiveness of the Air Force Drug Testing Program and Four Potential Modifications

    Science.gov (United States)

    1993-09-01

    Another hair testing methodology uses an enzyme immunoassay (EIA) technique, which is also commonly used for testing urine for drugs in commercial...1992, urine specimens collected for the USAF Drug Testing Program were tested for the following drugs: Cannabis (Marijuana), Cocaine, Amphetamine ...abuse in the previous 12 months, and of the 196,476 urine specimens tested in fiscal year 1992, less than 0.5 percent testea positive (2:14; 8:Ch 5, 12

  12. Creatinine normalization of workplace urine drug tests: does it make a difference?

    Science.gov (United States)

    Price, James W

    2013-01-01

    This study examines the effect of creatinine normalization on urine drug concentrations of 5 substances (amphetamines, cocaine, marijuana, opiates, and phencyclidine) and how this affects the proportion of reported positives. The Wilcoxon matched-pairs signed-ranks test was used to compare the mean prenormalization urinary drug concentration with the mean postnormalization urinary drug concentration. Frequency analysis was performed on dichotomous drug test results and the information was used to complete McNemar testing for each drug to determine the difference of proportions for prenormalization positive drug tests to postnormalization positive drug test. Each drug tested (N = 4460) was found to have a statistically significant increase in mean urinary drug concentration after creatinine normalization with effect sizes ranging from small to medium with cocaine having the largest effect size (r = 0.229) and phencyclidine having the lowest effect size (r = 0.121). The differences in proportion of dichotomous results between study and control groups for drugs tested were compared with the McNemar test. Each drug had a statistically significant (P = 0.0010) increase of positive drug tests. This result indicates that specimen dilution does affect the number of laboratory-positive results confirmed.

  13. Sports drug testing using complementary matrices: Advantages and limitations.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Tretzel, Laura; Schänzer, Wilhelm

    2016-10-25

    Today, routine doping controls largely rely on testing whole blood, serum, and urine samples. These matrices allow comprehensively covering inorganic as well as low and high molecular mass organic analytes relevant to doping controls and are collecting and transferring from sampling sites to accredited anti-doping laboratories under standardized conditions. Various aspects including time and cost-effectiveness as well as intrusiveness and invasiveness of the sampling procedure but also analyte stability and breadth of the contained information have been motivation to consider and assess values potentially provided and added to modern sports drug testing programs by alternative matrices. Such alternatives could be dried blood spots (DBS), dried plasma spots (DPS), oral fluid (OF), exhaled breath (EB), and hair. In this review, recent developments and test methods concerning these alternative matrices and expected or proven contributions as well as limitations of these specimens in the context of the international anti-doping fight are presented and discussed, guided by current regulations for prohibited substances and methods of doping as established by the World Anti-Doping Agency (WADA). Focusing on literature published between 2011 and 2015, examples for doping control analytical assays concerning non-approved substances, anabolic agents, peptide hormones/growth factors/related substances and mimetics, β2-agonists, hormone and metabolic modulators, diuretics and masking agents, stimulants, narcotics, cannabinoids, glucocorticoids, and beta-blockers were selected to outline the advantages and limitations of the aforementioned alternative matrices as compared to conventional doping control samples (i.e. urine and blood/serum).

  14. Rifampin Drug Resistance Tests for Tuberculosis: Challenging the Gold Standard

    Science.gov (United States)

    Aung, Kya J. M.; Bola, Valentin; Lebeke, Rossin; Hossain, Mohamed Anwar; de Rijk, Willem Bram; Rigouts, Leen; Gumusboga, Aysel; Torrea, Gabriela; de Jong, Bouke C.

    2013-01-01

    The rapid diagnosis of rifampin resistance is hampered by a reported insufficient specificity of molecular techniques for detection of rpoB mutations. Our objective for this study was to document the prevalence and prognostic value of rpoB mutations with unclear phenotypic resistance. The study design entailed sequencing directly from sputum of first failure or relapse patients without phenotypic selection and comparison of the standard retreatment regimen outcome, according to the mutation present. We found that among all rpoB mutations, the best-documented “disputed” rifampin resistance mutations (511Pro, 516Tyr, 526Asn, 526Leu, 533Pro, and 572Phe) made up 13.1% and 10.6% of all mutations in strains from Bangladesh and Kinshasa, respectively. Except for the 511Pro and 526Asn mutations, most of these strains with disputed mutations tested rifampin resistant in routine Löwenstein-Jensen medium proportion method drug susceptibility testing (DST; 78.7%), but significantly less than those with common, undisputed mutations (96.3%). With 63% of patients experiencing failure or relapse in both groups, there was no difference in outcome of first-line retreatment between patients carrying a strain with disputed versus common mutations. We conclude that rifampin resistance that is difficult to detect by the gold standard, phenotypic DST, is clinically and epidemiologically highly relevant. Sensitivity rather than specificity is imperfect with any rifampin DST method. Even at a low prevalence of rifampin resistance, a rifampin-resistant result issued by a competent laboratory may not warrant confirmation, although the absence of a necessity for confirmation needs to be confirmed for molecular results among new cases. However, a result of rifampin susceptibility should be questioned when suspicion is very high, and further DST using a different system (i.e., genotypic after phenotypic testing) would be fully justified. PMID:23761144

  15. Urine drug testing: current recommendations and best practices.

    Science.gov (United States)

    Owen, Graves T; Burton, Allen W; Schade, Cristy M; Passik, Steve

    2012-07-01

    The precise role of urine drug testing (UDT) in the practice of pain medicine is currently being defined. Confusion exists as to best practices, and even to what constitutes standard of care. A member survey by our state pain society revealed variability in practice and a lack of consensus. The authors sought to further clarify the importance of routine UDT as an important part of an overall treatment plan that includes chronic opioid prescribing. Further, we wish to clarify best practices based on consensus and data where available. A 20-item membership survey was sent to Texas Pain Society members. A group of chronic pain experts from the Texas Pain Society undertook an effort to review the best practices in the literature. The rationale for current UDT practices is clarified, with risk management strategies outlined, and recommendations for UDT outlined in detail. A detailed insight into the limitations of point-of-care (enzyme-linked immunosorbent assay, test cups, test strips) versus the more sensitive and specific laboratory methods is provided. Our membership survey was of a limited sample size in one geographic area in the United States and may not represent national patterns. Finally, there is limited data as to the efficacy of UDT practices in improving compliance and curtailing overall medication misuse. UDT must be done routinely as part of an overall best practice program in order to prescribe chronic opioid therapy. This program may include risk stratification; baseline and periodic UDT; behavioral monitoring; and prescription monitoring programs as the best available tools to monitor chronic opioid compliance.

  16. Full-course drug challenge test in the diagnosis of delayed allergic reactions to penicillin

    DEFF Research Database (Denmark)

    Borch, Jakob E; Bindslev-Jensen, Carsten

    2011-01-01

    Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy.......Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy....

  17. 10 CFR 707.9 - Drug testing as a result of an occurrence.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Drug testing as a result of an occurrence. 707.9 Section... Drug testing as a result of an occurrence. When there is an occurrence which is required to be reported... regulations, it may be necessary to test individuals in testing designated positions, or individuals with...

  18. Trends in reports of driving following illicit drug consumption among regular drug users in Australia, 2007-2013: Has random roadside drug testing had a deterrent effect?

    Science.gov (United States)

    Horyniak, Danielle; Dietze, Paul; Lenton, Simon; Alati, Rosa; Bruno, Raimondo; Matthews, Allison; Breen, Courtney; Burns, Lucy

    2017-07-01

    Driving following illicit drug consumption ('drug-driving') is a potential road safety risk. Roadside drug testing (RDT) is conducted across Australia with the dual aims of prosecuting drivers with drugs in their system and deterring drug-driving. We examined trends over time in self-reported past six-month drug-driving among sentinel samples of regular drug users and assessed the impact of experiences of RDT on drug-driving among these participants. Data from 1913 people who inject drugs (PWID) and 3140 regular psychostimulant users (RPU) who were first-time participants in a series of repeat cross-sectional sentinel studies conducted in Australian capital cities from 2007 to 2013 and reported driving in the past six months were analysed. Trends over time were assessed using the χ(2) test for trend. Multivariable logistic regressions assessed the relationship between experiences of RDT and recent drug-driving, adjusting for survey year, jurisdiction of residence and socio-demographic and drug use characteristics. The percentage of participants reporting recent (past six months) drug-driving decreased significantly over time among both samples (PWID: 83% [2007] vs. 74% [2013], pdrug-driving remained prevalent. Lifetime experience of RDT increased significantly over time (PWID: 6% [2007] vs. 32% [2013], pdrug-driving among either PWID or RPU. Although there is some evidence that drug-driving among key risk groups of regular drug users is declining in Australia, possibly reflecting a general deterrent effect of RDT, experiencing RDT appears to have no specific deterrent effect on drug-driving. Further intervention, with a particular focus on changing attitudes towards drug-driving, may be needed to further reduce this practice among these groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Non-negative matrix factorization based unmixing for principal component transformed hyperspectral data

    Institute of Scientific and Technical Information of China (English)

    Xiu-rui GENG; Lu-yan JI; Kang SUN

    2016-01-01

    Non-negative matrix factorization (NMF) has been widely used in mixture analysis for hyperspectral remote sensing. When used for spectral unmixing analysis, however, it has two main shortcomings: (1) since the dimensionality of hyperspectral data is usually very large, NMF tends to suffer from large computational complexity for the popular multiplicative iteration rule;(2) NMF is sensitive to noise (outliers), and thus the corrupted data will make the results of NMF meaningless. Although principal component analysis (PCA) can be used to mitigate these two problems, the transformed data will contain negative numbers, hindering the direct use of the multiplicative iteration rule of NMF. In this paper, we analyze the impact of PCA on NMF, and fi nd that multiplicative NMF can also be applicable to data after principal component transformation. Based on this conclusion, we present a method to perform NMF in the principal component space, named ‘principal component NMF’ (PCNMF). Experimental results show that PCNMF is both accurate and time-saving.

  20. Robust and Non-Negative Collective Matrix Factorization for Text-to-Image Transfer Learning.

    Science.gov (United States)

    Yang, Liu; Jing, Liping; Ng, Michael K

    2015-12-01

    Heterogeneous transfer learning has recently gained much attention as a new machine learning paradigm in which the knowledge can be transferred from source domains to target domains in different feature spaces. Existing works usually assume that source domains can provide accurate and useful knowledge to be transferred to target domains for learning. In practice, there may be noise appearing in given source (text) and target (image) domains data, and thus, the performance of transfer learning can be seriously degraded. In this paper, we propose a robust and non-negative collective matrix factorization model to handle noise in text-to-image transfer learning, and make a reliable bridge to transfer accurate and useful knowledge from the text domain to the image domain. The proposed matrix factorization model can be solved by an efficient iterative method, and the convergence of the iterative method can be shown. Extensive experiments on real data sets suggest that the proposed model is able to effectively perform transfer learning in noisy text and image domains, and it is superior to the popular existing methods for text-to-image transfer learning.

  1. Exploring Mixed Membership Stochastic Block Models via Non-negative Matrix Factorization

    KAUST Repository

    Peng, Chengbin

    2014-12-01

    Many real-world phenomena can be modeled by networks in which entities and connections are represented by nodes and edges respectively. When certain nodes are highly connected with each other, those nodes forms a cluster, which is called community in our context. It is usually assumed that each node belongs to one community only, but evidences in biology and social networks reveal that the communities often overlap with each other. In other words, one node can probably belong to multiple communities. In light of that, mixed membership stochastic block models (MMB) have been developed to model those networks with overlapping communities. Such a model contains three matrices: two incidence matrices indicating in and out connections and one probability matrix. When the probability of connections for nodes between communities are significantly small, the parameter inference problem to this model can be solved by a constrained non-negative matrix factorization (NMF) algorithm. In this paper, we explore the connection between the two models and propose an algorithm based on NMF to infer the parameters of MMB. The proposed algorithms can detect overlapping communities regardless of knowing or not the number of communities. Experiments show that our algorithm can achieve a better community detection performance than the traditional NMF algorithm. © 2014 IEEE.

  2. Discovering Recurrent Copy Number Aberrations in Complex Patterns via Non-Negative Sparse Singular Value Decomposition.

    Science.gov (United States)

    Xi, Jianing; Li, Ao

    2016-01-01

    Recurrent copy number aberrations (RCNAs) in multiple cancer samples are strongly associated with tumorigenesis, and RCNA discovery is helpful to cancer research and treatment. Despite the emergence of numerous RCNA discovering methods, most of them are unable to detect RCNAs in complex patterns that are influenced by complicating factors including aberration in partial samples, co-existing of gains and losses and normal-like tumor samples. Here, we propose a novel computational method, called non-negative sparse singular value decomposition (NN-SSVD), to address the RCNA discovering problem in complex patterns. In NN-SSVD, the measurement of RCNA is based on the aberration frequency in a part of samples rather than all samples, which can circumvent the complexity of different RCNA patterns. We evaluate NN-SSVD on synthetic dataset by comparison on detection scores and Receiver Operating Characteristics curves, and the results show that NN-SSVD outperforms existing methods in RCNA discovery and demonstrate more robustness to RCNA complicating factors. Applying our approach on a breast cancer dataset, we successfully identify a number of genomic regions that are strongly correlated with previous studies, which harbor a bunch of known breast cancer associated genes.

  3. Superradiant instabilities for short-range non-negative potentials on Kerr spacetimes and applications

    CERN Document Server

    Moschidis, Georgios

    2016-01-01

    The wave equation $\\square_{g_{M,a}}\\psi=0$ on subextremal Kerr spacetimes $(\\mathcal{M}_{M,a},g_{M,a})$, $0<|a|non-negative potential $V$ to the wave equation or under changes of the metric $g_{M,a}$ in the far away region of $\\mathcal{M}_{M,a}$ (retaining the causality of $T$ there). In particular, we first establish, for any $0<|a|

  4. Detecting heterogeneity in single-cell RNA-Seq data by non-negative matrix factorization

    Science.gov (United States)

    Zhu, Xun; Ching, Travers; Pan, Xinghua; Weissman, Sherman M.

    2017-01-01

    Single-cell RNA-Sequencing (scRNA-Seq) is a fast-evolving technology that enables the understanding of biological processes at an unprecedentedly high resolution. However, well-suited bioinformatics tools to analyze the data generated from this new technology are still lacking. Here we investigate the performance of non-negative matrix factorization (NMF) method to analyze a wide variety of scRNA-Seq datasets, ranging from mouse hematopoietic stem cells to human glioblastoma data. In comparison to other unsupervised clustering methods including K-means and hierarchical clustering, NMF has higher accuracy in separating similar groups in various datasets. We ranked genes by their importance scores (D-scores) in separating these groups, and discovered that NMF uniquely identifies genes expressed at intermediate levels as top-ranked genes. Finally, we show that in conjugation with the modularity detection method FEM, NMF reveals meaningful protein-protein interaction modules. In summary, we propose that NMF is a desirable method to analyze heterogeneous single-cell RNA-Seq data. The NMF based subpopulation detection package is available at: https://github.com/lanagarmire/NMFEM. PMID:28133571

  5. A perturbation-based framework for link prediction via non-negative matrix factorization

    Science.gov (United States)

    Wang, Wenjun; Cai, Fei; Jiao, Pengfei; Pan, Lin

    2016-12-01

    Many link prediction methods have been developed to infer unobserved links or predict latent links based on the observed network structure. However, due to network noises and irregular links in real network, the performances of existed methods are usually limited. Considering random noises and irregular links, we propose a perturbation-based framework based on Non-negative Matrix Factorization to predict missing links. We first automatically determine the suitable number of latent features, which is inner rank in NMF, by Colibri method. Then, we perturb training set of a network by perturbation sets many times and get a series of perturbed networks. Finally, the common basis matrix and coefficients matrix of these perturbed networks are obtained via NMF and form similarity matrix of the network for link prediction. Experimental results on fifteen real networks show that the proposed framework has competitive performances compared with state-of-the-art link prediction methods. Correlations between the performances of different methods and the statistics of networks show that those methods with good precisions have similar consistence.

  6. Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

    NARCIS (Netherlands)

    Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

    2014-01-01

    OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

  7. College Athletes and Drug Testing: Attitudes and Behaviors by Gender and Sport

    OpenAIRE

    Schneider, Dona; Morris, Joyce

    1993-01-01

    We surveyed varsity athletes at a Big East university to assess attitudes toward a mandatory drug education and testing program and examined whether there were differences in drug-related attitudes and behaviors based on gender or varsity sport. We found no statistically significant differences in personal drug use behaviors based on gender or team affiliation. Attitudes about drug use and knowledge of a teammate using drugs did show significant differences based on varsity sport. Tennis play...

  8. Women's opinions of legal requirements for drug testing in prenatal care.

    Science.gov (United States)

    Tucker Edmonds, Brownsyne; Mckenzie, Fatima; Austgen, MacKenzie B; Carroll, Aaron E; Meslin, Eric M

    2017-07-01

    To explore women's attitudes and perceptions regarding legal requirements for prenatal drug testing. Web-based survey of 500 US women (age 18-45) recruited from a market research survey panel. A 24-item questionnaire assessed their opinion of laws requiring doctors to routinely verbal screen and urine drug test patients during pregnancy; recommendations for consequences for positive drug tests during pregnancy; and opinion of laws requiring routine drug testing of newborns. Additional questions asked participants about the influence of such laws on their own care-seeking behaviors. Data were analyzed for associations between participant characteristics and survey responses using Pearson's chi-squared test. The majority of respondents (86%) stated they would support a law requiring verbal screening of all pregnant patients and 73% would support a law requiring universal urine drug testing in pregnancy. Fewer respondents were willing to support laws that required verbal screening or urine drug testing (68% and 61%, respectively) targeting only Medicaid recipients. Twenty-one percent of respondents indicated they would be offended if their doctors asked them about drug use and 14% indicated that mandatory drug testing would discourage prenatal care attendance. Women would be more supportive of policies requiring universal rather than targeted screening and testing for prenatal drug use. However, a noteworthy proportion of women would be discouraged from attending prenatal care - a reminder that drug testing policies may have detrimental effects on maternal child health.

  9. Recreational drug use and fluctuating asymmetry: testing the handicap principle.

    Science.gov (United States)

    Borkowska, Barbara; Pawlowski, Boguslaw

    2014-08-26

    Zahavi's handicap principle suggests that only organisms with good genetic quality can afford to engage in costly behaviors. Recreational drug use can be harmful to one's health and therefore might be viewed as a costly signal of one's genetic quality. One of the measurements of genetic quality is bodily symmetry assessed by fluctuating asymmetry. If unhealthy drug use is a behavioral example of Zahavi's handicap principle, then men who use different stimulants or recreational drugs should be more symmetrical than men who do not use them at all or use them only in low quantity. The aim of this study was to examine the relationships between drug use and fluctuating asymmetry. The subjects were 190 young women and 202 young men. Six bilaterally symmetrical traits were measured: length of II-V digits, wrist breadth, and ear height. Questionnaires included questions about smoking, alcohol drinking, drug use, and designer drug use. There was no relationship between bodily symmetry and smoking frequency, alcohol drinking frequency, drug or designer drug use, total substance use, age of smoking initiation, or reason of this initiation. The results indicate that drug use does not reflect genetic quality and does not necessarily relate to the handicap hypothesis.

  10. Frequently Asked Questions about Drug Testing in Schools

    Science.gov (United States)

    ... Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ...

  11. Test-Retest Stability and Concurrent Validity of Two Reading Tests with a Drug-Abusing Population.

    Science.gov (United States)

    Johnson, Mark E.; Fisher, Dennis G.; Rhodes, Fen; Booth, Robert

    1996-01-01

    The Wide Range Achievement Test-Revised and the Woodcock Reading Mastery Tests-Revised were administered twice to 269 current drug abusers over an average time interval of 204.2 days. Overall, the study demonstrates that the two instruments have strong psychometric properties and that results from current drug abusers are reliable. (SLD)

  12. Non-negative least squares for high-dimensional linear models: consistency and sparse recovery without regularization

    CERN Document Server

    Slawski, Martin

    2012-01-01

    Least squares fitting is in general not useful for high-dimensional linear models, in which the number of predictors is of the same or even larger order of magnitude than the number of samples. Theory developed in recent years has coined a paradigm according to which sparsity-promoting regularization is regarded as a necessity in such setting. Deviating from this paradigm, we show that non-negativity constraints on the regression coefficients may be similarly effective as explicit regularization. For a broad range of designs with Gram matrix having non-negative entries, we establish bounds on the $\\ell_2$-prediction error of non-negative least squares (NNLS) whose form qualitatively matches corresponding results for $\\ell_1$-regularization. Under slightly stronger conditions, it is established that NNLS followed by hard thresholding performs excellently in terms of support recovery of an (approximately) sparse target, in some cases improving over $\\ell_1$-regularization. A substantial advantage of NNLS over r...

  13. Personalized Medicine : Pharmacogenetic Testing in Drug Development and Clinical Practice

    NARCIS (Netherlands)

    van der Baan, F.H.

    2012-01-01

    For drugs that are registered on the market, efficacy was proven on a population level. However, on an individual level, most drugs have a different effect in different patients. They may fail to work in some patients or cause serious side effects. Pharmacogenetic research studies the contribution o

  14. Functional biogeography of ocean microbes revealed through non-negative matrix factorization.

    Directory of Open Access Journals (Sweden)

    Xingpeng Jiang

    Full Text Available The direct "metagenomic" sequencing of genomic material from complex assemblages of bacteria, archaea, viruses and microeukaryotes has yielded new insights into the structure of microbial communities. For example, analysis of metagenomic data has revealed the existence of previously unknown microbial taxa whose spatial distributions are limited by environmental conditions, ecological competition, and dispersal mechanisms. However, differences in genotypes that might lead biologists to designate two microbes as taxonomically distinct need not necessarily imply differences in ecological function. Hence, there is a growing need for large-scale analysis of the distribution of microbial function across habitats. Here, we present a framework for investigating the biogeography of microbial function by analyzing the distribution of protein families inferred from environmental sequence data across a global collection of sites. We map over 6,000,000 protein sequences from unassembled reads from the Global Ocean Survey dataset to [Formula: see text] protein families, generating a protein family relative abundance matrix that describes the distribution of each protein family across sites. We then use non-negative matrix factorization (NMF to approximate these protein family profiles as linear combinations of a small number of ecological components. Each component has a characteristic functional profile and site profile. Our approach identifies common functional signatures within several of the components. We use our method as a filter to estimate functional distance between sites, and find that an NMF-filtered measure of functional distance is more strongly correlated with environmental distance than a comparable PCA-filtered measure. We also find that functional distance is more strongly correlated with environmental distance than with geographic distance, in agreement with prior studies. We identify similar protein functions in several components and

  15. Finding Imaging Patterns of Structural Covariance via Non-Negative Matrix Factorization

    Science.gov (United States)

    Sotiras, Aristeidis; Resnick, Susan M.; Davatzikos, Christos

    2015-01-01

    In this paper, we investigate the use of Non-Negative Matrix Factorization (NNMF) for the analysis of structural neuroimaging data. The goal is to identify the brain regions that co-vary across individuals in a consistent way, hence potentially being part of underlying brain networks or otherwise influenced by underlying common mechanisms such as genetics and pathologies. NNMF offers a directly data-driven way of extracting relatively localized co-varying structural regions, thereby transcending limitations of Principal Component Analysis (PCA), Independent Component Analysis (ICA) and other related methods that tend to produce dispersed components of positive and negative loadings. In particular, leveraging upon the well known ability of NNMF to produce parts-based representations of image data, we derive decompositions that partition the brain into regions that vary in consistent ways across individuals. Importantly, these decompositions achieve dimensionality reduction via highly interpretable ways and generalize well to new data as shown via split-sample experiments. We empirically validate NNMF in two data sets: i) a Diffusion Tensor (DT) mouse brain development study, and ii) a structural Magnetic Resonance (sMR) study of human brain aging. We demonstrate the ability of NNMF to produce sparse parts-based representations of the data at various resolutions. These representations seem to follow what we know about the underlying functional organization of the brain and also capture some pathological processes. Moreover, we show that these low dimensional representations favorably compare to descriptions obtained with more commonly used matrix factorization methods like PCA and ICA. PMID:25497684

  16. Non-negative Matrix Factorization as a Method for Studying Coronal Heating

    Science.gov (United States)

    Barnes, Will; Bradshaw, Stephen

    2015-04-01

    Many theoretical efforts have been made to model the response of coronal loops to nanoflare heating, but the theory has long suffered from a lack of direct observations. Nanoflares, originally proposed by Parker (1988), heat the corona through short, impulsive bursts of energy. Because of their short duration and comparatively low amplitude, emission signatures from nanoflare heating events are often difficult to detect. Past algorithms (e.g. Ugarte-Urra and Warren, 2014) for measuring the frequency of transient brightenings in active region cores have provided only a lower bound for such measurements. We present the use of non-negative matrix factorization (NMF) to analyze spectral data in active region cores in order to provide more accurate determinations of nanoflare heating properties. NMF, a matrix deconvolution technique, has a variety of applications , ranging from Raman spectroscopy to face recognition, but, to our knowledge, has not been applied in the field of solar physics. The strength of NMF lies in its ability to estimate sources (heating events) from measurements (observed spectral emission) without any knowledge of the mixing process (Cichocki et al., 2009). We apply our NMF algorithm to forward-modeled emission representative of that produced by nanoflare heating events in an active region core. The heating events are modeled using a state-of-the-art hydrodynamics code (Bradshaw and Cargill, 2013) and the emission and active regions are synthesized using advanced forward modeling and visualization software (Bradshaw and Klimchuk, 2011; Reep et al., 2013). From these active region visualizations, our NMF algorithm is then able to predict the heating event frequency and amplitudes. Improved methods of nanoflare detection will help to answer fundamental questions regarding the frequency of energy release in the solar corona and how the corona responds to such impulsive heating. Additionally, development of reliable, automated nanoflare detection

  17. 10 CFR 707.12 - Specimen collection, handling and laboratory analysis for drug testing.

    Science.gov (United States)

    2010-01-01

    ... drug testing. 707.12 Section 707.12 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.12 Specimen collection, handling and laboratory analysis for drug testing... collection to final disposition of specimens, and testing laboratories shall use appropriate cutoff levels in...

  18. The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

    Directory of Open Access Journals (Sweden)

    Malcolm J. Reid

    2011-12-01

    Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

  19. Hair drug testing results and self-reported drug use among primary care patients with moderate-risk illicit drug use.

    Science.gov (United States)

    Gryczynski, Jan; Schwartz, Robert P; Mitchell, Shannon Gwin; O'Grady, Kevin E; Ondersma, Steven J

    2014-08-01

    This study sought to examine the utility of hair testing as a research measure of drug use among individuals with moderate-risk drug use based on the internationally validated Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). This study is a secondary analysis using baseline data from a randomized trial of brief intervention for drug misuse, in which 360 adults with moderate-risk drug use were recruited from two community clinics in New Mexico, USA. The current study compared self-reported drug use on the ASSIST with laboratory analysis of hair samples using a standard commercially available 5-panel test with assay screening and gas chromatography/mass spectrometry (GC/MS) confirmation. Both self-report and hair testing covered a 3-month period. Overall concordance between hair testing and self-report was 57.5% (marijuana), 86.5% (cocaine), 85.8% (amphetamines), and 74.3% (opioids). Specificity of hair testing at standard laboratory cut-offs exceeded 90% for all drugs, but sensitivity of hair testing relative to self-report was low, identifying only 52.3% (127/243) of self-disclosed marijuana users, 65.2% (30/46) of cocaine users, 24.2% (8/33) of amphetamine users, and 2.9% (2/68) of opioid users. Among participants who disclosed using marijuana or cocaine in the past 3 months, participants with a negative hair test tended to report lower-frequency use of those drugs (ptesting can be useful in studies with moderate-risk drug users, but the potential for under-identification of low-frequency use suggests that researchers should consider employing low detection cut-offs and using hair testing in conjunction with self-report. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. FDA, companies test RFID tracking to prevent drug counterfeiting.

    Science.gov (United States)

    James, John S

    2005-12-01

    The U.S. has an apparently growing problem with fake, counterfeit drugs entering the mainstream drug supply, and being fraudulently sold at full price in regular pharmacies and hospitals; some have no active ingredient, or too little, or substitute a cheap drug for an expensive one. The FDA has asked drug manufacturers to develop technology to track all shipments electronically as they move through the distribution chain; currently, RFID (radio frequency identification) is the preferred method for doing so. This article explains what is happening, and why we do not believe that this use of RFID is a privacy threat--though other privacy issues are among the most important questions we face today.

  1. A hybrid-optimization method for large-scale non-negative full regualarization in image restoration

    NARCIS (Netherlands)

    Guerrero, J.; Raydan, M.; Rojas, M.

    2011-01-01

    We describe a new hybrid-optimization method for solving the full-regularization problem of comput- ing both the regularization parameter and the corresponding regularized solution in 1-norm and 2-norm Tikhonov regularization with additional non-negativity constraints. The approach combines the simu

  2. NMF-mGPU: non-negative matrix factorization on multi-GPU systems.

    Science.gov (United States)

    Mejía-Roa, Edgardo; Tabas-Madrid, Daniel; Setoain, Javier; García, Carlos; Tirado, Francisco; Pascual-Montano, Alberto

    2015-02-13

    In the last few years, the Non-negative Matrix Factorization ( NMF ) technique has gained a great interest among the Bioinformatics community, since it is able to extract interpretable parts from high-dimensional datasets. However, the computing time required to process large data matrices may become impractical, even for a parallel application running on a multiprocessors cluster. In this paper, we present NMF-mGPU, an efficient and easy-to-use implementation of the NMF algorithm that takes advantage of the high computing performance delivered by Graphics-Processing Units ( GPUs ). Driven by the ever-growing demands from the video-games industry, graphics cards usually provided in PCs and laptops have evolved from simple graphics-drawing platforms into high-performance programmable systems that can be used as coprocessors for linear-algebra operations. However, these devices may have a limited amount of on-board memory, which is not considered by other NMF implementations on GPU. NMF-mGPU is based on CUDA ( Compute Unified Device Architecture ), the NVIDIA's framework for GPU computing. On devices with low memory available, large input matrices are blockwise transferred from the system's main memory to the GPU's memory, and processed accordingly. In addition, NMF-mGPU has been explicitly optimized for the different CUDA architectures. Finally, platforms with multiple GPUs can be synchronized through MPI ( Message Passing Interface ). In a four-GPU system, this implementation is about 120 times faster than a single conventional processor, and more than four times faster than a single GPU device (i.e., a super-linear speedup). Applications of GPUs in Bioinformatics are getting more and more attention due to their outstanding performance when compared to traditional processors. In addition, their relatively low price represents a highly cost-effective alternative to conventional clusters. In life sciences, this results in an excellent opportunity to facilitate the

  3. Student drug testing and positive school climates: testing the relation between two school characteristics and drug use behavior in a longitudinal study.

    Science.gov (United States)

    Sznitman, Sharon R; Romer, Daniel

    2014-01-01

    Fostering positive school climates and student drug testing have been separately proposed as strategies to reduce student drug use in high schools. To assess the promise of these strategies, the present research examined whether positive school climates and/or student drug testing successfully predicted changes in youth substance use over a 1-year follow-up. Two waves of panel data from a sample of 361 high school students, assessed 1 year apart, were analyzed. Changes in reported initiation and escalation in frequency of alcohol, cigarette, and marijuana use as a function of perceived student drug testing and positive school climates were analyzed, while we held constant prior substance use. Perceived student drug testing was not associated with changes in substance use, whereas perceived positive school climates were associated with a reduction in cigarette and marijuana initiation and a reduction in escalation of frequency of cigarette use at 1-year follow-up. However, perceived positive school climates were not associated with a reduction in alcohol use. Student drug testing appears to be less associated with substance use than positive school climates. Nevertheless, even favorable school climates may not be able to influence the use of alcohol, which appears to be quite normative in this age group.

  4. The role of urine drug testing for patients on opioid therapy.

    Science.gov (United States)

    Pergolizzi, Joseph; Pappagallo, Macro; Stauffer, Joseph; Gharibo, Christopher; Fortner, Neil; De Jesus, Mathew N; Brennan, Michael J; Richmond, Charlotte; Hussey, Desmond

    2010-01-01

    Opioid analgesics must be prescribed with discernment and their appropriate use should be periodically assessed. Urine drug testing, although not designed specifically for this role, is a widely available and familiar method for monitoring opioid use in chronic pain patients. Urine drug testing can help track patient compliance and expose possible drug misuse and abuse. We sought to evaluate current attitudes and practices regarding the use of urine drug testing among chronic pain patients taking opioids. To the best of our knowledge, this is one of the first such attempts in the literature to examine and document the practice patterns of urine drug testing in this context. A total of 99 attendees at the American Congress of Pain Medicine were surveyed in 2008 about their urine testing practices for patients on opioid therapy. Surprisingly, more urine testing was motivated by a desire to detect undisclosed substances than to evaluate appropriate opioid use. Some respondents never urine-tested their opioid patients, and about two-thirds of respondents had no formal training in urine testing of patients on opioid therapy. The literature does not thoroughly address the role of urine drug testing in this patient population. Most respondents did random rather than scheduled testing; few had any urine testing protocol. The study found motivations for urine testing and testing practices varied widely, and urine testing, despite its clinical utility, is not used consistently. © 2010 The Authors. Pain Practice © 2010 World Institute of Pain.

  5. Forensic Toxicology Program: alcohol and drug testing in Wisconsin drivers.

    Science.gov (United States)

    Harding, Patrick; Liddicoat, Laura J

    2003-01-01

    The Forensic Toxicology Program of the Wisconsin State Laboratory of Hygiene (WSLH) provides analytical and support services to assist in the identification of alcohol- and/or drug-impaired drivers and to assist in determining cause of death. These services are provided to law enforcement agencies, the Wisconsin Department of Natural Resources, the Wisconsin Department of Transportation, and county medical examiners and coroners. Program staff is active in alcohol and drug training, policy-making, and research on a national and international level.

  6. Urine drug testing for social service agencies in Nova Scotia, Canada.

    Science.gov (United States)

    Fraser, A D

    1998-01-01

    In Nova Scotia Canada, governmental authorities expressed concern in the late 1980s about the adverse effects of drug use by parents on the welfare of their children. Since 1991, parents with a history of drug abuse may be required to submit to urine drug and alcohol testing when ordered by the Family Courts of this province. The objective of this paper is to present this drug testing program and the results of drug testing on 125 clients from 1994-1996. Urine specimens were collected in the parents' residence by a nurse and transferred directly to the laboratory by the collector or a courier. Specimens were screened by immunoassay and TLC followed by GC-MS confirmation. Results were sent directly to the social worker. In the 3,613 urine specimens analyzed, 50.2% of specimens were negative, 45.6% were positive for one or more drug/metabolite and 4.2% of specimens were dilute (creatinine Drug testing has been considered a success by these agencies since testing provides an objective indication of recent drug use and the overall prevalence of drug use in this drug abusing population has reduced from 100% to < 50%.

  7. Flow cytometry susceptibility testing for conventional antifungal drugs and Comparison with the NCCLS Broth Macrodilution Test

    Directory of Open Access Journals (Sweden)

    M.J. Najafzadeh

    2009-08-01

    Full Text Available Introduction: During the last decade, the incidence of fungal infection has been increased in many countries. Because of the advent of resistant to antifungal agents, determination of an efficient strategic plan for treatment of fungal disease is an important issue in clinical mycology. Many methods have been introduced and developed for determination of invitro susceptibility tests. During the recent years, flow cytometry has developed to solving the problem and many papers have documented the usefulness of this technique. Materials and methods: As the first step, the invitro susceptibility of standard PTCC (Persian Type of Culture Collection strain and some clinical isolates of Candida consisting of Candida albicans, C. dubliniensis, C. glabrata, C. kefyer and C. parapsilosis were evaluated by macrodilution broth method according to NCCLS (National Committee for Clinical Laboratory Standards guidelines and flow cytometry susceptibility test. Results:  The data indicated that macro dilution broth methods and flow cytometry have the same results in determination of MIC (Minimum Inhibitory Concentration for amphotericin B, clotrimazole, fluconazole, ketoconazole and miconazole in C. albicans PTCC 5027 as well as clinical Candida isolates, such as C.albicans, C.dubliniensis, C.glabrata C.kefyr, and C.parapsilosis. Discussion: Comparing the results obtained by macrodilution broth and flow cytometry methods revealed that flow cytometry was faster. It is suggested that flow cytometry susceptibility test can be used as a powerful tool for determination of MIC and administration of the best antifungal drug in treatment of patients with Candida infections.

  8. The Effectiveness of Mandatory-Random Student Drug Testing. NCEE 2010-4025

    Science.gov (United States)

    James-Burdumy, Susanne; Goesling, Brian; Deke, John; Einspruch, Eric

    2010-01-01

    To help assess the effects of school-based random drug testing programs, the U.S. Department of Education's Institute of Education Sciences (IES) contracted with RMC Research Corporation and Mathematica Policy Research to conduct an experimental evaluation of the Mandatory-Random Student Drug Testing (MRSDT) programs in 36 high schools within…

  9. 49 CFR 40.341 - Must service agents comply with DOT drug and alcohol testing requirements?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Must service agents comply with DOT drug and alcohol testing requirements? 40.341 Section 40.341 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Roles and...

  10. 21 CFR 211.110 - Sampling and testing of in-process materials and drug products.

    Science.gov (United States)

    2010-04-01

    ... PHARMACEUTICALS Production and Process Controls § 211.110 Sampling and testing of in-process materials and drug... production process, e.g., at commencement or completion of significant phases or after storage for long... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sampling and testing of in-process materials...

  11. Second Thoughts on Drug Testing: Balancing Students' Health and Welfare with Their Expectations of Privacy.

    Science.gov (United States)

    Dowling-Sendor, Benjamin

    2000-01-01

    In its "stare decisis" ruling upholding a Pennsylvania school district's random drug-testing policy, a three-judge panel of the Seventh Circuit Court of Appeals nonetheless declared its disagreement with a similar panel's 1998 decision upholding another district's policy of random, suspicionless drug, alcohol, and tobacco testing. (MLH)

  12. 75 FR 22809 - Mandatory Guidelines for Federal Workplace Drug Testing Programs

    Science.gov (United States)

    2010-04-30

    ...: Final rule: Change in effective date. SUMMARY: The Department of Health and Human Services (HHS) is changing the effective date of the Revisions to the Mandatory Guidelines for Federal Workplace Drug Testing... HUMAN SERVICES Mandatory Guidelines for Federal Workplace Drug Testing Programs AGENCY: Substance Abuse...

  13. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    Science.gov (United States)

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the

  14. 49 CFR 219.903 - Retention of drug testing records.

    Science.gov (United States)

    2010-10-01

    .... (4) Records related to employee training: (i) Materials on drug abuse awareness, including a copy of... the following records for a minimum of five years: (i) A summary record of each covered employee's... verifying the existence of a medical explanation of the inability of a covered employee to provide...

  15. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Soolingen, D. van; Mouton, J.W.

    2012-01-01

    Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans. For most NTM infections the therapy of choice is drug treatment, but treatment regimens differ by species, in particular between slow (e.g. Mycobacterium avium complex,

  16. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Soolingen, D. van; Mouton, J.W.

    2012-01-01

    Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans. For most NTM infections the therapy of choice is drug treatment, but treatment regimens differ by species, in particular between slow (e.g. Mycobacterium avium complex, Mycobacter

  17. Meconium drug testing reveals maternal misuse of medicinal opioids among addicted mothers.

    Science.gov (United States)

    Launiainen, Terhi; Nupponen, Irmeli; Halmesmäki, Erja; Ojanperä, Ilkka

    2013-07-01

    Meconium drug testing is a non-invasive method to detect prenatal drug exposure, which can cause severe problems for the infant, indicating the need for follow-up measures to ensure the welfare of the child. Meconium samples for drug testing were collected from 143 infants as part of routine clinical work among addicted mothers. The drug testing findings were combined with medical records including clinical background and follow-up data. The substances screened for included medicinal opioids, 6-monoacetylmorphine (a metabolite of heroin), amphetamines and tetrahydrocannabinolic acid. At least one of the 13 target drugs was detected in 57 (40%) meconium samples. In 21 cases, the findings were unexpected on the basis of clinical data or denied by the mother. Medicinal opioids, especially the opioid substitution treatment drugs buprenorphine and methadone, comprised the majority of the findings of both admitted and unexpected drug misuse. Meconium drug testing methods should target not just traditional illicit drugs but also prescription drugs with misuse potential. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Drug testing welfare recipients--false positives, false negatives, unanticipated opportunities.

    Science.gov (United States)

    Pollack, Harold A; Danziger, Sheldon; Jayakody, Rukmalie; Seefeldt, Kristin S

    2002-01-01

    Substance abuse and dependence are among the most common psychiatric disorders among pregnant and parenting women. These disorders among welfare recipients have attracted special concern. Chemical testing has been proposed to identify illicit drug use in this population. This analysis scrutinizes the potential value of drug testing, using recent data from the Women's Employment Study and the National Household Survey of Drug Abuse. One-fifth of recipients reported illicit substance use during the previous year. However, less than 5% satisfied diagnostic screening criteria for illicit drug dependence. Most recipients with psychiatric disorders or alcohol dependence reported no recent illicit drug use, and, thus, would not be detected through chemical tests. Although illicit drug users are rarely dependent, many face barriers to self-sufficiency. Screening and assessment programs should distinguish use from dependence, and should also identify alcohol dependence and psychiatric disorders. States should provide a range of treatment services to address these concerns.

  19. HIV resistance testing and detected drug resistance in Europe

    NARCIS (Netherlands)

    Schultze, A.; Phillips, A.N.; Paredes, R.; Battegay, M.; Rockstroh, J.K.; Machala, L.; Tomazic, J.; Girard, P.M.; Januskevica, I.; Gronborg-Laut, K.; Lundgren, J.D.; Cozzi-Lepri, A.; Burger, D.M.

    2015-01-01

    OBJECTIVES: To describe regional differences and trends in resistance testing among individuals experiencing virological failure and the prevalence of detected resistance among those individuals who had a genotypic resistance test done following virological failure. DESIGN: Multinational cohort

  20. 49 CFR Appendix C to Part 40 - DOT Drug Testing Semi-Annual Laboratory Report to DOT

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false DOT Drug Testing Semi-Annual Laboratory Report to... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. C Appendix C to Part 40—DOT Drug Testing... of Drug and Alcohol Policy and Compliance, W62-300, 1200 New Jersey Avenue, SE., Washington, DC 20590...

  1. 21 CFR 312.160 - Drugs for investigational use in laboratory research animals or in vitro tests.

    Science.gov (United States)

    2010-04-01

    ... research animals or in vitro tests. 312.160 Section 312.160 Food and Drugs FOOD AND DRUG ADMINISTRATION... Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests § 312.160 Drugs for investigational use in laboratory research animals or in vitro tests. (a) Authorization to ship. (1)(i) A...

  2. 46 CFR 4.06-3 - Requirements for alcohol and drug testing following a serious marine incident.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Requirements for alcohol and drug testing following a... drug testing following a serious marine incident. When a marine employer determines that a casualty or... drug testing is conducted: (a) Alcohol testing. (1) Alcohol testing must be conducted on each...

  3. Army Drug Development Program. Phase I. Clinical Testing.

    Science.gov (United States)

    1980-03-01

    ingestion of each formulation. Various symptoms occured - "twitching", "fuzzy spots on ceiling", "feeling hot" and " bad dreams" - which could not be...Counter, Model S. Scientific Product diluents were used for diluting the blood samples ( Isotonic Buffered Saline; Automated Lysing and Hemoglobin Reagent...1), and at 6 a.m. will drink 360 ml of Sustacal (Mead Johnson product), containing a total of 360 calories. The drug will be administered at 8 a.m

  4. Pumpless microfluidic platform for drug testing on human skin equivalents

    OpenAIRE

    Abaci, Hasan Erbil; Gledhill, Karl; Guo, Zongyou; Christiano, Angela M.; Shuler, Michael L.

    2015-01-01

    Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies. In this study, we designed and developed a microfluidic platform that allows for long-term maintenance of full thickness human skin equivalents (HSE) which are comprised of both the epidermal and dermal compartments. The design is based on the physiologically relevant blood residence times in human skin tissue and allows for the establishment of an air-epidermal interface which is crucial for...

  5. Status of drugs-of-abuse testing in urine under blind conditions: an AACC study.

    Science.gov (United States)

    Frings, C S; Battaglia, D J; White, R M

    1989-05-01

    We report results of a blind study designed to determine the accuracy of drugs-of-abuse testing in urine as done in 31 laboratories across the United States. The drugs studied were amphetamines, cannabinoids, cocaine, opiates, and phencyclidine. These laboratories confirmed all positive drug results with a different analytical method. Ten urine samples were sent to each laboratory, which resulted in 1486 trials. There were no false-positive results. The overall accuracy rate was 97%. Our study demonstrates that urine drug testing can be accurate when performed by qualified staff, using up-to-date screening and confirmation methods, appropriate quality-assurance measures, and a chain of custody.

  6. Development, implementation and management of a drug testing program in the workplace

    Energy Technology Data Exchange (ETDEWEB)

    Burtis, C.A.

    1990-01-01

    To combat the rising use of drugs in the workplace many American companies have implemented drug testing programs and are testing employees and job applicants for use of illegal drugs. In addition, on September 15, 1986, Executive Order No.12564 was issued by President Reagan, which requires all federal agencies to develop programs and policies, one of the goals of which is to achieve a drug-free federal workplace. Included in this Executive Order is the requirement that federal agencies implement drug testing has become a prevalent practice as a means to detect and deter drug use in the workplace. Before a drug testing program is implemented, it is imperative that policies and procedures are developed that (1) ensure the accuracy of test results, (2) protect the validity and integrity of the specimen, (3) guarantee due process, and (4) maintain confidentiality. To make certain that these prerequisites were met in the government drug testing programs, the US Department of Health and Human Services (HHS) was directed to develop technical and scientific guidelines for conducting such programs. 15 refs., 1 fig., 2 tabs.

  7. Non-negative Tensor Factorization with missing data for the modeling of gene expressions in the Human Brain

    DEFF Research Database (Denmark)

    Nielsen, Søren Føns Vind; Mørup, Morten

    2014-01-01

    of the component matrices. We examine three gene expression prediction scenarios based on data missing at random, whole genes missing and whole areas missing within a subject. We find that the column-wise updating approach also known as HALS performs the most efficient when fitting the model. We further observe...... that the non-negativity constrained CP model is able to predict gene expressions better than predicting by the subject average when data is missing at random. When whole genes and whole areas are missing it is in general better to predict by subject averages. However, we find that when whole genes are missing...... missing in our problem. Our analysis is based on the non-negativity constrained Canonical Polyadic (CP) decomposition where we handle the missing data using marginalization considering three prominent alternating least squares procedures; multiplicative updates, column-wise, and row-wise updating...

  8. International Conference on Harmonisation; guidance on Q6A specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. Notice.

    Science.gov (United States)

    2000-12-29

    The Food and Drug Administration (FDA) is publishing a guidance entitled "Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes or provides recommendations concerning the selection of test procedures and the setting and justification of acceptance criteria for new chemical drug substances and new drug products produced from them. The guidance is intended to assist in the establishment of a single set of global specifications for new drug substances and new drug products.

  9. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    DEFF Research Database (Denmark)

    Brockow, K; Garvey, L H; Aberer, W

    2013-01-01

    search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group...

  10. Formation of the diuretic chlorazanil from the antimalarial drug proguanil--implications for sports drug testing.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Thomas, Andreas; Tretzel, Laura; Bailloux, Isabelle; Buisson, Corinne; Lasne, Francoise; Schaefer, Maximilian S; Kienbaum, Peter; Mueller-Stoever, Irmela; Schänzer, Wilhelm

    2015-11-10

    Chlorazanil (Ordipan, N-(4-chlorophenyl)-1,3,5-triazine-2,4-diamine) is a diuretic agent and as such prohibited in sport according to the regulations of the World Anti-Doping Agency (WADA). Despite its introduction into clinical practice in the late 1950s, the worldwide very first two adverse analytical findings were registered only in 2014, being motive for an in-depth investigation of these cases. Both individuals denied the intake of the drug; however, the athletes did declare the use of the antimalarial prophylactic agent proguanil due to temporary residences in African countries. A structural similarity between chlorazanil and proguanil is given but no direct metabolic relation has been reported in the scientific literature. Moreover, chlorazanil has not been confirmed as a drug impurity of proguanil. Proguanil however is metabolized in humans to N-(4-chlorophenyl)-biguanide, which represents a chemical precursor in the synthesis of chlorazanil. In the presence of formic acid, formaldehyde, or formic acid esters, N-(4-chlorophenyl)-biguanide converts to chlorazanil. In order to probe for potential sources of the chlorazanil detected in the doping control samples, drug formulations containing proguanil and urine samples of individuals using proguanil as antimalarial drug were subjected to liquid chromatography-high resolution/high accuracy mass spectrometry. In addition, in vitro simulations with 4-chlorophenyl-biguanide and respective reactants were conducted in urine and resulting specimens analyzed for the presence of chlorazanil. While no chlorazanil was found in drug formulations, the urine samples of 2 out of 4 proguanil users returned findings for chlorazanil at low ng/mL levels, similar to the adverse analytical findings in the doping control samples. Further, in the presence of formaldehyde, formic acid and related esters, 4-chlorophenyl-biguanide was found to produce chlorazanil in human urine, suggesting that the detection of the obsolete diuretic

  11. Psychometric properties of the Turkish versions of the Drug Use Disorders Identification Test (DUDIT) and the Drug Abuse Screening Test (DAST-10) in the prison setting.

    Science.gov (United States)

    Evren, Cuneyt; Ogel, Kultegin; Evren, Bilge; Bozkurt, Muge

    2014-01-01

    The aim of this study was to evaluate psychometric properties of the Drug Use Disorders Identification Test (DUDIT) and the Drug Abuse Screening Test (DAST-10) in prisoners with (n = 124) or without (n = 78) drug use disorder. Participants were evaluated with the DUDIT, the DAST-10, and the Addiction Profile Index-Short (API-S). The DUDIT and the DAST-10 were found to be psychometrically sound drug abuse screening measures with high convergent validity when compared with each other (r = 0.86), and API-S (r = 0.88 and r = 0.84, respectively), and to have a Cronbach's α of 0.93 and 0.87, respectively. In addition, a single component accounted for 58.28% of total variance for DUDIT, whereas this was 47.10% for DAST-10. The DUDIT had sensitivity and specificity scores of 0.95 and 0.79, respectively, when using the optimal cut-off score of 10, whereas these scores were 0.88 and 0.74 for the DAST-10 when using the optimal cut-off score of 4. Additionally, both the DUDIT and the DAST-10 showed good discriminant validity as they differentiated prisoners with drug use disorder from those without. Findings support the Turkish versions of both the DUDIT and the DAST-10 as reliable and valid drug abuse screening instruments that measure unidimensional constructs.

  12. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

    Science.gov (United States)

    Mayorga, C; Celik, G; Rouzaire, P; Whitaker, P; Bonadonna, P; Rodrigues-Cernadas, J; Vultaggio, A; Brockow, K; Caubet, J C; Makowska, J; Nakonechna, A; Romano, A; Montañez, M I; Laguna, J J; Zanoni, G; Gueant, J L; Oude Elberink, H; Fernandez, J; Viel, S; Demoly, P; Torres, M J

    2016-08-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.

  13. European recommendations for the clinical use of HIV drug resistance testing: 2011 update

    DEFF Research Database (Denmark)

    Vandamme, Anne-Mieke; Camacho, Ricardo J; Ceccherini-Silberstein, Francesca

    2011-01-01

    ) consider testing earliest detectable plasma RNA when a successful nonnucleoside reverse transcriptase inhibitor-containing therapy was inappropriately interrupted; (v) genotype source patient when postexposure prophylaxis is considered; for HIV-2, (vi) consider resistance testing where treatment change......The European HIV Drug Resistance Guidelines Panel, established to make recommendations to clinicians and virologists, felt that sufficient new information has become available to warrant an update of its recommendations, explained in both pocket guidelines and this full paper. The Panel makes...... the following recommendations concerning the indications for resistance testing: for HIV-1 (i) test earliest sample for protease and reverse transcriptase drug resistance in drug-naive patients with acute or chronic infection; (ii) test protease and reverse transcriptase drug resistance at virologic failure...

  14. Rapid confirmation of drug susceptibility in Mycobacterium tuberculosis using MPT 64 Ag based test

    Directory of Open Access Journals (Sweden)

    Ernest Afu Ochang

    2013-06-01

    Full Text Available Objective: To evaluate the possible use of MPT64 based rapid test to detect multi-drug resistant Mycobacterium tuberculosis (M. tuberculosis in antibiotic broth dilution cultures. Methods: Twenty five isolates of M. tuberculosis whose susceptibility pattern had previously been identified by HAIN Genotype MTBDRplus (HainLifecience, Herhen, Germany were processed and cultured according to the microscopic-observation drug susceptibility technique. These included 20 susceptible, two multi-drug resistant M. tuberculosis and three isoniazid mono-resistant isolates. After 10-day incubation, aspirates from each well were tested with the MPT64 rapid test. Results: The rapid test correctly identified all 25 isolates and detected rifampicin and isoniazid resistance in all but one isoniazid mono-resistant isolate. Conclusions: MPT64 rapid test could be useful in detecting M. tuberculosis and drug resistance from Middlebrook 7H9 antimicrobial broth dilution in resource poor settings without an inverted microscope.

  15. European recommendations for the clinical use of HIV drug resistance testing: 2011 update

    DEFF Research Database (Denmark)

    Vandamme, Anne-Mieke; Camacho, Ricardo J; Ceccherini-Silberstein, Francesca;

    2011-01-01

    The European HIV Drug Resistance Guidelines Panel, established to make recommendations to clinicians and virologists, felt that sufficient new information has become available to warrant an update of its recommendations, explained in both pocket guidelines and this full paper. The Panel makes...... the following recommendations concerning the indications for resistance testing: for HIV-1 (i) test earliest sample for protease and reverse transcriptase drug resistance in drug-naive patients with acute or chronic infection; (ii) test protease and reverse transcriptase drug resistance at virologic failure......) consider testing earliest detectable plasma RNA when a successful nonnucleoside reverse transcriptase inhibitor-containing therapy was inappropriately interrupted; (v) genotype source patient when postexposure prophylaxis is considered; for HIV-2, (vi) consider resistance testing where treatment change...

  16. Perceived fairness of employee drug testing as a predictor of employee attitudes and job performance.

    Science.gov (United States)

    Konovsky, M A; Cropanzano, R

    1991-10-01

    Although management of drug testing programs is becoming a critical organizational issue, no systematic conceptual framework has been applied to the study of employee reactions to drug testing. In this study an organizational justice framework was used to explain and predict the relationships among two types of justice (procedural justice and outcome fairness) employee attitudes (job satisfaction, commitment, and management trust), and behavior (turnover intentions and performance). Survey data from 195 employees in a pathology laboratory indicated that justice predicts employee attitudes and performance. Specifically, procedural justice, but not outcome fairness, predicted all 5 criterion variables. These results demonstrate the importance of procedural justice perceptions for predicting employee reactions to drug testing programs.

  17. Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?

    OpenAIRE

    Hammond, Timothy; Allen, Patricia; Birdsall, Holly

    2016-01-01

    Even the finest state-of-the art preclinical drug testing, usually in primary hepatocytes, remains an imperfect science. Drugs continue to be withdrawn from the market due to unforeseen toxicity, side effects, and drug interactions. The space program may be able to provide a lifeline. Best known for rockets, space shuttles, astronauts and engineering, the space program has also delivered some serious medical science. Optimized suspension culture in NASA’s specialized suspension culture device...

  18. Army Drug Development Program. Phase I. Clinical Testing.

    Science.gov (United States)

    1982-02-01

    34 " Donald Giancoli 457 Physical 7 Interview -:1 ’p Vital signs 100 Lab tests < Dose 750mg -3- ZA9-2~ ~ j~I l ~~I~Ii Assay ,-9 .- 2 ’ii Stuart Varner 458...3 9 2 -2J 2 ~ J~~~ Donald Giancoli 7 Physical // Interview___j/ <- Vital signs__- /7 Lab tests ZEN-/ f Dose 1500mng ~4,~747~/ Assay 91 _-L’ 2 A_ XJ I_

  19. 49 CFR Appendix B to Part 40 - DOT Drug Testing Semi-Annual Laboratory Report to Employers

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false DOT Drug Testing Semi-Annual Laboratory Report to... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. B Appendix B to Part 40—DOT Drug Testing...) (b) Negative and Dilute (number) 3. Specimens Reported as Rejected for Testing (total number) By...

  20. Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

    Science.gov (United States)

    Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmäki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A

    2017-08-22

    Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.

  1. Drug Testing in Schools: A Brief Review and Analysis of Recent Events

    Science.gov (United States)

    Velasquez, James

    2010-01-01

    Random drug testing (RSDT) in schools is a controversial topic. The U.S. Supreme Court has ruled that RSDT is constitutional for certain groups of students. Moreover, funding has been made available for schools to implement RSDT programs through the U.S. Department of Education and the White House Office of National Drug Control Policy. This…

  2. Predictive value of molecular drug resistance testing of Mycobacterium tuberculosis isolates in Valle del Cauca, Colombia.

    NARCIS (Netherlands)

    Ferro, B.E.; Garcia, P.K.; Nieto, L.M.; Soolingen, D. van

    2013-01-01

    Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium

  3. Introducing rapid diagnostic tests for malaria into drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Magnussen, Pascal; Chandler, Clare Ir;

    2014-01-01

    BACKGROUND: 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...

  4. Clinical trial of a new technique for drugs of abuse testing: a new possible sampling technique.

    Science.gov (United States)

    Skoglund, Charlotte; Hermansson, Ulric; Beck, Olof

    2015-01-01

    Exhaled breath has recently been proposed as a matrix for drug testing. This study aims to further explore, develop and validate exhaled breath as a safe and effective non-invasive method for drug testing in a clinical setting. Self-reported drug use was recorded and drug testing was performed by mass spectrometry and immunochemical methods using breath, plasma and urine samples from 45 individuals voluntarily seeking treatment for recreational drug use. Cannabis was the most prevalent drug detected by any method. Urine sampling detected most cases. The exhaled breath technique was less sensitive (73%) than plasma analysis for detection of cannabis uses but captures a more recent drug intake than both plasma and urine. Exhaled breath was the preferred specimen to donate according to interview data of the participants. Testing illicit drugs with the exhaled breath sampling technique is a sufficient, non-invasive and safe alternative and complement to plasma and/or urine sampling. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Molecular drug susceptibility testing in the Netherlands: performance of the MTBDRplus and MTBDRsl assays

    NARCIS (Netherlands)

    Simons, S.O.; Laan, T. van der; Zwaan, R. de; Kamst, M.; Ingen, J. van; Dekhuijzen, P.N.; Boeree, M.J.; Soolingen, D. van

    2015-01-01

    BACKGROUND: The performance of molecular drug susceptibility testing in countries with a low prevalence of drug resistance, such as the Netherlands, has not been adequately studied. OBJECTIVE: To evaluate the diagnostic accuracy of the GenoType((R)) MTBDRplus and MTBDRsl assays to detect resistance

  6. A review of guidelines on home drug testing web sites for parents.

    Science.gov (United States)

    Washio, Yukiko; Fairfax-Columbo, Jaymes; Ball, Emily; Cassey, Heather; Arria, Amelia M; Bresani, Elena; Curtis, Brenda L; Kirby, Kimberly C

    2014-01-01

    To update and extend prior work reviewing Web sites that discuss home drug testing for parents, and assess the quality of information that the Web sites provide, to assist them in deciding when and how to use home drug testing. We conducted a worldwide Web search that identified 8 Web sites providing information for parents on home drug testing. We assessed the information on the sites using a checklist developed with field experts in adolescent substance abuse and psychosocial interventions that focus on urine testing. None of the Web sites covered all the items on the 24-item checklist, and only 3 covered at least half of the items (12, 14, and 21 items, respectively). The remaining 5 Web sites covered less than half of the checklist items. The mean number of items covered by the Web sites was 11. Among the Web sites that we reviewed, few provided thorough information to parents regarding empirically supported strategies to effectively use drug testing to intervene on adolescent substance use. Furthermore, most Web sites did not provide thorough information regarding the risks and benefits to inform parents' decision to use home drug testing. Empirical evidence regarding efficacy, benefits, risks, and limitations of home drug testing is needed.

  7. An investigation of classification algorithms for predicting HIV drug resistance without genotype resistance testing

    CSIR Research Space (South Africa)

    Brandt, P

    2014-01-01

    Full Text Available is limited in low-resource settings. In this paper we investigate machine learning techniques for drug resistance prediction from routine treatment and laboratory data to help clinicians select patients for confirmatory genotype testing. The techniques...

  8. [Reduction of animal experiments in experimental drug testing].

    Science.gov (United States)

    Behrensdorf-Nicol, H; Krämer, B

    2014-10-01

    In order to ensure the quality of biomedical products, an experimental test for every single manufactured batch is required for many products. Especially in vaccine testing, animal experiments are traditionally used for this purpose. For example, efficacy is often determined via challenge experiments in laboratory animals. Safety tests of vaccine batches are also mostly performed using laboratory animals. However, many animal experiments have clear inherent disadvantages (low accuracy, questionable transferability to humans, unclear significance). Furthermore, for ethical reasons and animal welfare aspects animal experiments are also seen very critical by the public. Therefore, there is a strong trend towards replacing animal experiments with methods in which no animals are used ("replacement"). If a replacement is not possible, the required animal experiments should be improved in order to minimize the number of animals necessary ("reduction") and to reduce pain and suffering caused by the experiment to a minimum ("refinement"). This "3R concept" is meanwhile firmly established in legislature. In recent years many mandatory animal experiments have been replaced by alternative in vitro methods or improved according to the 3R principles; numerous alternative methods are currently under development. Nevertheless, the process from the development of a new method to its legal implementation takes a long time. Therefore, supplementary regulatory measures to facilitate validation and acceptance of new alternative methods could contribute to a faster and more consequent implementation of the 3R concept in the testing of biomedical products.

  9. HIV resistance testing and detected drug resistance in Europe

    DEFF Research Database (Denmark)

    Schultze, Anna; Phillips, Andrew N; Paredes, Roger

    2015-01-01

    calculated using logistic regression with generalized estimating equations. RESULTS: Compared to 74.2% of ART-experienced individuals in 1997, only 5.1% showed evidence of virological failure in 2012. The odds of resistance testing declined after 2004 (global P 

  10. 10 CFR 26.31 - Drug and alcohol testing.

    Science.gov (United States)

    2010-01-01

    ... testing, an undetected or untreated substance abuse problem, or other factors. At a minimum, these... FFD program personnel before assignment to tasks directly associated with administration of the FFD...) At a minimum, be administered by the FFD program on a nominal weekly frequency; (iii) Require...

  11. Skin models for the testing of transdermal drugs

    Science.gov (United States)

    Abd, Eman; Yousef, Shereen A; Pastore, Michael N; Telaprolu, Krishna; Mohammed, Yousuf H; Namjoshi, Sarika; Grice, Jeffrey E; Roberts, Michael S

    2016-01-01

    The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro–in vivo correlation and the demonstration of bioequivalence. PMID:27799831

  12. Hypothesis testing in high-throughput screening for drug discovery.

    Science.gov (United States)

    Prummer, Michael

    2012-04-01

    Following the success of small-molecule high-throughput screening (HTS) in drug discovery, other large-scale screening techniques are currently revolutionizing the biological sciences. Powerful new statistical tools have been developed to analyze the vast amounts of data in DNA chip studies, but have not yet found their way into compound screening. In HTS, characterization of single-point hit lists is often done only in retrospect after the results of confirmation experiments are available. However, for prioritization, for optimal use of resources, for quality control, and for comparison of screens it would be extremely valuable to predict the rates of false positives and false negatives directly from the primary screening results. Making full use of the available information about compounds and controls contained in HTS results and replicated pilot runs, the Z score and from it the p value can be estimated for each measurement. Based on this consideration, we have applied the concept of p-value distribution analysis (PVDA), which was originally developed for gene expression studies, to HTS data. PVDA allowed prediction of all relevant error rates as well as the rate of true inactives, and excellent agreement with confirmation experiments was found.

  13. Growing pains : how drug testing keeps workers and assets safe in a booming oil patch

    Energy Technology Data Exchange (ETDEWEB)

    Paulgaard, T.S.

    2006-06-15

    Drug abuse has become a subject of concern to the oil and gas industry, where mistakes in the operation of large machines can result in injury, death and the loss of millions of dollars. Pre-employment urine tests are becoming standard procedure in the oil field. Many supervisors refuse to let employees start work without a clear test. Urine samples are tested for the presence of cannabis, cocaine, opiates, amphetamines and phencyclidine. When a worker is injured or killed on the job, or after an uncommon error that causes significant damage, all parties involved are tested as soon as possible and a receipt of the results are expedited. The Alberta Human Rights and Citizenship Commission is now addressing the issue of drug testing, and has ascertained that drug and alcohol testing are only allowable in certain circumstances, and that it is discriminatory to test potential or existing employees for drug and alcohol use if the testing is not reasonable or justifiable. They have also suggested that there is a duty to accommodate persons with disabilities in the workplace. Drug and alcohol dependency fall within the meaning of disabled. Under the Construction Owner's Association of Alberta's Canadian Model for a Safe Workplace, testing must work in concert with treatment. Current employees are directed to seek help via an employee assistant plan. Workers and supervisors report that drug use is rampant in work camps. Industry-wide, fail rates for those who take part in drug testing are quoted by experts as ranging from between 2 to 14 per cent. 2 figs.

  14. In vitro drug testing based on contractile activity of C2C12 cells in an epigenetic drug model

    Science.gov (United States)

    Ikeda, Kazushi; Ito, Akira; Imada, Ryusuke; Sato, Masanori; Kawabe, Yoshinori; Kamihira, Masamichi

    2017-01-01

    Skeletal muscle tissue engineering holds great promise for pharmacological studies. Herein, we demonstrated an in vitro drug testing system using tissue-engineered skeletal muscle constructs. In response to epigenetic drugs, myotube differentiation of C2C12 myoblast cells was promoted in two-dimensional cell cultures, but the levels of contractile force generation of tissue-engineered skeletal muscle constructs prepared by three-dimensional cell cultures were not correlated with the levels of myotube differentiation in two-dimensional cell cultures. In contrast, sarcomere formation and contractile activity in two-dimensional cell cultures were highly correlated with contractile force generation of tissue-engineered skeletal muscle constructs. Among the epigenetic drugs tested, trichostatin A significantly improved contractile force generation of tissue-engineered skeletal muscle constructs. Follistatin expression was also enhanced by trichostatin A treatment, suggesting the importance of follistatin in sarcomere formation of muscular tissues. These observations indicate that contractility data are indispensable for in vitro drug screening. PMID:28300163

  15. Drug target mining and analysis of the Chinese tree shrew for pharmacological testing.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

  16. Analytical evaluation of four on-site oral fluid drug testing devices.

    Science.gov (United States)

    Vanstechelman, Sylvie; Isalberti, Cristina; Van der Linden, Trudy; Pil, Kristof; Legrand, Sara-Ann; Verstraete, Alain G

    2012-03-01

    The use of oral fluid (OF) as an alternative matrix for the detection of drugs of abuse has increased over the last decade, leading to the need for a rapid, simple, and reliable on-site OF testing device. Four on-site OF drug testing devices (Dräger DrugTest 5000, Cozart DDS, Mavand Rapid STAT, and Innovacon OrAlert) were evaluated on 408 volunteers at drug treatment centers. UPLC-MS-MS results were used as reference to determine sensitivity, specificity and accuracy for each device, applying Belgian legal confirmation cutoffs for benzoylecgonine, cocaine, and THC (10 ng/mL); morphine and 6-acetylmorphine (5 ng/mL); and amphetamine and 3,4-methylenedioxymethylamphetamine (25 ng/mL). Sensitivity for cocaine was 50%, 50%, 27%, and 11% for DrugTest, OrAlert, Rapid STAT, and DDS 806, respectively. For opiates, sensitivities were 84%, 73%, 77%, and 65%, respectively. For THC, the sensitivities were 81%, 23%, 43%, and 28%, respectively. For amphetamines, the sensitivities were 75%, 33%, 17%, and 67%, respectively. Specificity was >88% for opiates and THC, > 90% for amphetamines, and > 97% for cocaine. All tests showed good specificity. DrugTest had the highest sensitivity, although it was still low for some analytes.

  17. A cluster randomised trial introducing rapid diagnostic tests into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Magnussen, Pascal; Lal, Sham;

    2015-01-01

    the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. METHODS: A cluster-randomized trial...... adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7- 98·4), pDiagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops...... of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive...

  18. Skin models for the testing of transdermal drugs

    Directory of Open Access Journals (Sweden)

    Abd E

    2016-10-01

    Full Text Available Eman Abd,1 Shereen A Yousef,1 Michael N Pastore,2 Krishna Telaprolu,1 Yousuf H Mohammed,1 Sarika Namjoshi,1 Jeffrey E Grice,1 Michael S Roberts1,2 1Translational Research Institute, School of Medicine, University of Queensland, Brisbane, 2School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia Abstract: The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro–in vivo correlation and the demonstration of bioequivalence. Keywords: percutaneous permeation, dermal delivery, transdermal, bioequivalence, ex vivo skin models, reconstructed skin

  19. Pluripotent Stem Cell-Based Platforms in Cardiac Disease Modeling and Drug Testing.

    Science.gov (United States)

    Shaheen, N; Shiti, A; Gepstein, L

    2017-08-01

    The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  20. Patient-reported multiple drug reactions: Clinical profile and results of challenge testing

    Directory of Open Access Journals (Sweden)

    Ramam M

    2010-01-01

    Full Text Available Background: Some patients report hypersensitivity reactions to many drugs making it difficult to prescribe medications when they fall ill. Aim: To describe the clinical profile of multiple drug hypersensitivity and the results of challenge testing in a large teaching hospital.Methods: We performed a five-year retrospective review of the records of patients who complained of reactions to two or more unrelated drugs and avoided medication because of a fear of developing reactions. Oral challenge testing was carried out in hospital with drugs suspected by the patient to cause reactions and/or commonly prescribed medications. A positive reaction was diagnosed when symptoms and signs resembled previously experienced episodes and there was no such reaction with placebo. Results: Twenty three patients (aged 14-65 years; 19 females underwent challenge testing. Their complaints had been present for 1-30 years, with 2-40 drug reaction episodes reported. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs were most commonly implicated, and urticaria/angioedema were the most often reported manifestations. The patients underwent 3-27 challenges with 1-24 drugs. Three had positive challenge reactions with various NSAIDs, 13 developed symptoms and signs that were judged not to be true reactions, and 7 had no reactions. None of our patients qualified for a diagnosis of true multiple drug hypersensitivity. Conclusion: Patients who believe they are allergic to multiple, pharmacologically unrelated drugs are usually mistaken. Challenge testing is a reliable way of demonstrating this and providing patients with a list of safe drugs.

  1. Laboratory and clinical evaluation of on-site urine drug testing.

    Science.gov (United States)

    Beck, Olof; Carlsson, Sten; Tusic, Marinela; Olsson, Robert; Franzen, Lisa; Hulten, Peter

    2014-11-01

    Products for on-site urine drug testing offer the possibility to perform screening for drugs of abuse directly at the point-of-care. This is a well-established routine in emergency and dependency clinics but further evaluation of performance is needed due to inherent limitations with the available products. Urine drug testing by an on-site product was compared with routine laboratory methods. First, on-site testing was performed at the laboratory in addition to the routine method. Second, the on-site testing was performed at a dependency clinic and urine samples were subsequently sent to the laboratory for additional analytical investigation. The on-site testing products did not perform with assigned cut-off levels. The subjective reading between the presence of a spot (i.e. negative test result) being present or no spot (positive result) was difficult in 3.2% of the cases, and occurred for all parameters. The tests performed more accurately in drug negative samples (specificity 96%) but less accurately for detecting positives (sensitivity 79%). Of all incorrect results by the on-site test the proportion of false negatives was 42%. The overall agreement between on-site and laboratory testing was 95% in the laboratory study and 98% in the clinical study. Although a high degree of agreement was observed between on-site and routine laboratory urine drug testing, the performance of on-site testing was not acceptable due to significant number of false negative results. The limited sensitivity of on-site testing compared to laboratory testing reduces the applicability of these tests.

  2. Non-negative Tensor Factorization with missing data for the modeling of gene expressions in the Human Brain

    DEFF Research Database (Denmark)

    Nielsen, Søren Føns Vind; Mørup, Morten

    2014-01-01

    forms a promising framework for imputing missing values and characterizing gene expression in the human brain. However, care also has to be taken in particular when predicting the genetic expression levels at a whole region of the brain missing as our analysis indicates that this requires a substantial......Non-negative Tensor Factorization (NTF) has become a prominent tool for analyzing high dimensional multi-way structured data. In this paper we set out to analyze gene expression across brain regions in multiple subjects based on data from the Allen Human Brain Atlas [1] with more than 40 % data...

  3. Matrix Representation in Quantum Mechanics with Non-Negative QDF in the Case of a Hydrogen-Like Atom

    CERN Document Server

    Zhidkov, E P; Lovetsky, K P; Tretiakov, N P

    2002-01-01

    The correspondence rules A(q,p)\\mapsto\\hat{A} of the orthodoxal quantum mechanics do not allow one to introduce into the theory the non-negative quantum distribution function F(q,p). The correspondence rules A(q,p)\\mapsto\\hat{O}(A) of Kuryshkin's quantum mechanics (QMK) do allow one to do it. Besides, the operators \\hat{O}(A) turn out to be \\hat{A} bounded and \\hat{A} small at infinity for all systems of auxiliary functions {\\varphi_k}. This allows one to realise canonical matrix representation of QMK to investigate its dependence on the systems of functions {\\varphi_k}.

  4. Improving the robustness of Surface Enhanced Raman Spectroscopy based sensors by Bayesian Non-negative Matrix Factorization

    DEFF Research Database (Denmark)

    2014-01-01

    Due to applications in areas such as diagnostics and environmental safety, detection of molecules at very low concentrations has attracted recent attention. A powerful tool for this is Surface Enhanced Raman Spectroscopy (SERS) where substrates form localized areas of electromagnetic “hot spots...... a Bayesian Non-negative Matrix Factorization (NMF) approach to identify locations of target molecules. The proposed method is able to successfully analyze the spectra and extract the target spectrum. A visualization of the loadings of the basis vector is created and the results show a clear SNR enhancement...

  5. 75 FR 32950 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-06-10

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  6. 75 FR 45128 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-08-02

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... Engaged in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  7. 75 FR 75485 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-12-03

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... Federal Workplace Drug Testing Programs (Mandatory Guidelines). The Mandatory Guidelines were first... section 503 of Public Law 100-71. The ``Mandatory Guidelines for Federal Workplace Drug Testing Programs...

  8. 75 FR 27348 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-05-14

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in order to...

  9. 75 FR 16813 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-04-02

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... Engaged in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  10. 75 FR 5088 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-02-01

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  11. 75 FR 9229 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-03-01

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  12. 75 FR 55795 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-09-14

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  13. Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey

    Science.gov (United States)

    Sznitman, Sharon R.; Dunlop, Sally M.; Nalkur, Priya; Khurana, Atika; Romer, Daniel

    2012-01-01

    Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools…

  14. 75 FR 62842 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-10-13

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... Federal Workplace Drug Testing Programs (Mandatory Guidelines). The Mandatory Guidelines were first... section 503 of Public Law 100-71. The ``Mandatory Guidelines for Federal Workplace Drug Testing Programs...

  15. 77 FR 72905 - Pipeline Safety: Random Drug Testing Rate; Contractor MIS Reporting; and Obtaining DAMIS Sign-In...

    Science.gov (United States)

    2012-12-06

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate... for random drug testing, reminder for operators to report contractor MIS data, and new method for... minimum random drug testing rate for covered employees will remain at 25 percent during calendar year 2013...

  16. 75 FR 39023 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-07-07

    ... Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies AGENCY: Substance... standards of Subpart C of the Mandatory Guidelines for Federal Workplace Drug Testing Programs (Mandatory... in Urine Drug Testing for Federal Agencies,'' sets strict standards that laboratories must meet in...

  17. Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey

    Science.gov (United States)

    Sznitman, Sharon R.; Dunlop, Sally M.; Nalkur, Priya; Khurana, Atika; Romer, Daniel

    2012-01-01

    Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools…

  18. Testing New Drugs for Treatment of Melanoma Patients Applying Connectivity Map Database Analysis with Melanoma Gene Signatures

    Science.gov (United States)

    2012-10-01

    AD_________________ Award Number: W81XWH-11-1-0794 TITLE: Testing New Drugs for Treatment of...TYPE Final 3. DATES COVERED 15 September 2011 – 14 September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Testing New Drugs for Treatment of...4 Introduction: Project Title: Testing New Drugs for treatment of Melanoma Patients Applying Connectivity Map Database Analysis with Melanoma

  19. Annual banned-substance review: analytical approaches in human sports drug testing.

    Science.gov (United States)

    Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

    2017-01-01

    There has been an immense amount of visibility of doping issues on the international stage over the past 12 months with the complexity of doping controls reiterated on various occasions. Hence, analytical test methods continuously being updated, expanded, and improved to provide specific, sensitive, and comprehensive test results in line with the World Anti-Doping Agency's (WADA) 2016 Prohibited List represent one of several critical cornerstones of doping controls. This enterprise necessitates expediting the (combined) exploitation of newly generated information on novel and/or superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, and recent advances in instrumental developments. This paper is a continuation of the series of annual banned-substance reviews appraising the literature published between October 2015 and September 2016 concerning human sports drug testing in the context of WADA's 2016 Prohibited List. Copyright © 2016 John Wiley & Sons, Ltd.

  20. The effects of adulterants and selected ingested compounds on drugs-of-abuse testing in urine.

    Science.gov (United States)

    Dasgupta, Amitava

    2007-09-01

    Household chemicals such as bleach, table salt, laundry detergent, toilet bowl cleaner, vinegar, lemon juice, and eyedrops are used for adulterating urine specimens. Most of these adulterants except eyedrops can be detected by routine specimen integrity tests (creatinine, pH, temperature, and specific gravity); however, certain adulterants such as Klear, Whizzies, Urine Luck, and Stealth cannot. These adulterants can successfully mask drug testing if the concentrations of certain abused drugs are moderate. Several spot tests have been described to detect the presence of such adulterants in urine. Urine dipsticks are commercially available for detecting the presence of such adulterants, along with performance of tests for creatinine, pH, and specific gravity. Certain hair shampoo and saliva-cleaning mouthwashes are available to escape detection in hair or saliva samples, but the effectiveness of such products in masking drugs-of-abuse testing has not been demonstrated. Ingestion of poppy seed cake may result in positive screening test results for opiates, and hemp oil exposure can cause positive results for marijuana. These would be identified as true-positive results in drugs-of-abuse testing even though they do not represent the actual drug of abuse.

  1. How effective is drug testing as a workplace safety strategy? A systematic review of the evidence.

    Science.gov (United States)

    Pidd, Ken; Roche, Ann M

    2014-10-01

    The growing prevalence of workplace drug testing and the narrow scope of previous reviews of the evidence base necessitate a comprehensive review of research concerning the efficacy of drug testing as a workplace strategy. A systematic qualitative review of relevant research published between January 1990 and January 2013 was undertaken. Inclusion criteria were studies that evaluated the effectiveness of drug testing in deterring employee drug use or reducing workplace accident or injury rates. Methodological adequacy was assessed using a published assessment tool specifically designed to assess the quality of intervention studies. A total of 23 studies were reviewed and assessed, six of which reported on the effectiveness of testing in reducing employee drug use and 17 which reported on occupational accident or injury rates. No studies involved randomised control trials. Only one study was assessed as demonstrating strong methodological rigour. That study found random alcohol testing reduced fatal accidents in the transport industry. The majority of studies reviewed contained methodological weaknesses including; inappropriate study design, limited sample representativeness, the use of ecological data to evaluate individual behaviour change and failure to adequately control for potentially confounding variables. This latter finding is consistent with previous reviews and indicates the evidence base for the effectiveness of testing in improving workplace safety is at best tenuous. Better dissemination of the current evidence in relation to workplace drug testing is required to support evidence-informed policy and practice. There is also a pressing need for more methodologically rigorous research to evaluate the efficacy and utility of drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Laboratory tests in the clinical risk management of potential drug-drug interactions: a cross-sectional study using drug-dispensing data from 100 Dutch community pharmacies.

    Science.gov (United States)

    Geerts, Arjen F J; De Koning, Fred H P; De Smet, Peter A G M; Van Solinge, Wouter W; Egberts, Toine C G

    2009-01-01

    Patient safety and the life cycle of a drug are negatively influenced by the still increasing occurrence of potential drug-drug interactions (DDIs). Clinical risk management of potential DDIs is required in patients using drugs to influence the benefit-risk profile positively. Information about laboratory test results, in particular, may be useful in the assessment of potential DDIs for the individual patient. The objective of this study was to examine the frequency and nature of laboratory tests required for the assessment of the clinical relevance of potential DDIs in Dutch community pharmacies. In addition, the nature and clinical relevance of these potential DDIs is analysed. All patients from 100 Dutch community pharmacies using, according to dispensing information, two or more drugs concomitantly on a specified date (Wednesday, 4 April 2007), were included (n = 223,019). The anonymous dispensing data of the included patients were analysed against a list of DDIs requiring laboratory tests for the assessment of their clinical relevance. The number of patients at risk for these potential DDIs with severe adverse reactions was calculated. The frequency of potential DDIs requiring laboratory tests were stratified by age, sex and degree of polypharmacy. Of the included patients, 24.4% had one or more potential DDIs (n = 54,427). In 9.0% of the included patients, one or more laboratory tests for the assessment of clinical relevance of the potential DDI were required (n = 19,968). The frequency of DDIs requiring laboratory tests increased with increasing age and number of drugs, but was not related to sex. The most commonly required laboratory tests were for renal function (42.2%), electrolytes (20.1%) and coagulation (13.1%). The percentage of patients at risk for potential DDIs requiring laboratory tests with adverse reaction category F (serious, irrecoverable disablement or death) was 2.5%; category E (increased risk of failure of life-saving therapy) was 0

  3. Drug-excipient compatibility testing using a high-throughput approach and statistical design.

    Science.gov (United States)

    Wyttenbach, Nicole; Birringer, Christian; Alsenz, Jochem; Kuentz, Martin

    2005-01-01

    The aim of our research was to develop a miniaturized high throughput drug-excipient compatibility test. Experiments were planned and evaluated using statistical experimental design. Binary mixtures of a drug, acetylsalicylic acid, or fluoxetine hydrochloride, and of excipients commonly used in solid dosage forms were prepared at a ratio of approximately 1:100 in 96-well microtiter plates. Samples were exposed to different temperature (40 degrees C/ 50 degrees C) and humidity (10%/75%) for different time (1 week/4 weeks), and chemical drug degradation was analyzed using a fast gradient high pressure liquid chromatography (HPLC). Categorical statistical design was applied to identify the effects and interactions of time, temperature, humidity, and excipient on drug degradation. Acetylsalicylic acid was least stable in the presence of magnesium stearate, dibasic calcium phosphate, or sodium starch glycolate. Fluoxetine hydrochloride exhibited a marked degradation only with lactose. Factor-interaction plots revealed that the relative humidity had the strongest effect on the drug excipient blends tested. In conclusion, the developed technique enables fast drug-excipient compatibility testing and identification of interactions. Since only 0.1 mg of drug is needed per data point, fast rational preselection of the pharmaceutical additives can be performed early in solid dosage form development.

  4. Non-negative infrared patch-image model: Robust target-background separation via partial sum minimization of singular values

    Science.gov (United States)

    Dai, Yimian; Wu, Yiquan; Song, Yu; Guo, Jun

    2017-03-01

    To further enhance the small targets and suppress the heavy clutters simultaneously, a robust non-negative infrared patch-image model via partial sum minimization of singular values is proposed. First, the intrinsic reason behind the undesirable performance of the state-of-the-art infrared patch-image (IPI) model when facing extremely complex backgrounds is analyzed. We point out that it lies in the mismatching of IPI model's implicit assumption of a large number of observations with the reality of deficient observations of strong edges. To fix this problem, instead of the nuclear norm, we adopt the partial sum of singular values to constrain the low-rank background patch-image, which could provide a more accurate background estimation and almost eliminate all the salient residuals in the decomposed target image. In addition, considering the fact that the infrared small target is always brighter than its adjacent background, we propose an additional non-negative constraint to the sparse target patch-image, which could not only wipe off more undesirable components ulteriorly but also accelerate the convergence rate. Finally, an algorithm based on inexact augmented Lagrange multiplier method is developed to solve the proposed model. A large number of experiments are conducted demonstrating that the proposed model has a significant improvement over the other nine competitive methods in terms of both clutter suppressing performance and convergence rate.

  5. Informed Source Separation of Atmospheric and Surface Signal Contributions in Shortwave Hyperspectral Imagery using Non-negative Matrix Factorization

    Science.gov (United States)

    Wright, L.; Coddington, O.; Pilewskie, P.

    2015-12-01

    Current challenges in Earth remote sensing require improved instrument spectral resolution, spectral coverage, and radiometric accuracy. Hyperspectral instruments, deployed on both aircraft and spacecraft, are a growing class of Earth observing sensors designed to meet these challenges. They collect large amounts of spectral data, allowing thorough characterization of both atmospheric and surface properties. The higher accuracy and increased spectral and spatial resolutions of new imagers require new numerical approaches for processing imagery and separating surface and atmospheric signals. One potential approach is source separation, which allows us to determine the underlying physical causes of observed changes. Improved signal separation will allow hyperspectral instruments to better address key science questions relevant to climate change, including land-use changes, trends in clouds and atmospheric water vapor, and aerosol characteristics. In this work, we investigate a Non-negative Matrix Factorization (NMF) method for the separation of atmospheric and land surface signal sources. NMF offers marked benefits over other commonly employed techniques, including non-negativity, which avoids physically impossible results, and adaptability, which allows the method to be tailored to hyperspectral source separation. We adapt our NMF algorithm to distinguish between contributions from different physically distinct sources by introducing constraints on spectral and spatial variability and by using library spectra to inform separation. We evaluate our NMF algorithm with simulated hyperspectral images as well as hyperspectral imagery from several instruments including, the NASA Airborne Visible/Infrared Imaging Spectrometer (AVIRIS), NASA Hyperspectral Imager for the Coastal Ocean (HICO) and National Ecological Observatory Network (NEON) Imaging Spectrometer.

  6. A hybrid approach to urine drug testing using high-resolution mass spectrometry and select immunoassays.

    Science.gov (United States)

    McMillin, Gwendolyn A; Marin, Stephanie J; Johnson-Davis, Kamisha L; Lawlor, Bryan G; Strathmann, Frederick G

    2015-02-01

    The major objective of this research was to propose a simplified approach for the evaluation of medication adherence in chronic pain management patients, using liquid chromatography time-of-flight (TOF) mass spectrometry, performed in parallel with select homogeneous enzyme immunoassays (HEIAs). We called it a "hybrid" approach to urine drug testing. The hybrid approach was defined based on anticipated positivity rates, availability of commercial reagents for HEIAs, and assay performance, particularly analytical sensitivity and specificity for drug(s) of interest. Subsequent to implementation of the hybrid approach, time to result was compared with that observed with other urine drug testing approaches. Opioids, benzodiazepines, zolpidem, amphetamine-like stimulants, and methylphenidate metabolite were detected by TOF mass spectrometry to maximize specificity and sensitivity of these 37 drug analytes. Barbiturates, cannabinoid metabolite, carisoprodol, cocaine metabolite, ethyl glucuronide, methadone, phencyclidine, propoxyphene, and tramadol were detected by HEIAs that performed adequately and/or for which positivity rates were very low. Time to result was significantly reduced compared with the traditional approach. The hybrid approach to urine drug testing provides a simplified and analytically specific testing process that minimizes the need for secondary confirmation. Copyright© by the American Society for Clinical Pathology.

  7. Testing for drug and alcohol аbuse at the workplace

    Directory of Open Access Journals (Sweden)

    Zoran Kavrakovski

    2009-12-01

    Full Text Available Drug and alcohol abuse in the workplace represents a great risk to employee’s health and safety. More than 50% of the employees worldwide are related to easily accessible drug abuse, while 70% of the employees are related to alcohol abuse in the workplace. Tests for detecting drug and alcohol abuse in the workplace should be part of a new regulation, compulsory for all employees in the Republic of Macedonia. Implementing this sort of testing program should at the same time be a step towards devising particular solutions that shall bring about greater safety in the working environment. A key element in the implementation is to devise and establish an adequate policy that shall determine the risk factors within a working establishment which shall clearly express its position regarding drug and alcohol abuse during working hours. Along with the risk factors, the policy may also include the program for testing both, employees and the ones who are about to be employed, for drug and alcohol abuse. In order to implement this sort of test, it must be in accordance with the Occupational Safety and Health Act (Official gazette of the Republic of Macedonia, No 92/07, 2007 and a legal framework has to be defined, that shall regulate and solve numerous aspects of this issue, in order to fully implement the program for drug free working environment pursuant to the Declaration and the decrees of the United Nations General Assembly in 1998.

  8. Etoricoxib-induced fixed drug eruption with positive lesional patch tests.

    Science.gov (United States)

    Calistru, Ana Maria; Cunha, Ana Paula; Nogueira, Ana; Azevedo, Filomena

    2011-06-01

    Fixed drug eruption (FDE) is most commonly associated with antibiotics, anticonvulsants, and nonnarcotic analgens, including nonsteroidal anti-inflammatory drugs (NSAIDs). However, the newer cyclooxygenase 2 (COX-2) inhibitors have been rarely reported to cause FDE. We report the case of a 52-year-old Caucasian woman with erythematous pruritic plaques on the neck, left forearm, and second finger of the right hand, healing with hyperpigmentation and recurring in the same locations. The patient was sporadically taking oral etoricoxib 90 mg for her back pain and noticed the relation between administration of the drug and skin lesions, the time interval decreasing progressively from 1 week to 30 minutes. No other signs, symptoms, or drug intake was mentioned. The patch tests with etoricoxib 1% and 5% in petrolatum were positive at the location of the lesions and negative on the back (nonlesional skin). Standard European and NSAID series were negative. Patch tests of 10 healthy controls with etoricoxib 1% and 5% in petrolatum were negative. After the avoidance of the drug, no relapse was mentioned. The patch test was reliable for the diagnosis of FDE, avoiding the need for subsequent oral provocation testing and therefore preventing the possible adverse effects. Despite being regarded as a safe drug, the occurrence of cutaneous adverse reactions to etoricoxib should be considered, especially in the setting of its increasing use in pain control.

  9. Urine Trouble: Drug Testing of Students and Teachers in Public Schools

    Science.gov (United States)

    Butler, Frank

    2012-01-01

    Non-individualized (so-called "random") drug testing in public schools presents issues of Constitutional law on both the federal and state levels, particularly with regard to citizens' freedom from "unreasonable searches and seizures." The trend toward increasing acceptance of such testing by the courts (and particularly the U.S. Supreme Court)…

  10. Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

    NARCIS (Netherlands)

    Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

    2011-01-01

    The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

  11. Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

    NARCIS (Netherlands)

    Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

    2011-01-01

    The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

  12. Drug Testing US Student-Athletes for Performance-Enhancing Substance Misuse: A Flawed Process.

    Science.gov (United States)

    Bahrke, Michael S

    2015-01-01

    The author argues that drug testing of U.S. high school students for performance-enhancing substance misuse is invasive, expensive, and the low number of positive test results do not justify the costs, especially in financially strapped school districts where this money would be better spent on injury prevention for athletes and the education of all students.

  13. Withdrawal of fall-risk-increasing drugs in older persons: Effect on mobility test outcomes

    NARCIS (Netherlands)

    N. van der Velde (Nathalie); B.H.Ch. Stricker (Bruno); H.A.P. Pols (Huib); T.J.M. van der Cammen (Tischa)

    2007-01-01

    textabstractBackground: Previously, we have shown that withdrawal of fall-risk-increasing drugs (FRIDs) as a single intervention reduces falls incidence. Improvement of mobility may be an important factor in this finding and we therefore tested whether mobility tests improved after FRID withdrawal.

  14. A cluster randomised trial introducing rapid diagnostic tests into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Magnussen, Pascal; Lal, Sham

    2015-01-01

    the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. METHODS: A cluster-randomized trial...... of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 - 50·9), ptested mRDT-positive. Drug shop vendors...... adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7- 98·4), pdrug shop vendors using presumptive diagnosis (control arm). CONCLUSION: Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops...

  15. The K(a)ihler-Ricci Flow on K(a)hler Manifolds with 2-Non-negative Traceless Bisectional Curvature Operator

    Institute of Scientific and Technical Information of China (English)

    Xiuxiong CHEN; Haozhao LI

    2008-01-01

    The authors show that the 2-non-negative traceless bisectional curvature is preserved along the K(a)hler-Ricci flow.The positivity of Ricci curvature is also preserved along the K(a)hler-Ricci flow with 2-non-negative traceless bisectional curvature.As a corollary,the K(a)hler-Ricci flow with 2-non-negative traceless bisectional curvature will converge to a K(a)hler-Ricci soliton in the sense of Cheeger-Gromov-Hausdorff topology if complex dimension n≥3.

  16. [Drug information for patients (Package Leaflets), and user testing in EU].

    Science.gov (United States)

    Yamamoto, Michiko; Doi, Hirohisa; Furukawa, Aya

    2015-01-01

    Patients and consumers have desired high quality drug information in their pharmacotherapy, and are entitled to receive it. It is desirable that the information should be aimed at shared decision-making between patients and healthcare professionals about medications. The quality of drug information available to patients should also be assured. With an aim to improve the quality of "Drug Guide for Patients", we investigated Patient Information Leaflets (PILs) which are approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom (UK) with regard to the criteria of development and user testing for assuring the quality of the PILs. In the European Union (EU), these are called Package Leaflets (PLs). PILs have been a legal requirement in the UK since 1999 for all medications. The user testing of PILs has been implemented as evidence since 2005 so that people can rely on the information provided in the leaflet. Execution of PILs which follow the guidance of the user testing, according to the guidance of this user testing, would reflect the views of patients. Here, we introduce the development process and implementation of user testing of PILs. In terms of readability, accessibility and understandability of drug information for patients, we need to discuss involving the public in decisions on how its quality should be assured and how it can be made easily be comprehensible for patients, in order to make effective use of "Drug Guide for Patients" in the future in Japan.

  17. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes

    Science.gov (United States)

    Canetti, G.; Fox, Wallace; Khomenko, A.; Mahler, H. T.; Menon, N. K.; Mitchison, D. A.; Rist, N.; Šmelev, N. A.

    1969-01-01

    In a paper arising out of an informal international consultation of specialists in the bacteriology of tuberculosis held in 1961, an attempt was made to formulate criteria, and specify technical procedures, for reliable tests of sensitivity (the absolute-concentration method, the resistance-ratio method and the proportion method) to the 3 main antituberculosis drugs (isoniazid, streptomycin and p-aminosalicylic acid). Seven years later, a further consultation was held to review the latest developments in the field and to suggest how sensitivity tests might be put to practical use in tuberculosis control programmes. The participants reached agreement on how to define drug sensitivity and resistance, and stressed the importance of using a discrimination approach to the calibration of sensitivity tests. Their views are contained in the present paper, which also includes descriptions of the sensitivity tests used by the Medical Research Council of Great Britain for first- and second-line drugs (minimal inhibitory concentration and resistance-ratio methods), the two main variants of the proportion method developed by the Institut Pasteur, Paris, and a method for calibrating sensitivity tests. PMID:5309084

  18. Policing, massive street drug testing and poly-substance use chaos in Georgia - a policy case study.

    Science.gov (United States)

    Otiashvili, David; Tabatadze, Mzia; Balanchivadze, Nino; Kirtadze, Irma

    2016-01-16

    Since early 2000, intensive policing, wide scale street drug testing, and actions aimed at limiting the availability of specific drugs have been implemented in Georgia. Supporters of this approach argue that fear of drug testing and resulting punishment compels drug users to stop using and prevents youth from initiating drug use. It has been also stated that reduction in the availability of specific drugs should be seen as an indication of the overall success of counter-drug efforts. The aim of the current review is to describe the drug-related law enforcement response in Georgia and its impact on illicit drug consumption and drug-related harm. We reviewed relevant literature that included peer-reviewed scientific articles, stand-alone research reports, annual drug situation reports, technical reports and program data. This was also supplemented by the review of relevant legislation and judicial practices for the twelve year period between 2002 and 2014. Every episode of reduced availability of any "traditional" injection drug was followed by the discovery/introduction of a new injection preparation. The pattern of drug consumption was normally driven by users' attempts to substitute their drug of choice through mixing together available alternative substances. Chaotic poly-substance use and extensive utilization of home-made injection drugs, prepared from toxic precursors, became common. Massive random street drug testing had little or no effect on the prevalence of problem drug use. Intensive harassment of drug users and exclusive focus on reducing the availability of specific drugs did not result in reduction of the prevalence of injecting drug use. Repressive response of Georgian anti-drug authorities relied heavily on consumer sanctions, which led to shifts in drug users' behavior. In most cases, these shifts were associated with the introduction and use of new toxic preparations and subsequent harm to the physical and mental health of drug consumers.

  19. HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

    Science.gov (United States)

    Rhee, Soo-Yon; Jordan, Michael R; Raizes, Elliot; Chua, Arlene; Parkin, Neil; Kantor, Rami; Van Zyl, Gert U; Mukui, Irene; Hosseinipour, Mina C; Frenkel, Lisa M; Ndembi, Nicaise; Hamers, Raph L; Rinke de Wit, Tobias F; Wallis, Carole L; Gupta, Ravindra K; Fokam, Joseph; Zeh, Clement; Schapiro, Jonathan M; Carmona, Sergio; Katzenstein, David; Tang, Michele; Aghokeng, Avelin F; De Oliveira, Tulio; Wensing, Annemarie M J; Gallant, Joel E; Wainberg, Mark A; Richman, Douglas D; Fitzgibbon, Joseph E; Schito, Marco; Bertagnolio, Silvia; Yang, Chunfu; Shafer, Robert W

    2015-01-01

    The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

  20. The Influence of Drug Testing Attributes, Participation, and Personality on Potential Applicant's Attitudes and Job Pursuit Intentions.

    Science.gov (United States)

    Stoffey, Ronald W.

    Researchers are increasingly aware of the importance of job applicants' reactions to the personnel selection process. This study examines three variables in connection with drug testing policies: (1) the potential applicant's reactions to two different drug testing policies which varied in terms of drug policy characteristics and their impact on…

  1. 49 CFR 40.323 - May program participants release drug or alcohol test information in connection with legal...

    Science.gov (United States)

    2010-10-01

    ... PROGRAMS Confidentiality and Release of Information § 40.323 May program participants release drug or... information pertaining to an employee's drug or alcohol test without the employee's consent in certain legal... the drug or alcohol test information sought is relevant to the case and issues an order directing...

  2. Attitudes about Advances in Sweat Patch Testing in Drug Courts: Insights from a Case Study in Southern California

    Science.gov (United States)

    Polzer, Katherine

    2010-01-01

    Drug courts are reinventing the drug testing framework by experimenting with new methods, including use of the sweat patch. The sweat patch is a band-aid like strip used to monitor drug court participants. The validity and reliability of the sweat patch as an effective testing method was examined, as well as the effectiveness, meaning how likely…

  3. Impact of the emergence of designer drugs upon sports doping testing.

    Science.gov (United States)

    Teale, P; Scarth, J; Hudson, S

    2012-01-01

    Historically, dope-testing methods have been developed to target specific and known threats to the integrity of sport. Traditionally, the source of new analytical targets for which testing was required were derived almost exclusively from the pharmaceutical industry. More recently, the emergence of designer drugs, such as tetrahydrogestrinone that are specifically intended to evade detection, or novel chemicals intended to circumvent laws controlling the sale and distribution of recreational drugs, such as anabolic steroids, stimulants and cannabinoids, have become a significant issue. In this review, we shall consider the emergence of designer drugs and the response of dope-testing laboratories to these new threats, in particular developments in analytical methods, instrumentation and research intended to detect their abuse, and we consider the likely future impact of these approaches.

  4. Drug-induced exanthems: correlation of allergy testing with histologic diagnosis.

    Science.gov (United States)

    Seitz, Cornelia S; Rose, Christian; Kerstan, Andreas; Trautmann, Axel

    2013-11-01

    Skin biopsies are commonly performed to confirm drug-induced exanthem (DIE). However, the relevance of histologic examination in discriminating between DIE and non-DIE (NDIE) is controversial. A retrospective analysis was performed to evaluate the reliability of histologic diagnosis of DIE. In all, 91 patients with a skin biopsy specimen of an acute exanthem temporally related to a single identifiable drug underwent complete allergy testing. Their biopsy specimens were retrospectively re-evaluated by 2 dermatopathologists blinded to the original reports to test for discrimination between DIE versus NDIE. In 35 patients, non-IgE-mediated drug allergy was confirmed by allergy testing, whereas in 56 patients drug hypersensitivity could be excluded. Sensitivity of pathology reports for diagnosis of DIE reached 62.9% with a positive predictive value of 40.7%. Specificity was 41.1% with a negative predictive value of 69.7%. No significant difference in tissue eosinophilia was detected between DIE and NDIE. This was a retrospective study. Dermatopathologic evaluation of skin biopsy specimens is of limited use in differentiating between DIE and NDIE. All efforts should be made to subject these patients to thorough allergy testing for definitely confirming or ruling out drug hypersensitivity. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  5. Pill testing or drug checking in Australia: Acceptability of service design features.

    Science.gov (United States)

    Barratt, Monica J; Bruno, Raimondo; Ezard, Nadine; Ritter, Alison

    2017-06-20

    This study aimed to determine design features of a drug-checking service that would be feasible, attractive and likely to be used by Australian festival and nightlife attendees. Web survey of 851 Australians reporting use of psychostimulants and/or hallucinogens and attendance at licensed venues past midnight and/or festivals in the past year (70% male; median age 23 years). A drug-checking service located at festivals or clubs would be used by 94%; a fixed-site service external to such events by 85%. Most (80%) were willing to wait an hour for their result. Almost all (94%) would not use a service if there was a possibility of arrest, and a majority (64%) would not use a service that did not provide individual feedback of results. Drug-checking results were only slightly more attractive if they provided comprehensive quantitative results compared with qualitative results of key ingredients. Most (93%) were willing to pay up to $5, and 68% up to $10, per test. One-third (33%) reported willingness to donate a whole dose for testing: they were more likely to be male, younger, less experienced, use drugs more frequently and attend venues/festivals less frequently. In this sample, festival- or club-based drug-checking services with low wait times and low cost appear broadly attractive under conditions of legal amnesty and individualised feedback. Quantitative analysis of ecstasy pills requiring surrender of a whole pill may appeal to a minority in Australia where pills are more expensive than elsewhere. [Barratt MJ, Bruno R, Ezard N, Ritter A. Pill testing or drug checking in Australia: Acceptability of service design features. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  6. Automatic segmentation of odor maps in the mouse olfactory bulb using regularized non-negative matrix factorization.

    Science.gov (United States)

    Soelter, Jan; Schumacher, Jan; Spors, Hartwig; Schmuker, Michael

    2014-09-01

    Segmentation of functional parts in image series of functional activity is a common problem in neuroscience. Here we apply regularized non-negative matrix factorization (rNMF) to extract glomeruli in intrinsic optical signal (IOS) images of the olfactory bulb. Regularization allows us to incorporate prior knowledge about the spatio-temporal characteristics of glomerular signals. We demonstrate how to identify suitable regularization parameters on a surrogate dataset. With appropriate regularization segmentation by rNMF is more resilient to noise and requires fewer observations than conventional spatial independent component analysis (sICA). We validate our approach in experimental data using anatomical outlines of glomeruli obtained by 2-photon imaging of resting synapto-pHluorin fluorescence. Taken together, we show that rNMF provides a straightforward method for problem tailored source separation that enables reliable automatic segmentation of functional neural images, with particular benefit in situations with low signal-to-noise ratio as in IOS imaging.

  7. Two pitfalls of BOLD fMRI magnitude-based neuroimage analysis: non-negativity and edge effect.

    Science.gov (United States)

    Chen, Zikuan; Calhoun, Vince D

    2011-08-15

    BOLD fMRI is accepted as a noninvasive imaging modality for neuroimaging and brain mapping. A BOLD fMRI dataset consists of magnitude and phase components. Currently, only the magnitude is used for neuroimage analysis. In this paper, we show that the fMRI-magnitude-based neuroimage analysis may suffer two pitfalls: one is that the magnitude is non-negative and cannot differentiate positive from negative BOLD activity; the other is an edge effect that may manifest as an edge enhancement or a spatial interior dip artifact at a local uniform BOLD region. We demonstrate these pitfalls via numeric simulations using a BOLD fMRI model and also via a phantom experiment. We also propose a solution by making use of the fMRI phase image, the counterpart of the fMRI magnitude.

  8. Detecting the community structure and activity patterns of temporal networks: a non-negative tensor factorization approach

    CERN Document Server

    Gauvin, Laetitia; Cattuto, Ciro

    2014-01-01

    The increasing availability of temporal network data is calling for more research on extracting and characterizing mesoscopic structures in temporal networks and on relating such structure to specific functions or properties of the system. An outstanding challenge is the extension of the results achieved for static networks to time-varying networks, where the topological structure of the system and the temporal activity patterns of its components are intertwined. Here we investigate the use of a latent factor decomposition technique, non-negative tensor factorization, to extract the community-activity structure of temporal networks. The method is intrinsically temporal and allows to simultaneously identify communities and to track their activity over time. We represent the time-varying adjacency matrix of a temporal network as a three-way tensor and approximate this tensor as a sum of terms that can be interpreted as communities of nodes with an associated activity time series. We summarize known computationa...

  9. Navigating the Functional Landscape of Transcription Factors via Non-Negative Tensor Factorization Analysis of MEDLINE Abstracts

    Directory of Open Access Journals (Sweden)

    Sujoy Roy

    2017-08-01

    Full Text Available In this study, we developed and evaluated a novel text-mining approach, using non-negative tensor factorization (NTF, to simultaneously extract and functionally annotate transcriptional modules consisting of sets of genes, transcription factors (TFs, and terms from MEDLINE abstracts. A sparse 3-mode term × gene × TF tensor was constructed that contained weighted frequencies of 106,895 terms in 26,781 abstracts shared among 7,695 genes and 994 TFs. The tensor was decomposed into sub-tensors using non-negative tensor factorization (NTF across 16 different approximation ranks. Dominant entries of each of 2,861 sub-tensors were extracted to form term–gene–TF annotated transcriptional modules (ATMs. More than 94% of the ATMs were found to be enriched in at least one KEGG pathway or GO category, suggesting that the ATMs are functionally relevant. One advantage of this method is that it can discover potentially new gene–TF associations from the literature. Using a set of microarray and ChIP-Seq datasets as gold standard, we show that the precision of our method for predicting gene–TF associations is significantly higher than chance. In addition, we demonstrate that the terms in each ATM can be used to suggest new GO classifications to genes and TFs. Taken together, our results indicate that NTF is useful for simultaneous extraction and functional annotation of transcriptional regulatory networks from unstructured text, as well as for literature based discovery. A web tool called Transcriptional Regulatory Modules Extracted from Literature (TREMEL, available at http://binf1.memphis.edu/tremel, was built to enable browsing and searching of ATMs.

  10. Detecting the community structure and activity patterns of temporal networks: a non-negative tensor factorization approach.

    Directory of Open Access Journals (Sweden)

    Laetitia Gauvin

    Full Text Available The increasing availability of temporal network data is calling for more research on extracting and characterizing mesoscopic structures in temporal networks and on relating such structure to specific functions or properties of the system. An outstanding challenge is the extension of the results achieved for static networks to time-varying networks, where the topological structure of the system and the temporal activity patterns of its components are intertwined. Here we investigate the use of a latent factor decomposition technique, non-negative tensor factorization, to extract the community-activity structure of temporal networks. The method is intrinsically temporal and allows to simultaneously identify communities and to track their activity over time. We represent the time-varying adjacency matrix of a temporal network as a three-way tensor and approximate this tensor as a sum of terms that can be interpreted as communities of nodes with an associated activity time series. We summarize known computational techniques for tensor decomposition and discuss some quality metrics that can be used to tune the complexity of the factorized representation. We subsequently apply tensor factorization to a temporal network for which a ground truth is available for both the community structure and the temporal activity patterns. The data we use describe the social interactions of students in a school, the associations between students and school classes, and the spatio-temporal trajectories of students over time. We show that non-negative tensor factorization is capable of recovering the class structure with high accuracy. In particular, the extracted tensor components can be validated either as known school classes, or in terms of correlated activity patterns, i.e., of spatial and temporal coincidences that are determined by the known school activity schedule.

  11. Detecting the community structure and activity patterns of temporal networks: a non-negative tensor factorization approach.

    Science.gov (United States)

    Gauvin, Laetitia; Panisson, André; Cattuto, Ciro

    2014-01-01

    The increasing availability of temporal network data is calling for more research on extracting and characterizing mesoscopic structures in temporal networks and on relating such structure to specific functions or properties of the system. An outstanding challenge is the extension of the results achieved for static networks to time-varying networks, where the topological structure of the system and the temporal activity patterns of its components are intertwined. Here we investigate the use of a latent factor decomposition technique, non-negative tensor factorization, to extract the community-activity structure of temporal networks. The method is intrinsically temporal and allows to simultaneously identify communities and to track their activity over time. We represent the time-varying adjacency matrix of a temporal network as a three-way tensor and approximate this tensor as a sum of terms that can be interpreted as communities of nodes with an associated activity time series. We summarize known computational techniques for tensor decomposition and discuss some quality metrics that can be used to tune the complexity of the factorized representation. We subsequently apply tensor factorization to a temporal network for which a ground truth is available for both the community structure and the temporal activity patterns. The data we use describe the social interactions of students in a school, the associations between students and school classes, and the spatio-temporal trajectories of students over time. We show that non-negative tensor factorization is capable of recovering the class structure with high accuracy. In particular, the extracted tensor components can be validated either as known school classes, or in terms of correlated activity patterns, i.e., of spatial and temporal coincidences that are determined by the known school activity schedule.

  12. A cost-effective smartphone-based antimicrobial susceptibility test reader for drug resistance testing (Conference Presentation)

    Science.gov (United States)

    Feng, Steve W.; Tseng, Derek; Di Carlo, Dino; Garner, Omai B.; Ozcan, Aydogan

    2017-03-01

    Antimicrobial susceptibility testing (AST) is commonly used for determining microbial drug resistance, but routine testing, which can significantly reduce the spread of multi-drug resistant organisms, is not regularly performed in resource-limited and field-settings due to technological challenges and lack of trained diagnosticians. We developed a portable cost-effective smartphone-based colorimetric 96-well microtiter plate (MTP) reader capable of automated AST without the need for a trained diagnostician. This system is composed of a smartphone used in conjunction with a 3D-printed opto-mechanical attachment, which holds a set of inexpensive light-emitting-diodes and fiber-optic cables coupled to the 96-well MTP for enabling the capture of the transmitted light through each well by the smartphone camera. Images of the MTP plate are captured at multiple exposures and uploaded to a local or remote server (e.g., a laptop) for automated processing/analysis of the results using a custom-designed smartphone application. Each set of images are combined to generate a high dynamic-range image and analyzed for well turbidity (indicative of bacterial growth), followed by interpretative analysis per plate to determine minimum inhibitory concentration (MIC) and drug susceptibility for the specific bacterium. Results are returned to the originating device within 1 minute and shown to the user in tabular form. We demonstrated the capability of this platform using MTPs prepared with 17 antibiotic drugs targeting Gram-negative bacteria and tested 82 patient isolate MTPs of Klebsiella pneumoniae, achieving well turbidity accuracy of 98.19%, MIC accuracy of 95.15%, and drug susceptibility interpretation accuracy of 99.06%, meeting the FDA defined criteria for AST.

  13. Drug susceptibility testing of Mycobacterium Avium subsp. Avium isolates from naturally infected domestic pigeons to avian tuberculosis

    Directory of Open Access Journals (Sweden)

    Kaveh Parvandar

    2016-01-01

    Conclusion: We suggest drug susceptibility testing for more nontuberculous mycobateria, particularly M. avium complex isolated from infected birds and humans, as well as molecular basics of drug sensitivity in order to detect resistance genes of pathogenic M. avium subsp. avium.

  14. Epidemiological control of drug resistance and compensatory mutation under resistance testing and second-line therapy.

    Science.gov (United States)

    Saddler, Clare A; Wu, Yue; Valckenborgh, Frank; Tanaka, Mark M

    2013-12-01

    The fitness cost of antibiotic resistance in the absence of treatment raises the possibility that prudent use of drugs may slow or reverse the rise of resistance. Unfortunately, compensatory mutations that lower this cost may lead to entrenched resistance. Here, we develop a mathematical model of resistance evolution and compensatory mutation to determine whether reversion to sensitivity can occur, and how disease control might be facilitated by a second-line therapy. When only a single antibiotic is available, sensitive bacteria reach fixation only under treatment rates so low that hardly any cases are treated. We model a scenario in which drug sensitivity can be accurately tested so that a second-line therapy is administered to resistant cases. Before the rise of resistance to the second drug, disease eradication is possible if resistance testing and second-line treatment are conducted at a high enough rate. However, if double drug resistance arises, the possibility of disease eradication is greatly reduced and compensated resistance prevails in most of the parameter space. The boundary separating eradication from fixation of compensated resistance is strongly influenced by the underlying basic reproductive number of the pathogen and drug efficacy in sensitive cases, but depends less on the resistance cost and compensation. When double resistance is possible, the boundary is affected by the relative strengths of resistance against the two drugs in the double-resistant-compensated strain.

  15. Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?

    Science.gov (United States)

    Hammond, Timothy; Allen, Patricia; Birdsall, Holly

    2016-07-01

    Even the finest state-of-the art preclinical drug testing, usually in primary hepatocytes, remains an imperfect science. Drugs continue to be withdrawn from the market due to unforeseen toxicity, side effects, and drug interactions. The space program may be able to provide a lifeline. Best known for rockets, space shuttles, astronauts and engineering, the space program has also delivered some serious medical science. Optimized suspension culture in NASA's specialized suspension culture devices, known as rotating wall vessels, uniquely maintains Phase I and Phase II drug metabolizing pathways in hepatocytes for weeks in cell culture. Previously prohibitively expensive, new materials and 3D printing techniques have the potential to make the NASA rotating wall vessel available inexpensively on an industrial scale. Here we address the tradeoffs inherent in the rotating wall vessel, limitations of alternative approaches for drug metabolism studies, and the market to be addressed. Better pre-clinical drug testing has the potential to significantly reduce the morbidity and mortality of one of the most common problems in modern medicine: adverse events related to pharmaceuticals.

  16. Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Hyejin Kim

    2013-01-01

    Full Text Available Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required.

  17. Test Sample for the Spatially Resolved Quantification of Illicit Drugs on Fingerprints Using Imaging Mass Spectrometry.

    Science.gov (United States)

    Muramoto, Shin; Forbes, Thomas P; van Asten, Arian C; Gillen, Greg

    2015-01-01

    A novel test sample for the spatially resolved quantification of illicit drugs on the surface of a fingerprint using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and desorption electrospray ionization mass spectrometry (DESI-MS) was demonstrated. Calibration curves relating the signal intensity to the amount of drug deposited on the surface were generated from inkjet-printed arrays of cocaine, methamphetamine, and heroin with a deposited-mass ranging nominally from 10 pg to 50 ng per spot. These curves were used to construct concentration maps that visualized the spatial distribution of the drugs on top of a fingerprint, as well as being able to quantify the amount of drugs in a given area within the map. For the drugs on the fingerprint on silicon, ToF-SIMS showed great success, as it was able to generate concentration maps of all three drugs. On the fingerprint on paper, only the concentration map of cocaine could be constructed using ToF-SIMS and DESI-MS, as the signals of methamphetamine and heroin were completely suppressed by matrix and substrate effects. Spatially resolved quantification of illicit drugs using imaging mass spectrometry is possible, but the choice of substrates could significantly affect the results.

  18. Thoroughfares, crossroads and cul-de-sacs: drug testing of welfare recipients.

    Science.gov (United States)

    Wincup, Emma

    2014-09-01

    Over the past five years, proposals to introduce drug testing for welfare recipients have proliferated across the globe. In England, it was included in the Welfare Reform Act 2009 (yet never implemented) and in 2013, the New Zealand government introduced legislation which requires claimants to take pre-employment drug tests when requested by a prospective employer or training provider. Similarly, in over 20 US states there have been attempts to initiate drug testing of welfare recipients as a condition of eligibility for welfare, although frequently these controversial plans have either stalled or once introduced they have been halted through legal challenge. This article examines the process of introducing drug testing of welfare claimants in the UK as part of a broader strategy to address worklessness among problem drug users. Using Hudson and Lowe's (2004) multi-level analytic framework, which disputes 'top down' rational models of policy-making, it explores the mechanisms used for challenging drug testing policies. In so doing, it identifies the key policy actors involved, noting the alliances forged and strategies adopted to persuade the government to pursue alternative policies. Whilst the primary focus of the article is on the UK, consideration of the US and New Zealand facilitates comparison of the types of policy networks which emerge to oppose similar policies proposed in different socio-political contexts, and the forms of argument and/or evidence they inject into policy discussions. It is argued that a heavy reliance on rights-based arguments was a feature of opposing drug testing in the UK, US and New Zealand, and these featured more heavily than attempts to refute evidence underpinning these policies. However, there were important differences between jurisdictions in relation to the mechanisms used to challenge drug testing policies. These do not simply reflect the nature of the policies proposed but instead are reflective of different modes of

  19. Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.

    Science.gov (United States)

    Andersson, E I; Pützer, S; Yadav, B; Dufva, O; Khan, S; He, L; Sellner, L; Schrader, A; Crispatzu, G; Oleś, M; Zhang, H; Adnan-Awad, S; Lagström, S; Bellanger, D; Mpindi, J P; Eldfors, S; Pemovska, T; Pietarinen, P; Lauhio, A; Tomska, K; Cuesta-Mateos, C; Faber, E; Koschmieder, S; Brümmendorf, T H; Kytölä, S; Savolainen, E-R; Siitonen, T; Ellonen, P; Kallioniemi, O; Wennerberg, K; Ding, W; Stern, M-H; Huber, W; Anders, S; Tang, J; Aittokallio, T; Zenz, T; Herling, M; Mustjoki, S

    2017-08-14

    T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clinical testing.Leukemia advance online publication, 1 September 2017; doi:10.1038/leu.2017.252.

  20. Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Clarke, Sîan E; Lal, Sham

    2015-01-01

    BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence...... to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control...... in the private health sector. METHODS: A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons...

  1. Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA.

    Science.gov (United States)

    Ilkhani, Hoda; Hughes, Taylor; Li, Jing; Zhong, Chuan Jian; Hepel, Maria

    2016-06-15

    Widely used anti-cancer treatments involving chemotherapeutic drugs result in cancer cell damage due to their strong interaction with DNA. In this work, we have developed laboratory biosensors for screening chemotherapeutic drugs and to aid in the assessment of DNA modification/damage caused by these drugs. The sensors utilize surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods to monitor sensory film modification and observe the drug-DNA reactivity. The self-assembled monolayer protected gold-disk electrode (AuDE) was coated with a reduced graphene oxide (rGO), decorated with plasmonic gold-coated Fe2Ni@Au magnetic nanoparticles functionalized with double-stranded DNA (dsDNA), a sequence of the breast cancer gene BRCA1. The nanobiosensors AuDE/SAM/rGO/Fe2Ni@Au/dsDNA were then subjected to the action of a model chemotherapeutic drug, doxorubicin (DOX), to assess the DNA modification and its dose dependence. The designed novel nanobiosensors offer SERS/electrochemical transduction, enabling chemically specific and highly sensitive analytical signals generation. The SERS measurements have corroborated the DOX intercalation into the DNA duplex whereas the electrochemical scans have indicated that the DNA modification by DOX proceeds in a concentration dependent manner, with limit of detection LOD=8 µg/mL (S/N=3), with semilog linearity over 3 orders of magnitude. These new biosensors are sensitive to agents that interact with DNA and facilitate the analysis of functional groups for determination of the binding mode. The proposed nanobiosensors can be applied in the first stage of the drug development for testing the interactions of new drugs with DNA before the drug efficacy can be assessed in more expensive testing in vitro and in vivo.

  2. Effectiveness of saliva and fingerprints as alternative specimens to urine and blood in forensic drug testing.

    Science.gov (United States)

    Kuwayama, Kenji; Miyaguchi, Hajime; Yamamuro, Tadashi; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

    2016-07-01

    In forensic drug testing, it is important to immediately take biological specimens from suspects and victims to prove their drug intake. We evaluated the effectiveness of saliva and fingerprints as alternative specimens to urine and blood in terms of ease of sampling, drug detection sensitivity, and drug detection periods for each specimen type. After four commercially available pharmaceutical products were administered to healthy subjects, each in a single dose, their urine, blood, saliva, and fingerprints were taken at predetermined sampling times over approximately four weeks. Fourteen analytes (the administered drugs and their main metabolites) were extracted from each specimen using simple pretreatments, such as dilution and deproteinization, and were analyzed using liquid chromatography/mass spectrometry (LC/MS). Most of the analytes were detected in saliva and fingerprints, as well as in urine and blood. The time-courses of drug concentrations were similar between urine and fingerprints, and between blood and saliva. Compared to the other compounds, the acidic compounds, for example ibuprofen, acetylsalicylic acid, were more difficult to detect in all specimens. Acetaminophen, dihydrocodeine, and methylephedrine were detected in fingerprints at later sampling times than in urine. However, a relationship between the drug structures and their detection periods in each specimen was not found. Saliva and fingerprints could be easily sampled on site without using special techniques or facilities. In addition, fingerprints could be immediately analyzed after simple and rapid treatment. In cases where it would be difficult to immediately obtain urine and blood, saliva and fingerprints could be effective alternative specimens for drug testing. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Evaluation of 5-fluorouracil applicability by multi-point collagen gel droplet embedded drug sensitivity test.

    Science.gov (United States)

    Ochiai, Takumi; Nishimura, Kazuhiko; Noguchi, Hajime; Kitajima, Masayuki; Tsuruoka, Yuko; Takahashi, Yuka

    2005-07-01

    The drug sensitivity of tumor cells is one of key issues to explore individualized therapy for cancer patients. One of such methods is in vitro anticancer drug sensitivity test which is generally based on one drug concentration and contact time. In this study, 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer patients was evaluated by collagen gel droplet embedded drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Cancer cells from 19 patients were measured for 9 drug concentration/contact time conditions (cohort 1) and from 34 patients were measured for 2 drug concentration/contact time conditions (cohort 2) using CD-DST. There was not significant difference in growth inhibition rate for 1.0 microg/ml for 24 h and 0.2 microg/ml for 120 h, which gives the same area under the curve (AUC) (p=0.832) in all 53 patients (cohort 1 and 2). In cohort 1, 9 conditions were successfully measured in 18 of 19 cohort 1 patients (94.7%). The drug concentrations and growth inhibition rate approximated to logarithmic curve for all 3 contact times and 50% inhibitory concentration (IC50) values at 3 contact times could be calculated in these 18 patients. Growth inhibition rate and AUC also approximated to logarithmic curve. These values varied several orders of magnitude among patients. In vitro antitumor effect of 5-FU depended on AUC in colorectal tumor and it might support the use of continuous infusion or oral therapy which generates significant AUC with manageable toxicity. Some patients demonstrating low 5-FU sensitivity could not be indicated for 5-FU based therapy, and non-5-FU therapy should be explored for them.

  4. Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience.

    Science.gov (United States)

    Hoffner, S; Angeby, K; Sturegård, E; Jönsson, B; Johansson, A; Sellin, M; Werngren, J

    2013-11-01

    Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organization's yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.

  5. Optimizing urine drug testing for monitoring medication compliance in pain management.

    Science.gov (United States)

    Melanson, Stacy E F; Ptolemy, Adam S; Wasan, Ajay D

    2013-12-01

    It can be challenging to successfully monitor medication compliance in pain management. Clinicians and laboratorians need to collaborate to optimize patient care and maximize operational efficiency. The test menu, assay cutoffs, and testing algorithms utilized in the urine drug testing panels should be periodically reviewed and tailored to the patient population to effectively assess compliance and avoid unnecessary testing and cost to the patient. Pain management and pathology collaborated on an important quality improvement initiative to optimize urine drug testing for monitoring medication compliance in pain management. We retrospectively reviewed 18 months of data from our pain management center. We gathered data on test volumes, positivity rates, and the frequency of false positive results. We also reviewed the clinical utility of our testing algorithms, assay cutoffs, and adulterant panel. In addition, the cost of each component was calculated. The positivity rate for ethanol and 3,4-methylenedioxymethamphetamine were testing from our panel. We also lowered the screening cutoff for cocaine to meet the clinical needs of the pain management center. In addition, we changed our testing algorithm for 6-acetylmorphine, benzodiazepines, and methadone. For example, due the high rate of false negative results using our immunoassay-based benzodiazepine screen, we removed the screening portion of the algorithm and now perform benzodiazepine confirmation up front in all specimens by liquid chromatography-tandem mass spectrometry. Conducting an interdisciplinary quality improvement project allowed us to optimize our testing panel for monitoring medication compliance in pain management and reduce cost. Wiley Periodicals, Inc.

  6. The constitutionality of random drug and alcohol testing of students in secondary schools.

    Science.gov (United States)

    Estrin, Irene; Sher, Leo

    2006-01-01

    Adolescent drug and alcohol use is a major public health problem. Multiple studies indicate that substance use is a risk factor for physical and mental disorders in adolescents. Secondary schools and the communities they serve have been facing a long-standing problem of substance abuse. American adolescents have become quite accustomed to drug prevention being a part of their curriculum. However, some policy decisions made by school administrators have been legally challenged. In 1989, Vernonia School District serving a small community in Oregon, instituted a random drug testing policy of its athletes. In 1991, the parents of a seventh grader refused to give their consent for random drug testing. The seventh grader was denied participation in the sport and sued the School District arguing that the school policy violated the Fourth and Fourteenth Amendments to the United States Constitution, and Article I, Section 9 of the Oregon Constitution. In 1995, on appeal to the Supreme Court of the United States, the School District won the case. The Vernonia School District versus Acton case became a landmark case, but random drug and alcohol testing in secondary schools has been a subject of multiple court cases. The authors discuss three of them. Both Federal and State Courts have recognized that a secondary school environment in itself represents "a special need," for which suspicionless searches are sometimes necessary to maintain order, safety, and discipline. Drug and alcohol testing programs in secondary schools may still be challenged on its legality. Therefore, examining court sanctioned programs and their long-term efficacy statistics is recommended.

  7. Receipt and timing of HIV drug resistance testing in six U.S. jurisdictions.

    Science.gov (United States)

    Dasgupta, Sharoda; Hall, H Irene; Hernandez, Angela L; Ocfemia, M Cheryl Bañez; Saduvala, Neeraja; Oster, Alexandra M

    2017-05-03

    The Department of Health and Human Services recommends drug resistance testing at linkage to HIV care. Because receipt and timing of testing are not well characterized, we examined testing patterns among persons with diagnosed HIV who are linked to care. Using surveillance data in six jurisdictions for persons aged ≥13 years with HIV infection diagnosed in 2013, we assessed the proportion receiving testing, and among these, the proportion receiving testing at linkage. Multivariable log-binomial regression modeling estimated associations between selected characteristics and receipt of testing (1) overall, and (2) at linkage among those tested. Of 9,408 persons linked to care, 66% received resistance testing, among whom 68% received testing at linkage. Less testing was observed among male persons who inject drugs (PWID), compared with men who have sex with men (adjusted prevalence ratio [aPR]: 0.88; 95% confidence interval [CI]: 0.81-0.97) and persons living in areas with population testing was lower for persons with initial CD4 counts ≥500 cells/mm(3), compared with those with CD4 counts tested, testing at linkage was lower among male PWID (aPR: 0.85; CI: 0.75-0.95) and, in some jurisdictions, persons with CD4 counts ≥500 cells/mm(3) (aPR range: 0.63-0.73). Two-thirds of persons with diagnosed HIV who were linked to care received resistance testing, and most received testing at linkage as recommended. Improving receipt and timing of testing among male PWID, persons in less populous settings, and in all jurisdictions, regardless of CD4 count, may improve care outcomes.

  8. Comprehensive Drug Testing of Patient-derived Conditionally Reprogrammed Cells from Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Saeed, Khalid; Rahkama, Vesa; Eldfors, Samuli; Bychkov, Dmitry; Mpindi, John Patrick; Yadav, Bhagwan; Paavolainen, Lassi; Aittokallio, Tero; Heckman, Caroline; Wennerberg, Krister; Peehl, Donna M; Horvath, Peter; Mirtti, Tuomas; Rannikko, Antti; Kallioniemi, Olli; Östling, Päivi; Af Hällström, Taija M

    2017-03-01

    Technology development to enable the culture of human prostate cancer (PCa) progenitor cells is required for the identification of new, potentially curative therapies for PCa. We established and characterized patient-derived conditionally reprogrammed cells (CRCs) to assess their biological properties and to apply these to test the efficacies of drugs. CRCs were established from seven patient samples with disease ranging from primary PCa to advanced castration-resistant PCa (CRPC). The CRCs were characterized by genomic, transcriptomic, protein expression, and drug profiling. The phenotypic quantification of the CRCs was done based on immunostaining followed by image analysis with Advanced Cell Classifier using Random Forest supervised machine learning. Copy number aberrations (CNAs) were called from whole-exome sequencing and transcriptomics using in-house pipelines. Dose-response measurements were used to generate multiparameter drug sensitivity scores using R-statistical language. We generated six benign CRC cultures which all had an androgen receptor-negative, basal/transit-amplifying phenotype with few CNAs. In three-dimensional cell culture, these cells could re-express the androgen receptor. The CRCs from a CRPC patient (HUB.5) displayed multiple CNAs, many of which were shared with the parental tumor. We carried out high-throughput drug-response studies with 306 emerging and clinical cancer drugs. Using the benign CRCs as controls, we identified the Bcl-2 family inhibitor navitoclax as the most potent cancer-specific drug for the CRCs from a CRPC patient. Other drug efficacies included taxanes, mepacrine, and retinoids. Comprehensive cancer pharmacopeia-wide drug testing of CRCs from a CRPC patient highlighted both known and novel drug sensitivities in PCa, including navitoclax, which is currently being tested in clinical trials of CRPC. We describe an approach to generate patient-derived cancer cells from advanced prostate cancer and apply such cells to

  9. 10 CFR 707.11 - Drugs for which testing is performed.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Drugs for which testing is performed. 707.11 Section 707.11 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.11...; cocaine; opiates; phencyclidine; and amphetamines. However, when conducting reasonable suspicion...

  10. Rapid drug susceptibility testing of mycobacteria by culture on a highly porous ceramic support

    NARCIS (Netherlands)

    Ingham, C.J.; Ayad, A.B.; Nolsen, K.; Mulder, B.

    2008-01-01

    BACKGROUND: Phenotypic, culture-based methods for drug susceptibility testing (DST) of Mycobacterium tuberculosis are relatively simple and may be particularly appropriate for resource-limited settings where tuberculosis (TB) is most prevalent. However, these methods can be slow and generate signifi

  11. The "Anatomy" of a Performance-Enhancing Drug Test in Sports

    Science.gov (United States)

    Werner, T. C.

    2012-01-01

    The components of a performance-enhancing drug (PED) test in sports include sample selection, collection, establishing sample integrity, sample pretreatment, analyte detection, data evaluation, reporting results, and action taken based on the result. Undergraduate curricula generally focus on the detection and evaluation steps of an analytical…

  12. Test Sample for the Spatially Resolved Quantification of Illicit Drugs on Fingerprints Using Imaging Mass Spectrometry

    NARCIS (Netherlands)

    Muramoto, S.; Forbes, T.P.; van Asten, A.C.; Gillen, G.

    2015-01-01

    A novel test sample for the spatially resolved quantification of illicit drugs on the surface of a fingerprint using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and desorption electrospray ionization mass spectrometry (DESI-MS) was demonstrated. Calibration curves relating the signal

  13. 77 FR 10509 - Agency Information Collection Activities; Proposed Collection; Comment Request; Drug Testing for...

    Science.gov (United States)

    2012-02-22

    ... AGENCY Agency Information Collection Activities; Proposed Collection; Comment Request; Drug Testing for... Information Collection Request (ICR) has been forwarded to the Office of Management and Budget (OMB) for... abstracted below, describes the nature of the information collection and its estimated burden and cost....

  14. Test Sample for the Spatially Resolved Quantification of Illicit Drugs on Fingerprints Using Imaging Mass Spectrometry

    NARCIS (Netherlands)

    Muramoto, S.; Forbes, T.P.; van Asten, A.C.; Gillen, G.

    2015-01-01

    A novel test sample for the spatially resolved quantification of illicit drugs on the surface of a fingerprint using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and desorption electrospray ionization mass spectrometry (DESI-MS) was demonstrated. Calibration curves relating the signal i

  15. Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Clarke, Sîan E; Lal, Sham;

    2015-01-01

    BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence...

  16. 75 FR 8526 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs

    Science.gov (United States)

    2010-02-25

    ... Office of the Secretary 49 CFR Part 40 RIN 2105-AD64 Procedures for Transportation Workplace Drug and... required method. However, in response to comments requesting additional flexibility in testing methods, the... may increase flexibility and lower costs for employers who choose to use them over more expensive...

  17. Drug-resistant tuberculosis in Central Mozambique: the role of a rapid genotypic susceptibility testing.

    Science.gov (United States)

    Namburete, Evangelina Inácio; Tivane, Inês; Lisboa, Miguelhete; Passeri, Margarida; Pocente, Renata; Ferro, Josefo Joao; Harrison, Lee H; Bollela, Valdes Roberto

    2016-08-17

    Genotypic molecular testing may be very helpful for tuberculosis (TB) drug-resistance surveillance and for treatment guidance in low resource settings. Descriptive analysis of M. tuberculosis isolates from Beira Central Hospital, Mozambique, during 2014-2015. Genotype MTBDRplus and MTBDRsl were used and patient medical records reviewed. To explore genotypic susceptibility profile of Mycobacterium tuberculosis, to first and second line drugs (SLD) in Beira Mozambique. Of 155 isolates, 16.1 % (25) were multidrug resistant (MDR), 8.4 % (13) isoniazid-monoresistant and 1.3 % (2) rifampicin-monoresistant. Among MDR-TB, 22.2 % showed primary and 77.8 % represented acquired resistance. The majority of patients with drug resistance had a history of previous TB treatment. Among 125 isolates tested for ethambutol and SLD, 7.2 % (9) were resistant to ethambutol, 4.8 % (6) to fluoroquinolones and 0.8 % (1) to ethambutol and fluoroquinolones. Resistance to injectable SLD was not detected. As far as we know this is the first report of a genotypic testing used to provide information about SLD resistance in Mozambique, where phenotypic susceptibility testing is usually unavailable. Extensively drug resistant TB was not detected in this isolates from Beira Mozambique.

  18. Cost and Efficacy Assessment of an Alternative Medication Compliance Urine Drug Testing Strategy.

    Science.gov (United States)

    Doyle, Kelly; Strathmann, Frederick G

    2017-02-01

    This study investigates the frequency at which quantitative results provide additional clinical benefit compared to qualitative results alone. A comparison between alternative urine drug screens and conventional screens including the assessment of cost-to-payer differences, accuracy of prescription compliance or polypharmacy/substance abuse was also included. In a reference laboratory evaluation of urine specimens from across the United States, 213 urine specimens with provided prescription medication information (302 prescriptions) were analyzed by two testing algorithms: 1) conventional immunoassay screen with subsequent reflexive testing of positive results by quantitative mass spectrometry; and 2) a combined immunoassay/qualitative mass-spectrometry screen that substantially reduced the need for subsequent testing. The qualitative screen was superior to immunoassay with reflex to mass spectrometry in confirming compliance per prescription (226/302 vs 205/302), and identifying non-prescription abuse (97 vs 71). Pharmaceutical impurities and inconsistent drug metabolite patterns were detected in only 3.8% of specimens, suggesting that quantitative results have limited benefit. The percentage difference between the conventional testing algorithm and the alternative screen was projected to be 55%, and a 2-year evaluation of test utilization as a measure of test order volume follows an exponential trend for alternative screen test orders over conventional immunoassay screens that require subsequent confirmation testing. Alternative, qualitative urine drug screens provide a less expensive, faster, and more comprehensive evaluation of patient medication compliance and drug abuse. The vast majority of results were interpretable with qualitative results alone indicating a reduced need to automatically reflex to quantitation or provide quantitation for the majority of patients. This strategy highlights a successful approach using an alternative strategy for both the

  19. In vitro anticancer drug test: A new method emerges from the model of glioma stem cells

    Directory of Open Access Journals (Sweden)

    Gabriele Riva

    2014-01-01

    Full Text Available Glioblastoma multiforme (GBM is a grade IV astrocytoma and the most common malignant brain tumor. Current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. The failure of current therapies may be due to the presence, within the tumor, of cells characterized by enhanced self-renewal capacity, multilineage differentiation potential and elevated invasive behavior, called glioma stem cells (GSCs. To evaluate the pharmacological efficacy of selected drugs on six GSC lines, we set up a multiple drug responsivity assay based on the combined evaluation of cytomorphological and functional parameters, including the analysis of polymorphic nuclei, mitotic index and cell viability. In order to understand the real pharmacological efficacy of the tested drugs, we assigned a specific drug responsivity score to each GSC line, integrating the data produced by multiple assays. In this work we explored the antineoplastic effects of paclitaxel (PTX, an inhibitor of microtubule depolymerization, utilized as standard treatment in several cancers, and of valproic acid (VPA, an inhibitor of histone deacetylases (HDACs with multiple anticancer properties. We classified the six GSC lines as responsive or resistant to these drugs, on the basis of their responsivity scores. This method can also be useful to identify the best way to combine two or more drugs. In particular, we utilized the pro-differentiating effect of VPA to improve the PTX effectiveness and we observed a significant reduction of cell viability compared to single treatments.

  20. A Microfluidic Channel Method for Rapid Drug-Susceptibility Testing of Pseudomonas aeruginosa.

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    Yoshimi Matsumoto

    Full Text Available The recent global increase in the prevalence of antibiotic-resistant bacteria and lack of development of new therapeutic agents emphasize the importance of selecting appropriate antimicrobials for the treatment of infections. However, to date, the development of completely accelerated drug susceptibility testing methods has not been achieved despite the availability of a rapid identification method. We proposed an innovative rapid method for drug susceptibility testing for Pseudomonas aeruginosa that provides results within 3 h. The drug susceptibility testing microfluidic (DSTM device was prepared using soft lithography. It consisted of five sets of four microfluidic channels sharing one inlet slot, and the four channels are gathered in a small area, permitting simultaneous microscopic observation. Antimicrobials were pre-introduced into each channel and dried before use. Bacterial suspensions in cation-adjusted Mueller-Hinton broth were introduced from the inlet slot and incubated for 3 h. Susceptibilities were microscopically evaluated on the basis of differences in cell numbers and shapes between drug-treated and control cells, using dedicated software. The results of 101 clinically isolated strains of P. aeruginosa obtained using the DSTM method strongly correlated with results obtained using the ordinary microbroth dilution method. Ciprofloxacin, meropenem, ceftazidime, and piperacillin caused elongation in susceptible cells, while meropenem also induced spheroplast and bulge formation. Morphological observation could alternatively be used to determine the susceptibility of P. aeruginosa to these drugs, although amikacin had little effect on cell shape. The rapid determination of bacterial drug susceptibility using the DSTM method could also be applicable to other pathogenic species, and it could easily be introduced into clinical laboratories without the need for expensive instrumentation.

  1. Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis

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    Hoffner Sven

    2009-05-01

    Full Text Available Abstract Background One of the challenges facing the tuberculosis (TB control programmes in resource-limited settings is lack of rapid techniques for detection of drug resistant TB, particularly multi drug resistant tuberculosis (MDR TB. Results obtained with the conventional indirect susceptibility testing methods come too late to influence a timely decision on patient management. More rapid tests directly applied on sputum samples are needed. This study compared the sensitivity, specificity and time to results of four direct drug susceptibility testing tests with the conventional indirect testing for detection of resistance to rifampicin and isoniazid in M. tuberculosis. The four direct tests included two in-house phenotypic assays – Nitrate Reductase Assay (NRA and Microscopic Observation Drug Susceptibility (MODS, and two commercially available tests – Genotype® MTBDR and Genotype® MTBDRplus (Hain Life Sciences, Nehren, Germany. Methods A literature review and meta-analysis of study reports was performed. The Meta-Disc software was used to analyse the reports and tests for sensitivity, specificity, and area under the summary receiver operating characteristic (sROC curves. Heterogeneity in accuracy estimates was tested with the Spearman correlation coefficient and Chi-square. Results Eighteen direct DST reports were analysed: NRA – 4, MODS- 6, Genotype MTBDR® – 3 and Genotype® MTBDRplus – 5. The pooled sensitivity and specificity for detection of resistance to rifampicin were 99% and 100% with NRA, 96% and 96% with MODS, 99% and 98% with Genotype® MTBDR, and 99% and 99% with the new Genotype® MTBDRplus, respectively. For isoniazid it was 94% and 100% for NRA, 92% and 96% for MODS, 71% and 100% for Genotype® MTBDR, and 96% and 100% with the Genotype® MTBDRplus, respectively. The area under the summary receiver operating characteristic (sROC curves was in ranges of 0.98 to 1.00 for all the four tests. Molecular tests were

  2. Preventing prescription drug misuse: field test of the SmartRx Web program.

    Science.gov (United States)

    Deitz, Diane K; Cook, Royer F; Hendrickson, April

    2011-01-01

    Purpose of the project was to test a Web-based program designed to prevent prescription drug misuse. Study sample consisted of 346 working women randomized into either an experimental or wait-list control condition. Analysis of covariance and logistic regression were used to compare responses. Women receiving the intervention had greater knowledge of drug facts and greater self-efficacy in medication adherence and ability to manage problems with medications compared with controls. Women receiving the intervention also had reduced symptoms reported on the CAGE for prescription medications. Findings suggest that multimedia Web-based programs can be a beneficial addition to substance misuse prevention services. The study's limitations are noted.

  3. HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

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    Soo-Yon Rhee

    Full Text Available The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART in the low- and middle-income countries (LMICs hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR and enable care-providers to determine which individuals with virological failure (VF on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs. This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI-associated DRMs (M184V and K65R and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

  4. On non-negative matrix factorization algorithms for signal-dependent noise with application to electromyography data

    Science.gov (United States)

    Devarajan, Karthik; Cheung, Vincent C.K.

    2017-01-01

    Non-negative matrix factorization (NMF) by the multiplicative updates algorithm is a powerful machine learning method for decomposing a high-dimensional nonnegative matrix V into two nonnegative matrices, W and H where V ~ WH. It has been successfully applied in the analysis and interpretation of large-scale data arising in neuroscience, computational biology and natural language processing, among other areas. A distinctive feature of NMF is its nonnegativity constraints that allow only additive linear combinations of the data, thus enabling it to learn parts that have distinct physical representations in reality. In this paper, we describe an information-theoretic approach to NMF for signal-dependent noise based on the generalized inverse Gaussian model. Specifically, we propose three novel algorithms in this setting, each based on multiplicative updates and prove monotonicity of updates using the EM algorithm. In addition, we develop algorithm-specific measures to evaluate their goodness-of-fit on data. Our methods are demonstrated using experimental data from electromyography studies as well as simulated data in the extraction of muscle synergies, and compared with existing algorithms for signal-dependent noise. PMID:24684448

  5. Using Dynamic Multi-Task Non-Negative Matrix Factorization to Detect the Evolution of User Preferences in Collaborative Filtering.

    Science.gov (United States)

    Ju, Bin; Qian, Yuntao; Ye, Minchao; Ni, Rong; Zhu, Chenxi

    2015-01-01

    Predicting what items will be selected by a target user in the future is an important function for recommendation systems. Matrix factorization techniques have been shown to achieve good performance on temporal rating-type data, but little is known about temporal item selection data. In this paper, we developed a unified model that combines Multi-task Non-negative Matrix Factorization and Linear Dynamical Systems to capture the evolution of user preferences. Specifically, user and item features are projected into latent factor space by factoring co-occurrence matrices into a common basis item-factor matrix and multiple factor-user matrices. Moreover, we represented both within and between relationships of multiple factor-user matrices using a state transition matrix to capture the changes in user preferences over time. The experiments show that our proposed algorithm outperforms the other algorithms on two real datasets, which were extracted from Netflix movies and Last.fm music. Furthermore, our model provides a novel dynamic topic model for tracking the evolution of the behavior of a user over time.

  6. Whole Reproductive System Non-Negative Matrix Factorization Mass Spectrometry Imaging of an Early-Stage Ovarian Cancer Mouse Model.

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    Martin R L Paine

    Full Text Available High-grade serous carcinoma (HGSC is the most common and deadliest form of ovarian cancer. Yet it is largely asymptomatic in its initial stages. Studying the origin and early progression of this disease is thus critical in identifying markers for early detection and screening purposes. Tissue-based mass spectrometry imaging (MSI can be employed as an unbiased way of examining localized metabolic changes between healthy and cancerous tissue directly, at the onset of disease. In this study, we describe MSI results from Dicer-Pten double-knockout (DKO mice, a mouse model faithfully reproducing the clinical nature of human HGSC. By using non-negative matrix factorization (NMF for the unsupervised analysis of desorption electrospray ionization (DESI datasets, tissue regions are segregated based on spectral components in an unbiased manner, with alterations related to HGSC highlighted. Results obtained by combining NMF with DESI-MSI revealed several metabolic species elevated in the tumor tissue and/or surrounding blood-filled cyst including ceramides, sphingomyelins, bilirubin, cholesterol sulfate, and various lysophospholipids. Multiple metabolites identified within the imaging study were also detected at altered levels within serum in a previous metabolomic study of the same mouse model. As an example workflow, features identified in this study were used to build an oPLS-DA model capable of discriminating between DKO mice with early-stage tumors and controls with up to 88% accuracy.

  7. Whole Reproductive System Non-Negative Matrix Factorization Mass Spectrometry Imaging of an Early-Stage Ovarian Cancer Mouse Model

    Science.gov (United States)

    Kim, Jaeyeon; Bennett, Rachel V.; Parry, R. Mitchell; Gaul, David A.; Wang, May D.; Matzuk, Martin M.; Fernández, Facundo M.

    2016-01-01

    High-grade serous carcinoma (HGSC) is the most common and deadliest form of ovarian cancer. Yet it is largely asymptomatic in its initial stages. Studying the origin and early progression of this disease is thus critical in identifying markers for early detection and screening purposes. Tissue-based mass spectrometry imaging (MSI) can be employed as an unbiased way of examining localized metabolic changes between healthy and cancerous tissue directly, at the onset of disease. In this study, we describe MSI results from Dicer-Pten double-knockout (DKO) mice, a mouse model faithfully reproducing the clinical nature of human HGSC. By using non-negative matrix factorization (NMF) for the unsupervised analysis of desorption electrospray ionization (DESI) datasets, tissue regions are segregated based on spectral components in an unbiased manner, with alterations related to HGSC highlighted. Results obtained by combining NMF with DESI-MSI revealed several metabolic species elevated in the tumor tissue and/or surrounding blood-filled cyst including ceramides, sphingomyelins, bilirubin, cholesterol sulfate, and various lysophospholipids. Multiple metabolites identified within the imaging study were also detected at altered levels within serum in a previous metabolomic study of the same mouse model. As an example workflow, features identified in this study were used to build an oPLS-DA model capable of discriminating between DKO mice with early-stage tumors and controls with up to 88% accuracy. PMID:27159635

  8. Modeling Polio Data Using the First Order Non-Negative Integer-Valued Autoregressive, INAR(1), Model

    Science.gov (United States)

    Vazifedan, Turaj; Shitan, Mahendran

    Time series data may consists of counts, such as the number of road accidents, the number of patients in a certain hospital, the number of customers waiting for service at a certain time and etc. When the value of the observations are large it is usual to use Gaussian Autoregressive Moving Average (ARMA) process to model the time series. However if the observed counts are small, it is not appropriate to use ARMA process to model the observed phenomenon. In such cases we need to model the time series data by using Non-Negative Integer valued Autoregressive (INAR) process. The modeling of counts data is based on the binomial thinning operator. In this paper we illustrate the modeling of counts data using the monthly number of Poliomyelitis data in United States between January 1970 until December 1983. We applied the AR(1), Poisson regression model and INAR(1) model and the suitability of these models were assessed by using the Index of Agreement(I.A.). We found that INAR(1) model is more appropriate in the sense it had a better I.A. and it is natural since the data are counts.

  9. Class-specific discriminant time-frequency analysis using novel jointly learnt non-negative matrix factorization

    Science.gov (United States)

    Ghoraani, Behnaz

    2016-12-01

    Time-frequency (TF) representation has found wide use in many challenging signal processing tasks including classification, interference rejection, and retrieval. Advances in TF analysis methods have led to the development of powerful techniques, which use non-negative matrix factorization (NMF) to adaptively decompose the TF data into TF basis components and coefficients. In this paper, standard NMF is modified for TF data, such that the improved TF bases can be used for signal classification applications with overlapping classes and data retrieval. The new method, called jointly learnt NMF (JLNMF) method, identifies both distinct and shared TF bases and is able to use the decomposed bases to successfully retrieve and separate the class-specific information from data. The paper provides the framework of the proposed JLNMF cost function and proposes a projected gradient framework to solve for limit point stationarity solutions. The developed algorithm has been applied to a synthetic data retrieval experiment and epileptic spikes in EEG signals of infantile spasms and discrimination of pathological voice disorder. The experimental results verified that JLNMF successfully identified the class-specific information, thus enhancing data separation performance.

  10. Discovering perturbation of modular structure in HIV progression by integrating multiple data sources through non-negative matrix factorization.

    Science.gov (United States)

    Ray, Sumanta; Maulik, Ujjwal

    2016-12-20

    Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF). As the identified metamodules inherit those information so, detecting perturbation of these, reflects the changes in expression pattern, in PPI structure and in functional similarity of genes during the infection progression. To integrate modules of different data sources into strong meta-modules, NMF based clustering is utilized here. Perturbation in meta-modular structure is identified by investigating the topological and intramodular properties and putting rank to those meta-modules using a rank aggregation algorithm. We have also analyzed the preservation structure of significant GO terms in which the human proteins of the meta-modules participate. Moreover, we have performed an analysis to show the change of coregulation pattern of identified transcription factors (TFs) over the HIV progression stages.

  11. Using Dynamic Multi-Task Non-Negative Matrix Factorization to Detect the Evolution of User Preferences in Collaborative Filtering.

    Directory of Open Access Journals (Sweden)

    Bin Ju

    Full Text Available Predicting what items will be selected by a target user in the future is an important function for recommendation systems. Matrix factorization techniques have been shown to achieve good performance on temporal rating-type data, but little is known about temporal item selection data. In this paper, we developed a unified model that combines Multi-task Non-negative Matrix Factorization and Linear Dynamical Systems to capture the evolution of user preferences. Specifically, user and item features are projected into latent factor space by factoring co-occurrence matrices into a common basis item-factor matrix and multiple factor-user matrices. Moreover, we represented both within and between relationships of multiple factor-user matrices using a state transition matrix to capture the changes in user preferences over time. The experiments show that our proposed algorithm outperforms the other algorithms on two real datasets, which were extracted from Netflix movies and Last.fm music. Furthermore, our model provides a novel dynamic topic model for tracking the evolution of the behavior of a user over time.

  12. A Pilot Test of a Mobile App for Drug Court Participants.

    Science.gov (United States)

    Johnson, Kimberly; Richards, Stephanie; Chih, Ming-Yuan; Moon, Tae Joon; Curtis, Hilary; Gustafson, David H

    2016-01-01

    The U.S. criminal justice system refers more people to substance abuse treatment than any other system. Low treatment completion rates and high relapse rates among addicted offenders highlight the need for better substance use disorder treatment and recovery tools. Mobile health applications (apps) may fill that need by providing continuous support. In this pilot test, 30 participants in a Massachusetts drug court program used A-CHESS, a mobile app for recovery support and relapse prevention, over a four-month period. Over the course of the study period, participants opened A-CHESS on average of 62% of the days that they had the app. Social networking tools were the most utilized services. The study results suggest that drug court participants will make regular use of a recovery support app. This pilot study sought to find out if addicted offenders in a drug court program would use a mobile application to support and manage their recovery.

  13. Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

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    Matthew Arentz

    Full Text Available INTRODUCTION: Rapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB. However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection. METHODS: We searched MEDLINE, Embase and the Cochrane Library through January 1, 2012. For each rapid test, we determined pooled sensitivity and specificity estimates using a hierarchical random effects model. Predictive values of the tests were determined at different prevalence rates of rifampicin resistance and MDR-TB. RESULTS: We identified 60 publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI assay, Nitrate Reductase Assay (NRA and MODS tests: for all tests, negative predictive values were high when rifampicin resistance prevalence was ≤ 30%. However, positive predictive values were considerably reduced for the INNO-LiPA Rif. TB assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was < 5%. LIMITATIONS: In many studies, it was unclear whether patient selection or index test performance could have introduced bias. In addition, we were unable to evaluate critical concentration thresholds for the colorimetric tests. DISCUSSION: Rapid tests for rifampicin resistance alone cannot accurately predict rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin resistance. However, in areas with a high prevalence of rifampicin resistance and MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.

  14. Nevirapine patch testing in Thai human immunodeficiency virus infected patients with nevirapine drug hypersensitivity.

    Science.gov (United States)

    Prasertvit, Piyatida; Chareonyingwattana, Angkana; Wattanakrai, Penpun

    2017-08-06

    Antiretroviral drug hypersensitivity in HIV patients is common. Publications have shown that Abacavir (ABC) patch testing is useful in confirming ABC hypersensitivity in 24-50% of cases with a 100% sensitivity of HLA-B*5701 in patch test positive cases. However, Nevirapine (NVP) patch testing has not been reported. (1) To evaluate the usefulness and safety of NVP patch testing in Thai HIV patients with NVP hypersensitivity. (2) To assess the correlation of positive patch tests with HLA-B*3505. Patients were classified into two groups: (1) study group of 20 HIV NVP hypersensitivity patients and (2) control group of 15 volunteers without NVP hypersensitivity. Both groups were patch tested with purified and commercialized form of NVP in various vehicles. Two HIV patients with NVP hypersensitivity were patch test positive. All controls tested negative. Three HIV patients were positive for HLA-B*3505 and the two patients with positive patch testing were both HLA-B*3505 positive. NVP patch testing in Thai HIV patients is safe and can be used to help confirm the association between NVP and hypersensitivity skin reactions. NVP patch test results significantly correlated with HLA-B*3505. The sensitivity of HLA-B*3505 for positive patch test was 100%. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Changes in gene expression induced by aromatic amine drugs: testing the danger hypothesis.

    Science.gov (United States)

    Ng, Winnie; Uetrecht, Jack

    2013-01-01

    Virtually all drugs that contain a primary aromatic amine are associated with a high incidence of idiosyncratic drug reactions (IDRs), suggesting that this functional group has biological effects that may be used as biomarkers to predict IDR risk. Most IDRs exhibit evidence of immune involvement and the ability of aromatic amines to form reactive metabolites and redox cycle may be responsible for initiation of an immune response through induction of cell stress, as postulated by the Danger Hypothesis. If true, danger signals could be biomarkers of IDR risk. A previous attempt to test the Danger Hypothesis found that sulfamethoxazole (SMX), the only aromatic amine tested, was also the only drug not associated with an increase of cell stress genes in mice. To ensure that these observations were not species-specific, and to determine biomarkers of IDR risk common to aromatic amines, rats were treated with SMX and two other aromatic amine drugs, dapsone (DDS) and aminoglutethimide (AMG), and hepatic gene expression was determined using microarrays. As in mice, SMX induced minimal gene changes in the rat, and none indicated cell stress, whereas DDS and AMG induced several changes including up-regulation of enzymes such as aldo-keto reductase, glutathione-S-transferase, and aldehyde dehydrogenase, which may represent danger signals. Early insulin-induced hepatic gene (Eiih) was up-regulated by all three drugs. Some mRNA changes were observed in the Keap-1-Nrf2-ARE pathway; however, the pattern was significantly different for each drug. Overall, the most salient finding was that the changes in the liver were minimal, even though aromatic amines cause a high incidence of IDRs. The liver generates a large number of reactive species; however, the ability of aromatic amines to be bioactivated by cells of the immune system may be why they cause a high incidence of IDRs.

  16. Drug testing at the 10th Asian Games and 24th Seoul Olympic Games.

    Science.gov (United States)

    Park, J; Park, S; Lho, D; Choo, H P; Chung, B; Yoon, C; Min, H; Choi, M J

    1990-01-01

    Drug testing (doping test) procedures in the 1986 10th Asian Olympic Games and 1988 24th Seoul Olympic Games are reported. The International Olympic Committee Medical Commission (IOC-MC) conducted its first doping tests at the 1968 Olympics in Grenoble. With the guidance of the International Olympic Committee (IOC), the Olympic Council of Asia (OCA) introduced doping tests at the 1986 10th Asian Olympic Games in Seoul, Korea, September 21st to October 5th, 1986. 585 samples were tested at the Doping Control Center, Korea Advanced Institute of Science and Technology (DCC/KAIST), for stimulants, narcotics, anabolic steroids, and beta-blockers by gas chromatography/mass spectrometry, high pressure liquid chromatography, and fluorescence polarization immunoassay. These tests covered about 100 different drugs and another 400 as metabolites in addition to pharmacologically related substances. For the Seoul Olympic Games from September 17 to October 2, 1988, the IOC-MC with the DCC/KAIST conducted doping tests on 1601 samples for stimulants, narcotics, beta-blockers, diuretics, and anabolic steroids using GC, HPLC, GC/MSD, GC/MS, LC/MS, and TDx.

  17. Pediatric Exposure to Drugs of Abuse by Hair Testing: Monitoring 15 Years of Evolution in Spain

    Directory of Open Access Journals (Sweden)

    Simona Pichini

    2014-08-01

    Full Text Available Hair testing is a useful tool to investigate the prevalence of unsuspected chronic exposure to drugs of abuse in pediatric populations and it has been applied to three different cohorts of children from Barcelona, Spain along fifteen years to evaluate eventual changes in this exposure. Children were recruited from three independent studies performed at Hospital del Mar (Barcelona, Spain and approved by the local Ethics Committee. Hair samples were collected from the first 187 children cohort (around 4 years of age in 1998, from the second 90 children cohort (1.5–5 years of age in 2008 and from the third 114 children cohort (5–14 years of age in 2013. Hair samples were analysed for the presence of opiates, cocaine, amphetamines, and cannabis by validated methodologies using gas or liquid chromatography-mass spectrometry. Familiar sociodemographics and eventual consumption of drugs of abuse by parents, and caregivers were recorded. Hair samples from 24.6% children in 1998 were positive for any drug of abuse (23.0% cocaine, 25.5% in 2008 (23.3% cocaine, and 28.1% in 2013 (20.1% cocaine and 11.4% cannabis. In none of the cohorts, parental sociodemographics were associated with children exposure to drugs of abuse. The results of the three study cohorts demonstrated a significant prevalence of unsuspected pediatric exposure to drugs of abuse which mainly involved cocaine maintained along fifteen years in Barcelona, Spain. We recommend to be aware about unsuspected passive exposure to drugs of abuse in general population and to use general or selected hair screening to disclose exposure to drugs of abuse in children from risky environments to provide the basis for specific social and health interventions.

  18. A standalone perfusion platform for drug testing and target validation in micro-vessel networks.

    Science.gov (United States)

    Zhang, Boyang; Peticone, Carlotta; Murthy, Shashi K; Radisic, Milica

    2013-01-01

    Studying the effects of pharmacological agents on human endothelium includes the routine use of cell monolayers cultivated in multi-well plates. This configuration fails to recapitulate the complex architecture of vascular networks in vivo and does not capture the relationship between shear stress (i.e. flow) experienced by the cells and dose of the applied pharmacological agents. Microfluidic platforms have been applied extensively to create vascular systems in vitro; however, they rely on bulky external hardware to operate, which hinders the wide application of microfluidic chips by non-microfluidic experts. Here, we have developed a standalone perfusion platform where multiple devices were perfused at a time with a single miniaturized peristaltic pump. Using the platform, multiple micro-vessel networks, that contained three levels of branching structures, were created by culturing endothelial cells within circular micro-channel networks mimicking the geometrical configuration of natural blood vessels. To demonstrate the feasibility of our platform for drug testing and validation assays, a drug induced nitric oxide assay was performed on the engineered micro-vessel network using a panel of vaso-active drugs (acetylcholine, phenylephrine, atorvastatin, and sildenafil), showing both flow and drug dose dependent responses. The interactive effects between flow and drug dose for sildenafil could not be captured by a simple straight rectangular channel coated with endothelial cells, but it was captured in a more physiological branching circular network. A monocyte adhesion assay was also demonstrated with and without stimulation by an inflammatory cytokine, tumor necrosis factor-α.

  19. [Equivalence studies of pravastatin original and generic drugs by dissolution test].

    Science.gov (United States)

    Nakauchi, Takao; Takeuchi, Ena; Okamoto, Takuya; Teramoto, Katsuya; Nozaki, Aoi; Seko, Fuko; Yuminoki, Kayo; Katakawa, Junichi; Hashimoto, Naofumi

    2012-01-01

    There are various opinions regarding the different functions of original and generic drugs. We used the paddle method to perform dissolution tests on pravastatin sodium tablets (10 mg) to investigate the causes for these differences. We used water and buffer solutions adjusted to pH 1.2 (JP1) and pH 6.8 (JP2), which are described in the Japanese Pharmacopoeia. The pravastatin concentration was measured by UV spectroscopy and HPLC. There were significant differences in the percentages dissolved of original and generic drugs after 5 and 10 min. On the other hand, the dissolution behaviors using water and JP2 measured by HPLC were similar to the results obtained by UV spectroscopy. However, the percentage dissolved of pravastatin using JP1 decreased with time because pravastatin degraded in JP1. There were also significant differences in the pravastatin concentrations of the original and generic drugs at 5, 15, 30, and 45 min. Based on the above results, since the original drug has a slower dissolution rate than the generic drugs, it is necessary to be cautious about the degradation of pravastatin in the stomach and the bioavailability of pravastatin due to the different dissolution rates and the different residual amount of pravastatin in the stomach.

  20. Not to catch but to deter : simple, less intrusive drug and alcohol tests can improve workplace safety

    Energy Technology Data Exchange (ETDEWEB)

    Stastny, P.

    2009-04-15

    Canadian employees who test positive for drug use have access to a wide range of substance counselling and rehabilitation options. As a result of Canadian human right legislation, drug dependence is considered a disability, and Canadian employers are required to accommodate the employee and retain their position when they are deemed fit for work. While Alberta is considered an employee-friendly province, the oil and gas industry has significant hazards that require a lucid and attentive workforce. As a result, Alberta courts approved pre-employment drug testing in a recent court case. The decision involved an employee who tested positive for traces of marijuana. After being fired, the employee filed a complaint. Although the Queen's Bench decided in favour of the employee, the Alberta Court of Appeal stated that the company's pre-employment drug testing policy did not discriminate against the employee on the basis of a disability. Drug use amongst construction workers and employees in the energy industry has now reached upwards of 24 per cent. While urine testing is a commonly used drug testing method, oral fluid testing is now being more widely adopted in industry. Oral fluids can be used to detect recent drug and alcohol use rather than historical use and can be conducted in the presence of a test administrator. It was concluded that the aim of drug and alcohol testing is to deter substance abuse on the job. 3 figs.

  1. Human engineered heart tissue as a model system for drug testing.

    Science.gov (United States)

    Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

    2016-01-15

    Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening.

  2. Expanding analytical options in sports drug testing: Mass spectrometric detection of prohibited substances in exhaled breath.

    Science.gov (United States)

    Thevis, Mario; Krug, Oliver; Geyer, Hans; Schänzer, Wilhelm

    2017-08-15

    Continuously refining and advancing the strategies and methods employed in sports drug testing is critical for efficient doping controls. Besides improving and expanding the spectrum of target analytes, alternative test matrices have warranted in-depth evaluation as they commonly allow for minimal-/non-invasive and non-intrusive sample collection. In this study, the potential of exhaled breath (EB) as doping control specimen was assessed. EB collection devices employing a non-woven electret-based air filter unit were used to generate test specimens, simulating a potential future application in doping controls. A multi-analyte sports drug testing approach configured for a subset of 12 model compounds that represent specific classes of substances prohibited in sports (anabolic agents, hormone and metabolic modulators, stimulants, and beta-blockers) was established using unispray liquid chromatography/tandem mass spectrometry (LC/MS/MS) and applied to spiked and elimination study EB samples. The test method was characterized concerning specificity, assay imprecision, and limits of detection. The EB collection device allowed for retaining and extracting all selected model compounds from the EB aerosol. Following elution and concentration, LC/MS/MS analysis enabled detection limits between 5 and 100 pg/filter and imprecisions ranging from 3% to 20% for the 12 selected model compounds. By means of EB samples from patients and participants of administration studies, the elimination of relevant compounds and, thus, their traceability in EB for doping control purposes, was investigated. Besides stimulants such as methylhexaneamine and pseudoephedrine, also the anabolic-androgenic steroid dehydrochloromethyltestosterone, the metabolic modulator meldonium, and the beta-blocker bisoprolol was detected in exhaled breath. The EB aerosol has provided a promising proof-of-concept suggesting the expansion of this testing strategy as a complement to currently utilized sports drug

  3. Two preclinical tests to evaluate anticancer activity and to help validate drug candidates for clinical trials

    Science.gov (United States)

    López-Lázaro, Miguel

    2015-01-01

    Current approaches to assessing preclinical anticancer activity do not reliably predict drug efficacy in cancer patients. Most of the compounds that show remarkable anticancer effects in preclinical models actually fail when tested in clinical trials. We blame these failures on the complexity of the disease and on the limitations of the preclinical tools we require for our research. This manuscript argues that this lack of clinical response may also be caused by poor in vitro and in vivo preclinical designs, in which cancer patients' needs are not fully considered. Then, it proposes two patient-oriented tests to assess in vitro and in vivo anticancer activity and to help validate drug candidates for clinical evaluation. PMID:25859551

  4. [Effect of psychotropic drugs on activity of anticonvulsants in maximal electroshock test].

    Science.gov (United States)

    Alikina, N A; Tregubov, A L; Kotegov, V P

    2010-08-01

    The effect ofpsychotropic drugs on the pharmacological properties of anticonvulsants was studied on white mice under maximal electroshock (ME) test conditions. Changes in the anticonvulsant effect of phenobarbital, diphenin, carbamazepine, hexamidine were traced upon their joint administration with psychotropic drugs, including piracetam, aminalon, amitriptyline, imizine, levomepromazine, and lithium oxybutyrate. An important result of research is the fact, that in no one of combinations the basic pharmacological effect of anticonvulsants was decreased. Based on the results of experiments, the most rational combinations of anticonvulsants with psychotropic preparations were revealed as manifested in the ME test. As criterion of rational combination was the increase in the activity of anticonvulsants and reduction of their toxicity in combination or at least invariance of this parameter. Rational combinations include (i) phenobarbital with piracetam, amitriptyline, levomepromazine, and lithium oxybutyrate; (ii) carbamazepine with piracetam; and (iii) hexamidine with amitriptyline, levomepromazine and imizine.

  5. 77 FR 2935 - Revision to Chemical Testing Regulations for Mariners and Marine Employers

    Science.gov (United States)

    2012-01-20

    ... Officers (MROs) Reporting Non-Negative Test Results Directly to the Coast Guard A non-negative specimen is.../or invalid. (1) For MROs, how would a requirement to report all non-negative test results to the Coast Guard (in addition to the marine employer) impact your business? (2) For MROs, what would be...

  6. The Balance between Student Drug Testing and Fourth Amendment Rights in Response to Board of Education v. Earls.

    Science.gov (United States)

    Edmonson, Stacey L.

    This report--part of a collection of 54 papers from the 48th annual conference of the Education Law Association held in November 2002-- discusses student drug testing in Texas public schools. It contains the results of a 2001 study of student drug-testing policies in all 1,056 Texas public-school districts. In response to the Supreme Court's June…

  7. 49 CFR Appendix H to Part 40 - DOT Drug and Alcohol Testing Management Information System (MIS) Data Collection Form

    Science.gov (United States)

    2010-10-01

    ..., App. H Appendix H to Part 40—DOT Drug and Alcohol Testing Management Information System (MIS) Data... 49 Transportation 1 2010-10-01 2010-10-01 false DOT Drug and Alcohol Testing Management Information System (MIS) Data Collection Form H Appendix H to Part 40 Transportation Office of the...

  8. 49 CFR 40.321 - What is the general confidentiality rule for drug and alcohol test information?

    Science.gov (United States)

    2010-10-01

    ... Release of Information § 40.321 What is the general confidentiality rule for drug and alcohol test... explicitly authorize or require the transmission of information in the course of the drug or alcohol testing... 49 Transportation 1 2010-10-01 2010-10-01 false What is the general confidentiality rule for...

  9. Comparative study on genotypic and phenotypic second-line drug resistance testing of Mycobacterium tuberculosis complex isolates.

    NARCIS (Netherlands)

    Ingen, J. van; Simons, S.O.; Zwaan, R. de; Laan, T. van der; Kamst-van Agterveld, M.; Boeree, M.J.; Soolingen, D. van

    2010-01-01

    The mycobacterium growth indicator tube (MGIT960) automated liquid medium testing method is becoming the international gold standard for second-line drug susceptibility testing of multidrug- and extensively drug-resistant Mycobacterium tuberculosis complex isolates. We performed a comparative study

  10. Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives.

    Science.gov (United States)

    Schön, T; Miotto, P; Köser, C U; Viveiros, M; Böttger, E; Cambau, E

    2017-03-01

    Drug-resistance testing, or antimicrobial susceptibility testing (AST), is mandatory for Mycobacterium tuberculosis in cases of failure on standard therapy. We reviewed the different methods and techniques of phenotypic and genotypic approaches. Although multiresistant and extensively drug-resistant (MDR/XDR) tuberculosis is present worldwide, AST for M. tuberculosis (AST-MTB) is still mainly performed according to the resources available rather than the drug-resistance rates. Phenotypic methods, i.e. culture-based AST, are commonly used in high-income countries to confirm susceptibility of new cases of tuberculosis. They are also used to detect resistance in tuberculosis cases with risk factors, in combination with genotypic tests. In low-income countries, genotypic methods screening hot-spot mutations known to confer resistance were found to be easier to perform because they avoid the culture and biosafety constraint. Given that genotypic tests can rapidly detect the prominent mechanisms of resistance, such as the rpoB mutation for rifampicin resistance, we are facing new challenges with the observation of false-resistance (mutations not conferring resistance) and false-susceptibility (mutations different from the common mechanism) results. Phenotypic and genotypic approaches are therefore complementary for obtaining a high sensitivity and specificity for detecting drug resistances and susceptibilities to accurately predict MDR/XDR cure and to gather relevant data for resistance surveillance. Although AST-MTB was established in the 1960s, there is no consensus reference method for MIC determination against which the numerous AST-MTB techniques can be compared. This information is necessary for assessing in vitro activity and setting breakpoints for future anti-tuberculosis agents. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. A Low Cost/Low Power Open Source Sensor System for Automated Tuberculosis Drug Susceptibility Testing

    OpenAIRE

    Kyukwang Kim; Hyeong Keun Kim; Hwijoon Lim; Hyun Myung

    2016-01-01

    In this research an open source, low power sensor node was developed to check the growth of mycobacteria in a culture bottle with a nitrate reductase assay method for a drug susceptibility test. The sensor system reports the temperature and color sensor output frequency change of the culture bottle when the device is triggered. After the culture process is finished, a nitrite ion detecting solution based on a commercial nitrite ion detection kit is injected into the culture bottle by a syring...

  12. Basophil activation test in the study of food and drug hypersensitivity reactions

    OpenAIRE

    Carrapatoso, I; Cadinha, S; Sanz, ML

    2005-01-01

    The increase in the prevalence of adverse reactions to foods and drugs represents a constant challenge to the development of new methods of diagnosis. A meta-analysis on published studies concerning the clinical usefulness of the Basophil activation test (BAT) in these reactions was performed. High sensibilities and specificities can be achieved if certain technical requirements are observed. BAT results have a positive and high significant correlations with other routine diagnostic ...

  13. An overview of forensic drug testing methods and their suitability for harm reduction point-of-care services.

    Science.gov (United States)

    Harper, Lane; Powell, Jeff; Pijl, Em M

    2017-07-31

    Given the current opioid crisis around the world, harm reduction agencies are seeking to help people who use drugs to do so more safely. Many harm reduction agencies are exploring techniques to test illicit drugs to identify and, where possible, quantify their constituents allowing their users to make informed decisions. While these technologies have been used for years in Europe (Nightlife Empowerment & Well-being Implementation Project, Drug Checking Service: Good Practice Standards; Trans European Drugs Information (TEDI) Workgroup, Factsheet on Drug Checking in Europe, 2011; European Monitoring Centre for Drugs and Drug Addiction, An Inventory of On-site Pill-Testing Interventions in the EU: Fact Files, 2001), they are only now starting to be utilized in this context in North America. The goal of this paper is to describe the most common methods for testing illicit substances and then, based on this broad, encompassing review, recommend the most appropriate methods for testing at point of care.Based on our review, the best methods for point-of-care drug testing are handheld infrared spectroscopy, Raman spectroscopy, and ion mobility spectrometry; mass spectrometry is the current gold standard in forensic drug analysis. It would be prudent for agencies or clinics that can obtain the funding to contact the companies who produce these devices to discuss possible usage in a harm reduction setting. Lower tech options, such as spot/color tests and immunoassays, are limited in their use but affordable and easy to use.

  14. Illicit drugs, testing, prevention and work in France: ethical and legal issues.

    Science.gov (United States)

    Fantoni-Quinton, Sophie; Bossu, Bernard; Morgenroth, Thomas; Frimat, Paul

    2010-09-01

    The use of illicit drugs in the workplace raises issues pertaining to prevention and safety and the responsibility of the various members of staff. It also brings into question the interface between work and private life. If employees are in theory responsible for their own safety and risk heavy penalties in the event of the consumption of illicit drugs in the workplace, such behaviour has to be proved. In reality, the worker can only be partially and marginally held liable, given the fact that the employer is prohibited from infringing on their rights and liberties (restrictions on the searching of their personal belongings and lockers as well as on the carrying out of breath testing and saliva testing under restrictive conditions). Employers have for their part a broader range of responsibilities and, above all, an absolute obligation to achieve specific goals in terms of health and safety resulting in the need to take action. In accordance with the International Labour Organization recommendations, European and national legislation, the employer has to implement a suitable preventive policy. However, where is the balance between prevention and repression? Very few studies have raised these issues and our aim is to precisely situate the place of drug testing in the employer's repressive arsenal in France and to try to answer the legal and ethical issues raised. Thus, for example, repression can only be acceptable when it deals with moderate and non-addicted users, or it could be tantamount to discrimination.

  15. Visual features as stepping stones toward semantics: Explaining object similarity in IT and perception with non-negative least squares.

    Science.gov (United States)

    Jozwik, Kamila M; Kriegeskorte, Nikolaus; Mur, Marieke

    2016-03-01

    Object similarity, in brain representations and conscious perception, must reflect a combination of the visual appearance of the objects on the one hand and the categories the objects belong to on the other. Indeed, visual object features and category membership have each been shown to contribute to the object representation in human inferior temporal (IT) cortex, as well as to object-similarity judgments. However, the explanatory power of features and categories has not been directly compared. Here, we investigate whether the IT object representation and similarity judgments are best explained by a categorical or a feature-based model. We use rich models (>100 dimensions) generated by human observers for a set of 96 real-world object images. The categorical model consists of a hierarchically nested set of category labels (such as "human", "mammal", and "animal"). The feature-based model includes both object parts (such as "eye", "tail", and "handle") and other descriptive features (such as "circular", "green", and "stubbly"). We used non-negative least squares to fit the models to the brain representations (estimated from functional magnetic resonance imaging data) and to similarity judgments. Model performance was estimated on held-out images not used in fitting. Both models explained significant variance in IT and the amounts explained were not significantly different. The combined model did not explain significant additional IT variance, suggesting that it is the shared model variance (features correlated with categories, categories correlated with features) that best explains IT. The similarity judgments were almost fully explained by the categorical model, which explained significantly more variance than the feature-based model. The combined model did not explain significant additional variance in the similarity judgments. Our findings suggest that IT uses features that help to distinguish categories as stepping stones toward a semantic representation

  16. Biohybrid Membrane Systems and Bioreactors as Tools for In Vitro Drug Testing.

    Science.gov (United States)

    Salerno, Simona; Bartolo, Loredana De

    2017-01-01

    In drug development, in vitro human model systems are absolutely essential prior to the clinical trials, considering the increasing number of chemical compounds in need of testing, and, keeping in mind that animals cannot predict all the adverse human health effects and reactions, due to the species-specific differences in metabolic pathways. The liver plays a central role in the clearance and biotransformation of chemicals and xenobiotics. In vitro liver model systems by using highly differentiated human cells could have a great impact in preclinical trials. Membrane biohybrid systems constituted of human hepatocytes and micro- and nano-structured membranes, represent valuable tools for studying drug metabolism and toxicity. Membranes act as an extracellular matrix for the adhesion of hepatocytes, and compartmentalise them in a well-defined physical and chemical microenvironment with high selectivity. Advanced 3-D tissue cultures are furthermore achieved by using membrane bioreactors (MBR), which ensure the continuous perfusion of cells protecting them from shear stress. MBRs with different configurations allow the culturing of cells at high density and under closely monitored high perfusion, similarly to the natural liver. These devices that promote the long-term maintenance and differentiation of primary human hepatocytes with preserved liver specific functions can be employed in drug testing for prolonged exposure to chemical compounds and for assessing repeated-dose toxicity. The use of primary human hepatocytes in MBRs is the only system providing a faster and more cost-effective method of analysis for the prediction of in vitro human drug metabolism and enzyme induction alternative and/or complementary to the animal experimentation. In this paper, in vitro models for studying drug metabolism and toxicity as advanced biohybrid membrane systems and MBRs will be reviewed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Investigation of drugs responsible for perioperative anaphylactic reactions using cellular allergen stimulation test

    Institute of Scientific and Technical Information of China (English)

    Xin Xin; Zou Yi; Xing Lijiao; Yin Jia; Gu Jianqing; Wang Zixi; Huang Yuguang

    2014-01-01

    Background Anaphylactic reactions during anesthesia and operation are common and life threatening.Follow-up investigation is necessary for avoiding potential re-exposure of the patients to the offending drugs.The purpose of this study was to assess cellular allergen stimulation test (CAST) as a diagnostic instrument in immunoglobulin E (IgE)-and non-lgE-mediated anaphylactic reactions.Methods This study included 25 patients who developed perioperative anaphylactic reactions and 10 subjects that tolerated anesthetics and other drugs during perioperative period from September 2009 to October 2013 in Peking Union Medical College Hospital.We performed skin tests and flow cytometric analysis of basophil activation-based CAST in all subjects.Results Of the 25 patients,17 had IgE-mediated anaphylactic reactions (causative agent identified by skin tests) and 8 had non-lgE-mediated anaphylactic reactions (negative skin tests).CAST showed a sensitivity of 42.9%,specificity of 90%,and negative predictive value of 80.6% for neuromuscular blocking agents.Conclusions CAST may be useful for the diagnosis of anaphylactic reactions during perioperative period.Our findings call for further investigation to increase the sensitivity of the test.

  18. Primary HIV drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing.

    Science.gov (United States)

    Oette, Mark; Kaiser, Rolf; Däumer, Martin; Petch, Ruth; Fätkenheuer, Gerd; Carls, Horst; Rockstroh, Jürgen Kurt; Schmalöer, Dirk; Stechel, Jürgen; Feldt, Torsten; Pfister, Herbert; Häussinger, Dieter

    2006-04-15

    Primary HIV drug resistance has been associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART) in several trials. The aim of the study was to assess the efficacy of first-line HAART guided by resistance testing. In a prospective multicenter study in the state of Nordrhein-Westfalen, Germany, chronically HIV-infected patients underwent genotypic resistance testing and were monitored for 48 weeks after initiation of HAART. Primary drug resistance was found in 30 of 269 patients entering the study between January 2001 and December 2003 [11.2%; 95% confidence interval, 7.4-14.9]. In intent-to-treat analysis, the proportion of patients with viral load below 50 copies/mL after 24 and 48 weeks was 70.0% and 66.7%, respectively, in patients with resistance and 74.1% and 73.6%, respectively, in patients without (P = 0.66 and 0.51). In on-treatment analysis, the proportions were 80.8% and 83.3%, respectively, in patients with resistance and 81.9% and 85.0%, respectively, in patients without (P= 0.79 and 0.77). These results were also valid considering a detection limit of 400 copies/mL. The prevalence of primary drug resistance was 11.2% in chronically HIV-infected patients. HAART guided by resistance testing had similar efficacy in patients with primary drug resistance as compared with patients with wild-type virus. Based on these facts, resistance-adapted first-line HAART is suggested as routine practice.

  19. High throughput analysis of drugs of abuse in hair by combining purposely designed sample extraction compatible with immunometric methods used for drug testing in urine.

    Science.gov (United States)

    de la Torre, R; Civit, E; Svaizer, F; Lotti, A; Gottardi, M; Miozzo, M

    2010-03-20

    Drug testing in hair usually requires a rather complex sample treatment before drugs are amenable to analysis by either immunological and/or chromatographic coupled to mass spectrometry methods. Immunological methods applied are usually dedicated to hair analysis as analytes present in this matrix are not always the same present in urine. Comedical s.a.s. laboratories recently commercialized reagents (VMA-T) purposely designed for hair sample treatment which are compatible with current immunometric methods used for urine drug testing. This is possible as some analytes (6-MAM and cocaine) present in hair after sample treatment are converted to those detected in urine (morphine and benzoylecgonine). A correlation study for several drug classes performed in two laboratories with 32 clinical and 12 spiked drug free (controls) hair samples shows that implementation of the method on clinical chemistry analyzers is easy and that results obtained by different operators and instruments are comparable and reproducible. The main advantage of VMA-T method is the possibility to simultaneously extract from hair main drug classes, in a period of time lower than 2h and its compatibility with immunological methods applied in urine drug testing.

  20. A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis.

    Science.gov (United States)

    Yu, Ruoxing; Miyamura, Norio; Okamoto-Uchida, Yoshimi; Arima, Norie; Ishigami-Yuasa, Mari; Kagechika, Hiroyuki; Nishina, Hiroshi

    2015-01-01

    Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA) formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat.) D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST) that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium.

  1. A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Ruoxing Yu

    Full Text Available Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat. D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium.

  2. Upgrading HepG2 cells with adenoviral vectors that encode drug-metabolizing enzymes: application for drug hepatotoxicity testing.

    Science.gov (United States)

    Gómez-Lechón, M José; Tolosa, Laia; Donato, M Teresa

    2017-02-01

    Drug attrition rates due to hepatotoxicity are an important safety issue considered in drug development. The HepG2 hepatoma cell line is currently being used for drug-induced hepatotoxicity evaluations, but its expression of drug-metabolizing enzymes is poor compared with hepatocytes. Different approaches have been proposed to upgrade HepG2 cells for more reliable drug-induced liver injury predictions. Areas covered: We describe the advantages and limitations of HepG2 cells transduced with adenoviral vectors that encode drug-metabolizing enzymes for safety risk assessments of bioactivable compounds. Adenoviral transduction facilitates efficient and controlled delivery of multiple drug-metabolizing activities to HepG2 cells at comparable levels to primary human hepatocytes by generating an 'artificial hepatocyte'. Furthermore, adenoviral transduction enables the design of tailored cells expressing particular metabolic capacities. Expert opinion: Upgraded HepG2 cells that recreate known inter-individual variations in hepatic CYP and conjugating activities due to both genetic (e.g., polymorphisms) or environmental (e.g., induction, inhibition) factors seems a suitable model to identify bioactivable drug and conduct hepatotoxicity risk assessments. This strategy should enable the generation of customized cells by reproducing human pheno- and genotypic CYP variability to represent a valuable human hepatic cell model to develop new safer drugs and to improve existing predictive toxicity assays.

  3. Racial/ethnic differences in report of drug testing practices at the workplace level in the U.S.

    Science.gov (United States)

    Becker, William C; Meghani, Salimah; Tetrault, Jeanette M; Fiellin, David A

    2014-01-01

    It is unknown whether racial/ethnic differences in report of workplace drug testing persist when analyzed within and across various occupations. We sought to examine the association between worker demographics, workplace characteristics, and report of employment in a workplace that performs drug testing. We performed a cross-sectional study of the 2008-2010 National Survey on Drug Use and Health examining the relationship between race/ethnicity and report of workplace drug testing among employed, white, black, or Hispanic respondents ≥18 years old. In logistic regression analysis, we adjusted for demographic, occupational, and other relevant variables and performed stratified analyses among three specific occupations. Among 69,163 respondents, 48.2% reported employment in a workplace that performs drug testing. On multivariable analysis, younger age, male sex, black race, income greater than $20,000, completion of high school and non-urban residence were associated with report of drug testing at one's workplace among the full sample as were non-white collar occupation, work in medium or large workplace, and absence of other substance abuse/dependence. In stratified analyses, black race was associated with report of workplace level drug testing among executive/administrative/managerial/financial workers and technicians/related support occupations; Hispanic ethnicity was associated with the outcome among technicians/related support occupations. Racial/ethnic differences in report of workplace drug testing exist within and across various occupations. These differences have important public health implications deserving further study. Increased report of drug testing where racial/ethnic minorities work highlights the potential bias that can be introduced when drug testing policies are not implemented in a universal fashion. © American Academy of Addiction Psychiatry.

  4. Structured evaluation of rodent behavioral tests used in drug discovery research

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2014-07-01

    Full Text Available A large variety of rodent behavioral tests are currently being used to evaluate traits such as sensory-motor function, social interactions, anxiety-like and depressive-like behavior, substance dependence and various forms of cognitive function. Most behavioral tests have an inherent complexity, and their use requires consideration of several aspects such as the source of motivation in the test, the interaction between experimenter and animal, sources of variability, the sensory modality required by the animal to solve the task as well as costs and required work effort. Of particular importance is a test’s validity because of its influence on the chance of successful translation of preclinical results to clinical settings. High validity may, however, have to be balanced against practical constraints and there are no behavioral tests with optimal characteristics. The design and development of new behavioral tests is therefore an ongoing effort and there are now well over one hundred tests described in the contemporary literature. Some of them are well established following extensive use, while others are novel and still unproven. The task of choosing a behavioral test for a particular project may therefore be daunting and the aim of the present review is to provide a structured way to evaluate rodent behavioral tests aimed at drug discovery research.

  5. Counselors' Clinical Use of Definitive Drug Testing Results in Their Work with Substance-Use Clients: a Qualitative Study.

    Science.gov (United States)

    Rzetelny, Adam; Zeller, Barbara; Miller, Nicholas; City, Kathy Egan; Kirsh, Kenneth L; Passik, Steven D

    We conducted a psychotherapeutic examination of the use of definitive drug testing (liquid chromatography with tandem mass spectrometry) in the treatment of substance use disorders (SUD). Employing a generic qualitative method (Caelli et al. in International Journal of Qualitative Methods, 2(2), 2003; Merriam, 2009) we asked SUD counselors to provide narratives about cases where drug testing had revealed new or unexpected information about clients' drug-taking behaviors. Semi-structured interviews with 12 SUD counselors were conducted by phone and analyzed for themes derived from the literature. These counselors reported many new positive drug tests in clients previously believed to be adherent with treatment. Key themes assessed in counselors' narratives included initial client denial that was often followed by later acknowledgement of relapse and increased motivation, at times presenting new opportunities for clients to engage in treatment and enhance the therapeutic alliance. These results suggest that definitive drug testing can be used in a non-stigmatizing and therapeutic manner.

  6. Workplace drug testing and alcohol policy in Italy; there is still a long way to go.

    Science.gov (United States)

    Rosso, Gian Luca; Perotto, Massimo; Feola, Mauro; Caramella, Michele

    2014-09-01

    The effectiveness of workplace drug testing (WDT) in Italy has recently been questioned, while very little is known about the real consumption of alcoholic beverages among workers performing hazardous jobs, such as professional drivers (PDs). The aim of this study is to investigate the modality and frequency of WDT execution and of alcohol consumption in the above category. Anonymous questionnaires were used to collect information. Four hundred and ninety-seven questionnaires were collected; 50.1% declared that they know well in advance when they will be subjected to screening tests for drugs, while 19.5% claimed they have never been subjected to such a test. The greater the number of employees in a company, the greater the likelihood that the tests are performed with a genuinely surprise effect [odds ratio (OR) 2.41, 5.39 and 9.07, respectively, for businesses with 5-14 employees, 15-50 and more than 50, compared with companies with less than 5 employees, p restaurants (OR 4.27, CI 1.19-15.42 p < 0.05). Fifteen percent of the participants have an AUDIT C score ≥ 5. In conclusion WDT is largely ineffective, particularly in small businesses. The high percentage of PDs who claim to drink during working hours and who are hazardous drinkers requires a further strengthening of prevention strategies in this area. Copyright © 2013 John Wiley & Sons, Ltd.

  7. An alternative in vitro drug screening test using Leishmania amazonensis transfected with red fluorescent protein✩

    Science.gov (United States)

    Rocha, Marcele N.; Corrêa, Célia M.; Melo, Maria N.; Beverley, Stephen M.; Martins-Filho, Olindo Assis; Madureira, Ana Paula; Soares, Rodrigo P.

    2013-01-01

    Fluorescent and colorimetric reporter genes are valuable tools for drug screening models, since microscopy is labor intensive and subject to observer variation. In this work, we propose a fluorimetric method for drug screening using red fluorescent parasites. Fluorescent Leishmania amazonensis were developed after transfection with integration plasmids containing either red (RFP) or green fluorescent protein (GFP) genes. After transfection, wild-type (LaWT) and transfected (LaGFP and LaRFP) parasites were subjected to flow cytometry, macrophage infection, and tests of susceptibility to current antileishmanial agents and propranolol derivatives previously shown to be active against Trypanosoma cruzi. Flow cytometry analysis discriminated LaWT from LaRFP and LaGFP parasites, without affecting cell size or granulosity. With microscopy, transfection with antibiotic resistant genes was not shown to affect macrophage infectivity and susceptibility to amphotericin B and propranolol derivatives. Retention of fluorescence remained in the intracellular amastigotes in both LaGFP and LaRFP transfectants. However, detection of intracellular RFP parasites was only achieved in the fluorimeter. Murine BALB/c macrophages were infected with LaRFP parasites, exposed to standard (meglumine antimoniate, amphotericin B, Miltefosine, and allopurinol) and tested molecules. Although it was possible to determine IC50 values for 4 propranolol derivatives (1, 2b, 3, and 4b), all compounds were considered inactive. This study is the first to develop a fluorimetric drug screening test for L. amazonensis RFP. The fluorimetric test was comparable to microscopy with the advantage of being faster and not requiring manual counting. PMID:23312610

  8. Cognitive Motivations for Drug Use among Adolescents: Longitudinal Tests of Gender Differences and Predictors of Change in Drug Use.

    Science.gov (United States)

    Newcomb, Michael D.; And Others

    1988-01-01

    Examined cognitive motivations for alcohol and cannabis use among adolescents. Identified four factors for drug use. Boys were more motivated to use alcohol and cannabis for Social Cohesion and cannabis for Enhancing Positive Affect and Creativity than girls. Older, more than younger, adolescents used drugs to Reduce Negative Affect. All…

  9. Testing whether drugs that weaken norepinephrine signaling prevent or treat various types of cancer

    Directory of Open Access Journals (Sweden)

    Paul J Fitzgerald

    2009-12-01

    Full Text Available Paul J FitzgeraldThe Zanvyl Krieger Mind/Brain Institute, Solomon H. Snyder, Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USAAbstract: Recently, I put forth the hypothesis that the signaling molecule, norepinephrine (NE, is an etiological factor in a number of types of cancer. In this brief commentary, I summarize evidence that NE plays a role in cancer and describe details involved in testing the hypothesis in humans through epidemiological investigation of existing medical records of persons who have taken pharmaceutical drugs that affect NE. If NE plays an etiological role in cancers of a number of organs, then taking a single pharmaceutical drug (such as clonidine, prazosin, or propranolol that weakens NE signaling systemically, may simultaneously prevent or treat many different types of cancer, and this may represent a breakthrough in pharmaceutical prevention and possibly treatment of cancer.Keywords: norepinephrine, acetylcholine, cancer, clonidine, prazosin, propranolol

  10. HIV Testing in Non-Injection Drug Users: Prevalence and Associated Factors.

    Science.gov (United States)

    Alves Guimarães, Rafael; Lucchese, Roselma; Lara Fernandes, Inaina; Vera, Ivânia; Goulart Rodovalho, Aurélio; Alves Guimarães, Vanessa; Cristina Silva, Graciele; Lopes de Felipe, Rodrigo; Alexandre de Castro, Paulo; Martins Ferreira, Priscilla

    2017-05-24

    The objective of this study was to estimate the prevalence of and identify factors associated with lifetime testing for the human immunodeficiency virus (HIV) in non-injection drug users (NIDU). A cross-sectional study was conducted with 323 individuals in clinics for chemical dependency in the state of Goiás in the Central-West region of Brazil. Logistic regression analysis was used to identify factors associated with lifetime HIV testing. Testing for HIV was associated with age, female gender, crack use, history of sexually transmitted infections, acquaintance with people living with HIV/AIDS and/or who had died from AIDS, and history of having received some instruction on HIV/AIDS prevention methods. It was found that only 26.6% reported having access to the HIV rapid test. We concluded determinants for HIV testing must be taken into account when planning prevention and programming strategies. These include the widening of testing coverage among NIDU, educational health actions, establishment of links between sexually transmitted infection prevention services and addiction treatment services, and the use of rapid tests to help people who are in contact with the virus learn about their HIV status, enter treatment, and improve their quality of life.

  11. Seven years of workplace drug testing in Italy: A systematic review and meta-analysis.

    Science.gov (United States)

    Rosso, Gian Luca; Montomoli, Cristina; Morini, Luca; Candura, Stefano M

    2017-06-01

    In Italy, Workplace Drug Testing (WDT) has been compulsory by law for specific categories of workers since 2008, offering the opportunity to compare studies conducted within a single regulatory framework. The aims of this paper are to estimate the overall prevalence of WDT positivity (at screening survey) among Italian workers and evaluate the percentage of true and false positives at confirmation analysis. A systematic review and meta-analysis of the scientific literature on WDT in Italy from January 2008 to March 2015 was carried out, according to the MOOSE guidelines. A random effects model was utilized to calculate pooled prevalence. Potential sources of heterogeneity were explored using sensitivity test and subgroup analysis. The overall meta-analytical prevalence of positivity at WDT among Italian workers was 1.4% [95% confidence interval (CI) = 1.1-1.7%]. It was significantly lower among workers screened with an on-site test (1%; 95% CI = 0.5-1.5%), compared with a bench-top test (1.7%; 95% CI = 1.3-2.1%). Nine studies provided data on false positives at the screening test, with a combined prevalence estimate - calculated on positive cases - of 30% (95% CI = 16-44%). In Italy, the number of true positives at first-level workplace drug testing is low, while the frequency of false positives is relatively high. A revision of the Italian legislation on the subject seems advisable. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Functionality test for drug safety alerting in computerized physician order entry systems.

    Science.gov (United States)

    van der Sijs, Heleen; Bouamar, Rachida; van Gelder, Teun; Aarts, Jos; Berg, Marc; Vulto, Arnold

    2010-04-01

    To evaluate the functionality of drug safety alerting in hospital computerized physician order entry (CPOE) systems by a newly developed comprehensive test. Comparative evaluation of drug safety alerting quality in 6 different CPOEs used in Dutch hospitals, by means of 29 test items for sensitivity and 19 for specificity in offices of CPOE system vendors. Sensitivity and specificity were calculated for the complete test, and for the categories "within-order checks", "patient-specific checks", and "checks related to laboratory data and new patient conditions". Qualitative interviews with 16 hospital pharmacists evaluating missing functionality and corresponding pharmacy checks. Sensitivity ranged from 0.38 to 0.79 and specificity from 0.11 to 0.84. The systems achieved the same ranking for sensitivity as for specificity. Within-order checks and patient-specific checks were present in all systems; alert generation or suppression due to laboratory data and new patient conditions was largely absent. Hospital pharmacists unanimously rated checks on contra-indications (absent in 2 CPOEs) and dose regimens less than once a day (absent in 4 CPOEs) as important. Pharmacists' opinions were more divergent for other test items. A variety of pharmacy checks were used, and clinical rules developed, to address missing functionality. Our test revealed widely varying functionality and appeared to be highly discriminative. Basic clinical decision support was partly absent in two CPOEs. Hospital pharmacists did not rate all test items as important and tried to accommodate the lacking functionality by performing additional checks and developing clinical rules. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K.; Lal, Sham; Cundill, Bonnie

    2013-01-01

    BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial...... to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation...... of the cluster randomized trial. METHODS: A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider...

  14. Urine toxicology screen in multiple sleep latency test: the correlation of positive tetrahydrocannabinol, drug negative patients, and narcolepsy.

    Science.gov (United States)

    Dzodzomenyo, Samuel; Stolfi, Adrienne; Splaingard, Deborah; Earley, Elizabeth; Onadeko, Oluwole; Splaingard, Mark

    2015-01-15

    Drugs can influence results of multiple sleep latency tests (MSLT). We sought to identify the effect of marijuana on MSLT results in pediatric patients evaluated for excessive daytime sleepiness (EDS). This is a retrospective study of urine drug screens performed the morning before MSLT in 383 patients narcolepsy, 0% consistent with idiopathic hypersomnia, 29% other, and 29% normal. This was statistically different from those with (-) screens (24% narcolepsy, 20% idiopathic hypersomnia, 6% other, 50% normal), and those (+) for drugs other than THC (17% narcolepsy, 33% idiopathic hypersomnia, 4% other, 46% normal (p = 0.01). Six percent (6/93) of patients with MSLT findings consistent with narcolepsy were drug screen (+) for THC; 71% of patients with drug screen (+) for THC had multiple sleep onset REM periods (SOREMS). There were no (+) urine drug screens in patients narcolepsy or had multiple SOREMs. Drug screening is important in interpreting MSLT findings for children ≥13 years. © 2014 American Academy of Sleep Medicine.

  15. Drug susceptibility testing of clinical isolates of streptococci and enterococci by the Phoenix automated microbiology system

    Directory of Open Access Journals (Sweden)

    Sokeng Gertrude

    2007-05-01

    Full Text Available Abstract Background Drug resistance is an emerging problem among streptococcal and enterococcal species. Automated diagnostic systems for species identification and antimicrobial susceptibility testing (AST have become recently available. We evaluated drug susceptibility of clinical isolates of streptococci and enterococci using the recent Phoenix system (BD, Sparks, MD. Diagnostic tools included the new SMIC/ID-2 panel for streptococci, and the PMIC/ID-14 for enterococci. Two-hundred and fifty isolates have been investigated: β-hemolytic streptococci (n = 65, Streptococcus pneumoniae (n = 50, viridans group streptococci (n = 32, Enterococcus faecium (n = 40, Enterococcus faecalis (n = 43, other catalase-negative cocci (n = 20. When needed, species ID was determined using molecular methods. Test bacterial strains were chosen among those carrying clinically-relevant resistance determinants (penicillin, macrolides, fluoroquinolones, glycopeptides. AST results of the Phoenix system were compared to minimal inhibitory concentration (MIC values measured by the Etest method (AB Biodisk, Solna, Sweden. Results Streptococci: essential agreement (EA and categorical agreement (CA were 91.9% and 98.8%, respectively. Major (ME and minor errors (mE accounted for 0.1% and 1.1% of isolates, respectively. No very major errors (VME were produced. Enterococci: EA was 97%, CA 96%. Small numbers of VME (0.9%, ME (1.4% and mE (2.8% were obtained. Overall, EA and CA rates for most drugs were above 90% for both genera. A few VME were found: a teicoplanin and high-level streptomycin for E. faecalis, b high-level gentamicin for E. faecium. The mean time to results (± SD was 11.8 ± 0.9 h, with minor differences between streptococci and enterococci. Conclusion The Phoenix system emerged as an effective tool for quantitative AST. Panels based on dilution tests provided rapid and accurate MIC values with regard to clinically-relevant streptococcal and enterococcal

  16. Test implementation of a school-oriented drug prevention program “Study without Drugs”: pre- and post-testing for effectiveness

    OpenAIRE

    Ishaak, Fariel; de Vries, Nanne Karel; Wolf, Kees van der

    2014-01-01

    Background In this article, the test implementation of a school-oriented drug prevention program “Study without Drugs” is discussed. The aims of this study were to determine the results of the process evaluation and to determine whether the proposed school-oriented drug prevention program during a pilot project was effective for the participating pupils. Methods Sixty second-grade pupils at a junior high school in Paramaribo, Suriname participated in the test implementation. They were divided...

  17. 26 CFR 1.28-1 - Credit for clinical testing expenses for certain drugs for rare diseases or conditions.

    Science.gov (United States)

    2010-04-01

    ... muscular dystrophies; Huntington's disease, a hereditary chorea; myoclonus; Tourette's syndrome; and... drugs for rare diseases or conditions. 1.28-1 Section 1.28-1 Internal Revenue INTERNAL REVENUE SERVICE... clinical testing expenses for certain drugs for rare diseases or conditions. (a) General rule. Section 28...

  18. Evaluation of on-site oral fluid screening using Drugwipe-5(+), RapidSTAT and Drug Test 5000 for the detection of drugs of abuse in drivers.

    Science.gov (United States)

    Wille, Sarah M R; Samyn, Nele; Ramírez-Fernández, Maria del Mar; De Boeck, Gert

    2010-05-20

    Driving under the influence of drugs is a major problem worldwide. At the moment, several countries have adopted a 'per se' legislation to address this problem. One of the key elements in the enforcement process is the possibility of rapid on-site screening tests to take immediate administrative measures. In this study, the reliability of three oral fluid screening devices (Mavand RapidSTAT, Securetec Drugwipe-5(+), and Dräger DrugTest 5000) was assessed by comparing their on-site results with confirmatory GC-MS plasma analysis. Our results demonstrate that for amphetamine screening, the oral fluid on-site devices on the market today are certainly sensitive enough. RapidSTAT, Drugwipe-5(+), and DrugTest 5000 demonstrated respectively a sensitivity of 93%, 100% and 92% for amphetamine/MDMA. For cocaine screening, sensitivities of 75%, 78% and 67% were obtained for the RapidSTAT, Drugwipe-5(+), and DrugTest 5000 devices, respectively. The studied devices were able to detect about 70% of all cannabis users in a roadside setting. However, a newer version of the DrugTest 5000 test cassette demonstrated a sensitivity of 93%, indicating an increased detection of Delta(9)-tetrahydrocannabinol using 'new generation' oral fluid screening tests with lowered cut-offs. Due to these promising results police officers and judicial experts are keen to use oral fluid screening devices. They believe that their ease of use and diminished amount of false positive results in comparison with urine screening will lead to more roadside tests and more appropriate juridical measures.

  19. An international multicenter study on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing.

    Science.gov (United States)

    Simen, Birgitte B; Braverman, Michael S; Abbate, Isabella; Aerssens, Jeroen; Bidet, Yannick; Bouchez, Olivier; Gabriel, Christian; Izopet, Jacques; Kessler, Harald H; Stelzl, Evelyn; Di Giallonardo, Francesca; Schlapbach, Ralph; Radonic, Aleksander; Paredes, Roger; Recordon-Pinson, Patricia; Sakwa, James; St John, Elizabeth P; Schmitz-Agheguian, Gudrun G; Metzner, Karin J; Däumer, Martin P

    2014-08-01

    The detection of mutant spectra within the viral quasispecies is critical for therapeutic management of HIV-1 infections. Routine clinical application of ultrasensitive genotyping requires reproducibility and concordance within and between laboratories. The goal of the study was to evaluate a new protocol on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing (454-UDS) in an international multicenter study. Sixteen blinded HIV-1 subtype B samples were provided for 454-UDS as both RNA and cDNA with viral titers of 88,600-573,000 HIV-1 RNA copies/ml. Eight overlapping amplicons spanning protease (PR) codons 10-99 and reverse transcriptase (RT) codons 1-251 were generated using molecular barcoded primers. 454-UDS was performed using the 454 Life Sciences/Roche GS FLX platform. PR and RT sequences were analyzed using 454 Life Sciences Amplicon Variant Analyzer (AVA) software. Quantified variation data were analyzed for intra-laboratory reproducibility and inter-laboratory concordance. Routine population sequencing was performed using the ViroSeq HIV-1 genotyping system. Eleven laboratories and the reference laboratory 454 Life Sciences sequenced the HIV-1 sample set. Data presented are derived from seven laboratories and the reference laboratory since severe study protocol execution errors occurred in four laboratories leading to exclusion. The median sequencing depth across all sites was 1364 reads per position (IQR=809-2065). 100% of the ViroSeq-reported mutations were also detected by 454-UDS. Minority HIV-1 drug resistance mutations, defined as HIV-1 drug resistance mutations identified at frequencies of 1-25%, were only detected by 454-UDS. Analysis of 10 preselected majority and minority mutations were consistently found across sites. The analysis of drug-resistance mutations detected between 1 and 10% demonstrated high intra- and inter-laboratory consistency in frequency estimates for both RNA and prepared cDNA samples, indicating robustness of the

  20. A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

    Science.gov (United States)

    Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

    2016-01-01

    The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

  1. International Conference on Harmonisation; guidance on the duration of chronic toxicity testing in animals (rodent and nonrodent toxicity testing); availability. Notice. Food and Drug Administration, HHS.

    Science.gov (United States)

    1999-06-25

    The Food and Drug Administration (FDA) is publishing a guidance entitled "S4A Duration of Chronic Toxicity Testing in Animals (Rodent and Nonrodent Toxicity Testing)." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and is intended to provide guidance on the duration of chronic toxicity testing in rodents and nonrodents as part of the safety evaluation of a drug product. FDA is also noting circumstances in which it may accept durations of chronic toxicity testing in nonrodents that differ from the duration generally recommended by ICH.

  2. Molecular characterization and antiviral activity test of common drugs against echovirus 18 isolated in Korea

    Directory of Open Access Journals (Sweden)

    Park KwiSung

    2011-11-01

    Full Text Available Abstract Genetic diversity and antiviral activity for five common antiviral drugs of echovirus (ECV 5 isolated in Korea have been described. The present study extended these tests to a Korean ECV 18 isolate. An outbreak of aseptic meningitis caused by the ECV 18 isolate was reported in Korea in 2005, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from stool specimen of a 5-year-old male patient with aseptic meningitis, the complete genome sequence was obtained and was compared it with the Metcalf prototype strain. Unlike the ECV5 isolate, the 3' untranslated region had the highest identity value (94.2% at the nucleotide level, while, at the amino acid level, the P2 region displayed the highest identity value (96.9%. These two strains shared all cleavage sites, with the exception of the 2B/2C site, which was RQ/NN in the Metcalf strain but RQ/NS in the Korean ECV 18 isolate. In Vero cells infected with the Korean ECV 18 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 μg/mL. Of the five drugs, only amantadine (IC50: 4.97 ± 0.77 μg/mL, TI: 20.12 and ribavirin (IC50: 7.63 ± 0.87 μg/mL, TI: 13.11 had any antiviral activity against the Korean ECV 18 isolate in the five antiviral drugs. These antiviral activity effects were similar with results of the Korean ECV5 isolate.

  3. Portable Upconversion Nanoparticles-Based Paper Device for Field Testing of Drug Abuse.

    Science.gov (United States)

    He, Mengyuan; Li, Zhen; Ge, Yiying; Liu, Zhihong

    2016-02-01

    We report the first portable upconversion nanoparticles (UCNPs)-based paper device for road-side field testing of cocaine. Upon the recognition of cocaine by two pieces of rationally designed aptamer fragments, the luminescence of UCNPs immobilized on the paper is quenched by Au nanoparticles (AuNPs), which indicates the cocaine concentration. This device can give quantitative results in a short time with high sensitivity using only a smartphone as the apparatus. Moreover, this device is applicable in human saliva samples, and it also can be used to monitor the cocaine content change in blood samples. The results of this work demonstrate the prospect of developing UCNPs-based paper devices for field testing of drug abuse.

  4. 77 FR 29307 - Control of Alcohol and Drug Use: Addition of Post-Accident Toxicological Testing for Non...

    Science.gov (United States)

    2012-05-17

    ... prohibited or strictly regulated because of their potential for abuse or addiction. The Drug Enforcement... sedating antihistamines. Of the 150 re-tested samples, 14 (9.3 percent) tested positive for at least one... number of positive post-accident test results should FRA decide to report tramadol or...

  5. Drug-addiction and boundaries of the Self A psychoanalytical reading through the Rorschach test

    Directory of Open Access Journals (Sweden)

    Silvia Marfisi

    2016-05-01

    Full Text Available The present research intends to analyse the phenomenon of drug addiction through the Rorschach test. The protocols, analysed according to the French School Method, have been administered to a sample of 10 subjects. The data have been evaluated integrating quantitative and qualitative aspects, which have revealed the main dimensions of the drug addicted personality, mainly regarding the functioning modes of the narcissistic personality based on the over-investment of limits. The results show an impoverished cognitive set where the capacity of the investment in the imaginary activity is absent and a certain rigidity of thinking is revealed. The investment in the formal aspects of the table provides justification of the emotional isolation where the attention to the external reality acts as a defence from an internal reality whose impoverishment is perceived as threatening and distressing. Interesting outcomes are evident in relation to the emotional sphere and the attempt of social adaptation from some indexes such as the quantity of human responses which result to be in the normative range. The Rorschach test provided an important contribution in this evaluation/understanding of the drug addicted personality: if on the one hand it confirmed some basic traits of the functioning of these subjects, on the other hand it provided the possibility to research new and unexpected frontiers that,  from the closure and the over investment of the boundaries of the Self (predominance of formal responses, of “reponses peau”, reaches an attempt of psychic stimulation addressing a “primitive” emotional sphere, in the form of specular relations (reflection responses or partial (Hd.

  6. A microcosting study of immunogenicity and tumour necrosis factor alpha inhibitor drug level tests for therapeutic drug monitoring in clinical practice.

    Science.gov (United States)

    Jani, Meghna; Gavan, Sean; Chinoy, Hector; Dixon, William G; Harrison, Beverley; Moran, Andrew; Barton, Anne; Payne, Katherine

    2016-12-01

    To identify and quantify resource required and associated costs for implementing TNF-α inhibitor (TNFi) drug level and anti-drug antibody (ADAb) tests in UK rheumatology practice. A microcosting study, assuming the UK National Health Service perspective, identified the direct medical costs associated with providing TNFi drug level and ADAb testing in clinical practice. Resource use and costs per patient were identified via four stages: identification of a patient pathway with resource implications; estimation of the resources required; identification of the cost per unit of resource (2015 prices); and calculation of the total costs per patient. Univariate and multiway sensitivity analyses were performed using the variation in resource use and unit costs. Total costs for TNFi drug level and concurrent ADAb testing, assessed using ELISAs on trough serum levels, were £152.52/patient (range: £147.68-159.24) if 40 patient samples were tested simultaneously. For the base-case analysis, the pre-testing phase incurred the highest costs, which included booking an additional appointment to acquire trough blood samples. The additional appointment was the key driver of costs per patient (67% of the total cost), and labour accounted for 10% and consumables 23% of the total costs. Performing ELISAs once per patient (rather than in duplicate) reduced the total costs to £133.78/patient. This microcosting study is the first assessing the cost of TNFi drug level and ADAb testing. The results could be used in subsequent cost-effectiveness analyses of TNFi pharmacological tests to target treatments and inform future policy recommendations. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  7. Annual banned-substance review: the Prohibited List 2008-analytical approaches in human sports drug testing.

    Science.gov (United States)

    Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

    2009-01-01

    The list of prohibited substances and methods of doping issued by the World Anti-Doping Agency is updated and modified annually based on most recent developments and scientific data. Compounds and methods are maintained, added, or removed from the list, or they are placed in so-called monitoring programmes that have been established to obtain reliable data on the prevalence of particular substances and methods in- and/or out-of-competition. Consequently, doping control laboratories continuously update, modify and optimize existing screening and confirmation assays to ensure utmost comprehensiveness in detecting the prohibited and monitored substances as well as chemically and pharmacologically related analogs. The annual banned-substance review for human sports drug testing critically summarizes recent innovations in analytical approaches supporting the detection of established and newly outlawed substances and methods of doping. Literature from January 2007 through September 2008 as indexed in Medline and Web of Science was screened and articles on detection methods for substances and methods of doping in humans were compiled according to the 2008 Prohibited List of the World Anti-Doping Agency. Few new approaches were presented for individual doping agents and the majority of reports demonstrated new options for increasing the comprehensiveness of existing doping control assays. In addition, new techniques in separation and/or ionization of analytes complementary to commonly used procedures were described, which, so far, did not meet all requirements of sports drug testing. (c) 2009 John Wiley & Sons, Ltd.

  8. Evaluation of ten oral fluid point-of-collection drug-testing devices.

    Science.gov (United States)

    Walsh, J Michael; Crouch, Dennis J; Danaceau, Jonathan P; Cangianelli, Leo; Liddicoat, Laura; Adkins, Randy

    2007-01-01

    Previously, the laboratory evaluations of six point-of-collection oral fluid (POC-OF) drug testing devices were reported. Four additional devices, Oralstat (American Bio Medica); SmartClip (Envitec); Impact (LifePoint); and OraLine IV s.a.t (Sun Biomedical Laboratories), were recently evaluated for their ability to meet the claimed (and proposed) cutoff concentrations set by the manufacturers for the detection of amphetamine(s), cocaine/metabolite, opiates, and cannabinoids (Oralstat also benzodiazepines). With the exception of the Sun Biomedical device, actual false-positive results were not encountered. Most devices performed well for the detection of opiates and amphetamine(s), but approximately half had amphetamine(s) cutoff concentrations greater than that proposed by the Substance Abuse and Mental Health Services Administration (SAMHSA). Only three devices had cocaine cutoffs less than or equal to 20 ng/mL (SAMHSA), and a number of false-negative results were obtained. The devices still were not capable of detecting Delta(9)-tetrahydrocannabinol at 4 ng/mL (SAMHSA). However, sensitivities improved since the initial studies, and approximately half of the devices met the THC-COOH cutoff proposed by SAMHSA. Results from the current and previous evaluations are presented in the paper and indicate that the sensitivity and performance of commercial OF drug testing devices is improving, but remains problematic for the reliable detection of cannabinoid use.

  9. SARM-S4 and metabolites detection in sports drug testing: a case report.

    Science.gov (United States)

    Grata, Elia; Perrenoud, Laurent; Saugy, Martial; Baume, Norbert

    2011-12-10

    Recently, pharmaceutical industry developed a new class of therapeutics called Selective Androgen Receptor Modulator (SARM) to substitute the synthetic anabolic drugs used in medical treatments. Since the beginning of the anti-doping testing in sports in the 1970s, steroids have been the most frequently detected drugs mainly used for their anabolic properties. The major advantage of SARMs is the reduced androgenic activities which are the main source of side effects following anabolic agents' administration. In 2010, the Swiss laboratory for doping analyses reported the first case of SARMs abuse during in-competition testing. The analytical steps leading to this finding are described in this paper. Screening and confirmation results were obtained based on liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Additional information regarding the SARM S-4 metabolism was investigated by ultra high-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in Mycobacterium tuberculosis.

    Science.gov (United States)

    Coeck, Nele; de Jong, Bouke C; Diels, Maren; de Rijk, Pim; Ardizzoni, Elisa; Van Deun, Armand; Rigouts, Leen

    2016-05-01

    Molecular resistance testing fails to explain all fluoroquinolone resistance, with a continued need for a suitable rapid phenotypic drug susceptibility testing method. To evaluate the optimal method for phenotypic fluoroquinolone susceptibility testing. Using Löwenstein-Jensen medium, Middlebrook 7H11 agar, BACTEC-MGIT 960 and the resazurin microtitre plate assay, we determined susceptibility to fluoroquinolones in Mycobacterium tuberculosis and investigated cross-resistance between ofloxacin, levofloxacin, moxifloxacin and gatifloxacin. We compared MICs of all four fluoroquinolones for 91 strains on Löwenstein-Jensen (as the gold standard) with their MICs in resazurin plates, and with ofloxacin susceptibility at a single concentration in MGIT and on 7H11 agar, in addition to sequencing of the gyrAB genes. Applying a cut-off of 2 mg/L ofloxacin, 1 mg/L levofloxacin and 0.5 mg/L moxifloxacin and gatifloxacin in all methods, some discordance between solid medium and MGIT methods was observed, yet this tended to be explained by MICs around the cut-off. The high discordance between Löwenstein-Jensen (LJ) and resazurin plates suggests that the currently applied cut-offs for all fluoroquinolones in the resazurin method should decrease and minor changes in colour (from blue to purple) be considered as meaningful. High-level resistance in all assays to all drugs correlated well with the presence of gyrA mutations, in support of recent findings that fluoroquinolone resistance should be tested at different concentrations, as patients with lower levels of resistance may continue to benefit from high-dose fluoroquinolone-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  11. A normalized scaled gradient method to solve non-negativity and equality constrained linear inverse problem - Application to spectral mixture analysis

    CERN Document Server

    Theys, Céline; Dobigeon, Nicolas; Richard, Cédric; Tourneret, Jean-Yves; Ferrari, André

    2013-01-01

    This paper addresses the problem of minimizing a convex cost function under non-negativity and equality constraints, with the aim of solving the linear unmixing problem encountered in hyperspectral imagery. This problem can be formulated as a linear regression problem whose regression coefficients (abundances) satisfy sum-to-one and positivity constraints. A normalized scaled gradient iterative method (NSGM) is proposed for estimating the abundances of the linear mixing model. The positivity constraint is ensured by the Karush Kuhn Tucker conditions whereas the sum-to-one constraint is fulfilled by introducing normalized variables in the algorithm. The convergence is ensured by a one-dimensional search of the step size. Note that NSGM can be applied to any convex cost function with non negativity and flux constraints. In order to compare the NSGM with the well-known fully constraint least squares (FCLS) algorithm, this latter is reformulated in term of a penalized function, which reveals its suboptimality. Si...

  12. Clinical application of HIV drug resistance testing%HIV耐药检测的临床应用

    Institute of Scientific and Technical Information of China (English)

    李敬云

    2012-01-01

    检测HIV耐药毒株可采用基因型和表型方法.由于HIV及其准种的高度变异性、抗HIV药物种类及其作用机制的多样性及HIV耐药检测方法的复杂性,目前,熟练运用HIV耐药检测方法并将检测结果整合到临床常规治疗的管理还存在很大问题,制订合理的临床应用指南是耐药检测面临的最大挑战.本文针对常用的2种HIV耐药检测方法,分析解释检测结果使用的方法及存在的问题,介绍国际最新的HIV耐药检测临床使用规范,并提出未来HIV耐药检测及临床应用应关注和解决的问题.%Genotype and phenotype testing can be used for HIV drug resistance testing. Because of the high diversity of HIV and its quasispecies, the variety of antiretroviral drugs and its mechanism and the complexity of HIV drug resistance testing, skillful use of the drug resistance testing and integration of the testing results into clinical management remains a big problem, and working out the rational clinical application guideline is a rigorous challenge for HIV drug resistance testing. In this paper, the author interprets and analyzes the results of genotype and phenotype testing and the exsiting problems, introduces the updated international clinical specifications of HIV drug resistance testing, and puts forward the problems to be focused on and be resolved in the future in the field of HIV drug resistance testing and its clinical application.

  13. Immunoassay-Based Drug Tests Are Inadequately Sensitive for Medication Compliance Monitoring in Patients Treated for Chronic Pain.

    Science.gov (United States)

    Snyder, Marion L; Fantz, Corrine R; Melanson, Stacy

    2017-02-01

    Enzyme immunoassays (EIA) have notable limitations for monitoring therapeutic compliance in pain management. Chromatography coupled with mass spectrometry provides definitive results and superior sensitivity and specificity over traditional EIA testing. To analyze and compare the sensitivity of EIA results together with known prescriptions to liquid chromatography-tandem mass spectrometry (LC-MS/MS) for monitoring drug use (and abuse) in patients treated for chronic pain. A total of 530 urine samples from patients being treated for chronic pain were studied. Pain management clinic in the United States. The samples were tested for a profile of chronic pain medications and illicit drugs with commercially available EIA kits followed by analysis with Agilent LC-MS/MS system. The EIAs exhibited poor sensitivity and high rates of false negative results in the pain management setting. For example, 21% of EIA for opiates show false negative results. Mass spectrometry methods were more sensitive, detected a broader range of drugs and metabolites, and could detect non-prescribed drug use and simulations in compliance. Patients do not always accurately report drug use information, and some drugs do not have EIA methods available for comparative purposes. Mass spectrometry is a more robust and reliable method for detection of drugs used in the pain management setting. Due to the extent of undisclosed use and abuse of medications and illicit drugs, LC-MS/MS testing is necessary for adequate and accurate drug detection. In addition, LC-MS/MS methods are superior in terms of sensitivity and number of compounds that can be screened, making this a better method for use in pain management. Key words: Pain management, enzyme immunoassays, mass spectrometry, urine drug testing, prescription status, compliance.

  14. Cross-reactivity of stimulants found in sports drug testing by two fluorescence polarization immunoassays.

    Science.gov (United States)

    de la Torre, R; Badia, R; Gonzàlez, G; García, M; Pretel, M J; Farré, M; Segura, J

    1996-01-01

    We investigated the usefulness of immunological methods for presumptive detection of stimulants found in sports drug testing. The ingestion of substances that show no cross-reactivity in tests commercially available for the detection of amphetamines can produce positive results in the urine. Human metabolism contributes to the positive results of some urine samples when the parent compound does not cross-react with the antibodies of the assay. Urine samples from healthy volunteers given stimulants were tested by chromatographic methods and by two different fluorescence polarization immunoassays (FPIA) from Abbott Laboratories for the analysis of amphetamines. According to the results obtained, we classified stimulants into four groups: detectable stimulants that gave rise to amphetamine by human metabolism (group 1); detectable ephedrines and related compounds, appearing in the urine either as parent compounds or originated by metabolism (group 2); detectable stimulants that displayed actual cross-reactivity with amphetamine tests (group 3); and stimulants not detected by FPIA (group 4). Most of the true doping cases due to the ingestion of stimulants may be detected by FPIA. The specificity of the results may be increased by combining immunological assays with different antibodies.

  15. A patch test confirmed phenobarbital-induced fixed drug eruption in a child.

    Science.gov (United States)

    Chadly, Zohra; Aouam, Karim; Chaabane, Amel; Belhadjali, Hichem; Abderrazzak Boughattas, Naceur; Zili, Jamel Eddine

    2014-06-01

    A-10-year-old girl was referred to our department for multiple hyperpigmented plaques. One week previously, she had been given one suppository of acetylsalicylic acid - phenobarbital for fever. Twelve hours after the drug intake the child developed pruritic red plaques on the left thigh. Six weeks after resolution of the acute reaction, patch tests were performed separately, with phenobarbital and acetylsalicylic acid. On 48-hour reading, only the phenobarbital patch test on residual pigmented lesion was positive. Because of possible cross-reactions between aromatic anticonvulsants, subsequent patch tests using carbamazepine and phenytoin on residual pigmented lesions were performed. They were all negative at 48-hour reading. To our knowledge, only two isolated pediatric cases of Phenobarbital-induced FDE have been reported in the literature. In this case report, as it was difficult to determine whether phenobarbital or acetylsalicylic acid was responsible for this reaction, subsequent patch tests allowed the identification of the culprit component since it was positive to phenobarbital.

  16. Evaluation of rapid alternative methods for drug susceptibility testing in clinical isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Luciano Mengatto

    2006-08-01

    Full Text Available A study was carried out to compare the performance of a commercial method (MGIT and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA, microscopic observation drug susceptibility (MODS assay, MTT test, and broth microdilution method (BMM. A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87% whereas for streptomycin, sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety, they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8; more standardization is needed for ethambutol.

  17. A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media

    Directory of Open Access Journals (Sweden)

    Kotla NG

    2016-03-01

    Full Text Available Niranjan G Kotla,1,2 Sima Singh,1,3 Balaji Maddiboyina,4 Omprakash Sunnapu,2 Thomas J Webster5,6 1School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India; 2Technologies for the Advancement of Science, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, India; 3Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 4Department of Pharmaceutics, Vishwabharathi College of Pharmaceutical Sciences, Guntur, Andhra Pradesh, India; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media. In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus were cultured in 12% w/v skimmed milk powder and 5% w/v grade “A” honey. Approximately 1010–1011 colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were

  18. Drug Testing in Schools: An Effective Deterrent? Hearing before the Subcommittee on Criminal Justice, Drug Policy, and Human Resources of the Committee on Government Reform. House of Representatives, One Hundred Sixth Congress, Second Session (May 30, 2000).

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Government Reform.

    This document presents testimonies from a hearing discussing the drug threat in the nations schools and the issue of whether drug testing is an effective deterrent. The subcommittee conducted the hearing as part of an effort to fully understand the nations drug crisis, how it impacts different parts of our nation, and what effective drug control…

  19. Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption

    NARCIS (Netherlands)

    Olbrich, C.; Gessner, A.; Schroder, W.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To

  20. Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption

    NARCIS (Netherlands)

    Olbrich, C.; Gessner, A.; Schroder, W.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To po

  1. Optimization and validation of CEDIA drugs of abuse immunoassay tests in serum on Hitachi 912.

    Science.gov (United States)

    Kirschbaum, Katrin M; Musshoff, Frank; Schmithausen, Ricarda; Stockhausen, Sarah; Madea, Burkhard

    2011-10-10

    Due to sensitive limits of detection of chromatographic methods and low limit values regarding the screening of drugs under the terms of impairment in safe driving (§ 24a StVG, Street Traffic Law in Germany), preliminary immunoassay (IA) tests should be able to detect also low concentrations of legal and illegal drugs in serum in forensic cases. False-negatives should be avoided, the rate of false-positive samples should be low due to cost and time. An optimization of IA cutoff values and a validation of the assay is required for each laboratory. In a retrospective study results for serum samples containing amphetamine, methylenedioxy derivatives, cannabinoids, benzodiazepines, cocaine (metabolites), methadone and opiates obtained with CEDIA drugs of abuse reagents on a Hitachi 912 autoanalyzer were compared with quantitative results of chromatographic methods (gas or liquid chromatography coupled with mass spectrometry (GC/MS or LC/MS)). Firstly sensitivity, specificity, positive and negative predictive values and overall misclassification rates were evaluated by contingency tables and compared to ROC-analyses and Youden-Indices. Secondly ideal cutoffs were statistically calculated on the basis of sensitivity and specificity as decisive statistical criteria with focus on a high sensitivity (low rates of false-negatives), i.e. using the Youden-Index. Immunoassay (IA) and confirmatory results were available for 3014 blood samples. Sensitivity was 90% or more for nearly all analytes: amphetamines (IA cutoff 9.5 ng/ml), methylenedioxy derivatives (IA cutoff 5.5 ng/ml), cannabinoids (IA cutoff 14.5 ng/ml), benzodiazepines (IA cutoff >0 ng/ml). Test of opiates showed a sensitivity of 86% for a IA cutoff value of >0 ng/ml. Values for specificity ranged between 33% (methadone, IA cutoff 10 ng/ml) and 90% (cocaine, IA cutoff 20 ng/ml). Lower cutoff values as recommended by ROC analyses were chosen for most tests to decrease the rate of false-negatives. Analyses enabled

  2. Drug Testing Incoming Residents and Medical Students in Family Medicine Training: A Survey of Program Policies and Practices.

    Science.gov (United States)

    Bell, Paul F; Semelka, Michael W; Bigdeli, Laleh

    2015-03-01

    Despite well-established negative consequences, high rates of substance use and related disorders continue to be reported. Physicians in training are not immune from this, or the associated risks to their health and careers, while impaired physicians are a threat to patient safety. We surveyed family medicine residency programs' practices relating to drug testing of medical students and incoming residents. The survey asked about the extent to which residency programs are confronted with trainees testing positive for prohibited substances, and how they respond. The survey was sent to the directors of family medicine residency programs. A total of 205 directors (47.2%) completed the survey. A majority of the responding programs required drug testing for incoming residents (143, 68.9%). Most programs did not require testing of medical students (161, 81.7%). Few programs reported positive drug tests among incoming residents (9, 6.5%), and there was only 1 reported instance of a positive result among medical students (1, 3.3%). Respondents reported a range of responses to positive results, with few reporting that they would keep open training spots or offer supportive services for a medical student who tested positive. Changing laws legalizing certain drugs may require corresponding changes in the focus on drug testing and associated issues in medical training; however, many residency program directors were not aware of their institution's current policies. Programs will need to reexamine drug testing policies as new generations of physicians, growing up under altered legal circumstances concerning drug use, progress to clinical training.

  3. Effect In Vitro of Antiparasitic Drugs on Microbial Inhibitor Test Responses for Screening Antibiotic Residues in Goat's Milk.

    Science.gov (United States)

    Romero, T; Beltrán, M C; Reybroeck, W; Molina, M P

    2015-09-01

    Microbial inhibitor tests are widely used to screen antibiotic residues in milk; however, these tests are nonspecific and may be affected by various substances capable of inhibiting the growth of the test microorganism. The objective of this study was to determine the effect of antiparasitic drugs in goat's milk on the microbial inhibitor test response. Raw antibiotic-free milk from Murciano-Granadina goats was supplemented with eight concentrations of seven antiparasitic substances (albendazole, 10 to 170 mg/kg; closantel, 1 to 140 mg/kg; diclazuril, 8 to 45 mg/kg; febendazole, 10 to 140 mg/kg; levamisole, 40 to 440 mg/kg; diazinon, 8 to 45 mg/kg; and ivermectin, 40 to 200 mg/kg). Twelve replicates for each concentration were analyzed with three microbial inhibitor tests: BRT MRL, Delvotest SP-NT MSC, and Eclipse 100. The results were interpreted visually (negative or positive). Using a logistic regression model, the concentrations of the antiparasitic drugs producing 5% (IC5), 10% (IC10), and 50% (IC50) positive results were determined. In general, the Eclipse 100 test was less sensitive to the effect of antiparasitic substances; the inhibitory concentrations of almost all the drugs assayed were higher than those for other tests. Conversely, the BRT MRL test was most affected, with high levels of interference at lower antiparasitic drug concentrations. Closantel and diazinon interfered with all microbial tests at lower concentrations than did other drugs (IC5 = 1 to 26 and 12 to 20 mg/kg, respectively), and higher concentrations of levamisole and diclazuril (IC5 = 30 to 240 and 50 to 117 mg/kg, respectively) were required to produce 5% positive results. These findings indicate that microbial inhibitor tests can be affected by elevated concentrations of antiparasitic drugs in goat's milk.

  4. Hair testing to assess both known and unknown use of drugs amongst ecstasy users in the electronic dance music scene.

    Science.gov (United States)

    Palamar, Joseph J; Salomone, Alberto; Gerace, Enrico; Di Corcia, Daniele; Vincenti, Marco; Cleland, Charles M

    2017-08-12

    Data on both known and unknown drug use in the electronic dance music (EDM) scene is important to inform prevention and harm reduction. While surveys are the most common method of querying drug use, additional biological data can help validate use and detect unknown/unintentional use of drugs such as new psychoactive substances (NPS). We sought to determine the extent of both known and unknown use of various substances in this high-risk scene. We hair-tested 90 self-reported past-year ecstasy/MDMA/Molly users attending EDM parties in New York City during the summer of 2016 using UHPLC-MS/MS. Results were compared to self-reported past-year use. Three quarters (74.4%) tested positive for MDMA, a third (33.3%) tested positive for an NPS, and 27.8% tested positive specifically for one or more synthetic cathinones (e.g., butylone, ethylone, pentylone, methylone, alpha-PVP). Half (51.1%) of participants tested positive for a drug not self-reported, with most testing positive for synthetic cathinones (72.0%), methamphetamine (69.0%), other NPS stimulants (e.g., 4-FA, 5/6-APB; 66.7%), or new dissociatives (e.g., methoxetamine, diphenidine; 60.0%). Attending parties every other week or more often, reporting higher-frequency ecstasy pill use, having tested one's ecstasy, and having found out one's ecstasy was adulterated, were risk factors for testing positive for synthetic cathinones and NPS in general. Hair testing appears to be a valuable addition to drug epidemiology studies. Many EDM party attendees-even those who test their ecstasy-are unknowingly using NPS and/or other drugs. Prevention information and harm reduction may help reduce unknown/unintentional use. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Establishing a human renal cell carcinoma tumorgraft platform for preclinical drug testing.

    Science.gov (United States)

    Pavía-Jiménez, Andrea; Tcheuyap, Vanina Toffessi; Brugarolas, James

    2014-08-01

    Traditionally, xenograft models have been used to study tumors in vivo. However, their utility is reduced by the use of tumor cell lines for implantation. Tumorgrafts (TGs; also known as patient-derived xenografts (PDXs)), which involve patient-derived tumor samples, are increasingly recognized as more representative models than traditional xenografts. Furthermore, we showed previously that renal cell carcinoma (RCC) TGs retain the histology, gene expression, DNA copy number alterations, mutations and treatment responsiveness of patient tumors. In skilled hands, implantations require ≤5 min per mouse, and TGs typically grow to 1 cm in 1-4 months. Here we outline the process of implantation of patient-derived RCC samples into the kidneys of immunodeficient mice, as well as the s.c. implantation for preclinical drug testing, including guidelines for the design and execution of drug trials. TGs have extensive applications besides therapeutic studies and may identify biomarkers and mechanisms of resistance. In addition, they may provide insights into tumor biology.

  6. HIV Testing, Care, and Treatment Among Women Who Use Drugs From a Global Perspective: Progress and Challenges.

    Science.gov (United States)

    Metsch, Lisa; Philbin, Morgan M; Parish, Carrigan; Shiu, Karen; Frimpong, Jemima A; Giang, Le Minh

    2015-06-01

    The article reviews data on HIV testing, treatment, and care outcomes for women who use drugs in 5 countries across 5 continents. We chose countries in which the HIV epidemic has, either currently or historically, been fueled by injection and non-injection drug use and that have considerable variation in social structural and drug policies: Argentina, Vietnam, Australia, Ukraine, and the United States. There is a dearth of available HIV care continuum outcome data [ie, testing, linkage, retention, antiretroviral therapy (ART) provision, viral suppression] among women drug users, particularly among noninjectors. Although some progress has been made in increasing HIV testing in this population, HIV-positive women drug users in 4 of the 5 countries have not fully benefitted from ART nor are they regularly engaged in HIV care. Issues such as the criminalization of drug users, HIV-specific criminal laws, and the lack of integration between substance use treatment and HIV primary care play a major role. Strategies that effectively address the pervasive factors that prevent women drug users from engaging in HIV care and benefitting from ART and other prevention services are critical. Future success in enhancing the HIV continuum for women drug users should consider structural and contextual level barriers and promote social, economic, and legal policies that overhaul the many years of discrimination and stigmatization faced by women drug users worldwide. Such efforts must emphasis the translation of policies into practice and approaches to implementation that can help HIV-infected women who use drugs engage at all points of the HIV care continuum.

  7. Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

    Science.gov (United States)

    Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

    2016-02-01

    Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

  8. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Science.gov (United States)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  9. Suggesting a testing strategy for possible endocrine effects of drug metabolites.

    Science.gov (United States)

    Jacobsen, N W; Brooks, B W; Halling-Sørensen, B

    2012-04-01

    Most pharmaceuticals are extensively metabolized by organisms, which results in internal exposure to mixtures of parent compounds and various metabolites. Many of these metabolites are considered non-toxic, but some metabolites retain toxic properties of the parent compound or elicit other undesirable outcomes. Unfortunately, the effects of metabolites are often not considered when endocrine activities of chemicals are evaluated in vitro. In this study two approaches, an "effect-based" and a "compound-by-compound" testing design, were used to determine the effects of metabolites of the antidepressant sertraline on aromatase enzyme activity. In the "effect-based" approach, a mixture of sertraline metabolites, produced by liver microsomes, inhibited aromatase, but was less potent than sertraline. In the "compound-by-compound" testing design, three specific metabolites were evaluated individually and in mixtures. Though two N-desmethylated metabolites were more potent aromatase inhibitors than sertraline, hydroxyl ketone sertraline did not inhibit the enzyme and mixtures of these metabolites and sertraline were less potent than predicted from a concentration addition model. Our findings highlight the importance of considering aromatase inhibition, and potentially other biological activities, of pharmaceutical metabolites produced by liver microsome preparations and then comparing such observations to studies of specific metabolites available for testing in pure form. Subsequently, a five step integrated strategy for screening of the potential endocrine effects of drugs and their metabolites are proposed. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Towards a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolising enzymes. Gene/drug pairs and barriers perceived in Spain.

    Directory of Open Access Journals (Sweden)

    José A G Agúndez

    2012-11-01

    Full Text Available The development of clinical practice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance with regard to adverse drug reactions. The potential of pharmacogenomic biomarkers has been extensively investigated in recent years. However, several barriers to implementing the use of pharmacogenomics testing exist. We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of major gene/drug pairs.Of 11 potential barriers, the highest importance was attributed to lack of institutional support for pharmacogenomics testing, and to the issues related to the lack of guidelines. Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan and CYP2D6/tamoxifen. In this perspective article we compare the relative importance of 29 gene/drug pairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology & Therapeutics study, and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testing.

  11. [Application of the BACspreader™ Microbe Dispersion Counter in drug susceptibility test on Mycobacterium tuberculosis].

    Science.gov (United States)

    Jiang, Y; Li, J; Zhang, Y Y; Wu, J; Wang, L L; Yu, C L; Shen, X; Zhu, G F

    2017-04-12

    Objective: To evaluate the application of the BACspreader™ Microbe Dispersion Counter in drug susceptibility test (DST) on Mycobacterium tuberculosis (MTB). Methods: The MTB strains were dispersed and diluted to 1.0 McFarland standard turbidity, by means of BACspreader™ Microbe Dispersion Counter and manual grinding method, respectively. The bacterial dispersion effect and bacterial activity were tested by microscope and colony counting method. During Jan. 2015 to June 2015, a total of 726 isolates of MTB were collected in all district tuberculosis hospitals of Shanghai. The bacterial suspension dispersed by instrument and manual grinding, were inoculated in slant medium for DST (Proportion Method), and then incubated in 37 ℃ incubator for 28 days and the DST results were reported. The effects of the 2 different bacterial dispersion methods were compared by comparing DST results and counting the bacterial colony which grew in high and low concentration control media. Paired chi-square test was used for statistical analysis, and the significance level was 0.05. Results: Compared to the manual grinding method, the MTB colony could be better dispersed by BACspreader™ Microbe Dispersion Counter, without reducing the bacterial activity. The DST results of 726 mycobacterial isolates were the same by different bacterial dispersion methods. The count of bacterial colony growing in high concentration control medium was significantly different between of the 2 dispersion methods (χ(2)=8.0, PDispersion Counter, and 4.3% by manual grinding method; the difference being significant between the 2 dispersion methods (χ(2)=674, PDispersion Counter had better countability in low concentration control slants, and had more significant contrast between high and low concentration control slants, which was useful to determine the DST results. Introducing the BACspreader™ Microbe Dispersion Counter to MTB DST could automate the DST process, make the testing results objective

  12. Sports drug testing: Analytical aspects of selected cases of suspected, purported, and proven urine manipulation.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Sigmund, Gerd; Schänzer, Wilhelm

    2012-01-01

    Manipulation of urine specimens provided by elite athletes for doping control purposes has been reported several times in the past, and in most of these cases urine substitution was eventually proven. Recent findings of suspected and substantiated manipulation have outlined the complexity and diversity of tampering options, sample appearance alterations resulting from non-manipulative influence, and the analytical challenges arising from these scenarios. Using state-of-the-art mass spectrometric and immunological doping control and forensic chemistry methodologies, four unusual findings were observed. One sports drug testing specimen was found to contain an unusually high content of saccharides accompanied by hordenine and Serpine-Z4, while no endogenous steroid (e.g. testosterone, epitestosterone, androsterone and etiocholanolone) was detected. This specimen was identified as non-alcoholic beer filled into the doping control sample container, constituting an undisputed doping offense. A doping control sample of bright green color was received and found to contain residues of methylene blue, which is not considered relevant for doping controls as no masking or manipulative effect is known. In addition, the number of urine samples of raspberry to crimson red coloration received at doping control laboratories has constantly increased during the last years, attributed to the presence of hemoglobin or betanin/isobetanin. Also here, no doping rule violation was given and an impact on routine analytical results was not observed. Finally, a total of 8 sports drug testing samples collected at different competition sites was shown to contain identical urine specimens as indicated by steroid profile analysis and conclusively proven by DNA-STR (short tandem repeat) analysis. Here, the athletes in question were not involved in the urine substitution act but the doping control officer was convicted of sample manipulation.

  13. A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context

    Directory of Open Access Journals (Sweden)

    Stefano Gentili

    2016-01-01

    Full Text Available The reliability of DrugWipe 5A on site test for principal drugs of abuse (cannabis, amphetamines, cocaine, and opiates detection in oral fluid was assessed by comparing the on-site results with headspace solid-phase microextraction (HS-SPME gas chromatography-mass spectrometry (GC-MS analysis on samples extracted by the device collection pad. Oral fluid samples were collected at recreational settings (e.g., discos, pubs, and music bars of Rome metropolitan area. Eighty-three club goers underwent the on-site drug screening test with one device. Independently from the result obtained, a second device was used just to collect another oral fluid sample subsequently extracted and analyzed in the laboratory following HS-SPME procedure, gas chromatographic separation by a capillary column, and MS detection by electron impact ionization. DrugWipe 5A on-site test showed 54 samples (65.1% positive to one or more drugs of abuse, whereas 75 samples (90.4% tested positive for one or more substances following GC-MS assay. Comparing the obtained results, the device showed sensitivity, specificity, and accuracy around 80% for amphetamines class. Sensitivity (67 and 50% was obtained for cocaine and opiates, while both sensitivity and accuracy were unsuccessful (29 and 53%, resp. for cannabis, underlying the limitation of the device for this latter drug class.

  14. A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Z.; Liao, Q.; Hu, Y.; You, L.; Zhou, L.; Zhao, Y. [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tsinghua University, Beijing (China)

    2013-08-10

    Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.

  15. A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay

    Directory of Open Access Journals (Sweden)

    Z. Wen

    2013-08-01

    Full Text Available Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.

  16. 78 FR 14217 - Control of Alcohol and Drug Use: Addition of Post-Accident Toxicological Testing for Non...

    Science.gov (United States)

    2013-03-05

    ... will be posted without change to http://www.regulations.gov ; this includes any personal information... monitor its post-accident test results and other data to see if changes in policy or additional action are... procedures (see Procedures for Transportation Workplace Drug and Alcohol Testing Programs (49 CFR part 40...

  17. Annular phased array transducer for preclinical testing of anti-cancer drug efficacy on small animals.

    Science.gov (United States)

    Kujawska, Tamara; Secomski, Wojciech; Byra, Michał; Postema, Michiel; Nowicki, Andrzej

    2017-04-01

    A technique using pulsed High Intensity Focused Ultrasound (HIFU) to destroy deep-seated solid tumors is a promising noninvasive therapeutic approach. A main purpose of this study was to design and test a HIFU transducer suitable for preclinical studies of efficacy of tested, anti-cancer drugs, activated by HIFU beams, in the treatment of a variety of solid tumors implanted to various organs of small animals at the depth of the order of 1-2cm under the skin. To allow focusing of the beam, generated by such transducer, within treated tissue at different depths, a spherical, 2-MHz, 29-mm diameter annular phased array transducer was designed and built. To prove its potential for preclinical studies on small animals, multiple thermal lesions were induced in a pork loin ex vivo by heating beams of the same: 6W, or 12W, or 18W acoustic power and 25mm, 30mm, and 35mm focal lengths. Time delay for each annulus was controlled electronically to provide beam focusing within tissue at the depths of 10mm, 15mm, and 20mm. The exposure time required to induce local necrosis was determined at different depths using thermocouples. Location and extent of thermal lesions determined from numerical simulations were compared with those measured using ultrasound and magnetic resonance imaging techniques and verified by a digital caliper after cutting the tested tissue samples. Quantitative analysis of the results showed that the location and extent of necrotic lesions on the magnetic resonance images are consistent with those predicted numerically and measured by caliper. The edges of lesions were clearly outlined although on ultrasound images they were fuzzy. This allows to conclude that the use of the transducer designed offers an effective noninvasive tool not only to induce local necrotic lesions within treated tissue without damaging the surrounding tissue structures but also to test various chemotherapeutics activated by the HIFU beams in preclinical studies on small animals.

  18. 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... Operators to Report Contractor Management Information System (MIS) Data; and New Method for Operators to... ``user name'' and ``password'' for the Drug and Alcohol Management Information System (DAMIS)...

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

    OpenAIRE

    Mbonye, AK; Magnussen, P; Chandler, CI; Hansen, KS; S. Lal; Cundill, B; Lynch, CA; Clarke, SE

    2014-01-01

    BACKGROUND: 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, trea...

  20. System-approach methods for modeling and testing similarity of in vitro dissolutions of drug dosage formulations.

    Science.gov (United States)

    Dedík, Ladislav; Durisová, Mária

    2002-07-01

    System-approach based modeling methods are used to model dynamic systems describing in vitro dissolutions of drug dosage formulations. Employing the models of these systems, model-dependent criteria are proposed for testing similarity between in vitro dissolutions of different drug dosage formulations. The criteria proposed are exemplified and compared with the criterion called the similarity factor f(2), commonly used in the field of biomedicine. Advantages of the criteria proposed over this factor are presented.

  1. Rapid drug-susceptibility testing of Mycobacterium tuberculosis clinical isolates to first-line antitubercular drugs by nitrate reductase assay: A comparison with proportion method.

    Science.gov (United States)

    Kohli, Amrish; Bashir, Gulnaz; Fatima, Akeela; Jan, Abiroo; Wani, Nayeem-U-Din; Ahmad, Junaid

    2016-12-01

    Early initiation of therapy in patients with tuberculosis is imperative for its control. Conventional methods of susceptibility testing such as the proportion method (PM) require visual detection and counting of colonies that takes up to 6weeks. Rapid and simple phenotypic methods that have been endorsed by the World Health Organization can serve as alternatives. In this study, we evaluated the colorimetric nitrate reductase assay, which utilizes the detection of nitrate reduction as an indicator of growth much earlier compared with PM (within 7-14days). The susceptibility of 75 clinical isolates of Mycobacterium tuberculosis to four first-line antitubercular drugs was tested by nitrate reductase assay and compared with the standard PM. In this assay, inoculation was done on both drug-free and drug-containing Löwenstein-Jensen medium containing sodium nitrate. After incubation for 7-14days, reduction to nitrite was taken as an indicator of growth, which was detected by color change on addition of Griess reagent. Agreement between nitrate reductase assay and PM was 100% for rifampicin, 97.30% for isoniazid, 93.30% for streptomycin, and 98.60% for ethambutol. Cost/isolate with this assay was found to be approximately two times lesser than that of PM. All results were obtained in 7-14days by nitrate reductase assay, which was significantly rapid compared with 42days taken for obtaining results by PM. Nitrate reductase assay can be used as a rapid and inexpensive method for drug-susceptibility testing of M. tuberculosis for first-line antitubercular drugs without compromising accuracy of standard methods. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

  2. Toxicogenetics: population-based testing of drug and chemical safety in mouse models.

    Science.gov (United States)

    Rusyn, Ivan; Gatti, Daniel M; Wiltshire, Timothy; Wilshire, Timothy; Kleeberger, Steven R; Threadgill, David W

    2010-08-01

    The rapid decline in the cost of dense genotyping is paving the way for new DNA sequence-based laboratory tests to move quickly into clinical practice, and to ultimately help realize the promise of 'personalized' therapies. These advances are based on the growing appreciation of genetics as an important dimension in science and the practice of investigative pharmacology and toxicology. On the clinical side, both the regulators and the pharmaceutical industry hope that the early identification of individuals prone to adverse drug effects will keep advantageous medicines on the market for the benefit of the vast majority of prospective patients. On the environmental health protection side, there is a clear need for better science to define the range and causes of susceptibility to adverse effects of chemicals in the population, so that the appropriate regulatory limits are established. In both cases, most of the research effort is focused on genome-wide association studies in humans where de novo genotyping of each subject is required. At the same time, the power of population-based preclinical safety testing in rodent models (e.g., mouse) remains to be fully exploited. Here, we highlight the approaches available to utilize the knowledge of DNA sequence and genetic diversity of the mouse as a species in mechanistic toxicology research. We posit that appropriate genetically defined mouse models may be combined with the limited data from human studies to not only discover the genetic determinants of susceptibility, but to also understand the molecular underpinnings of toxicity.

  3. Modified protocol for drug susceptibility testing of MGIT cultures of Mycobacterium tuberculosis by the MGIT 960.

    Science.gov (United States)

    Adami, Aline Gois; Gallo, Juliana Failde; Pinhata, Juliana Maira Watanabe; Martins, Maria Conceição; Giampaglia, Carmen Maria Saraiva; de Oliveira, Rosangela Siqueira

    2017-02-01

    A rapid detection of resistance in Mycobacterium tuberculosis is crucial for management and control of tuberculosis. This study evaluated a more rapid and cost-effective drug susceptibility testing (DST) protocol using primary isolates of M. tuberculosis in mycobacteria growth indicator tube (MGIT). Ninety-four M. tuberculosis isolates in MGIT were subjected to DST by the manufacturer's method, i.e., primary isolates were subcultured and DST was performed from positive cultures for a maximum of 5days; and by our modified method, i.e., DST was performed directly from primary MGIT cultures positive for more than 5days. Results were concordant for 76 (81%) isolates. Agreement between both methods was 92.0%, 98.9%, 97.7%, and 95.5% for streptomycin, isoniazid, rifampicin, and ethambutol, respectively. Six isolates failed to grow on the recommended method, including 3 resistant isolates. Not performing subculture of primary M. tuberculosis isolates yields reliable results, decreasing the turnaround time and the cost of the test.

  4. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria.

    Science.gov (United States)

    Sun, Wei; Weingarten, Rebecca A; Xu, Miao; Southall, Noel; Dai, Sheng; Shinn, Paul; Sanderson, Philip E; Williamson, Peter R; Frank, Karen M; Zheng, Wei

    2016-11-09

    Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.

  5. Diagnostic Plausibility of MTBDRplus and MTBDRsl Line Probe Assays for Rapid Drug Susceptibility Testing of Drug Resistant Mycobacterium tuberculosis Strains in Pakistan

    Directory of Open Access Journals (Sweden)

    Javaid

    2016-06-01

    Full Text Available Background World health organization (WHO recommends the use of line probe assays (LiPAs for rapid drug susceptibility testing (DST. However, only a limited number of studies from Pakistan have documented the performance characteristics of line probe assays in testing multi-drug resistant (MDR strains of Mycobacterium tuberculosis (MTB. Objectives The objective of this work is to evaluate the diagnostic plausibility of the LiPA tests MTBDRplus and MTBDRsl on MDR MTB isolates from Pakistan. Patients and Methods This was a cross-sectional study conducted at the Indus hospital, Karachi. LiPA testing was performed on 196 smear-positive samples using BACTEC MGIT 960 as a gold standard. Results The sensitivity of MTBDRplus for isoniazid and rifampicin was found to be 88.8% and 90.2%, respectively, while sensitivity of MTBDRsl for fluoroquinolones, amikacin/capreomycin, and ethambutol was found to be 72.9%, 81.8%, and 56.6%, respectively. Conclusions The MTBDRplus and MTBDRsl genotypic testing can serve as useful additional tools for DST in a high-burden country like Pakistan provided it is used in combination with phenotypic testing.

  6. Face Super-resolution With Non-negative Featrue Basis Constraint%非负特征基约束的人脸超分辨率

    Institute of Scientific and Technical Information of China (English)

    兰诚栋; 胡瑞敏; 韩镇; 卢涛

    2011-01-01

    Principal Component Analysis (PC A) is commonly used for human face images representation in face super-resolution. But the features extracted by PCA are holistic and difficult to have semantic interpretation. In order to synthesize a better super-resolution face image with the results of the face images representation, we propose face a super-resolution algorithm with non-negative featrue basis constraint The algorithm uses the NMF to obtain non-negative featrue basis of face sample images, and the target image is regularized by Markov random fields, with maximum a posteriori probability approach. Finally, the steepest descent method is used to optimize non-negative featrue basis coefficient of high-resolution image. Experimental results show that, in the subjective and objective quality, the face super-resolution algorithm with non-negative feature basis constrait performs better than PCA-based algorithms.%主成分分析(PCA)是人脸超分辨率申常用的人脸图像表达方法,但是PCA方法的特征是整体的且难以语义解释.为了使表达的结果更好地用于合成超分辨率人脸图像,提出一种非负特征基约束的人脸超分辨率算法.该算法利用非负矩阵分解(NMF)获取样本人脸图像的非负特征基,结合最大后验概率的方法,对目标图像进行马尔可夫随机场正则约束,最速下降法优化得到高分辨率人脸图像的非负特征基系数.实验结果表明,在主客观质量上,非负特征基约束的人脸超分辨率算法的性能胜过基于PCA的算法.

  7. Evaluating the impact of hemp food consumption on workplace drug tests.

    Science.gov (United States)

    Leson, G; Pless, P; Grotenhermen, F; Kalant, H; ElSohly, M A

    2001-01-01

    Foods containing seeds or oil of the hemp plant (Cannabis sativa L.) are increasingly found in retail stores in the U.S. The presence of delta9-tetrahydrocannabinol (THC) in these foods has raised concern over their impact on the results of workplace drug tests for marijuana. Previous studies have shown that eating hemp foods can cause screening and confirmed positive results in urine specimens. This study evaluated the impact of extended daily ingestion of THC via hemp oil on urine levels of its metabolite 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH) for four distinct daily THC doses. Doses were representative of THC levels now commonly found in hemp seed products and a range of conceivable daily consumption rates. Fifteen THC-naïve adults ingested, over four successive 10-day periods, single daily THC doses ranging from 0.09 to 0.6 mg. Subjects self-administered THC in 15-mL aliquots (20 mL for the 0.6-mg dose) of four different blends of hemp and canola oils. Urine specimens were collected prior to the first ingestion of oil, on days 9 and 10 of each of the four study periods, and 1 and 3 days after the last ingestion. All specimens were screened for cannabinoids by radioimmunoassay (Immunalysis Direct RIA Kit), confirmed for THC-COOH by gas chromatography-mass spectrometry (GC-MS), and analyzed for creatinine to identify dilute specimens. None of the subjects who ingested daily doses of 0.45 mg of THC screened positive at the 50-ng/mL cutoff. At a daily THC dose of 0.6 mg, one specimen screened positive. The highest THC-COOH level found by GC-MS in any of the specimens was 5.2 ng/mL, well below the 15-ng/mL confirmation cutoff used in federal drug testing programs. A THC intake of 0.6 mg/day is equivalent to the consumption of approximately 125 mL of hemp oil containing 5 microg/g of THC or 300 g of hulled seeds at 2 microg/g. These THC concentrations are now typical in Canadian hemp seed products. Based on our findings, these concentrations appear

  8. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. 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…

  10. Performance-based testing for drugs of abuse: dose and time profiles of marijuana, amphetamine, alcohol, and diazepam.

    Science.gov (United States)

    Kelly, T H; Foltin, R W; Emurian, C S; Fischman, M W

    1993-09-01

    The time courses of the effects of acute doses of amphetamine (5 and 10 mg/70 kg), alcohol (0.3 and 0.6 g/kg), diazepam (5 and 10 mg/70 kg), and marijuana (2.0% and 3.5% delta 9-THC) on performance engendered by each of four computerized behavioral tasks were evaluated in six human subjects. These performance-based tasks have potential commercial utility for drug-use detection in the workplace. Alcohol and marijuana effects were reliably detected for up to three hours following dose administration with most procedures. Amphetamine and diazepam effects were also detected, but the dose effects and time courses were variable. The profile of behavioral effects varied across drugs, suggesting that performance-based testing procedures might be useful in discriminating which drug was administered and the time course of the drug's effects. Results indicate that repeated measurement with performance-based drug detection procedures can provide immediate indications of performance impairment in a cost-effective and noninvasive manner and, as such, would be a useful supplement to biological sample testing for drug-use detection.

  11. Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair.

    Science.gov (United States)

    Joseph, R E; Höld, K M; Wilkins, D G; Rollins, D E; Cone, E J

    1999-10-01

    A 10-week inpatient study was performed to evaluate cocaine, codeine, and metabolite disposition in biological matrices collected from volunteers. An initial report described drug disposition in plasma, sebum, and stratum corneum collected from five African-American males. This report focuses on drug disposition in hair and sweat collected from the same five subjects. Following a three-week washout period, three doses of cocaine HCl (75 mg/70 kg, subcutaneous) and three doses of codeine SO4 (60 mg/70 kg, oral) were administered on alternating days in week 4 (low-dose week). The same dosing sequence was repeated in week 8 with doubled doses (high-dose week). Hair was collected by shaving the entire scalp once each week. Hair from the anterior vertex was divided into two portions. One portion was washed with isopropanol and phosphate buffer; the other portion was not washed. Hair was enzymatically digested, samples were centrifuged, and the supernatant was collected. Sweat was collected periodically by placing PharmChek sweat patches on the torso. Drugs were extracted from sweat patches with methanol/0.2 M sodium acetate buffer (75:25, v/v). Supernatants from hair digests, hair washes, and sweat patch extracts were processed by solid-phase extraction followed by gas chromatography-mass spectrometry analysis for cocaine, codeine, 6-acetylmorphine, and metabolites. Cocaine and codeine were the primary analytes identified in sweat patches and hair. Drugs were detected in sweat within 8 h after dosing, and drug secretion primarily occurred within 24 h after dosing. No clear relationship was observed between dose and drug concentrations in sweat. Drug incorporation into hair appeared to be dose-dependent. Drugs were detected in hair within 1-3 days after the last drug administration; peak drug concentrations generally occurred in the following 1-2 weeks; thereafter, drug concentrations decreased. Solvent washes removed 50-55% of cocaine and codeine from hair collected 1

  12. Risk mitigation for children exposed to drugs during gestation: A critical role for animal preclinical behavioral testing.

    Science.gov (United States)

    Zucker, Irving

    2017-06-01

    Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, analgesic, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital and acetaminophen. Rodent data helpful in identifying and predicting adverse effects of prenatal drug exposure in children were first generated many years after drugs were FDA-approved and administered to pregnant women. I recommend that enhanced behavioral testing of rodent offspring exposed to drugs prenatally should begin during preclinical drug evaluation and continue during Phase I clinical trials, with findings communicated to physicians and patients in drug labels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.

    Science.gov (United States)

    Domínguez, J; Boettger, E C; Cirillo, D; Cobelens, F; Eisenach, K D; Gagneux, S; Hillemann, D; Horsburgh, R; Molina-Moya, B; Niemann, S; Tortoli, E; Whitelaw, A; Lange, C

    2016-01-01

    The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

  14. Choosing the right laboratory: a review of clinical and forensic toxicology services for urine drug testing in pain management.

    Science.gov (United States)

    Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L

    2015-01-01

    Urine drug testing (UDT) services are provided by a variety of clinical, forensic, and reference/specialty laboratories. These UDT services differ based on the principal activity of the laboratory. Clinical laboratories provide testing primarily focused on medical care (eg, emergency care, inpatients, and outpatient clinics), whereas forensic laboratories perform toxicology tests related to postmortem and criminal investigations, and drug-free workplace programs. Some laboratories now provide UDT specifically designed for monitoring patients on chronic opioid therapy. Accreditation programs for clinical laboratories have existed for nearly half a century, and a federal certification program for drug-testing laboratories was established in the 1980s. Standards of practice for forensic toxicology services other than workplace drug testing have been established in recent years. However, no accreditation program currently exists for UDT in pain management, and this review considers several aspects of laboratory accreditation and certification relevant to toxicology services, with the intention to provide guidance to clinicians in their selection of the appropriate laboratory for UDT surveillance of their patients on opioid therapy.

  15. Public assistance, drug testing, and the law: the limits of population-based legal analysis.

    Science.gov (United States)

    Player, Candice T

    2014-01-01

    In Populations, Public Health and the Law, legal scholar Wendy Parmet urges courts to embrace population-based legal analysis, a public health inspired approach to legal reasoning. Parmet contends that population-based legal analysis offers a way to analyze legal issues--not unlike law and economics--as well as a set of values from which to critique contemporary legal discourse. Population-based analysis has been warmly embraced by the health law community as a bold new way of analyzing legal issues. Still, population-based analysis is not without its problems. At times, Parmet claims too much territory for the population perspective. Moreover, Parmet urges courts to recognize population health as an important norm in legal reasoning. What should we do when the insights of public health and conventional legal reasoning conflict? Still in its infancy, population-based analysis offers little in the way of answers to these questions. This Article applies population-based legal analysis to the constitutional problems that arise when states condition public assistance benefits on passing a drug test, thereby highlighting the strengths of the population perspective and exposing its weaknesses.

  16. A Low Cost/Low Power Open Source Sensor System for Automated Tuberculosis Drug Susceptibility Testing

    Directory of Open Access Journals (Sweden)

    Kyukwang Kim

    2016-06-01

    Full Text Available In this research an open source, low power sensor node was developed to check the growth of mycobacteria in a culture bottle with a nitrate reductase assay method for a drug susceptibility test. The sensor system reports the temperature and color sensor output frequency change of the culture bottle when the device is triggered. After the culture process is finished, a nitrite ion detecting solution based on a commercial nitrite ion detection kit is injected into the culture bottle by a syringe pump to check bacterial growth by the formation of a pigment by the reaction between the solution and the color sensor. Sensor status and NRA results are broadcasted via a Bluetooth low energy beacon. An Android application was developed to collect the broadcasted data, classify the status of cultured samples from multiple devices, and visualize the data for the end users, circumventing the need to examine each culture bottle manually during a long culture period. The authors expect that usage of the developed sensor will decrease the cost and required labor for handling large amounts of patient samples in local health centers in developing countries. All 3D-printerable hardware parts, a circuit diagram, and software are available online.

  17. A Low Cost/Low Power Open Source Sensor System for Automated Tuberculosis Drug Susceptibility Testing.

    Science.gov (United States)

    Kim, Kyukwang; Kim, Hyeong Keun; Lim, Hwijoon; Myung, Hyun

    2016-06-22

    In this research an open source, low power sensor node was developed to check the growth of mycobacteria in a culture bottle with a nitrate reductase assay method for a drug susceptibility test. The sensor system reports the temperature and color sensor output frequency change of the culture bottle when the device is triggered. After the culture process is finished, a nitrite ion detecting solution based on a commercial nitrite ion detection kit is injected into the culture bottle by a syringe pump to check bacterial growth by the formation of a pigment by the reaction between the solution and the color sensor. Sensor status and NRA results are broadcasted via a Bluetooth low energy beacon. An Android application was developed to collect the broadcasted data, classify the status of cultured samples from multiple devices, and visualize the data for the end users, circumventing the need to examine each culture bottle manually during a long culture period. The authors expect that usage of the developed sensor will decrease the cost and required labor for handling large amounts of patient samples in local health centers in developing countries. All 3D-printerable hardware parts, a circuit diagram, and software are available online.

  18. Assessment of Substances Abuse in Burn Patients by Using Drug Abuse Screening Test

    Directory of Open Access Journals (Sweden)

    Kobra Gaseminegad

    2012-04-01

    Full Text Available There has been an increase in the frequency of substance abuse among hospitalized burn injury patients. However, few studies have investigated substance abuse among burn patients. This study was aimed to identify the incidence of substance abuse in burn injury patients using the "Drug Abuse Screening Test" (DAST-20. We determined the validity of DAST-20 in spring 2010. Subsequently, this descriptive study was performed on 203 burn injury patients who fit the study's inclusion criteria. We chose a score of 6 as the cutoff and thus achieved a sensitivity of 89% and a specificity of 85% for the DAST-20. During the study, we gathered demographic data, burn features and DAST-20 results for all patients. Patients with scores of 6 or more were considered to be substances abusers. A statistical analysis was conducted using SPSS v16 software. According to the DAST-20 results, 33% of the patients were in the user group. The mean score of DAST-20 was significantly higher among users than it was among nonusers (P<0.05. The level of substance abuse was severe in 77% of users. No significant differences were found among the substances, with the exception of alcohol. Substance abuse is an important risk factor for burn patients. In addition, this study showed that DAST-20 is a valid screening measure for studies on burn patients.

  19. Estimation of Validation and Reliability of Screening Test of Tobacco, Alcohol and Addictive Drugs in Iran

    Directory of Open Access Journals (Sweden)

    zahra Hooshyari

    2013-04-01

    Full Text Available Objective: the aim of the present study was the estimation of validation and reliability test of ASSIST instrument in Iran. Method: our research populations were Iranian alcohol and drugs users and abusers in the year 1390 that had referred to rehabilitation camps and addiction treatment centers for self-improving. Sample sizes of 2600, average age 36/5, were selected by cluster random sampling in eight provinces. The ASSIST and demographic form exercised for all of sample group. Also in order to validity estimation, 300 number of main sample we interviewed by ASI, SDS, DAST and DSM-IV criteria. Findings: ASSIST reliability estimated by Cronbach’s alpha for all of domains was between %79 to %95. Data analyses showed fair criteria, construct, discriminate and multi dimension validity. These types of validity for other domains were Discriminative validity of the ASSIST was investigated by comparison of ASSIST scores as groupes of dependence, abuser and user. There were significant confirmation between this scores and DSM-IV scores. Construct validity of the ASSIST was investigated by statistical comparison with health scores. ASSIST's cut off points classify clients in 3 categories in term of intensity of addiction. Conclusion: we surely recommend researchers to use this instrument in research and screening purposes or other situations in Iran.

  20. Deformable microparticles with multiple functions for drug delivery and device testing

    Science.gov (United States)

    Thula, Taili T.

    Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of

  1. International Conference on Harmonisation; guidance on Q1A stability testing of new drug substances and products; availability. Notice.

    Science.gov (United States)

    2001-11-07

    The Food and Drug Administration (FDA) is announcing the availability of a revised guidance entitled "Q1A(R) Stability Testing of New Drug Substances and Products." The revised guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance sets forth recommendations on the information to be submitted in the stability data package for a new drug substance or drug product for a registration application within the three regions of the European Union (EU), Japan, and the United States. The purpose of there vision is to add information to certain sections and to provide clarification to other sections of the guidance.

  2. Review of Urinalysis Drug Testing Program. Report by a Panel of Army and Civilian Experts in Toxicology and Drug Testing Legal Issues for the Surgeon General of the U.S. Army

    Science.gov (United States)

    1983-12-12

    placed on a urine sample which is drug positive by an immunoassay method, such as EMIT (or RIA), if it is also positive by a method based on completely...other laboratories visited by the Panel. The amphetamine procedure has its inherent problems due to urine interference peaks, pro- bably caused by...specific criteria for test results to assure that test results will meet scientific requirements and be considered legally sufficient to label a urine

  3. Barriers and missed opportunities to HIV testing among injection drug users in two Mexico--US border cities.

    Science.gov (United States)

    Moyer, Laura B; Brouwer, Kimberley C; Brodine, Stephanie K; Ramos, Rebeca; Lozada, Remedios; Cruz, Michelle Firestone; Magis-Rodriguez, Carlos; Strathdee, Steffanie A

    2008-01-01

    Despite increasing HIV prevalence in cities along the Mexico--US border, HIV testing among high-risk populations remains low. We sought to identify barriers associated with HIV testing among injection drug users (IDUs) in Tijuana and Ciudad Juarez, the two largest Mexican border cities located across from San Diego, California and El Paso, Texas, respectively. In 2005, 222 IDUs in Tijuana and 205 IDUs in Ciudad Juarez were recruited by respondent-driven sampling and administered a questionnaire to collect socio-demographic, behavioural and HIV testing history data. Blood samples were provided for serological testing of HIV, hepatitis C virus (HCV) and syphilis. Only 38% and 30% of respondents in Tijuana and Ciudad Juarez, respectively, had ever had an HIV test. The factors independently associated with never having been tested for HIV differed between the two sites, except for lack of knowledge on HIV transmission, which was independently associated in both locales. Importantly, 65% of those who had never been tested for HIV in both cities experienced at least one missed opportunity for voluntary testing, including medical visits, drug treatment and spending time in jail. Among this high-risk IDU population we found HIV testing to be low, with voluntary testing in public and private settings utilised inadequately. These findings underscore the need to expand voluntary HIV education and testing and to integrate it into services and locales frequented by IDUs in these Mexico--US border cities.

  4. Assessment of drug hypersensitivity with non-irritating concentrations of antibacterial agents for allergic skin tests: a review

    Directory of Open Access Journals (Sweden)

    Pritam Biswas

    2014-08-01

    Full Text Available Hypersensitivity reactions to antibiotics are common with a prevalence of 6-10% of all adverse reactions. There is a lack of guidelines and standardization of skin tests for the screening of hypersensitivity to all antibiotics, in terms of the methodology, dose and time of evaluation of the tests. Literature from Europe and America suggests the use of non-irritating concentration (NIC of antibiotics for skin testing such as intra dermal test (IDT, skin prick test (SPT. These are concentrations at which the drug is unlikely to produce irritation by virtue of its chemical nature resulting in false positive reactions. These concentrations have been validated by trials in their populations. Due to the increase of antibiotic resistance in our country, declaring a patient allergic to a specific class of antibiotics based on positive skin tests can further narrow the therapeutic armory. These individuals have an increased incidence of infections with resistant organisms as well as increased cost of hospitalization. This is due to the use of alternative broad spectrum antibiotics. Therefore, there is a need for a standardized protocol for the use of skin tests in screening of hypersensitivity, with validated NIC of all antibacterial agents. The aim of this article is to review literature of protocols for assessment of drug hypersensitivity with NIC of antibacterial drugs for SPT, IDT and also establish the need for research in this area in our country. [Int J Basic Clin Pharmacol 2014; 3(4.000: 586-590

  5. A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms

    Directory of Open Access Journals (Sweden)

    Susan D’Souza

    2014-01-01

    Full Text Available This review summarizes the methods used to study real-time (37°C drug release from nanoparticulate drug delivery systems and establish an IVIVC. Since no compendial standards exist, drug release is currently assessed using a variety of methods including sample and separate (SS, continuous flow (CF, dialysis membrane (DM methods, and a combination thereof, as well as novel techniques like voltametry and turbidimetry. This review describes the principle of each method along with their advantages and disadvantages, including challenges with set-up and sampling. The SS method allows direct measurement of drug release with simple set-up requirements, but sampling is cumbersome. With the CF method, sampling is straightforward but the set-up is time consuming. Set-up as well as sampling is easier with the DM, but it may not be suitable for drugs that bind to the membrane. Novel methods offer the possibility of real-time drug release measurement but may be restricted to certain types of drugs. Of these methods, Level A IVIVCs have been obtained with dialysis, alone or in combination with the sample and separate technique. Future efforts should focus on developing mathematical models that describe drug release mechanisms as well as facilitate formulation development of nano-sized dosage forms.

  6. Drug Prevention in Junior High: A Multi-Site Longitudinal Test.

    Science.gov (United States)

    Ellickson, Phyllis L.; Bell, Robert M.

    Although concern about adolescent drug use has grown over the past two decades, strategies for controlling use have not kept pace. Project ALERT (Adolescent Learning Experiences in Resistance Training), a school-based program, specifically targets cigarettes, alcohol and marijuana, the so-called gateway drugs. It is based on the social influence…

  7. 49 CFR Appendix F to Part 40 - Drug and Alcohol Testing Information that C/TPAs May Transmit to Employers

    Science.gov (United States)

    2010-10-01

    ... intermediaries is prohibited in all other cases, such as transmission of laboratory drug test results to MROs, the transmission of medical information from MROs to employers, the transmission of SAP reports to... from MROs to employers. 2. In every case, you must ensure that, in transmitting the information,...

  8. 75 FR 22150 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

    Science.gov (United States)

    2010-04-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance Abuse and Mental Health Services Administration Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies Correction In notice...

  9. The importance of class-I antiarrhythmic drug test in the evaluation of patients with syncope: unmasking Brugada syndrome.

    NARCIS (Netherlands)

    Roos, M.; Sarkozy, A.; Brodbeck, J.; Henkens, S.; Chierchia, G.B.; Asmundis, C. de; Capulzini, L.; Muller-Burri, S.A.; Yakazi, Y.; Brugada, P.

    2012-01-01

    INTRODUCTION: The Brugada syndrome (BrS) can first present with syncope. Class-I antiarrhythmic drug (AAD) test is used to unmask the diagnostic coved-type ECG pattern in case it is not spontaneously present. The aim of the study was to analyze patients with BrS presenting with syncope as first mani

  10. Rapid detection of in vitro antituberculous drug resistance among smear-positive respiratory samples using microcolony detection-based direct drug susceptibility testing method.

    Science.gov (United States)

    Iftikhar, Irim; Irfan, Seema; Farooqi, Joveria; Azizullah, Zahida; Hasan, Rumina

    2017-01-01

    With the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant Mycobacterium tuberculosis. Although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate microcolony method thin layer agar (TLA) for quick detection of resistance against the first- and second-line antituberculous drugs in clinical isolates. This was a cross-sectional study performed at Aga Khan University Hospital. A total of 87 Z-N stain smear-positive pulmonary samples were received and indirect drug susceptibility test (ID-DST) was performed using Lowenstein-Jensen and mycobacteria growth indicator tube. Direct DST was performed using TLA on 7H10 agar. TLA was observed twice weekly under microscope for 4 weeks. Sensitivity, specificity, and accuracy were calculated for TLA using indirect susceptibility method as the gold standard. Level of agreement was calculated using Kappa score. TLA showed sensitivity of 89% and 95.2% for isoniazid and rifampicin, while for ethionamide, ofloxacin, and injectable aminoglycosides, it was 96.6%, 92.1%, and 100%, respectively. Specificity for the first-line drugs was >95% while second-line drugs ranged from 70% to 100%. Mean time to positivity was 10.2 days by TLA as compared to 43.1 days by ID-DST. TLA is a quick and reliable method in identifying resistance, especially in resource-limited settings. However, additional liquid culture can be set up as backup, especially in patients on therapy to avoid false negative results.

  11. 'Drug users stick together': HIV testing in peer-based drop-in centres among people who inject drugs in Thailand.

    Science.gov (United States)

    Ti, Lianping; Hayashi, Kanna; Hattirat, Sattara; Suwannawong, Paisan; Kaplan, Karyn; Kerr, Thomas

    2015-06-01

    Introduction Although there is a well recognised need for novel approaches to HIV testing, particularly for marginalised populations at high risk for HIV infection, there remains a dearth of information on the acceptability of peer-based HIV testing among people who inject drugs (PWID). Between July 2011 and June 2012, 22 in-depth interviews were conducted with PWID participating in the Mitsampan Community Research Project in Bangkok, Thailand. Semi-structured interviews explored willingness to access rapid HIV testing delivered by a healthcare professional or a trained peer within peer-based drop-in centres. Audio-recorded interviews were transcribed verbatim and a thematic analysis was conducted. All participants indicated interest in accessing rapid HIV testing by a healthcare professional at peer-based drop-in centres due to the advantage of receiving immediate results. Experiencing stigma and discrimination by healthcare workers and wanting to avoid administrative barriers in hospitals were also reported as reasons for why PWID preferred HIV testing in peer-based settings. Peer support and shared lived experiences were repeatedly mentioned as benefits of peer-based testing. However, some concerns regarding peer-delivered testing were expressed and included a fear of peers' violating confidentiality and concerns regarding peers' qualifications for conducting an HIV test. Many PWID in this study sample noted the value of a peer-based approach to receiving testing and indicated their willingness to access rapid HIV testing in peer-based drop-in centres. The findings from this study highlight the potential for novel peer-based methods to complement existing HIV services in an effort to improve access to testing among this population.

  12. Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests.

    Science.gov (United States)

    Musshoff, F; Driever, F; Lachenmeier, K; Lachenmeier, D W; Banger, M; Madea, B

    2006-01-27

    Urine as well as head and pubic hair samples from drug abusers were analysed for opiates, cocaine and its metabolites, amphetamines, methadone and cannabinoids. Urine immunoassay results and the results of hair tests by means of gas chromatography-mass spectrometry were compared to the self-reported data of the patients in an interview protocol. With regard to the study group, opiate abuse was claimed from the majority in self-reports (89%), followed by cannabinoids (55%), cocaine (38%), and methadone (32%). Except for opiates the comparison between self-reported drug use and urinalysis at admission showed a low correlation. In contrast to urinalysis, hair tests revealed consumption in more cases. There was also a good agreement between self-reports of patients taking part in an official methadone maintenance program and urine test results concerning methadone. However, hair test results demonstrated that methadone abuse in general was under-reported by people who did not participate in a substitution program. Comparing self-reports and the results of hair analyses drug use was dramatically under-reported, especially cocaine. Cocaine hair tests appeared to be highly sensitive and specific in identifying past cocaine use even in settings of negative urine tests. In contrast to cocaine, hair lacks sensitivity as a detection agent for cannabinoids and a proof of cannabis use by means of hair analysis should include the sensitive detection of the metabolite THC carboxylic acid in the lower picogram range.

  13. Spectrofluorimetric determination of certain adrenergic agonist drugs in their pure forms and pharmaceutical formulations: Content uniformity test application.

    Science.gov (United States)

    Badr El-Din, Khalid M; Attia, Tamer Z

    2016-11-29

    A new, simple, sensitive and rapid spectrofluorimetric method has been developed for determination of certain adrenergic agonists such as isoxsuprine hydrochloride, ritodrine hydrochloride and etilefrine hydrochloride in their pure forms and pharmaceutical dosage forms. The method depends on micellar enhancement of the native fluorescence of investigated drugs by using 2% w/v sodium dodecyl sulfate (SDS) as an anionic surfactant. The enhanced fluorescence intensity of investigated drugs was measured at 305 nm after excitation at 278 nm. The interaction of studied drugs with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of investigated drugs. The relative fluorescence intensity-concentration plots were rectilinear over the range 0.15-3.00 μg ml(-1) , with low quantification limits of 0.132, 0.123 and 0.118 μg mL(-1) for isoxsuprine, ritodrine and etilefrine, respectively. The proposed method was successfully applied for determination of studied drugs in their pharmaceutical formulations. Moreover, the high sensitivity of the proposed method allows performing the content uniformity testing of the studied drugs in their tablets by using the official United States Pharmacopeia (USP) guidelines. Statistical comparisons of the results with those of the reported methods revealed excellent agreement and indicated no significant difference in accuracy and precision.

  14. Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset.

    Science.gov (United States)

    Tardif, Suzette; Ross, Corinna; Bergman, Phillip; Fernandez, Elizabeth; Javors, Marty; Salmon, Adam; Spross, Jennifer; Strong, Randy; Richardson, Arlan

    2015-05-01

    This report is the first description of dosing procedures, pharmacokinetics, biochemical action, and general tolerability of the antiaging drug rapamycin in the common marmoset, a small and short-lived monkey. Eudragit-encapsulated rapamycin was given orally to trained marmosets in a short-term (3 weeks) and a long-term (14 months) study. Circulating trough rapamycin levels (mean = 5.2 ng/mL; 1.93-10.73 ng/mL) achieved at roughly 1.0 mg/kg/day was comparable to those reported in studies of rodents and within the therapeutic range for humans. Long-term treated animals (6/8) indicated a reduction in mammalian target of rapamycin complex 1 signaling as noted by a decrease in the phospho rpS6 to total rpS6 ratio after 2 weeks of treatment. All long-term treated subjects had detectable concentrations of rapamycin in liver (4.7-19.9 pg/mg) and adipose tissue (2.2-32.8 pg/mg) with reduced mammalian target of rapamycin signaling in these tissues. There was no evidence of clinical anemia, fibrotic lung changes, or mouth ulcers. The observed death rate in the long-term study was as expected given the animals' ages. The ability to rapidly and reliably dose socially housed marmosets with an oral form of rapamycin that is well tolerated and that demonstrates a suppression of the mammalian target of rapamycin pathway leads us to conclude that this species offers a viable model for rapamycin testing to establish safety and efficacy for long-term antiaging intervention.

  15. American parents' willingness to prescribe psychoactive drugs to children: a test of cultural mediators.

    Science.gov (United States)

    Cohen, David; Dillon, Frank R; Gladwin, Hugh; De La Rosa, Mario

    2013-12-01

    In the USA, white children receive psychoactive drugs more often than black or Hispanic children. This study investigates whether cultural attitudes statistically mediate differences between American parents' self-identified racial-ethnic group membership and their willingness to medicate children for behavioral problems. Using data from telephone interviews with 1,145 parents in two Florida counties, structural models tested associations between each group compared with the other, in willingness to medicate children exhibiting different problematic behaviors and hypothesized cultural (familism, fatalism, attitude toward corporal punishment, religiosity, concern about treatment stigma, birth abroad, language of interview) and other mediators (views about medications and causes of children's problems). Respondent gender, age, socioeconomic status, parent-type household, taking psychoactive medication, and having a child with behavioral problems were used as covariates. Race-ethnicity was strongly associated with specific cultural attitudes and views about medications and problems, but only Hispanics distinguished themselves significantly from whites in willingness to medicate children. Across groups, parents who viewed medication favorably and endorsed biomedical causes for problems were more willing to medicate. In Hispanic-white and Hispanic-black comparisons, being interviewed in Spanish was the sole but modest cultural mediator of willingness, and in black-white comparisons, only concern about treatment stigma weakly mediated differences in willingness. These findings provide faint support for a parent-centered cultural explanation of reported prescription differences among youths of different racial-ethnic groups in the USA. However, structural and professional components of a broader cultural hypothesis for such differences, within the USA and between different countries, still require evaluation.

  16. Drug susceptibility testing of Mycobacterium Avium subsp. Avium isolates from naturally infected domestic pigeons to avian tuberculosis.

    Science.gov (United States)

    Parvandar, Kaveh; Mayahi, Mansour; Mosavari, Nader; Pajoohi, Reza Aref

    2016-12-01

    Avian tuberculosis is one of the most important infections affecting most species of birds. Several mycobacterial species have been identified causing avian tuberculosis, and the organisms confirmed most frequently are Mycobacterium avium and Mycobacterium genavense. Any species of birds can be infected with M. avium. Generally, domesticated fowl or captive wild birds are affected more frequently than those living in the wild. M. avium can not only infect all species of birds, but can also infect some domesticated mammals to cause disease, usually with localized lesion. In immunocompetent individuals, M. avium complex isolates produce localized soft tissue infections, including chronic pulmonary infections in the elderly and cervical lymphadenitis in children, but rarely any disseminated disease. In patients infected with HIV and AIDS or in other immunocompromised individuals, M. avium complex isolates frequently cause severe systemic infections. The importance of avian tuberculosis and the risk of its zoonotic spread motivated our interest to determine the drug susceptibility testing of M. avium subsp. avium isolates from naturally infected domestic pigeons to avian tuberculosis. Based on their clinical signs, 80 pigeons suspected with avian tuberculosis were subjected to the study. Out of the 51 identified isolates, 20 M. avium subsp. avium were subjected to the test. Drug susceptibly testing was performed according to the guidelines by Centers for Disease Control and Prevention and using proportional method. In the drug susceptibility testing, all isolates were resistant to streptomycin, kanamycin, ethionamide, and thiophene carboxylic acid hydrazide. Additionally, 3, 2, and 1 isolates were susceptible to isoniazid, rifampin, and ethambutol, respectively. To date, no study has documented the drug susceptibility testing of M. avium isolates from infected birds to avian tuberculosis. Pigeons are extensively kept in urban and rural areas for homing and racing

  17. Drugs as instruments: Describing and testing a behavioral approach to the study of neuroenhancement

    Directory of Open Access Journals (Sweden)

    Ralf Brand

    2016-08-01

    Full Text Available Neuroenhancement (NE is the non-medical use of psychoactive substances to produce a subjective enhancement in psychological functioning and experience. So far empirical investigations of individuals’ motivation for NE however have been hampered by the lack of theoretical foundation. This study aimed to apply drug instrumentalization theory to user motivation for NE. We argue that NE should be defined and analyzed from a behavioral perspective rather than in terms of the characteristics of substances used for NE. In the empirical study we explored user behavior by analyzing relationships between drug options (use over-the-counter products, prescription drugs, illicit drugs and postulated drug instrumentalization goals (e.g. improved cognitive performance, counteracting fatigue, improved social interaction. Questionnaire data from 1,438 university students were subjected to exploratory and confirmatory factor analysis to address the question of whether analysis of drug instrumentalization should be based on the assumption that users are aiming to achieve a certain goal and choose their drug accordingly or whether NE behavior is more strongly rooted in a decision to try or use a certain drug option. We used factor mixture modeling to explore whether users could be separated into qualitatively different groups defined by a shared ‘goal × drug option’ configuration. Our results indicate, first, that individuals’ decisions about NE are eventually based on personal attitude to drug options (e.g. willingness to use an over-the-counter product but not to abuse prescription drugs rather than motivated by desire to achieve a specific goal (e.g. fighting tiredness for which different drug options might be tried. Second, data analyses suggested two qualitatively different classes of users. Both predominantly used over-the-counter products, but ‘neuroenhancers’ might be characterized by a higher propensity to instrumentalize over

  18. Drugs As Instruments: Describing and Testing a Behavioral Approach to the Study of Neuroenhancement.

    Science.gov (United States)

    Brand, Ralf; Wolff, Wanja; Ziegler, Matthias

    2016-01-01

    Neuroenhancement (NE) is the non-medical use of psychoactive substances to produce a subjective enhancement in psychological functioning and experience. So far empirical investigations of individuals' motivation for NE however have been hampered by the lack of theoretical foundation. This study aimed to apply drug instrumentalization theory to user motivation for NE. We argue that NE should be defined and analyzed from a behavioral perspective rather than in terms of the characteristics of substances used for NE. In the empirical study we explored user behavior by analyzing relationships between drug options (use over-the-counter products, prescription drugs, illicit drugs) and postulated drug instrumentalization goals (e.g., improved cognitive performance, counteracting fatigue, improved social interaction). Questionnaire data from 1438 university students were subjected to exploratory and confirmatory factor analysis to address the question of whether analysis of drug instrumentalization should be based on the assumption that users are aiming to achieve a certain goal and choose their drug accordingly or whether NE behavior is more strongly rooted in a decision to try or use a certain drug option. We used factor mixture modeling to explore whether users could be separated into qualitatively different groups defined by a shared "goal × drug option" configuration. Our results indicate, first, that individuals' decisions about NE are eventually based on personal attitude to drug options (e.g., willingness to use an over-the-counter product but not to abuse prescription drugs) rather than motivated by desire to achieve a specific goal (e.g., fighting tiredness) for which different drug options might be tried. Second, data analyses suggested two qualitatively different classes of users. Both predominantly used over-the-counter products, but "neuroenhancers" might be characterized by a higher propensity to instrumentalize over-the-counter products for virtually all

  19. Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings

    DEFF Research Database (Denmark)

    Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo

    2014-01-01

    BACKGROUND: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations...... being identified. METHODS: An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa....... Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted...

  20. Injecting drugs of abuse and immunity: implications for HIV vaccine testing and efficacy.

    Science.gov (United States)

    Ugen, Kenneth E; Nyland, Susan B

    2006-11-01

    The recreational use of legal and illegal drugs has significant effects on immune responses and can potentially modulate susceptibility to infection by a number of pathogens. A number of agents including cannabinoids (marijuana), cocaine opiates, amphetamines, nicotine and alcohol were demonstrated to have potentially adverse effects on the susceptibility to infections, mediated most likely, by adverse effects on immunity. As such, these drugs of abuse could have significant and potentially adverse effects on the vaccination efficacy of a number of vaccines currently on the market and on potential experimental vaccines currently in the pipeline. This review will present an overview on how drugs of abuse potentially impacts immune responses and vaccination efficacy. The emphasis of this review will be the effects of opiate abuse, as exemplified by injecting/intravenous drug users (IDU), on HIV/AIDS and its potential impact on vaccine efficacy trials against this devastating infection/syndrome.