Hao, Ge-Fei; Yang, Guang-Fu; Zhan, Chang-Guo
2012-10-01
Drug resistance has become one of the biggest challenges in drug discovery and/or development and has attracted great research interests worldwide. During the past decade, computational strategies have been developed to predict target mutation-induced drug resistance. Meanwhile, various molecular design strategies, including targeting protein backbone, targeting highly conserved residues and dual/multiple targeting, have been used to design novel inhibitors for combating the drug resistance. In this article we review recent advances in development of computational methods for target mutation-induced drug resistance prediction and strategies for rational design of novel inhibitors that could be effective against the possible drug-resistant mutants of the target.
Zoghbi, Jad; Xu, Yuanxin; Grabert, Ryan; Theobald, Valerie; Richards, Susan
2015-11-01
Biological matrix interference in detection and quantitation immunoassays remains a major challenge in the field of bioanalysis. For example, circulating drug may interfere with the detection of anti-drug antibodies (ADA) and drug target, or ADA may interfere with quantitation of drug levels in PK/TK analysis. Monoclonal antibody drug interference, especially for human IgG4 drugs, presents an additional challenge for ADA analysis due to its longer half-life and higher dose. Assay tolerance to such interference may depend on assay platform and reagents. Various approaches have been used to improve drug tolerance in ADA analysis but limited success was observed. We have developed a breakthrough novel method that uses Precipitation and Acid dissociation (PandA) to overcome drug interference in the ADA assay. The method principle is based on four components for detection of total ADA (free ADA and drug bound ADA) in the presence of drug in patient samples: (1) use excess drug to saturate free ADA to form drug bound ADA as drug:ADA complexes, (2) precipitate the complex using an agent such as PEG, (3) acid dissociate ADA from drug and immobilize (capture) free ADA (and free drug) under acidic conditions (without neutralization) onto a large capacity surface, and (4) detect free ADA (not the captured drug) using specific anti-human Ig detection reagent. In this manuscript, we are describing case studies for three humanized monoclonal antibodies (an IgG1 and two IgG4 drugs). The three drug specific PandA ADA assays resulted in complete recovery of ADA in samples containing drug levels in excess of those expected in patients, in contrast to the commonly used acid dissociation approach in ECL bridging assays. This breakthrough novel method shows significant improvement over the current approaches. In fact, the drug interference or under detecting of ADA in all three cases was eliminated. This assay principle could be used not only for ADA assays but also PK and biomarker
ERIC Educational Resources Information Center
Jonas, Steven
1989-01-01
Concludes that the principle drug problems in the United States arise from the use of cigarette tobacco and alcoholic beverages. Identifies a drug culture as the persistent force in society that promotes drug use. Points out that the influence of the primary drug industries inhibit attempts to deal effectively with drug problems. (KO)
Problems with drugs in Croatia.
Vrhovac, B
1997-01-01
Croatia has 4.8 million inhabitants, 11,800 physicians, 2000 pharmacists, two now shareholding, pharmaceutical companies (about 6500 employees, total sales of about 350 million US dollars). There are a number of problems due to the war (GNP fell from 3800 to about 1500 US dollars), occupation of 25% of its territory, 0.5 million refugees and lack of resources (139 US dollars/capita for health, about 40 US dollars i.e. 30%!! for drugs)--about three times less than before the aggression. The drug situation is controlled with the help of: (1) donations (approximate value of 600 million US dollars since 1991 from Europe and US), (2) (essential) drug formularies--250 for outpatients, and 580 generic names for various levels of hospital use, (3) special efforts to purchase drugs of good quality at a reasonable price (a kind of tender), (4) control of prescribing (prescriptions, specialists referral) especially by GPs. A new Medicines Act is in preparation and about 1000 generic names are on the market. DRUG EDUCATION: Pharmaca: the Croatian journal of pharmacotherapy has been published since 1962, there are several Drug bulletins (one published since 1975); special chapters on clinical pharmacology in textbooks, translation of three editions of Laurence's textbook with special commentary and adaptation to local needs; ADR spontaneous and intensive monitoring (WHO programme) with a personal feedback to the reporters and regular articles on drug use in a number of periodicals. Data on drug consumption indicates that there is room for improvement of prescribing. There is an enthusiasm for 'vasoactive drugs'--after dipirydamole came oxpentifylline and antimicrobials are always overprescribed. All these problems will hopefully decrease when the war finally stops and when industry (especially tourism) starts being fruitful again. In any case the importance of teaching of pharmacotherapy at the under- and postgraduate level should be recognized.
Illicit Drug Use and Problem Gambling
Wayne Skinner, W. J.; Matheson, Flora I.
2013-01-01
Problem gambling, substance use disorders, and their cooccurrence are serious public health concerns. We conducted a comprehensive review of the literature to understand the present state of the evidence on these coaddictions. Our main focus was illicit drug use rather than misuse of legal substances. The review covers issues related to gambling as a hidden problem in the illicit drug use community; prevalence, problem gambling, and substance use disorders as kindred afflictions; problem gambling as an addiction similar to illicit drug use; risk factors and problems associated with comorbidity, and gender issues. We end with some suggestions for future research. PMID:25938114
Drug problems among health professionals.
Janecek, E; Marshman, J A; Brewster, J M
1989-03-01
Available information on patterns of alcohol and drug abuse among health professionals, as well as information on abuse versus impairment, is reviewed. Past and present attitudes and approaches to helping the alcohol- or drug-impaired health professional in Ontario are examined.
Prescription drug abuse: problem, policies, and implications.
Phillips, Janice
2013-01-01
This article provides an overview on prescription drug abuse and highlights a number of related legislative bills introduced during the 112th Congress in response to this growing epidemic. Prescription drug abuse has emerged as the nation's fastest growing drug problem. Although prescription drugs have been used effectively and appropriately for decades, deaths from prescription pain medicine in particular have reached epidemic proportions. Bills related to prescription drug abuse introduced during the 112th Congress focus on strengthening provider and consumer education, tracking and monitoring prescription drug abuse, improving data collection on drug overdose fatalities, combating fraud and abuse in Medicare and Medicaid programs, reclassifying drugs to make them more difficult to prescribe and obtain, and enforcing stricter penalties for individuals who operate scam pain clinics and sell pain pills illegitimately. This article underscores the importance of a multifaceted approach to combating prescription drug abuse and concludes with implications for nursing.
Addressing the clinical needs of problem drug user patients
Krupski, Antoinette; West, Imara I.; Graves, Meredith C.; Atkins, David C.; Maynard, Charles; Bumgardner, Kristin; Donovan, Dennis; Ries, Richard; Roy-Byrne, Peter
2016-01-01
Introduction Illicit drug use is a serious public health problem associated with significant co-occurring medical disorders, mental disorders, and social problems. Yet most individuals with drug use disorders have never been treated, though they often seek medical treatment in primary care. The purpose of the present study was to examine baseline characteristics of persons presenting in primary care across a range of problem drug use severity to identify their clinical needs. Methods We examined socio-demographic characteristics, medical and psychiatric comorbidities, drug use severity, social and legal problems, and service utilization for 868 patients with drug problems recruited from primary care clinics in a safety-net medical setting. Based on Drug Abuse Screening Test (DAST-10) results, individuals were categorized as having low, intermediate, or substantial/severe drug use severity. Results Patients with substantial/severe drug use severity had serious drug use (opiates, stimulants, sedatives, intravenous drug use), high levels of homelessness (50%), psychiatric comorbidity (69%), arrests for serious crimes (24%), and frequent use of expensive emergency department and inpatient hospitals. Patients with low drug use severity were primarily users of marijuana with little reported use of other drugs, less psychiatric co-morbidity, and more stable lifestyles. Patients with intermediate drug use severity fell in-between the substantial/severe and low drug use severity subgroups on most variables. Conclusions Patients with highest drug use severity are likely to require specialized psychiatric and substance abuse care in addition to ongoing medical care that is equipped to address the consequences of severe/substantial drug use including intravenous drug use. Because of their milder symptoms, patients with low drug use severity may benefit from a collaborative care model that integrates psychiatric and substance abuse care in the primary care setting. Patients
Drug problem in southeast and southwest Asia.
Kulsudjarit, Kongpetch
2004-10-01
In 2002, the drug problem in Southeast and Southwest Asia was serious, particularly in the production of opium and heroin in Afghanistan, Myanmar, and Laos, the three largest producers of illicit opium in the world. The increasing illicit manufacture of ATS, particularly methamphetamine, in Southeast Asia, mainly in China and Myanmar, was also a major concern. Some reports indicated that ephedrine, used for illicitly producing methamphetamine in Southeast Asia, is diverted and smuggled out of China and India, whereas caffeine, the adulterant used for producing methamphetamine tablets, is mainly smuggled into Myanmar through its border with Thailand. Seizure data showed a dramatic increase in trafficking in MDMA through Southeast Asia. In terms of the drug epidemic, in 2002, cannabis remained overall the main drug of abuse in all of the countries of Southeast and Southwest Asia. Opiates, mainly opium and heroin, were also the drugs of choice except in Thailand, where opiate abuse declined, but ATS was the main drug of abuse due to its low cost and availability. A significant increase in ATS abuse, amphetamine, methamphetamine, and MDMA among the youth who smoked, sniffed, and inhaled them was reported in Cambodia, China, Indonesia, Laos, Myanmar, the Philippines, and Thailand. Injecting drug use among opiate abusers has been identified as the prime cause of the rapid spread of HIV/AIDS in Southeast and Southwest Asia.
Wang, Yan; Buckingham-Howes, Stacy; Nair, Prasanna; Zhu, Shijun; Magder, Larry; Black, Maureen M.
2014-01-01
Purpose To examine how prenatal heroin/cocaine exposure (PDE) and behavioral problems relate to adolescent drug experimentation. Methods The sample included African American adolescents (mean age=14.2 yr, SD=1.2) with PDE (n=73) and a non-exposed community comparison (n=61). PDE status was determined at delivery through toxicology analysis and maternal-report. Internalizing/externalizing problems were assessed during adolescence with the Behavior Assessment System for Children, Second Edition. Drug experimentation was assessed by adolescent-report and urine analysis. Logistic regression evaluated the likelihood of drug experimentation related to PDE and behavioral problems, adjusting for age, gender, prenatal tobacco/alcohol exposure, perceived peer drug use and caregiver drug use. Interaction terms examined gender modification. Results 67 (50%) used drugs. 25 (19%) used tobacco/alcohol only and 42 (31%) used marijuana/illegal drugs. 94 (70%) perceived peer drug use. PDE significantly increased the risk of tobacco/alcohol experimentation (OR=3.07, 95% CI: 1.09–8.66, p=0.034), but not after covariate adjustment (aOR=1.31, 95% CI: 0.39–4.36, p>0.05). PDE was not related to overall or marijuana/illegal drug experimentation. The likelihood of overall drug experimentation was doubled per Standard Deviation (SD) increase in externalizing problems (aOR=2.28, 95% CI: 1.33–3.91, p=0.003) and, among girls, 2.82 times greater (aOR=2.82, 95% CI: 1.34–5.94, p=0.006) per SD increase in internalizing problems. Age and perceived peer drug use were significant covariates. Conclusions Drug experimentation was relatively common (50%), especially in the context of externalizing problems, internalizing problems (girls only), age, and perceived peer drug use. Findings support Problem Behavior Theory and suggest that adolescent drug prevention address behavioral problems and promote prosocial peer groups. PMID:24768161
Spectral methods for discontinuous problems
NASA Technical Reports Server (NTRS)
Abarbanel, S.; Gottlieb, D.; Tadmor, E.
1985-01-01
Spectral methods yield high-order accuracy even when applied to problems with discontinuities, though not in the sense of pointwise accuracy. Two different procedures are presented which recover pointwise accurate approximations from the spectral calculations.
Affinnih, Yahya H
2002-02-01
This article takes an international perspective on the drug problem in sub-Saharan Africa. This analysis borrows ideas from physical and economic geography as a heuristic device to conceptualize the global narcoscapes in which drug trafficking occurs. Both the legitimate and the illegal drug trade operate within the same global capitalist system and draw on the same technological innovations and business processes. Central to the paper's argument is evidence that sub-Saharan African countries are now integrated into the political economy of drug consumption due to the spill-over effect. These countries are now minor markets for "hard drugs" as the result of the activities of organizations and individual traffickers that use Africa as a staging point in their trade with Europe and the United States. As a result, sub-Saharan African countries have drug consumption problems that were essentially absent prior to 1980, along with associated health, social, and economic costs. The emerging drug problem has forced African countries to develop their own drug control policy. The sub-Saharan African countries mentioned below vary to some extent in the level of drug use and misuse problems: Burundi, Comoros, Djibouti, Eritrea, Ethiopia, Kenya, Madagascar, Malawi, Mauritius, Mozambique, Reunion, Rwanda, Seychelles, Somalia, Tanzania, Uganda, Zambia, Angola, Cameroon, Central African Republic, Chad, Congo, Congo (Zaire), Equatorial Guinea, Gabon, Sao Tome and Principe, Botswana, Lesotho, Namibia, South Africa, Swaziland, Benin, Burkina Faso, Cape Verde, Cote d'Ivoire, Gambia, Ghana, Guinea, Guinea Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, and Togo. As part of this effort, African countries are assessing the health, social, and economic costs of drug-use-related problems to pinpoint methods which are both effective and inexpensive, since their budgets for social programs are severely constrained. Many have progressed to the point of adopting anti-drug
Computational methods in drug discovery
Leelananda, Sumudu P
2016-01-01
The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. PMID:28144341
Computational methods in drug discovery.
Leelananda, Sumudu P; Lindert, Steffen
2016-01-01
The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein-ligand docking, pharmacophore modeling and QSAR techniques are reviewed.
Computational Methods in Drug Discovery
Sliwoski, Gregory; Kothiwale, Sandeepkumar; Meiler, Jens
2014-01-01
Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature. PMID:24381236
Operational analysis for the drug detection problem
NASA Astrophysics Data System (ADS)
Hoopengardner, Roger L.; Smith, Michael C.
1994-10-01
New techniques and sensors to identify the molecular, chemical, or elemental structures unique to drugs are being developed under several national programs. However, the challenge faced by U.S. drug enforcement and Customs officials goes far beyond the simple technical capability to detect an illegal drug. Entry points into the U.S. include ports, border crossings, and airports where cargo ships, vehicles, and aircraft move huge volumes of freight. Current technology and personnel are able to physically inspect only a small fraction of the entering cargo containers. The complexities of how to best utilize new technology to aid the detection process and yet not adversely affect the processing of vehicles and time-sensitive cargo is the challenge faced by these officials. This paper describes an ARPA sponsored initiative to develop a simple, yet useful, method for examining the operational consequences of utilizing various procedures and technologies in combination to achieve an `acceptable' level of detection probability. Since Customs entry points into the U.S. vary from huge seaports to a one lane highway checkpoint between the U.S. and Canadian or Mexico border, no one system can possibly be right for all points. This approach can examine alternative concepts for using different techniques/systems for different types of entry points. Operational measures reported include the average time to process vehicles and containers, the average and maximum numbers in the system at any time, and the utilization of inspection teams. The method is implemented via a PC-based simulation written in GPSS-PC language. Input to the simulation model is (1) the individual detection probabilities and false positive rates for each detection technology or procedure, (2) the inspection time for each procedure, (3) the system configuration, and (4) the physical distance between inspection stations. The model offers on- line graphics to examine effects as the model runs.
The Problem-Drinking Drug Addict. Services Research Report.
ERIC Educational Resources Information Center
Barr, Harriet L.; Cohen, Arie
An increasingly important consideration in drug abuse policy and programming is the growing number of multiple substance abusers, i.e., problem-drinking drug addicts. A longitudinal study of two drug addict populations examined drug and alcohol usage, psychological variables, and criminal justice and employment indicators. Findings indicated that…
Multigrid Methods for EHL Problems
NASA Technical Reports Server (NTRS)
Nurgat, Elyas; Berzins, Martin
1996-01-01
In many bearings and contacts, forces are transmitted through thin continuous fluid films which separate two contacting elements. Objects in contact are normally subjected to friction and wear which can be reduced effectively by using lubricants. If the lubricant film is sufficiently thin to prevent the opposing solids from coming into contact and carries the entire load, then we have hydrodynamic lubrication, where the lubricant film is determined by the motion and geometry of the solids. However, for loaded contacts of low geometrical conformity, such as gears, rolling contact bearings and cams, this is not the case due to high pressures and this is referred to as Elasto-Hydrodynamic Lubrication (EHL) In EHL, elastic deformation of the contacting elements and the increase in fluid viscosity with pressure are very significant and cannot be ignored. Since the deformation results in changing the geometry of the lubricating film, which in turn determines the pressure distribution, an EHL mathematical model must simultaneously satisfy the complex elasticity (integral) and the Reynolds lubrication (differential) equations. The nonlinear and coupled nature of the two equations makes numerical calculations computationally intensive. This is especially true for highly loaded problems found in practice. One novel feature of these problems is that the solution may exhibit sharp pressure spikes in the outlet region. To this date both finite element and finite difference methods have been used to solve EHL problems with perhaps greater emphasis on the use of the finite difference approach. In both cases, a major computational difficulty is ensuring convergence of the nonlinear equations solver to a steady state solution. Two successful methods for achieving this are direct iteration and multigrid methods. Direct iteration methods (e.g Gauss Seidel) have long been used in conjunction with finite difference discretizations on regular meshes. Perhaps one of the best examples of
Methods of assessment of antiepileptic drugs.
Milligan, N; Richens, A
1981-01-01
Epilepsy is a symptom with protean manifestations and as such it is a difficult disease in which to carry out a therapeutic trial. The methods available to research workers for the assessment of new antiepileptic drugs are hampered by the fact that epilepsy is a fluctuant condition. Although it is a chronic disorder open to study using cross-over trials and within-patient comparisons, accurate assessment cannot be easily made at any one point in time. Research workers are therefore automatically placed at a time factor disadvantage and this is especially so for those searching for quick methods of evaluating new compounds. The need for a quick and reliable method of assessing a new antiepileptic drug has long been appreciated. This article will discuss the methods currently available and we will begin by considering the most commonly used method of assessment with particular reference to some of the problems involved in conducting a controlled clinical trial in epilepsy. PMID:7272157
Influences of motivational contexts on prescription drug misuse and related drug problems.
Kelly, Brian C; Rendina, H Jonathon; Vuolo, Mike; Wells, Brooke E; Parsons, Jeffrey T
2015-01-01
Prescription drug misuse has emerged as a significant problem among young adults. While the effects of motivational contexts have been demonstrated for illicit drugs, the role of motivational contexts in prescription drug misuse remains understudied. Using data from 400 young adults recruited via time-space sampling, we examined the role of motivational contexts in the frequency of misuse of three prescription drug types as well as drug-related problems and symptoms of dependency. Both negative and positive motivations to use drugs are associated with increases in prescription drug misuse frequency. Only negative motivations are associated directly with drug problems and drug dependence, as well as indirectly via prescription pain killer misuse. Addressing positive and negative motivational contexts of prescription drug misuse may not only provide a means to reduce misuse and implement harm reduction measures, but may also inform the content of treatment plans for young adults with prescription drug misuse problems.
The Social Construction of the Minority Drug Problem.
ERIC Educational Resources Information Center
Covington, Jeanette
1997-01-01
Examines how the minority drug problem is framed in terms of anomie and underclass models suggesting that drug subcultures in urban black areas are formed as an adaptation to aggregate community conditions. The article considers how researchers use ecological and ethnographic data to back up claims that drug subcultures are a response to inner…
Selective Prevention: Addressing Vulnerability to Problem Drug Use in Europe
ERIC Educational Resources Information Center
Burkhart, Gregor; Gyarmathy, V. Anna; Bo, Alessandra
2011-01-01
Following the 2003 publication of the European Union (EU) Council Recommendations and the 2005-2008 and 2009-2012 EU Drugs Action Plans, increasing attention has been given in EU member states' drug policies to populations that are vulnerable to problem drug use (PDU). Monitoring data reported to the EMCDDA by designated agencies from 30 countries…
Early Twentieth Century Responses to the Drug Problem.
ERIC Educational Resources Information Center
Pfennig, Dennis Joseph
1991-01-01
Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)
Problem drug users known to Bristol general practitioners
Parker, Julie; Gay, Martyn
1987-01-01
A 12-month prospective survey was undertaken of all 239 problem drug users known to general practitioners in Bristol and the doctors' attitudes towards them. The drug users were predominantly young, aged 15-35 years, and males outnumbered females by approximately two to one. Seventy-eight per cent had problems associated with opiates, almost invariably heroin, 10% had problems with stimulants (mainly amphetamine powder), and others had problems with hallucinogens, cannabis, barbiturates and solvents. Opiate dependence was the commonest single problem but ill health, hepatitis, psychiatric illnesses, relationship problems, work and financial difficulties were also frequently mentioned. There was a wide variation in the numbers of problem drug users seen by individual practices, which related both to the situation of the practice and the widely varying attitudes of the partners towards drug users and drug problems. General practitioners were aware of the grapevine that transmits news of their treatment to other users, and individual practices had typically evolved a general strategy for all drug users, to minimize arguments. General practitioners were asked their views about specialist services: they thought that services in the area for drug users were inadequate to help them and their patients in 58% of cases. Several suggestions were made for additional services which were needed. PMID:3448214
Drug laws and the 'derivative' problem.
King, Leslie A; Ujváry, István; Brandt, Simon D
2014-01-01
The concept of a 'derivative' is used widely in chemistry, where its precise meaning depends on the circumstances. However, numerous examples of derivative also occur in domestic drugs legislation, some of which stem from the 1961 United Nations Single Convention on Narcotic Drugs. There is a commonly held view that only 'first-order' derivatives should be considered: substances that can be created from a parent structure in a single chemical reaction. In other words, 'derivatives of derivatives' are excluded. However, some substances related to ecgonine (e.g. 2-carbomethoxytropinone) are clearly convertible to cocaine, even though this may require more than one reaction step. It follows that 2-carbomethoxytropinone is a controlled drug, a situation that most chemists would regard as perverse. A more extreme example of the complexity of 'derivative' is shown by the conversion of thebaine to buprenorphine. Even though this requires six or more stages, the US Drug Enforcement Administration successfully argued in a 1986 case that for the purposes of the Controlled Substances Act, the number of steps required was irrelevant; buprenorphine was a derivative of thebaine. Because the term derivative is rarely defined in statutes, the legal status of some substances, such as 2-bromo-LSD, is uncertain. Although a number of definitions of derivative can be found in the chemical literature, no single definition is adequate to describe all situations where it occurs in legislation. Unless qualified, it is suggested that the term derivative should be avoided in any future legislation.
[Drugs, a current problem: difficulties in handling drug addictions].
Amigo Tadín, Montserrat
2005-12-01
A patient suffering a drug addiction usually presents some characteristic demands and necessities. A professional's attitude must be clear and firm, showing empathy and being an active listener offering assistance, but not expressing either rebuke or threats. The professional attending such a patient takes advantage of a consultation to motivate the patient to begin, or continue, treatment in a corresponding specialized center and will process the necessary paperwork to contact such a center.
2010 drug packaging review: identifying problems to prevent errors.
2011-06-01
Prescrire's analyses showed that the quality of drug packaging in 2010 still left much to be desired. Potentially dangerous packaging remains a significant problem: unclear labelling is source of medication errors; dosing devices for some psychotropic drugs create a risk of overdose; child-proof caps are often lacking; and too many patient information leaflets are misleading or difficult to understand. Everything that is needed for safe drug packaging is available; it is now up to regulatory agencies and drug companies to act responsibly. In the meantime, health professionals can help their patients by learning to identify the pitfalls of drug packaging and providing safe information to help prevent medication errors.
Parent Drug Education Programs: Reasons, Problems, and Implications.
ERIC Educational Resources Information Center
Fox, Tricia A.
1991-01-01
Presents an overview of parent drug education programs together with information regarding those problems, concerns, and needs faced by parents who are dealing with an offspring drug user/abuser. Emphasizes the unique, individual characteristics of parents and suggests that these influences may be the main determinants of the effectiveness of…
Preventing Alcohol and Other Drug Problems through Drug Education. Policy Bulletin No. 3.
ERIC Educational Resources Information Center
Bailey, William J.
Public schools have a responsibility to educate students about drug abuse, and states have a responsibility to assist schools in their efforts. Properly designed and implemented drug education programs are the most cost-effective means of preventing alcohol and other drug problems. Poorly designed and implemented programs, on the other hand, can…
Drug Response Prediction as a Link Prediction Problem
Stanfield, Zachary; Coşkun, Mustafa; Koyutürk, Mehmet
2017-01-01
Drug response prediction is a well-studied problem in which the molecular profile of a given sample is used to predict the effect of a given drug on that sample. Effective solutions to this problem hold the key for precision medicine. In cancer research, genomic data from cell lines are often utilized as features to develop machine learning models predictive of drug response. Molecular networks provide a functional context for the integration of genomic features, thereby resulting in robust and reproducible predictive models. However, inclusion of network data increases dimensionality and poses additional challenges for common machine learning tasks. To overcome these challenges, we here formulate drug response prediction as a link prediction problem. For this purpose, we represent drug response data for a large cohort of cell lines as a heterogeneous network. Using this network, we compute “network profiles” for cell lines and drugs. We then use the associations between these profiles to predict links between drugs and cell lines. Through leave-one-out cross validation and cross-classification on independent datasets, we show that this approach leads to accurate and reproducible classification of sensitive and resistant cell line-drug pairs, with 85% accuracy. We also examine the biological relevance of the network profiles. PMID:28067293
Outcome Trajectories in Drug Court: Do All Participants Have Drug Problems?
Dematteo, David; Marlowe, Douglas B; Festinger, David S; Arabia, Patricia L
2009-04-01
Graduation rates in drug courts average 50% to 70%, but it is unclear what proportion of graduates responded to the drug court services and what proportion might not have had serious drug problems upon entry. This study cluster-analyzed urine drug screen results during the first 14 weeks of treatment on 284 participants from three misdemeanor drug courts. A four-cluster solution (R(2) > .75) produced distinct subgroups characterized by (1) consistently drug-negative urine specimens (34% of the sample), (2) consistently drug-positive specimens (21%), (3) consistently missed urine specimens (26%), and (4) urine specimens that began as drug-positive but became progressively drug-negative over time (19%). These data suggest that approximately one-third of the participants might not have had serious drug problems upon entry. Approximately one-fifth appeared to respond to drug court services, and nearly one-half continued to exhibit problems after 14 weeks. Implications for adaptive programming in drug courts are discussed.
Drug permeability prediction using PMF method.
Meng, Fancui; Xu, Weiren
2013-03-01
Drug permeability determines the oral availability of drugs via cellular membranes. Poor permeability makes a drug unsuitable for further development. The permeability may be estimated as the free energy change that the drug should overcome through crossing membrane. In this paper the drug permeability was simulated using molecular dynamics method and the potential energy profile was calculated with potential of mean force (PMF) method. The membrane was simulated using DPPC bilayer and three drugs with different permeability were tested. PMF studies on these three drugs show that doxorubicin (low permeability) should pass higher free energy barrier from water to DPPC bilayer center while ibuprofen (high permeability) has a lower energy barrier. Our calculation indicates that the simulation model we built is suitable to predict drug permeability.
Lam, Charlene; Wiederman, Michael W.
2011-01-01
Objective: Previous research indicates relationships between alcohol/substance misuse and criminal behavior, but past studies have restricted investigations to atypical samples and/or utilized limited assessments of illegal behavior. In the present study, we explored relationships between alcohol/drug problems and charges for 27 criminal behaviors in a primary care sample. Method: Participants were a cross-sectional sample of 376 consecutive men and women, aged 18 years or older, being seen for nonemergent medical care at an outpatient internal medicine clinic staffed predominantly by residents and located in a midsized, midwestern city in October 2010. Using a self-report survey methodology, we examined relationships between alcohol and drug problems (“Have you ever had a problem with alcohol?” and “Have you ever had a problem with drugs?”) and 27 illegal behaviors as delineated by the categories used by the US Federal Bureau of Investigation. Results: Men with alcohol or drug problems statistically exhibited the greatest number of charges for different forms of illegal behavior (P < .001). These charges were directly related to alcohol/drug misuse (eg, driving under the influence of alcohol or drugs) and otherwise (eg, aggravated assault, simple assault, gambling, larceny-theft). Conclusions: In primary care settings, men with alcohol/drug problems may also have a history of illegal behaviors—a finding that is relevant in terms of social and legal implications. PMID:22454803
Community Development Strategies To Prevent Alcohol and Other Drug Problems.
ERIC Educational Resources Information Center
Strategy Alert, 1992
1992-01-01
How community-based groups are confronting and preventing alcohol and other drug problems and related crime in their communities is the focus of this publication. A wide range of approaches and strategies, used by 10 nonprofit, community-based organizations representative of urban and rural areas, are presented. Case studies describe two community…
Potential and problems in ultrasound-responsive drug delivery systems
Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping
2013-01-01
Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531
Multi-objective optimization methods in drug design.
Nicolaou, Christos A; Brown, Nathan
2013-09-01
Drug discovery is a challenging multi-objective problem where numerous pharmaceutically important objectives need to be adequately satisfied for a solution to be found. The problem is characterized by vast, complex solution spaces further perplexed by the presence of conflicting objectives. Multi-objective optimization methods, designed specifically to address such problems, have been introduced to the drug discovery field over a decade ago and have steadily gained in acceptance ever since. This paper reviews the latest multi-objective methods and applications reported in the literature, specifically in quantitative structure–activity modeling, docking, de novo design and library design. Further, the paper reports on related developments in drug discovery research and advances in the multi-objective optimization field.
Policy Issues and the Drug Abuse Problem in America: Overview, Critique, and Recommendations.
ERIC Educational Resources Information Center
Johnston, Lloyd D.
The so-called "drug abuse problem" in America is really a constellation of separate but related problems; since a variety of drugs are illicitly used, and drug abuse leads to many derivative problems, both within and outside the United States. This monograph begins by assessing the current state of the drug abuse problem in America, and analyzing…
Automated method for study of drug metabolism
NASA Technical Reports Server (NTRS)
Furner, R. L.; Feller, D. D.
1973-01-01
Commercially available equipment can be modified to provide automated system for assaying drug metabolism by continuous flow-through. System includes steps and devices for mixing drug with enzyme and cofactor in the presence of pure oxygen, dialyzing resulting metabolite against buffer, and determining amount of metabolite by colorimetric method.
Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.
Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun
2015-01-01
Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.
Spectral methods for time dependent problems
NASA Technical Reports Server (NTRS)
Tadmor, Eitan
1990-01-01
Spectral approximations are reviewed for time dependent problems. Some basic ingredients from the spectral Fourier and Chebyshev approximations theory are discussed. A brief survey was made of hyperbolic and parabolic time dependent problems which are dealt with by both the energy method and the related Fourier analysis. The ideas presented above are combined in the study of accuracy stability and convergence of the spectral Fourier approximation to time dependent problems.
Regulatory Solutions to the Problem of High Generic Drug Costs
Luo, Jing; Sarpatwari, Ameet; Kesselheim, Aaron S.
2015-01-01
Recent reports have highlighted dramatic price increases for several older generic drugs, including a number of essential products used to treat deadly infectious diseases. Although most of these medicines have been widely available at reasonable prices for decades, some manufacturers have seized on unique features of the pharmaceutical marketplace to seek substantial profits. In this Perspective, we examine limitations in current price regulation among public and private payors and consider several reforms that could address the problem of expensive generic drugs through improved competition. PMID:26693494
Random Walk Method for Potential Problems
NASA Technical Reports Server (NTRS)
Krishnamurthy, T.; Raju, I. S.
2002-01-01
A local Random Walk Method (RWM) for potential problems governed by Lapalace's and Paragon's equations is developed for two- and three-dimensional problems. The RWM is implemented and demonstrated in a multiprocessor parallel environment on a Beowulf cluster of computers. A speed gain of 16 is achieved as the number of processors is increased from 1 to 23.
Annual Report on the State of the Drugs Problem in the European Union, 2000.
ERIC Educational Resources Information Center
European Monitoring Centre for Drugs and Drug Addiction, Lisbon (Portugal).
This report presents an overview of the drug phenomenon in Europe at the start of the new millennium. The first chapter begins with a discussion of overall drug trends. Specifically, it examines trends in drug use and the consequences including multiple drug use; problem drug use and demand for treatment; drug-related deaths; drug-related…
Computer-Aided Drug Design Methods.
Yu, Wenbo; MacKerell, Alexander D
2017-01-01
Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.
Problems in the regulatory policy of the drug market
Miziara, Nathália Molleis; Coutinho, Diogo Rosenthal
2015-01-01
OBJECTIVE Analyze the implementation of drug price regulation policy by the Drug Market Regulation Chamber. METHODS This is an interview-based study, which was undertaken in 2012, using semi-structured questionnaires with social actors from the pharmaceutical market, the pharmaceuticals industry, consumers and the regulatory agency. In addition, drug prices were compiled based on surveys conducted in the state of Sao Paulo, at the point of sale, between February 2009 and May 2012. RESULTS The mean drug prices charged at the point of sale (pharmacies) were well below the maximum price to the consumer, compared with many drugs sold in Brazil. Between 2009 and 2012, 44 of the 129 prices, corresponding to 99 drugs listed in the database of compiled prices, showed a variation of more than 20.0% in the mean prices at the point of sale and the maximum price to the consumer. In addition, many laboratories have refused to apply the price adequacy coefficient in their sales to government agencies. CONCLUSIONS The regulation implemented by the pharmaceutical market regulator was unable to significantly control prices of marketed drugs, without succeeding to push them to levels lower than those determined by the pharmaceutical industry and failing, therefore, in its objective to promote pharmaceutical support for the public. It is necessary reconstruct the regulatory law to allow market prices to be reduced by the regulator as well as institutional strengthen this government body. PMID:26083945
How the US Food and Drug Administration Can Solve the Prescription Drug Shortage Problem
2013-01-01
Drug shortages are threatening care quality and cost-containment efforts. I describe the pharmaceutical marketplace changes that have caused the problem, and propose new policies to solve it, through changing incentives for producers and purchasers. I propose a grading scheme for the Food and Drug Administration when it inspects manufacturing facilities in the United States and abroad. The inspections’ focus would change from closing unsafe plants to improving production process quality, reducing the likelihood that plants will be closed—the most frequent cause of drug shortages. PMID:23488502
[The Swiss population and drug problems: perception of the problems and proposals for solutions].
Leuthold, A; Cattaneo, M; Dubois-Arber, F
1993-01-01
The aim of this study is to investigate which problems in relation with drug abuse are considered to be the most important by the Swiss population and which measures do they support to reduce them. Base for this study are the results of a representative telephone survey realized in october 1991 with 1004 Swiss residents. People are mostly concerned with problems related to the danger for youth and those concerning public order but also with the human condition of addicts. Drug addicts are considered as people who have lost the sense of live, as sick but also as dangerous and less truthful. Supported are overall prevention, offers for therapies, the repression of trafficking and money-laundering but not of drug users as well as measures going in the direction of harm-minimisation (shooting rooms, medical prescription of drugs). Younger people, those with higher education and the german-speaking population have a more positive view of drug addicts and support measures in the sense of harm-minimisation. Elder people and the french-speaking population have a rather negative view of drug addicts and don't favour measures for harm-minimisation.
Spectral methods for exterior elliptic problems
NASA Technical Reports Server (NTRS)
Canuto, C.; Hariharan, S. I.; Lustman, L.
1984-01-01
Spectral approximations for exterior elliptic problems in two dimensions are discussed. As in the conventional finite difference or finite element methods, the accuracy of the numerical solutions is limited by the order of the numerical farfield conditions. A spectral boundary treatment is introduced at infinity which is compatible with the infinite order interior spectral scheme. Computational results are presented to demonstrate the spectral accuracy attainable. Although a simple Laplace problem is examined, the analysis covers more complex and general cases.
An efficient method for inverse problems
NASA Technical Reports Server (NTRS)
Daripa, Prabir
1987-01-01
A new inverse method for aerodynamic design of subcritical airfoils is presented. The pressure distribution in this method can be prescribed in a natural way, i.e. as a function of arclength of the as yet unknown body. This inverse problem is shown to be mathematically equivalent to solving a single nonlinear boundary value problem subject to known Dirichlet data on the boundary. The solution to this problem determines the airfoil, the free stream Mach number M(sub x) and the upstream flow direction theta(sub x). The existence of a solution for any given pressure distribution is discussed. The method is easy to implement and extremely efficient. We present a series of results for which comparisons are made with the known airfoils.
Researching the spiritual dimensions of alcohol and other drug problems.
Miller, W R
1998-07-01
Although religions have been far from silent on the use of psychoactive drugs, and spirituality has long been emphasized as an important factor in recovery from addiction, surprisingly little research has explored the relationships between these two phenomena. Current findings indicate that spiritual/religious involvement may be an important protective factor against alcohol/drug abuse. Individuals currently suffering from these problems are found to have a low level of religious involvement, and spiritual (re)engagement appears to be correlated with recovery. Reasons are explored for the lack of studies testing spiritual hypotheses, and promising avenues for future research are discussed. Comprehensive addictions research should include not only biomedical, psychological and socio-cultural factors but spiritual aspects of the individual as well.
Transport Test Problems for Hybrid Methods Development
Shaver, Mark W.; Miller, Erin A.; Wittman, Richard S.; McDonald, Benjamin S.
2011-12-28
This report presents 9 test problems to guide testing and development of hybrid calculations for the ADVANTG code at ORNL. These test cases can be used for comparing different types of radiation transport calculations, as well as for guiding the development of variance reduction methods. Cases are drawn primarily from existing or previous calculations with a preference for cases which include experimental data, or otherwise have results with a high level of confidence, are non-sensitive, and represent problem sets of interest to NA-22.
Adjoint variational methods in nonconservative stability problems.
NASA Technical Reports Server (NTRS)
Prasad, S. N.; Herrmann, G.
1972-01-01
A general nonself-adjoint eigenvalue problem is examined and it is shown that the commonly employed approximate methods, such as the Galerkin procedure, the method of weighted residuals and the least square technique lack variational descriptions. When used in their previously known forms they do not yield stationary eigenvalues and eigenfunctions. With the help of an adjoint system, however, several analogous variational descriptions may be developed and it is shown in the present study that by properly restating the method of least squares, stationary eigenvalues may be obtained. Several properties of the adjoint eigenvalue problem, known only for a restricted group, are shown to exist for the more general class selected for study.
[Drug-facilitated crime: a public health problem?].
Goullé, Jean-Pierre; Saussereau, Elodie; Guerbet, Michel; Lacroix, Christian
2010-02-01
Drug-facilitated crime (DFC) is well known to the public, yet general practitioners and other physicians are unfamiliar with this issue, largely because toxicology is not part of the medical curriculum. This often leads to diagnostic errors. The frequency of DFC is underestimated, often owing to late examination and analytical problems. On 24 December 2002 the French authorities issued a circular defining DFC as "the administration of a psychoactive drug without the victim's knowledge, as a means of aggression"; and listing places where victims can be managed On 19 July 2005, the French Agency for Health Product Safety (Afssaps) sent a letter to all professionals potentially concerned by this issue, offering guidelines for both medical personnel and laboratory staff conducting toxicological investigations. One difficulty in drug identification is that the doses administered are often low. Toxicology laboratories need sophisticated equipment and expertise to ensure that the perpetrator is prosecuted or, alternatively, to rule out DFC. More information is needed, not only for the public but also for physicians and toxicologists. Benzodiazepines and related compounds are identified in about 75% of DFC cases.
New drug treatments for alcohol problems: a critical appraisal.
Moncrieff, J; Drummond, D C
1997-08-01
This review considers the novel drug treatments that have been suggested to help prevent relapse or attenuate drinking in people with alcohol problems. The evidence from randomized controlled trials for the efficacy of some of the main candidates: acamprosate, naltrexone, bromocriptine, selective serotonin re-uptake inhibitors and buspirone, was examined. Important methodological problems which may have introduced bias were detected in many of the trials. These included failure to test the integrity of the double blind, excluding or estimating outcome in early withdrawals and the comparison of groups on multiple outcome measures with selective reporting of results. In addition, the generalizability of some studies was limited by the procedures used for sample selection. In view of the potential adverse effects of drug treatment it is concluded that the evidence is not strong enough to support the introduction of any of these substances into routine clinical practice at present. The review also emphasizes the importance of methodological rigour to maximize objectivity in treatment evaluation research.
The linear separability problem: some testing methods.
Elizondo, D
2006-03-01
The notion of linear separability is used widely in machine learning research. Learning algorithms that use this concept to learn include neural networks (single layer perceptron and recursive deterministic perceptron), and kernel machines (support vector machines). This paper presents an overview of several of the methods for testing linear separability between two classes. The methods are divided into four groups: Those based on linear programming, those based on computational geometry, one based on neural networks, and one based on quadratic programming. The Fisher linear discriminant method is also presented. A section on the quantification of the complexity of classification problems is included.
An inverse problem by boundary element method
Tran-Cong, T.; Nguyen-Thien, T.; Graham, A.L.
1996-02-01
Boundary Element Methods (BEM) have been established as useful and powerful tools in a wide range of engineering applications, e.g. Brebbia et al. In this paper, we report a particular three dimensional implementation of a direct boundary integral equation (BIE) formulation and its application to numerical simulations of practical polymer processing operations. In particular, we will focus on the application of the present boundary element technology to simulate an inverse problem in plastics processing.by extrusion. The task is to design profile extrusion dies for plastics. The problem is highly non-linear due to material viscoelastic behaviours as well as unknown free surface conditions. As an example, the technique is shown to be effective in obtaining the die profiles corresponding to a square viscoelastic extrudate under different processing conditions. To further illustrate the capability of the method, examples of other non-trivial extrudate profiles and processing conditions are also given.
Prevalence of skin problems and leg ulceration in a sample of young injecting drug users
2014-01-01
Background Drug users suffer harm from the injecting process, and clinical services are reporting increasing numbers presenting with skin-related problems such as abscesses and leg ulcers. Skin breakdown can lead to long-term health problems and increased service costs and is often the first indication of serious systemic ill health. The extent of skin problems in injecting drug users has not previously been quantified empirically, and there is a dearth of robust topical literature. Where skin problems have been reported, this is often without clear definition and generic terms such as ‘soft tissue infection’ are used which lack specificity. The aim of this study was to identify the range and extent of skin problems including leg ulceration in a sample of injecting drug users. Definitions of skin problems were developed and applied to descriptions from drug users to improve rigour. Methods Data were collected in needle exchanges and methadone clinics across Glasgow, Scotland, from both current and former drug injectors using face-to-face interviews. Results Two hundred participants were recruited, of which 74% (n = 148) were males and 26% (n = 52) were females. The age range was 21–44 years (mean 35 years). Just under two thirds (64%, n = 127) were currently injecting or had injected within the last 6 months, and 36% (n = 73) had previously injected and had not injected for more than 6 months. Sixty per cent (n = 120) of the sample had experienced a skin problem, and the majority reported more than one problem. Most common were abscesses, lumps, track marks and leg ulcers. Fifteen per cent (n = 30) of all participants reported having had a leg ulcer. Conclusions This is an original empirical study which demonstrated unique findings of a high prevalence of skin disease (60%) and surprisingly high rates of leg ulceration (15%). Skin disease in injecting drug users is clearly widespread. Leg ulceration in particular is a chronic recurring
Variational Bayesian Approximation methods for inverse problems
NASA Astrophysics Data System (ADS)
Mohammad-Djafari, Ali
2012-09-01
Variational Bayesian Approximation (VBA) methods are recent tools for effective Bayesian computations. In this paper, these tools are used for inverse problems where the prior models include hidden variables and where where the estimation of the hyper parameters has also to be addressed. In particular two specific prior models (Student-t and mixture of Gaussian models) are considered and details of the algorithms are given.
Lattice Boltzmann Methods for Multiscale Fluid Problems
NASA Astrophysics Data System (ADS)
Succi, Sauro; E, Weinan; Kaxiras, Efthimios
Complex interdisciplinary phenomena, such as drug design, crackpropagation, heterogeneous catalysis, turbulent combustion and many others, raise a growing demand of simulational methods capable of handling the simultaneous interaction of multiple space and time scales. Computational schemes aimed at such type of complex applications often involve multiple levels of physical and mathematical description, and are consequently referred to as to multiphysics methods [1-3]. The opportunity for multiphysics methods arises whenever single-level methods, say molecular dynamics and partial differential equations of continuum mechanics, expand their range of scales to the point where overlap becomes possible. In order to realize this multiphysics potential specific efforts must be directed towards the development of robust and efficient interfaces dealing with "hand-shaking" regions where the exchange of information between the different schemes takes place. Two-level schemes combing atomistic and continuum methods for crack propagation in solids or strong shock fronts in rarefied gases have made their appearance in the early 90s. More recently, threelevel schemes for crack dynamics, combining finite-element treatment of continuum mechanics far away from the crack with molecular dynamics treatment of atomic motion in the near-crack region and a quantum mechanical description of bond-snapping in the crack tip have been demonstrated.
ERIC Educational Resources Information Center
Lowinger, Robert Jay
2012-01-01
A sample of 201 college students were surveyed with respect to their perceptions of severity and willingness to seek psychological help for drug and alcohol problems. Results indicated that students perceive alcohol problems as significantly less serious than drug problems and are significantly less willing to seek help for alcohol problems. Males…
Morino, Taichi; Okazaki, Mitsuhiro; Toda, Takaki; Yokoyama, Takashi
2015-12-01
Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future.
Drug-related problems in medical wards of Tikur Anbessa specialized hospital, Ethiopia
Ayalew, Mohammed Biset; Megersa, Teshome Nedi; Mengistu, Yewondwossen Taddese
2015-01-01
Objective: This study was aimed to determine the prevalence of drug-related problems (DRPs), identify the most common drugs, and drug classes involved in DRPs as well as associated factors with the occurrence of DRPs. Methods: A prospective cross-sectional study was conducted on 225 patients admitted to medical wards of Tikur Anbessa Specialized Hospital, Addis Ababa from March to June 2014. Data regarding patient characteristics, medications, diagnosis, length of hospitalization, investigation, and laboratory results were collected using data abstraction forms through review of patients’ medical card and medication charts. Identified DRPs were recorded and classified using DRP registration forms. The possible intervention measures for the identified DRPs were proposed and communicated to either the physician or the patient. Data were entered into Epi Info 7 and analyzed using SPSS version 21 (IBM Corp. Released 2012, Armonk, NY: IBM Corp). Findings: DRPs were found in 52% of study subjects. A drug-drug interaction (48% of all DRPs) was the most common DRP followed by adverse drug reaction (23%). Anti-infectives and gastrointestinal medicines were commonly involved in DRPs. Drugs with the highest drug risk ratio were gentamycin, warfarin, nifedipine, and cimetidine. The number of drugs taken by the patient per day is an important risk factor for DRPs. Conclusion: DRPs are common among medical ward patients. Polypharmacy has a significant association with the occurrence of DRP. Drugs such as gentamycin, warfarin, nifedipine, and cimetidine have the highest probability of causing DRP. So, patients who are taking either of these drugs or polypharmacy should be closely assessed for identification and timely correction of DRPs. PMID:26645029
A meshless method for unbounded acoustic problems.
Shojaei, Arman; Boroomand, Bijan; Soleimanifar, Ehsan
2016-05-01
In this paper an effective meshless method is proposed to solve time-harmonic acoustic problems defined on unbounded domains. To this end, the near field is discretized by a set of nodes and the far field effect is taken into account by considering radiative boundary conditions. The approximation within the near field is performed using a set of local residual-free basis functions defined on a series of finite clouds. For considering the far field effect, a series of infinite clouds are defined on which another set of residual-free bases, satisfying the radiation conditions, are considered for the approximation. Validation of the results is performed through solving some acoustic problems.
ERIC Educational Resources Information Center
Cargill, Tamsin; Weaver, Tim D.; Patterson, Sue
2012-01-01
Aims: This study investigated the commissioning and delivery of advocacy for problem drug users. We aimed to quantify provision, describe the commissioning of advocacy services in Drug Action Teams (DATs) and to identify factors influencing advocacy provision. Methods: A cross-sectional survey of a randomly selected sample of 50 English DATs. The…
Potential new methods for antiepileptic drug delivery.
Fisher, Robert S; Ho, Jet
2002-01-01
Use of novel drug delivery methods could enhance the efficacy and reduce the toxicity of antiepileptic drugs (AEDs). Slow-release oral forms of medication or depot drugs such as skin patches might improve compliance and therefore seizure control. In emergency situations, administration via rectal, nasal or buccal mucosa can deliver the drug more quickly than can oral administration. Slow-release oral forms and rectal forms of AEDs are already approved for use, nasal and buccal administration is currently off-label and skin patches for AEDs are an attractive but currently hypothetical option. Therapies under development may result in the delivery of AEDs directly to the regions of the brain involved in seizures. Experimental protocols are underway to allow continuous infusion of potent excitatory amino acid antagonists into the CSF. In experiments with animal models of epilepsy, AEDs have been delivered successfully to seizure foci in the brain by programmed infusion pumps, acting in response to computerised EEG seizure detection. Inactive prodrugs can be given systemically and activated at the site of the seizure focus by locally released compounds. One such drug under development is DP-VPA (or DP16), which is cleaved to valproic acid (sodium valproate) by phospholipases at the seizure focus. Liposomes and nanoparticles are engineered micro-reservoirs of a drug, with attached antibodies or receptor-specific binding agents designed to target the particles to a specific region of the body. Liposomes in theory could deliver a high concentration of an AED to a seizure focus. Penetration of the blood-brain barrier can be accomplished by linking large particles to iron transferrin or biological toxins that can cross the barrier. In the near future, it is likely that cell transplants that generate neurotransmitters and neuromodulators will accomplish renewable endogenous drug delivery. However, the survival and viability of transplanted cells have yet to be demonstrated
Numerical methods for problems in computational aeroacoustics
NASA Astrophysics Data System (ADS)
Mead, Jodi Lorraine
1998-12-01
A goal of computational aeroacoustics is the accurate calculation of noise from a jet in the far field. This work concerns the numerical aspects of accurately calculating acoustic waves over large distances and long time. More specifically, the stability, efficiency, accuracy, dispersion and dissipation in spatial discretizations, time stepping schemes, and absorbing boundaries for the direct solution of wave propagation problems are determined. Efficient finite difference methods developed by Tam and Webb, which minimize dispersion and dissipation, are commonly used for the spatial and temporal discretization. Alternatively, high order pseudospectral methods can be made more efficient by using the grid transformation introduced by Kosloff and Tal-Ezer. Work in this dissertation confirms that the grid transformation introduced by Kosloff and Tal-Ezer is not spectrally accurate because, in the limit, the grid transformation forces zero derivatives at the boundaries. If a small number of grid points are used, it is shown that approximations with the Chebyshev pseudospectral method with the Kosloff and Tal-Ezer grid transformation are as accurate as with the Chebyshev pseudospectral method. This result is based on the analysis of the phase and amplitude errors of these methods, and their use for the solution of a benchmark problem in computational aeroacoustics. For the grid transformed Chebyshev method with a small number of grid points it is, however, more appropriate to compare its accuracy with that of high- order finite difference methods. This comparison, for an order of accuracy 10-3 for a benchmark problem in computational aeroacoustics, is performed for the grid transformed Chebyshev method and the fourth order finite difference method of Tam. Solutions with the finite difference method are as accurate. and the finite difference method is more efficient than, the Chebyshev pseudospectral method with the grid transformation. The efficiency of the Chebyshev
Methods for Anticipating Problems with Electrical Wiring
NASA Technical Reports Server (NTRS)
Yost, William T. (Inventor); Cramer, K. Elliott (Inventor); Perey, Daniel F. (Inventor)
2005-01-01
Passive and active methods for anticipating problems with electrical wiring are provided. An insulative material in contact with an electrical conductor has at least one impurity that is impregnated in the insulative material and/or disposed thereon. An environment around the electrical conductor is monitored for the presence or the level of the impurity(ies) emanating from the insulative material in the form of a gaseous effluent. An alarm signal is generated when a predetermined level of the gaseous effluent is detected.
Drug susceptibility testing by dilution methods.
Jeannot, Katy; Plésiat, Patrick
2014-01-01
Serial twofold dilution methods are widely used to assess the bacteriostatic activities of antibiotics. This can be achieved by dilution of considered drugs in agar medium or in culture broth, and inoculation by calibrated inoculums. Although seemingly simple, these methods are greatly influenced by the experimental conditions used and may lead to discrepant results, in particular with untrained investigators. The present step-by-step protocol has been validated for Pseudomonas species, including P. aeruginosa. Introduction of appropriate control strains is crucial to ascertain minimal inhibitory concentration values and compare the results of independent experiments.
Kinetics methods for clinical epidemiology problems.
Corlan, Alexandru Dan; Ross, John
2015-11-17
Calculating the probability of each possible outcome for a patient at any time in the future is currently possible only in the simplest cases: short-term prediction in acute diseases of otherwise healthy persons. This problem is to some extent analogous to predicting the concentrations of species in a reactor when knowing initial concentrations and after examining reaction rates at the individual molecule level. The existing theoretical framework behind predicting contagion and the immediate outcome of acute diseases in previously healthy individuals is largely analogous to deterministic kinetics of chemical systems consisting of one or a few reactions. We show that current statistical models commonly used in chronic disease epidemiology correspond to simple stochastic treatment of single reaction systems. The general problem corresponds to stochastic kinetics of complex reaction systems. We attempt to formulate epidemiologic problems related to chronic diseases in chemical kinetics terms. We review methods that may be adapted for use in epidemiology. We show that some reactions cannot fit into the mass-action law paradigm and solutions to these systems would frequently exhibit an antiportfolio effect. We provide a complete example application of stochastic kinetics modeling for a deductive meta-analysis of two papers on atrial fibrillation incidence, prevalence, and mortality.
Tuberculosis in London: the importance of homelessness, problem drug use and prison
Story, A; Murad, S; Roberts, W; Verheyen, M; Hayward, A C
2007-01-01
Background The control of tuberculosis (TB) is founded on early case detection and complete treatment of disease. In the UK, TB is concentrated in subgroups of the population in large urban centres. The impact of homelessness, imprisonment and problem drug use on TB control in London is reviewed. Methods A cohort study was undertaken of all patients with TB in Greater London to determine the point prevalence of disease in different groups and to examine risk factors for smear positivity, drug resistance, treatment adherence, loss to follow‐up and use of directly observed therapy (DOT). Results Data were collected on 97% (1941/1995) of eligible patients. The overall prevalence of TB was 27 per 100 000. An extremely high prevalence of TB was seen in homeless people (788/100 000), problem drug users (354/100 000) and prisoners (208/100 000). Multivariate analysis showed that problem drug use was associated with smear positive disease (OR 2.2, p<0.001), being part of a known outbreak of drug resistant TB (OR 3.5, p = 0.001) and loss to follow‐up (OR 2.7, p<0.001). Imprisonment was associated with being part of the outbreak (OR 10.3, p<0.001) and poor adherence (OR 3.9, p<0.001). Homelessness was associated with infectious TB (OR 1.6, p = 0.05), multidrug resistance (OR 2.1, p = 0.03), poor adherence (OR 2.5, p<0.001) and loss to follow‐up (OR 3.8, p<0.001). In London, homeless people, prisoners and problem drug users collectively comprise 17% of TB cases, 44% of smear positive drug resistant cases, 38% of poorly compliant cases and 44% of cases lost to follow‐up. 15% of these patients start treatment on DOT but 46% end up on DOT. Conclusions High levels of infectious and drug resistant disease, poor adherence and loss to follow‐up care indicate that TB is not effectively controlled among homeless people, prisoners and problem drug users in London. PMID:17289861
Alcohol and Drugs in Schools: Teachers' Reactions to the Problem
ERIC Educational Resources Information Center
Finn, Kristin V.; Willert, H. Jeannette
2006-01-01
Although schools are places for learning and growth, they are also places where students engage in alcohol and drug use. This study showed that most teachers were aware of drugs in their schools, but did not regard drug use as an interference in their own classrooms. Many teachers were knowledgeable about their schools' drug policy, but did not…
Hybrid intelligent optimization methods for engineering problems
NASA Astrophysics Data System (ADS)
Pehlivanoglu, Yasin Volkan
The purpose of optimization is to obtain the best solution under certain conditions. There are numerous optimization methods because different problems need different solution methodologies; therefore, it is difficult to construct patterns. Also mathematical modeling of a natural phenomenon is almost based on differentials. Differential equations are constructed with relative increments among the factors related to yield. Therefore, the gradients of these increments are essential to search the yield space. However, the landscape of yield is not a simple one and mostly multi-modal. Another issue is differentiability. Engineering design problems are usually nonlinear and they sometimes exhibit discontinuous derivatives for the objective and constraint functions. Due to these difficulties, non-gradient-based algorithms have become more popular in recent decades. Genetic algorithms (GA) and particle swarm optimization (PSO) algorithms are popular, non-gradient based algorithms. Both are population-based search algorithms and have multiple points for initiation. A significant difference from a gradient-based method is the nature of the search methodologies. For example, randomness is essential for the search in GA or PSO. Hence, they are also called stochastic optimization methods. These algorithms are simple, robust, and have high fidelity. However, they suffer from similar defects, such as, premature convergence, less accuracy, or large computational time. The premature convergence is sometimes inevitable due to the lack of diversity. As the generations of particles or individuals in the population evolve, they may lose their diversity and become similar to each other. To overcome this issue, we studied the diversity concept in GA and PSO algorithms. Diversity is essential for a healthy search, and mutations are the basic operators to provide the necessary variety within a population. After having a close scrutiny of the diversity concept based on qualification and
MIB Galerkin method for elliptic interface problems
Xia, Kelin; Zhan, Meng; Wei, Guo-Wei
2014-01-01
Summary Material interfaces are omnipresent in the real-world structures and devices. Mathematical modeling of material interfaces often leads to elliptic partial differential equations (PDEs) with discontinuous coefficients and singular sources, which are commonly called elliptic interface problems. The development of high-order numerical schemes for elliptic interface problems has become a well defined field in applied and computational mathematics and attracted much attention in the past decades. Despite of significant advances, challenges remain in the construction of high-order schemes for nonsmooth interfaces, i.e., interfaces with geometric singularities, such as tips, cusps and sharp edges. The challenge of geometric singularities is amplified when they are associated with low solution regularities, e.g., tip-geometry effects in many fields. The present work introduces a matched interface and boundary (MIB) Galerkin method for solving two-dimensional (2D) elliptic PDEs with complex interfaces, geometric singularities and low solution regularities. The Cartesian grid based triangular elements are employed to avoid the time consuming mesh generation procedure. Consequently, the interface cuts through elements. To ensure the continuity of classic basis functions across the interface, two sets of overlapping elements, called MIB elements, are defined near the interface. As a result, differentiation can be computed near the interface as if there is no interface. Interpolation functions are constructed on MIB element spaces to smoothly extend function values across the interface. A set of lowest order interface jump conditions is enforced on the interface, which in turn, determines the interpolation functions. The performance of the proposed MIB Galerkin finite element method is validated by numerical experiments with a wide range of interface geometries, geometric singularities, low regularity solutions and grid resolutions. Extensive numerical studies confirm
MIB Galerkin method for elliptic interface problems.
Xia, Kelin; Zhan, Meng; Wei, Guo-Wei
2014-12-15
Material interfaces are omnipresent in the real-world structures and devices. Mathematical modeling of material interfaces often leads to elliptic partial differential equations (PDEs) with discontinuous coefficients and singular sources, which are commonly called elliptic interface problems. The development of high-order numerical schemes for elliptic interface problems has become a well defined field in applied and computational mathematics and attracted much attention in the past decades. Despite of significant advances, challenges remain in the construction of high-order schemes for nonsmooth interfaces, i.e., interfaces with geometric singularities, such as tips, cusps and sharp edges. The challenge of geometric singularities is amplified when they are associated with low solution regularities, e.g., tip-geometry effects in many fields. The present work introduces a matched interface and boundary (MIB) Galerkin method for solving two-dimensional (2D) elliptic PDEs with complex interfaces, geometric singularities and low solution regularities. The Cartesian grid based triangular elements are employed to avoid the time consuming mesh generation procedure. Consequently, the interface cuts through elements. To ensure the continuity of classic basis functions across the interface, two sets of overlapping elements, called MIB elements, are defined near the interface. As a result, differentiation can be computed near the interface as if there is no interface. Interpolation functions are constructed on MIB element spaces to smoothly extend function values across the interface. A set of lowest order interface jump conditions is enforced on the interface, which in turn, determines the interpolation functions. The performance of the proposed MIB Galerkin finite element method is validated by numerical experiments with a wide range of interface geometries, geometric singularities, low regularity solutions and grid resolutions. Extensive numerical studies confirm the
Problems and Solutions in Click Chemistry Applied to Drug Probes
Zhong, Weilong; Sun, Bo; Lu, Cheng; Yu, Hengheng; Wang, Changhua; He, Lingfei; Gu, Ju; Chen, Shuang; Liu, Yanrong; Jing, Xiangyan; Bi, Zhun; Yang, Guang; Zhou, Honggang; Sun, Tao; Yang, Cheng
2016-01-01
Small-molecule fluorescent probes have been widely used in target identification, but this method has many disadvantages. For example, the identified proteins are usually complex, and additional biochemical studies are needed to distinguish real targets from interference results. To address this problem, we propose a series of strategies for improving the efficiency of target identification. First, pretreatment with a lower concentration of hydrogen peroxide can shield against thiol interference. Second, the use of benzophenone as a photo-affinity group is not appropriate, and diazirines are preferred. Third, if cytoskeleton proteins or stress proteins are captured, the interference must be carefully eliminated. The specificity of target identification can be improved by optimizing these three strategies. In this paper, we discuss the problems associated with the use of the click reaction in living cells and provide important complementary techniques for photo-affinity probes based on the click chemistry reaction. PMID:27782133
ERIC Educational Resources Information Center
Stein, Judith A.; And Others
1993-01-01
Grandparents' and mothers' drug use predicted hyperactivity, psychosomatic complaints, and social problems for boys, and acting-out behaviors for boys and girls. Maternal drug use predicted fearfulness, hyperactivity, and social problems for boys, and developmental problems for boys and girls. (BC)
Drug use, mental health and problems related to crime and violence: cross-sectional study1
Claro, Heloísa Garcia; de Oliveira, Márcia Aparecida Ferreira; Bourdreaux, Janet Titus; Fernandes, Ivan Filipe de Almeida Lopes; Pinho, Paula Hayasi; Tarifa, Rosana Ribeiro
2015-01-01
Objective: to investigate the correlation between disorders related to the use of alcohol and other drugs and symptoms of mental disorders, problems related to crime and violence and to age and gender. Methods: cross-sectional descriptive study carried out with 128 users of a Psychosocial Care Center for Alcohol and other Drugs, in the city of São Paulo, interviewed by means of the instrument entitled Global Appraisal of Individual Needs - Short Screener. Univariate and multiple linear regression models were used to verify the correlation between the variables. Results: using univariate regression models, internalizing and externalizing symptoms and problems related to crime/violence proved significant and were included in the multiple model, in which only the internalizing symptoms and problems related to crime and violence remained significant. Conclusions: there is a correlation between the severity of problems related to alcohol use and severity of mental health symptoms and crime and violence in the study sample. The results emphasize the need for an interdisciplinary and intersectional character of attention to users of alcohol and other drugs, since they live in a socially vulnerable environment. PMID:26626010
Drug Abuse: Methadone Becomes the Solution and the Problem
ERIC Educational Resources Information Center
Bazell, Robert J.
1973-01-01
Methadone is used to divert heroin addicts from using stronger drugs. Rate of crimes committed by drug addicts has fallen considerably after putting them on methadone. Despite criticisms, methadone use seems to be encouraging for the future. (PS)
Problems of applicability of statistical methods in cosmology
Levin, S. F.
2015-12-15
The problems arising from the incorrect formulation of measuring problems of identification for cosmological models and violations of conditions of applicability of statistical methods are considered.
Developing natural product drugs: Supply problems and how they have been overcome.
Newman, David J
2016-06-01
The development of natural product-derived drugs has some unique problems associated with the process, which can be best described as the "problem of supply". In this short review, four examples are given demonstrating how the "supply problem" was overcome using as examples the development of Picato® from a plant, Kyprolis® modified from a microbial metabolite, Halaven® a totally synthetic compound based on a marine sponge metabolite and Yondelis® isolated from a marine tunicate and now known to be from an as yet uncultured microbe in the tunicate. The methods used are described in each case and show how all scientific disciplines are necessary to succeed. All of these are antitumor agents and the time involved ranged from a low of 13years to greater than 29years from the initial identification of an active compound.
ERIC Educational Resources Information Center
CSR, Inc., Washington, DC.
This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…
Interpersonal and Emotional Problem Solving among Narcotic Drug Abusers.
ERIC Educational Resources Information Center
Appel, Philip W.; Kaestner, Elisabeth
1979-01-01
Measured problem-solving abilities of narcotics abusers using the modified means-ends problem-solving procedure. Good subjects had more total relevent means (RMs) for solving problems, used more introspective and emotional RMs, and were better at RM recognition, but did not have more sufficient narratives than poor subjects. (Author/BEF)
The Drug Problem and the Schools. ERIC Abstracts Series, Number Sixteen.
ERIC Educational Resources Information Center
American Association of School Administrators, Washington, DC.
ERIC abstracts on the drug problem and the schools, announced in RIE through December 1970, are presented. The key terms used in compiling this collection are "drug abuse" and "drug addiction." The following information is presented for each document: Author, title, place of publication, publisher, publication date, number of pages, ERIC document…
Drug Abuse--A School Disaster and A Problem for Guidance.
ERIC Educational Resources Information Center
Brayer, Herbert O.
Drug abuse is an increasingly common problem that must be faced by the school and community. Since counselors have a great deal of responsibility in working with students who abuse drugs, more effective ways of handling this problem need to be considered by them. The first part of this paper is concerned with a plan for working with the secondary…
Currie, Cheryl L; Wild, T Cameron; Schopflocher, Donald P; Laing, Lory; Veugelers, Paul
2013-07-01
Illicit and prescription drug use disorders are two to four times more prevalent among Aboriginal peoples in North America than the general population. Research suggests Aboriginal cultural participation may be protective against substance use problems in rural and remote Aboriginal communities. As Aboriginal peoples continue to urbanize rapidly around the globe, the role traditional Aboriginal beliefs and practices may play in reducing or even preventing substance use problems in cities is becoming increasingly relevant, and is the focus of the present study. Mainstream acculturation was also examined. Data were collected via in-person surveys with a community-based sample of Aboriginal adults living in a mid-sized city in western Canada (N = 381) in 2010. Associations were analysed using two sets of bootstrapped linear regression models adjusted for confounders with continuous illicit and prescription drug problem scores as outcomes. Psychological mechanisms that may explain why traditional culture is protective for Aboriginal peoples were examined using the cross-products of coefficients mediation method. The extent to which culture served as a resilience factor was examined via interaction testing. Results indicate Aboriginal enculturation was a protective factor associated with reduced 12-month illicit drug problems and 12-month prescription drug problems among Aboriginal adults in an urban setting. Increased self-esteem partially explained why cultural participation was protective. Cultural participation also promoted resilience by reducing the effects of high school incompletion on drug problems. In contrast, mainstream acculturation was not associated with illicit drug problems and served as a risk factor for prescription drug problems in this urban sample. Findings encourage the growth of programs and services that support Aboriginal peoples who strive to maintain their cultural traditions within cities, and further studies that examine how Aboriginal
[The therapeutic problem of current drug addiction in Italy].
De Caro, D
1980-04-28
Psicosocial factors which are of main importance for drug-dependences, especially in young people, are examined. Then the most important elements of the therapy of drug-dependences are indicated, which first of all consists in the necessary treatment in the hospital and farmacological therapy (particularly during acute and over-dose states), and also psicotherapeutic--generally speaking--and social approaches. Among those therapeutic Communities seem to be extremely significant, whose most important patterns are described.
Matrix iteration method for nonlinear eigenvalue problems with applications
NASA Astrophysics Data System (ADS)
Ram, Y. M.
2016-12-01
A simple and intuitive matrix iteration method for solving nonlinear eigenvalue problems is described and demonstrated in detail by two problems: (i) the boundary value problem associated with large deflection of a flexible rod, and (ii) the initial value problem associated with normal mode motion of a double pendulum. The two problems are solved by two approaches, the finite difference approach and a continuous realization approach which is similar in spirit to the Rayleigh-Ritz method.
Discontinuous Mixed Covolume Methods for Parabolic Problems
Zhu, Ailing
2014-01-01
We present the semidiscrete and the backward Euler fully discrete discontinuous mixed covolume schemes for parabolic problems on triangular meshes. We give the error analysis of the discontinuous mixed covolume schemes and obtain optimal order error estimates in discontinuous H(div) and first-order error estimate in L2. PMID:24983008
Optimization Problems: Duality and Multiplier Methods.
1982-02-19
provides a new computational handle on many problems in partial differential equations that can be represented as variational inequalities. Much remains...abstract entered in Block 20. If different from Report) DTIC III SUPPLEMENTARY NOTES MARO0 61M8 Nonlinear programming, stochastic programming, subgradient...following headings: (1) nonlinear programming algorithms, (2) multistage gradient analysis and nonsmooth optimization, (5) marginal values and sensitivity
Solution of acoustic workshop problems by a spectral multidomain method
NASA Technical Reports Server (NTRS)
Kopriva, Davis A.; Kolias, John H.
1995-01-01
We use a new staggered grid Chebyshev spectral multidomain method to solve three of the Workshop benchmark problems. The method defines solution unknowns at the nodes of the Chebyshev Gauss quadrature, and the fluxes at the nodes of the Chebyshev Gauss-Lobatto quadrature. The Chebyshev spectral method gives exponentially convergent phase and dissipation errors. The multidomain approximation gives the method flexibility. Using the method, we solve problems in Categories 1 and 5 of the benchmark problems.
Who's to Blame for America's Drug Problem?: The Search for Scapegoats in the "War on Drugs."
ERIC Educational Resources Information Center
Mackey-Kallis, Susan; Hahn, Dan
1994-01-01
Analyzes six years (from 1986 to 1991) of political debate and social action in the United States' war on drugs. Explores the characteristics of guilt-based, scapegoating drug rhetoric and how scapegoating in the drug war has been problematic. Discusses the desirability and limits of guilt as a rhetorical strategy. (HB)
Methods in systems biology of experimental methamphetamine drug abuse.
Kobeissy, Firas H; Sadasivan, Shankar; Buchanan, Melinda; Zhang, Zhiqun; Gold, Mark S; Wang, Kevin K W
2010-01-01
The use of methamphetamine (METH) as recreational drugs is a growing problem worldwide with recent concerns that it might cause long-lasting harmful effects to the human brain. METH is an illicit drug that is known to exert neurotoxic effects on both dopaminergic and serotonergic neural systems. Our laboratory has been studying the biochemical mechanisms underlying METH-induced neurotoxic effects both in vivo and in vitro. Our psychoproteomics METH abuse research focuses on the global alteration of cortical protein expression in rats treated with acute METH. In our analysis, an altered protein expression was identified using a multistep protein separation/proteomic platform. Differential changes of the selected proteins were further confirmed by quantitative immunoblotting. Our study identified 82 differentially expressed proteins, 40 of which were downregulated and 42 of which were upregulated post acute METH treatment. In this chapter, we describe the current protocols for the neuronal cell culture in vitro and the in vivo rat model of acute METH treatment (4 x 10 mg/kg) coupled with the description current bioinformatics analysis utilized to analyze the different implicated interaction protein/gene maps that reflected on the altered functions observed. These methods and protocols are discussed in the paradigm of the acute model of METH drug abuse and neuronal cell culture and can be applied on other models of substance abuse such as on MDMA or cocaine.
Drug delivery systems: polymers and drugs monitored by capillary electromigration methods.
Simó, Carolina; Cifuentes, Alejandro; Gallardo, Alberto
2003-11-25
In this paper, different electromigration methods used to monitor drugs and polymers released from drug delivery systems are reviewed. First, an introduction to the most typical arrangements used as drug delivery systems (e.g., polymer-drug covalent conjugates, membrane or matrix-based devices) is presented. Next, the principles of different capillary electromigration procedures are discussed, followed by a revision on the different procedures employed to monitor the release of drugs and the degradation or solubilization of the polymeric matrices from drug delivery systems during both in vitro and in vivo assays. A critical comparison between these capillary electrophoretic methods and the more common chromatographic methods employed to analyze drugs and polymers from drug delivery systems is presented. Finally, future outlooks of these electromigration procedures in the controlled release field are discussed.
Drug Education--A Problem In Moral Philosophy
ERIC Educational Resources Information Center
Bethell, B. J.; Bellward, G. D.
1973-01-01
During the development or assessment of drug education programs, many individuals insist on the avoidance of "moralizing". An awareness of moral principles, rules and values is a necessary criterion to rational thought processes. This paper attempts to clarify these philosophical issues in a manner which can be put into practice in many types of…
[Selected Readings for the Professional Working with Drug Related Problems.
ERIC Educational Resources Information Center
Wisconsin Univ., Madison.
A bibliography of selected readings compiled at the University of Wisconsin for the National Drug Education Training Program. These selected readings include information on narcotics, amphetamines, mescaline, psilogybin, hallucinogens, LSD, barbiturates, alcohol, and other stimulants. The intended user of this bibliography is the professional…
Ending Discrimination against People with Alcohol and Drug Problems.
ERIC Educational Resources Information Center
Join Together, Boston, MA.
People with alcohol or other drug disease face public and private policies that restrict their access to appropriate health care, employment, and public benefits, discouraging them from seeking treatment, robbing them of hope for recovery, and costing society millions of dollars. Join Together, a project of Boston University School of Public…
Cell averaging Chebyshev methods for hyperbolic problems
NASA Technical Reports Server (NTRS)
Wei, Cai; Gottlieb, David; Harten, Ami
1990-01-01
A cell averaging method for the Chebyshev approximations of first order hyperbolic equations in conservation form is described. Formulas are presented for transforming between pointwise data at the collocation points and cell averaged quantities, and vice-versa. This step, trivial for the finite difference and Fourier methods, is nontrivial for the global polynomials used in spectral methods. The cell averaging methods presented are proven stable for linear scalar hyperbolic equations and present numerical simulations of shock-density wave interaction using the new cell averaging Chebyshev methods.
Brunelle, Natacha; Bertrand, Karine; Beaudoin, Isabelle; Ledoux, Cinthia; Gendron, Annie; Arseneault, Catherine
2013-08-01
Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency.
Alcohol and Other Drugs on Campus: The Scope of the Problem. Infofacts/Resources
ERIC Educational Resources Information Center
Kapner, Daniel Ari
2008-01-01
The most widespread health problem on college and university campuses in the United States is high-risk alcohol and other drug (AOD) use. Recent reports confirm that the nation's campuses continue to encounter significant consequences as a result of this problem. This "Infofacts/Resources" offers an overview of the problem and highlights effective…
Preconditioned Krylov subspace methods for eigenvalue problems
Wu, Kesheng; Saad, Y.; Stathopoulos, A.
1996-12-31
Lanczos algorithm is a commonly used method for finding a few extreme eigenvalues of symmetric matrices. It is effective if the wanted eigenvalues have large relative separations. If separations are small, several alternatives are often used, including the shift-invert Lanczos method, the preconditioned Lanczos method, and Davidson method. The shift-invert Lanczos method requires direct factorization of the matrix, which is often impractical if the matrix is large. In these cases preconditioned schemes are preferred. Many applications require solution of hundreds or thousands of eigenvalues of large sparse matrices, which pose serious challenges for both iterative eigenvalue solver and preconditioner. In this paper we will explore several preconditioned eigenvalue solvers and identify the ones suited for finding large number of eigenvalues. Methods discussed in this paper make up the core of a preconditioned eigenvalue toolkit under construction.
Drug-eluting stents: some first-generation problems.
Murphy, Bruce E
2004-01-01
The recent fervor surrounding the introduction of drug-eluting stents into the practice of cardiology has proven to be problematic. The experience with the Cypher Sirolimus-Eluting Coronary Stent (Cordis Corp., Miami Lakes, FL) at Arkansas Heart Hospital progressed from anxious anticipation to complete removal of the stent from inventory in a 6-month period. Several cases involving edge dissection and subacute thrombosis were the catalyst for the decision to cease use of the device. While new products may entice, each new modality must be approached with measured enthusiasm. Drug-eluting stents are first-generation devices that may have unexposed flaws when used as first-line treatment in routine practice. The first-generation Cypher stent, as with many new devices, offers treatment-not a cure-for coronary atherosclerosis and enhances the desire for an evolved product.
Numerical Methods for Initial Value Problems.
1980-07-01
of general multistep methods for ordinary differential equations a4 to implement an efficient algorithm for the solution of stiff equations . Still...integral equations II. Roundoff error for variants of Gaussian elimination III. Multistep methods for ordinary differential equations IV. Multi-grid...62 -! Paige III. NUMERICAL SOLUTION OF ORDINARY DIFFERENTIAL EQUATIONS ....... 63 1. Equivalent Forms of Multistep
Postmarketing surveillance of adverse drug reactions: problems and solutions.
Lortie, F M
1986-01-01
The surveillance of adverse drug reactions (ADRs) is an unqualified must. However, the optimal means of surveillance is still unclear. Although anecdotal reports are the backbone of an ADR surveillance system, they are not enough. The pharmaceutical industry, academics and regulatory agencies need to expand their efforts in monitoring ADRs. The author discusses the various techniques for counting and evaluating adverse reactions and suggests ways in which the system could be improved. PMID:3719483
The problems of classification: Method of committees
NASA Astrophysics Data System (ADS)
Nikonov, Oleg I.; Chernavin, Fedor P.; Medvedeva, Marina A.
2016-06-01
In the paper, we consider a particular case of a neural network - a committee method. The described approach was first introduced by the paper of Ablow and Kaylor (1965). Then further development of the committee machine methods have been carried out by Yekaterinburg pattern recognition school in Institute of Mathematics and Mechanics, Ural Branch of Russian Academy of Sciences Nowadays theory of committee machine structures is based on results of Mazurov and Hachay (1990, 1999).
Computational Methods Applied to Rational Drug Design.
Ramírez, David
2016-01-01
Due to the synergic relationship between medical chemistry, bioinformatics and molecular simulation, the development of new accurate computational tools for small molecules drug design has been rising over the last years. The main result is the increased number of publications where computational techniques such as molecular docking, de novo design as well as virtual screening have been used to estimate the binding mode, site and energy of novel small molecules. In this work I review some tools, which enable the study of biological systems at the atomistic level, providing relevant information and thereby, enhancing the process of rational drug design.
Computational Methods Applied to Rational Drug Design
Ramírez, David
2016-01-01
Due to the synergic relationship between medical chemistry, bioinformatics and molecular simulation, the development of new accurate computational tools for small molecules drug design has been rising over the last years. The main result is the increased number of publications where computational techniques such as molecular docking, de novo design as well as virtual screening have been used to estimate the binding mode, site and energy of novel small molecules. In this work I review some tools, which enable the study of biological systems at the atomistic level, providing relevant information and thereby, enhancing the process of rational drug design. PMID:27708723
Multigrid Methods for Aerodynamic Problems in Complex Geometries
NASA Technical Reports Server (NTRS)
Caughey, David A.
1995-01-01
Work has been directed at the development of efficient multigrid methods for the solution of aerodynamic problems involving complex geometries, including the development of computational methods for the solution of both inviscid and viscous transonic flow problems. The emphasis is on problems of complex, three-dimensional geometry. The methods developed are based upon finite-volume approximations to both the Euler and the Reynolds-Averaged Navier-Stokes equations. The methods are developed for use on multi-block grids using diagonalized implicit multigrid methods to achieve computational efficiency. The work is focused upon aerodynamic problems involving complex geometries, including advanced engine inlets.
Meshless Local Petrov-Galerkin Method for Bending Problems
NASA Technical Reports Server (NTRS)
Phillips, Dawn R.; Raju, Ivatury S.
2002-01-01
Recent literature shows extensive research work on meshless or element-free methods as alternatives to the versatile Finite Element Method. One such meshless method is the Meshless Local Petrov-Galerkin (MLPG) method. In this report, the method is developed for bending of beams - C1 problems. A generalized moving least squares (GMLS) interpolation is used to construct the trial functions, and spline and power weight functions are used as the test functions. The method is applied to problems for which exact solutions are available to evaluate its effectiveness. The accuracy of the method is demonstrated for problems with load discontinuities and continuous beam problems. A Petrov-Galerkin implementation of the method is shown to greatly reduce computational time and effort and is thus preferable over the previously developed Galerkin approach. The MLPG method for beam problems yields very accurate deflections and slopes and continuous moment and shear forces without the need for elaborate post-processing techniques.
Methods and applications of structure based pharmacophores in drug discovery.
Pirhadi, Somayeh; Shiri, Fereshteh; Ghasemi, Jahan B
2013-01-01
A pharmacophore model does not describe a real molecule or a real association of functional groups but illustrates a molecular recognition of a biological target shared by a group of compounds. Pharmacophores also represent the spatial arrangement of essential interactions in a receptor-binding pocket. Structure based pharmacophores (SBPs) can work both with a free (apo) structure or a macromolecule-ligand complex (holo) structure. The SBP methods that derive pharmacophore from protein-ligand complexes use the potential interactions observed between ligand and protein, whereas, the SBP method that aims to derive pharmacophore from ligand free protein, uses only protein active site information. Therefore SBPs do not encounter to challenging problems such as ligand flexibility, molecular alignment as well as proper selection of training set compounds in ligand based pharmacophore modeling. The current review deals with Hot Spot' analysis of binding site to feature generation, several approaches to feature reduction, and considers shape and excluded volumes to SBP model building. This review continues to represent several applications of SBPs in virtual screening especially in parallel screening approach and multi-target drug design. Also it reports the applications of SBPs in QSAR. This review emphasizes that SBPs are valuable tools for hit to lead optimization, virtual screening, scaffold hopping, and multi-target drug design.
Highlighting the Scientific Method through Mathematics Problems.
ERIC Educational Resources Information Center
McGalliard, William A., Jr.
This paper argues that the introduction of the scientific method in the very rich environments of the natural sciences or human sciences may disguise the process and create difficulties for students because of the multiplicity of variables involved, whereas the variables present in a mathematical context can be readily manipulated and their…
A Bright Future for Evolutionary Methods in Drug Design.
Le, Tu C; Winkler, David A
2015-08-01
Most medicinal chemists understand that chemical space is extremely large, essentially infinite. Although high-throughput experimental methods allow exploration of drug-like space more rapidly, they are still insufficient to fully exploit the opportunities that such large chemical space offers. Evolutionary methods can synergistically blend automated synthesis and characterization methods with computational design to identify promising regions of chemical space more efficiently. We describe how evolutionary methods are implemented, and provide examples of published drug development research in which these methods have generated molecules with increased efficacy. We anticipate that evolutionary methods will play an important role in future drug discovery.
Approved drugs and their problems in patient care: routes of administration and dosing.
Cook, Stuart D
2007-08-15
Problems in patient care with regard to route of administration and dosing of currently approved drugs are reviewed. Dose, frequency and route of administration can make a difference in efficacy, side effects, quality of life, antigenicity, cost, and compliance.
Drug therapy for Helicobacter pylori infection: problems and pitfalls.
Glupczynski, Y; Burette, A
1990-12-01
Antibacterial chemotherapy against Helicobacter pylori is currently being assessed by open or randomized controlled clinical studies for its efficacy in eradicating this bacterium from the stomach of patients with gastritis or gastroduodenal ulcer. Whereas there is presently no "optimal" agent and treatment scheme, the combination of some antibiotics (metronidazole, tinidazole, amoxicillin) with bismuth salts proves definitely superior in vivo to either of these agents administered alone. Several reasons have been proposed, to explain the clinical failure after treatment: insufficient concentration of active drugs in gastric mucus, instability of some agents at an acidic pH, inappropriate formulation of drug, insufficient duration of treatment, and variable compliance of patients. Recently, it has appeared from several clinical trials that H. pylori may rapidly acquire resistance to some antibiotics, and that this event might also account for clinical failure. A critical review of the literature on H. pylori treatment indicates that association of bismuth and antibiotics or of antibiotics alone both may efficiently reduce the risk of emergence of resistance and improve the therapeutic outcome. Guidelines of treatment are suggested in order to avoid the future misuse of antibiotics that would increase selection of antibiotic-resistant H. pylori and negatively affect the ecology of the gastric microflora. Likewise, an accurate definition of a subset of patients with H. pylori who really will require treatment needs to be rapidly established.
ERIC Educational Resources Information Center
Neman, Robert Lynn
This study was designed to assess the effects of the problem-oriented method compared to those of the traditional approach in general chemistry at the college level. The problem-oriented course included topics such as air and water pollution, drug addiction and analysis, tetraethyl-lead additives, insecticides in the environment, and recycling of…
Problems with the Baade-Wesselink method
NASA Technical Reports Server (NTRS)
Bohm-Vitense, E.; Garnavich, P.; Lawler, M.; Mena-Werth, J.; Morgan, S.
1989-01-01
The discrepancy noted in radii obtained by the Baade-Wesselink method when different colors are used to determine the effective temperatures is explored. The discrepancy is found to be due to an inconsistency in the applied temperature-color calibrations. The assumption of the maximum likelihood method that beta (the effective temperature + 0.1 times the bolometric correction) is a linear function of the color is valid for the B-V and V-I colors, but not for the V-R colors. It is suggested that the errors introduced by the nonlinearity in the relation between beta and the V-R colors will produce radii which are too large. The radii derived from the V-B colors appear to be too small.
Computational Methods for Probabilistic Target Tracking Problems
2007-09-01
Undergraduate Students: Ms. Angela Edwards, Mr. Bryahn Ivery, Mr. Dustin Lupton, Mr. James Pender, Mr. Terrell Felder , Ms. Krystal Knight Under...two more graduate students, Mr. Ricardo Bernal and Ms Alisha Williams, and two more undergraduate students, Ms Krystal Knight and Mr. Terrell Felder ...Technical State University, April 24, 2006 “Using Tree Based Methods to Classify Messages”, Terrell A. Felder , Math Awareness Mini-Conference
Identifying and Preventing Health Problems among Young Drug-Misusing Offenders
ERIC Educational Resources Information Center
Bennett, Trevor; Holloway, Katy
2008-01-01
Purpose: The purpose of this paper is to identify the health problems and treatment needs of drug-misusing offenders and to draw out the implications of the findings for health education and prevention. Design/methodology/approach: This analysis is based on data collected as part of the New English and Welsh Arrestee Drug Abuse Monitoring…
Recovery from Problem Drug Use: What Can We Learn from the Dociologist Erving Goffman?
ERIC Educational Resources Information Center
Neale, Joanne; Nettleton, Sarah; Pickering, Lucy
2011-01-01
In this commentary, we critically review the contribution of the sociologist Erving Goffman (1922-1982) to understanding recovery from problem drug use. Previous research has indicated that drug users have a "spoiled identity" and must restore a "normal" or "unspoiled" identity in order to recover. This argument has been linked to Goffman's…
Lessons from the Field: Profiling State Alcohol, Tobacco & Other Drug Problems.
ERIC Educational Resources Information Center
Drug Strategies, Washington, DC.
This document is a step-by-step guide to profiling statewide alcohol, tobacco, and other drug problems and policies. Profiles of this sort capture the complexity of alcohol, tobacco, and other drug abuse indicators at the local level, incorporating data from a range of disciplines and making it possible to design data-driven interventions. The…
2013-01-01
Background Illicit drug use is an important public health problem. Identifying conditions that coexist with illicit drug use is necessary for planning health services. This study described the prevalence and factors associated with social and health problems among clients seeking treatment for illicit drug use. Methods We carried out cross-sectional analyses of baseline data of 2526 clients who sought treatment for illicit drug use at Helsinki Deaconess Institute between 2001 and 2008. At the clients’ first visit, trained clinicians conducted face-to-face interviews using a structured questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with social and health problems. Results The mean age of the clients was 25 years, 21% (n = 519) were homeless, 54% (n = 1363) were unemployed and 7% (n = 183) had experienced threats of violence. Half of the clients (50%, n = 1258) were self-referred and 31% (n = 788) used opiates as their primary drugs of abuse. Hepatitis C (25%, n = 630) was more prevalent than other infectious diseases and depressive symptoms (59%, n = 1490) were the most prevalent psychological problems. Clients who were self-referred to treatment were most likely than others to report social problems (AOR = 1.86; 95% CI = 1.50–2.30) and psychological problems (AOR = 1.51; 95% CI = 1.23–1.85). Using opiates as primary drugs of abuse was the strongest factor associated with infectious diseases (AOR = 3.89; 95% CI = 1.32–11.46) and for reporting a combination of social and health problems (AOR = 3.24; 95% CI = 1.58–6.65). Conclusion The existence of illicit drug use with other social and health problems could lead to increased utilisation and cost of healthcare services. Coexisting social and health problems may interfere with clients’ treatment response. Our findings support the call for integration of
Preparation of drug nanoparticles by emulsion evaporation method
NASA Astrophysics Data System (ADS)
Hoa, Le Thi Mai; Chi, Nguyen Tai; Triet, Nguyen Minh; Thanh Nhan, Le Ngoc; Mau Chien, Dang
2009-09-01
Polymeric drug nanoparticles were prepared by emulsion solvent evaporation method. In this study, prepared the polymeric drug nanoparticles consist of ketoprofen and Eudragit E 100. The morphology structure was investigated by scanning electron microscopy (SEM). The interactions between the drug and polymer were investigated by Fourier transform infrared spectroscopy (FTIR). The size distribution was measured by means of Dynamic Light Scattering. The nanoparticles have an average size of about 150 nm. The incorporation ability of drugs in the polymeric nanoparticles depended on the integration between polymer and drug as well as the glass transition temperature of the polymer.
Decomposition method for zonal resource allocation problems in telecommunication networks
NASA Astrophysics Data System (ADS)
Konnov, I. V.; Kashuba, A. Yu
2016-11-01
We consider problems of optimal resource allocation in telecommunication networks. We first give an optimization formulation for the case where the network manager aims to distribute some homogeneous resource (bandwidth) among users of one region with quadratic charge and fee functions and present simple and efficient solution methods. Next, we consider a more general problem for a provider of a wireless communication network divided into zones (clusters) with common capacity constraints. We obtain a convex quadratic optimization problem involving capacity and balance constraints. By using the dual Lagrangian method with respect to the capacity constraint, we suggest to reduce the initial problem to a single-dimensional optimization problem, but calculation of the cost function value leads to independent solution of zonal problems, which coincide with the above single region problem. Some results of computational experiments confirm the applicability of the new methods.
Using Lin's method to solve Bykov's problems
NASA Astrophysics Data System (ADS)
Knobloch, Jürgen; Lamb, Jeroen S. W.; Webster, Kevin N.
2014-10-01
We consider nonwandering dynamics near heteroclinic cycles between two hyperbolic equilibria. The constituting heteroclinic connections are assumed to be such that one of them is transverse and isolated. Such heteroclinic cycles are associated with the termination of a branch of homoclinic solutions, and called T-points in this context. We study codimension-two T-points and their unfoldings in Rn. In our consideration we distinguish between cases with real and complex leading eigenvalues of the equilibria. In doing so we establish Lin's method as a unified approach to (re)gain and extend results of Bykov's seminal studies and related works. To a large extent our approach reduces the study to the discussion of intersections of lines and spirals in the plane. Case (RR): Under open conditions on the eigenvalues, there exist open sets in parameter space for which there exist periodic orbits close to the heteroclinic cycle. In addition, there exist two one-parameter families of homoclinic orbits to each of the saddle points p1 and p2.See Theorem 2.1 and Proposition 2.2 for precise statements and Fig. 2 for bifurcation diagrams. Cases (RC) and (CC): At the bifurcation point μ=0 and for each N≥2, there exists an invariant set S0N close to the heteroclinic cycle on which the first return map is topologically conjugated to a full shift on N symbols. For any fixed N≥2, the invariant set SμN persists for |μ| sufficiently small.In addition, there exist infinitely many transversal and non-transversal heteroclinic orbits connecting the saddle points p1 and p2 in a neighbourhood of μ=0, as well as infinitely many one-parameter families of homoclinic orbits to each of the saddle points.For full statements of the results see Theorem 2.3 and Propositions 2.4, 2.5 and Fig. 3 for bifurcation diagrams. The dynamics near T-points has been studied previously by Bykov [6-10], Glendinning and Sparrow [20], Kokubu [27,28] and Labouriau and Rodrigues [30,31,38]. See also the surveys
Numerical methods for solving terminal optimal control problems
NASA Astrophysics Data System (ADS)
Gornov, A. Yu.; Tyatyushkin, A. I.; Finkelstein, E. A.
2016-02-01
Numerical methods for solving optimal control problems with equality constraints at the right end of the trajectory are discussed. Algorithms for optimal control search are proposed that are based on the multimethod technique for finding an approximate solution of prescribed accuracy that satisfies terminal conditions. High accuracy is achieved by applying a second-order method analogous to Newton's method or Bellman's quasilinearization method. In the solution of problems with direct control constraints, the variation of the control is computed using a finite-dimensional approximation of an auxiliary problem, which is solved by applying linear programming methods.
A Modified Alternating Direction Method for Variational Inequality Problems
Han, D.
2002-07-01
The alternating direction method is an attractive method for solving large-scale variational inequality problems whenever the subproblems can be solved efficiently. However, the subproblems are still variational inequality problems, which are as structurally difficult to solve as the original one. To overcome this disadvantage, in this paper we propose a new alternating direction method for solving a class of nonlinear monotone variational inequality problems. In each iteration the method just makes an orthogonal projection to a simple set and some function evaluations. We report some preliminary computational results to illustrate the efficiency of the method.
Solving Fluid Structure Interaction Problems with an Immersed Boundary Method
NASA Technical Reports Server (NTRS)
Barad, Michael F.; Brehm, Christoph; Kiris, Cetin C.
2016-01-01
An immersed boundary method for the compressible Navier-Stokes equations can be used for moving boundary problems as well as fully coupled fluid-structure interaction is presented. The underlying Cartesian immersed boundary method of the Launch Ascent and Vehicle Aerodynamics (LAVA) framework, based on the locally stabilized immersed boundary method previously presented by the authors, is extended to account for unsteady boundary motion and coupled to linear and geometrically nonlinear structural finite element solvers. The approach is validated for moving boundary problems with prescribed body motion and fully coupled fluid structure interaction problems. Keywords: Immersed Boundary Method, Higher-Order Finite Difference Method, Fluid Structure Interaction.
Current HPLC Methods for Assay of Nano Drug Delivery Systems.
Tekkeli, Serife Evrim Kepekci; Kiziltas, Mustafa Volkan
2016-12-22
In nano drug formulations the mechanism of release is a critical process to recognize controlled and targeted drug delivery systems. In order to gain high bioavailability and specificity from the drug to reach its therapeutic goal, the active substance must be loaded into the nanoparticles efficiently. Therefore, the amount in biological fluids or tissues and the remaining amount in nano carriers are very important parameters to understand the potential of the nano drug delivery systems. For this aim, suitable and validated quantitation methods are required to determine released drug concentrations from nano pharmaceutical formulations. HPLC (High Performance Liquid Chromatography) is one of the most common techniques used for determination of released drug content out of nano drug formulations, in different physical conditions, over different periods of time. Since there are many types of HPLC methods depending on detector and column types, it is a challenge for the researchers to choose a suitable method that is simple, fast and validated HPLC techniques for their nano drug delivery systems. This review's goal is to compare HPLC methods that are currently used in different nano drug delivery systems in order to provide detailed and useful information for researchers.
Efficient numerical methods for entropy-linear programming problems
NASA Astrophysics Data System (ADS)
Gasnikov, A. V.; Gasnikova, E. B.; Nesterov, Yu. E.; Chernov, A. V.
2016-04-01
Entropy-linear programming (ELP) problems arise in various applications. They are usually written as the maximization of entropy (minimization of minus entropy) under affine constraints. In this work, new numerical methods for solving ELP problems are proposed. Sharp estimates for the convergence rates of the proposed methods are established. The approach described applies to a broader class of minimization problems for strongly convex functionals with affine constraints.
Application of the Discontinuous Galerkin Method to Acoustic Scatter Problems
NASA Technical Reports Server (NTRS)
Atkins, H. L.
1997-01-01
The application of the quadrature-free form of the discontinuous Galerkin method to two problems from Category 1 of the Second Computational Aeroacoustics Workshop on Benchmark problems is presented. The method and boundary conditions relevant to this work are described followed by two test problems, both of which involve the scattering of an acoustic wave off a cylinder. The numerical test performed to evaluate mesh-resolution requirements and boundary-condition effectiveness are also described.
Educational Policy and the Drug Problem--A Redistributive Politics Issue
ERIC Educational Resources Information Center
Caliguri, Joseph P.
1975-01-01
The drug problem exists as a cluster of problems affecting broad interests or groups. The issues are redistributive in that everything relates to everything else. It seems apparent that a cluster of policies and programs need development as well as genuine citizen participation in the formulation of these policies. (Author)
Novel Methods of Lipidic Nanoparticle Preparation and Drug Loading
NASA Astrophysics Data System (ADS)
Maitani, Y.
2013-09-01
In improving cancer chemotherapy, lipidic nanoparticle systems for drug delivery, such as liposomes and emulsions, have received much attention because they are capable of delivering their drug payload selectively to cancer cells and of circulating for a long period in the bloodstream. In addition, lipidic nanoparticles have been examined for use in gene delivery as a non-viral vector. Preparation methods of particles and drug loading methods are crucial for the physicochemical properties of nanoparticles, which are the key aspects for pharmaceutical applications. This review describes new preparation methods for nanoparticles and a loading method for drugs using nanotechnology, including an evaluation of nanoparticles from the point of drug release for applications in cancer therapy and gene delivery.
Applications of Genetic Methods to NASA Design and Operations Problems
NASA Technical Reports Server (NTRS)
Laird, Philip D.
1996-01-01
We review four recent NASA-funded applications in which evolutionary/genetic methods are important. In the process we survey: the kinds of problems being solved today with these methods; techniques and tools used; problems encountered; and areas where research is needed. The presentation slides are annotated briefly at the top of each page.
Written consent to use the drug in children: the problem of off-label drugs.
Maid, Gustavo; Guerchicoff, Marianna; Falconi, Mariano; de Arenaza, Diego Perez
2008-01-01
Cardiac arrhythmias in pediatric patients have different mechanisms and frequencies compared to adult patients. There are many physiological differences between children and adults that may affect the pharmacodynamic and pharmacokinetic of the antiarrhythmic drugs in pediatric population. Children, and specially breast feeding children, cannot be considered low weighted adults to select antiarrhythmic drug doses. Although radiofrequency ablation has experienced great technological advances, it is performed in selected pediatric patients. Therefore, the main therapeutic strategy is the use of antiarrhythmic drugs in children. The medical management of arrhythmias in pediatric patients is challenging and complex. There are few clinical guidelines. There is scarce and incomplete information about the efficacy and safety of antiarrhythmic drugs in pediatric population. Most of the doses and drug administration intervals are extrapolated from adult population and applied to children. Antiarrhythmic drug doses have been extensively studied in adult population. However, in pediatric population, there are very few clinical trials and the safety of these drugs is not well known. In general, dose regimens are based on small uncontrolled studies, extrapolation of drug doses from studies performed in the adult population or physician experience. As a consequence, there is a need for further studies to assess the most effective antiarrhythmic drug regimens in children reducing the risk of side effects. Evidence suggests that medical research in pediatric population is necessary and morally valuable. But investigators involved must take care of moral and ethical values, including the respect for the child-subject and his parents or legal representatives, and this respect compels them to consider the patient and family in the decision making process. The participation request and the informed consent must be obtained according to the competitions the patient exhibits, trying to
Levenberg-Marquardt method for the eigenvalue complementarity problem.
Chen, Yuan-yuan; Gao, Yan
2014-01-01
The eigenvalue complementarity problem (EiCP) is a kind of very useful model, which is widely used in the study of many problems in mechanics, engineering, and economics. The EiCP was shown to be equivalent to a special nonlinear complementarity problem or a mathematical programming problem with complementarity constraints. The existing methods for solving the EiCP are all nonsmooth methods, including nonsmooth or semismooth Newton type methods. In this paper, we reformulate the EiCP as a system of continuously differentiable equations and give the Levenberg-Marquardt method to solve them. Under mild assumptions, the method is proved globally convergent. Finally, some numerical results and the extensions of the method are also given. The numerical experiments highlight the efficiency of the method.
Analyzing HIV/AIDS and Alcohol and Other Drug Use as a Social Problem
PATTERSON, DAVID A.; Wolf (Adelv unegv Waya), Silver
2012-01-01
Most prevention and intervention activities directed toward HIV/AIDS and alcohol and other drug use separately as well as the combining of the two (e.g., those who are both HIV/AIDS and using alcohol and other drugs) comes in the form of specific, individualized therapies without consideration of social influences that may have a greater impact on this population. Approaching this social problem from the narrowed view of individualized, mi-cro solutions disregards the larger social conditions that affect or perhaps even are at the root of the problem. This paper analyzes the social problem of HIV/AIDS and alcohol and other drug abuse using three sociological perspectives—social construction theory, ethnomethodology, and conflict theory—informing the reader of the broader influences accompanying this problem. PMID:23264724
Solving Sturm-Liouville problems by piecewise perturbation methods, revisited
NASA Astrophysics Data System (ADS)
Ledoux, V.; Van Daele, M.
2010-08-01
We present the extension of the successful Constant Perturbation Method (CPM) for Schrödinger problems to the more general class of Sturm-Liouville eigenvalue problems. Whereas the original CPM can only be applied to Sturm-Liouville problems after a Liouville transformation, the more general CPM presented here solves the Sturm-Liouville problem directly. This enlarges the range of applicability of the CPM to a wider variety of problems and allows a more efficient solution of many problems. The CPMs are closely related to the second-order coefficient approximation method underlying the SLEDGE software package, but provide for higher order approximations. These higher order approximations can also be obtained by applying a modified Neumann method. The CPM approach, however, leads to simpler formulae in a more convenient form.
Finite element method for eigenvalue problems in electromagnetics
NASA Technical Reports Server (NTRS)
Reddy, C. J.; Deshpande, Manohar D.; Cockrell, C. R.; Beck, Fred B.
1994-01-01
Finite element method (FEM) has been a very powerful tool to solve many complex problems in electromagnetics. The goal of the current research at the Langley Research Center is to develop a combined FEM/method of moments approach to three-dimensional scattering/radiation problem for objects with arbitrary shape and filled with complex materials. As a first step toward that goal, an exercise is taken to establish the power of FEM, through closed boundary problems. This paper demonstrates the developed of FEM tools for two- and three-dimensional eigenvalue problems in electromagnetics. In section 2, both the scalar and vector finite elements have been used for various waveguide problems to demonstrate the flexibility of FEM. In section 3, vector finite element method has been extended to three-dimensional eigenvalue problems.
Methods for reduction of cohesive forces between carrier and drug in DPI formulation.
Desai, Swapnil S; Aher, Abhijeet A; Kadaskar, Preeti T
2013-11-01
Dry powder inhaler (DPI) has become a well accepted drug delivery for pulmonary system to treat many related diseases including symptomatic and life threatening diseases. Successful delivery of dry powder to the lung requires careful consideration of powder production process, formulation and inhaler device. The formulation of DPI mostly comprises of lactose as a carrier for drug delivery. In DPI formulation, particulate interactions within the formulation govern both the drug dissociation from carrier particles and the disaggregation of drug into primary particles with a capacity to penetrate deep into lung. Two contradictory requirements must be fulfilled for this type of dry powder formulation. On one hand, adhesion between carrier and drug must be sufficient for the blend drug/carrier to be stable. On the other hand, adhesion drug/carrier has to be weak enough to enable the release of drug from carrier during patient inhalation. Thus the carrier use restricted due to detachment problem. Different methods are proposed to reduce the cohesive forces between drug and carrier to desired level. Various studies conducted for understanding the mechanism of deposition into lungs and making formulation with optimum carrier drug cohesive force. This review provides information on various processes involved in reducing the cohesive forces between drug and carrier, to a required level.
Extension of modified power method to two-dimensional problems
Zhang, Peng; Lee, Hyunsuk; Lee, Deokjung
2016-09-01
In this study, the generalized modified power method was extended to two-dimensional problems. A direct application of the method to two-dimensional problems was shown to be unstable when the number of requested eigenmodes is larger than a certain problem dependent number. The root cause of this instability has been identified as the degeneracy of the transfer matrix. In order to resolve this instability, the number of sub-regions for the transfer matrix was increased to be larger than the number of requested eigenmodes; and a new transfer matrix was introduced accordingly which can be calculated by the least square method. The stability of the new method has been successfully demonstrated with a neutron diffusion eigenvalue problem and the 2D C5G7 benchmark problem. - Graphical abstract:.
Methods to Design and Synthesize Antibody-Drug Conjugates (ADCs)
Yao, Houzong; Jiang, Feng; Lu, Aiping; Zhang, Ge
2016-01-01
Antibody-drug conjugates (ADCs) have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes and azides. PMID:26848651
Solving a Class of Nonlinear Eigenvalue Problems by Newton's Method
Gao, Weiguo; Yang, Chao; Meza, Juan C.
2009-07-02
We examine the possibility of using the standard Newton's method for solving a class of nonlinear eigenvalue problems arising from electronic structure calculation. We show that the Jacobian matrix associated with this nonlinear system has a special structure that can be exploited to reduce the computational complexity of the Newton's method. Preliminary numerical experiments indicate that the Newton's method can be more efficient for small problems in which a few smallest eigenpairs are needed.
ERIC Educational Resources Information Center
Hurst, Hunter, Ed.; And Others
1984-01-01
This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…
Child abuse, drug addiction and mental health problems of incarcerated women in Israel.
Chen, Gila; Gueta, Keren
2015-01-01
The mental health problems and pathways to drug addiction and crime among female inmates have long been of interest to researchers and practitioners. The purpose of the current study was to examine the possible association between multiple types of childhood abuse, mental health problems, and drug addiction and the incarceration of 50 Israeli women in prison. The findings indicated that female inmates come from risky families with a high prevalence of family mental health problems, parental drug addiction and crime, and sibling drug addiction and crime. Furthermore, they revealed that incarcerated women from risky families were victims of multiple types of childhood abuse and neglect by their parents, as well as their siblings. Overall, the results suggest that the adverse consequences of a family's mental health problems are much more dramatic than we assumed to date, and that women are more likely than men to be the victims of multiple types of childhood abuse and neglect, as well as suffering more severe psychiatric problems, depression, and drug addiction. The implications of these findings are discussed.
Materials and methods for delivery of biological drugs
NASA Astrophysics Data System (ADS)
Zelikin, Alexander N.; Ehrhardt, Carsten; Healy, Anne Marie
2016-11-01
Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs. Depot-type release systems are available to achieve sustained release of drugs over time. Conjugation to synthetic or biological polymers affords long circulating formulations. Administration of biological drugs through non-parenteral routes shows excellent performance and the first products have reached the market. This Review presents the main accomplishments in this field and illustrates the materials and methods behind existing and upcoming successful formulations and delivery strategies for biological drugs.
Newton's method for large bound-constrained optimization problems.
Lin, C.-J.; More, J. J.; Mathematics and Computer Science
1999-01-01
We analyze a trust region version of Newton's method for bound-constrained problems. Our approach relies on the geometry of the feasible set, not on the particular representation in terms of constraints. The convergence theory holds for linearly constrained problems and yields global and superlinear convergence without assuming either strict complementarity or linear independence of the active constraints. We also show that the convergence theory leads to an efficient implementation for large bound-constrained problems.
Schwarz alternating methods for anisotropic problems with prolate spheroid boundaries.
Dai, Zhenlong; Du, Qikui; Liu, Baoqing
2016-01-01
The Schwarz alternating algorithm, which is based on natural boundary element method, is constructed for solving the exterior anisotropic problem in the three-dimension domain. The anisotropic problem is transformed into harmonic problem by using the coordinate transformation. Correspondingly, the algorithm is also changed. Continually, we analysis the convergence and the error estimate of the algorithm. Meanwhile, we give the contraction factor for the convergence. Finally, some numerical examples are computed to show the efficiency of this algorithm.
Methods for Managing Variation in Clinical Drug Names
Peters, Lee; Kapusnik-Uner, Joan E.; Bodenreider, Olivier
2010-01-01
Objectives: To develop normalization methods for managing the variation in clinical drug names. Methods: Manual examination of drug names from RxNorm and local variants collected from formularies led to the identification of three types of drug-specific normalization rules: expansion of abbreviations (e.g., tab to tablet);reformatting of specific elements (e.g., space between number and unit); and removal of salt variants (e.g., succinate from metoprolol succinate). Results: After drug-specific normalization, recall of 3397 previously non-matching names from formularies reaches 45% overall (70% of some subsets), compared to 10–20% after generic normalization. Ambiguity has not increased significantly in the RxNorm dataset. Conclusions: A limited number of drug-specific normalization operations provide significant improvement over general language normalization. PMID:21347056
Data sources and methods for ascertaining human exposure to drugs.
Jones, J K; Kennedy, D L
Estimates of population exposure based on drug use data are critical elements in the post marketing surveillance of drugs and provide a context for assessing the various risks and benefits associated with drug treatment. Such information is important in predicting morbidity and planning public health protection strategies, indepth studies, and regulatory actions. Knowledge that a population of one thousand instead of one million may potentially be exposed to a drug can help determine how a particular regulatory problem will be handled and would obviously be a major determinant in designing a case-control or cohort study. National estimates of drug use give an overview of the most commonly used drug therapies in current practice. They also furnish valuable comparison data for specific studies of drug use limited to one group of drugs, one geographic region, or one medical care setting. The FDA has access to several different national drug use data bases, each measuring a different point in the drug distribution channels. None covers the entire spectrum of drug exposures. The major "holes" in this patchwork of data bases are the inability to measure OTC drug use with any accuracy and the lack of qualitative information on drug use in hospitals. In addition, there is no patient linkage with the data. The data can only show trends in drug use. They impart no sense of the longitudinal use of drugs for individual patients. There is no direct connection between the different data bases, all of which have their own sampling frames and their own projection methodologies. The market research companies have complete control over these methodologies and they are subject to periodic changes, a situation not entirely satisfactory for epidemiologic research. Sometimes it is a struggle to keep up with these changes. Over the past two years, every one of these data bases has undergone some type of sampling or projection methodology change. One important limitation to the use of all
A numerical method for phase-change problems
NASA Technical Reports Server (NTRS)
Kim, Charn-Jung; Kaviany, Massoud
1990-01-01
A highly accurate and efficient finite-difference method for phase-change problems with multiple moving boundaries of irregular shape is developed by employing a coordinate transformation that immobilizes moving boundaries and preserves the conservative forms of the original governing equations. The numerical method is first presented for one-dimensional phase-change problems (involving large density variation between phases, heat generation, and multiple moving boundaries) and then extended to solve two-dimensional problems (without change of densities between phases). Numerical solutions are obtained non-iteratively using an explicit treatment of the interfacial mass and energy balances and an implicit treatment of the temperature field equations. The accuracy and flexibility of the present numerical method are verified by solving some phase-change problems and comparing the results with existing analytical, semi-analytical and numerical solutions. Results indicate that one- and two-dimensional phase-change problems can be handled easily with excellent accuracies.
A Semantic-Linguistic Method of Solving Verbal Problems.
ERIC Educational Resources Information Center
Hoggard, Franklin R.
1987-01-01
Suggests a method for solving verbal problems in chemistry using a linguistic algorithm that is partly adapted from two artificial intelligence languages. Provides examples of problems solved using the mental concepts of translation, rotation, mirror image symmetry, superpositioning, disjoininng, and conjoining. (TW)
Meshless method for solving fixed boundary problem of plasma equilibrium
NASA Astrophysics Data System (ADS)
Imazawa, Ryota; Kawano, Yasunori; Itami, Kiyoshi
2015-07-01
This study solves the Grad-Shafranov equation with a fixed plasma boundary by utilizing a meshless method for the first time. Previous studies have utilized a finite element method (FEM) to solve an equilibrium inside the fixed separatrix. In order to avoid difficulties of FEM (such as mesh problem, difficulty of coding, expensive calculation cost), this study focuses on the meshless methods, especially RBF-MFS and KANSA's method to solve the fixed boundary problem. The results showed that CPU time of the meshless methods was ten to one hundred times shorter than that of FEM to obtain the same accuracy.
Diffuse interface methods for inverse problems: case study for an elliptic Cauchy problem
NASA Astrophysics Data System (ADS)
Burger, Martin; Løseth Elvetun, Ole; Schlottbom, Matthias
2015-12-01
Many inverse problems have to deal with complex, evolving and often not exactly known geometries, e.g. as domains of forward problems modeled by partial differential equations. This makes it desirable to use methods which are robust with respect to perturbed or not well resolved domains, and which allow for efficient discretizations not resolving any fine detail of those geometries. For forward problems in partial differential equations methods based on diffuse interface representations have gained strong attention in the last years, but so far they have not been considered systematically for inverse problems. In this work we introduce a diffuse domain method as a tool for the solution of variational inverse problems. As a particular example we study ECG inversion in further detail. ECG inversion is a linear inverse source problem with boundary measurements governed by an anisotropic diffusion equation, which naturally cries for solutions under changing geometries, namely the beating heart. We formulate a regularization strategy using Tikhonov regularization and, using standard source conditions, we prove convergence rates. A special property of our approach is that not only operator perturbations are introduced by the diffuse domain method, but more important we have to deal with topologies which depend on a parameter \\varepsilon in the diffuse domain method, i.e. we have to deal with \\varepsilon -dependent forward operators and \\varepsilon -dependent norms. In particular the appropriate function spaces for the unknown and the data depend on \\varepsilon . This prevents the application of some standard convergence techniques for inverse problems, in particular interpreting the perturbations as data errors in the original problem does not yield suitable results. We consequently develop a novel approach based on saddle-point problems. The numerical solution of the problem is discussed as well and results for several computational experiments are reported. In
Methods and problems in heat and mass transfer
NASA Astrophysics Data System (ADS)
Kotliar, Iakov Mikhailovich; Sovershennyi, Viacheslav Dmitrievich; Strizhenov, Dmitrii Sergeevich
The book focuses on the mathematical methods used in heat and mass transfer problems. The theory, statement, and solution of some problems of practical importance in heat and mass transfer are presented, and methods are proposed for solving algebraic, transcendental, and differential equations. Examples of exact solutions to heat and mass transfer equations are given. The discussion also covers some aspects of the development of a mathematical model of turbulent flows.
Parallel decomposition methods for the solution of electromagnetic scattering problems
NASA Technical Reports Server (NTRS)
Cwik, Tom
1992-01-01
This paper contains a overview of the methods used in decomposing solutions to scattering problems onto coarse-grained parallel processors. Initially, a short summary of relevant computer architecture is presented as background to the subsequent discussion. After the introduction of a programming model for problem decomposition, specific decompositions of finite difference time domain, finite element, and integral equation solutions to Maxwell's equations are presented. The paper concludes with an outline of possible software-assisted decomposition methods and a summary.
Conjugate Gradient Methods for Constrained Least Squares Problems
1990-01-01
TINO Hi!AGL . edi"o ar m m Conjugate Gradient Methods for Constrained Least Squares Problems by Douglas James A thesis 3ubmitted to the Graduate Faculty...Methods for Constrained Least uares Problems (directed by Robert J . Plemmons). Nreiw• 1\\ . ’iu 1988, Barlow, Nichols, and Plemmons proposed order...typical). The blocks 13 element j / F __- . F= %.GEi ,,,mo node Figure 2.4: Matrices for Static Structurem Prcblem associated with t’e planar square
A reduced basis Landweber method for nonlinear inverse problems
NASA Astrophysics Data System (ADS)
Garmatter, Dominik; Haasdonk, Bernard; Harrach, Bastian
2016-03-01
We consider parameter identification problems in parametrized partial differential equations (PDEs). These lead to nonlinear ill-posed inverse problems. One way of solving them is using iterative regularization methods, which typically require numerous amounts of forward solutions during the solution process. In this article we consider the nonlinear Landweber method and couple it with the reduced basis method as a model order reduction technique in order to reduce the overall computational time. In particular, we consider PDEs with a high-dimensional parameter space, which are known to pose difficulties in the context of reduced basis methods. We present a new method that is able to handle such high-dimensional parameter spaces by combining the nonlinear Landweber method with adaptive online reduced basis updates. It is then applied to the inverse problem of reconstructing the conductivity in the stationary heat equation.
Are therapeutic vaccines an answer to the global problem of drug and alcohol abuse?
Brashier, Dick B. S.; Sharma, Ashok Kumar; Akhoon, Neha
2016-01-01
Drug Abuse has become a major challenging problem for the society. It effects people of all countries economical strata's and all ages. According. Monetary loss all over the world regarding drug abuse is in million dollars, it not only has an impact on human productivity and healthcare cost but also on cost of crimes conducted by these drugs and alcohol abuse. Therapeutic vaccine has come as new approach to deal with this problem, after failures in search for a pharmaceutical agent to deal with drug of abuse and alcohol. Research in field of nicotine abuse has gone a way ahead with number of vaccines being tried clinically followed by cocaine, opioids, methamphetamine, phencyclidine and alcohol. All of them have a common mechanism of action by antibody production whereas alcohol acts by genetic intervention. None have being approved yet due to poor results in phase II trials, possibly due to not able to trigger an adequate immunological response. But still quest is on for cracking the ice by developing first successful vaccine against drug of abuse, that would follow for other drugs too. It would be great step in field of therapeutic vaccines for drug abuse after similar successful vaccines being approved for other diseases like cancer. PMID:27721531
A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects
Prinz, Jeanette; Vogt, Ingo; Adornetto, Gianluca; Campillos, Mónica
2016-01-01
The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments. PMID:27673331
A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.
Prinz, Jeanette; Vogt, Ingo; Adornetto, Gianluca; Campillos, Mónica
2016-09-01
The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.
A weak Hamiltonian finite element method for optimal control problems
NASA Technical Reports Server (NTRS)
Hodges, Dewey H.; Bless, Robert R.
1989-01-01
A temporal finite element method based on a mixed form of the Hamiltonian weak principle is developed for dynamics and optimal control problems. The mixed form of Hamilton's weak principle contains both displacements and momenta as primary variables that are expanded in terms of nodal values and simple polynomial shape functions. Unlike other forms of Hamilton's principle, however, time derivatives of the momenta and displacements do not appear therein; instead, only the virtual momenta and virtual displacements are differentiated with respect to time. Based on the duality that is observed to exist between the mixed form of Hamilton's weak principle and variational principles governing classical optimal control problems, a temporal finite element formulation of the latter can be developed in a rather straightforward manner. Several well-known problems in dynamics and optimal control are illustrated. The example dynamics problem involves a time-marching problem. As optimal control examples, elementary trajectory optimization problems are treated.
Finite element methods for nonlinear elastostatic problems in rubber elasticity
NASA Technical Reports Server (NTRS)
Oden, J. T.; Becker, E. B.; Miller, T. H.; Endo, T.; Pires, E. B.
1983-01-01
A number of finite element methods for the analysis of nonlinear problems in rubber elasticity are outlined. Several different finite element schemes are discussed. These include the augmented Lagrangian method, continuation or incremental loading methods, and associated Riks-type methods which have the capability of incorporating limit point behavior and bifurcations. Algorithms for the analysis of limit point behavior and bifurcations are described and the results of several numerical experiments are presented. In addition, a brief survey of some recent work on modelling contact and friction in elasticity problems is given. These results pertain to the use of new nonlocal and nonlinear friction laws.
Fluorescence And Alternative Methods In Urine Drug Testing
NASA Astrophysics Data System (ADS)
Jain, Naresh C.
1988-04-01
Drug abuse has become-one of the most compelling realities _ ot contemporary society. It has penetrated every segment ot our population: trom schools to sports and trom organized crime to board rooms . Drugs in tie w9rkplace allegedly cost government agencies and business millions ot dollars each year in increased absenteeism,. poor work performance, thefts,accidents andwastedtime. The President's Commission on Organized Crime and the federal government are in tavor ot urine drug testing. In fact many employers are now resorting to urine drug testing on current and prospective employees. This presep.tation discusses different laboratory methods used in urine drug.testing, including immunoassays, fluorescence polarization, thin layer chromatography, high pressure liquid chromatography, gas chromatography and gas-chromatography-mass spectrometry.
Application of supercritical antisolvent method in drug encapsulation: a review
Kalani, Mahshid; Yunus, Robiah
2011-01-01
The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO2 flow rate, and the liquid phase flow rate on particle size and its distribution. PMID:21796245
Application of supercritical antisolvent method in drug encapsulation: a review.
Kalani, Mahshid; Yunus, Robiah
2011-01-01
The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO(2) flow rate, and the liquid phase flow rate on particle size and its distribution.
Solution of exterior acoustic problems by the boundary element method
NASA Astrophysics Data System (ADS)
Kirkup, Stephen Martin
The boundary element method is described and investigated, especially in respect of its application to exterior two-dimensional Laplace problems. Both empirical and algebraic analyses (including the effects of approximation of the boundary and boundary functions and the precision of the evaluation of the discrete forms) are developed. Methods for the automatic evaluation of the discrete forms of the Laplace and Helmholtz integral operators are reviewed and extended. Boundary element methods for the solution of exterior Helmholtz problems with general (but most importantly Neumann) boundary conditions are reviewed and some are explicitly stated using a new notation. Boundary element methods based on the boundary integral equations introduced by Brakhage and Werner/Leis/Panich/Kussmaul (indirect) and Burton and Miller (direct) are given prime consideration and implemented for three-dimensional problems. The influence of the choice of weighting parameter on the performance of the methods is explored and further guidance is given. The application of boundary element methods and methods based on the Rayleigh integral to acoustic radiation problems are considered. Methods for speeding up their solution via the boundary element method are developed. Library subroutines for the solution of acoustic radiation problems are described and demonstrated. Computational techniques for the problem of predicting the noise produced by a running engine are reviewed and appraised. The application of the boundary element method to low-noise engine design and in the design of noise shields is considered. The boundary element method is applied to the Ricardo crankcase simulation rig, which is an engine-like structure. A comparison of predicted and measured sound power spectra is given.
Solution of Exterior Acoustic Problems by the Boundary Element Method.
NASA Astrophysics Data System (ADS)
Kirkup, Stephen Martin
Available from UMI in association with The British Library. The boundary element method is described and investigated, especially in respect of its application to exterior two -dimensional Laplace problems. Both empirical and algebraic analyses (including the effects of approximation of the boundary and boundary functions and the precision of the evaluation of the discrete forms) are developed. Methods for the automatic evaluation of the discrete forms of the Laplace and Helmholtz integral operators are reviewed and extended. Boundary element methods for the solution of exterior Helmholtz problems with general (but most importantly Neumann) boundary conditions are reviewed and some are explicitly stated using a new notation. Boundary element methods based on the boundary integral equations introduced by Brakhage & Werner/ Leis/ Panich/ Kussmaul (indirect) and Burton & Miller (direct) are given prime consideration and implemented for three -dimensional problems. The influence of the choice of weighting parameter on the performance of the methods is explored and further guidance is given. The application of boundary element methods and methods based on the Rayleigh integral to acoustic radiation problems are considered. Methods for speeding up their solution via the boundary element method are developed. Library subroutines for the solution of acoustic radiation problems are described and demonstrated. Computational techniques for the problem of predicting the noise produced by a running engine are reviewed and appraised. The application of the boundary element method to low-noise engine design and in the design of noise shields is considered. The boundary element method is applied to the Ricardo crankcase simulation rig, which is an engine -like structure. A comparison of predicted and measured sound power spectra is given.
Domain decomposition methods for solving an image problem
Tsui, W.K.; Tong, C.S.
1994-12-31
The domain decomposition method is a technique to break up a problem so that ensuing sub-problems can be solved on a parallel computer. In order to improve the convergence rate of the capacitance systems, pre-conditioned conjugate gradient methods are commonly used. In the last decade, most of the efficient preconditioners are based on elliptic partial differential equations which are particularly useful for solving elliptic partial differential equations. In this paper, the authors apply the so called covering preconditioner, which is based on the information of the operator under investigation. Therefore, it is good for various kinds of applications, specifically, they shall apply the preconditioned domain decomposition method for solving an image restoration problem. The image restoration problem is to extract an original image which has been degraded by a known convolution process and additive Gaussian noise.
Boundary data completion: the method of boundary value problem factorization
NASA Astrophysics Data System (ADS)
Ben Abda, Amel; Henry, Jacques; Jday, Fadhel
2011-05-01
We consider the following data completion problem for the Laplace equation in the cylindrical domain: \\Omega =\\left]0,a\\right[\\times { O},{ O}\\subset {R}^{n-1} ({ O} is a smooth bounded open set and a > 0), limited by the faces \\Gamma _{0}=\\lbrace 0\\rbrace \\times { O} and \\Gamma _{a}=\\lbrace a\\rbrace \\times { O}. The Neumann and Dirichlet boundary conditions are given on Γ0 while no condition is given on Γa. The completion data problem consists in recovering a boundary condition on Γa. This problem has been known to be ill-posed since Hadamard [12]. The problem is set as an optimal control problem with a regularized cost function. To obtain directly an approximation of the missing data on Γa we use the method of factorization of elliptic boundary value problems. This method allows us to factorize a boundary value problem in the product of two parabolic problems. Here it is applied to the optimality system (i.e. jointly on the state and adjoint state equations).
Aerosol flow reactor method for synthesis of drug nanoparticles.
Eerikäinen, Hannele; Watanabe, Wiwik; Kauppinen, Esko I; Ahonen, P Petri
2003-05-01
An aerosol flow reactor method, a one-step continuous process to produce nanometer-sized drug particles with unimodal size distribution, was developed. This method involves first dissolving the drug material in question into a suitable solvent, which is then followed by atomising the solution as fine droplets into carrier gas. A heated laminar flow reactor tube is used to evaporate the solvent, and solid drug nanoparticles are formed. In this study, the effect of drying temperature on the particle size and morphology was examined. A glucocorticosteroid used for asthma therapy, beclomethasone dipropionate, was selected as an experimental model drug. The geometric number mean particle diameter increases significantly with increasing reactor temperatures due to formation of hollow nanoparticles. Above 160 degrees C, however, further increase in temperature results in decreasing particle size. The produced nanoparticles are spherical and show smooth surfaces at all studied experimental conditions.
Problems of drug abuse, HIV and AIDS: the burden of care in one general practice.
Ronald, P J; Witcomb, J C; Robertson, J R; Roberts, J J; Shishodia, P C; Whittaker, A
1992-01-01
Responsibility for many of the problems of intravenous drug abuse and human immunodeficiency virus (HIV) infection lies with community care agencies, such as general practitioners, community psychiatric and district nurses and drug agencies. It is in general practice that this burden is most clearly observed, given that general practitioners are in charge of the day-to-day care of patients. In an attempt to quantify this workload in an inner city practice with 11,200 patients, data were gathered from several sources relating to drug use and HIV infection. The study identified 432 patients who had consulted with problems of drug abuse and/or HIV infection over the period 1981-90. Among this group of patients 161 (37%) were HIV antibody positive. Among 191 drug abusers who were still registered with the practice in 1990 dihydrocodeine was the most commonly prescribed substitute treatment (130 patients) and only nine patients were prescribed methadone. Forty seven per cent of drug users continued to inject drugs occasionally. However, analysis of urine samples revealed that there was a shift away from injecting mainly heroin to multiple drug use, including benzodiazepines, usually originating from prescribed sources. Drug abusers who were HIV positive consulted their general practitioner significantly more often over one year than those who were not (mean 24.9 versus 15.8 consultations, P < 0.01). However, there was no significant difference between these two groups in terms of days spent in hospital. A total of 61 patients were referred to a community psychiatric nurse over an eight month period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1419244
Methods of centers and methods of feasible directions for the solution of optimal control problems.
NASA Technical Reports Server (NTRS)
Polak, E.; Mukai, H.; Pironneau, O.
1971-01-01
Demonstration of the applicability of methods of centers and of methods of feasible directions to optimal control problems. Presented experimental results show that extensions of Frank-Wolfe (1956), Zoutendijk (1960), and Pironneau-Polak (1971) algorithms for nonlinear programming problems can be quite efficient in solving optimal control problems.
Application of essentially nonoscillatory methods to aeroacoustic flow problems
NASA Technical Reports Server (NTRS)
Atkins, Harold L.
1995-01-01
A finite-difference essentially nonoscillatory (ENO) method has been applied to several of the problems prescribed for the workshop sponsored jointly by the Institute for Computer Applications in Science and Engineering and by NASA Langley Research Center entitled 'Benchmark Problems in Computational Aeroacoustics'. The workshop focused on computational challenges specific to aeroacoustics. Among these are long-distance propagation of a short-wavelength disturbance, propagation of small-amplitude disturbances, and nonreflective boundary conditions. The shock capturing-capability inherent to the ENO method effectively eliminates oscillations near shock waves without the need to add and tune dissipation or filter terms. The method-of-lines approach allows the temporal and spatial operators to be chosen separately in accordance with the demands of a particular problem. The ENO method was robust and accurate for all problems in which the propagating wave was resolved with 8 or more points per wavelength. The finite-wave-model boundary condition, a local nonlinear acoustic boundary condition, performed well for the one-dimensional problems. The buffer-domain approach performed well for the two-dimensional test problem. The amplitude of nonphysical reflections were less than 1 percent of the exiting wave's amplitude.
Computational methods for drug design and discovery: focus on China.
Zheng, Mingyue; Liu, Xian; Xu, Yuan; Li, Honglin; Luo, Cheng; Jiang, Hualiang
2013-10-01
In the past decades, China's computational drug design and discovery research has experienced fast development through various novel methodologies. Application of these methods spans a wide range, from drug target identification to hit discovery and lead optimization. In this review, we firstly provide an overview of China's status in this field and briefly analyze the possible reasons for this rapid advancement. The methodology development is then outlined. For each selected method, a short background precedes an assessment of the method with respect to the needs of drug discovery, and, in particular, work from China is highlighted. Furthermore, several successful applications of these methods are illustrated. Finally, we conclude with a discussion of current major challenges and future directions of the field.
Proposal of Evolutionary Simplex Method for Global Optimization Problem
NASA Astrophysics Data System (ADS)
Shimizu, Yoshiaki
To make an agile decision in a rational manner, role of optimization engineering has been notified increasingly under diversified customer demand. With this point of view, in this paper, we have proposed a new evolutionary method serving as an optimization technique in the paradigm of optimization engineering. The developed method has prospects to solve globally various complicated problem appearing in real world applications. It is evolved from the conventional method known as Nelder and Mead’s Simplex method by virtue of idea borrowed from recent meta-heuristic method such as PSO. Mentioning an algorithm to handle linear inequality constraints effectively, we have validated effectiveness of the proposed method through comparison with other methods using several benchmark problems.
A meshless method for solving the EEG forward problem.
von Ellenrieder, Nicolas; Muravchik, Carlos H; Nehorai, Arye
2005-02-01
We present a numerical method to solve the quasistatic Maxwell equations and compute the electroencephalography (EEG) forward problem solution. More generally, we develop a computationally efficient method to obtain the electric potential distribution generated by a source of electric activity inside a three-dimensional body of arbitrary shape and layers of different electric conductivities. The method needs only a set of nodes on the surface and inside the head, but not a mesh connecting the nodes. This represents an advantage over traditional methods like boundary elements or finite elements since the generation of the mesh is typically computationally intensive. The performance of the proposed method is compared with the boundary element method (BEM) by numerically solving some EEG forward problems examples. For a large number of nodes and the same precision, our method has lower computational load than BEM due to a faster convergence rate and to the sparsity of the linear system to be solved.
Formalization of a synthesis problem and methods for its solution
NASA Astrophysics Data System (ADS)
Dokukin, A. A.
2014-06-01
A formal formulation is proposed for the synthesis problem of finding objects with certain properties described only by a collection of precedents. A key feature of this formalization is that it is closely related to the pattern recognition theory. A general approach to solving the synthesis problem is described, and particular solution methods are presented in two important cases. For this purpose, a new recognition method is proposed that exhibits a high speed as applied to the data of the structure under study. The performance of the methods is demonstrated on actual data.
Off-label drug use in paediatrics: a world-wide problem.
Lenk, Christian
2012-06-01
Since more than 35 years, the international medical scientific community tries to solve the problem of the off-label use of paediatric drugs. The aim is simple, but ambitious: to supply children and adolescents with effective drugs, as safe as possible, with known and well-documented side effects, and with accurate and up-to-date information on dosage and administration form. However, despite the significant efforts of paediatricians, researchers and international health politics, a number of severe obstacles for the optimal supply of children and adolescents with safe drugs remain. The detailed analysis of the problem shows not only a still remaining lack of medical knowledge, but also persistent weaknesses in the ethical, legal, medical, pharmacological, and political practices that surround the phenomenon of off-label use in paediatrics. The article gives an overview about the remaining difficulties in the field of paediatric off-label medication with special consideration to ethical and regulatory questions.
A Review of Computational Methods for Predicting Drug Targets.
Huang, Guohua; Yan, Fengxia; Tan, Duoduo
2016-11-14
Drug discovery and development is not only a time-consuming and labor-intensive process but also full of risk. Identifying targets of small molecules helps evaluate safety of drugs and find new therapeutic applications. The biotechnology measures a wide variety of properties related to drug and targets from different perspectives, thus generating a large body of data. This undoubtedly provides a solid foundation to explore relationships between drugs and targets. A large number of computational techniques have recently been developed for drug target prediction. In this paper, we summarize these computational methods and classify them into structure-based, molecular activity-based, side-effect-based and multi-omics-based predictions according to the used data for inference. The multi-omics-based methods are further grouped into two types: classifier-based and network-based predictions. Furthermore，the advantages and limitations of each type of methods are discussed. Finally, we point out the future directions of computational predictions for drug targets.
Preconditioned Mixed Spectral Element Methods for Elasticity and Stokes Problems
NASA Technical Reports Server (NTRS)
Pavarino, Luca F.
1996-01-01
Preconditioned iterative methods for the indefinite systems obtained by discretizing the linear elasticity and Stokes problems with mixed spectral elements in three dimensions are introduced and analyzed. The resulting stiffness matrices have the structure of saddle point problems with a penalty term, which is associated with the Poisson ratio for elasticity problems or with stabilization techniques for Stokes problems. The main results of this paper show that the convergence rate of the resulting algorithms is independent of the penalty parameter, the number of spectral elements Nu and mildly dependent on the spectral degree eta via the inf-sup constant. The preconditioners proposed for the whole indefinite system are block-diagonal and block-triangular. Numerical experiments presented in the final section show that these algorithms are a practical and efficient strategy for the iterative solution of the indefinite problems arising from mixed spectral element discretizations of elliptic systems.
Error Analysis for Discontinuous Galerkin Method for Parabolic Problems
NASA Technical Reports Server (NTRS)
Kaneko, Hideaki
2004-01-01
In the proposal, the following three objectives are stated: (1) A p-version of the discontinuous Galerkin method for a one dimensional parabolic problem will be established. It should be recalled that the h-version in space was used for the discontinuous Galerkin method. An a priori error estimate as well as a posteriori estimate of this p-finite element discontinuous Galerkin method will be given. (2) The parameter alpha that describes the behavior double vertical line u(sub t)(t) double vertical line 2 was computed exactly. This was made feasible because of the explicitly specified initial condition. For practical heat transfer problems, the initial condition may have to be approximated. Also, if the parabolic problem is proposed on a multi-dimensional region, the parameter alpha, for most cases, would be difficult to compute exactly even in the case that the initial condition is known exactly. The second objective of this proposed research is to establish a method to estimate this parameter. This will be done by computing two discontinuous Galerkin approximate solutions at two different time steps starting from the initial time and use them to derive alpha. (3) The third objective is to consider the heat transfer problem over a two dimensional thin plate. The technique developed by Vogelius and Babuska will be used to establish a discontinuous Galerkin method in which the p-element will be used for through thickness approximation. This h-p finite element approach, that results in a dimensional reduction method, was used for elliptic problems, but the application appears new for the parabolic problem. The dimension reduction method will be discussed together with the time discretization method.
TWO-GRID METHODS FOR MAXWELL EIGENVALUE PROBLEMS
ZHOU, J.; HU, X.; ZHONG, L.; SHU, S.; CHEN, L.
2015-01-01
Two new two-grid algorithms are proposed for solving the Maxwell eigenvalue problem. The new methods are based on the two-grid methodology recently proposed by Xu and Zhou [Math. Comp., 70 (2001), pp. 17–25] and further developed by Hu and Cheng [Math. Comp., 80 (2011), pp. 1287–1301] for elliptic eigenvalue problems. The new two-grid schemes reduce the solution of the Maxwell eigenvalue problem on a fine grid to one linear indefinite Maxwell equation on the same fine grid and an original eigenvalue problem on a much coarser grid. The new schemes, therefore, save total computational cost. The error estimates reveals that the two-grid methods maintain asymptotically optimal accuracy, and the numerical experiments presented confirm the theoretical results. PMID:26190866
Hybrid Monte Carlo/deterministic methods for radiation shielding problems
NASA Astrophysics Data System (ADS)
Becker, Troy L.
For the past few decades, the most common type of deep-penetration (shielding) problem simulated using Monte Carlo methods has been the source-detector problem, in which a response is calculated at a single location in space. Traditionally, the nonanalog Monte Carlo methods used to solve these problems have required significant user input to generate and sufficiently optimize the biasing parameters necessary to obtain a statistically reliable solution. It has been demonstrated that this laborious task can be replaced by automated processes that rely on a deterministic adjoint solution to set the biasing parameters---the so-called hybrid methods. The increase in computational power over recent years has also led to interest in obtaining the solution in a region of space much larger than a point detector. In this thesis, we propose two methods for solving problems ranging from source-detector problems to more global calculations---weight windows and the Transform approach. These techniques employ sonic of the same biasing elements that have been used previously; however, the fundamental difference is that here the biasing techniques are used as elements of a comprehensive tool set to distribute Monte Carlo particles in a user-specified way. The weight window achieves the user-specified Monte Carlo particle distribution by imposing a particular weight window on the system, without altering the particle physics. The Transform approach introduces a transform into the neutron transport equation, which results in a complete modification of the particle physics to produce the user-specified Monte Carlo distribution. These methods are tested in a three-dimensional multigroup Monte Carlo code. For a basic shielding problem and a more realistic one, these methods adequately solved source-detector problems and more global calculations. Furthermore, they confirmed that theoretical Monte Carlo particle distributions correspond to the simulated ones, implying that these methods
Solution of prey-predator problem by multistage decomposition method
NASA Astrophysics Data System (ADS)
Chowdhury, M. S. H.; Hashim, I.; Mawa, S.
2008-01-01
The prey-predator problem is simulated by an adaptation of the classical Adomian decomposition method (ADM). The classical ADM is converted into a hybrid numeric-analytic method called the multistage ADM (MADM). The decomposition solutions presented by previous authors are corrected. The numerical results obtained from the MADM and the classical fourth-order Rungge-Kutta (RK4) method are in complete agreement.
Application of the boundary integral method to immiscible displacement problems
Masukawa, J.; Horne, R.N.
1988-08-01
This paper presents an application of the boundary integral method (BIM) to fluid displacement problems to demonstrate its usefulness in reservoir simulation. A method for solving two-dimensional (2D), piston-like displacement for incompressible fluids with good accuracy has been developed. Several typical example problems with repeated five-spot patterns were solved for various mobility ratios. The solutions were compared with the analytical solutions to demonstrate accuracy. Singularity programming was found to be a major advantage in handling flow in the vicinity of wells. The BIM was found to be an excellent way to solve immiscible displacement problems. Unlike analytic methods, it can accommodate complex boundary shapes and does not suffer from numerical dispersion at the front.
Integrated Force Method Solution to Indeterminate Structural Mechanics Problems
NASA Technical Reports Server (NTRS)
Patnaik, Surya N.; Hopkins, Dale A.; Halford, Gary R.
2004-01-01
Strength of materials problems have been classified into determinate and indeterminate problems. Determinate analysis primarily based on the equilibrium concept is well understood. Solutions of indeterminate problems required additional compatibility conditions, and its comprehension was not exclusive. A solution to indeterminate problem is generated by manipulating the equilibrium concept, either by rewriting in the displacement variables or through the cutting and closing gap technique of the redundant force method. Compatibility improvisation has made analysis cumbersome. The authors have researched and understood the compatibility theory. Solutions can be generated with equal emphasis on the equilibrium and compatibility concepts. This technique is called the Integrated Force Method (IFM). Forces are the primary unknowns of IFM. Displacements are back-calculated from forces. IFM equations are manipulated to obtain the Dual Integrated Force Method (IFMD). Displacement is the primary variable of IFMD and force is back-calculated. The subject is introduced through response variables: force, deformation, displacement; and underlying concepts: equilibrium equation, force deformation relation, deformation displacement relation, and compatibility condition. Mechanical load, temperature variation, and support settling are equally emphasized. The basic theory is discussed. A set of examples illustrate the new concepts. IFM and IFMD based finite element methods are introduced for simple problems.
[Applications of the Fragment Molecular Orbital Method in Drug Discovery].
Ishikawa, Takeshi
2016-01-01
Recently, ab initio quantum mechanical calculations have been applied to large molecules, including biomolecular systems. The fragment molecular orbital (FMO) method is one of the most efficient approaches for the quantum mechanical investigation of such molecules. In the FMO method, dividing a target molecule into small fragments reduces computational effort. The clear definition of inter-fragment interaction energy (IFIE) as an expression of total energy is another valuable feature of the FMO method because it provides the ability to analyze interactions in biomolecules. Thus, the FMO method is expected to be useful for drug discovery. This study demonstrates applications of the FMO method related to drug discovery. First, IFIE, according to FMO calculations, was used in the optimization of drug candidates for the development of anti-prion compounds. The second example involved interaction analysis of the human immunodeficiency virus type 1 (HIV-1) protease and a drug compound that used a novel analytical method for dispersion interaction, i.e., fragment interaction analysis based on LMP2 (FILM).
Method for Solving Physical Problems Described by Linear Differential Equations
NASA Astrophysics Data System (ADS)
Belyaev, B. A.; Tyurnev, V. V.
2017-01-01
A method for solving physical problems is suggested in which the general solution of a differential equation in partial derivatives is written in the form of decomposition in spherical harmonics with indefinite coefficients. Values of these coefficients are determined from a comparison of the decomposition with a solution obtained for any simplest particular case of the examined problem. The efficiency of the method is demonstrated on an example of calculation of electromagnetic fields generated by a current-carrying circular wire. The formulas obtained can be used to analyze paths in the near-field magnetic (magnetically inductive) communication systems working in moderately conductive media, for example, in sea water.
The caustics method in the contact problems of anisotropic materials
NASA Astrophysics Data System (ADS)
Bakić, A.; Semenski, D.; Jecić, S.
2010-06-01
Regions with high stress gradients represent critical zones of engineering structures such as crack tip or vicinity of the contact zone. The optical method of caustics is one of the few experimental methods which provide applicable results in these locations. This method was originally developed for crack-tip measurements of stress intensity factors and J-integral for isotropic and then for anisotropic materials. Subsequently, it was extended to contact problems where the size and shape of caustics on the screen are related to the amount and the inclination of loading force. Here, the method of caustics is extended to the analysis of contact problems for mechanically anisotropic materials. This makes the caustics method widely applicable to the analysis of any high stress gradient locations in a structure.
Grigsby, Timothy J; Forster, Myriam; Baezconde-Garbanati, Lourdes; Soto, Daniel W; Unger, Jennifer B
2014-03-01
The present study compares statistical models for three conceptualizations of drug use in 11th grade (past 30 day ever/never use, past 30 day frequency of drug use and past 30 day drug use consequences) with externalizing and internalizing problems in emerging adulthood when controlling for age, academic achievement and socioeconomic status in a Hispanic sample. Multivariate logistic regression models for the different drug use variables were compared when modeling weapon carrying, arrest, multiple lifetime sex partners, drug/alcohol use before sex and condom use in emerging adulthood. A multivariate linear regression model was used to model depression in emerging adulthood as a function of drug use measurement controlling for other covariates and depression in adolescence. Our findings suggest that any conceptualization of drug use will produce equitable results and model fit statistics when examining externalizing problems. However, when investigating internalizing problems, such as depression, lower frequency drug use-and not high frequency-was more strongly associated with depression whereas experiencing high levels of drug use consequences-and not low levels of consequences-was associated with depression in emerging adulthood despite similar model fit values. Variation between drug use and the experience of drug use consequences may lead to misspecification of "at-risk" subgroups of drug users. Implications and future directions are discussed.
Grigsby, Timothy J.; Forster, Myriam; Baezconde-Garbanati, Lourdes; Soto, Daniel W.; Unger, Jennifer B.
2014-01-01
The present study compares statistical models for three conceptualizations of drug use in 11th grade (past 30 day ever/never use, past 30 day frequency of drug use and past 30 day drug use consequences) with externalizing and internalizing problems in emerging adulthood when controlling for age, academic achievement and socioeconomic status in a Hispanic sample. Multivariate logistic regression models for the different drug use variables were compared when modeling weapon carrying, arrest, multiple lifetime sex partners, drug/alcohol use before sex and condom use in emerging adulthood. A multivariate linear regression model was used to model depression in emerging adulthood as a function of drug use measurement controlling for other covariates and depression in adolescence. Our findings suggest that any conceptualization of drug use will produce equitable results and model fit statistics when examining externalizing problems. However, when investigating internalizing problems, such as depression, lower frequency drug use—and not high frequency—was more strongly associated with depression whereas experiencing high levels of drug use consequences—and not low levels of consequences—was associated with depression in emerging adulthood despite similar model fit values. Variation between drug use and the experience of drug use consequences may lead to misspecification of “at-risk” subgroups of drug users. Implications and future directions are discussed. PMID:24345310
[The problem of post-marketing surveillance planning on drugs for infectious disease].
Sato, J
2001-12-01
In principle, a new drug is approved via the assessments of safety and efficacy by the Ministry of Health, Labor and Welfare (MHLW). After approval, conduct of post-marketing surveillance is requested by law in order to assess the safety and efficacy of the drug in a large number of patients. Before initiating a surveillance, submission to MHLW of a document on the plan of survey is necessary in the purpose of inspection if it includes any ethical or regulatory problem or not. Through the inspections of the plans submitted during the period of April 1998 and March 2000, many problems have been pointed out. In this report, the author introduces some of the concrete problems noted in the plans on drugs for infectious diseases and shows some of the guidance made by the authority how to improve them. It is expected that such practical analyses of cases may be useful for future planning of post-marketing surveillance on drugs for infectious diseases.
Schjøtt, Jan; Bergman, Jenny
2014-01-01
Background RELIS is a Norwegian network of four regional medicine-information and pharmacovigilance centers where pharmacists and clinical pharmacologists provide feedback to health care professionals in spontaneous drug-related questions and adverse drug-reaction (ADR) reports published in a question–answer pair (QAP) database (the RELIS database) and the Norwegian ADR database, respectively. Objective To describe the potential of RELIS’s dual service to improve detection and communication of drug-safety problems. Materials and methods We searched the RELIS database for QAPs about ADRs with use of the Norwegian ADR database as a reference. We also searched the Norwegian ADR database for reports that used the RELIS database as a reference. Both searches were limited to the years 2003–2012. We then selected the example of pregabalin and drug abuse after the marketing of Lyrica in Norway in September 2004 to illustrate RELIS’s potential to detect new drug-safety information through a limited number of QAPs and ADR reports. Results A total of 5,427 (26%) of 21,071 QAPs in the RELIS database concerned ADRs. QAPs from this database were used as references in 791 (4%) of a total of 22,090 reports in the Norwegian ADR database. The Norwegian ADR database was used as a reference in 363 (7%) of 5,427 QAPs that concerned ADRs. Between September 2004 and September 2008, RELIS received eleven questions and 13 ADR reports about suspicion of Lyrica (pregabalin) and different aspects of abuse. Conclusion RELIS processes data through two databases that facilitate communication about ADRs. Our service also has the potential to detect new drug-safety problems with a limited number of questions and ADR reports. PMID:25061339
Multigrid methods for bifurcation problems: The self adjoint case
NASA Technical Reports Server (NTRS)
Taasan, Shlomo
1987-01-01
This paper deals with multigrid methods for computational problems that arise in the theory of bifurcation and is restricted to the self adjoint case. The basic problem is to solve for arcs of solutions, a task that is done successfully with an arc length continuation method. Other important issues are, for example, detecting and locating singular points as part of the continuation process, switching branches at bifurcation points, etc. Multigrid methods have been applied to continuation problems. These methods work well at regular points and at limit points, while they may encounter difficulties in the vicinity of bifurcation points. A new continuation method that is very efficient also near bifurcation points is presented here. The other issues mentioned above are also treated very efficiently with appropriate multigrid algorithms. For example, it is shown that limit points and bifurcation points can be solved for directly by a multigrid algorithm. Moreover, the algorithms presented here solve the corresponding problems in just a few work units (about 10 or less), where a work unit is the work involved in one local relaxation on the finest grid.
Problem solving styles among people who use alcohol and other drugs in South Africa.
Sorsdahl, Katherine; Stein, Dan J; Carrara, Henri; Myers, Bronwyn
2014-01-01
The present study examines the relationship between problem-solving styles, socio-demographic variables and risk of alcohol and other drug (AOD)-related problems among a South African population. The Social Problem-Solving Inventory-Revised, Center for Epidemiologic Studies Depression Scale (CES-D) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were administered to a convenience sample of 1000 respondents. According to the ASSIST, 32% and 49% of respondents met criteria for moderate to high risk of alcohol use and illicit drug use respectively. After adjusting for the effects of other variables in the model, respondents who were of "Coloured" ancestry (PR=1.20, 95% CI 1.0-1.4), male (PR=1.19, 95% CI 1.04-1.37), older (PR=1.01, 95% CI 1.00-1.02), who adopted an avoidance style of coping with problems (PR=1.03, 95% CI 1.01-1.05) and who met criteria for depression (PR=1.42, 95% CI 1.12-1.79) were more likely to be classified as having risky AOD use. This suggests that interventions to improve problem solving and provide people with cognitive strategies to cope better with their problems may hold promise for reducing risky AOD use.
Illicit drug use, alcohol use and problem drinking among infrequent and frequent road ragers.
Butters, Jennifer E; Smart, Reginald G; Mann, Robert E; Asbridge, Mark
2005-11-01
The purpose of this paper is to investigate the relationships between illicit drug and alcohol use, problem drinking, and road rage. Particular attention is devoted to the association between these behaviors and frequent involvement in road rage activities. The data are taken from the 2002 Centre for Addiction and Mental Health (CAMH) Monitor, a representative telephone survey with a sample of 2421 adults aged 18 and older in Ontario. A cluster analysis was performed and analysis of variance procedures were used to test for group differences. The cluster analysis revealed five distinct groups involved in various types of road rage behavior. Frequent road ragers, accounting for 5.3% of the sample, were involved in the most severe forms of road rage behavior and were most likely (24%) to report problem drinking and past year cannabis (23.8%), cocaine (5.4%), and ecstasy (10%) use. These data indicate that illicit drug use and alcohol problems are significantly greater for those involved in the most serious forms of road rage behavior. Further work is needed to identify the mechanisms by which illicit drug use and problem drinking are linked to road rage.
Problems of Mathematical Finance by Stochastic Control Methods
NASA Astrophysics Data System (ADS)
Stettner, Łukasz
The purpose of this paper is to present main ideas of mathematics of finance using the stochastic control methods. There is an interplay between stochastic control and mathematics of finance. On the one hand stochastic control is a powerful tool to study financial problems. On the other hand financial applications have stimulated development in several research subareas of stochastic control in the last two decades. We start with pricing of financial derivatives and modeling of asset prices, studying the conditions for the absence of arbitrage. Then we consider pricing of defaultable contingent claims. Investments in bonds lead us to the term structure modeling problems. Special attention is devoted to historical static portfolio analysis called Markowitz theory. We also briefly sketch dynamic portfolio problems using viscosity solutions to Hamilton-Jacobi-Bellman equation, martingale-convex analysis method or stochastic maximum principle together with backward stochastic differential equation. Finally, long time portfolio analysis for both risk neutral and risk sensitive functionals is introduced.
Finite element methods on supercomputers - The scatter-problem
NASA Technical Reports Server (NTRS)
Loehner, R.; Morgan, K.
1985-01-01
Certain problems arise in connection with the use of supercomputers for the implementation of finite-element methods. These problems are related to the desirability of utilizing the power of the supercomputer as fully as possible for the rapid execution of the required computations, taking into account the gain in speed possible with the aid of pipelining operations. For the finite-element method, the time-consuming operations may be divided into three categories. The first two present no problems, while the third type of operation can be a reason for the inefficient performance of finite-element programs. Two possibilities for overcoming certain difficulties are proposed, giving attention to a scatter-process.
Extrapolation techniques applied to matrix methods in neutron diffusion problems
NASA Technical Reports Server (NTRS)
Mccready, Robert R
1956-01-01
A general matrix method is developed for the solution of characteristic-value problems of the type arising in many physical applications. The scheme employed is essentially that of Gauss and Seidel with appropriate modifications needed to make it applicable to characteristic-value problems. An iterative procedure produces a sequence of estimates to the answer; and extrapolation techniques, based upon previous behavior of iterants, are utilized in speeding convergence. Theoretically sound limits are placed on the magnitude of the extrapolation that may be tolerated. This matrix method is applied to the problem of finding criticality and neutron fluxes in a nuclear reactor with control rods. The two-dimensional finite-difference approximation to the two-group neutron fluxes in a nuclear reactor with control rods. The two-dimensional finite-difference approximation to the two-group neutron-diffusion equations is treated. Results for this example are indicated.
The Use of Qsar and Computational Methods in Drug Design
NASA Astrophysics Data System (ADS)
Bajot, Fania
The application of quantitative structure-activity relationships (QSARs) has significantly impacted the paradigm of drug discovery. Following the successful utilization of linear solvation free-energy relationships (LSERs), numerous 2D- and 3D-QSAR methods have been developed, most of them based on descriptors for hydrophobicity, polarizability, ionic interactions, and hydrogen bonding. QSAR models allow for the calculation of physicochemical properties (e.g., lipophilicity), the prediction of biological activity (or toxicity), as well as the evaluation of absorption, distribution, metabolism, and excretion (ADME). In pharmaceutical research, QSAR has a particular interest in the preclinical stages of drug discovery to replace tedious and costly experimentation, to filter large chemical databases, and to select drug candidates. However, to be part of drug discovery and development strategies, QSARs need to meet different criteria (e.g., sufficient predictivity). This chapter describes the foundation of modern QSAR in drug discovery and presents some current challenges and applications for the discovery and optimization of drug candidates
New high throughput screening method for drug release measurements.
Pelczarska, Aleksandra; Delie, Florence; Domańska, Urszula; Carrupt, Pierre-Alain; Martel, Sophie
2013-09-01
In the field of drug delivery systems, microparticles made of polymeric matrix appear as an attractive approach. The in vitro release kinetic profile is crucial information when developing new particulate formulations. These data are essential for batch to batch comparison, quality control as well as for anticipation of in vivo behavior to select the best formulation to go further in preclinical investigations. The methods available present common drawbacks such as the time- and compound-consumption that does not fit with formulation screening requirements in early development stages. In this study, a new microscale high throughput screening (HTS) method has been developed to investigate drug release kinetic from piroxicam-loaded polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA) microparticles. The method is a sample- and separation-based method where separation is performed by filtration using 96-well micro filter plates. 96 experiments can therefore be performed on one plate in one time in a fully automated way and with a very low sample and particle consumption. The influence of different parameters controlling release profiles was also investigated using this technique. The HTS method gave the same release profile than the standard dialysis method. Shaking, particle concentration, and the nature of the release medium were found to be of influence. The HTS method appears as a reliable method to evaluate drug release from particles with smaller standard deviation and less consumption of material.
Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?
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.
Monitoring of air pollution by plants methods and problems
Steubing, L.; Jager, H.J.
1985-01-01
Ecosystem pollution is often discovered too late for preventive measure to be implemented. Papers include the topics of methods and problems of bioindication of air pollution. The participants discussed passive and active biological monitoring, including mapping of natural vegetation (lichens and mosses, for example) and plant exposure. Morphological and microscopical studies, chemical, physiological and biochemical investigations are presented.
Problems in Choosing Tools and Methods for Teaching Programming
ERIC Educational Resources Information Center
Vitkute-Adžgauskiene, Davia; Vidžiunas, Antanas
2012-01-01
The paper analyses the problems in selecting and integrating tools for delivering basic programming knowledge at the university level. Discussion and analysis of teaching the programming disciplines, the main principles of study programme design, requirements for teaching tools, methods and corresponding languages is presented, based on literature…
Approximate proximal point methods for convex programming problems
Eggermont, P.
1994-12-31
We study proximal point methods for the finite dimensional convex programming problem minimize f(x) such that x {element_of} C, where f : dom f {contained_in} RIR is a proper convex function and C {contained_in} R is a closed convex set.
Discontinuous Galerkin Finite Element Method for Parabolic Problems
NASA Technical Reports Server (NTRS)
Kaneko, Hideaki; Bey, Kim S.; Hou, Gene J. W.
2004-01-01
In this paper, we develop a time and its corresponding spatial discretization scheme, based upon the assumption of a certain weak singularity of parallel ut(t) parallel Lz(omega) = parallel ut parallel2, for the discontinuous Galerkin finite element method for one-dimensional parabolic problems. Optimal convergence rates in both time and spatial variables are obtained. A discussion of automatic time-step control method is also included.
Sensitivity analysis and approximation methods for general eigenvalue problems
NASA Technical Reports Server (NTRS)
Murthy, D. V.; Haftka, R. T.
1986-01-01
Optimization of dynamic systems involving complex non-hermitian matrices is often computationally expensive. Major contributors to the computational expense are the sensitivity analysis and reanalysis of a modified design. The present work seeks to alleviate this computational burden by identifying efficient sensitivity analysis and approximate reanalysis methods. For the algebraic eigenvalue problem involving non-hermitian matrices, algorithms for sensitivity analysis and approximate reanalysis are classified, compared and evaluated for efficiency and accuracy. Proper eigenvector normalization is discussed. An improved method for calculating derivatives of eigenvectors is proposed based on a more rational normalization condition and taking advantage of matrix sparsity. Important numerical aspects of this method are also discussed. To alleviate the problem of reanalysis, various approximation methods for eigenvalues are proposed and evaluated. Linear and quadratic approximations are based directly on the Taylor series. Several approximation methods are developed based on the generalized Rayleigh quotient for the eigenvalue problem. Approximation methods based on trace theorem give high accuracy without needing any derivatives. Operation counts for the computation of the approximations are given. General recommendations are made for the selection of appropriate approximation technique as a function of the matrix size, number of design variables, number of eigenvalues of interest and the number of design points at which approximation is sought.
Biophysical methods in drug discovery from small molecule to pharmaceutical.
Holdgate, Geoffrey; Geschwindner, Stefan; Breeze, Alex; Davies, Gareth; Colclough, Nicola; Temesi, David; Ward, Lara
2013-01-01
Biophysical methods have become established in many areas of drug discovery. Application of these methods was once restricted to a relatively small number of scientists using specialized, low throughput technologies and methods. Now, automated high-throughput instruments are to be found in a growing number of laboratories. Many biophysical methods are capable of measuring the equilibrium binding constants between pairs of molecules crucial for molecular recognition processes, encompassing protein-protein, protein-small molecule, and protein-nucleic acid interactions, and several can be used to measure the kinetic or thermodynamic components controlling these biological processes. For a full characterization of a binding process, determinations of stoichiometry, binding mode, and any conformational changes associated with such interactions are also required. The suite of biophysical methods that are now available represents a powerful toolbox of techniques which can effectively deliver this full characterization.The aim of this chapter is to provide the reader with an overview of the drug discovery process and how biophysical methods, such as surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), nuclear magnetic resonance, mass spectrometry (MS), and thermal unfolding methods can answer specific questions in order to influence project progression and outcomes. The selection of these examples is based upon the experiences of the authors at AstraZeneca, and relevant approaches are highlighted where they have utility in a particular drug discovery scenario.
Variational Methods For Sloshing Problems With Surface Tension
NASA Astrophysics Data System (ADS)
Tan, Chee Han; Carlson, Max; Hohenegger, Christel; Osting, Braxton
2016-11-01
We consider the sloshing problem for an incompressible, inviscid, irrotational fluid in a container, including effects due to surface tension on the free surface. We restrict ourselves to a constant contact angle and we seek time-harmonic solutions of the linearized problem, which describes the time-evolution of the fluid due to a small initial disturbance of the surface at rest. As opposed to the zero surface tension case, where the problem reduces to a partial differential equation for the velocity potential, we obtain a coupled system for the velocity potential and the free surface displacement. We derive a new variational formulation of the coupled problem and establish the existence of solutions using the direct method from the Calculus of Variations. In the limit of zero surface tension, we recover the variational formulation of the classical Steklov eigenvalue problem, as derived by B. A. Troesch. For the particular case of an axially symmetric container, we propose a finite element numerical method for computing the sloshing modes of the coupled system. The scheme is implemented in FEniCS and we obtain a qualitative description of the effect of surface tension on the sloshing modes.
In Vivo Methods for the Assessment of Topical Drug Bioavailability
Herkenne, Christophe; Alberti, Ingo; Naik, Aarti; Kalia, Yogeshvar N.; Mathy, François-Xavier; Préat, Véronique
2007-01-01
This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described. PMID:17985216
Alchemical free energy methods for drug discovery: Progress and challenges
Chodera, John D.; Mobley, David L.; Shirts, Michael R.; Dixon, Richard W.; Branson, Kim; Pande, Vijay S.
2011-01-01
Improved rational drug design methods are needed to lower the cost and increase the success rate of drug discovery and development. Alchemical binding free energy calculations, one potential tool for rational design, have progressed rapidly over the last decade, but still fall short of providing robust tools for pharmaceutical engineering. Recent studies, especially on model receptor systems, have clarified many of the challenges that must be overcome for robust predictions of binding affnity to be useful in rational design. In this review, inspired by a recent joint academic/industry meeting organized by the authors, we discuss these challenges and suggest a number of promising approaches for overcoming them. PMID:21349700
Formulations and computational methods for contact problems in solid mechanics
NASA Astrophysics Data System (ADS)
Mirar, Anand Ramchandra
2000-11-01
A study of existing formulations and computational methods for contact problems is conducted. The purpose is to gain insights into the solution procedures and pinpoint their limitations so that alternate procedures can be developed. Three such procedures based on the augmented Lagrangian method (ALM) are proposed. Small-scale benchmark problems are solved analytically as well as numerically to study the existing and proposed methods. The variational inequality formulation for frictionless contact is studied using the two bar truss-wall problem in a closed form. Sub-differential formulation is investigated using the spring-wall contact and the truss-wall friction problems. A two-phase analytical procedure is developed for solving the truss-wall frictional contact benchmark problem. The variational equality formulation for contact problems is studied using the penalty method along with the Newton-Raphson procedure. Limitations of such procedures, mainly due to their dependence on the user defined parameters (i.e., the penalty values and the number of time steps), are identified. Based on the study it is concluded that alternate formulations need to be developed. Frictionless contact formulation is developed using the basic concepts of ALM from optimization theory. A new frictional contact formulation (ALM1) is then developed employing ALM. Automatic penalty update procedure is used to eliminate dependence of the solution on the penalty values. Dependence of the solution on the number of time steps in the existing as well as ALM1 formulations is attributed to a flaw in the return mapping procedure for friction. Another new frictional contact formulation (ALM2) is developed to eliminate the dependence of solution on the number of time steps along with the penalty values. Effectiveness of ALM2 is demonstrated by solving the two bar and five bar truss-wall problems. The solutions are compared with the analytical and existing formulations. Design sensitivity analysis of
In silico machine learning methods in drug development.
Dobchev, Dimitar A; Pillai, Girinath G; Karelson, Mati
2014-01-01
Machine learning (ML) computational methods for predicting compounds with pharmacological activity, specific pharmacodynamic and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties are being increasingly applied in drug discovery and evaluation. Recently, machine learning techniques such as artificial neural networks, support vector machines and genetic programming have been explored for predicting inhibitors, antagonists, blockers, agonists, activators and substrates of proteins related to specific therapeutic targets. These methods are particularly useful for screening compound libraries of diverse chemical structures, "noisy" and high-dimensional data to complement QSAR methods, and in cases of unavailable receptor 3D structure to complement structure-based methods. A variety of studies have demonstrated the potential of machine-learning methods for predicting compounds as potential drug candidates. The present review is intended to give an overview of the strategies and current progress in using machine learning methods for drug design and the potential of the respective model development tools. We also regard a number of applications of the machine learning algorithms based on common classes of diseases.
Emerging Computational Methods for the Rational Discovery of Allosteric Drugs
2016-01-01
Allosteric drug development holds promise for delivering medicines that are more selective and less toxic than those that target orthosteric sites. To date, the discovery of allosteric binding sites and lead compounds has been mostly serendipitous, achieved through high-throughput screening. Over the past decade, structural data has become more readily available for larger protein systems and more membrane protein classes (e.g., GPCRs and ion channels), which are common allosteric drug targets. In parallel, improved simulation methods now provide better atomistic understanding of the protein dynamics and cooperative motions that are critical to allosteric mechanisms. As a result of these advances, the field of predictive allosteric drug development is now on the cusp of a new era of rational structure-based computational methods. Here, we review algorithms that predict allosteric sites based on sequence data and molecular dynamics simulations, describe tools that assess the druggability of these pockets, and discuss how Markov state models and topology analyses provide insight into the relationship between protein dynamics and allosteric drug binding. In each section, we first provide an overview of the various method classes before describing relevant algorithms and software packages. PMID:27074285
Projected discrete ordinates methods for numerical transport problems
Larsen, E.W.
1985-01-01
A class of Projected Discrete-Ordinates (PDO) methods is described for obtaining iterative solutions of discrete-ordinates problems with convergence rates comparable to those observed using Diffusion Synthetic Acceleration (DSA). The spatially discretized PDO solutions are generally not equal to the DSA solutions, but unlike DSA, which requires great care in the use of spatial discretizations to preserve stability, the PDO solutions remain stable and rapidly convergent with essentially arbitrary spatial discretizations. Numerical results are presented which illustrate the rapid convergence and the accuracy of solutions obtained using PDO methods with commonplace differencing methods.
A parallel Lanczos method for symmetric generalized eigenvalue problems
Wu, K.; Simon, H.D.
1997-12-01
Lanczos algorithm is a very effective method for finding extreme eigenvalues of symmetric matrices. It requires less arithmetic operations than similar algorithms, such as, the Arnoldi method. In this paper, the authors present their parallel version of the Lanczos method for symmetric generalized eigenvalue problem, PLANSO. PLANSO is based on a sequential package called LANSO which implements the Lanczos algorithm with partial re-orthogonalization. It is portable to all parallel machines that support MPI and easy to interface with most parallel computing packages. Through numerical experiments, they demonstrate that it achieves similar parallel efficiency as PARPACK, but uses considerably less time.
Branch and Bound Methods for the Traveling Salesman Problem.
1983-03-01
42 318 BRANCH AND ROUND METHODS FOR THE TRAVELING SALESMAN I PRO EM U) CARNEGIE-MELLON UNIV PITSBURGH PA MANAGEMENT SCIENCES RESEARCH GROUP E RU AS...fl 2.2 1 1 6 5 4 .6 MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU Of SIANARDS ) Qh A i . ’i ’V aBRANCH AND BOUND METHODS FOR THE TRAVELING ...06 20 126 a 77 W.P.#45-82-83 Management Science Research Report No. MSRR 488 BRANCH AND BOUND METHODS FOR THE TRAVELING SALESMAN PROBLEM by Egon Balas
Optimal least-squares finite element method for elliptic problems
NASA Technical Reports Server (NTRS)
Jiang, Bo-Nan; Povinelli, Louis A.
1991-01-01
An optimal least squares finite element method is proposed for two dimensional and three dimensional elliptic problems and its advantages are discussed over the mixed Galerkin method and the usual least squares finite element method. In the usual least squares finite element method, the second order equation (-Delta x (Delta u) + u = f) is recast as a first order system (-Delta x p + u = f, Delta u - p = 0). The error analysis and numerical experiment show that, in this usual least squares finite element method, the rate of convergence for flux p is one order lower than optimal. In order to get an optimal least squares method, the irrotationality Delta x p = 0 should be included in the first order system.
Meshless Petrov-Galerkin Method Applied to Axisymmetric Problems
NASA Technical Reports Server (NTRS)
Raju, I. S.; Chen, T.
2001-01-01
An axisymmetric Meshless Local Petrov-Galerkin (MLPG) algorithm is presented for the potential and elasticity problems. In this algorithm the trial and test functions are chosen from different spaces. By a judicious choice of these functions, the integrals involved in the weak form can be restricted to a local neighborhood. This makes the method truly meshless. The MLPG algorithm is used to study various potential and elasticity problems for which exact solutions are available. The sensitivity and effectiveness of the MLPG algorithm to various parameters such as the weight functions, basis functions and support domain radius, etc. was studied. The MLPG algorithm yielded accurate solutions for all weight functions, basis functions and support domain radii considered for all of the problems studied.
Drug and alcohol abuse: The pattern and magnitude of the problem
Ajayi, P.A.
1996-12-31
In the last 12 months, many more cases of alcohol and drug (substance) abuse in the workplace were seen in the Escravos operations of Chevron Nigeria Limited than in previous years. This called the attention to the rising prevalence of drug and alcohol abuse in contradistinction to reports from similar organizations in other parts of the world. Chevron Nigeria has a written Drug and Alcohol Policy which has been dormant for some time because of the apparent rarity of the problem of substance abuse in the workplace. This Policy is being reviewed to broaden its scope and make it more effective. A total of 30 employees were tested for drugs and alcohol .6 exceeded the legal limits of Blood Alcohol Concentration (BAC) and 5 tested positive for drugs. Tests were mainly post-accident, reasonable cause and random. The common substances abused were alcohol, cannabis, cocaine and morphine in that order. The findings are compared with those of similar organizations in UK and USA. Efforts to control substance abuse in the workplace are being put into place.
Multidrug and extensively drug-resistant TB (M/XDR-TB): problems and solutions.
Prasad, Rajendra
2010-10-01
Multi Drug Resistant Tuberculosis (MDR-TB) and Extensively Drug Resistant Tuberculosis (XDR-TB) are posing a threat to the control of tuberculosis. The first WHO-IUATLD antituberculosis drug resistance surveillance carried out in 1994 in 35 countries reported the median prevalence of primary and acquired multi drug resistance as 1.4% and 13% respectively. Subsequently, second, third and fourth WHO-IUATLD global drug resistance surveillances were carried out in 1996-99, 1999-2002 and 2002-2007 respectively. Based on drug resistance information from 114 countries, the proportion of MDR-TB among all cases was estimated for countries with no survey information. It was estimated that 4,89,139 cases of MDR-TB emerged in 2006. China and India carry approximately 50% of the global burden. 35 countries and two Special Administrative Regions (SARs) reported data on XDR-TB for the first time in 2006. Multidrug and extensively drug-resistant TB 2010 Global report on Surveillance and response estimated that 4,40,000 cases of MDR-TB emerged globally in 2008 and caused an estimated 1,50,000 deaths. 5.4% of MDR-TB cases were found to have XDR-TB. To date, a cumulative total of 58 countries have confirmed at least one case of XDR-TB. M/XDR-TB is a man-made problem and its emergence can be prevented by prompt diagnosis and effective use of first line drugs in every new patient. The DOTS Plus proposed by WHO highlights the comprehensive management strategy to control MDR-TB. Laboratory services for adequate and timely diagnosis of M/XDR-TB must be strengthened and programmatic management of M/XDR-TB must be scaled up as per target set by global plan. Proper use of second-line drugs must be ensured to cure existing MDR-TB, to reduce its transmission and to prevent XDR-TB. Sound infection control measures to avoid further transmission of M/XDR-TB and research towards development of new diagnostics, drugs and vaccines should be promoted to control M/XDR-TB.
Methods for solving reasoning problems in abstract argumentation - A survey.
Charwat, Günther; Dvořák, Wolfgang; Gaggl, Sarah A; Wallner, Johannes P; Woltran, Stefan
2015-03-01
Within the last decade, abstract argumentation has emerged as a central field in Artificial Intelligence. Besides providing a core formalism for many advanced argumentation systems, abstract argumentation has also served to capture several non-monotonic logics and other AI related principles. Although the idea of abstract argumentation is appealingly simple, several reasoning problems in this formalism exhibit high computational complexity. This calls for advanced techniques when it comes to implementation issues, a challenge which has been recently faced from different angles. In this survey, we give an overview on different methods for solving reasoning problems in abstract argumentation and compare their particular features. Moreover, we highlight available state-of-the-art systems for abstract argumentation, which put these methods to practice.
Fully converged iterative method for coupled channel problems
NASA Astrophysics Data System (ADS)
Shu, Di; Simbotin, I.; Côté, R.
2016-05-01
We implemented a numerical method using a distorted-wave perturbative approach for coupled-channel scattering problems. Our new method provides a way to avoid costly computations for the propagation of the full solutions in coupled-channel problems to large distances for slowly vanishing couplings. Thus, instead of dealing with large matrices, all computations are performed in a channel by channel fashion. The distorted wavefunction for each channel is initialized with the appropriate solution (which includes the diagonal element of the coupling potential matrix). We then solve single-channel inhomogeneous radial equations which contain the (off-diagonal) couplings as a perturbation, and we iterate until desired accuracy is achieved. We tested for stability by continuing to iterate even after convergence has been achieved, e.g., for a total of 75 iterations. Partial support from the US Army Research Office (ARO-MURI W911NF-14-1-0378), and from NSF (Grant No. PHY-1415560).
Fast Implicit Methods For Elliptic Moving Interface Problems
2015-12-11
THIS PAGE Unclassified 14. ABSTRACT Two notable advances in numerical methods were supported by this grant. First, a fast algorithm was derived...play a key role in computational problems ranging from medical imaging to partial differential equations, and existing algorithms are inaccurate and...or prohibitively slow for d > 0. The algorithm employs low-rank approximation by Taylor series organized in a butterfly scheme, with moments evaluated
Algebraic Methods Applied to Network Reliability Problems. Revision.
1986-09-01
RD-RIBs 38? ALGEBRAIC METHODS APPLIED TO NETHORK RELIABILITY 1/1 PROBLEMS REVISIOU(U) CLEMSON UNIV SC DEPT OF MATEMATICAL SCIENCES D R SHIER ET AL...class of directed networks, Oper. Res., 32 (1984), pp. 493-515. -2 " 16 [3] A. AGRAWAL AND A. SATYANARAYANA, Network reliability analysis using 2...Networks, 13 (1983), pp. 107-120. [20] A. SATYANARAYANA AND A. PRABHAKAR, A new topological formula and rapid algorithm for reliability analysis of complex
On the Application of the Energy Method to Stability Problems
NASA Technical Reports Server (NTRS)
Marguerre, Karl
1947-01-01
Since stability problems have come into the field of vision of engineers, energy methods have proved to be one of the most powerful aids in mastering them. For finding the especially interesting critical loads special procedures have evolved that depart somewhat from those customary in the usual elasticity theory. A clarification of the connections seemed desirable,especially with regard to the post-critical region, for the treatment of which these special methods are not suited as they are. The present investigation discusses this question-complex (made important by shell construction in aircraft) especially in the classical example of the Euler strut, because in this case - since the basic features are not hidden by difficulties of a mathematical nature - the problem is especially clear. The present treatment differs from that appearing in the Z.f.a.M.M. (1938) under the title "Uber die Behandlung von Stabilittatsproblemen mit Hilfe der energetischen Methode" in that, in order to work out the basic ideas still more clearly,it dispenses with the investigation of behavior at large deflections and of the elastic foundation;in its place the present version gives an elaboration of the 6th section and (in its 7 th and 8th secs.)a new example that shows the applicability of the general criterion to a stability problem that differs from that of Euler in many respects.
Solving ODE Initial Value Problems With Implicit Taylor Series Methods
NASA Technical Reports Server (NTRS)
Scott, James R.
2000-01-01
In this paper we introduce a new class of numerical methods for integrating ODE initial value problems. Specifically, we propose an extension of the Taylor series method which significantly improves its accuracy and stability while also increasing its range of applicability. To advance the solution from t (sub n) to t (sub n+1), we expand a series about the intermediate point t (sub n+mu):=t (sub n) + mu h, where h is the stepsize and mu is an arbitrary parameter called an expansion coefficient. We show that, in general, a Taylor series of degree k has exactly k expansion coefficients which raise its order of accuracy. The accuracy is raised by one order if k is odd, and by two orders if k is even. In addition, if k is three or greater, local extrapolation can be used to raise the accuracy two additional orders. We also examine stability for the problem y'= lambda y, Re (lambda) less than 0, and identify several A-stable schemes. Numerical results are presented for both fixed and variable stepsizes. It is shown that implicit Taylor series methods provide an effective integration tool for most problems, including stiff systems and ODE's with a singular point.
Don't Flush! Why Your Drug Disposal Method Matters ...
April 30th is the U.S. Drug Enforcement Administration’s National Drug Take-Back Day. All over the country there will be facilities accepting any unwanted or expired medications from 10:00 AM – 2:00 PM – it is the perfect opportunity to clean out your medicine cabinet while simultaneously helping to protect aquatic animals and their environment from chemical exposure!Have you ever participated in a drug take-back program? If not, what do you typically do with leftover medications after you defeat a bacterial infection or find an old bottle of Tylenol? Many people may flush unwanted or expired pharmaceuticals down the toilet or throw them in the trash, but those methods can actually harm our environment.When flushed or thrown-out, these drugs end up in our coastal ecosystems; and all the chemicals in those little pills that were once working together to make us feel better, are now dissolving in our waterways where they can negatively impact aquatic animals.Scientists throughout EPA continue to evaluate the potential toxicity of different drugs in order to determine what specific effects they have on aquatic wildlife, and to develop new ways to detect if an organism has been exposed to those drugs.I recently spoke with Bushra Khan (NRC post-doc) and Theresa Johnson (ORISE fellow) of the EPA’s Atlantic Ecology Division to learn about some of the specific effects they have observed in their research. Bushra talked to me about the effects beta blockers, m
Application the particle method in problems of mechanics deformable media
NASA Astrophysics Data System (ADS)
Berezhnoi, D. V.; Gabsalikova, N. F.; Miheev, V. V.
2016-11-01
The work implemented method of deformation of ground-based particle method, which is a collection of mineral grains, which are linked to some system of forces on the contact areas between the mineral particles. Two-parameter potential Lennard-Jones and it is modified version were selected for describing the behavior of ground. Some model problems of straining layer of ground in the gravity field was decided. The calculations were performed on a heterogeneous computing cluster, on each of the seven components that were installed on three GPU AMD Radeon HD 7970.
Conforming and nonconforming virtual element methods for elliptic problems
Cangiani, Andrea; Manzini, Gianmarco; Sutton, Oliver J.
2016-08-03
Here we present, in a unified framework, new conforming and nonconforming virtual element methods for general second-order elliptic problems in two and three dimensions. The differential operator is split into its symmetric and nonsymmetric parts and conditions for stability and accuracy on their discrete counterparts are established. These conditions are shown to lead to optimal H^{1}- and L^{2}-error estimates, confirmed by numerical experiments on a set of polygonal meshes. The accuracy of the numerical approximation provided by the two methods is shown to be comparable.
Conforming and nonconforming virtual element methods for elliptic problems
Cangiani, Andrea; Manzini, Gianmarco; Sutton, Oliver J.
2016-08-03
Here we present, in a unified framework, new conforming and nonconforming virtual element methods for general second-order elliptic problems in two and three dimensions. The differential operator is split into its symmetric and nonsymmetric parts and conditions for stability and accuracy on their discrete counterparts are established. These conditions are shown to lead to optimal H1- and L2-error estimates, confirmed by numerical experiments on a set of polygonal meshes. The accuracy of the numerical approximation provided by the two methods is shown to be comparable.
Validation of analytic methods for biomarkers used in drug development.
Chau, Cindy H; Rixe, Olivier; McLeod, Howard; Figg, William D
2008-10-01
The role of biomarkers in drug discovery and development has gained precedence over the years. As biomarkers become integrated into drug development and clinical trials, quality assurance and, in particular, assay validation become essential with the need to establish standardized guidelines for analytic methods used in biomarker measurements. New biomarkers can revolutionize both the development and use of therapeutics but are contingent on the establishment of a concrete validation process that addresses technology integration and method validation as well as regulatory pathways for efficient biomarker development. This perspective focuses on the general principles of the biomarker validation process with an emphasis on assay validation and the collaborative efforts undertaken by various sectors to promote the standardization of this procedure for efficient biomarker development.
Statistical methods for active pharmacovigilance, with applications to diabetes drugs.
Zhuo, Lan; Farrell, Patrick J; McNair, Doug; Krewski, Daniel
2014-01-01
Pharmacovigilance aims to identify adverse drug reactions using postmarket surveillance data under real-world conditions of use. Unlike passive pharmacovigilance, which is based on largely voluntary (and hence incomplete) spontaneous reports of adverse drug reactions with limited information on patient characteristics, active pharmacovigilance is based on electronic health records containing detailed information about patient populations, thereby allowing consideration of modifying factors such as polypharmacy and comorbidity, as well as sociodemographic characteristics. With the present shift toward active pharmacovigilance, statistical methods capable of addressing the complexities of such data are needed. We describe four such methods here, and demonstrate their application in the analysis of a large retrospective cohort of diabetics taking anti-hyperglycemic medications that may increase the risk of adverse cardiovascular events.
Orwat, John; Saitz, Richard; Tompkins, Christopher P; Cheng, Debbie M; Dentato, Michael P; Samet, Jeffrey H
2011-10-01
This is a prospective cohort study to identify factors associated with receipt of substance abuse treatment (SAT) among adults with alcohol problems and HIV/AIDS. Data from the HIV Longitudinal Interrelationships of Viruses and Ethanol study were analyzed. Generalized estimating equation logistic regression models were fit to identify factors associated with any service utilization. An alcohol dependence diagnosis had a negative association with SAT (adjusted odds ratio [AOR] = 0.36, 95% confidence interval [95% CI] = 0.19-0.67), as did identifying sexual orientation other than heterosexual (AOR = 0.46, CI = 0.29-0.72) and having social supports that use alcohol/drugs (AOR = 0.62, CI = 0.45-0.83). Positive associations with SAT include presence of hepatitis C antibody (AOR = 3.37, CI = 2.24-5.06), physical or sexual abuse (AOR = 2.12, CI = 1.22-3.69), social supports that help with sobriety (AOR = 1.92, CI = 1.28-2.87), homelessness (AOR = 2.40, CI = 1.60-3.62), drug dependence diagnosis (AOR = 2.64, CI = 1.88-3.70), and clinically important depressive symptoms (AOR = 1.52, CI = 1.08-2.15). While reassuring that factors indicating need for SAT among people with HIV and alcohol problems (e.g., drug dependence) are associated with receipt, nonneed factors (e.g., sexual orientation, age) that should not decrease likelihood of receipt of treatment were identified.
Comparison of Optimal Design Methods in Inverse Problems.
Banks, H T; Holm, Kathleen; Kappel, Franz
2011-07-01
Typical optimal design methods for inverse or parameter estimation problems are designed to choose optimal sampling distributions through minimization of a specific cost function related to the resulting error in parameter estimates. It is hoped that the inverse problem will produce parameter estimates with increased accuracy using data collected according to the optimal sampling distribution. Here we formulate the classical optimal design problem in the context of general optimization problems over distributions of sampling times. We present a new Prohorov metric based theoretical framework that permits one to treat succinctly and rigorously any optimal design criteria based on the Fisher Information Matrix (FIM). A fundamental approximation theory is also included in this framework. A new optimal design, SE-optimal design (standard error optimal design), is then introduced in the context of this framework. We compare this new design criteria with the more traditional D-optimal and E-optimal designs. The optimal sampling distributions from each design are used to compute and compare standard errors; the standard errors for parameters are computed using asymptotic theory or bootstrapping and the optimal mesh. We use three examples to illustrate ideas: the Verhulst-Pearl logistic population model [13], the standard harmonic oscillator model [13] and a popular glucose regulation model [16, 19, 29].
Do You or a Loved One Have a Drug Use Problem?
... Families? Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use Hurts Other People Drug ... do to you? Have you ever taken one drug to get over the effects of another? Have you ever made mistakes at ...
ERIC Educational Resources Information Center
Friedman, Alfred S.; Utada, Arlene
1989-01-01
Describes development of Adolescent Drug Abuse Diagnosis (ADAD), a 150-item instrument with a structured interview format, which produces a comprehensive evaluation of the life problem areas pertinent to the needs of adolescent drug abuse clients. A series of validity and reliability tests are described, along with characteristics of the…
In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.
Mayorga, C; Sanz, M L; Gamboa, P; Garcia-Aviles, M C; Fernandez, J; Torres, M J
2013-01-01
Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.
Substructure method in high-speed monorail dynamic problems
NASA Astrophysics Data System (ADS)
Ivanchenko, I. I.
2008-12-01
The study of actions of high-speed moving loads on bridges and elevated tracks remains a topical problem for transport. In the present study, we propose a new method for moving load analysis of elevated tracks (monorail structures or bridges), which permits studying the interaction between two strained objects consisting of rod systems and rigid bodies with viscoelastic links; one of these objects is the moving load (monorail rolling stock), and the other is the carrying structure (monorail elevated track or bridge). The methods for moving load analysis of structures were developed in numerous papers [1-15]. At the first stage, when solving the problem about a beam under the action of the simplest moving load such as a moving weight, two fundamental methods can be used; the same methods are realized for other structures and loads. The first method is based on the use of a generalized coordinate in the expansion of the deflection in the natural shapes of the beam, and the problem is reduced to solving a system of ordinary differential equations with variable coefficients [1-3]. In the second method, after the "beam-weight" system is decomposed, just as in the problem with the weight impact on the beam [4], solving the problem is reduced to solving an integral equation for the dynamic weight reaction [6, 7]. In [1-3], an increase in the number of retained forms leads to an increase in the order of the system of equations; in [6, 7], difficulties arise when solving the integral equations related to the conditional stability of the step procedures. The method proposed in [9, 14] for beams and rod systems combines the above approaches and eliminates their drawbacks, because it permits retaining any necessary number of shapes in the deflection expansion and has a resolving system of equations with an unconditionally stable integration scheme and with a minimum number of unknowns, just as in the method of integral equations [6, 7]. This method is further developed for
On path-following methods for structural failure problems
NASA Astrophysics Data System (ADS)
Stanić, Andjelka; Brank, Boštjan; Korelc, Jože
2016-08-01
We revisit the consistently linearized path-following method that can be applied in the nonlinear finite element analysis of solids and structures in order to compute a solution path. Within this framework, two constraint equations are considered: a quadratic one (that includes as special cases popular spherical and cylindrical forms of constraint equation), and another one that constrains only one degree-of-freedom (DOF), the critical DOF. In both cases, the constrained DOFs may vary from one solution increment to another. The former constraint equation is successful in analysing geometrically nonlinear and/or standard inelastic problems with snap-throughs, snap-backs and bifurcation points. However, it cannot handle problems with the material softening that are computed e.g. by the embedded-discontinuity finite elements. This kind of problems can be solved by using the latter constraint equation. The plusses and minuses of the both presented constraint equations are discussed and illustrated on a set of numerical examples. Some of the examples also include direct computation of critical points and branch switching. The direct computation of the critical points is performed in the framework of the path-following method by using yet another constraint function, which is eigenvector-free and suited to detect critical points.
ERIC Educational Resources Information Center
Nigg, Joel T.; Wong, Maria M.; Martel, Michelle M.; Jester, Jennifer M.; Puttler, Leon I.; Glass, Jennifer M.; Adams, Kenneth M.; Fitzgerald, Hiram E.; Zucker, Robert A.
2006-01-01
Objective: To evaluate the predictive power of executive functions, in particular, response inhibition, in relation to alcohol-related problems and illicit drug use in adolescence. Method: A total of 498 children from 275 families from a longitudinal high-risk study completed executive function measures in early and late adolescence and lifetime…
ERIC Educational Resources Information Center
Gray, Calonie M. K.; Montgomery, Marilyn J.
2012-01-01
Objectives: This study examined the links between maltreatment, posttraumatic stress symptoms, ethnicity-specific factors (i.e., perceived discrimination, ethnic identity, and ethnic orientation), and alcohol and/or other drug (AOD) problems among adolescent girls. Methods: These relations were examined using archived data from a community sample…
The Problem Solving Method in Teaching Physics in Elementary School
NASA Astrophysics Data System (ADS)
Jandrić, Gordana Hajduković; Obadović, Dušanka Ž.; Stojanović, Maja
2010-01-01
The most of the teachers ask if there is a "best" known way to teach. The most effective teaching method depends on the specific goals of the course and the needs of the students. An investigation has been carried out to compare the effect of teaching selected physics topics using problem-solving method on the overall achievements of the acquired knowledge and teaching the same material by traditional teaching method. The investigation was performed as a pedagogical experiment of the type of parallel groups with randomly chosen sample of students attending grades eight. The control and experimental groups were equalized in the relevant pedagogical parameters. The obtained results were treated statistically. The comparison showed a significant difference in respect of the speed of acquiring knowledge, the problem-solving teaching being advantageous over traditional methodDo not replace the word "abstract," but do replace the rest of this text. If you must insert a hard line break, please use Shift+Enter rather than just tapping your "Enter" key. You may want to print this page and refer to it as a style sample before you begin working on your paper.
WEAK GALERKIN METHODS FOR SECOND ORDER ELLIPTIC INTERFACE PROBLEMS
MU, LIN; WANG, JUNPING; WEI, GUOWEI; YE, XIU; ZHAO, SHAN
2013-01-01
Weak Galerkin methods refer to general finite element methods for partial differential equations (PDEs) in which differential operators are approximated by their weak forms as distributions. Such weak forms give rise to desirable flexibilities in enforcing boundary and interface conditions. A weak Galerkin finite element method (WG-FEM) is developed in this paper for solving elliptic PDEs with discontinuous coefficients and interfaces. Theoretically, it is proved that high order numerical schemes can be designed by using the WG-FEM with polynomials of high order on each element. Extensive numerical experiments have been carried to validate the WG-FEM for solving second order elliptic interface problems. High order of convergence is numerically confirmed in both L2 and L∞ norms for the piecewise linear WG-FEM. Special attention is paid to solve many interface problems, in which the solution possesses a certain singularity due to the nonsmoothness of the interface. A challenge in research is to design nearly second order numerical methods that work well for problems with low regularity in the solution. The best known numerical scheme in the literature is of order O(h) to O(h1.5) for the solution itself in L∞ norm. It is demonstrated that the WG-FEM of the lowest order, i.e., the piecewise constant WG-FEM, is capable of delivering numerical approximations that are of order O(h1.75) to O(h2) in the L∞ norm for C1 or Lipschitz continuous interfaces associated with a C1 or H2 continuous solution. PMID:24072935
WEAK GALERKIN METHODS FOR SECOND ORDER ELLIPTIC INTERFACE PROBLEMS.
Mu, Lin; Wang, Junping; Wei, Guowei; Ye, Xiu; Zhao, Shan
2013-10-01
Weak Galerkin methods refer to general finite element methods for partial differential equations (PDEs) in which differential operators are approximated by their weak forms as distributions. Such weak forms give rise to desirable flexibilities in enforcing boundary and interface conditions. A weak Galerkin finite element method (WG-FEM) is developed in this paper for solving elliptic PDEs with discontinuous coefficients and interfaces. Theoretically, it is proved that high order numerical schemes can be designed by using the WG-FEM with polynomials of high order on each element. Extensive numerical experiments have been carried to validate the WG-FEM for solving second order elliptic interface problems. High order of convergence is numerically confirmed in both L2 and L∞ norms for the piecewise linear WG-FEM. Special attention is paid to solve many interface problems, in which the solution possesses a certain singularity due to the nonsmoothness of the interface. A challenge in research is to design nearly second order numerical methods that work well for problems with low regularity in the solution. The best known numerical scheme in the literature is of order [Formula: see text] to [Formula: see text] for the solution itself in L∞ norm. It is demonstrated that the WG-FEM of the lowest order, i.e., the piecewise constant WG-FEM, is capable of delivering numerical approximations that are of order [Formula: see text] to [Formula: see text] in the L∞ norm for C(1) or Lipschitz continuous interfaces associated with a C(1) or H(2) continuous solution.
Tiessen, Renger G; Lagerwey, Hendrik Jan G; Jager, Gea J; Sprenger, Herman G
2010-01-01
A 58-year-old man, who spoke very little Dutch, had various symptoms and used several drugs including simvastatin. He was prescribed itraconazole for onychomycosis. Simvastatin was concurrently replaced with pravastatin to prevent drug interactions. However, the interaction still occurred when the pravastatin ran out, and the patient resumed taking simvastatin on his own initiative. Myalgia and muscle weakness developed after one week. The general practitioner found a strongly elevated creatine kinase level in the blood. The patient required hospitalisation for severe rhabdomyolysis. He was treated with an infusion of an ample quantity of physiological saline solution and made a full recovery. Due to the elevated risk of toxic interactions, doctors should beware of communication problems in complex patients and avoid new prescriptions not strictly required.
Drug-related problems in patients with erectile dysfunctions and multiple comorbidities
Huri, Hasniza Zaman; Ling, Chui Fang; Razack, Azad Hassan Abdul
2017-01-01
This study was conducted in a tertiary medical center in Kuala Lumpur, Malaysia. A total of 200 erectile dysfunction (ED) patients with 499 cases who had received pharmacological treatments for their ED participated in this study. Types, causes and factors associated with drug-related problems (DRPs) in ED patients with multiple comorbidities were assessed. A total of 244 DRPs with an average of 1.2±2.1 DRPs per patient were identified. Drug interaction contributed the most to DRPs occurrence. There was a significant higher risk of DRPs in patients with benign prostatic hyperplasia, lower urinary tract infection and elderly and end-stage renal disease. Early identification of types of DRPs and factors associated may enhance their prevention and management.
Limnell, Tarja; Santos, Hélder A; Mäkilä, Ermei; Heikkilä, Teemu; Salonen, Jarno; Murzin, Dmitry Yu; Kumar, Narendra; Laaksonen, Timo; Peltonen, Leena; Hirvonen, Jouni
2011-08-01
A poorly soluble model drug, indomethacin (IMC), was loaded into two types of silica particles using three different loading methods. The loading efficiency and the extent/rate of drug release were evaluated. Widely used equipment in pharmaceutical laboratories, rotavapor and fluid bed, were used in the loading. The porous materials used were ordered mesoporous silica MCM-41 and nonordered silica gel Syloid 244 FP EU. The materials differ both in their pore properties and particle sizes. Tablets were successfully compressed from the IMC-loaded particles. Mechanical stability of the porous structures was studied with XRPD and nitrogen sorption after tableting and drug release was evaluated at pH 5.5 before and after tableting. The release of the poorly soluble IMC was faster from the Syloid than from the MCM-41, presumably due to the larger pore size and smaller particle size. Loading of IMC into the MCM-41 microparticles improved the drug dissolution, and blending the microparticles with pharmaceutical excipients improved the IMC release even further. The fast release was also maintained after tableting. Loading of IMC into the Syloid particles alone was sufficient to produce similar IMC release profiles, as in the case of MCM-41 with the excipients.
New drugs and methods of doping and manipulation.
Thevis, Mario; Kohler, Maxie; Schänzer, Wilhelm
2008-01-01
The issue of doping in sport is multifaceted. New drugs not only with anabolic properties such as selective androgen receptor modulators, synthetic insulins, blood doping with erythropoietins or homologous and autologous blood transfusions but also with sample manipulation have necessitated sensitive, comprehensive and specific detection assays allowing for the identification of cheats. New methods based on mass spectrometry, flow cytometry and immunological techniques have been introduced and improved in the past years to support and enhance the antidoping fight. Although numerous approaches are successful and promising, these methods still have some shortcomings.
Variance reduction methods applied to deep-penetration problems
Cramer, S.N.
1984-01-01
All deep-penetration Monte Carlo calculations require variance reduction methods. Before beginning with a detailed approach to these methods, several general comments concerning deep-penetration calculations by Monte Carlo, the associated variance reduction, and the similarities and differences of these with regard to non-deep-penetration problems will be addressed. The experienced practitioner of Monte Carlo methods will easily find exceptions to any of these generalities, but it is felt that these comments will aid the novice in understanding some of the basic ideas and nomenclature. Also, from a practical point of view, the discussions and developments presented are oriented toward use of the computer codes which are presented in segments of this Monte Carlo course.
Fully decoupled monolithic projection method for natural convection problems
NASA Astrophysics Data System (ADS)
Pan, Xiaomin; Kim, Kyoungyoun; Lee, Changhoon; Choi, Jung-Il
2017-04-01
To solve time-dependent natural convection problems, we propose a fully decoupled monolithic projection method. The proposed method applies the Crank-Nicolson scheme in time and the second-order central finite difference in space. To obtain a non-iterative monolithic method from the fully discretized nonlinear system, we first adopt linearizations of the nonlinear convection terms and the general buoyancy term with incurring second-order errors in time. Approximate block lower-upper decompositions, along with an approximate factorization technique, are additionally employed to a global linearly coupled system, which leads to several decoupled subsystems, i.e., a fully decoupled monolithic procedure. We establish global error estimates to verify the second-order temporal accuracy of the proposed method for velocity, pressure, and temperature in terms of a discrete l2-norm. Moreover, according to the energy evolution, the proposed method is proved to be stable if the time step is less than or equal to a constant. In addition, we provide numerical simulations of two-dimensional Rayleigh-Bénard convection and periodic forced flow. The results demonstrate that the proposed method significantly mitigates the time step limitation, reduces the computational cost because only one Poisson equation is required to be solved, and preserves the second-order temporal accuracy for velocity, pressure, and temperature. Finally, the proposed method reasonably predicts a three-dimensional Rayleigh-Bénard convection for different Rayleigh numbers.
Matched Interface and Boundary Method for Elasticity Interface Problems
Wang, Bao; Xia, Kelin; Wei, Guo-Wei
2015-01-01
Elasticity theory is an important component of continuum mechanics and has had widely spread applications in science and engineering. Material interfaces are ubiquity in nature and man-made devices, and often give rise to discontinuous coefficients in the governing elasticity equations. In this work, the matched interface and boundary (MIB) method is developed to address elasticity interface problems. Linear elasticity theory for both isotropic homogeneous and inhomogeneous media is employed. In our approach, Lamé’s parameters can have jumps across the interface and are allowed to be position dependent in modeling isotropic inhomogeneous material. Both strong discontinuity, i.e., discontinuous solution, and weak discontinuity, namely, discontinuous derivatives of the solution, are considered in the present study. In the proposed method, fictitious values are utilized so that the standard central finite different schemes can be employed regardless of the interface. Interface jump conditions are enforced on the interface, which in turn, accurately determines fictitious values. We design new MIB schemes to account for complex interface geometries. In particular, the cross derivatives in the elasticity equations are difficult to handle for complex interface geometries. We propose secondary fictitious values and construct geometry based interpolation schemes to overcome this difficulty. Numerous analytical examples are used to validate the accuracy, convergence and robustness of the present MIB method for elasticity interface problems with both small and large curvatures, strong and weak discontinuities, and constant and variable coefficients. Numerical tests indicate second order accuracy in both L∞ and L2 norms. PMID:25914439
Global Regularization Method for Planar Restricted Three-body Problem
NASA Astrophysics Data System (ADS)
Sharaf, M. A.; Dwidar, H. R.
2015-12-01
In this paper, global regularization method for planar restricted three-body problem is purposed by using the transformation z=x+iy=ν cos n(u+iv), where i=√{-1}, 0 < ν ≤ 1 and n is a positive integer. The method is developed analytically and computationally. For the analytical developments, analytical solutions in power series of the pseudo-time τ are obtained for positions and velocities (u,v,u',v') and (x,y,dot{x},dot{y}) in both regularized and physical planes respectively, the physical time {t} is also obtained as power series in τ. Moreover, relations between the coefficients of the power series are obtained for two consequent values of {n}. Also, we developed analytical solutions in power series form for the inverse problem of finding τ in terms of {t}. As typical examples, three symbolic expressions for the coefficients of the power series were developed in terms of the initial values. As to the computational developments, the global regularized equations of motion are developed together with their initial values in forms suitable for digital computations using any differential equations solver. On the other hand, for the numerical evolutions of power series, an efficient method depending on the continued fraction theory is provided.
Matched Interface and Boundary Method for Elasticity Interface Problems.
Wang, Bao; Xia, Kelin; Wei, Guo-Wei
2015-09-01
Elasticity theory is an important component of continuum mechanics and has had widely spread applications in science and engineering. Material interfaces are ubiquity in nature and man-made devices, and often give rise to discontinuous coefficients in the governing elasticity equations. In this work, the matched interface and boundary (MIB) method is developed to address elasticity interface problems. Linear elasticity theory for both isotropic homogeneous and inhomogeneous media is employed. In our approach, Lamé's parameters can have jumps across the interface and are allowed to be position dependent in modeling isotropic inhomogeneous material. Both strong discontinuity, i.e., discontinuous solution, and weak discontinuity, namely, discontinuous derivatives of the solution, are considered in the present study. In the proposed method, fictitious values are utilized so that the standard central finite different schemes can be employed regardless of the interface. Interface jump conditions are enforced on the interface, which in turn, accurately determines fictitious values. We design new MIB schemes to account for complex interface geometries. In particular, the cross derivatives in the elasticity equations are difficult to handle for complex interface geometries. We propose secondary fictitious values and construct geometry based interpolation schemes to overcome this difficulty. Numerous analytical examples are used to validate the accuracy, convergence and robustness of the present MIB method for elasticity interface problems with both small and large curvatures, strong and weak discontinuities, and constant and variable coefficients. Numerical tests indicate second order accuracy in both L∞ and L2 norms.
Empirical likelihood method for non-ignorable missing data problems.
Guan, Zhong; Qin, Jing
2017-01-01
Missing response problem is ubiquitous in survey sampling, medical, social science and epidemiology studies. It is well known that non-ignorable missing is the most difficult missing data problem where the missing of a response depends on its own value. In statistical literature, unlike the ignorable missing data problem, not many papers on non-ignorable missing data are available except for the full parametric model based approach. In this paper we study a semiparametric model for non-ignorable missing data in which the missing probability is known up to some parameters, but the underlying distributions are not specified. By employing Owen (1988)'s empirical likelihood method we can obtain the constrained maximum empirical likelihood estimators of the parameters in the missing probability and the mean response which are shown to be asymptotically normal. Moreover the likelihood ratio statistic can be used to test whether the missing of the responses is non-ignorable or completely at random. The theoretical results are confirmed by a simulation study. As an illustration, the analysis of a real AIDS trial data shows that the missing of CD4 counts around two years are non-ignorable and the sample mean based on observed data only is biased.
Comparison of optimal design methods in inverse problems
NASA Astrophysics Data System (ADS)
Banks, H. T.; Holm, K.; Kappel, F.
2011-07-01
Typical optimal design methods for inverse or parameter estimation problems are designed to choose optimal sampling distributions through minimization of a specific cost function related to the resulting error in parameter estimates. It is hoped that the inverse problem will produce parameter estimates with increased accuracy using data collected according to the optimal sampling distribution. Here we formulate the classical optimal design problem in the context of general optimization problems over distributions of sampling times. We present a new Prohorov metric-based theoretical framework that permits one to treat succinctly and rigorously any optimal design criteria based on the Fisher information matrix. A fundamental approximation theory is also included in this framework. A new optimal design, SE-optimal design (standard error optimal design), is then introduced in the context of this framework. We compare this new design criterion with the more traditional D-optimal and E-optimal designs. The optimal sampling distributions from each design are used to compute and compare standard errors; the standard errors for parameters are computed using asymptotic theory or bootstrapping and the optimal mesh. We use three examples to illustrate ideas: the Verhulst-Pearl logistic population model (Banks H T and Tran H T 2009 Mathematical and Experimental Modeling of Physical and Biological Processes (Boca Raton, FL: Chapman and Hall/CRC)), the standard harmonic oscillator model (Banks H T and Tran H T 2009) and a popular glucose regulation model (Bergman R N, Ider Y Z, Bowden C R and Cobelli C 1979 Am. J. Physiol. 236 E667-77 De Gaetano A and Arino O 2000 J. Math. Biol. 40 136-68 Toffolo G, Bergman R N, Finegood D T, Bowden C R and Cobelli C 1980 Diabetes 29 979-90).
[Drug-resistant malaria: problems with its definition and technical approaches].
Basco, L; Ringwald, P
2000-01-01
% inhibitory concentration IC50). The in vitro assay not only yields quantitative results, it also determines the phenotype of the parasite independently of the immune and physiopathological conditions of the host. However, this in vitro assay requires highly skilled personnel and laboratory equipment. In addition, parasites isolated from patients who have taken medication on their own initiative a few days before consultation usually do not grow in vitro and the interpretation of assay results for patients with multiple infections may be equivocal. One of the major problems with in vitro tests is the determination of the threshold IC50 values that distinguish susceptible from resistant parasites. There are currently no fully validated cut-off points for assessing in vitro resistance. Despite these shortcomings, in vitro tests are of value, particularly if performed in parallel with the in vivo test. Molecular biology has made a major contribution to our understanding of the mechanisms of drug resistance. Discrete point mutations in the genes encoding dihydrofolate reductase and dihydropteroate synthase are strongly associated with resistance in vitro to pyrimethamine and sulfadoxine, respectively. Preliminary results have also suggested that these mutations are responsible for the failure of sulfadoxine-pyrimethamine combination treatment. No causal relationship between discrete polymorphisms in the candidate genes and in vitro chloroquine resistance has yet been established. High-performance liquid chromatography is being increasingly used to determine the plasma concentrations of antimalarial drugs in patients with prophylactic or therapeutic failure, to check that the failure of the treatment is not due to inadequate levels of the drug in the patient. Taking into account all these aspects of resistance to antimalarial drugs we think that the WHO definition of drug resistance is now inadequate. (ABSTRACT TRUNCATED)
Finite volume method for geodetic boundary value problem
NASA Astrophysics Data System (ADS)
Medľa, Matej; Mikula, Karol; Macák, Marek
2016-04-01
We present new finite volume numerical scheme for solving the Geodetic boundary value problem on non-uniform logically rentangular grids together with new second-order upwind treatment of the oblique derivative. First the logically rectangular grid is built above the Earth topography by evolving surface approach. Then the Laplace equation is solved on such grid by using the finite volume method in which the normal derivative on finite volume boundary face is split into derivative in tangential direction and a derivative in direction of the vector connecting representative points of neigbouring finite volumes. The oblique derivative boundary condition is understood as a stationary advection equation and second-order upwind method is developed for its discretization. The numerical experiments will be presented.
Nonlinear Multidimensional Assignment Problems Efficient Conic Optimization Methods and Applications
2015-06-24
problems. The size 16 three-dimensional quadratic assignment problem Q3AP from wireless communications was solved using a sophisticated approach...combinatorial optimization problem, the Directional Sensor Problem, was solved in two ways. First, heuristically in an engineering fashion and second, exactly...the sensor problem was solved as a nonlinear MINLP problem. Specifically, the information gain obtained was maximized in order to determine the optimal
Tharwat, Alaa; Moemen, Yasmine S.; Hassanien, Aboul Ella
2016-01-01
Measuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets. PMID:27934950
Gnassi, J. A.; Barnett, G. O.
1993-01-01
Drug information resources are increasingly becoming electronically available. They differ in scope, granularity, and purpose. These considerations have shaped the selection of dissimilar drug name keys, complicating access. An abbreviated and simplified historical context of the development of official controlled vocabularies and their relationships is followed by a review of the kinds of information available in several electronic drug information resources. The key vocabularies used are discussed with examples. Problems using the differing terms of the resource vocabularies are identified. PMID:8130551
[Development of a Drug Discovery Method Targeted to Stromal Tissue].
Kamada, Haruhiko
2016-01-01
Several diseases are characterized by alterations in the molecular distribution of vascular structures, presenting the opportunity to use monoclonal antibodies for clinical therapies. This pharmaceutical strategy, often referred to as "vascular targeting", has promise in promoting the discovery and development of selective biological drugs to regulate angiogenesis-related diseases such as cancer. Various experimental approaches have been utilized to discover accessible vascular markers of health and disease at the protein level. Our group has developed a new chemical proteomics technology to identify and quantify accessible vascular proteins in normal organs and at disease sites. Our developed methodology relies on the perfusion of animal models with suitable ester derivatives of biotin, which react with the primary amine groups of proteins as soon as the molecules are attached. This presentation reports biomedical applications based on vascular targeting strategies, as well as methodologies that have been used to discover new vascular targets. The identification of antigens located in the stromal tissue of pathological blood vessels may provide attractive targets for the development of antibody drugs. This method will also provide an efficient discovery target that could lead to the development of novel antibody drugs.
ERIC Educational Resources Information Center
Newcomb, Michael D.; Rickards, Shannae
1995-01-01
Used community samples to determine the effects of childhood family support or dysfunction and the extent of parent drug-use problems on adult intimacy issues, such as sexual satisfaction. Results showed that parent drug-use predicted poor family support; family support correlated strongly with good adult intimate relations. (RJM)
Locke, Thomas F; Newcomb, Michael
2004-03-01
The authors tested how adverse childhood experiences (child maltreatment and parent alcohol- and drug-related problems) and adult polydrug use (as a mediator) predict poor parenting in a community sample (237 mothers and 81 fathers). These relationships were framed within several theoretical perspectives, including observational learning, impaired functioning, self-medication, and parentification-pseudomaturity. Structural models revealed that child maltreatment predicted poor parenting practices among mothers. Parent alcohol- and drug-related problems had an indirect detrimental influence on mothers' parenting and practices through self-drug problems. Among fathers, emotional neglect experienced as a child predicted lack of parental warmth more parental neglect, and sexual abuse experienced as a child predicted a rejecting style of parenting.
Methods for the coupled Stokes-Darcy problem
NASA Astrophysics Data System (ADS)
Feuillebois, F.; Khabthani, S.; Elasmi, L.; Sellier, A.
2010-11-01
The motion of particles in a viscous fluid close to a porous membrane is modelled for the case when particles are large compared with the size of pores of the membrane. The hydrodynamic interactions of one particle with the membrane are detailed here. The model involves Stokes equations for the fluid motion around the particle together with Darcy equations for the flow in the porous membrane and Stokes equations for the flow on the other side of the membrane. Boundary conditions at the fluid-membrane interface are the continuity of pressure and velocity in the normal direction and the Beavers and Joseph slip condition on the fluid side in the tangential directions. The no-slip condition applies on the particle. This problem is solved here by two different methods. The first one is an extended boundary integral method (EBIM). A Green function is derived for the flow close to a porous membrane. This function is non-symmetric, leading to difficulties hindering the application of the classical boundary integral method (BIM). Thus, an extended method is proposed, in which the unknown distribution of singularities on the particle surface is not the stress, like in the classical boundary integral method. Yet, the hydrodynamic force and torque on the particle are obtained by integrals of this distribution on the particle surface. The second method consists in searching the solution as an asymptotic expansion in term of a small parameter that is the ratio of the typical pore size to the particle size. The various boundary conditions are taken into account at successive orders: order (0) simply represents an impermeable wall without slip and order (1) an impermeable wall with a peculiar slip prescribed by order (0); at least the 3rd order is necessary to enforce all boundary conditions. The methods are applied numerically to a spherical particle and comparisons are made with earlier works in particular cases.
Hiroyasu, Tomoyuki; Miyabe, Yota; Yokouchi, Hisatake
2011-01-01
Here, we propose a training data selection method using a Support Vector Machine (SVM) to predict the effects of anticancer drugs. Conventionally, SVM is used for distinguishing between several types of data. However, in the method proposed here, the SVM is used to distinguish areas with only one or two types of data. The proposed method treats training data selection as an optimization problem and involves application of a genetic algorithm (GA). Moreover, GA with local search was applied to find the solution as the target problem was difficult to find. The composition method of GA for proposed method was examined. To determine its effectiveness, the proposed method was applied to an artificial anticancer drug data set. The verification results showed that the proposed method can be used to create a verifiable and predictable discriminant function by training data selection.
The residual method for regularizing ill-posed problems
Grasmair, Markus; Haltmeier, Markus; Scherzer, Otmar
2011-01-01
Although the residual method, or constrained regularization, is frequently used in applications, a detailed study of its properties is still missing. This sharply contrasts the progress of the theory of Tikhonov regularization, where a series of new results for regularization in Banach spaces has been published in the recent years. The present paper intends to bridge the gap between the existing theories as far as possible. We develop a stability and convergence theory for the residual method in general topological spaces. In addition, we prove convergence rates in terms of (generalized) Bregman distances, which can also be applied to non-convex regularization functionals. We provide three examples that show the applicability of our theory. The first example is the regularized solution of linear operator equations on Lp-spaces, where we show that the results of Tikhonov regularization generalize unchanged to the residual method. As a second example, we consider the problem of density estimation from a finite number of sampling points, using the Wasserstein distance as a fidelity term and an entropy measure as regularization term. It is shown that the densities obtained in this way depend continuously on the location of the sampled points and that the underlying density can be recovered as the number of sampling points tends to infinity. Finally, we apply our theory to compressed sensing. Here, we show the well-posedness of the method and derive convergence rates both for convex and non-convex regularization under rather weak conditions. PMID:22345828
[Drug design ideas and methods of Chinese herb prescriptions].
Ren, Jun-guo; Liu, Jian-xun
2015-09-01
The new drug of Chinese herbal prescription, which is the best carrier for the syndrome differentiation and treatment of Chinese medicine and is the main form of the new drug research and development, plays a very important role in the new drug research and development. Although there are many sources of the prescriptions, whether it can become a new drug, the necessity, rationality and science of the prescriptions are the key to develop the new drug. In this article, aiming at the key issues in prescriptions design, the source, classification, composition design of new drug of Chinese herbal prescriptions are discussed, and provide a useful reference for research and development of new drugs.
Domain Decomposition Methods for Problems in H(curl)
NASA Astrophysics Data System (ADS)
Calvo, Juan Gabriel
Two domain decomposition methods for solving vector field problems posed in H(curl) and discretized with Nedelec finite elements are considered. These finite elements are conforming in H(curl). A two-level overlapping Schwarz algorithm in two dimensions is analyzed, where the subdomains are only assumed to be uniform in the sense of Peter Jones. The coarse space is based on energy minimization and its dimension equals the number of interior subdomain edges. Local direct solvers are based on the overlapping subdomains. The bound for the condition number depends only on a few geometric parameters of the decomposition. This bound is independent of jumps in the coefficients across the interface between the subdomains for most of the different cases considered. A bound is also obtained for the condition number of a balancing domain decomposition by constraints (BDDC) algorithm in two dimensions, with Jones subdomains. For the primal variable space, a continuity constraint for the tangential average over each interior subdomain edge is imposed. For the averaging operator, a new technique named deluxe scaling is used. The optimal bound is independent of jumps in the coefficients across the interface between the subdomains. Furthermore, a new coarse function for problems in three dimensions is introduced, with only one degree of freedom per subdomain edge. In all the cases, it is established that the algorithms are scalable. Numerical results that verify the results are provided, including some with subdomains with fractal edges and others obtained by a mesh partitioner.
NASA Astrophysics Data System (ADS)
Ali, Elaf Jaafar; Gao, David Yang
2016-10-01
The goal of this paper is to solve the post buckling phenomena of a large deformed elastic beam by a canonical dual mixed finite element method (CD-FEM). The total potential energy of this beam is a nonconvex functional which can be used to model both pre-and post-buckling problems. Different types of dual stress interpolations are used in order to verify the triality theory. Applications are illustrated with different boundary conditions and external loads by using semi-definite programming (SDP) algorithm. The results show that the global minimum of the total potential energy is stable buckled configuration, the local maximum solution leads to the unbuckled state, and both of these two solutions are numerically stable. While the local minimum is unstable buckled configuration and very sensitive to both stress interpolations and the external loads.
Multiresolution subspace-based optimization method for inverse scattering problems.
Oliveri, Giacomo; Zhong, Yu; Chen, Xudong; Massa, Andrea
2011-10-01
This paper investigates an approach to inverse scattering problems based on the integration of the subspace-based optimization method (SOM) within a multifocusing scheme in the framework of the contrast source formulation. The scattering equations are solved by a nested three-step procedure composed of (a) an outer multiresolution loop dealing with the identification of the regions of interest within the investigation domain through an iterative information-acquisition process, (b) a spectrum analysis step devoted to the reconstruction of the deterministic components of the contrast sources, and (c) an inner optimization loop aimed at retrieving the ambiguous components of the contrast sources through a conjugate gradient minimization of a suitable objective function. A set of representative reconstruction results is discussed to provide numerical evidence of the effectiveness of the proposed algorithmic approach as well as to assess the features and potentialities of the multifocusing integration in comparison with the state-of-the-art SOM implementation.
A numerical method for interface problems in elastodynamics
NASA Technical Reports Server (NTRS)
Mcghee, D. S.
1984-01-01
The numerical implementation of a formulation for a class of interface problems in elastodynamics is discussed. This formulation combines the use of the finite element and boundary integral methods to represent the interior and the exteriro regions, respectively. In particular, the response of a semicylindrical alluvial valley in a homogeneous halfspace to incident antiplane SH waves is considered to determine the accuracy and convergence of the numerical procedure. Numerical results are obtained from several combinations of the incidence angle, frequency of excitation, and relative stiffness between the inclusion and the surrounding halfspace. The results tend to confirm the theoretical estimates that the convergence is of the order H(2) for the piecewise linear elements used. It was also observed that the accuracy descreases as the frequency of excitation increases or as the relative stiffness of the inclusion decreases.
Multigrid methods for parabolic distributed optimal control problems
NASA Astrophysics Data System (ADS)
Borzì, Alfio
2003-08-01
Multigrid schemes that solve parabolic distributed optimality systems discretized by finite differences are investigated. Accuracy properties of finite difference approximation are discussed and validated. Two multigrid methods are considered which are based on a robust relaxation technique and use two different coarsening strategies: semicoarsening and standard coarsening. The resulting multigrid algorithms show robustness with respect to changes of the value of [nu], the weight of the cost of the control, is sufficiently small. Fourier mode analysis is used to investigate the dependence of the linear twogrid convergence factor on [nu] and on the discretization parameters. Results of numerical experiments are reported that demonstrate sharpness of Fourier analysis estimates. A multigrid algorithm that solves optimal control problems with box constraints on the control is considered.
Panda, Abinash; Pradhan, Supriya; Mohapatra, Gurukrushna; Mohapatra, Jigyansa
2016-01-01
Objectives: The objective of this study is to identify and compare the nature of the drug-related problems (DRPs) associated with self-medication and non-self-medication (drug use guided by a prescription). Materials and Methods: The cross-sectional, observational study was conducted on 1100 adult participants at a convenience sample of six retail private pharmacy counters. The data collection form was based on the Pharmaceutical Care Network Europe version 6.2 classification for DRPs. Descriptive statistics was used to represent the prevalence of DRPs. Chi-square test was used to find out the association between the type of medication and DRPs. Odds ratio (OR) with confidence interval (CI) was computed to find the factors determining the occurrence of DRPs. P < 0.05 was considered to be statistically significant. Data were analyzed using SPSS version 16.0. Results: The prevalence of self-medication was 18.72%. The prevalence of DRPs was 17.36%. In the self-medication group, the prevalence of DRPs was high (40.78%) as compared to the non-self-medication group (11.97%). DRP related to inappropriate drug dosing was observed in 44.83% and 40.45% subjects in self-medication and non-self-medication group, respectively (P < 0.001). The subjects in the self-medication group were about 5 times likely to have a DRP (OR: 5.06, CI: 3.59-7.14, P < 0.001). Conclusions: Self-medication is associated with a higher risk of various DRPs. Since retail pharmacy outlet is often the first point of contact between the patient and the health care system in a developing country, interventions like drug information activities at the retail pharmacy is likely to bring down the DRPs associated with self-medication. PMID:27721536
Validated spectrophotometric methods for determination of some oral hypoglycemic drugs.
Farouk, M; Abdel-Satar, O; Abdel-Aziz, O; Shaaban, M
2011-02-01
Four accurate, precise, rapid, reproducible, and simple spectrophotometric methods were validated for determination of repaglinide (RPG), pioglitazone hydrochloride (PGL) and rosiglitazone maleate (RGL). The first two methods were based on the formation of a charge-transfer purple-colored complex of chloranilic acid with RPG and RGL with a molar absorptivity 1.23 × 10^{3} and 8.67 × 10^{2} l•mol^{-1}•cm^{-1} and a Sandell's sensitivity of 0.367 and 0.412 μg•cm^{-2}, respectively, and an ion-pair yellow-colored complex of bromophenol blue with RPG, PGL and RGL with molar absorptivity 8.86 × 10^{3}, 6.95 × 10^{3}, and 7.06 × 10^{3} l•mol^{-1}•cm^{-1}, respectively, and a Sandell's sensitivity of 0.051 μg•cm^{-2} for all ion-pair complexes. The influence of different parameters on color formation was studied to determine optimum conditions for the visible spectrophotometric methods. The other spectrophotometric methods were adopted for demtermination of the studied drugs in the presence of their acid-, alkaline- and oxidative-degradates by computing derivative and pH-induced difference spectrophotometry, as stability-indicating techniques. All the proposed methods were validated according to the International Conference on Harmonization guidelines and successfully applied for determination of the studied drugs in pure form and in pharmaceutical preparations with good extraction recovery ranges between 98.7-101.4%, 98.2-101.3%, and 99.9-101.4% for RPG, PGL, and RGL, respectively. Results of relative standard deviations did not exceed 1.6%, indicating that the proposed methods having good repeatability and reproducibility. All the obtained results were statistically compared to the official method used for RPG analysis and the manufacturers methods used for PGL and RGL analysis, respectively, where no significant differences were found.
Ophthalmic Drug Dosage Forms: Characterisation and Research Methods
Baranowski, Przemysław; Karolewicz, Bożena; Gajda, Maciej; Pluta, Janusz
2014-01-01
This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient's compliance. PMID:24772038
Ophthalmic drug dosage forms: characterisation and research methods.
Baranowski, Przemysław; Karolewicz, Bożena; Gajda, Maciej; Pluta, Janusz
2014-01-01
This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient's compliance.
Using Problem Fields as a Method of Change.
ERIC Educational Resources Information Center
Pehkonen, Erkki
1992-01-01
Discusses the rationale and use of problem fields which are sets of related and/or connected open-ended problem-solving tasks within mathematics instruction. Polygons with matchsticks and the number triangle are two examples of problem fields presented along with variations in conditions that promote other matchstick puzzles. (11 references) (JJK)
Radiation methods for decontamination of liquid wastes and ecological problems
Shubin, V.N.; Brusentseva, S.A.; Vysotskaya, N.A.
1986-01-01
The authors discuss several possible approaches to the use of radiation for the purposes of rational use of water resources and protecting them from pollution and depletion. The authors note that radiation decontamination makes it possible to solve a number of important problems in protecting fundamental elements of the biosphere by: reducing the uptake of fresh water from natural sources for industrial and household needs and sharply cutting the release of unpurified waste water by creating circulating water systems based on rapid methods of thorough purification; employing a combination of different physical and chemical methods with a final stage that uses radiation-prolonged adsorption to give the water a high degree of purity; preventing bacterial contamination of soils when liquid and semiliquid wastes from cities and livestock farms are used as fertilizers; utilizing the excess active sludges that accumulate in biological treatment factilities as feed additives and fertilizer; and eliminating the release to the atmosphere of effluents from the incineration of highly polluted waste water which often contains carcinogenic and poisonous substances.
Electrospinning: methods and development of biodegradable nanofibres for drug release.
Ashammakhi, N; Wimpenny, I; Nikkola, L; Yang, Y
2009-02-01
It is clear that nanofibrous structures can be used as tools for many applications. It is already known that electrospinning is a highly versatile method of producing nanofibres and recent developments in the technique of electrospinning have led to the development of aligned nanofibres and biphasic, core-sheath fibres which can be used to encapsulate different materials from molecules to cells. Natural extracellular matrix (ECM) contains fibres in both micro and nano-scales and provides a structural scaffold which allows cells to localize, migrate, proliferate and differentiate. Polymer nanofibres can provide the structural cues of ECM. However, current literature gives new hope to further functionalising polymeric nanofibres by using them for drug delivery devices and improving their design to improve control of delivery. By encapsulating active agents within nanofibres (multifunctional nanofibres), a degree of control can be exerted over the release of encapsulated agents and therefore, the behaviour of cells can be manipulated for developing effective therapies and is extremely encouraging in the tissue engineering field by combining factors like fibre diameter, alignment and chemicals in new ways. Such multifunctional nanofibre-based systems are already being investigated in vivo. Experiments have shown the significant potential for treatments of disease and engineering of neural and bone tissues. Further, phase III clinical trials of nanofibrous patches for applications in wound treatment were encouraging. Hopefully, clinical applications of these drug delivery devices will follow, to enhance regenerative medicine applications.
ERIC Educational Resources Information Center
Vitaro, Frank; And Others
1992-01-01
This article, written in French, describes and evaluates the first phase of a program to prevent drug addiction among 110 fifth-grade girls with behavior problems in Montreal (Quebec, Canada). Evaluation of the instructional program showed positive results for student knowledge level, attitudes, and behaviors and supported program continuation…
Alzheimer's disease drug development and the problem of the blood-brain barrier
Pardridge, William M.
2009-01-01
Alzheimer's disease (AD) drug development is limited by the presence of the blood-brain barrier (BBB). More than 98% of all small molecule drugs, and ∼100% of all large molecule drugs, do not cross the BBB. Despite the fact that the vast majority of AD drug candidates do not cross the BBB, the present-day AD drug development effort is characterized by an imbalance, whereby >99% of the drug development effort is devoted to CNS drug discovery, and <1% of drug development is devoted to CNS drug delivery. Future AD drug development needs a concerted effort to incorporate the BBB sciences early in the CNS drug discovery process. This can be accomplished by a reallocation of resources, and an expansion of the effort in the pure science of BBB biology and the applied science of brain drug targeting technology. PMID:19751922
Misiak, Majus; Mantegazza, Francesco; Beretta, Giovanni L
2016-01-01
DNA damaging agents including anthracyclines, camptothecins and platinum drugs are among most frequently used drugs in the chemotherapeutic routine. Due to their relatively low selectivity for cancer cells, administration of these drugs is associated with adverse side effects, inherent genotoxicity with risk of developing secondary cancers. Development of new drugs, which could be spared of these drawbacks and characterize by improved antitumor efficacy, remains challenging yet vitally important task. These properties are in large part dictated by the selectivity of interaction between the drug and DNA and in this way the studies aimed at elucidating the complex interactions between ligand and DNA represent a key step in the drug development. Studies of the drug-DNA interactions encompass determination of DNA sequence specificity and mode of DNA binding as well as kinetic, dynamic and structural parameters of binding. Here, we consider the types of interactions between small molecule ligands and polynucleotides, how they are affected by DNA sequence and structure, and what is their significance for the antitumor activity. Based on this knowledge, we discuss the wide array of experimental techniques available to researchers for studying drug-DNA interactions, which include absorption and emission spectroscopies, NMR, magnetic and optical tweezers or atomic force microscopy. We show, using the clinical and experimental anticancer drugs as examples, how these methods provide various types of information and at the same time complement each other to provide full picture of drug- DNA interaction and aid in the development of new drugs.
21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.
Code of Federal Regulations, 2010 CFR
2010-04-01
..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification....
21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.
Code of Federal Regulations, 2013 CFR
2013-04-01
..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification....
21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.
Code of Federal Regulations, 2011 CFR
2011-04-01
..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification....
21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.
Code of Federal Regulations, 2014 CFR
2014-04-01
..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification....
21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.
Code of Federal Regulations, 2012 CFR
2012-04-01
..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification....
Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods.
Reese, Jessica A; Li, Xiaoning; Hauben, Manfred; Aster, Richard H; Bougie, Daniel W; Curtis, Brian R; George, James N; Vesely, Sara K
2010-09-23
Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia.
Tuan, Nguyen Van; Dalman, Christina; Thiem, Nguyen Viet; Nghi, Tran Viet; Allebeck, Peter
2009-01-01
The objective of this paper was to investigate methods of poisoning, presence of mental problems, and the rate of psychiatric care among suicide attempters in Vietnam. Three hundred and nine suicide attempters by poisoning admitted to Bach Mai Hospital's Poison Control Center were investigated by trained nurses and qualified psychiatrists. Standardized questionnaires were used to assess methods of suicide, presence of mental problems, and psychiatric care. The most common methods were poisoning by psychotropic drugs in urban, and pesticides in rural areas. ICD-10 confirmed disorders were present in 68% of the cases and 73% rated positive on SRQ-20. Most patients were not in contact with psychiatric care. Restrictions on availability and handling of drugs and pesticides should be reinforced. Better infrastructures are needed for identification and treatment of persons with mental disorders.
Boundary-integral methods in elasticity and plasticity. [solutions of boundary value problems
NASA Technical Reports Server (NTRS)
Mendelson, A.
1973-01-01
Recently developed methods that use boundary-integral equations applied to elastic and elastoplastic boundary value problems are reviewed. Direct, indirect, and semidirect methods using potential functions, stress functions, and displacement functions are described. Examples of the use of these methods for torsion problems, plane problems, and three-dimensional problems are given. It is concluded that the boundary-integral methods represent a powerful tool for the solution of elastic and elastoplastic problems.
ERIC Educational Resources Information Center
Corkill, Jeffrey A.
1988-01-01
Proposes a series of experiments that integrate analytical techniques in order that students are able to compare, based on their laboratory results, the relative reliabilities of the most common therapeutic drug monitoring methods. Discusses materials, procedures, and results of three experiments on the determination of drug concentration by…
An efficient iterative method for the generalized Stokes problem
Sameh, A.; Sarin, V.
1996-12-31
This paper presents an efficient iterative scheme for the generalized Stokes problem, which arises frequently in the simulation of time-dependent Navier-Stokes equations for incompressible fluid flow. The general form of the linear system is where A = {alpha}M + vT is an n x n symmetric positive definite matrix, in which M is the mass matrix, T is the discrete Laplace operator, {alpha} and {nu} are positive constants proportional to the inverses of the time-step {Delta}t and the Reynolds number Re respectively, and B is the discrete gradient operator of size n x k (k < n). Even though the matrix A is symmetric and positive definite, the system is indefinite due to the incompressibility constraint (B{sup T}u = 0). This causes difficulties both for iterative methods and commonly used preconditioners. Moreover, depending on the ratio {alpha}/{nu}, A behaves like the mass matrix M at one extreme and the Laplace operator T at the other, thus complicating the issue of preconditioning.
An Application of Wedelin's Method to Railway Crew Scheduling Problem
NASA Astrophysics Data System (ADS)
Miura, Rei; Imaizumi, Jun; Fukumura, Naoto; Morito, Susumu
So many scheduling problems arise in railway industries. One of the typical scheduling problems is Crew Scheduling Problem. Much attention has been paid to this problem by a lot of researchers, but many studies have not been done to the problems in railway industries in Japan. In this paper, we consider a railway crew scheduling problem in Japan. The problem can be formulated into Set Covering Problem (SCP). In SCP, a row corresponds to a trip representing a minimal task and a column corresponds to a pairing representing a sequence of trips performed by a certain crew. Many algorithms have been developed and proposed for it. On the other hand, in practical use, it is important to investigate how these algorithms behave and work on a certain problem. Therefore, we focus on Wedelin's algorithm, which is based on Lagrange relaxation and is known as one of the high performance algorithms for SCP, and mainly examine the basic idea of this algorithm. Furthermore, we show effectiveness of this procedure through computational experiments on instances from Japanese railway.
ERIC Educational Resources Information Center
Reynolds, John C., Jr.
1976-01-01
Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)
Des Jarlais, Don C; Perlis, Theresa E; Stimson, Gerry V; Poznyak, Vladimir
2006-01-01
Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs). Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups; security problems for users
Other Drug Use and Abuse on Campus: The Scope of the Problem. Infofacts/Resources
ERIC Educational Resources Information Center
Ross, Virginia; DeJong, William
2009-01-01
Of all drugs abused on college and university campuses, alcohol causes the greatest harm. Other drugs (the prevention field uses the term "other drugs" to distinguish them from alcohol, which also is a drug) also take a significant toll--diminishing the quality of campus life, undermining academic performance, compromising students' health and…
Application of the method of maximum entropy in the mean to classification problems
NASA Astrophysics Data System (ADS)
Gzyl, Henryk; ter Horst, Enrique; Molina, German
2015-11-01
In this note we propose an application of the method of maximum entropy in the mean to solve a class of inverse problems comprising classification problems and feasibility problems appearing in optimization. Such problems may be thought of as linear inverse problems with convex constraints imposed on the solution as well as on the data. The method of maximum entropy in the mean proves to be a very useful tool to deal with this type of problems.
New Testing Methods to Assess Technical Problem-Solving Ability.
ERIC Educational Resources Information Center
Hambleton, Ronald K.; And Others
Tests to assess problem-solving ability being provided for the Air Force are described, and some details on the development and validation of these computer-administered diagnostic achievement tests are discussed. Three measurement approaches were employed: (1) sequential problem solving; (2) context-free assessment of fundamental skills and…
The Method To Acquire the Strategic Knowledge on Problem Solving.
ERIC Educational Resources Information Center
Takaoka, Ryo; Okamoto, Toshio
As a person learns, his problem solving ability improves and one reason for this is the increased acquisition of "macro-rules" which make problem solving more efficient. An intelligent computer assisted learning (ICAI) system is being developed which automatically acquires the useful knowledge from the domain experts; as experts give the learning…
Manzini, Gianmarco
2012-07-13
We develop and analyze a new family of virtual element methods on unstructured polygonal meshes for the diffusion problem in primal form, that use arbitrarily regular discrete spaces V{sub h} {contained_in} C{sup {alpha}} {element_of} N. The degrees of freedom are (a) solution and derivative values of various degree at suitable nodes and (b) solution moments inside polygons. The convergence of the method is proven theoretically and an optimal error estimate is derived. The connection with the Mimetic Finite Difference method is also discussed. Numerical experiments confirm the convergence rate that is expected from the theory.
Li, Yi; Gu, Christine; Gruenhagen, Jason; Yehl, Peter; Chetwyn, Nik P.; Medley, Colin D.
2016-01-01
ABSTRACT Antibody-drug conjugates (ADCs) are complex therapeutic agents that use the specific targeting properties of antibodies and the highly potent cytotoxicity of small molecule drugs to selectively eliminate tumor cells while limiting the toxicity to normal healthy tissues. Two critical quality attributes of ADCs are the purity and stability of the active small molecule drug linked to the ADC, but these are difficult to assess once the drug is conjugated to the antibody. In this study, we report a enzyme deconjugation approach to cleave small molecule drugs from ADCs, which allows the drugs to be subsequently characterized by reversed-phase high performance liquid chromatography. The model ADC we used in this study utilizes a valine-citrulline linker that is designed to be sensitive to endoproteases after internalization by tumor cells. We screened several proteases to determine the most effective enzyme. Among the 3 cysteine proteases evaluated, papain had the best efficiency in cleaving the small molecule drug from the model ADC. The deconjugation conditions were further optimized to achieve complete cleavage of the small molecule drug. This papain deconjugation approach demonstrated excellent specificity and precision. The purity and stability of the active drug on an ADC drug product was evaluated and the major degradation products of the active drug were identified. The papain deconjugation method was also applied to several other ADCs, with the results suggesting it could be applied generally to ADCs containing a valine-citrulline linker. Our results indicate that the papain deconjugation method is a powerful tool for characterizing the active small molecule drug conjugated to an ADC, and may be useful in ensuring the product quality, efficacy and the safety of ADCs. PMID:26891281
NASA Astrophysics Data System (ADS)
Bussetta, Philippe; Marceau, Daniel; Ponthot, Jean-Philippe
2012-02-01
The aim of this work is to propose a new numerical method for solving the mechanical frictional contact problem in the general case of multi-bodies in a three dimensional space. This method is called adapted augmented Lagrangian method (AALM) and can be used in a multi-physical context (like thermo-electro-mechanical fields problems). This paper presents this new method and its advantages over other classical methods such as penalty method (PM), adapted penalty method (APM) and, augmented Lagrangian method (ALM). In addition, the efficiency and the reliability of the AALM are proved with some academic problems and an industrial thermo-electromechanical problem.
ERIC Educational Resources Information Center
Dewey, William L., Ed.; Harris, Louis S., Ed.
This publication summarizes the activities of the most recent meeting of the nation's most influential drug abuse professionals and measures progress in a variety of areas. Outcomes of symposia, meetings, and presentations are discussed. Symposia include: (1) "Is Dopamine the Answer? Evidence for the Importance of Other Systems in the…
Multi-level adaptive finite element methods. 1: Variation problems
NASA Technical Reports Server (NTRS)
Brandt, A.
1979-01-01
A general numerical strategy for solving partial differential equations and other functional problems by cycling between coarser and finer levels of discretization is described. Optimal discretization schemes are provided together with very fast general solvers. It is described in terms of finite element discretizations of general nonlinear minimization problems. The basic processes (relaxation sweeps, fine-grid-to-coarse-grid transfers of residuals, coarse-to-fine interpolations of corrections) are directly and naturally determined by the objective functional and the sequence of approximation spaces. The natural processes, however, are not always optimal. Concrete examples are given and some new techniques are reviewed. Including the local truncation extrapolation and a multilevel procedure for inexpensively solving chains of many boundary value problems, such as those arising in the solution of time-dependent problems.
Quasistatic Evolution in Debonding Problems via Capacitary Methods
NASA Astrophysics Data System (ADS)
Bucur, Dorin; Buttazzo, Giuseppe; Lux, Anne
2008-09-01
We discuss quasistatic evolution processes for capacitary measures and shapes in order to model debonding membranes. Minimizing movements as well as rate-independent processes are investigated and some models are described, together with a series of open problems.
Don’t Flush! Why Your Drug Disposal Method Matters
April 30th is the U.S. Drug Enforcement Administration’s National Drug Take-Back Day. All over the country there will be facilities accepting any unwanted or expired medications from 10:00 AM – 2:00 PM – it is the perfect opportunity to clean out your medicine cabinet while simu...
Adverse drug events and medication errors: detection and classification methods.
Morimoto, T; Gandhi, T K; Seger, A C; Hsieh, T C; Bates, D W
2004-08-01
Investigating the incidence, type, and preventability of adverse drug events (ADEs) and medication errors is crucial to improving the quality of health care delivery. ADEs, potential ADEs, and medication errors can be collected by extraction from practice data, solicitation of incidents from health professionals, and patient surveys. Practice data include charts, laboratory, prescription data, and administrative databases, and can be reviewed manually or screened by computer systems to identify signals. Research nurses, pharmacists, or research assistants review these signals, and those that are likely to represent an ADE or medication error are presented to reviewers who independently categorize them into ADEs, potential ADEs, medication errors, or exclusions. These incidents are also classified according to preventability, ameliorability, disability, severity, stage, and responsible person. These classifications, as well as the initial selection of incidents, have been evaluated for agreement between reviewers and the level of agreement found ranged from satisfactory to excellent (kappa = 0.32-0.98). The method of ADE and medication error detection and classification described is feasible and has good reliability. It can be used in various clinical settings to measure and improve medication safety.
What to Do If You Have a Problem with Drugs: For Teens and Young Adults
... The NIDA website also has information on specific drugs, including their effects on the body, brain, and behavior . NIDA also has an Easy-to-Read website with information about many drugs. You can also check out NIDA's PEERx interactive ...
What to Do If Your Teen or Young Adult Has a Problem with Drugs
... The NIDA website also has information on specific drugs, including their effects on the body, brain, and behavior . NIDA also has an Easy-to-Read website with information about many drugs. In addition, you can suggest your teen review ...
What to Do If Your Adult Friend or Loved One Has a Problem with Drugs
... main NIDA site also has information on specific drugs, including their effects on the body, brain, and behavior . NIDA also has an Easy-to-Read website with information about many drugs. If my friend does go into treatment, how ...
Khani-Jazani, Reza; Molavi-Taleghani, Yasamin; Seyedin, Hesam; Vafaee-Najar, Ali; Ebrahimipour, Hossein; Pourtaleb, Arefeh
2015-01-01
Evaluation and improvement of drug management process are essential for patient safety. The present study was performed whit the aim of assessing risk of drug management process in Women Surgery Department of QEH using HFMEA method in 2013. A mixed method was used to analyze failure modes and their effects with HFMEA. To classify failure modes; nursing errors in clinical management model, for classifying factors affecting error; approved model by the UK National Health System, and for determining solutions for improvement; Theory of Inventive Problem Solving, were used. 48 failure modes were identified for 14 sub-process of five steps drug management process. The frequency of failure modes were as follow :35.3% in supplying step, 20.75% in prescription step, 10.4% in preparing step, 22.9% in distribution step and 10.35% in follow up and monitoring step. Seventeen failure modes (35.14%) were considered as non-acceptable risk (hazard score≥ 8) and were transferred to decision tree. Among 51 Influencing factors, the most common reasons for error were related to environmental factors (21.5%), and the less common reasons for error were related to patient factors (4.3%). HFMEA is a useful tool to evaluating, prioritization and analyzing failure modes in drug management process. Revision drug management process based focus-PDCA, assessing adverse drug reactions (ADR), USE patient identification bracelet, holding periodical pharmaceutical conferences to improve personnel knowledge, patient contribution in drug therapy; are performance solutions which were placed in work order.
ERIC Educational Resources Information Center
Fernandez-Montalvo, Javier; Lopez-Goni, Jose J.; Arteaga, Alfonso
2012-01-01
This study explored the prevalence of violent behaviors in patients who are addicted to drugs. A sample of 252 addicted patients (203 male and 49 female) who sought outpatient treatment was assessed. Information on violent behaviors, sociodemographic factors, consumption factors (assessed by the European version of the Addiction Severity Index…
Shibata, Yoshihiro; Takahashi, Hiroyuki; Chiba, Masato; Ishii, Yasuyuki
2008-01-01
A novel method for the prediction of drug-drug interaction has been established based on the in vitro metabolic stability in the "serum incubation method" using cryopreserved human hepatocytes suspended in 100% human serum. As a novel approach, the inhibitory effect of inhibitors on the metabolism of substrates during the first-pass elimination process in the liver (hepatic availability) and in the elimination process from the systemic circulation (hepatic clearance) were separately predicted with the anticipated inhibitor/substrate concentrations during absorption and in the systemic circulation, respectively. Ketoconazole strongly inhibited CYP3A4-mediated terfenadine metabolism in vitro, and the method predicted 6- to 37-fold increase of terfenadine AUC by the concomitant dosing of ketoconazole, which reasonably well agreed with the observed 13- to 59-fold increase of AUC in clinical studies. The CYP3A4-mediated metabolism of indinavir was also subject to the inhibition by ketoconazole in vitro at the lower indinavir concentration (2 microM), whereas no substantial inhibition was observed at 12 microM due to the saturation of indinavir metabolism. Predicted no interaction between ketoconazole and indinavir was consistent with the minimal increase (1.3-fold increase) of indinavir AUC by ketoconazole observed in clinical study. In addition, the method was applied to the CYP2D6-mediated desipramine-quinidine interaction: the predicted 6.4-fold increase of desipramine AUC by quinidine was consistent with the observed 6.7-fold increase of AUC in the clinical drug-drug interaction study. On the other hand, desipramine metabolism was little affected by ketoconazole in vitro, and consequently, it predicted no drug-drug interaction between desipramine and ketoconazole in humans, which agreed with the negligible interaction observed in clinical study. The accuracy of predictions for drug-drug interaction by the serum incubation method was evaluated by comparing the
Solving Fuzzy Optimization Problem Using Hybrid Ls-Sa Method
NASA Astrophysics Data System (ADS)
Vasant, Pandian
2011-06-01
Fuzzy optimization problem has been one of the most and prominent topics inside the broad area of computational intelligent. It's especially relevant in the filed of fuzzy non-linear programming. It's application as well as practical realization can been seen in all the real world problems. In this paper a large scale non-linear fuzzy programming problem has been solved by hybrid optimization techniques of Line Search (LS), Simulated Annealing (SA) and Pattern Search (PS). As industrial production planning problem with cubic objective function, 8 decision variables and 29 constraints has been solved successfully using LS-SA-PS hybrid optimization techniques. The computational results for the objective function respect to vagueness factor and level of satisfaction has been provided in the form of 2D and 3D plots. The outcome is very promising and strongly suggests that the hybrid LS-SA-PS algorithm is very efficient and productive in solving the large scale non-linear fuzzy programming problem.
Managing Mental Health Problems in Everyday Life: Drug Treatment Client's Self-Care Strategies
ERIC Educational Resources Information Center
Holt, Martin; Treloar, Carla
2008-01-01
Little is understood about the self-care activities undertaken by drug treatment clients. Using data from a qualitative study of drug treatment and mental health we identify the self-care practices of drug treatment clients diagnosed with anxiety and depression. Seventy-seven participants were interviewed in four sites across Australia.…
The CG-BFGS method for unconstrained optimization problems
NASA Astrophysics Data System (ADS)
Ibrahim, Mohd Asrul Hery Bin; Mamat, Mustafa; June, Leong Wah; Sofi, Azfi Zaidi Mohammad
2014-07-01
In this paper we present a new search direction known as the CG-BFGS method, which uses the search direction of the conjugate gradient method approach in the quasi-Newton methods. The new algorithm is compared with the quasi-Newton methods in terms of the number of iterations and CPU-time. The Broyden-Fletcher-Goldfarb-Shanno (BFGS) method is used as an updating formula for the approximation of the Hessian for both methods. Our numerical analysis provides strong evidence that our CG-BFGS method is more efficient than the ordinary BFGS method. Besides, we also prove that the new algorithm is globally convergent.
A locally implicit method for fluid flow problems
NASA Technical Reports Server (NTRS)
Reddy, K. C.
1986-01-01
The fluid flow inside the space shuttle main engine (SSME) traverses through a complex geometrical configuration. The flow is compressible, viscous, and turbulent with pockets of separated regions. Several computer codes are being developed to solve three dimensional Navier-Stokes equations with different turbulence models for analyzing the SSME internal flow. The locally implicit scheme is a computationally efficient scheme which converges rapidly in multi-grid modes for elliptic problems. It has the promise of providing a rapidly converging algorithm for steady-state viscous flow problems.
Iterative method for elliptic problems on regions partitioned into substructures
Bramble, J.H.; Pasciak, J.E.; Schatz, A.H.
1986-04-01
Some new preconditioners for discretizations of elliptic boundary problems are studied. With these preconditioners, the domain under consideration is broken into subdomains and preconditioners are defined which only require the solution of matrix problems on the subdomains. Analytic estimates are given which guarantee that under appropriate hypotheses, the preconditioned iterative procedure converges to the solution of the discrete equations with a rate per iteration that is independent of the number of unknowns. Numerical examples are presented which illustrate the theoretically predicted iterative convergence rates.
Globally Convergent Numerical Methods for Coefficient Inverse Problems
2008-09-23
Analysis, 39, 1863-1889, 2008. 11. M.V. Klibanov and S.E. Pamyatnykh, Lipschitz stability of a non-standard problem for the non-stationary transport...classical one. We first formulate a Lipschitz stability estimate for this problem, which is Theorem 8.1. This theorem is proven via a Carleman estimate...cmin, cmax) such that the following Lipschitz stability estimate holds ‖v‖H1(QT ) ≤ C [ ‖Lv‖L2(QT ) + ‖v |ST ‖H1(ST ) + ‖v |ST ‖L2(ST ) ] ,∀v ∈ H2 (QT
Grave, K; Horsberg, T E; Lunestad, B T; Litleskare, I
2004-08-09
Sea lice are a major problem in Norwegian fish farms; however, data on drug treatment patterns or treatment rates of sea lice infestations are not available. Such data are important for analysing resistance patterns against drugs used for such infestations. The main objective of the present study was to develop a method to estimate the treatment patterns and treatment rates for drugs used in the treatment against sea lice (Lepeophtheirus salmonis and Caligus elongatus) in farm salmonids by means of national sales statistics. Annual sales figures, as weight of active substances, were obtained from the drug wholesalers and the feed mills. The weight of active drug substances is not useful as a unit of measurement of drug use in an epidemiological context because it does not correct for dosage differences and number of repeat treatments. To correct for these factors, we introduced approved daily dose (ADD(farm fish)) and treatment course-doses(farm fish) kg(-1) live-weight fish. To express the drug treatment patterns, the biomass (in weight) of farm salmonids treated with 1 course of a drug were estimated. When measured as kg active substance, the quantities of drugs for the treatment of sea lice infestations declined by 98% during the study period (1989 to 2002) but this figure increased 5-fold when it was corrected for differences in dosage. To correct for amounts of farm salmonids liable to require treatment we estimated the annual treatment rate, defined as the number of treatments for sea lice infestations per biomass slaughtered Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss. The annual treatment rate increased gradually during the study period; however, it varied considerably (range 0.45 to 1.34, mean 0.90). Before 1995, organophosphates were the most frequently used drugs against sea lice; since then pyrethroids have become the dominating drug group.
Miyamoto, Yuki; Kawakami, Norito; Matsumoto, Toshihiko
2016-01-01
Background Although drug abuse has been a serious public health concern, there have been problems with implementation of treatment for drug users in Japan because of poor accessibility to treatment, concerns about stigma and confidentiality, and costs. Therapeutic interventions using the Internet and computer technologies could improve this situation and provide more feasible and acceptable approaches. Objective The objective of the study was to show how we developed a pilot version of a new Web-based cognitive behavioral relapse prevention program with tailored feedback to assist people with drug problems and assessed its acceptance and usability. Methods We developed the pilot program based on existing face-to-face relapse prevention approaches using an open source Web application to build an e-learning website, including relapse prevention sessions with videos, exercises, a diary function, and self-monitoring. When users submitted exercise answers and their diary, researchers provided them with personalized feedback comments using motivational interviewing skills. People diagnosed with drug dependence were recruited in this pilot study from a psychiatric outpatient ward and nonprofit rehabilitation facilities and usability was evaluated using Internet questionnaires. Overall, website usability was assessed by the Web Usability Scale. The adequacy of procedures in the program, ease of use, helpfulness of content, and adverse effects, for example, drug craving, mental distress, were assessed by original structured questionnaires and descriptive form questions. Results In total, 10 people participated in the study and completed the baseline assessment, 60% completed all relapse prevention sessions within the expected period. The time needed to complete one session was about 60 minutes and most of the participants took 2 days to complete the session. Overall website usability was good, with reasonable scores on subscales of the Web Usability Scale. The participants
Hathaway, A D; Callaghan, R C; Macdonald, S; Erickson, P G
2009-01-01
Few studies have focused on cannabis dependence as compared to other drugs more commonly acknowledged as presenting a substantial need for treatment. This paper presents findings from a 2004-2005 study of drug user treatment clients in Southern Ontario, Canada. Clients with cannabis (n = 128) or cocaine (n = 300) as their primary drug problem were compared on psychosocial and demographic characteristics, drug effects, and clinical impairment. There are more similarities than differences between groups, with DAST and DSM scores showing high rates of "dependence" and reported symptoms of "abuse." However, cannabis consistently scored lower on these items, supporting the idea of a continuum of risk on which its rank compared with other potentially misused drugs holds across a wide range of symptoms of impairment. The less disruptive nature of cannabis use-related problems poses greater challenges for drug user treatment providers guided by strict abstinence agendas. The authors call for the expansion of harm reduction treatment options and educational initiatives beyond primary prevention that acknowledge benefits of moderate controlled use when addressing cannabis misuse.
The Needs of Pregnant and Parenting American Indian Women at Risk for Problem Alcohol or Drug Use.
ERIC Educational Resources Information Center
Zahnd, Elaine; Klein, Dorie
1997-01-01
A survey of 171 American Indian women in California who were pregnant or parenting and were considered at risk for problem substance abuse covered demographic information; personal and family history; alcohol, tobacco, and drug use; HIV risk; and a needs assessment regarding health care, economic needs, and parenting and children's needs. (LP)
ERIC Educational Resources Information Center
Asadullin, Azat R.; Galeeva, Elena Kh.; Achmetova, Elvina A.; Nikolaev, Ivan V.
2016-01-01
The urgency of this study has become vivid in the light of the growing problem of prevalence and use of new synthetic drug types. Lately there has been a tendency of expanding the range of psychologically active substances (PAS) used by addicts with the purpose of their illegal taking. The aim of this research is an attempt of systematizing and…
ERIC Educational Resources Information Center
Baumgartner, R. Paul, Jr.
1979-01-01
Barriers to role expansion for pharmacists working in institutional settings are discussed, such as competency, interdisciplinary responsibilities, and financial reimbursement. Underlying principles that may be applied to overcome the traditional barriers to pharmacist intervention in drug use problems are examined. (SF)
Abdolmaleki, Azizeh; Ghasemi, Jahan B; Ghasemi, Fatemeh
2017-01-01
Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a preferred bioactivity outline and alternative bioactive molecules at an early stage. A number of in silico methods have been explored extensively in order to facilitate the investigation of individual target agents and to propose a selective drug. A different, progressively more significant field which is used to predict the bioactivity of chemical compounds is the data mining method. Some of the previously mentioned methods have been investigated for multi-target drug design (MTDD) to find drug leads interact simultaneously with multiple targets. Several cheminformatics methods and structure-based approaches try to extract information from units working cooperatively in a biomolecular system to fulfill their task. To dominate the difficulties of the experimental specification of ligand-target structures, rational methods, namely molecular docking, SAR and QSAR are vital substitutes to obtain knowledge for each structure in atomic insight. These procedures are logically successful for the prediction of binding affinity and have shown promising potential in facilitating MTDD. Here, we review some of the important features of the multi-target therapeutics discoveries using the computational approach, highlighting the SAR, QSAR, docking and pharmacophore methods to discover interactions between drug-target that could be leveraged for curative benefits. A summary of each, followed by examples of its applications in drug design has been provided. Computational efficiency of each method has been represented according to its main strengths and limitations.
Tracing Success: Graphical Methods for Analysing Successful Collaborative Problem Solving
ERIC Educational Resources Information Center
Joiner, Richard; Issroff, Kim
2003-01-01
The aim of this paper is to evaluate the use of trace diagrams for analysing collaborative problem solving. The paper describes a study where trace diagrams were used to analyse joint navigation in a virtual environment. Ten pairs of undergraduates worked together on a distributed virtual task to collect five flowers using two bees with each…
Fast marching methods for the continuous traveling salesman problem
Andrews, June; Sethian, J. A.
2007-01-01
We consider a problem in which we are given a domain, a cost function which depends on position at each point in the domain, and a subset of points (“cities”) in the domain. The goal is to determine the cheapest closed path that visits each city in the domain once. This can be thought of as a version of the traveling salesman problem, in which an underlying known metric determines the cost of moving through each point of the domain, but in which the actual shortest path between cities is unknown at the outset. We describe algorithms for both a heuristic and an optimal solution to this problem. The complexity of the heuristic algorithm is at worst case M·N log N, where M is the number of cities, and N the size of the computational mesh used to approximate the solutions to the shortest paths problems. The average runtime of the heuristic algorithm is linear in the number of cities and O(N log N) in the size N of the mesh. PMID:17220271
Fast marching methods for the continuous traveling salesman problem
Andrews, J.; Sethian, J.A.
2008-12-01
We consider a problem in which we are given a domain, a cost function which depends on position at each point in the domain, and a subset of points ('cities') in the domain. The goal is to determine the cheapest closed path that visits each city in the domain once. This can be thought of as a version of the Traveling Salesman Problem, in which an underlying known metric determines the cost of moving through each point of the domain, but in which the actual shortest path between cities is unknown at the outset. We describe algorithms for both a heuristic and an optimal solution to this problem. The order of the heuristic algorithm is at worst case M * N logN, where M is the number of cities, and N the size of the computational mesh used to approximate the solutions to the shortest paths problems. The average runtime of the heuristic algorithm is linear in the number of cities and O(N log N) in the size N of the mesh.
A multidomain spectral collocation method for the Stokes problem
NASA Technical Reports Server (NTRS)
Landriani, G. Sacchi; Vandeven, H.
1989-01-01
A multidomain spectral collocation scheme is proposed for the approximation of the two-dimensional Stokes problem. It is shown that the discrete velocity vector field is exactly divergence-free and we prove error estimates both for the velocity and the pressure.
Observed Methods for Generating Analogies in Scientific Problem Solving. Revised.
ERIC Educational Resources Information Center
Clement, John
Evidence from video tapes of experts thinking aloud and using analogies in scientific problem solving is presented. Four processes appear to be important in using an analogy: (1) generating the analogy; (2) establishing confidence in the validity of the analogy relation; (3) understanding the analogous case; and (4) applying findings to the…
A New Large-Scale Global Optimization Method and Its Application to Lennard-Jones Problems
1992-11-01
stochastic methods. Computational results on Lennard - Jones problems show that the new method is considerably more successful than any other method that...our method does not find as good a solution as has been found by the best special purpose methods for Lennard - Jones problems. This illustrates the inherent difficulty of large scale global optimization.
Party package travel: alcohol use and related problems in a holiday resort: a mixed methods study
Hesse, Morten; Tutenges, Sébastien; Schliewe, Sanna; Reinholdt, Tine
2008-01-01
Background People travelling abroad tend to increase their use of alcohol and other drugs. In the present study we describe organized party activities in connection with young tourists' drinking, and the differences between young people travelling with and without organized party activities. Methods We conducted ethnographic observations and a cross-sectional survey in Sunny Beach, Bulgaria. Results The behaviour of the guides from two travel agencies strongly promoted heavy drinking, but discouraged illicit drug use. Even after controlling for several potential confounders, young people who travelled with such "party package travel agencies" were more likely to drink 12 or more units when going out. In univariate analyses, they were also more likely to get into fights, but were not more likely to seek medical assistance or medical assistance for an accident or an alcohol-related problem. After controlling for confounders, the association between type of travel agency and getting into fights was no longer significant. Short-term consequences of drinking in the holiday resort did not differ between party package travellers and ordinary package travellers. Conclusion There may be a small impact of party package travels on young people's drinking. Strategies could be developed used to minimise the harm associated with both party package travel and other kinds of travel where heavy substance use is likely to occur. PMID:18840273
Method of approximation of the weak solution of elasticity problems
NASA Astrophysics Data System (ADS)
Anoufriev, Igor E.; Petukhov, Leonid V.
1999-05-01
Let tT be a bounded 3D domain with Lipschitz boundary (Gamma) , (sigma) equals (pi) R 2 is a prescribed displacement on (Gamma) (volume forces are absent). We denote by A(u,v) equals integral(Omega ) L(epsilon) (u) (DOT) (epsilon) (v) dx bilinear form corresponding to the first elasticity problem where L is a tensor of Hooke's law written in the tensor form (sigma) equals L(epsilon) (isotropic case will be the subject of consideration) and by V a subspace of Sobolev space W21((Omega) ,R3) that is V equals {v equalsV W21((Omega) ,R3) v equals 0 on (Gamma) }. We assume that gi equalsV W21/2((Gamma) ) and A(u,v) is V-elliptic bilinear form. A weak solution of the first elasticity problem is a vector- valued function.
Solution of elastoplastic torsion problem by boundary integral method
NASA Technical Reports Server (NTRS)
Mendelson, A.
1975-01-01
The boundary integral method was applied to the elastoplastic analysis of the torsion of prismatic bars, and the results are compared with those obtained by the finite difference method. Although fewer unknowns were used, very good accuracy was obtained with the boundary integral method. Both simply and multiply connected bodies can be handled with equal ease.
Mixed Methods Research: The "Thing-ness" Problem.
Hesse-Biber, Sharlene
2015-06-01
Contemporary mixed methods research (MMR) veers away from a "loosely bounded" to a "bounded" concept that has important negative implications for how qualitatively driven mixed methods approaches are positioned in the field of mixed methods and overall innovation in the praxis of MMR. I deploy the concept of reification defined as taking an object/abstraction and treating it as if it were real such that it takes on the quality of "thing-ness," having a concrete independent existence. I argue that the contemporary reification of mixed methods as a "thing" is fueled by three interrelated factors: (a) the growing formalization of mixed methods as design, (b) the unexamined belief in the "synergy" of mixed methods and, (c) the deployment of a "practical pragmatism" as the "philosophical partner" for mixed methods inquiry.
Bhardwaj, M.; Day, D.; Farhat, C.; Lesoinne, M; Pierson, K.; Rixen, D.
1999-04-01
We report on the application of the one-level FETI method to the solution of a class of substructural problems associated with the Department of Energy's Accelerated Strategic Computing Initiative (ASCI). We focus on numerical and parallel scalability issues, and on preliminary performance results obtained on the ASCI Option Red supercomputer configured with as many as one thousand processors, for problems with as many as 5 million degrees of freedom.
Two-Point Boundary Value Problems and the Method of Adjoints.
ERIC Educational Resources Information Center
Fay, Temple H.; Miller, H. Vincent
1990-01-01
Discusses a numerical technique called the method of adjoints, turning a linear two-point boundary value problem into an initial value problem. Described are steps for using the method in linear or nonlinear systems. Applies the technique to solve a simple pendulum problem. Lists 15 references. (YP)
Projected implicit Runge-Kutta methods for differential-algebraic boundary value problems
Ascher, U. ); Petzoid, L. )
1990-09-01
Differential-algebraic boundary value problems arise in the modelling of singular optimal control problems and in parameter estimation for singular systems. A new class of numerical methods for these problems is introduced, and shown to overcome difficulties with previously defined numerical methods. 4 refs., 1 tab.
A Network Centrality Method for the Rating Problem
2015-01-01
We propose a new method for aggregating the information of multiple users rating multiple items. Our approach is based on the network relations induced between items by the rating activity of the users. Our method correlates better than the simple average with respect to the original rankings of the users, and besides, it is computationally more efficient than other methods proposed in the literature. Moreover, our method is able to discount the information that would be obtained adding to the system additional users with a systematically biased rating activity. PMID:25830502
Arriving at a Method To Determine Phases in Family Problem Solving.
ERIC Educational Resources Information Center
Kieren, Dianne K.; Hurlbut, Nancy L.
This study focused on the problem-solving of family groups including an adolescent diabetic. The study sought to: compare three methods used to identify and analyze phases in family problem-solving interactions, establish criteria to evaluate the methods, utilize the criteria to evaluate the three methods, and select a method. The three methods…
A Solution Method for Large Deformation Contact Problems.
1984-10-01
number) Contact Problem Algorithm Implicit Solution Technique 20. ANSTNACT’ (rntftae r eves aIi N yaeemy mrd identify by block numnber) P. solution...WITHOUT oL0 H! 0-CONTACT ALGORITHM Z w 00 0 ev 0.8- w kL 0.0 0 U< O0.26 U)_ * z Z OBTINE 0H53 56 59 ANGE,4 Ficure~~~~~ ~*A G RI H 17 Peitdtatoso iesi itrae...41, Division of Applied Sciences, Harvard Univ., March 1983. [20] Rabinowicz , E., Friction and Wear of Materials, J. Wiley and Sons, 1965. [21
[Characterization of drug, narcotic and psychotropic drug chirality by statistical methods].
Noszál, B; Schiller, Z
1999-04-01
The percentage of chiral entities among drug, narcotic drug and psychotropic compounds is steadily increasing. Receptors of the human body recognize the enantiomeric forms of constitutionally identical compounds as entirely different chemical agents. Based upon these facts, this paper reports the percentage of chiral compounds in the various pharmacological classes, and related data. Pertinent terms, such as eutomer, distomer, eudismic index, eudismic affinity quotient are defined. Differences in biological activity between eutomers and distomers are exemplified. The pharmacological classes and subclasses of highest chirality, and the "most chiral" active principles are shown. Some puzzling observations on pharmacological behaviour of stereoisomers are highlighted. The necessity of "racemate switch" in the pharmaceutical industry, and the significance of stereo-specific interactions between the drug, narcotic drug and psychotropic ligands, and complementary, "pocket" moieties of the human body are emphasized. Some features of enantiopharmacology, a fledgling science in the interface of stereochemistry and traditional pharmacology are introduced. The statistical treatment of asymmetric compounds in pharmacological classes and subclasses shows that presently, the percentage of chirality in drug categories is more characteristic of the origin of the compound than its target molecule.
Mixing Interview and Questionnaire Methods: Practical Problems in Aligning Data
ERIC Educational Resources Information Center
Harris, Lois R.; Brown, Gavin T. L.
2010-01-01
Structured questionnaires and semi-structured interviews are often used in mixed method studies to generate confirmatory results despite differences in methods of data collection, analysis, and interpretation. A review of 19 questionnaire-interview comparison studies found that consensus and consistency statistics were generally weak between…
An Efficient Optimization Method for Solving Unsupervised Data Classification Problems
Shabanzadeh, Parvaneh; Yusof, Rubiyah
2015-01-01
Unsupervised data classification (or clustering) analysis is one of the most useful tools and a descriptive task in data mining that seeks to classify homogeneous groups of objects based on similarity and is used in many medical disciplines and various applications. In general, there is no single algorithm that is suitable for all types of data, conditions, and applications. Each algorithm has its own advantages, limitations, and deficiencies. Hence, research for novel and effective approaches for unsupervised data classification is still active. In this paper a heuristic algorithm, Biogeography-Based Optimization (BBO) algorithm, was adapted for data clustering problems by modifying the main operators of BBO algorithm, which is inspired from the natural biogeography distribution of different species. Similar to other population-based algorithms, BBO algorithm starts with an initial population of candidate solutions to an optimization problem and an objective function that is calculated for them. To evaluate the performance of the proposed algorithm assessment was carried on six medical and real life datasets and was compared with eight well known and recent unsupervised data classification algorithms. Numerical results demonstrate that the proposed evolutionary optimization algorithm is efficient for unsupervised data classification. PMID:26336509
An Efficient Optimization Method for Solving Unsupervised Data Classification Problems.
Shabanzadeh, Parvaneh; Yusof, Rubiyah
2015-01-01
Unsupervised data classification (or clustering) analysis is one of the most useful tools and a descriptive task in data mining that seeks to classify homogeneous groups of objects based on similarity and is used in many medical disciplines and various applications. In general, there is no single algorithm that is suitable for all types of data, conditions, and applications. Each algorithm has its own advantages, limitations, and deficiencies. Hence, research for novel and effective approaches for unsupervised data classification is still active. In this paper a heuristic algorithm, Biogeography-Based Optimization (BBO) algorithm, was adapted for data clustering problems by modifying the main operators of BBO algorithm, which is inspired from the natural biogeography distribution of different species. Similar to other population-based algorithms, BBO algorithm starts with an initial population of candidate solutions to an optimization problem and an objective function that is calculated for them. To evaluate the performance of the proposed algorithm assessment was carried on six medical and real life datasets and was compared with eight well known and recent unsupervised data classification algorithms. Numerical results demonstrate that the proposed evolutionary optimization algorithm is efficient for unsupervised data classification.
Overview: Applications of numerical optimization methods to helicopter design problems
NASA Technical Reports Server (NTRS)
Miura, H.
1984-01-01
There are a number of helicopter design problems that are well suited to applications of numerical design optimization techniques. Adequate implementation of this technology will provide high pay-offs. There are a number of numerical optimization programs available, and there are many excellent response/performance analysis programs developed or being developed. But integration of these programs in a form that is usable in the design phase should be recognized as important. It is also necessary to attract the attention of engineers engaged in the development of analysis capabilities and to make them aware that analysis capabilities are much more powerful if integrated into design oriented codes. Frequently, the shortcoming of analysis capabilities are revealed by coupling them with an optimization code. Most of the published work has addressed problems in preliminary system design, rotor system/blade design or airframe design. Very few published results were found in acoustics, aerodynamics and control system design. Currently major efforts are focused on vibration reduction, and aerodynamics/acoustics applications appear to be growing fast. The development of a computer program system to integrate the multiple disciplines required in helicopter design with numerical optimization technique is needed. Activities in Britain, Germany and Poland are identified, but no published results from France, Italy, the USSR or Japan were found.
Public Service Advertising and Social Problems: the Case of Drug Abuse Prevention.
ERIC Educational Resources Information Center
McEwen, William J.; Hanneman, Gerhard J.
This paper explores certain findings of a DAIR (Drug Abuse Information Research) project undertaken at the University of Connecticut which is investigating the dissemination and impact of drug abuse information. Specifically, findings regarding audience response to persuasive antidrug abuse messages on television are discussed. On the basis of the…
Drug-facilitated robbery or sexual assault: problems associated with amnesia.
Goullé, Jean-Pierre; Anger, Jean-Pierre
2004-04-01
Amnesia following sedative-hypnotic drug exposure is discussed. Anterograde amnesia clearly occurs with many benzodiazepines. Several drugs are assessed: benzodiazepines and two hypnotics in particular that are structurally unrelated to the benzodiazepines but share some of their properties: zolpidem and zopiclone. The amnesic effects of these drugs are described, memory process, biology of memory, and memory process impairment documented. With these drugs anterograde amnesia has been demonstrated to be dose dependent. This effect is associated with hypnotic drugs, however, the receptors are different. As regards forensic medicine, a significant and specific type of amnesia should be considered: amnesia automatism or amnesic complex automatism. Also, several cases observed in our laboratory are presented to demonstrate the impact of amnesia.
Numerical Method and Analysis of Consistency for Electrodiffusion Problem
NASA Astrophysics Data System (ADS)
Filipek, R.; Szyszkiewicz, K.; Danielewski, M.; Lewenstam, A.
2007-12-01
Numerical procedure based on method of lines for time-dependent electrodiffusion transport is developed. Finite difference space discretization with suitably selected weights based on a non-uniform grid is applied. Consistency of this method and the method put forward by Brumleve and Buck are analyzed and compared. The resulting stiff system of ODEs is effectively solved using the Radau IIa integrator. The applications to selected electrochemical systems: liquid junction, bi-ionic case and fused salts have been tested. Results for ion-selective electrodes are demonstrated.
Affinity-based methods in drug-target discovery.
Rylova, Gabriela; Ozdian, Tomas; Varanasi, Lakshman; Soural, Miroslav; Hlavac, Jan; Holub, Dusan; Dzubak, Petr; Hajduch, Marian
2015-01-01
Target discovery using the molecular approach, as opposed to the more traditional systems approach requires the study of the cellular or biological process underlying a condition or disease. The approaches that are employed by the "bench" scientist may be genetic, genomic or proteomic and each has its rightful place in the drug-target discovery process. Affinity-based proteomic techniques currently used in drug-discovery draw upon several disciplines, synthetic chemistry, cell-biology, biochemistry and mass spectrometry. An important component of such techniques is the probe that is specifically designed to pick out a protein or set of proteins from amongst the varied thousands in a cell lysate. A second component, that is just as important, is liquid-chromatography tandem massspectrometry (LC-MS/MS). LC-MS/MS and the supporting theoretical framework has come of age and is the tool of choice for protein identification and quantification. These proteomic tools are critical to maintaining the drug-candidate supply, in the larger context of drug discovery.
A Prospective Method to Guide Small Molecule Drug Design
ERIC Educational Resources Information Center
Johnson, Alan T.
2015-01-01
At present, small molecule drug design follows a retrospective path when considering what analogs are to be made around a current hit or lead molecule with the focus often on identifying a compound with higher intrinsic potency. What this approach overlooks is the simultaneous need to also improve the physicochemical (PC) and pharmacokinetic (PK)…
The intelligence of dual simplex method to solve linear fractional fuzzy transportation problem.
Narayanamoorthy, S; Kalyani, S
2015-01-01
An approach is presented to solve a fuzzy transportation problem with linear fractional fuzzy objective function. In this proposed approach the fractional fuzzy transportation problem is decomposed into two linear fuzzy transportation problems. The optimal solution of the two linear fuzzy transportations is solved by dual simplex method and the optimal solution of the fractional fuzzy transportation problem is obtained. The proposed method is explained in detail with an example.
The Intelligence of Dual Simplex Method to Solve Linear Fractional Fuzzy Transportation Problem
Narayanamoorthy, S.; Kalyani, S.
2015-01-01
An approach is presented to solve a fuzzy transportation problem with linear fractional fuzzy objective function. In this proposed approach the fractional fuzzy transportation problem is decomposed into two linear fuzzy transportation problems. The optimal solution of the two linear fuzzy transportations is solved by dual simplex method and the optimal solution of the fractional fuzzy transportation problem is obtained. The proposed method is explained in detail with an example. PMID:25810713
A numerical method for eigenvalue problems in modeling liquid crystals
Baglama, J.; Farrell, P.A.; Reichel, L.; Ruttan, A.; Calvetti, D.
1996-12-31
Equilibrium configurations of liquid crystals in finite containments are minimizers of the thermodynamic free energy of the system. It is important to be able to track the equilibrium configurations as the temperature of the liquid crystals decreases. The path of the minimal energy configuration at bifurcation points can be computed from the null space of a large sparse symmetric matrix. We describe a new variant of the implicitly restarted Lanczos method that is well suited for the computation of extreme eigenvalues of a large sparse symmetric matrix, and we use this method to determine the desired null space. Our implicitly restarted Lanczos method determines adoptively a polynomial filter by using Leja shifts, and does not require factorization of the matrix. The storage requirement of the method is small, and this makes it attractive to use for the present application.
Method of using thixotropic cements for combating gas migration problems
Sabins, F.; Childs, J. P.
1985-06-25
A thixotropic cement composition comprising water, hydraulic cement, a titanium chelate and a crosslinkable agent and methods of using same to combat migration of formation fluids in oil, gas and water wells are provided.
A new interior point method for the variational inequality problem
Iusem, A.; Burachik, R.
1994-12-31
We present an algorithm for the variational inequality problem on convex sets with nonempty interior. The use of Bregman functions whose zone is the convex set allows for the generation of a sequence contained in the interior, without taking explicitly into account the constraints which define the convex set. We establish full convergence to a solution with minimal conditions upon the monotone operator F, weaker than strong monotonicity or Lipschitz continuity, for instance, and including cases where the solution needs not be unique. We apply our algorithm to several relevant classes of convex sets, including orthants, boxes, polyhedra and balls, for which Bregman functions are presented which give raise to explicit iteration formulae, up to the determination of two scalar stepsizes, which can be found through finite search procedures.
The Short Inventory of Problems-Modified for Drug Use (SIP-DU): validity in a primary care sample.
Allensworth-Davies, Donald; Cheng, Debbie M; Smith, Peter C; Samet, Jeffrey H; Saitz, Richard
2012-01-01
Primary care physicians can help drug-dependent patients mitigate adverse drug use consequences; instruments validated in primary care to measure these consequences would aid in this effort. This study evaluated the validity of the Short Inventory of Problems-Alcohol and Drugs modified for Drug Use (SIP-DU) among subjects recruited from a primary care clinic (n= 106). SIP-DU internal consistency was evaluated using Cronbach's alphas, convergent validity by correlating the total SIP-DU score with the DAST-10, and construct validity by analyzing the factor structure. The SIP-DU demonstrated high internal consistency (Cronbach's alpha for overall scale .95, subscales .72-.90) comparable with other SIP versions and correlated well with the DAST-10 (r= .70). Confirmatory factor analysis suggested an unacceptable fit of previously proposed factors; exploratory factor analyses suggested a single factor of drug use consequences. The SIP-DU offers primary care clinicians a valid and practical assessment tool for drug use consequences.
Drug name recognition in biomedical texts: a machine-learning-based method.
He, Linna; Yang, Zhihao; Lin, Hongfei; Li, Yanpeng
2014-05-01
Currently, there is an urgent need to develop a technology for extracting drug information automatically from biomedical texts, and drug name recognition is an essential prerequisite for extracting drug information. This article presents a machine-learning-based approach to recognize drug names in biomedical texts. In this approach, a drug name dictionary is first constructed with the external resource of DrugBank and PubMed. Then a semi-supervised learning method, feature coupling generalization, is used to filter this dictionary. Finally, the dictionary look-up and the condition random field method are combined to recognize drug names. Experimental results show that our approach achieves an F-score of 92.54% on the test set of DDIExtraction2011.
Spectral methods and their implementation to solution of aerodynamic and fluid mechanic problems
NASA Technical Reports Server (NTRS)
Streett, C. L.
1987-01-01
Fundamental concepts underlying spectral collocation methods, especially pertaining to their use in the solution of partial differential equations, are outlined. Theoretical accuracy results are reviewed and compared with results from test problems. A number of practical aspects of the construction and use of spectral methods are detailed, along with several solution schemes which have found utility in applications of spectral methods to practical problems. Results from a few of the successful applications of spectral methods to problems of aerodynamic and fluid mechanic interest are then outlined, followed by a discussion of the problem areas in spectral methods and the current research under way to overcome these difficulties.
NASA Astrophysics Data System (ADS)
Swaidan, Waleeda; Hussin, Amran
2015-10-01
Most direct methods solve finite time horizon optimal control problems with nonlinear programming solver. In this paper, we propose a numerical method for solving nonlinear optimal control problem with state and control inequality constraints. This method used quasilinearization technique and Haar wavelet operational matrix to convert the nonlinear optimal control problem into a quadratic programming problem. The linear inequality constraints for trajectories variables are converted to quadratic programming constraint by using Haar wavelet collocation method. The proposed method has been applied to solve Optimal Control of Multi-Item Inventory Model. The accuracy of the states, controls and cost can be improved by increasing the Haar wavelet resolution.
Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection
NASA Astrophysics Data System (ADS)
Bear, Joseph C.; Patrick, P. Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J.; Pankhurst, Quentin A.; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P.; Mayes, Andrew G.
2016-09-01
Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.
Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection
Bear, Joseph C.; Patrick, P. Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J.; Pankhurst, Quentin A.; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P.; Mayes, Andrew G.
2016-01-01
Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine. PMID:27671546
Iterative methods for stationary convection-dominated transport problems
Bova, S.W.; Carey, G.F.
1994-12-31
It is well known that many iterative methods fail when applied to nonlinear systems of convection-dominated transport equations. Most successful methods for obtaining steady-state solutions to such systems rely on time-stepping through an artificial transient, combined with careful construction of artificial dissipation operators. These operators provide control over spurious oscillations which pollute the steady state solutions, and, in the nonlinear case, may become amplified and lead to instability. In the present study, we investigate Taylor Galerkin and SUPG-type methods and compare results for steady-state solutions to the Euler equations of gas dynamics. In particular, we consider the efficiency of different iterative strategies and present results for representative two-dimensional calculations.
A multilevel multiscale mimetic method for an anisotropic infiltration problem
Lipnikov, Konstantin; Moulton, David; Svyatskiy, Daniil
2009-01-01
Modeling of multiphase flow and transport in highly heterogeneous porous media must capture a broad range of coupled spatial and temporal scales. Recently, a hierarchical approach dubbed the Multilevel Multiscale Mimetic (M3) method, was developed to simulate two-phase flow in porous media. The M{sup 3} method is locally mass conserving at all levels in its hierarchy, it supports unstructured polygonal grids and full tensor permeabilities, and it can achieve large coarsening factors. In this work we consider infiltration of water into a two-dimensional layered medium. The grid is aligned with the layers but not the coordinate axes. We demonstrate that with an efficient temporal updating strategy for the coarsening parameters, fine-scale accuracy of prominent features in the flow is maintained by the M{sup 3} method.
The workshop on iterative methods for large scale nonlinear problems
Walker, H.F.; Pernice, M.
1995-12-01
The aim of the workshop was to bring together researchers working on large scale applications with numerical specialists of various kinds. Applications that were addressed included reactive flows (combustion and other chemically reacting flows, tokamak modeling), porous media flows, cardiac modeling, chemical vapor deposition, image restoration, macromolecular modeling, and population dynamics. Numerical areas included Newton iterative (truncated Newton) methods, Krylov subspace methods, domain decomposition and other preconditioning methods, large scale optimization and optimal control, and parallel implementations and software. This report offers a brief summary of workshop activities and information about the participants. Interested readers are encouraged to look into an online proceedings available at http://www.usi.utah.edu/logan.proceedings. In this, the material offered here is augmented with hypertext abstracts that include links to locations such as speakers` home pages, PostScript copies of talks and papers, cross-references to related talks, and other information about topics addresses at the workshop.
Methods for measuring denitrification: Diverse approaches to a difficult problem
Groffman, Peter M; Altabet, Mary A.; Böhlke, J.K.; Butterbach-Bahl, Klaus; David, Mary B.; Firestone, Mary K.; Giblin, Anne E.; Kana, Todd M.; Nielsen , Lars Peter; Voytek, Mary A.
2006-01-01
Denitrification, the reduction of the nitrogen (N) oxides, nitrate (NO3−) and nitrite (NO2−), to the gases nitric oxide (NO), nitrous oxide (N2O), and dinitrogen (N2), is important to primary production, water quality, and the chemistry and physics of the atmosphere at ecosystem, landscape, regional, and global scales. Unfortunately, this process is very difficult to measure, and existing methods are problematic for different reasons in different places at different times. In this paper, we review the major approaches that have been taken to measure denitrification in terrestrial and aquatic environments and discuss the strengths, weaknesses, and future prospects for the different methods. Methodological approaches covered include (1) acetylene-based methods, (2) 15N tracers, (3) direct N2 quantification, (4) N2:Ar ratio quantification, (5) mass balance approaches, (6) stoichiometric approaches, (7) methods based on stable isotopes, (8) in situ gradients with atmospheric environmental tracers, and (9) molecular approaches. Our review makes it clear that the prospects for improved quantification of denitrification vary greatly in different environments and at different scales. While current methodology allows for the production of accurate estimates of denitrification at scales relevant to water and air quality and ecosystem fertility questions in some systems (e.g., aquatic sediments, well-defined aquifers), methodology for other systems, especially upland terrestrial areas, still needs development. Comparison of mass balance and stoichiometric approaches that constrain estimates of denitrification at large scales with point measurements (made using multiple methods), in multiple systems, is likely to propel more improvement in denitrification methods over the next few years.
Prescription drug abuse as a public health problem in Ohio: a case report.
Winstanley, Erin L; Gay, Joe; Roberts, Lisa; Moseley, Judi; Hall, Orman; Beeghly, B Christine; Winhusen, Theresa; Somoza, Eugene
2012-11-01
Prescription drug overdose is the leading cause of injury death in Ohio, as well as in 16 other states. Responding to the prescription drug epidemic is particularly challenging given the fragmentation of the health care system and that the consequences of addiction span across systems that have not historically collaborated. This case study reports on how Ohio is responding to the prescription drug epidemic by developing cross-system collaboration from local public health nurses to the Governor's office. In summary, legal and regulatory policies can be implemented relatively quickly whereas changing the substance abuse treatment infrastructure requires significant financial investments.
Technology Transfer Automated Retrieval System (TEKTRAN)
The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C inf...
Application of the Spectral Element Method to Interior Noise Problems
NASA Technical Reports Server (NTRS)
Doyle, James F.
1998-01-01
The primary effort of this research project was focused the development of analytical methods for the accurate prediction of structural acoustic noise and response. Of particular interest was the development of curved frame and shell spectral elements for the efficient computational of structural response and of schemes to match this to the surrounding fluid.
PSYCHOLOGICAL PROBLEMS AND RESEARCH METHODS IN MATHEMATICS TRAINING.
ERIC Educational Resources Information Center
DU BOIS, PHILIP H.; FEIERABEND, ROSALIND L.
A CRITICAL REVIEW OF PSYCHOLOGICAL LITERATURE AND A RESEARCH METHODS INVENTORY, RELATING TO THE LEARNING OF MATHEMATICS AT ALL ACADEMIC LEVELS, WERE CONDUCTED TO DEVELOP A HANDBOOK OR GUIDE FOR USE BY INVESTIGATORS IN THE FIELD OF MATHEMATICS TEACHING. THIS EFFORT TOOK PLACE DURING A 3-MONTH PERIOD WHICH INCLUDED SYSTEMATIC SURVEYS OF LITERATURE…
Porebski, Grzegorz; Czarnobilska, Ewa
2015-01-01
The in vitro diagnosis of delayed drug hypersensitivity reactions remains a research problem. We measured drug-specific IFNγ release in peripheral blood mononuclear cells sampled from patients with drug-induced maculopapular exanthema and the age- and sex-matched control group. This is the first study to directly cross-compare an ultrasensitive assay based on an emerging electrochemiluminescence technology (ECL), the standard lymphocyte proliferation assay and three following tests detecting IFNγ at different steps of its production: intracellular in CD3+CD4+ cells (flow cytometry), secretion at the single cell level (enzyme-linked immunospot assay), bulk content in cell culture supernatant (enzyme-linked immunosorbent assay, ELISA). The highest rate of drug-positive responses were recorded for ELISA and ECL tests (56.25%). No false-positive responses were observed--all tests were negative in the control group. We demonstrated that IFNγ-detecting ELISA is not less efficient than ECL test, however, it is easily available and cheap, which makes it a potential method of choice in the future.
NASA Astrophysics Data System (ADS)
Kalogiratou, Z.; Monovasilis, Th.; Simos, T. E.
2016-12-01
In this work we consider trigonometrically fitted two step hybrid methods for the numerical solution of second-order initial value problems. We follow the approach of Simos and derive trigonometrically fitting conditions for methods with five stages. As an example we modify a seventh order method and apply to three well known oscillatory problems.
Inhalation injury associated with smoking, alcohol and drug abuse: an increasing problem.
Bennett, S P H; Trickett, R W; Potokar, T S
2009-09-01
This study investigated the association of inhalation injury (IHI) with smoking, alcohol and drug abuse in patients admitted to the Welsh Centre for Burns between 1995 and 2006. Common characteristics of these individuals were identified and contrasted with inhalation injury not associated with these social factors. Two hundred and fourteen patients were identified with inhalation injury. Ninety-two of these were associated with smoking, alcohol abuse and/or drug abuse. The proportion of IHI cases associated with smoking remained stable but IHI associated with alcohol and drug abuse increased dramatically over the course of the study and if current trends continue will increase further in future years. This study also showed that IHI associated with smoking alcohol and drug abuse were found to be largely caused by housefires and deliberate self-harm, and occurred between 22:00 and 05:59 h. These results were in sharp contrast with IHI not associated with these factors.
A boundary integral method for an inverse problem in thermal imaging
NASA Technical Reports Server (NTRS)
Bryan, Kurt
1992-01-01
An inverse problem in thermal imaging involving the recovery of a void in a material from its surface temperature response to external heating is examined. Uniqueness and continuous dependence results for the inverse problem are demonstrated, and a numerical method for its solution is developed. This method is based on an optimization approach, coupled with a boundary integral equation formulation of the forward heat conduction problem. Some convergence results for the method are proved, and several examples are presented using computationally generated data.
A numerical method for solving optimal control problems using state parametrization
NASA Astrophysics Data System (ADS)
Mehne, H.; Borzabadi, A.
2006-06-01
A numerical method for solving a special class of optimal control problems is given. The solution is based on state parametrization as a polynomial with unknown coefficients. This converts the problem to a non-linear optimization problem. To facilitate the computation of optimal coefficients, an improved iterative method is suggested. Convergence of this iterative method and its implementation for numerical examples are also given.
Drug Ingestions in Children 10-14 Years Old: An Old Problem Revisited
ERIC Educational Resources Information Center
Pomerantz, Wendy; Gittelman, Michael; Farris, Sarah; Frey, Lauren
2009-01-01
To determine changes in rates of drug ingestions in 10-14 year old children in our country, a retrospective chart review of 10-14 year olds hospitalized for drug ingestion between 1993-1995 and 2000-2004 was performed. Odds ratios and Chi-square were used for analyses. From 1993-1995 there were 92.8 ingestions/100,000 children/year; from 2000-2004…
The Application of Probabilistic Methods to the Mistuning Problem
NASA Technical Reports Server (NTRS)
Griffin, J. H.; Rossi, M. R.; Feiner, D. M.
2004-01-01
FMM is a reduced order model for efficiently calculating the forced response of a mistuned bladed disk. FMM ID is a companion program which determines the mistuning in a particular rotor. Together, these methods provide a way to acquire data on the mistuning in a population of bladed disks, and then simulate the forced response of the fleet. This process is tested experimentally, and the simulated results are compared with laboratory measurements of a fleet of test rotors. The method is shown to work quite well. It is found that accuracy of the results depends on two factors: the quality of the statistical model used to characterize mistuning, and how sensitive the system is to errors in the statistical modeling.
Problems in the NDT world: The penetrant inspection method
Marks, D. )
1994-10-01
When discussing a subject like non-destructive testing (NDT) with other professionals who have basically the same qualifications and certifications as yourself, it becomes apparent that the liquid penetrant method of examination is often chosen as the simplest and easiest method for many applications. No matter how simple an NDT application may seem, however, the bottom line is that the desired results of the application reveal the true status of the item under inspection. Therefore, it is very important that the personnel performing any NDT function possess the skills and knowledge of the specific discipline being applied. This article addresses some basic questions concerning liquid penetrant testing. It is the intent of this paper to help NDT personnel obtain a better understanding of the many approaches industry has in developing guidelines for the penetrant discipline.
Liu, Yang; Zhai, Hua-Qiang; Xiang, Jia-Mei; Wang, Jing-Juan; Zhao, Bao-Sheng; Wang, Gang; Dong, Hong-Huan; Ouyang, Guo-Qing
2014-07-01
With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.
Numerical Methods for Forward and Inverse Problems in Discontinuous Media
Chartier, Timothy P.
2011-03-08
The research emphasis under this grant's funding is in the area of algebraic multigrid methods. The research has two main branches: 1) exploring interdisciplinary applications in which algebraic multigrid can make an impact and 2) extending the scope of algebraic multigrid methods with algorithmic improvements that are based in strong analysis.The work in interdisciplinary applications falls primarily in the field of biomedical imaging. Work under this grant demonstrated the effectiveness and robustness of multigrid for solving linear systems that result from highly heterogeneous finite element method models of the human head. The results in this work also give promise to medical advances possible with software that may be developed. Research to extend the scope of algebraic multigrid has been focused in several areas. In collaboration with researchers at the University of Colorado, Lawrence Livermore National Laboratory, and Los Alamos National Laboratory, the PI developed an adaptive multigrid with subcycling via complementary grids. This method has very cheap computing costs per iterate and is showing promise as a preconditioner for conjugate gradient. Recent work with Los Alamos National Laboratory concentrates on developing algorithms that take advantage of the recent advances in adaptive multigrid research. The results of the various efforts in this research could ultimately have direct use and impact to researchers for a wide variety of applications, including, astrophysics, neuroscience, contaminant transport in porous media, bi-domain heart modeling, modeling of tumor growth, and flow in heterogeneous porous media. This work has already led to basic advances in computational mathematics and numerical linear algebra and will continue to do so into the future.
High-Precision Direct Method for the Radiative Transfer Problems
NASA Astrophysics Data System (ADS)
Zhang, Yan; Hou, Su-Qing; Yang, Ping; Wu, Kai-Su
2013-06-01
It is the main aim of this paper to investigate the numerical methods of the radiative transfer equation. Using the five-point formula to approximate the differential part and the Simpson formula to substitute for integral part respectively, a new high-precision numerical scheme, which has 4-order local truncation error, is obtained. Subsequently, a numerical example for radiative transfer equation is carried out, and the calculation results show that the new numerical scheme is more accurate.
Computational Methods for Sparse Solution of Linear Inverse Problems
2009-03-01
methods from harmonic analysis [5]. For example, natural images can be approximated with relatively few wavelet coefficients. As a consequence, in many...performed efficiently. For example, the cost of these products is O(N logN) when Φ is constructed from Fourier or wavelet bases. For algorithms that...stream community has proposed efficient algorithms for computing near-optimal histograms and wavelet -packet approximations from compressive samples [4
Data assimilation in problems of mantle dynamics: Methods and applications
NASA Astrophysics Data System (ADS)
Ismail-Zadeh, A.; Schubert, G.; Tsepelev, I.; Korotkii, A.
2009-05-01
We present and compare several methods (backward advection, adjoint, and quasi-reversibility) for assimilation of geophysical and geodetic data in geodynamical models. These methods allow for incorporating observations and unknown initial conditions for mantle temperature and flow into a three- dimensional dynamic model in order to determine the initial conditions in the geological past. Once the conditions are determined the evolution of mantle structures can be restore. Using the quasi-reversibility method we reconstruct the evolution of the descending lithospheric slab beneath the south-eastern Carpathians. We show that the geometry of the mantle structures changes with time diminishing the degree of surface curvature of the structures, because the heat diffusion tends to smooth the complex thermal surfaces of mantle bodies with time. Present seismic tomography images of mantle structures do not allow definition of the sharp shapes of these structures in the past. Assimilation of mantle temperature and flow instead provides a quantitative tool to restore thermal shapes of prominent structures in the past from their diffusive shapes at present.
Cabot, Joan M; Fuguet, Elisabet; Rosés, Martí
2014-10-13
A novel high-throughput method for determining acidity constants (pKa) by capillary electrophoresis (CE) is developed. The method, based on the use of an internal standard (IS-CE), is implemented as a routine method for accurate experimental pKa determination of drugs undergoing physicochemical measurements in drug discovery laboratories. Just two electropherograms at 2 different pH values are needed to calculate an acidity constant. Several ISs can be used in the same buffer and run to enhance precision. With 3 ISs, for example, the pKa of the test compound (TC) can be obtained in triplicate in less than 3 min of electrophoresis. It has been demonstrated that the IS-CE method eliminates some systematic errors, maintaining, or even increasing the precision of the results compared with other methods. Furthermore, pH buffer instability during electrophoretic runs is not a problem in the IS-CE method. It is also proved that after 16 h of electroseparation using the same buffer vial, pH may change by around one unit; but the pKa calculated by the IS-CE method remains constant. Thus, IS-CE is a powerful high-throughput method for pKa determination in drug discovery and development.
A two-step similarity-based method for prediction of drug's target group.
Chen, Lei; Zeng, Wei-Ming
2013-03-01
Determination of drug's target protein is very important for studying drug-target interaction network, while drug-target interaction network is a key area in the drug discovery pipeline. Thus correct prediction of drug's target protein is very helpful to promote the development of drug discovery. In this study, we developed a two-step similarity-based method to predict drug's target group. In each step, a similarity score (obtained by graph representation in the first step, and chemical functional group representation in the second step) was employed to make prediction. Since some drugs can target proteins distributing in more than one group of proteins, the method provided a series of candidate target groups for each drug. As a result, the first-order prediction accuracy on training set and test set were 79.01% and 76.43%, respectively, which were much higher than the success rate of a random guess. The results show that using graph representation to encode drug is a good choice in this area. We expect that this contribution will provide some help to understand drug-target interaction network.
Computational methods for long mean free path problems
NASA Astrophysics Data System (ADS)
Christlieb, Andrew Jason
This document describes work being done on particle transport in long mean free path environments. Two non statistical computational models are developed based on the method of propagators, which can have significant advantages in accuracy and efficiency over other methods. The first model has been developed primarily for charged particle transport and the second primarily for neutral particle transport. Both models are intended for application to transport in complex geometry using irregular meshes. The transport model for charged particles was inspired by the notion of obtaining a simulation that could handle complex geometry and resolve the bulk and sheath characteristics of a discharge, in a reasonable amount of computation time. The charged particle transport model has been applied in a self- consistent manner to the ion motion in a low density inductively coupled discharge. The electrons were assumed to have a Boltzmann density distribution for the computation of the electric field. This work assumes cylindrical geometry and focuses on charge exchange collisions as the primary ion collisional effect that takes place in the discharge. The results are compared to fluid simulations. The neutral transport model was constructed to solve the steady state Boltzmann equation on 3-D arbitrary irregular meshes. The neutral transport model was developed with the intent of investigating gas glow on the scale of micro-electrical-mechanical systems (MEMS), and is meant for tracking multiple species. The advantage of these methods is that the step size is determined by the mean free path of the particles rather than the mesh employed in the simulation.
Block Krylov-Schur method for large symmetric eigenvalue problems
NASA Astrophysics Data System (ADS)
Zhou, Yunkai; Saad, Yousef
2008-04-01
Stewart's Krylov-Schur algorithm offers two advantages over Sorensen's implicitly restarted Arnoldi (IRA) algorithm. The first is ease of deflation of converged Ritz vectors, the second is the avoidance of the potential forward instability of the QR algorithm. In this paper we develop a block version of the Krylov-Schur algorithm for symmetric eigenproblems. Details of this block algorithm are discussed, including how to handle rank deficient cases and how to use varying block sizes. Numerical results on the efficiency of the block Krylov-Schur method are reported.
NASA Astrophysics Data System (ADS)
Antipin, A. S.; Artem'eva, L. A.; Vasil'ev, F. P.
2017-01-01
An optimal control problem formulated as a system of linear ordinary differential equations with boundary conditions implicitly specified as a solution to a finite-dimensional minimization problem is considered. An extragradient method for solving this problem is proposed, and its convergence is studied.
A comparison of several methods of solving nonlinear regression groundwater flow problems.
Cooley, R.L.
1985-01-01
Computational efficiency and computer memory requirements for four methods of minimizing functions were compared for four test nonlinear-regression steady state groundwater flow problems. The fastest methods were the Marquardt and quasi-linearization methods, which required almost identical computer times and numbers of iterations; the next fastest was the quasi-Newton method, and last was the Fletcher-Reeves method, which did not converge in 100 iterations for two of the problems.-from Author
2014-08-19
finite element method, performance verification on experimental data, imaging of explosive devices, comparison with the classical Krein equation method...of the globally convergent numerical method of this project and the classical Krein equation method. It was established that while the first method...of a long standing problem about uniqueness of a phaseless 3-d inverse problem of quantum scattering. This was an open question since the publication
2011-01-01
Background There is an increasing recognition that modelling and simulation can assist in the process of designing health care policies, strategies and operations. However, the current use is limited and answers to questions such as what methods to use and when remain somewhat underdeveloped. Aim The aim of this study is to provide a mechanism for decision makers in health services planning and management to compare a broad range of modelling and simulation methods so that they can better select and use them or better commission relevant modelling and simulation work. Methods This paper proposes a modelling and simulation method comparison and selection tool developed from a comprehensive literature review, the research team's extensive expertise and inputs from potential users. Twenty-eight different methods were identified, characterised by their relevance to different application areas, project life cycle stages, types of output and levels of insight, and four input resources required (time, money, knowledge and data). Results The characterisation is presented in matrix forms to allow quick comparison and selection. This paper also highlights significant knowledge gaps in the existing literature when assessing the applicability of particular approaches to health services management, where modelling and simulation skills are scarce let alone money and time. Conclusions A modelling and simulation method comparison and selection tool is developed to assist with the selection of methods appropriate to supporting specific decision making processes. In particular it addresses the issue of which method is most appropriate to which specific health services management problem, what the user might expect to be obtained from the method, and what is required to use the method. In summary, we believe the tool adds value to the scarce existing literature on methods comparison and selection. PMID:21595946
Low-frequency sonophoresis: a noninvasive method of drug delivery and diagnostics.
Mitragotri, S; Kost, J
2000-01-01
Transdermal drug delivery offers an attractive alternative to injections and oral medications. However, applications of transdermal drug delivery are limited to only a few drugs as a result of low skin permeability. Application of low-frequency ultrasound enhances skin permeability, a phenomenon referred to as low-frequency sonophoresis. In this method, a short application of ultrasound is used to permeabilize skin for a prolonged period of time. During this period, ultrasonically permeabilized skin may be utilized for drug delivery. In addition, a sample of interstitial fluid or its components may be extracted through permeabilized skin for diagnostic applications. In this paper, we report our in vivo studies that demonstrate the principles of both of these concepts. Detailed studies on drug delivery are performed using inulin and mannitol as model drugs. Studies on diagnostics are performed using glucose as a model analyte. Applications of this technology to drug delivery and diagnostics are discussed.
Solving incompressible flow problems with parallel spectral element methods
Ma, Hong
1994-10-01
Parallel spectral element models are built for the Navier-Stokes equations and the shallow water equations with nonstaggered grid formulations. The optimized computational efficiency of these parallel spectral element models comes not only from the exponential convergence of their numerical solutions, but also from their efficient usage of the powerful vector-processing units of the latest parallel architectures. Furthermore, the communication cost of the spectral element model is lower than that of the h-type finite element model, partly because many fewer redundant nodal values have to be stored. The nonstaggered grid formulations perform well in iterative procedures which are highly in parallel. Implementations of these models are carried out on the Connection Machine systems. The present work shows that the high-order domain decomposition methods can be efficiently applied in a data parallel programming environment.
A Promising New Method to Estimate Drug-Polymer Solubility at Room Temperature.
Knopp, Matthias Manne; Gannon, Natasha; Porsch, Ilona; Rask, Malte Bille; Olesen, Niels Erik; Langguth, Peter; Holm, René; Rades, Thomas
2016-09-01
The established methods to predict drug-polymer solubility at room temperature either rely on extrapolation over a long temperature range or are limited by the availability of a liquid analogue of the polymer. To overcome these issues, this work investigated a new methodology where the drug-polymer solubility is estimated from the solubility of the drug in a solution of the polymer at room temperature using the shake-flask method. Thus, the new polymer in solution method does not rely on temperature extrapolations and only requires the polymer and a solvent, in which the polymer is soluble, that does not affect the molecular structure of the drug and polymer relative to that in the solid state. Consequently, as this method has the potential to provide fast and precise estimates of drug-polymer solubility at room temperature, we encourage the scientific community to further investigate this principle both fundamentally and practically.
Pseudospectral Collocation Methods for the Direct Transcription of Optimal Control Problems
2003-04-01
solving optimal control problems for trajectory optimization, spacecraft attitude control, jet thruster control, missile guidance and many other... optimal control problems using a pseudospectral direct transcription method. These problems are stated here so that they may be referred to elsewhere...e.g., [7]. 2.3 Prototypical Examples Throughout this thesis two example problems are used to demonstrate various prop- erties associated with solving
A restricted Steiner tree problem is solved by Geometric Method II
NASA Astrophysics Data System (ADS)
Lin, Dazhi; Zhang, Youlin; Lu, Xiaoxu
2013-03-01
The minimum Steiner tree problem has wide application background, such as transportation system, communication network, pipeline design and VISL, etc. It is unfortunately that the computational complexity of the problem is NP-hard. People are common to find some special problems to consider. In this paper, we first put forward a restricted Steiner tree problem, which the fixed vertices are in the same side of one line L and we find a vertex on L such the length of the tree is minimal. By the definition and the complexity of the Steiner tree problem, we know that the complexity of this problem is also Np-complete. In the part one, we have considered there are two fixed vertices to find the restricted Steiner tree problem. Naturally, we consider there are three fixed vertices to find the restricted Steiner tree problem. And we also use the geometric method to solve such the problem.
Sport, health and drugs: a critical re-examination of some key issues and problems.
Hanstad, Dag Vidar; Waddington, Ivan
2009-07-01
One of the major justifications for the ban on the use of performance-enhancing drugs in sport has been that relating to the protection of the health of athletes. This paper subjects this argument to critical analysis by putting it in the context of the broader relationship between sport and health. More particularly, the paper seeks to unravel some of the complexities of this relationship by an examination of: (i) some aspects of sports sponsorship, particularly with alcohol and tobacco companies; (ii) the health risks associated with elite level sport; and (iii) the widespread and legal use within the sporting context of drugs that can have dangerous side effects. The paper concludes with an examination of some aspects of anti-doping policies within sport and it is suggested that a more imaginative approach to athlete education is needed to prevent the misuse of drugs.
Recursive-operator method in vibration problems for rod systems
NASA Astrophysics Data System (ADS)
Rozhkova, E. V.
2009-12-01
Using linear differential equations with constant coefficients describing one-dimensional dynamical processes as an example, we show that the solutions of these equations and systems are related to the solution of the corresponding numerical recursion relations and one does not have to compute the roots of the corresponding characteristic equations. The arbitrary functions occurring in the general solution of the homogeneous equations are determined by the initial and boundary conditions or are chosen from various classes of analytic functions. The solutions of the inhomogeneous equations are constructed in the form of integro-differential series acting on the right-hand side of the equation, and the coefficients of the series are determined from the same recursion relations. The convergence of formal solutions as series of a more general recursive-operator construction was proved in [1]. In the special case where the solutions of the equation can be represented in separated variables, the power series can be effectively summed, i.e., expressed in terms of elementary functions, and coincide with the known solutions. In this case, to determine the natural vibration frequencies, one obtains algebraic rather than transcendental equations, which permits exactly determining the imaginary and complex roots of these equations without using the graphic method [2, pp. 448-449]. The correctness of the obtained formulas (differentiation formulas, explicit expressions for the series coefficients, etc.) can be verified directly by appropriate substitutions; therefore, we do not prove them here.
A computational method for drug repositioning using publicly available gene expression data
2015-01-01
Motivation The identification of new therapeutic uses of existing drugs, or drug repositioning, offers the possibility of faster drug development, reduced risk, lesser cost and shorter paths to approval. The advent of high throughput microarray technology has enabled comprehensive monitoring of transcriptional response associated with various disease states and drug treatments. This data can be used to characterize disease and drug effects and thereby give a measure of the association between a given drug and a disease. Several computational methods have been proposed in the literature that make use of publicly available transcriptional data to reposition drugs against diseases. Method In this work, we carry out a data mining process using publicly available gene expression data sets associated with a few diseases and drugs, to identify the existing drugs that can be used to treat genes causing lung cancer and breast cancer. Results Three strong candidates for repurposing have been identified- Letrozole and GDC-0941 against lung cancer, and Ribavirin against breast cancer. Letrozole and GDC-0941 are drugs currently used in breast cancer treatment and Ribavirin is used in the treatment of Hepatitis C. PMID:26679199
Manly, Jody Todd; Oshri, Assaf; Lynch, Michael; Herzog, Margaret; Wortel, Sanne
2013-02-01
Given the high prevalence of child neglect among maltreatment subtypes, and its association with exposure to additional environmental adversity, understanding the processes that potentiate child neglect and link neglect to subsequent child externalizing psychopathology may shed light on key targets for preventive intervention. Among 170 urban low-income children (ages 4-9) and their mothers, this 5-year prospective study examined the effects of early neglect severity and maternal substance abuse, as well as neighborhood crime, on children's later externalizing behavior problems. Severity of child neglect (up to age 6 years) mediated the relation between maternal drug dependence diagnosis (MDDD), determined at children's age of 4 years, and children's externalizing behavior problems at age 9. Rates of neighborhood crime mediated the link between presence of child neglect and children's externalizing behavior problems. The roles of MDDD, child neglect, and community violence in the development of child psychopathology are discussed in terms of their implications for intervention.
ERIC Educational Resources Information Center
Savoye, Philippe
2009-01-01
In recent years, I started covering difference equations and z transform methods in my introductory differential equations course. This allowed my students to extend the "classical" methods for (ordinary differential equation) ODE's to discrete time problems arising in many applications.
Kılıç, Emre Eibert, Thomas F.
2015-05-01
An approach combining boundary integral and finite element methods is introduced for the solution of three-dimensional inverse electromagnetic medium scattering problems. Based on the equivalence principle, unknown equivalent electric and magnetic surface current densities on a closed surface are utilized to decompose the inverse medium problem into two parts: a linear radiation problem and a nonlinear cavity problem. The first problem is formulated by a boundary integral equation, the computational burden of which is reduced by employing the multilevel fast multipole method (MLFMM). Reconstructed Cauchy data on the surface allows the utilization of the Lorentz reciprocity and the Poynting's theorems. Exploiting these theorems, the noise level and an initial guess are estimated for the cavity problem. Moreover, it is possible to determine whether the material is lossy or not. In the second problem, the estimated surface currents form inhomogeneous boundary conditions of the cavity problem. The cavity problem is formulated by the finite element technique and solved iteratively by the Gauss–Newton method to reconstruct the properties of the object. Regularization for both the first and the second problems is achieved by a Krylov subspace method. The proposed method is tested against both synthetic and experimental data and promising reconstruction results are obtained.
khani-Jazani, Reza; Molavi-Taleghani, Yasamin; Seyedin, Hesam; Vafaee-Najar, Ali; Ebrahimipour, Hossein; Pourtaleb, Arefeh
2015-01-01
Evaluation and improvement of drug management process are essential for patient safety. The present study was performed whit the aim of assessing risk of drug management process in Women Surgery Department of QEH using HFMEA method in 2013. A mixed method was used to analyze failure modes and their effects with HFMEA. To classify failure modes; nursing errors in clinical management model, for classifying factors affecting error; approved model by the UK National Health System, and for determining solutions for improvement; Theory of Inventive Problem Solving, were used. 48 failure modes were identified for 14 sub-process of five steps drug management process. The frequency of failure modes were as follow :35.3% in supplying step, 20.75% in prescription step, 10.4% in preparing step, 22.9% in distribution step and 10.35% in follow up and monitoring step. Seventeen failure modes (35.14%) were considered as non-acceptable risk (hazard score≥ 8) and were transferred to decision tree. Among 51 Influencing factors, the most common reasons for error were related to environmental factors (21.5%), and the less common reasons for error were related to patient factors (4.3%). HFMEA is a useful tool to evaluating, prioritization and analyzing failure modes in drug management process. Revision drug management process based focus-PDCA, assessing adverse drug reactions (ADR), USE patient identification bracelet, holding periodical pharmaceutical conferences to improve personnel knowledge, patient contribution in drug therapy; are performance solutions which were placed in work order. PMID:25901157
NASA Technical Reports Server (NTRS)
Ransom, Jonathan B.
2002-01-01
A multifunctional interface method with capabilities for variable-fidelity modeling and multiple method analysis is presented. The methodology provides an effective capability by which domains with diverse idealizations can be modeled independently to exploit the advantages of one approach over another. The multifunctional method is used to couple independently discretized subdomains, and it is used to couple the finite element and the finite difference methods. The method is based on a weighted residual variational method and is presented for two-dimensional scalar-field problems. A verification test problem and a benchmark application are presented, and the computational implications are discussed.
A Self-Adaptive Projection and Contraction Method for Linear Complementarity Problems
Liao Lizhi Wang Shengli
2003-10-15
In this paper we develop a self-adaptive projection and contraction method for the linear complementarity problem (LCP). This method improves the practical performance of the modified projection and contraction method by adopting a self-adaptive technique. The global convergence of our new method is proved under mild assumptions. Our numerical tests clearly demonstrate the necessity and effectiveness of our proposed method.
Adaptive finite element methods for two-dimensional problems in computational fracture mechanics
NASA Technical Reports Server (NTRS)
Min, J. B.; Bass, J. M.; Spradley, L. W.
1994-01-01
Some recent results obtained using solution-adaptive finite element methods in two-dimensional problems in linear elastic fracture mechanics are presented. The focus is on the basic issue of adaptive finite element methods for validating the new methodology by computing demonstration problems and comparing the stress intensity factors to analytical results.
Fundamental solution of the problem of linear programming and method of its determination
NASA Technical Reports Server (NTRS)
Petrunin, S. V.
1978-01-01
The idea of a fundamental solution to a problem in linear programming is introduced. A method of determining the fundamental solution and of applying this method to the solution of a problem in linear programming is proposed. Numerical examples are cited.
Reliable Multi Method Assessment of Metacognition Use in Chemistry Problem Solving
ERIC Educational Resources Information Center
Cooper, Melanie M.; Sandi-Urena, Santiago; Stevens, Ron
2008-01-01
Metacognition is fundamental in achieving understanding of chemistry and developing of problem solving skills. This paper describes an across-method-and-time instrument designed to assess the use of metacognition in chemistry problem solving. This multi method instrument combines a self report, namely the Metacognitive Activities Inventory…
2012-08-01
AFRL-RX-WP-TP-2012-0397 INVERSE PROBLEM FOR ELECTROMAGNETIC PROPAGATION IN A DIELECTRIC MEDIUM USING MARKOV CHAIN MONTE CARLO METHOD ...SUBTITLE INVERSE PROBLEM FOR ELECTROMAGNETIC PROPAGATION IN A DIELECTRIC MEDIUM USING MARKOV CHAIN MONTE CARLO METHOD (PREPRINT) 5a. CONTRACT...a stochastic inverse methodology arising in electromagnetic imaging. Nondestructive testing using guided microwaves covers a wide range of
Teenage Pregnancy and Drug Abuse: Sources of Problem Behaviors. ERIC/CUE Digest No. 58.
ERIC Educational Resources Information Center
Bempechat, Janine; And Others
Drug and alcohol abuse and teenage pregnancy are two behaviors manifested by at-risk children that are both a cause and a result of their lack of success in school and possible subsequent dropping out. The distinction between substance use and abuse may be determined using the following criteria: (1) age of onset; (2) physiological responses; (3)…
Problems Related to Alcohol, Other Drugs, and Violence among Military Students. Prevention Update
ERIC Educational Resources Information Center
Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011
2011-01-01
According to a Research Update from the National Institute on Drug Abuse, ongoing operations in Iraq and Afghanistan "continue to strain military personnel, returning veterans, and their families. Some have experienced long and multiple deployments, combat exposure, and physical injuries, as well as post-traumatic stress disorder (PTSD) and…
State Resources and Services for Alcohol and Drug Abuse Problems. Fiscal Year 1985.
ERIC Educational Resources Information Center
Butynski, William; And Others
This report presents and analyzes the results of the State Alcohol and Drug Abuse Profile data for the states' 1985 fiscal year (FY). Included is information from the 50 states, the District of Columbia, Guam, Puerto Rico, and the Virgin Islands. Highlights, an executive summary, an introduction, and a section on the study purpose and methodology…
Nomenclature and classification of drug- and alcohol-related problems: a WHO Memorandum*
1981-01-01
Earlier work in this field is reviewed and present concepts and terminologies are examined in detail. A revised way of dealing with ideas implicit in the terms ”drug abuse” or ”drug misuse” is proposed; the term ”neuroadaptive state” is suggested as an alternative to ”physical dependence”; a profile is given of the elements that constitute a ”drug dependence syndrome”; and the need to differentiate conceptually between ”dependence” and ”drug related disability” is stressed. A model of dependence is outlined in which dependence is considered as a psycho—physiological—social syndrome determined and kept going by a complex system of reinforcements. The association between substance use and mental illness is discussed with emphasis on possible two-way relationships. The need for population studies and in particular for longitudinal studies is emphasized. The bearing of all the fore-going considerations on work towards the revision of relevant classification systems is considered, and, in the final section, several recommendations on nomenclature are brought together and suggestions are made for research that might lead to refinement of classification and diagnostic systems. PMID:6972816
Social Marketing Strategies for Campus Prevention of Alcohol and Other Drug Problems.
ERIC Educational Resources Information Center
Zimmerman, Robert
This document sets out one segment of a comprehensive approach intended to assist institutions of higher education in developing and carrying out alcohol abuse and other drug prevention programs. Social marketing is described as a tool of environmental management, that seeks to produce a specified behavior in a target audience. Intended for a…
2012-09-03
use of so-called probability-one methods [22]. The significant advantage of homotopy method to compute steady state solutions is free of Courant ...A homotopy method based on WENO schemes for solving steady state problems of hyperbolic conservation laws Wenrui Hao∗ Jonathan D. Hauenstein† Chi...robustness of the new method . Keywords homotopy continuation, hyperbolic conservation laws, WENO scheme, steady state problems. ∗Department of Applied and
Successive over relaxation method in solving two-point fuzzy boundary value problems
NASA Astrophysics Data System (ADS)
Dahalan, A. A.; Muthuvalu, M. S.; Sulaiman, J.
2013-04-01
In this study, numerical methods are considered in solving the fuzzy boundary value problem (FBVP). This boundary value problem will then be discretized to derive second order finite difference equation and hence generated fuzzy linear system. The approximation solver towards system of linear equations is described through the implementation of the Gauss-Seidel (GS) and Successive Over Relaxation (SOR) iterative methods. Then several numerical experiments were shown to illustrate the effectiveness of SOR iterative method compared with the GS method.
Computational solution of acoustic radiation problems by Kussmaul's boundary element method
NASA Astrophysics Data System (ADS)
Kirkup, S. M.; Henwood, D. J.
1992-10-01
The problem of computing the properties of the acoustic field exterior to a vibrating surface for the complete wavenumber range by the boundary element method is considered. A particular computational method based on the Kussmaul formulation is described. The method is derived through approximating the surface by a set of planar triangles and approximating the surface functions by a constant on each element. The method is successfully applied to test problems and to the Ricardo crankcase simulation rig.
DETERMINING DRUG SENSITIVITY—Use of the Gel Diffusion Method
Chambers, Van Vleck
1960-01-01
A study was carried out to determine whether the double diffusion gel test when applied to the serum of patients with clear-cut penicillin reactions of various types, might be useful for demonstrating the presence of precipitating antibody. Results did not demonstrate the antibody. The difference in results with this test obtained by various workers was not explained by the observations in this study. Other approaches to determination of the mechanism of the penicillin reaction are discussed, and it is noted that the hemagglutination test, newly applied to the penicillin reaction problem, may be useful after further investigation. PMID:13692231
Gao, Bing; Wang, Jun; Wang, Dunju; Zhu, Ziqiang; Qiao, Zhiqiang; Yang, Guangcheng; Nie, Fude
2013-01-01
Purpose The purpose of this study was to develop a novel and continuous method for preparing a nanosized particle of drug crystals and to characterize its properties. Materials and methods A new apparatus was introduced to crystallize nanosized drug crystals of amitriptyline hydrochloride as a model drug. The samples were prepared in the pure state by ultrasonic spray, and elaborated deposition was completed via electrostatic adsorption. Scanning electron microscopy, X-ray powder diffraction, and atomic force microscopy were used to characterize the size of the particles; this was subsequently followed by differential scanning calorimetry. Results and discussion Nanoparticles of drug crystals were successfully prepared. The size of the drug crystals ranged from 20 nm to 400 nm; the particle size of amitriptyline hydrochloride was approximately 71 nm. The particles were spherical and rectangular in shape. Moreover, the melting point of the nanoparticles decreased from 198.2°C to 196.3°C when compared to raw particle crystals. Furthermore, the agglomeration effect was also attenuated as a result of electrostatic repulsion among each particle when absorbed, and depositing on the inner wall of the gathering unit occurred under the electrostatic effect. Conclusion Ultrasonic spray-assisted electrostatic adsorption is a very effective and continuous method to produce drug nanocrystals. This method can be applied to poorly water-soluble drugs, and it can also be a very effective alternative for industrial production. Once the working parameters are given, drug nanocrystals will be produced continuously. PMID:24143097
49 CFR 40.205 - How are drug test problems corrected?
Code of Federal Regulations, 2013 CFR
2013-10-01
... corrected? (a) As a collector, you have the responsibility of trying to successfully complete a collection...), you must try to correct the problem promptly, if doing so is practicable. You may conduct...
A Computationally Efficient Meshless Local Petrov-Galerkin Method for Axisymmetric Problems
NASA Technical Reports Server (NTRS)
Raju, I. S.; Chen, T.
2003-01-01
The Meshless Local Petrov-Galerkin (MLPG) method is one of the recently developed element-free methods. The method is convenient and can produce accurate results with continuous secondary variables, but is more computationally expensive than the finite element method. To overcome this disadvantage, a simple Heaviside test function is chosen. The computational effort is significantly reduced by eliminating the domain integral for the axisymmetric potential problems and by simplifying the domain integral for the axisymmetric elasticity problems. The method is evaluated through several patch tests for axisymmetric problems and example problems for which the exact solutions are available. The present method yielded very accurate solutions. The sensitivity of several parameters of the method is also studied.
ERIC Educational Resources Information Center
Bagner, Daniel M.; Sheinkopf, Stephen J.; Miller-Loncar, Cynthia; LaGasse, Linda L.; Lester, Barry M.; Liu, Jing; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta; Das, Abhik
2009-01-01
Objective: To examine the relationship between early parenting stress and later child behavior in a high-risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior. Methods: A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study (MLS), which is a large…
Proximal point methods for the inverse problem of identifying parameters in beam models
NASA Astrophysics Data System (ADS)
Jadamba, B.; Khan, A. A.; Paulhamus, M.; Sama, M.
2012-07-01
This paper studies the nonlinear inverse problem of identifying certain material parameters in the fourth-order boundary value problem representing the beam model. The inverse problem is solved by posing a convex optimization problem whose solution is an approximation of the sought parameters. The optimization problem is solved by the gradient based approaches, and in this setting, the most challenging aspect is the computation of the gradient of the objective functional. We present a detailed treatment of the adjoint stiffness matrix based approach for the gradient computation. We employ recently proposed self-adaptive inexact proximal point methods by Hager and Zhang [6] to solve the inverse problem. It is known that the regularization features of the proximal point methods are quite different from that of the Tikhonov regularization. We present a comparative analysis of the numerical efficiency of the used proximal point methods without using the Tikhonov regularization.
Eigensolutions to a vibroacoustic interior coupled problem with a perturbation method
NASA Astrophysics Data System (ADS)
Claude, Bertille; Duigou, Laetitia; Girault, Gregory; Cadou, Jean-Marc
2017-02-01
In this paper, an efficient and robust numerical method is proposed to solve non-symmetric eigenvalue problems resulting from the spatial discretization with the finite element method of a vibroacoustic interior problem. The proposed method relies on a perturbation method. Finding the eigenvalues consists in determining zero values of a scalar that depends on angular frequency. Numerical tests show that the proposed method is not sensitive to poorly conditioned matrices resulting from the displacement-pressure formulation. Moreover, the computational times required with this method are lower than those needed with a classical technique such as, for example, the Arnoldi method.
NASA Astrophysics Data System (ADS)
Pindza, Edson; Maré, Eben
2017-03-01
A modified discrete singular convolution method is proposed. The method is based on the single (SE) and double (DE) exponential transformation to speed up the convergence of the existing methods. Numerical computations are performed on a wide variety of singular boundary value and singular perturbed problems in one and two dimensions. The obtained results from discrete singular convolution methods based on single and double exponential transformations are compared with each other, and with the existing methods too. Numerical results confirm that these methods are considerably efficient and accurate in solving singular and regular problems. Moreover, the method can be applied to a wide class of nonlinear partial differential equations.
ERIC Educational Resources Information Center
Williams van Rooij, Shahron
2007-01-01
This study examined the impact of two Problem-Based Learning (PBL) approaches on knowledge transfer, problem-solving self-efficacy, and perceived learning gains among four intact classes of adult learners engaged in a group project in an online undergraduate business research methods course. With two of the classes using a text-only PBL workbook…
Siddiqi, S.H.; Hawkins, J.E.; Laszlo, A.
1985-12-01
A total of 224 recent isolates of Mycobacterium tuberculosis from 163 patients selected to have multidrug resistance were tested against streptomycin (SM), isoniazid, rifampin, and ethambutol (EMB) by the rapid radiometric BACTEC method and two conventional proportion methods: the World Health Organization (WHO) method, using Lowenstein-Jensen medium; and the Veterans Administration reference laboratory for mycobacteria (VA) method, using Middlebrook 7H10 agar medium. The results were compared, focusing on the concentrations of the drugs in all three methods. Among the four drugs tested, most of the discrepancies in measured activity were observed with SM and EMB, generally because of differences in the drug concentrations used by the three methods. A 4-micrograms amount of SM in the BACTEC method was found to be slightly less active than 10 micrograms in the VA method and significantly more active than 4 micrograms of dihydrostreptomycin in the WHO method. With EMB, 2.5 micrograms in BACTEC was similar to 5 micrograms in the VA method and 2 micrograms in the WHO method, while 10 micrograms in the BACTEC method was found to be more active than 10 and 2 micrograms in the VA and WHO methods, respectively. To attain close agreement, drug concentrations used in the BACTEC method should be carefully selected when a comparison is to be made with any conventional method employed in a laboratory. Standardization of in vitro susceptibility testing is greatly needed to achieve uniformity among the test methods used to evaluate tuberculosis therapeutics.
Siddiqi, S H; Hawkins, J E; Laszlo, A
1985-01-01
A total of 224 recent isolates of Mycobacterium tuberculosis from 163 patients selected to have multidrug resistance were tested against streptomycin (SM), isoniazid, rifampin, and ethambutol (EMB) by the rapid radiometric BACTEC method and two conventional proportion methods: the World Health Organization (WHO) method, using Lowenstein-Jensen medium; and the Veterans Administration reference laboratory for mycobacteria (VA) method, using Middlebrook 7H10 agar medium. The results were compared, focusing on the concentrations of the drugs in all three methods. Among the four drugs tested, most of the discrepancies in measured activity were observed with SM and EMB, generally because of differences in the drug concentrations used by the three methods. A 4-micrograms amount of SM in the BACTEC method was found to be slightly less active than 10 micrograms in the VA method and significantly more active than 4 micrograms of dihydrostreptomycin in the WHO method. With EMB, 2.5 micrograms in BACTEC was similar to 5 micrograms in the VA method and 2 micrograms in the WHO method, while 10 micrograms in the BACTEC method was found to be more active than 10 and 2 micrograms in the VA and WHO methods, respectively. To attain close agreement, drug concentrations used in the BACTEC method should be carefully selected when a comparison is to be made with any conventional method employed in a laboratory. Standardization of in vitro susceptibility testing is greatly needed to achieve uniformity among the test methods used to evaluate tuberculosis therapeutics. PMID:3934209
A least-squares finite element method for incompressible Navier-Stokes problems
NASA Technical Reports Server (NTRS)
Jiang, Bo-Nan
1989-01-01
A least-squares finite element method, based on the velocity-pressure-vorticity formulation, is developed for solving steady incompressible Navier-Stokes problems. This method leads to a minimization problem rather than to a saddle-point problem by the classic mixed method, and can thus accommodate equal-order interpolations. This method has no parameter to tune. The associated algebraic system is symmetric, and positive definite. Numerical results for the cavity flow at Reynolds number up to 10,000 and the backward-facing step flow at Reynolds number up to 900 are presented.
A least-squares finite element method for incompressible Navier-Stokes problems
NASA Technical Reports Server (NTRS)
Jiang, Bo-Nan
1992-01-01
A least-squares finite element method, based on the velocity-pressure-vorticity formulation, is developed for solving steady incompressible Navier-Stokes problems. This method leads to a minimization problem rather than to a saddle-point problem by the classic mixed method and can thus accommodate equal-order interpolations. This method has no parameter to tune. The associated algebraic system is symmetric, and positive definite. Numerical results for the cavity flow at Reynolds number up to 10,000 and the backward-facing step flow at Reynolds number up to 900 are presented.
An optimization method for the problems of thermal cloaking of material bodies
NASA Astrophysics Data System (ADS)
Alekseev, G. V.; Levin, V. A.
2016-11-01
Inverse heat-transfer problems related to constructing special thermal devices such as cloaking shells, thermal-illusion or thermal-camouflage devices, and heat-flux concentrators are studied. The heatdiffusion equation with a variable heat-conductivity coefficient is used as the initial heat-transfer model. An optimization method is used to reduce the above inverse problems to the respective control problem. The solvability of the above control problem is proved, an optimality system that describes necessary extremum conditions is derived, and a numerical algorithm for solving the control problem is proposed.
Larsen, S
1992-04-01
Saami people ("Lapps") and Norwegians make different use of primary health care services, and Larsen and Nergård (1) reported an under-representation of Saami clients at a treatment facility for drug and alcohol problems in Northern Norway in the years 1986-1988. However, Saami and Norwegian groups did not differ in number of days in treatment, number of treatment incidents, mean age or self-reported years of problem drinking. Since it is believed that Saami clients are under-represented in Norwegian treatment facilities because of cultural differences, the location of treatment facilities within a Saami municipality was expected to increase the incidence of Saami clients. The present study investigated the incidence of Saami clients at Karasjok treatment facility during 1988 and 1989, 8 and 9 years after the opening of this treatment centre. All clients registered at Finnmark County's treatment facility for drug and alcohol problems during 1988-89 were categorized as either Saami or Norwegian by their language preference. Unfortunately, the Saami group was still under-represented among clients at this treatment facility. In addition, a significant difference in the sex-ratio between the two groups was found, indicating that Saami women do not use the institution at all. Results are discussed in terms of availability of health services for minority groups.
Kendler, Kenneth S; Edwards, Alexis; Myers, John; Cho, Seung Bin; Adkins, Amy; Dick, Danielle
2015-01-01
A family history (FH) of psychiatric and substance use problems is a potent risk factor for common internalizing and externalizing disorders. In a large web-based assessment of mental health in college students, we developed a brief set of screening questions for a FH of alcohol problems (AP), drug problems (DP) and depression-anxiety in four classes of relatives (father, mother, aunts/uncles/grandparents, and siblings) as reported by the student. Positive reports of a history of AP, DP, and depression-anxiety were substantially correlated within relatives. These FH measures predicted in the student, in an expected pattern, dimensions of personality and impulsivity, alcohol consumption and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms of depression and anxiety. Using the mean score from the four classes of relatives was more predictive than using a familial/sporadic dichotomy. Interactions were seen between the FH of AP, DP, and depression-anxiety and peer deviance in predicting symptoms of alcohol and tobacco dependence. As the students aged, the FH of AP became a stronger predictor of alcohol problems. While we cannot directly assess the validity of these FH reports, the pattern of findings suggest that our brief screening items were able to assess, with some accuracy, the FH of substance misuse and internalizing psychiatric disorders in relatives. If correct, these measures can play an important role in the creation of developmental etiologic models for substance and internalizing psychiatric disorders which constitute one of the central goals of the overall project. PMID:25946510
Tuberculosis in Europe: a problem of drug resistance or much more?
Carvalho, Anna C C; Migliori, Giovanni B; Cirillo, Daniela M
2010-04-01
Tuberculosis has re-emerged as a public health concern in high-income countries in the last few decades. The European region accounts for only 5% of world TB cases. The incidence of new TB cases in Europe varies from very low rates in Scandinavian countries (six to eight cases/100,000 population) to rates as high as 231 cases/100,000 population in Tajikistan; the Russian Federation is eleventh among the 22 high-burden TB countries. The estimated detection rate of new sputum smear-positive pulmonary cases and the treatment success rate in 2007 were poor compared with other WHO regions: 51% of cases were diagnosed and 70% of them completed a full course of anti-TB therapy, which is still a long way from the World Health Assembly targets (detection of 70% of infectious cases and successful treatment of 85% of them). The low success rate is largely attributable to the increasing number of drug-resistant TB cases: Eastern European countries are among those with the highest rates of multidrug-resistant (MDR)-TB (TB resistant to rifampicin and isoniazid) in the world. By the end of September 2009, at least one case of extensively drug-resistant TB (named XDR-TB and defined as a MDR-TB strain with additional resistance to any fluoroquinolone, and to at least one of three injectable drugs used in anti-TB treatment) had been reported by 25 countries in the WHO European Region. In Western Europe, TB continues to cause disease among elderly native-born individuals, although high-risk groups including immigrants, prisoners, HIV-infected persons and drug addicts significantly contribute to the overall burden. Improved TB control in Europe requires a large coordinated effort by all stakeholders, including governments, governmental and non-governmental institutions, as well as the academic and private sectors and affected communities.
Foroughinia, Farzaneh; Tazarehie, Seyyed Ramtin; Petramfar, Peyman
2016-01-01
Objective: Nowadays, the role of clinical pharmacists has become more prominent by more clinical pharmacists joining the health-care teams. This study was aimed to assess the role of a clinical pharmacist specialist in detecting and managing drug-related problems (DRPs) in the neurology ward of a tertiary care teaching hospital in Iran. Methods: This is a prospective cross-sectional study conducted on 123 hospitalized patients admitted to the neurology ward of a teaching hospital. The clinical pharmacist visited the patients and filled out the designed pharmacotherapy sheet for each patient. Then, the general pharmacist checked the patients' files and pharmacotherapy sheets and categorized DRPs using modified method of “The Pharmaceutical Care Network Europe classification, Version 5.01.” Findings: A total of 168 errors were found and 346 interventions were done by the clinical pharmacist during the study period. The most common form of errors in our study was “drug choice problems” (57.76%). The acceptance rate of interventions was 41.91% among physicians. Conclusion: The large number of interventions reported in several studies, as well as this study, revealed that clinical pharmacy services could contribute to a rationalization of drug therapy and may eventually lead to more medication safety. PMID:27843966
Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?
Dua, Kamal; Shukla, Shakti D; Tekade, Rakesh K; Hansbro, Philip M
2017-02-01
Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.
Solution of the radiative transfer theory problems by the Monte Carlo method
NASA Technical Reports Server (NTRS)
Marchuk, G. I.; Mikhailov, G. A.
1974-01-01
The Monte Carlo method is used for two types of problems. First, there are interpretation problems of optical observations from meteorological satellites in the short wave part of the spectrum. The sphericity of the atmosphere, the propagation function, and light polarization are considered. Second, problems dealt with the theory of spreading narrow light beams. Direct simulation of light scattering and the mathematical form of medium radiation model representation are discussed, and general integral transfer equations are calculated. The dependent tests method, derivative estimates, and solution to the inverse problem are also considered.
Evaluation of a transfinite element numerical solution method for nonlinear heat transfer problems
NASA Technical Reports Server (NTRS)
Cerro, J. A.; Scotti, S. J.
1991-01-01
Laplace transform techniques have been widely used to solve linear, transient field problems. A transform-based algorithm enables calculation of the response at selected times of interest without the need for stepping in time as required by conventional time integration schemes. The elimination of time stepping can substantially reduce computer time when transform techniques are implemented in a numerical finite element program. The coupling of transform techniques with spatial discretization techniques such as the finite element method has resulted in what are known as transfinite element methods. Recently attempts have been made to extend the transfinite element method to solve nonlinear, transient field problems. This paper examines the theoretical basis and numerical implementation of one such algorithm, applied to nonlinear heat transfer problems. The problem is linearized and solved by requiring a numerical iteration at selected times of interest. While shown to be acceptable for weakly nonlinear problems, this algorithm is ineffective as a general nonlinear solution method.
Evaluation of a transfinite element numerical solution method for nonlinear heat transfer problems
NASA Astrophysics Data System (ADS)
Cerro, J. A.; Scotti, S. J.
1991-07-01
Laplace transform techniques have been widely used to solve linear, transient field problems. A transform-based algorithm enables calculation of the response at selected times of interest without the need for stepping in time as required by conventional time integration schemes. The elimination of time stepping can substantially reduce computer time when transform techniques are implemented in a numerical finite element program. The coupling of transform techniques with spatial discretization techniques such as the finite element method has resulted in what are known as transfinite element methods. Recently attempts have been made to extend the transfinite element method to solve nonlinear, transient field problems. This paper examines the theoretical basis and numerical implementation of one such algorithm, applied to nonlinear heat transfer problems. The problem is linearized and solved by requiring a numerical iteration at selected times of interest. While shown to be acceptable for weakly nonlinear problems, this algorithm is ineffective as a general nonlinear solution method.
Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs
Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi
2005-09-01
Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.
NASA Astrophysics Data System (ADS)
Ismail, Farzad; Chizari, Hossain
2017-02-01
This paper presents preliminary developments of entropy-stable residual distribution methods for scalar problems. Controlling entropy generation is achieved by formulating an entropy conserved signals distribution coupled with an entropy-stable signals distribution. Numerical results of the entropy-stable residual distribution methods are accurate and comparable with the classic residual distribution methods for steady-state problems. High order accurate extensions for the new method on steady-state problems are also demonstrated. Moreover, the new method preserves second order accuracy on unsteady problems using an explicit time integration scheme. The idea of the multi-dimensional entropy-stable residual distribution method is generic enough to be extended to the system of hyperbolic equations, which will be presented in the sequel of this paper.
Zhang, Ying-Nan; Xu, Wen
2014-03-01
Under the background of the new medical reform, a large variety of traditional Chinese medicine from complicated sources, Chinese traditional medicine of actor of true and false of the quality directly affect the drug safety and clinical efficacy, but also relate to the social and economic benefits of hospital. Along with the development of the modern management of medical institutions and drug circulation circulation system reform in our country, the hospital drug inventory, supply and management work is an important topic for the pharmaceutical trading. However, there is always contradiction, dispensary need to supple pharmacy, in order to satisfy the demands of hospital patients with normal diagnosis and treatment work. However, if the drug inventory is too much, not only increases the drug monitoring problem, at the same time, but also causes storage costs rise. Therefore, completing scientific and reasonable storage and management becomes urgent problems at present. Wherefore, our country administration of traditional Chinese medicine in 2007 promulgated the "Chinese traditional medicine yinpian management norms in hospital", aims to standardize management of Chinese traditional medicine quality and improve the safety of drugs. The author through looking up information and visiting survey, to understand the currently existing problems, and summarizes the literature inland and abroad in recent years Chinese medicine drug inventory management work experience, in view of status quo of Chinese medicine inventory management in China, put forward the solution. To guarantee TCM pharmacy management more standardized, more standard, to adapt to the new reform of Chinese traditional medicine industry, improve the management level of hospital, defend the hospital's reputation and the patient's interests.
Gillespie, James A; Quinn, Casey
2012-01-01
Background This is a methodological study investigating the online responses to a national debate over an important health and social problem in Russia. Russia is the largest Internet market in Europe, exceeding Germany in the absolute number of users. However, Russia is unusual in that the main search provider is not Google, but Yandex. Objective This study had two main objectives. First, to validate Yandex search patterns against those provided by Google, and second, to test this method's adequacy for investigating online interest in a 2010 national debate over Russian illicit drug policy. We hoped to learn what search patterns and specific search terms could reveal about the relative importance and geographic distribution of interest in this debate. Methods A national drug debate, centering on the anti-drug campaigner Egor Bychkov, was one of the main Russian domestic news events of 2010. Public interest in this episode was accompanied by increased Internet search. First, we measured the search patterns for 13 search terms related to the Bychkov episode and concurrent domestic events by extracting data from Google Insights for Search (GIFS) and Yandex WordStat (YaW). We conducted Spearman Rank Correlation of GIFS and YaW search data series. Second, we coded all 420 primary posts from Bychkov's personal blog between March 2010 and March 2012 to identify the main themes. Third, we compared GIFS and Yandex policies concerning the public release of search volume data. Finally, we established the relationship between salient drug issues and the Bychkov episode. Results We found a consistent pattern of strong to moderate positive correlations between Google and Yandex for the terms "Egor Bychkov" (r s = 0.88, P < .001), “Bychkov” (r s = .78, P < .001) and “Khimki”(r s = 0.92, P < .001). Peak search volumes for the Bychkov episode were comparable to other prominent domestic political events during 2010. Monthly search counts were 146,689 for “Bychkov” and
Weiß, V; Heinemann, S; Himmel, W; Nau, R; Hummers-Pradier, E
2016-07-01
Aim | Benzodiazepines and Z-drugs are frequently prescribed sleep medications in spite of their poor risk-benefit ratio when used over a longer period of time. The aim of the study was to find out how the medical and nursing staff in a general hospital estimated the frequency of use for these drugs, and the risk-benefit ratio for elderly patients as well as the factors which positively influence the perceived use of these drugs. Methods | All members of the medical and nursing staff of a hospital received a questionnaire about their use of, and attitudes towards, benzodiazepines and Z-drugs. Absolute and relative frequencies were calculated to estimate the perceived frequency of use and the risk-benefit ratio. Multiple logistic regressions were used to analyze which factors are associated with a perceived high use of benzodiazepines or Z-drugs for insomnia. Results | More nurses than hospital doctors believed that they dispensed benzodiazepines often or always (57 % vs. 29 %) to patients with insomnia; this was also the case for Z-drugs (66 % vs. 29 %). Nearly half of the hospital doctors and 29 % of the nurses perceived more harms than benefits for benzodiazepines in the elderly. The following factors were associated with a high perceived usage of Z-drugs: working as a nurse (OR: 13,95; 95%-CI: 3,87-50,28), working in a non-surgical department (5,41; 2,00-14,61), having < 5 years of professional experience (4,90; 1,43-16,81) and feeling that the benefits of Z-drugs outweigh the risks for elderly patients (5,07; 1,48-17,35). For benzodiazepines, only the perceived positive risk-benefit ratio had an influence on the perceived use (3,35; 1,28-8.79). Conclusion | The medical and nursing staff perceived the frequency of prescription of benzodiazepines and Z-drugs and the risk-benefit ratio in different ways. Other aspects, such as working in a non-surgical department or having a smaller amount of working experience may also influence the decision to use Z-drugs.
Szapocznik, José; Zarate, Monica; Duff, Johnathan; Muir, Joan
2013-01-01
Despite the efficacy of family-based interventions for improving outcomes for adolescent behavior problems such as substance use, engaging and retaining whole families in treatment is one of the greatest challenges therapists confront. This article illustrates how the Brief Strategic Family Therapy® (BSFT®) model, a family-based, empirically validated intervention designed to treat children and adolescents’ problem behaviors, can be used to increase engagement, improve retention, and bring about positive outcomes for families. Research evidence for efficacy and effectiveness is also presented. PMID:23731415
Preskorn, Sheldon H
2010-05-01
This column continues the discussion of outliers on the dose-response curve begun in earlier columns. It focuses on therapeutic drug monitoring (TDM) as an underutilized tool in psychiatry to minimize this problem. The scientific rationale for dose adjustment based on TDM is presented and its efficiency is contrasted with dose adjustment based on clinical assessment of response. In current practice, the use of TDM with psychiatric drugs is generally restricted to drugs with narrow therapeutic windows or drugs imported into psychiatry from neurology where TDM is more commonly used. Examples of each of these types of drugs are cited.
2007-11-02
chloroquine (and its metabolites), and 11-a multiple drug interaction study in dog plasma for WR 238,605, mefloquine, chloroquine, quinine ,, doxycycline...and reproducibility of the analytical method, describing the extent of recovery for the method, and reporting on the stability of compounds of...solvent with drug and internal standard. J. GENERATION OF STABILITY SAMPLES System stability samples were generated in the same way as precision
Analysis of Investigational Drugs in Biological Fluids Method Development and Routine Assay
1988-04-12
The purpose of work under this contract is to develop and routinely use analytical methods for the determination of the concentration in biological specimens of investigational drugs in support of pharmacokinetic and bioavailability studies undertaken for the purpose of new drug development for the US military establishment. Accepted scientific procedures including normal and reversed phase high-performance liquid chromatographic methods, post column derivatization, and protein precipitation and
Application of the Sinc method to a dynamic elasto-plastic problem
NASA Astrophysics Data System (ADS)
Abdella, K.; Yu, X.; Kucuk, I.
2009-01-01
This paper presents the application of Sinc bases to simulate numerically the dynamic behavior of a one-dimensional elastoplastic problem. The numerical methods that are traditionally employed to solve elastoplastic problems include finite difference, finite element and spectral methods. However, more recently, biorthogonal wavelet bases have been used to study the dynamic response of a uniaxial elasto-plastic rod [Giovanni F. Naldi, Karsten Urban, Paolo Venini, A wavelet-Galerkin method for elastoplasticity problems, Report 181, RWTH Aachen IGPM, and Math. Modelling and Scient. Computing, vol. 10, 2000]. In this paper the Sinc-Galerkin method is used to solve the straight elasto-plastic rod problem. Due to their exponential convergence rates and their need for a relatively fewer nodal points, Sinc based methods can significantly outperform traditional numerical methods [J. Lund, K.L. Bowers, Sinc Methods for Quadrature and Differential Equations, SIAM, Philadelphia, 1992]. However, the potential of Sinc-based methods for solving elastoplasticity problems has not yet been explored. The aim of this paper is to demonstrate the possible application of Sinc methods through the numerical investigation of the unsteady one dimensional elastic-plastic rod problem.
Solving nonlinear system of third-order boundary value problems using block method
NASA Astrophysics Data System (ADS)
See, Phang Pei; Majid, Zanariah Abdul; Suleiman, Mohamed; Ismail, Fudziah Bt; Othman, Khairil Iskandar
2015-05-01
In this paper, we propose an algorithm of two-point block method to solve the nonlinear system of third-order boundary value problems directly. The proposed method is presented in a simple form of Adams type and two approximate solutions will be obtained simultaneously with the block method using variable step size strategy. The method will be implemented with the multiple shooting technique via the three-step iterative method to generate the missing initial value. Most of the existence method will reduce the third-order boundary value problems to a system of first order equations where the systems of six equations need to be solved. The method we proposed in this paper will solve the third-order boundary value problems directly. Two numerical examples are given to illustrate the efficiency of the proposed method.
Zhang, Songchuan; Xia, Youshen
2016-12-28
Much research has been devoted to complex-variable optimization problems due to their engineering applications. However, the complex-valued optimization method for solving complex-variable optimization problems is still an active research area. This paper proposes two efficient complex-valued optimization methods for solving constrained nonlinear optimization problems of real functions in complex variables, respectively. One solves the complex-valued nonlinear programming problem with linear equality constraints. Another solves the complex-valued nonlinear programming problem with both linear equality constraints and an ℓ₁-norm constraint. Theoretically, we prove the global convergence of the proposed two complex-valued optimization algorithms under mild conditions. The proposed two algorithms can solve the complex-valued optimization problem completely in the complex domain and significantly extend existing complex-valued optimization algorithms. Numerical results further show that the proposed two algorithms have a faster speed than several conventional real-valued optimization algorithms.
ERIC Educational Resources Information Center
DeJong, William; Vehige, Tamara
2008-01-01
The presence of a college or university in a community can greatly enrich the lives of long-term residents, intellectually, culturally, and financially. But students who live, work, and play in nearby neighborhoods can sometimes create enormous problems, putting a strain on campus and community relations and compromising the health and safety of…
It's More than Drinking, Drugs, and Sex: College Student Perceptions of Family Problems
ERIC Educational Resources Information Center
Gorsline, Denise; Holl, Andrea; Pearson, Judy C.; Child, Jeffrey T.
2006-01-01
The colorful misbehavior of college students trumps considerations of college students' relationships with their families. With broad coverage of behaviors such as binge drinking, on-line gambling, and risky sexual behavior, the image of the college student is one of a person worrying about what time the bar opens, rather than problems at home.…
Drugs, Devices, and Desires: A Problem-Based Learning Course in the History of Medicine
ERIC Educational Resources Information Center
Levitt, Sarah; McKeage, Anne; Rangachari, P. K.
2013-01-01
Problem-based learning (PBL) is well suited for courses in the history of medicine, where multiple perspectives exist and information has to be gleaned from different sources. A student, an archivist, and a teacher offer three perspectives about a senior level course where students explored the antecedents and consequences of medical technology.…
Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao
ERIC Educational Resources Information Center
Witkiewitz, Katie; Marlatt, Alan G.
2004-01-01
Relapse prevention, based on the cognitive-behavioral model of relapse, has become an adjunct to the treatment of numerous psychological problems, including (but not limited to) substance abuse, depression, sexual offending, and schizophrenia. This article provides an overview of the efficacy and effectiveness of relapse prevention in the…
Ballard, T Eric; Orozco, Christine C; Obach, R Scott
2014-05-01
The prediction of human drug metabolites using in vitro experiments containing human-derived reagents is an important approach in modern drug research; however, this can be challenging for drugs that are slowly metabolized. In this report, we describe the use of a recently developed human hepatocyte relay method for the purpose of predicting human drug metabolite profiles. Five compounds for which in vivo human metabolism data were available were selected for the investigation of this method, and the results were compared with data gathered in hepatocyte suspensions as well as previous data from a micropatterned hepatocyte coculture method. The hepatocyte relay method demonstrated an improved performance (generation of 75% of human in vivo metabolites) for those drugs for which previous methods showed a relatively low rate of success (50% of human in vivo metabolites). Metabolites included those arising from both oxidative and conjugative reactions and metabolites that required sequential reactions. Two 4-hour relays were shown to adequately generate metabolites, and no further benefit was derived from more relays. Overall, it can be concluded that the hepatocyte relay assay method can be successfully used in the generation of relevant human metabolites, even for challenging drugs.
The FN method for anisotropic scattering in neutron transport theory: the critical slab problem.
NASA Astrophysics Data System (ADS)
Gülecyüz, M. C.; Tezcan, C.
1996-08-01
The FN method which has been applied to many physical problems for isotropic and anisotropic scattering in neutron transport theory is extended for problems for extremely anisotropic scattering. This method depends on the Placzek lemma and the use of the infinite medium Green's function. Here the Green's function for extremely anisotropic scattering which was expressed as a combination of the Green's functions for isotropic scattering is used to solve the critical slab problem. It is shown that the criticality condition is in agreement with the one obtained previously by reducing the transport equation for anisotropic scattering to isotropic scattering and solving using the FN method.
Causal co-expression method with module analysis to screen drugs with specific target.
Yu, Shuhao; Zheng, Lulu; Li, Yixue; Li, Chunyan; Ma, Chenchen; Yu, Yang; Li, Xuan; Hao, Pei
2013-04-10
The considerable increase of investment in research and development by the pharmaceutical industry over the past three decades has not added the number of approved new drugs. An important issue ignored by drug discovery practice is the multi-dimensional interaction network between drugs and their targets. Thus, it is essential to view drug actions through the lens of network biology. In the current study, based on the co-expression network of transcription factors and their downstream genes, we proposed a novel approach, called causal co-expression method with module analysis, to screen drugs with specific target and fewer side effects. We presented a causal co-expression method with module analysis and it could be used in analyzing the microarray data of different drug candidates. At first, the differential wiring value (DW) was calculated to find some causal transcription factors (TFs) by combining with differential expression genes in the regulated networks. After the discovery of the causal TFs, co-expression module analysis method was applied to mine molecular pharmacology pathways around these causal TFs at molecular level. We applied our methods to two drug candidates, Argyrin A and Bortezomib, both with anti-cancer activities. We first obtained some differentially expressed transcription factors of cells treated with Argyrin A or Bortezomib. Nearly all these transcription factors are associated with the tumor suppressor protein p27kip1. Furthermore, module analysis showed that Bortezomib inhibited tumor growth not specifically by cell cycle and cell proliferation pathway, but through many basic metabolic processes which result in cell toxicity. In contrast, Argyrin A had influence on cell cycle, and was involved in DNA damage repair at the same time, showing that Argyrin A was a more suitable drug for anti-cancer treatment. Our study revealed that the causal co-expression method with module analysis was effective and can be used as a tool to evaluate drug
TranScreen-N: Method for rapid screening of trans-ungual drug delivery enhancers.
Murthy, S Narasimha; Vaka, Siva Ram Kiran; Sammeta, Srinivasa Murthy; Nair, Anroop B
2009-11-01
Topical monotherapy of nail diseases such as onychomycosis and nail psoriasis has been less successful due to poor permeability of the human nail plate to topically administered drugs. Chemical enhancers are utilized to improve the drug delivery across the nail plate. Choosing the most effective chemical enhancers for the given drug and formulation is highly critical in determining the efficacy of topical therapy of nail diseases. Screening the large pool of enhancers using currently followed diffusion cell experiments would be tedious and expensive. The main objective of this study is to develop TranScreen-N, a high throughput method of screening trans-ungual drug permeation enhancers. It is a rapid microwell plate based method which involves two different treatment procedures; the simultaneous exposure treatment and the sequential exposure treatment. In the present study, several chemicals were evaluated by TranScreen-N and by diffusion studies in the Franz diffusion cell (FDC). Good agreement of in vitro drug delivery data with TranScreen-N data provided validity to the screening technique. In TranScreen-N technique, the enhancers can be grouped according to whether they need to be applied before or simultaneously with drugs (or by either procedures) to enhance the drug delivery across the nail plate. TranScreen-N technique can significantly reduce the cost and duration required to screen trans-ungual drug delivery enhancers.
Multigrid one shot methods for optimal control problems: Infinite dimensional control
NASA Technical Reports Server (NTRS)
Arian, Eyal; Taasan, Shlomo
1994-01-01
The multigrid one shot method for optimal control problems, governed by elliptic systems, is introduced for the infinite dimensional control space. ln this case, the control variable is a function whose discrete representation involves_an increasing number of variables with grid refinement. The minimization algorithm uses Lagrange multipliers to calculate sensitivity gradients. A preconditioned gradient descent algorithm is accelerated by a set of coarse grids. It optimizes for different scales in the representation of the control variable on different discretization levels. An analysis which reduces the problem to the boundary is introduced. It is used to approximate the two level asymptotic convergence rate, to determine the amplitude of the minimization steps, and the choice of a high pass filter to be used when necessary. The effectiveness of the method is demonstrated on a series of test problems. The new method enables the solutions of optimal control problems at the same cost of solving the corresponding analysis problems just a few times.
Vectorization and parallelization of the finite strip method for dynamic Mindlin plate problems
NASA Technical Reports Server (NTRS)
Chen, Hsin-Chu; He, Ai-Fang
1993-01-01
The finite strip method is a semi-analytical finite element process which allows for a discrete analysis of certain types of physical problems by discretizing the domain of the problem into finite strips. This method decomposes a single large problem into m smaller independent subproblems when m harmonic functions are employed, thus yielding natural parallelism at a very high level. In this paper we address vectorization and parallelization strategies for the dynamic analysis of simply-supported Mindlin plate bending problems and show how to prevent potential conflicts in memory access during the assemblage process. The vector and parallel implementations of this method and the performance results of a test problem under scalar, vector, and vector-concurrent execution modes on the Alliant FX/80 are also presented.
The adaptive problems of female teenage refugees and their behavioral adjustment methods for coping
Mhaidat, Fatin
2016-01-01
This study aimed at identifying the levels of adaptive problems among teenage female refugees in the government schools and explored the behavioral methods that were used to cope with the problems. The sample was composed of 220 Syrian female students (seventh to first secondary grades) enrolled at government schools within the Zarqa Directorate and who came to Jordan due to the war conditions in their home country. The study used the scale of adaptive problems that consists of four dimensions (depression, anger and hostility, low self-esteem, and feeling insecure) and a questionnaire of the behavioral adjustment methods for dealing with the problem of asylum. The results indicated that the Syrian teenage female refugees suffer a moderate degree of adaptation problems, and the positive adjustment methods they have used are more than the negatives. PMID:27175098
Extended ALE Method for fluid-structure interaction problems with large structural displacements
NASA Astrophysics Data System (ADS)
Basting, Steffen; Quaini, Annalisa; Čanić, Sunčica; Glowinski, Roland
2017-02-01
Standard Arbitrary Lagrangian-Eulerian (ALE) methods for the simulation of fluid-structure interaction (FSI) problems fail due to excessive mesh deformations when the structural displacement is large. We propose a method that successfully deals with this problem, keeping the same mesh connectivity while enforcing mesh alignment with the structure. The proposed Extended ALE Method relies on a variational mesh optimization technique, where mesh alignment with the structure is achieved via a constraint. This gives rise to a constrained optimization problem for mesh optimization, which is solved whenever the mesh quality deteriorates. The performance of the proposed Extended ALE Method is demonstrated on a series of numerical examples involving 2D FSI problems with large displacements. Two-way coupling between the fluid and structure is considered in all the examples. The FSI problems are solved using either a Dirichlet-Neumann algorithm, or a Robin-Neumann algorithm. The Dirichlet-Neumann algorithm is enhanced by an adaptive relaxation procedure based on Aitken's acceleration. We show that the proposed method has excellent performance in problems with large displacements, and that it agrees well with a standard ALE method in problems with mild displacement.
Abdela, Ousman Abubeker; Bhagavathula, Akshaya Srikanth; Getachew, Henok; Kelifa, Yohannes
2016-01-01
Background: Cardiovascular diseases (CVDs) are often accompanied with comoribidities and complications leading to taking multiple drugs and thus are more liable to be exposed to drug-related problems (DRPs). DRPs can occur at any stages of medication process from prescription to follow-up treatment. However, a few studies have assessed the specific risk factors for occurrence of at least one potential DRP per patient with CVDs in sub-Saharan African region. Aim: We aim to assess the risk factors for developing potential DRPs in patients with CVDs attending Gondar University Referral Hospital (GUH). Methodology: This was a cross-sectional study. A structured systematic data review was designed focusing on patients with CVDs (both out and inpatients) with age >18 years of both genders attending GUH from April to June 2015. All DRPs were assessed using drugs.com and Medscape. The causes of DRPs were classified using Pharmaceutical Care Network Europe version 6.2. Risk factors that could cause DRPs were assessed using binary logistic regression showing odds ratio with 95% confidential interval. Statistical significance was set at P < 0.05. Results: A total of 227 patients with CVDs were reviewed with a mean age of 52.0 ± 1.7 years. Majority were females (143, 63%), outpatients (133, 58.6%), and diagnosed with heart failure (71, 31.3%). Diuretics (199, 29.5%) were the most commonly prescribed drugs. A total of 265 DRPs were identified, 63.4% of patients have at least one DRP (1.17 ± 1.1). The most common DRPs were found to be an inappropriate selection of drug (36.1%) and dose (24.8%). The most identified risk factors causing DRPs were: Need of additional drug therapy and lack of therapeutic monitoring. Conclusion: The most identified risk factors for developing DRPs were the need of additional drug therapy and lack of therapeutic monitoring. There is a need for clinical pharmacist interventions to monitor and prevent the risk of developing DRPs and contribute to
Bogaert, Petronille; Bochenek, Tomasz; Prokop, Anna; Pilc, Andrzej
2015-01-01
The problem of drug shortages has been reported worldwide, gaining prominence in multiple domains and several countries in recent years. The aim of the study was to analyze, characterise and assess this problem in Belgium and France, while also adopting a wider perspective from the European Union. A qualitative methodological approach was employed, including semi-structured interviews with the representatives of respective national health authorities, pharmaceutical companies and wholesalers, as well as hospital and community pharmacists. The research was conducted in early 2014. Four themes, which were identified through the interviews, were addressed in the paper, i.e. a) defining drug shortages, b) their dynamics and perception, c) their determinants, d) the role of the European and national institutions in coping with the problem. Three groups of determinants of drug shortages were identified throughout this study: manufacturing problems, distribution and supply problems, and problems related to economic aspects. Currently, the Member States of the European Union are striving to resolve the problem very much on their own, although a far more focused and dedicated collaboration may well prove instrumental in coping with drug shortages throughout Europe more effectively. To the best of the authors' knowledge, this is the first qualitative study to investigate the characteristics, key determinants, and the problem drivers of drug shortages, focusing on this particular group of countries, while also adopting the European Union's perspective.
Prokop, Anna; Pilc, Andrzej
2015-01-01
The problem of drug shortages has been reported worldwide, gaining prominence in multiple domains and several countries in recent years. The aim of the study was to analyze, characterise and assess this problem in Belgium and France, while also adopting a wider perspective from the European Union. A qualitative methodological approach was employed, including semi-structured interviews with the representatives of respective national health authorities, pharmaceutical companies and wholesalers, as well as hospital and community pharmacists. The research was conducted in early 2014. Four themes, which were identified through the interviews, were addressed in the paper, i.e. a) defining drug shortages, b) their dynamics and perception, c) their determinants, d) the role of the European and national institutions in coping with the problem. Three groups of determinants of drug shortages were identified throughout this study: manufacturing problems, distribution and supply problems, and problems related to economic aspects. Currently, the Member States of the European Union are striving to resolve the problem very much on their own, although a far more focused and dedicated collaboration may well prove instrumental in coping with drug shortages throughout Europe more effectively. To the best of the authors’ knowledge, this is the first qualitative study to investigate the characteristics, key determinants, and the problem drivers of drug shortages, focusing on this particular group of countries, while also adopting the European Union’s perspective. PMID:25942432
Durbeej, Natalie; Berman, Anne H; Gumpert, Clara H; Palmstierna, Tom; Kristiansson, Marianne; Alm, Charlotte
2010-12-01
Substance abuse is common among offenders. One method widely used for the detection of substance abuse is screening. This study explored the concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) screening tools in relation to (a) substance abuse and dependency diagnoses and (b) three problem severity domains of the sixth version of the Addiction Severity Index in a sample of 181 suspected offenders with signs of mental health problems. The screening tools showed moderate to high accuracy for identification of dependency diagnoses. The AUDIT was associated with alcohol problem severity, whereas the DUDIT was associated with drug and legal problem severity. Administering the screening tools in the current population yields valid results. However, the suggested cutoff scores should be applied with caution due to the discrepancy between present and previous findings.
A Method for the Study of Medical Thinking and Problem Solving.
ERIC Educational Resources Information Center
Elstein, Arthur S.; Shulman, Lee S.
A method for studying medical reasoning in a life-like setting is reported. Simulated medical problems, amplified by concurrent thinking aloud, episodic retrospection during the work-up, and videotape-stimulated retrospection, are used to obtain records of the behavior and reasoning physicians use to solve diagnostic problems. The fundamental…
Implementing a Problem-Based Learning Approach for Teaching Research Methods in Geography
ERIC Educational Resources Information Center
Spronken-Smith, Rachel
2005-01-01
This paper first describes problem-based learning; second describes how a research methods course in geography is taught using a problem-based learning approach; and finally relates student and staff experiences of this approach. The course is run through regular group meetings, two residential field trips and optional skills-based workshops.…
Generator coordinate method and nuclear collective motions: VI on the problem of overcompleteness
Xu Gong-ou
1984-01-01
The problem of overcompleteness in the generator coordinate method is generally studied. It is shown that the effective operator (ON/sup -1/) as a whole excludes the coupling between the physical and unphysical states and the problem of overcompleteness is resolved in this sense. This conclusion is illustrated with an example of boson representations of the SU(6) group.
Peskin, Michael E
2003-02-13
In upper-division undergraduate physics courses, it is desirable to give numerical problem-solving exercises integrated naturally into weekly problem sets. I explain a method for doing this that makes use of the built-in class structure of the Java programming language. I also supply a Java class library that can assist instructors in writing programs of this type.
A modified form of conjugate gradient method for unconstrained optimization problems
NASA Astrophysics Data System (ADS)
Ghani, Nur Hamizah Abdul; Rivaie, Mohd.; Mamat, Mustafa
2016-06-01
Conjugate gradient (CG) methods have been recognized as an interesting technique to solve optimization problems, due to the numerical efficiency, simplicity and low memory requirements. In this paper, we propose a new CG method based on the study of Rivaie et al. [7] (Comparative study of conjugate gradient coefficient for unconstrained Optimization, Aus. J. Bas. Appl. Sci. 5(2011) 947-951). Then, we show that our method satisfies sufficient descent condition and converges globally with exact line search. Numerical results show that our proposed method is efficient for given standard test problems, compare to other existing CG methods.
NASA Astrophysics Data System (ADS)
Wang, Qian; Li, Xingwen; Song, Haoyong; Rong, Mingzhe
2010-04-01
Non-contact magnetic measurement method is an effective way to study the air arc behavior experimentally One of the crucial techniques is to solve an inverse problem for the electromagnetic field. This study is devoted to investigating different algorithms for this kind of inverse problem preliminarily, including the preconditioned conjugate gradient method, penalty function method and genetic algorithm. The feasibility of each algorithm is analyzed. It is shown that the preconditioned conjugate gradient method is valid only for few arc segments, the estimation accuracy of the penalty function method is dependent on the initial conditions, and the convergence of genetic algorithm should be studied further for more segments in an arc current.
Drugs of abuse detection in saliva based on actuated optical method
NASA Astrophysics Data System (ADS)
Shao, Jie; Li, Zhenyu; Jiang, Hong; Wang, Wenlong; Wu, Yixuan
2014-12-01
There has been a considerable increase in the abuse of drugs during the past decade. Combing drug use with driving is very dangerous. More than 11% of drivers in a roadside survey tested positive for drugs, while 18% of drivers killed in accidents tested positive for drugs as reported in USA, 2007. Toward developing a rapid drug screening device, we use saliva as the sample, and combining the traditional immunoassays method with optical magnetic technology. There were several methods for magnetic nanoparticles detection, such as magnetic coils, SQUID, microscopic imaging, and Hall sensors. All of these methods were not suitable for our demands. By developing a novel optical scheme, we demonstrate high-sensitivity detection in saliva. Drugs of abuse are detected at sub-nano gram per milliliter levels in less than 120 seconds. Evanescent wave principle has been applied to sensitively monitor the presence of magnetic nanoparticles on the binding surface. Like the total internal reflection fluorescence microscope (TIRFM), evanescent optical field is generated at the plastic/fluid interface, which decays exponentially and penetrates into the fluid by only a sub-wavelength distance. By disturbance total internal reflection with magnetic nanoparticles, the optical intensity would be influenced. We then detected optical output by imaging the sensor surface onto a CCD camera. We tested four drugs tetrahydrocannabinol (THC), methamphetamine (MAMP), ketamine (KET), morphine (OPI), using this technology. 100 ng mL-1 sensitivity was achieved, and obvious evidence showed that this results could be improved in further researches.
Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs
Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan
2016-01-01
With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs. PMID:27455239
Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs.
Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan
2016-07-21
With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs.
Microparticles Produced by the Hydrogel Template Method for Sustained Drug Delivery
Lu, Ying; Sturek, Michael; Park, Kinam
2014-01-01
Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles. PMID:24333903
GenStar: A method for de novo drug design
NASA Astrophysics Data System (ADS)
Rotstein, Sergio H.; Murcko, Mark A.
1993-02-01
A novel method, which we call GenStar, has been developed to suggest chemically reasonable structures which fill the active sites of enzymes. The proposed molecules provide good steric contact with the enzyme and exist in low-energy conformations. These structures are composed entirely of sp3 carbons which are grown sequentially, but which can also branch or form rings. User-selected enzyme seed atoms may be used to determine the area in which structure generation begins. Alternatively, GenStar may begin with a predocked `inhibitor core' from which atoms are grown. For each new atom generated by the program, several hundred candidate positions representing a range of reasonable bond lengths, bond angles, and torsion angles are considered. Each of these candidates is scored, based on a simple enzyme contact model. The selected position is chosen at random from among the highest scoring cases. Duplicate structures may be removed using a variety of criteria. The compounds may be energy minimized and displayed using standard modeling programs. Also, it is possible to analyze the collection of all structures created by GenStar and locate binding motifs for common fragments such as benzene and naphthylene. Tests of the method using HIV protease, FK506 binding protein (FKBP-12) and human carbonic anhydrase (HCA-II) demonstrated that structures similar to known potent inhibitors may be generated with GenStar.
Gim, Suzanna
2013-01-01
Objectives. To determine which teaching method in a drug-induced diseases and clinical toxicology course was preferred by students and whether their preference correlated with their learning of drug-induced diseases. Design. Three teaching methods incorporating active-learning exercises were implemented. A survey instrument was developed to analyze students’ perceptions of the active-learning methods used and how they compared to the traditional teaching method (lecture). Examination performance was then correlated to students’ perceptions of various teaching methods. Assessment. The majority of the 107 students who responded to the survey found traditional lecture significantly more helpful than active-learning methods (p=0.01 for all comparisons). None of the 3 active-learning methods were preferred over the others. No significant correlations were found between students’ survey responses and examination performance. Conclusions. Students preferred traditional lecture to other instructional methods. Learning was not influenced by the teaching method or by preference for a teaching method. PMID:23966726
A numerical study of hybrid optimization methods for the molecular conformation problems
Meza, J.C.; Martinez, M.L.
1993-05-01
An important area of research in computational biochemistry is the design of molecules for specific applications. The design of these molecules depends on the accurate determination of their three-dimensional structure or conformation. Under the assumption that molecules will settle into a configuration for which their energy is at a minimum, this design problem can be formulated as a global optimization problem. The solution of the molecular conformation problem can then be obtained, at least in principle, through any number of optimization algorithms. Unfortunately, it can easily be shown that there exist a large number of local minima for most molecules which makes this an extremely difficult problem for any standard optimization method. In this study, we present results for various optimization algorithms applied to a molecular conformation problem. We include results for genetic algorithms, simulated annealing, direct search methods, and several gradient methods. The major result of this study is that none of these standard methods can be used in isolation to efficiently generate minimum energy configurations. We propose instead several hybrid methods that combine properties of several local optimization algorithms. These hybrid methods have yielded better results on representative test problems than single methods.
A Network Flow-Based Method to Predict Anticancer Drug Sensitivity
Qin, Yufang; Chen, Ming; Wang, Haiyun; Zheng, Xiaoqi
2015-01-01
Predicting anticancer drug sensitivity can enhance the ability to individualize patient treatment, thus making development of cancer therapies more effective and safe. In this paper, we present a new network flow-based method, which utilizes the topological structure of pathways, for predicting anticancer drug sensitivities. Mutations and copy number alterations of cancer-related genes are assumed to change the pathway activity, and pathway activity difference before and after drug treatment is used as a measure of drug response. In our model, Contributions from different genetic alterations are considered as free parameters, which are optimized by the drug response data from the Cancer Genome Project (CGP). 10-fold cross validation on CGP data set showed that our model achieved comparable prediction results with existing elastic net model using much less input features. PMID:25992881
High Order And High Resolution Methods For a Model CAA Problem
NASA Technical Reports Server (NTRS)
Goodrich, John W.
2004-01-01
The initial value problem for the first order linear wave equation in one space dimension is treated for two cases with specified initial data and grid, and data from solutions at t = 400 and t = 800 are presented, as prescribed for Problem 1 in Category 1. Results are shown from computations with a sequence of recently developed high order and high resolution methods which combine Hermite interpolation, Cauchy-Kowaleskya recursion for time derivatives, and Taylor series time advancement. These methods have the same order of accuracy in time as in space. Results are shown from methods that range from third to nineteenth order. The stated problems with the prescribed coarse grid can be simulated with errors that are at the level of machine accuracy if the method is sufficiently high order. In addition, the growth of the maximum absolute error out to t = 100,000 is given for simulations with the stated problem data.
A Bio-Inspired Method for the Constrained Shortest Path Problem
Wang, Hongping; Lu, Xi; Wang, Qing
2014-01-01
The constrained shortest path (CSP) problem has been widely used in transportation optimization, crew scheduling, network routing and so on. It is an open issue since it is a NP-hard problem. In this paper, we propose an innovative method which is based on the internal mechanism of the adaptive amoeba algorithm. The proposed method is divided into two parts. In the first part, we employ the original amoeba algorithm to solve the shortest path problem in directed networks. In the second part, we combine the Physarum algorithm with a bio-inspired rule to deal with the CSP. Finally, by comparing the results with other method using an examples in DCLC problem, we demonstrate the accuracy of the proposed method. PMID:24959603
A bio-inspired method for the constrained shortest path problem.
Wang, Hongping; Lu, Xi; Zhang, Xiaoge; Wang, Qing; Deng, Yong
2014-01-01
The constrained shortest path (CSP) problem has been widely used in transportation optimization, crew scheduling, network routing and so on. It is an open issue since it is a NP-hard problem. In this paper, we propose an innovative method which is based on the internal mechanism of the adaptive amoeba algorithm. The proposed method is divided into two parts. In the first part, we employ the original amoeba algorithm to solve the shortest path problem in directed networks. In the second part, we combine the Physarum algorithm with a bio-inspired rule to deal with the CSP. Finally, by comparing the results with other method using an examples in DCLC problem, we demonstrate the accuracy of the proposed method.
ERIC Educational Resources Information Center
Schenk, H.
1979-01-01
Presents a simple way to introduce Direct Methods program systems to solve phase problems in x-ray crystal structure determination. It is intended for the undergraduate chemistry student laboratory. (Author/SA)
Advanced computational methods for nodal diffusion, Monte Carlo, and S{sub n} problems. Final Report
1994-12-31
The work addresses basic computational difficulties that arise in the numerical simulation of neutral particle radiation transport: discretized radiation transport problems, iterative methods, selection of parameters, and extension of current algorithms.
NASA Astrophysics Data System (ADS)
Zhadan, V. G.
2016-07-01
The linear semidefinite programming problem is considered. The dual affine scaling method in which all current iterations belong to the feasible set is proposed for its solution. Moreover, the boundaries of the feasible set may be reached. This method is a generalization of a version of the affine scaling method that was earlier developed for linear programs to the case of semidefinite programming.
Boundary Value Technique for Initial Value Problems Based on Adams-Type Second Derivative Methods
ERIC Educational Resources Information Center
Jator, S. N.; Sahi, R. K.
2010-01-01
In this article, we propose a family of second derivative Adams-type methods (SDAMs) of order up to 2k + 2 ("k" is the step number) for initial value problems. The methods are constructed through a continuous approximation of the SDAM which is obtained by multistep collocation. The continuous approximation is used to obtain initial value methods,…
On Numerical Methods of Solving Some Optimal Path Problems on the Plane
NASA Astrophysics Data System (ADS)
Ushakov, V. N.; Matviychuk, A. R.; Malev, A. G.
Three numerical methods of solution of some time optimal control problems for a system under phase constraints are described in the paper. Two suggested methods are based on transition to the discrete time model, constructing attainability sets and application of the guide construction. The third method is based on the Deikstra algorithm.
NASA Astrophysics Data System (ADS)
Pospelov, A. I.
2016-08-01
Adaptive methods for the polyhedral approximation of the convex Edgeworth-Pareto hull in multiobjective monotone integer optimization problems are proposed and studied. For these methods, theoretical convergence rate estimates with respect to the number of vertices are obtained. The estimates coincide in order with those for filling and augmentation H-methods intended for the approximation of nonsmooth convex compact bodies.
Modified Chebyshev-Picard Iteration Methods for Solution of Boundary Value Problems
NASA Astrophysics Data System (ADS)
Bai, Xiaoli; Junkins, John L.
2011-10-01
Modified Chebyshev-Picard iteration methods are presented for solving boundary value problems. Chebyshev polynomials are used to approximate the state trajectory in Picard iterations, while the boundary conditions are maintained by constraining the coefficients of the Chebyshev polynomials. Using Picard iteration and Clenshaw-Curtis quadrature, the presented methods iteratively refine an orthogonal function approximation of the entire state trajectory, in contrast to step-wise, forward integration approaches, which render the methods well-suited for parallel computation because computation of force functions along each path iteration can be rigorously distributed over many parallel cores with negligible cross communication needed. The presented methods solve optimal control problems through Pontryagin's principle without requiring shooting methods or gradient information. The methods are demonstrated to be computationally efficient and strikingly accurate when compared with Battin's method for a classical Lambert's problem and with a Chebyshev pseudospectral method for an optimal trajectory design problem. The reported simulation results obtained on a serial machine suggest a strong basis for optimism of using the presented methods for solving more challenging boundary value problems, especially when highly parallel architectures are fully exploited.
A Cubic Radial Basis Function in the MLPG Method for Beam Problems
NASA Technical Reports Server (NTRS)
Raju, I. S.; Phillips, D. R.
2002-01-01
A non-compactly supported cubic radial basis function implementation of the MLPG method for beam problems is presented. The evaluation of the derivatives of the shape functions obtained from the radial basis function interpolation is much simpler than the evaluation of the moving least squares shape function derivatives. The radial basis MLPG yields results as accurate or better than those obtained by the conventional MLPG method for problems with discontinuous and other complex loading conditions.
Methods for Improving the Tractability of the Block Sequencing Problem for Open Pit Mining
2008-07-01
severely alter the ultimate pit. Dynamic programming methods use intelligent enumeration to determine the ultimate pit limits. Lerchs and Grossman (1965...ultimate pit limits problem, Lerchs and Grossman (1965) model an open pit mine as a weighted, directed graph where vertices represent blocks and arcs...Zhao and Kim (1992) use a similar approach with some modifications that they claim solve problem instances faster than the Lerchs and Grossman method
A boundary element alternating method for two-dimensional mixed-mode fracture problems
NASA Technical Reports Server (NTRS)
Raju, I. S.; Krishnamurthy, T.
1992-01-01
A boundary element alternating method, denoted herein as BEAM, is presented for two dimensional fracture problems. This is an iterative method which alternates between two solutions. An analytical solution for arbitrary polynomial normal and tangential pressure distributions applied to the crack faces of an embedded crack in an infinite plate is used as the fundamental solution in the alternating method. A boundary element method for an uncracked finite plate is the second solution. For problems of edge cracks a technique of utilizing finite elements with BEAM is presented to overcome the inherent singularity in boundary element stress calculation near the boundaries. Several computational aspects that make the algorithm efficient are presented. Finally, the BEAM is applied to a variety of two dimensional crack problems with different configurations and loadings to assess the validity of the method. The method gives accurate stress intensity factors with minimal computing effort.
A penalty method for PDE-constrained optimization in inverse problems
NASA Astrophysics Data System (ADS)
van Leeuwen, T.; Herrmann, F. J.
2016-01-01
Many inverse and parameter estimation problems can be written as PDE-constrained optimization problems. The goal is to infer the parameters, typically coefficients of the PDE, from partial measurements of the solutions of the PDE for several right-hand sides. Such PDE-constrained problems can be solved by finding a stationary point of the Lagrangian, which entails simultaneously updating the parameters and the (adjoint) state variables. For large-scale problems, such an all-at-once approach is not feasible as it requires storing all the state variables. In this case one usually resorts to a reduced approach where the constraints are explicitly eliminated (at each iteration) by solving the PDEs. These two approaches, and variations thereof, are the main workhorses for solving PDE-constrained optimization problems arising from inverse problems. In this paper, we present an alternative method that aims to combine the advantages of both approaches. Our method is based on a quadratic penalty formulation of the constrained optimization problem. By eliminating the state variable, we develop an efficient algorithm that has roughly the same computational complexity as the conventional reduced approach while exploiting a larger search space. Numerical results show that this method indeed reduces some of the nonlinearity of the problem and is less sensitive to the initial iterate.
Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility.
Knopp, Matthias Manne; Tajber, Lidia; Tian, Yiwei; Olesen, Niels Erik; Jones, David S; Kozyra, Agnieszka; Löbmann, Korbinian; Paluch, Krzysztof; Brennan, Claire Marie; Holm, René; Healy, Anne Marie; Andrews, Gavin P; Rades, Thomas
2015-09-08
In this study, a comparison of different methods to predict drug-polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug-polymer solubility at 25 °C was predicted using the Flory-Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine-PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug-polymer solubility.
One algorithm for branch and bound method for solving concave optimization problem
NASA Astrophysics Data System (ADS)
Andrianova, A. A.; Korepanova, A. A.; Halilova, I. F.
2016-11-01
The article describes the algorithm for branch and bound method for solving the concave programming problem, which is based on the idea of similarity the necessary and sufficient conditions of optimum for the original problem and for a convex programming problem with another feasible set and reverse the sign of the objective function. To find the feasible set of the equivalent convex programming problem we construct an algorithm using the idea of the branch and bound method. We formulate various branching techniques and discusses the construction of the lower objective function evaluations for the node of the decision tree. The article discusses the results of experiments of this algorithm for some famous test problems of a particular form.
Using a derivative-free optimization method for multiple solutions of inverse transport problems
Armstrong, Jerawan C.; Favorite, Jeffrey A.
2016-01-14
Identifying unknown components of an object that emits radiation is an important problem for national and global security. Radiation signatures measured from an object of interest can be used to infer object parameter values that are not known. This problem is called an inverse transport problem. An inverse transport problem may have multiple solutions and the most widely used approach for its solution is an iterative optimization method. This paper proposes a stochastic derivative-free global optimization algorithm to find multiple solutions of inverse transport problems. The algorithm is an extension of a multilevel single linkage (MLSL) method where a mesh adaptive direct search (MADS) algorithm is incorporated into the local phase. Furthermore, numerical test cases using uncollided fluxes of discrete gamma-ray lines are presented to show the performance of this new algorithm.
Using a derivative-free optimization method for multiple solutions of inverse transport problems
Armstrong, Jerawan C.; Favorite, Jeffrey A.
2016-01-14
Identifying unknown components of an object that emits radiation is an important problem for national and global security. Radiation signatures measured from an object of interest can be used to infer object parameter values that are not known. This problem is called an inverse transport problem. An inverse transport problem may have multiple solutions and the most widely used approach for its solution is an iterative optimization method. This paper proposes a stochastic derivative-free global optimization algorithm to find multiple solutions of inverse transport problems. The algorithm is an extension of a multilevel single linkage (MLSL) method where a meshmore » adaptive direct search (MADS) algorithm is incorporated into the local phase. Furthermore, numerical test cases using uncollided fluxes of discrete gamma-ray lines are presented to show the performance of this new algorithm.« less