WorldWideScience

Sample records for rational drug development

  1. RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

    OpenAIRE

    YEŞİLADA, Akgül; ÖZKANLI, Fügen

    2004-01-01

    In this review, after a short introduction to definition and physiological roles of regulatory peptides, problems faced during the development of peptide drugs, studies directed to solve these problems and rational design of peptide drugs with special emphesis on peptidomimetics are mentioned

  2. Rationality and drug use: an experimental approach.

    Science.gov (United States)

    Blondel, Serge; Lohéac, Youenn; Rinaudo, Stéphane

    2007-05-01

    In rational addiction theory, higher discount rates encourage drug use. We test this hypothesis in the general framework of rationality and behaviour under risk. We do so using an experimental design with real monetary incentives. The decisions of 34 drug addicts are compared with those of a control group. The decisions of drug users (DU) are not any less consistent with standard theories of behaviour over time and under risk. Further, there is no difference in the estimated discount rate between drug users and the control group, but the former do appear to be more risk-seeking.

  3. Rational drug use--evaluation of a training programme for interns.

    Science.gov (United States)

    Natu, M V; Zachariah, P; Zachariah, A; Chand, S; Singh, T; Choudhry, K

    1995-09-01

    A workshop covering various aspects of rational drug use was conducted for interns of Christian Medical College, Ludhiana. Evaluation of the workshop revealed that it was able to bring about an attitudinal change regarding rational drug use. The methodology and evaluation procedures have been described. It is suggested that similar attempts should be made at all medical colleges so that every graduate enters medical practice with a positive attitude towards rational drug use.

  4. Rational drug design paradigms: the odyssey for designing better drugs.

    Science.gov (United States)

    Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

    2015-01-01

    Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

  5. Rational Drug Use of Nurses

    Directory of Open Access Journals (Sweden)

    Mehtap Sahingoz

    2013-02-01

    Full Text Available ABSTRACT Objective: At this study to be aimed to assess status of the knowledge of nurses who working in public and private health institutions in Sivas province use of medication fort he treatment during their illnesses and patients and the attitudes of rational drug application. Matherials and methods: the researc planned to attend 750 nurses but it has been completed with participation of 641 nurses (Reaching rate 85,5%. This is a descriptive and cross-sectional study. in the study data were collected with a questionaire, percentages stated and chi square test was used for analysis. Results: %95,3 of nurses were females and mean age of them 29.21±4.85 years. The rate of contacting a doktor in case of illness is higher in 39.1% of nurses in the 21-30 age group and 48.6% of nurses working in primary care institutions. The level of self-treating is higher in 45.5 % of nurses working less than a year in profession .In the case of illness, 53% of nurses stated that they had left the medicine when signs of disease over. %98.8 of nurses expressed that they know effects of drugs used and 99.1% of them stated they know the side effects of drugs used. The entire group of postgraduate education status stated that they have not received the drug recommended by others. The level of suggesting a drug to someone else fort he same disease is higher in 65.8% of the group 31 years and older and group working over 40 hours per week. It were determined that used in consultation with the physician 65.2% of nurses antibiotics, 87.5% of them weiht loss drug and 82.7% of them contraceptive . 99.5% of the nurses have expressed that they inform to patients about use of their medications. Among the issues that expressed informations took place the application form of drugs (51.0 %and information of need to consult one if deemed one unexpected effect (59.6% . Also has been identified that of nurses acquired inform about drugs from drug book (vademecum (87.5 % and they

  6. [Rational drug use: an economic approach to decision making].

    Science.gov (United States)

    Mota, Daniel Marques; da Silva, Marcelo Gurgel Carlos; Sudo, Elisa Cazue; Ortún, Vicente

    2008-04-01

    The present article approaches rational drug use (RDU) from the economical point of view. The implementation of RDU implies in costs and involves acquisition of knowledge and behavioral changes of several agents. The difficulties in implementing RDU may be due to shortage problems, information asymmetry, lack of information, uncertain clinical decisions, externalities, time-price, incentives for drug prescribers and dispensers, drug prescriber preferences and marginal utility. Health authorities, among other agencies, must therefore regularize, rationalize and control drug use to minimize inefficiency in pharmaceutical care and to prevent exposing the population to unnecessary health risks.

  7. Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

    Directory of Open Access Journals (Sweden)

    Charles H. Williams

    2011-04-01

    Full Text Available In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.

  8. An Outreach Program in Drug Education; Teaching a Rational Approach to Drug Use

    Science.gov (United States)

    Sorensen, James L.; Joffe, Stephen J.

    1975-01-01

    Aimed at encouraging rational decision making about drug use, a peer oriented drug education program was conducted in a community youth project. Youth and leaders shared feelings and knowledge about drugs. Compared with four program dropouts, six participants exhibited more positive attitudes toward the drug group, its leaders and themselves.…

  9. System of Objectified Judgement Analysis (SOJA) as a tool in rational and transparent drug-decision making.

    Science.gov (United States)

    Janknegt, Robert; Scott, Mike; Mairs, Jill; Timoney, Mark; McElnay, James; Brenninkmeijer, Rob

    2007-10-01

    Drug selection should be a rational process that embraces the principles of evidence-based medicine. However, many factors may affect the choice of agent. It is against this background that the System of Objectified Judgement Analysis (SOJA) process for rational drug-selection was developed. This article describes how the information on which the SOJA process is based, was researched and processed.

  10. From machine learning to deep learning: progress in machine intelligence for rational drug discovery.

    Science.gov (United States)

    Zhang, Lu; Tan, Jianjun; Han, Dan; Zhu, Hao

    2017-11-01

    Machine intelligence, which is normally presented as artificial intelligence, refers to the intelligence exhibited by computers. In the history of rational drug discovery, various machine intelligence approaches have been applied to guide traditional experiments, which are expensive and time-consuming. Over the past several decades, machine-learning tools, such as quantitative structure-activity relationship (QSAR) modeling, were developed that can identify potential biological active molecules from millions of candidate compounds quickly and cheaply. However, when drug discovery moved into the era of 'big' data, machine learning approaches evolved into deep learning approaches, which are a more powerful and efficient way to deal with the massive amounts of data generated from modern drug discovery approaches. Here, we summarize the history of machine learning and provide insight into recently developed deep learning approaches and their applications in rational drug discovery. We suggest that this evolution of machine intelligence now provides a guide for early-stage drug design and discovery in the current big data era. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The importance the pharmacist for rational use of drugs in children and teenagers

    Directory of Open Access Journals (Sweden)

    Regiane Cristina dos Santos Moreira Borges

    2013-01-01

    Full Text Available Medication use without orientation can cause damage, especially among children and teenagers. The World Health Organization (WHO recommends actions to encourage the rational drug use and the Pharmacist is pointed as an important health educator. The goal was to identify the profile of medication use in children and adolescents and discuss the role of pharmacists to promote the rational drug use. A cross-sectional epidemiological study was conducted in three schools in the urban area of Extrema-MG, Brazil. The study included 525 children and adolescents between 0 and 18 years who completed a questionnaire about drug use with their parents or guardians. Children and adolescents who participated in the study, 58.5% reported using drugs in the last 6 months. Most understood the indications of the drugs used. The main causes for the purchase of non-prescription drugs were headache, colds and flu, sore throat and cough. Only a small proportion (7.0% said they do not use "drugs" without prescription. Most have heard about the rational use of medicines (57.5% and seeks the help of the pharmacist for the purchase of OTC drugs ever (57.3% or sometimes (25.1%. The importance of the pharmacist to rational drug use was confirmed by the usage profile observed. Only a minority used only with prescription drugs and most calls for help from the pharmacist to buy non-prescription medicines.

  12. THE IMPORTANCE THE PHARMACIST FOR RATIONAL USE OF DRUGS IN CHILDREN AND TEENAGERS

    Directory of Open Access Journals (Sweden)

    Regiane Cristina dos Santos Moreira Borges

    2013-05-01

    Full Text Available Medication use without orientation can cause damage, especially among children and teenagers. The World Health Organization (WHO recommends actions to encourage the rational drug use and the Pharmacist is pointed as an important health educator. The goal was to identify the profile of medication use in children and adolescents and discuss the role of pharmacists to promote the rational drug use. A cross-sectional epidemiological study was conducted in three schools in the urban area of Extrema-MG, Brazil. The study included 525 children and adolescents between 0 and 18 years who completed a questionnaire about drug use with their parents or guardians. Children and adolescents who participated in the study, 58.5% reported using drugs in the last 6 months. Most understood the indications of the drugs used. The main causes for the purchase of non-prescription drugs were headache, colds and flu, sore throat and cough. Only a small proportion (7.0% said they do not use "drugs" without prescription. Most have heard about the rational use of medicines (57.5% and seeks the help of the pharmacist for the purchase of OTC drugs ever (57.3% or sometimes (25.1%. The importance of the pharmacist to rational drug use was confirmed by the usage profile observed. Only a minority used only with prescription drugs and most calls for help from the pharmacist to buy nonprescription medicines.

  13. Effecting attitudinal change towards rational drug use.

    Science.gov (United States)

    Singh, T; Natu, M V

    1995-01-01

    Attitudes of 40 interns towards rational drug use (RDU) were assessed, using a standardized Likert type scale. The assessment was repeated after 4 months to evaluate the effect of usual working conditions of the hospital. After this period, the attitudes had slided towards negative side (p attitudes of test group returned towards positive side (p attitudes.

  14. Rational Development of Addiction Pharmacotherapies: Successes, Failures, and Prospects

    OpenAIRE

    Christopher Pierce, R.; O’Brien, Charles P.; Kenny, Paul J.; Vanderschuren, Louk J. M. J.

    2012-01-01

    There are currently effective, U.S. Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid addiction. In some cases these therapeutics were rationally designed and tested using a combination of various animal models of addiction. In many cases, however, effective drug therapies for addiction were derived from the testing of compounds developed for other CNS disorders (e.g., analgesics and antidepressants), which were tested clinically in the absence of prior a...

  15. Multi-target drugs: the trend of drug research and development.

    Science.gov (United States)

    Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao

    2012-01-01

    Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.

  16. Differentiating drugs by harm potential: the rational versus the feasible.

    Science.gov (United States)

    Kalant, H

    1999-01-01

    In an ideal harm reduction model, drugs would be ranked according to their potential to cause harm, with varying implications for control policies and interventions. In such a public health oriented approach, the maximum protection of the public from harm would be balanced with the least possible restriction of freedom. In reality, however, the accuracy and completeness of the necessary information for such a ranking is highly limited. Many other factors not readily incorporated in a rational model, such as values, beliefs, and traditions, also affect drug policy decisions. Thus, rather than relying on acquisition of the necessary knowledge, it may be preferable to focus efforts on developing effective nonlegal measures to reduce drug use and harm. [Translations are provided in the International Abstracts Section of this issue.

  17. Rational drug therapy education in clinical phase carried out by task-based learning

    Science.gov (United States)

    Bilge, S. Sırrı; Akyüz, Bahar; Ağrı, Arzu Erdal; Özlem, Mıdık

    2017-01-01

    Objectives: Irrational drug use results in drug interactions, treatment noncompliance, and drug resistance. Rational pharmacotherapy education is being implemented in many faculties of medicine. Our aim is to introduce rational pharmacotherapy education by clinicians and to evaluate task-based rational drug therapy education in the clinical context. Methods: The Kirkpatrick's evaluation model was used for the evaluation of the program. The participants evaluated the program in terms of constituents of the program, utilization, and contribution to learning. Voluntary participants responded to the evaluation forms after the educational program. Data are evaluated using both quantitative and qualitative tools. SPSS (version 21) used for quantitative data for determining mean and standard deviation values. Descriptive qualitative analysis approach is used for the analysis of open-ended questions. Results: It was revealed that the program and its components have been favorable. A total 95.9% of the students consider the education to be beneficial. Simulated patients practice and personal drug choice/problem-based learning sessions were appreciated by the students in particular. 93.9% of the students stated that all students of medicine should undergo this educational program. Among the five presentations contained in the program, “The Principles of Prescribing” received the highest points (9 ± 1.00) from participating students in general evaluation of the educational program. Conclusion: This study was carried out to improve task-based rational drug therapy education. According to feedback from the students concerning content, method, resource, assessment, and program design; some important changes, especially in number of facilitators and indications, are made in rational pharmacotherapy education in clinical task-based learning program. PMID:28458432

  18. [Rational use of psychotropic drugs and social communication role].

    Science.gov (United States)

    Montero, F

    1994-06-01

    Extra-clinical factors about the influences affecting the prescription and use of drugs are reviewed. Special attention is given to regulatory agencies, the pharmaceutical industry, and mass media. The problems and public health consequences of the irrational use of drugs are rarely documented in Latin America. Analysis of these factors, information sources, and rational use of psychotropic drugs will require multiple strategies such as social communication and policy formulation to define goals and objectives related to population information, doctors' and individual citizens' decision making processes, and participation of consumers in improving the use of psychotropic drugs.

  19. Emerging Computational Methods for the Rational Discovery of Allosteric Drugs.

    Science.gov (United States)

    Wagner, Jeffrey R; Lee, Christopher T; Durrant, Jacob D; Malmstrom, Robert D; Feher, Victoria A; Amaro, Rommie E

    2016-06-08

    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.

  20. [Why rational drug use must be a priority?].

    Science.gov (United States)

    de Aquino, Daniela Silva L

    2008-04-01

    According to the World Health Organization, rational drug use means that patients receive medicines appropriate to their clinical needs, in doses that meet their individual requirements, for an adequate period of time, and at the lowest cost to them and their community. However, as far as one can see, the reality is very different. In Brazil, at least, 35% of medicines are purchased for self-medication. Medicaments are responsible for 27% of intoxications in Brazil and for 16% of deaths due to poisoning are caused by medicaments. Moreover, 50% of medicaments are prescribed, dispensed or used inappropriately and hospitals spend about 15 to 20% of their budgets to deal with the troubles caused by misuse of medicaments. The promise of immediate relief of suffering is a very attractive appeal, but it has its price. Sometimes the price we pay is our health. Rational drug use requires a very complex logical chain involving a number of variables and participation of different social actors including patients, health professionals, legislators, policy makers, industry, commerce and the government.

  1. Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

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    de Witte, Wilhelmus E A; Wong, Yin Cheong; Nederpelt, Indira; Heitman, Laura H; Danhof, Meindert; van der Graaf, Piet H; Gilissen, Ron A H J; de Lange, Elizabeth C M

    2016-01-01

    Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics. In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles. More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.

  2. Unpredictable drug shortages: an ethical framework for short-term rationing in hospitals.

    Science.gov (United States)

    Rosoff, Philip M

    2012-01-01

    Periodic and unexpected shortages of drugs, biologics, and even medical devices have become commonplace in the United States. When shortages occur, hospitals and clinics need to decide how to ration their available stock. When such situations arise, institutions can choose from several different allocation schemes, such as first-come, first-served, a lottery, or a more rational and calculated approach. While the first two approaches sound reasonable at first glance, there are a number of problems associated with them, including the inability to make fine, individual patient-centered decisions. They also do not discriminate between what kinds of patients and what types of uses may be more deserving or reasonable than others. In this article I outline an ethically acceptable procedure for rationing drugs during a shortage in which demand outstrips supply.

  3. Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin.

    Science.gov (United States)

    Judy, Eva; Pagariya, Darshna; Kishore, Nand

    2018-03-20

    Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

  4. Quality medicines for the poor: experience of the Delhi programme on rational use of drugs.

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    Chaudhury, R Roy; Parameswar, R; Gupta, U; Sharma, S; Tekur, U; Bapna, J S

    2005-03-01

    Prior to 1994, most Delhi hospitals and dispensaries experienced constant shortages of essential medicines. There was erratic prescribing of expensive branded products, frequent complaints about poor drug quality and low patient satisfaction. Delhi took the lead in developing a comprehensive Drug Policy in 1994 and was the only Indian state to have such a comprehensive policy. The policy's main objective is to improve the availability and accessibility of quality essential drugs for all those in need. The Delhi Society for the Promotion of Rational Use of Drugs (DSPRUD), a non-governmental organization, worked in close collaboration with the Delhi Government and with universities to implement various components of the policy. The first Essential Drugs List (EDL) was developed, a centralized pooled procurement system was set up and activities promoting rational use of drugs were initiated. In 1997, the Delhi Programme was designated the INDIA-WHO Essential Drugs Programme by the World Health Organization. The EDL was developed by a committee consisting of a multidisciplinary group of experts using balanced criteria of efficacy, safety, suitability and cost. The first list contained 250 drugs for hospitals and 100 drugs for dispensaries; the list is revised every 2 years. The pooled procurement system, including the rigorous selection of suppliers with a minimum annual threshold turnover and the introduction of Good Manufacturing Practice inspections, resulted in the supply of good quality drugs and in holding down the procurement costs of many drugs. Bulk purchasing of carefully selected essential drugs was estimated to save nearly 30% of the annual drugs bill for the Government of Delhi, savings which were mobilized for procuring more drugs, which in turn improved availability of drugs (more than 80%) at health facilities. Further, training programmes for prescribers led to a positive change in prescribing behaviour, with more than 80% of prescriptions being from

  5. Rational optimization of drug-target residence time: Insights from inhibitor binding to the S. aureus FabI enzyme-product complex

    Science.gov (United States)

    Chang, Andrew; Schiebel, Johannes; Yu, Weixuan; Bommineni, Gopal R.; Pan, Pan; Baxter, Michael V.; Khanna, Avinash; Sotriffer, Christoph A.; Kisker, Caroline; Tonge, Peter J.

    2013-01-01

    Drug-target kinetics has recently emerged as an especially important facet of the drug discovery process. In particular, prolonged drug-target residence times may confer enhanced efficacy and selectivity in the open in vivo system. However, the lack of accurate kinetic and structural data for series of congeneric compounds hinders the rational design of inhibitors with decreased off-rates. Therefore, we chose the Staphylococcus aureus enoyl-ACP reductase (saFabI) - an important target for the development of new anti-staphylococcal drugs - as a model system to rationalize and optimize the drug-target residence time on a structural basis. Using our new, efficient and widely applicable mechanistically informed kinetic approach, we obtained a full characterization of saFabI inhibition by a series of 20 diphenyl ethers complemented by a collection of 9 saFabI-inhibitor crystal structures. We identified a strong correlation between the affinities of the investigated saFabI diphenyl ether inhibitors and their corresponding residence times, which can be rationalized on a structural basis. Due to its favorable interactions with the enzyme, the residence time of our most potent compound exceeds 10 hours. In addition, we found that affinity and residence time in this system can be significantly enhanced by modifications predictable by a careful consideration of catalysis. Our study provides a blueprint for investigating and prolonging drug-target kinetics and may aid in the rational design of long-residence-time inhibitors targeting the essential saFabI enzyme. PMID:23697754

  6. Prescribing patterns and perceptions of health care professionals about rational drug use in a specialist hospital clinic.

    Directory of Open Access Journals (Sweden)

    Moses A. Ojo

    2014-12-01

    Full Text Available Irrational drug use is associated with adverse consequences including drug resistance and avoidable adverse drug reactions. Studies of rational drug use in psychiatric facilities are scanty. This study evaluated prescription practices and perception of health care professionals regarding causes of irrational drug use. A retrospective study conducted at the outpatient clinic of Federal Neuro- psychiatric Hospital, Yaba, Lagos. Data on drug use indicators were analyzed. A cross-sectional assessment of perception of prescribers and dispensers regarding rational drug use was conducted. A total of 600 prescriptions were analyzed. Mean number of drugs per encounter was 3.5 and percentage generic prescribed was 58.5%. Poly-pharmacy (P=0.024, 95% CI=1.082-1.315 and non-generic prescribing (P=0.032, 95% CI=1.495-1.821 were significantly associated with young prescribers. Factors associated with irrational drug use include demand from patients, patients’ beliefs about injection drugs and influence of pharmaceutical sale representatives. Certain aspect of prescribers indicators are still poor in the hospital studied. Health care professionals identified possible associated factors for irrational drug use. Concerted efforts are required to ensure rational drug use especially in psychiatric facilities in Nigeria.

  7. Differential Rationality and Personal Development.

    Science.gov (United States)

    Fincher, Cameron

    This publication discusses differential rationality; it asserts that the development of institutions, professions, and individuals involves the differentiation of forms and styles of thinking and knowing that are, in various ways, idiosyncratic. Based on this understanding, differential rationality can be seen as a developmental construct that…

  8. Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

    Science.gov (United States)

    Furlong, Michael; Seong, Jae Young

    2017-01-01

    Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

  9. Evidence on the cost of breast cancer drugs is required for rational decision making

    NARCIS (Netherlands)

    Berghuis, Anne Margreet Sofie; Koffijberg, Hendrik; Terstappen, Leonardus Wendelinus Mathias Marie; Sleijfer, Stefan; IJzerman, Maarten Joost

    2018-01-01

    Background: For rational decision making, assessing the cost-effectiveness and budget impact of new drugs and comparing the costs of drugs already on the market is required. In addition to value frameworks, such as the American Society of Clinical Oncology Value Framework and the European Society of

  10. Does mechanism of drug action matter to inform rational polytherapy in epilepsy?

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    Giussani, Giorgia; Beghi, Ettore

    2013-05-01

    When monotherapy for epilepsy fails, add-on therapy is an alternative option. There are several possible antiepileptic drug combinations based on their different and multiple mechanisms of action and pharmacokinetic interactions. However, only when benefits of drug combinations outweigh the harms, polytherapy can be defined as "rational". In the past 20 years, second generation AEDs have been marketed, some of which have better defined mechanisms of action and better pharmacokinetic profile. The mechanisms of action of AEDs involve, among others, blockade of voltage-gated sodium channels, blockade of voltage-gated calcium channel, activation of the ionotropic GABAA receptor and increase of GABA levels at the synaptic cleft, blockade of glutamate receptors, binding to synaptic vesicle protein 2A, and opening of KCNQ (Kv7) potassium channels. Aim of this review was to examine published reports on AEDs combinations in animal models and humans focusing on mechanisms of action and pharmacokinetic interactions. Studies in animals have shown that AED combinations are more effective when using drugs with different mechanisms of action. The most effective combination was found using a drug with a single mechanism of action and another with multiple mechanisms of action. In humans some combinations between a blocker of voltage-gated sodium channels and a drug with multiple mechanisms of action may be synergistic. Future studies are necessary to better define rational combinations and complementary mechanisms of action, considering also pharmacokinetic interactions and measures of toxicity and not only drug efficacy.

  11. Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

    Science.gov (United States)

    Kiyosawa, Naoki; Manabe, Sunao

    2016-01-01

    Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

  12. The System of Objectified Judgement Analysis (SOJA). A tool in rational drug selection for formulary inclusion.

    Science.gov (United States)

    Janknegt, R; Steenhoek, A

    1997-04-01

    Rational drug selection for formulary purposes is important. Besides rational selection criteria, other factors play a role in drug decision making, such as emotional, personal financial and even unconscious criteria. It is agreed that these factors should be excluded as much as possible in the decision making process. A model for drug decision making for formulary purposes is described, the System of Objectified Judgement Analysis (SOJA). In the SOJA method, selection criteria for a given group of drugs are prospectively defined and the extent to which each drug fulfils the requirements for each criterion is determined. Each criterion is given a relative weight, i.e. the more important a given selection criterion is considered, the higher the relative weight. Both the relative scores for each drug per selection criterion and the relative weight of each criterion are determined by a panel of experts in this field. The following selection criteria are applied in all SOJA scores: clinical efficacy, incidence and severity of adverse effects, dosage frequency, drug interactions, acquisition cost, documentation, pharmacokinetics and pharmaceutical aspects. Besides these criteria, group specific criteria are also used, such as development of resistance when a SOJA score was made for antimicrobial agents. The relative weight that is assigned to each criterion will always be a subject of discussion. Therefore, interactive software programs for use on a personal computer have been developed, in which the user of the system may enter their own personal relative weight to each selection criterion and make their own personal SOJA score. The main advantage of the SOJA method is that all nonrational selection criteria are excluded and that drug decision making is based solely on rational criteria. The use of the interactive SOJA discs makes the decision process fully transparent as it becomes clear on which criteria and weighting decisions are based. We have seen that the use of

  13. [Survey on junior high school student's attitudes toward rational drug use and the educational effect by school pharmacists].

    Science.gov (United States)

    Yamada, Junichi; Takayanagi, Risa; Yokoyama, Haruko; Suzuki, Yasuhiro; Sinohara, Satomi; Yamada, Yasuhiko

    2012-01-01

    The educational intervention could improve knowledge about rational drug use in the junior high school. Improving knowledge about rational drug use at an early age may be a good way to increase the population's awareness of health, medicines and self-medication. To educate the rational drug use, it is desirable that the school pharmacists participate in this educational program in the junior high school. So we conducted an educational lecture by school pharmacists to promote rational drug use and self-medication in junior high school students. The study compared participant responses before and after a lecture. After the first questionnaire, we lectured the mentioned above to them. Afterward, second questionnaire was conducted. In the second questionnaire, more than 95% of the students understood the contents of the lecture to some extent. After a lecture, students who answered that 'I don't have confidence that I can buy medicines rightly by myself' decreased from 42.7% to 11.7%. And students who answered that 'I don't have confidence that I can use medicines rightly by myself' decreased from 25.2% to 12.6%. It was possible to achieve a favorable modification of attitudes to rational use of medicines in junior high school students. Continuous interventions might allow better effects and could help to fill the gap in health education of the general population.

  14. Rational-Emotive Staff Development.

    Science.gov (United States)

    Forman, Susan G.; Forman, Bruce D.

    1980-01-01

    The application of Rational-Emotive Therapy principles and techniques in in-service education for school personnel is discussed. Teacher and counselor participation in a staff development program is described. (Author)

  15. Prediction of resistance development against drug combinations by collateral responses to component drugs

    DEFF Research Database (Denmark)

    Munck, Christian; Gumpert, Heidi; Nilsson Wallin, Annika

    2014-01-01

    the genomes of all evolved E. coli lineages, we identified the mutational events that drive the differences in drug resistance levels and found that the degree of resistance development against drug combinations can be understood in terms of collateral sensitivity and resistance that occurred during...... adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance......Resistance arises quickly during chemotherapeutic selection and is particularly problematic during long-term treatment regimens such as those for tuberculosis, HIV infections, or cancer. Although drug combination therapy reduces the evolution of drug resistance, drug pairs vary in their ability...

  16. A Study on the Application of the Information-Motivation-Behavioral Skills (IMB Model on Rational Drug Use Behavior among Second-Level Hospital Outpatients in Anhui, China.

    Directory of Open Access Journals (Sweden)

    Cheng Bian

    Full Text Available The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs.This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM to test predictive relations among the IMB model variables related to rational drug use behavior.Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills.The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second-level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge.

  17. A Study on the Application of the Information-Motivation-Behavioral Skills (IMB) Model on Rational Drug Use Behavior among Second-Level Hospital Outpatients in Anhui, China.

    Science.gov (United States)

    Bian, Cheng; Xu, Shuman; Wang, Heng; Li, Niannian; Wu, Jingya; Zhao, Yunwu; Li, Peng; Lu, Hua

    2015-01-01

    The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB) model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs. This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM) to test predictive relations among the IMB model variables related to rational drug use behavior. Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills. The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second-level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge.

  18. Economic evaluation and the Jordan Rational Drug List: an exploratory study of national-level priority setting.

    Science.gov (United States)

    Lafi, Rania; Robinson, Suzanne; Williams, Iestyn

    2012-01-01

    To explore the extent of and barriers to the use of economic evaluation in compiling the Jordan Rational Drug List in the health care system of Jordan. The research reported in this article involved a case study of the Jordan Rational Drug List. Data collection methods included semi-structured interviews with decision makers and analysis of secondary documentary sources. The case study was supplemented by additional interviews with a small number of Jordanian academics involved in the production of economic evaluation. The research found that there was no formal requirement for cost-effectiveness information submitted as part of the decision-making process for the inclusion of new technologies on the Jordan Rational Drug List. Both decision makers and academics suggested that economic evidence was not influential in formulary decisions. This is unusual for national formulary bodies. The study identified a number of barriers that prevent substantive and routine use of economic evaluation. While some of these echo findings of previous studies, others-notably the extent to which the sectional interests of clinical groups and commercial (pharmaceutical) industry exert undue influence over decision making-more obviously result from the specific Jordanian context. Economic evaluation was not found to be influential in the Jordan Rational Drug List. Recommendations for improvement include enhancing capacity in relation to generating, accessing, and/or applying health economic analysis to priority setting decisions. There is a further need to incentivize the use of economic evaluation, and this requires that organizational and structural impediments be removed. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  19. [Rational and emotional appeals in prescription drug advertising: study of a weight loss drug].

    Science.gov (United States)

    Huertas, Melby Karina Zuniga; Campomar, Marcos Cortez

    2008-04-01

    The Direct-to-Consumer (DTC) advertising of medicines encourages people to ask doctors for certain medicines and treatments that require medical prescription. In order to enhance their persuasive power, advertising models recommend matching the appeals (rational and/or emotional) to the consumer's attitude (cognitive and/ or affective) towards the product. This recommendation leads to controversies in the context of DTC advertising. Emotional appeals, although frequently used, would always be inadequate in that kind of advertising. In absence of empiric evidence of the consumer's perspective, a descriptive research was undertaken with the objective of evaluating: i) the components of the attitude toward medicines; ii) attitude and behavioral intentions in response to DTC ads (one appealing to reason and the other appealing to emotion). A prescription weight loss drug was chosen for this purpose. The results revealed a predominantly cognitive attitude toward the product and an attitude and behavioral intention more favorable to the rational ad. Negative cognition about the product played an outstanding role canceling the persuasive power of emotional appeals.

  20. [Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing].

    Science.gov (United States)

    Jin, Rui; Zhao, Kui-Jun; Guo, Gui-Ming; Zhang, Bing; Wang, Yu-Guang; Xue, Chun-Miao; Yang, Yi-Heng; Wang, Li-Xia; Li, Guo-Hui; Tang, Jin-Fa; Nie, Li-Xing; Zhang, Xiang-Lin; Zhao, Ting-Ting; Zhang, Yi; Yan, Can; Yuan, Suo-Zhong; Sun, Lu-Lu; Feng, Xing-Zhong; Yan, Dan

    2018-03-01

    With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use. Copyright© by the Chinese Pharmaceutical Association.

  1. A bibliometric study of publication patterns in rational use of medicines in Iran

    OpenAIRE

    Mousavi, Sarah; Mansouri, Ava; Ahmadvand, Alireza

    2013-01-01

    Background: Inappropriate use of drugs is commonly observed in health care system throughout the world especially in developing countries. The consequences of irrational use of drugs are enormous for patients and communities. Proper interventions would have important financial and public health benefits. Several studies have been performed about rational use of drugs in Iran. Objective: The objective of this study was to assess scientific output on rational use of drugs in Iran using a biblio...

  2. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  3. Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

    Science.gov (United States)

    Carter, Daniel C. (Inventor)

    1994-01-01

    This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

  4. Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib.

    Science.gov (United States)

    Amengual, Jennifer E; Prabhu, Sathyen A; Lombardo, Maximilian; Zullo, Kelly; Johannet, Paul M; Gonzalez, Yulissa; Scotto, Luigi; Serrano, Xavier Jirau; Wei, Ying; Duong, Jimmy; Nandakumar, Renu; Cremers, Serge; Verma, Akanksha; Elemento, Olivier; O'Connor, Owen A

    2017-06-15

    Purpose: Pan-class I/II histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. ACY-1215 (ricolinostat) is a first-in-class selective HDAC6 inhibitor. To better understand the discrete function of HDAC6 and its role in lymphoma, we developed a lymphoma cell line resistant to ACY-1215. Experimental Design: The diffuse large B-cell lymphoma cell line OCI-Ly10 was exposed to increasing concentrations of ACY-1215 over an extended period of time, leading to the development of a resistant cell line. Gene expression profiling (GEP) was performed to investigate differentially expressed genes. Combination studies of ACY-1215 and ibrutinib were performed in cell lines, primary human lymphoma tissue, and a xenograft mouse model. Results: Systematic incremental increases in drug exposure led to the development of distinct resistant cell lines with IC 50 values 10- to 20-fold greater than that for parental lines. GEP revealed upregulation of MAPK10, HELIOS, HDAC9, and FYN, as well as downregulation of SH3BP5 and LCK. Gene-set enrichment analysis (GSEA) revealed modulation of the BTK pathway. Ibrutinib was found to be synergistic with ACY-1215 in cell lines as well as in 3 primary patient samples of lymphoma. In vivo confirmation of antitumor synergy was demonstrated with a xenograft of DLBCL. Conclusions: The development of this ACY-1215-resistant cell line has provided valuable insights into the mechanistic role of HDAC6 in lymphoma and offered a novel method to identify rational synergistic drug combinations. Translation of these findings to the clinic is underway. Clin Cancer Res; 23(12); 3084-96. ©2016 AACR . ©2016 American Association for Cancer Research.

  5. The Impact of the National Essential Medicines Policy on Rational Drug Use in Primary Care Institutions in Jiangsu Province of China.

    Science.gov (United States)

    Chao, Jianqian; Gu, Jiangyi; Zhang, Hua; Chen, Huanghui; Wu, Zhenchun

    2018-01-01

    Essential medicine policy is a successful global health policy to promote rational drug use. The aim of this study was to evaluate the impact of the National Essential Medicines Policy (NEMP) on the rational drug use in primary care institutions in Jiangsu Province of China. In this exploratory study, a multistage, stratified, random sampling was used to select 3400 prescriptions from 17 primary care institutions who implemented the NEMP before (Jan 2010) and after the implementation of the NEMP (Jan 2014). The analyses were performed in SPSS 18.0 and SPSS Clementine client. After the implementation of the NEMP, the percentage of prescribed EML (Essential Medicines List) drugs rose significantly, the average number of drugs per prescription and average cost per prescription were declined significantly, while the differences of the prescription proportion of antibiotics and injection were not statistically significant. BP (Back Propagation) neural network analysis showed that the average number of drugs per prescription, the number of using antibiotics and hormone, regional differences, size of institutions, sponsorship, financial income of institutions, doctor degree, outpatient and emergency visits person times were important factors affecting the prescription costs, among these the average number of drugs per prescription has the greatest effect. The NEMP can promote the rational use of drugs in some degree, but its role is limited. We should not focus only on the EML but also make comprehensive NEMP.

  6. GREEN: A program package for docking studies in rational drug design

    Science.gov (United States)

    Tomioka, Nobuo; Itai, Akiko

    1994-08-01

    A program package, GREEN, has been developed that enables docking studies between ligand molecules and a protein molecule. Based on the structure of the protein molecule, the physical and chemical environment of the ligand-binding site is expressed as three-dimensional grid-point data. The grid-point data are used for the real-time evaluation of the protein-ligand interaction energy, as well as for the graphical representation of the binding-site environment. The interactive docking operation is facilitated by various built-in functions, such as energy minimization, energy contribution analysis and logging of the manipulation trajectory. Interactive modeling functions are incorporated for designing new ligand molecules while considering the binding-site environment and the protein-ligand interaction. As an example of the application of GREEN, a docking study is presented on the complex between trypsin and a synthetic trypsin inhibitor. The program package will be useful for rational drug design, based on the 3D structure of the target protein.

  7. Drug dealers' rational choices on which customers to rip-off.

    Science.gov (United States)

    Jacques, Scott; Allen, Andrea; Wright, Richard

    2014-03-01

    Drug dealers are infamous for overcharging customers and handing over less than owed. One reason rip-offs frequently occur is blackmarket participants have limited access to formal means of dispute resolution and, as such, are attractive prey. Yet drug dealers do not cheat every customer. Though this is implicitly understood in the literature, sparse theoretical attention has been given to which customers are ripped-off and why. To address that lacuna, this paper uses the rationality perspective to analyze qualitative data obtained in interviews with 25 unincarcerated drug sellers operating in disadvantaged neighborhoods of St. Louis, Missouri. We find that dealers typically rip-off six types of customers: persons who are strangers, first-time or irregular customers; do not have sufficient money on hand to make a purchase; are uninformed about going market rates; are deemed unlikely to retaliate; are offensive; or are addicted to drugs. Dealers target these groups due to perceiving them as unlikely to be repeat business; not worth the hassle of doing business with; unlikely to realize they are being ripped-off; in the wrong and thus deserving of payback; and, unwilling to retaliate or take their money elsewhere. Our findings are discussed in relation to their practical implications, including the importance of giving blackmarket participants greater access to law, and how customers may prevent being ripped-off. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Evaluation of rational drug use based on World Health Organization core drug use indicators in selected public hospitals of eastern Ethiopia: a cross sectional study.

    Science.gov (United States)

    Sisay, Mekonnen; Mengistu, Getnet; Molla, Bereket; Amare, Firehiwot; Gabriel, Tesfaye

    2017-02-23

    Despite the complexity of drug use, a number of indicators have been developed, standardized and evaluated by the World Health Organization (WHO). These indicators are grouped in to three categories namely: prescribing indicators, patient care indicators and facility indicators. The study was aimed to evaluate rational drug use based on WHO-core drug use indicators in Dilchora referral hospital, Dire Dawa; Hiwot Fana specialized university hospital, Harar and Karamara general hospital, Jigjiga, eastern Ethiopia. Hospital based quantitative cross sectional study design was employed to evaluate rational drug use based on WHO core drug use indicators in selected hospitals. Systematic random sampling for prescribing indicators and convenient sampling for patient care indicators was employed. Taking WHO recommendations in to account, a total of 1,500 prescription papers (500 from each hospitals) were investigated. In each hospital, 200 outpatient attendants and 30 key essential drugs were also selected using the WHO recommendation. Data were collected using retrospective and prospective structured observational check list. Data were entered to EPI Data Version 3.1, exported and analyzed using SPSS version 16.0. Besides, the data were evaluated as per the WHO guidelines. Statistical significance was determined by one way analysis of variance (ANOVA) for some variables. P-value of less than 0.05 was considered statistically significant. Finally, tabular presentation was used to present the data. Mean, 2.34 (±1.08) drugs were prescribed in the selected hospitals. Prescriptions containing antibiotics and that of injectables were 57.87 and 10.9% respectively. The average consultation and dispensing time were 276.5 s and 61.12 s respectively. Besides, 75.77% of the prescribed drugs were actually dispensed. Only 3.3% of prescriptions were adequately labeled and 75.7% patients know about the dosage of the prescription. Not more than, 20(66.7%) key drugs were available in

  9. Development of a rational scale to assess the harm of drugs of potential misuse.

    Science.gov (United States)

    Nutt, David; King, Leslie A; Saulsbury, William; Blakemore, Colin

    2007-03-24

    Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

  10. A study on regional comprehensive performance evaluation indicator system of rational use of drugs

    Directory of Open Access Journals (Sweden)

    Sun Tongda

    2017-01-01

    Full Text Available The current research presents the design of a 4-degree-3-level performance evaluation indicator system of rational use of drugs for health care institutions accord with the Balanced Score Card (BSC method. Financial index, patient index, professional process index, and development and blazing new trials index are adopted in the light of scientific, guiding, operable and generalizable principles. The index weight is based on the analytic hierarchy process, and comprehensive performance evaluation indicators are calculated by a linear integrated weighting method. Its practical application in 21 state-run health care institutions in Ningbo, from 2008 to 2012, has arrived at the finding that the comprehensive performance evaluation indicator system offers a scientific, practical and effective performance management quantification and is thus worth popularizing.

  11. Trends in the Outpatient Utilization of Antipsychotic Drugs in the City of Zagreb in the Ten-Year Period as a Tool to Assess Drug Prescribing Rationality.

    Science.gov (United States)

    Polić-Vižintin, Marina; Tripković, Ingrid; Štimac, Danijela; Šostar, Zvonimir; Orban, Mirjana

    2016-12-01

    The aim was to determine distribution and trends in the outpatient utilization of antipsychotics to evaluate the rationality of antipsychotic drug prescribing during the ten year period. The epidemiological method of descriptive and analytical observation was used. Data on drug utilization from Zagreb Municipal Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the World Health Organization Anatomical-Therapeutic-Chemical methodology. The ratio of typical versus atypical antipsychotics served as an indicator on assessing the rationality of the utilization. Data on the use of anticholinergics in the treatment of neuroleptic side effects were also included. Outpatient utilization of antipsychotics showed a declining pattern from 14.17 in 2001 to 8.42 DDD/TID in 2010. The utilization of atypical antipsychotics increased by 60% (from 3.68 to 5.89 DDD/TID), while the utilization of typical antipsychotics decreased by 76% (from 10.49 to 2.53 DDD/TID). The drugs showing the largest increase were olanzapine (from 1.21 to 2.78 DDD/TID) and quetiapine (from 0 to 0.68 DDD/TID). The typical/atypical antipsychotic ratio changed from 1:0.4 in 2001 to 1:2.3 in 2010. A 2.3-fold decrease was recorded in the utilization of anticholinergics (from 2.05 to 0.91 DDD/TID). Total consumption of neuroleptics significantly decreased. A decrease was also recorded in the utilization of anticholinergics. Study results pointed to two favorable features, i.e. low use of typical antipsychotics and the ratio of typical and atypical antipsychotics. Implementation of the new clinical guidelines for nervous system disorders and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in the prescribing patterns during the study period. Using the WHO ATC/DDD methodology and rationality indicators in the assessment of trends in the outpatient utilization of

  12. In Silico Augmentation of the Drug Development Pipeline: Examples from the study of Acute Inflammation.

    Science.gov (United States)

    An, Gary; Bartels, John; Vodovotz, Yoram

    2011-03-01

    The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high-throughput and -content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are utilized in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. In this article, we present a Translational Systems Biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism.

  13. Developing drug formularies for the "National Medical Holding" JSC.

    Science.gov (United States)

    Akhmadyar, N S; Khairulin, B E; Amangeldy-Kyzy, S; Ospanov, M A

    2015-01-01

    infrastructure, management systems, production environments, and developing program for medications management and use (MMU), etc.MMU is the Chapter 7 of the 5th edition of the standard JCI [1] which is an up-to-date recognized international standard for hospital drug supply and includes 7 points of medication management lifecycle for inpatient hospitals: drug management and organization; selection and procurement; storage; prescription; preparation and distribution; administering medications; monitoring.Due to the developed MMU program of subsidiary organizations the drug provision system was rationalized, starting from defining the individual therapy of a patient and ending with the drug procurement strategy. The practical activity was introduced to the use of drugs committeees with reliable evidence-based performance with obligatory consideration of cost-benefit analysis for each diagnosis-related group. Pre-collected applications for drugs for the year 2015 were submitted in a uniform format in accordance with the structure of the Republican form of the drug [2]. In view of the evidence-base physicians-clinical pharmacologists performed discussions and review of 851 drugs included on the uniform format of the list. Totally 51 (6%) positions were excluded from the list; it was suggested that the format of the application for Paracetamol and Ibuprofen in injectable form be revised; the committee revised the sections on the list for "Antianaemia drugs", iron preparations and methods of prevention of venous thromboembolism with oral anticoagulants.On the basis of this work, the new format, consisting of 449 international nonproprietary names was developed, representing 795 positions with pediatric formulations. In view of the exisitng data and the move to bring to the common standards and uniformity prices of drugs purchased for 2016, the NMH program of clinical pharmacology content with on-line and open access to physicians was created. Within 60 days the DSCHC work was carried

  14. Privileged Electrophile Sensors: A Resource for Covalent Drug Development.

    Science.gov (United States)

    Long, Marcus John Curtis; Aye, Yimon

    2017-07-20

    This Perspective delineates how redox signaling affects the activity of specific enzyme isoforms and how this property may be harnessed for rational drug design. Covalent drugs have resurged in recent years and several reports have extolled the general virtues of developing irreversible inhibitors. Indeed, many modern pharmaceuticals contain electrophilic appendages. Several invoke a warhead that hijacks active-site nucleophiles whereas others take advantage of spectator nucleophilic side chains that do not participate in enzymatic chemistry, but are poised to bind/react with electrophiles. The latest data suggest that innate electrophile sensing-which enables rapid reaction with an endogenous signaling electrophile-is a quintessential resource for the development of covalent drugs. For instance, based on recent work documenting isoform-specific electrophile sensing, isozyme non-specific drugs may be converted to isozyme-specific analogs by hijacking privileged first-responder electrophile-sensing cysteines. Because this approach targets functionally relevant cysteines, we can simultaneously harness previously untapped moonlighting roles of enzymes linked to redox sensing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Pharmacogenetics and rational drug use around the world.

    Science.gov (United States)

    Roederer, Mary W; Sanchez-Giron, Francisco; Kalideen, Kusha; Kudzi, William; McLeod, Howard L; Zhang, Wei

    2011-06-01

    The WHO embraces evidence-based medicine to formulate an essential medicines list (EML) considering disease prevalence, drug efficacy, drug safety and cost-effectiveness. The EML is used by developing countries to build a national formulary. As pharmacogenetics in developed countries evolves, the Pharmacogenetics for Every Nation Initiative (PGENI) convened with representatives from China, Mexico, Ghana and South Africa in August 2009 to evaluate the use of human pharmacogenetics to enhance global drug use policy. The diseases causing mortality, the lack of integration of pharmacovigilance at the national formulary level, the pharmacogenetics research agenda and pharmacogenetics clinician education did not differ greatly among the countries. While there are many unanswered questions, systematically incorporating pharmacogenetics at the national formulary level promises to improve global drug use.

  16. A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

    Science.gov (United States)

    Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

    2011-08-01

    Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

  17. Clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs in clinical practice»

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2015-01-01

    Full Text Available The paper presents the new version of the clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs in clinical practice » prepared by the Association of Rheumatologists of Russia, the Russian Pain Society, the Russian Gastroenterological Association, the Russian Society of Cardiology, the Association of Traumatologists and Orthopedists of Russia, the Association of Interdisciplinary Medicine, and the Russian Association of Palliative Medicine.In our country, NSAIDs are the most important and most popular class of analgesics. Unlike global practice, Russian physicians rather rarely recommend paracetamol as a first-line drug to relieve moderate or severe pain, by giving preference to NSAIDs; the use of opioid analgesics for noncancers is minimized because of tight legal restrictions.NSAIDs are effective and easy-to-use; however, they are far from safe; the administration of these medications may lead to serious gastrointestinal, cardiovascular, renal, and other complications in a number of cases. So the use of NSAIDs should be compulsorily monitored for adverse reactions and the choice of a specific drug for each clinical case should be based on the objective estimation of a ratio of its efficacy to safety.In recent years, there have been fresh data on the use of NSAIDs for different diseases and a few novel representatives of this drug group have appeared on the Russian pharmacological market.This all has necessitated a new version of the guidelines on the rational use of NSAIDs. These are based on the provisions that have high validity and have been confirmed by the results of well-organized clinical and large-scale population-based studies, as well as by their meta-analysis.The guidelines are intended for physicians of all specialties. 

  18. Self-medication practices and rational drug use habits among university students: a cross-sectional study from Kahramanmaraş, Turkey

    Directory of Open Access Journals (Sweden)

    Ramazan Azim Okyay

    2017-11-01

    Full Text Available Background Self-medication refers to the use of medicines to treat self-diagnosed diseases without consulting any healthcare professionals. Irrational drug use and self-medication have serious negative consequences both on health and economy. Therefore, the aim of this study is to assess the habits related to rational use of drugs (RUD and to estimate the prevalence of self-medication practices among university students. Methods This cross-sectional study was conducted on university students in Kahramanmaraş. From May 2017 to June 2017 a total of 960 students filled a “Rational Use of Drugs Questionnaire”. Results The prevalence of practicing self-medication in students was 63.4%. The most common medicines that the students had consumed without prescription were analgesics by 39.5%, antibiotics by 36.9% and cold remedies by 24.0%. The rate of students who declared that they were familiar with RUD and “rational use of antibiotics” (RUA was 45.9%. Reading/checking the instructions in the prospectus (OR = 1.529, 95% CI [1.176–1.990], understanding the context of the prospectus (OR = 1.893, 95% CI [1.387–2.584], compliance with the duration of antibiotic treatment (OR = 1.597, 95% CI [1.231–2.071] and consulting a physician in case of a side effect (OR = 1.350, 95% CI [1.037–1.757] were significantly higher among students who were familiar with RUD as compared to who were not. Discussion Since the awareness of RUD among university students was found to be inadequate, it has critical importance to hold educational activities with the cooperation of physicians, health organizations, universities, non-governmental organizations and media to avoid negative consequences of irrational drug use and self-medication.

  19. [How I treat: from specialized pharmacology to drug therapy: a plea for an optimal educational program for rational therapeutics, from decision making to drug prescription].

    Science.gov (United States)

    Scheen, A J

    2000-09-01

    Clinical pharmacology and therapeutics are two complementary disciplines which should lead the medical student, through an optimized training, to a rational prescription of drugs, ultimate and important step of the medical approach. Such a learning should occur progressively throughout the medical education, focusing, first, on the therapeutic reasoning ("why?") and, second, on the practical application leading to the prescription ("how?"). The medical student should learn the difficult task of integrating disease, drug and patient, in order to optimize the benefit/risk ratio, while being informed about new concepts such as "Evidence-Based Medicine" and pharmacoeconomics.

  20. Evidence on the cost of breast cancer drugs is required for rational decision making.

    Science.gov (United States)

    Berghuis, Anne Margreet Sofie; Koffijberg, Hendrik; Terstappen, Leonardus Wendelinus Mathias Marie; Sleijfer, Stefan; IJzerman, Maarten Joost

    2018-01-01

    For rational decision making, assessing the cost-effectiveness and budget impact of new drugs and comparing the costs of drugs already on the market is required. In addition to value frameworks, such as the American Society of Clinical Oncology Value Framework and the European Society of Medical Oncology-Magnitude of Clinical benefit Scale, this also requires a transparent overview of actual drug prices. While list prices are available, evidence on treatment cost is not. This paper aims to synthesise evidence on the reimbursement and costs of high-cost breast cancer drugs in The Netherlands (NL). A literature review was performed to identify currently reimbursed breast cancer drugs in the NL. Treatment costs were determined by multiplying list prices with the average length of treatment and dosing schedule. Comparing list prices to the estimated treatment cost resulted in substantial differences in the ranking of costliness of the drugs. The average mean treatment length was unknown for 11/31 breast cancer drugs (26.2%). The differences in the 15 highest-cost drugs were largest for Bevacizumab, Lapatinib and everolimus, with list prices of €541, €158, €1,168 and estimated treatment cost of €174,400, €18,682 and €31,207, respectively. The lowest-cost (patented) targeted drug is €1,818 more expensive than the highest-cost (off-patent) generic drug according to the estimated drug treatment cost. A lack of evidence on the reimbursement and cost of high-cost breast cancer drugs complicates rapid and transparent evidence synthesis, necessary to focus strategies aiming to limit the increasing healthcare costs. Interestingly, the findings show that off-patent generics (such as paclitaxel or doxorubicin), although substantially cheaper than patented drugs, are still relatively costly. Extending standardisation and increasing European and national regulations on presenting information on costs per cancer drug is highly recommended.

  1. Book Selection, Collection Development, and Bounded Rationality.

    Science.gov (United States)

    Schwartz, Charles A.

    1989-01-01

    Reviews previously proposed schemes of classical rationality in book selection, describes new approaches to rational choice behavior, and presents a model of book selection based on bounded rationality in a garbage can decision process. The role of tacit knowledge and symbolic content in the selection process are also discussed. (102 references)…

  2. Rational drug use in Cambodia: study of three pilot health centers in Kampong Thom Province.

    Science.gov (United States)

    Chareonkul, Chanin; Khun, Va Luong; Boonshuyar, Chaweewon

    2002-06-01

    This study obtained baseline information for the design of a strategy to address irrational prescribing practices in three health centers in Kampong Thom Province, Cambodia. Indicators of rational drug use have been measured and compared with Standard Guidelines. Data were collected from patients' registers and by interviewing patients immediately after patient-prescriber and patient-dispenser encounters. Checklists and pre-designed forms were used to collect data regarding the World Health Organization drug use indicators and some additional indices. Of the 330 prescriptions analyzed, the results showed that the average number of drugs per prescription was 2.35 and that a large proportion of the prescriptions contained two or more drugs that could result in adverse drug interactions. Prescribing by generic names (99.8%) was encouraging. The exposure of patients to antibiotics (66% to 100%) was high, and injection use (2.4%) was often unnecessary. Prescribing from the Essential Drugs List (99.7%) was satisfactory. The average consultation and dispensing times were short and not sufficient for patients to get health information. All the prescribed drugs were supplied, but all were inadequately labeled. Some 55% of patients knew the correct dosage of their drugs. The availability of key essential drugs (86.6%) was below the Standard. The percentages of appropriate prescriptions for treating malaria, diarrhea and acute respiratory infection treatment were 68.3%, 3.3%, and 45%, respectively. Inappropriate prescriptions were mostly due to unsuitable dosages, incorrect drugs, and the improper duration of treatment. The results suggest a need for intervention to curb the irrational use of drugs in prescribing at the three pilot health centers. Continuing education of prescribers and healthcare providers, monitoring, supervision, public education would be beneficial.

  3. Development of modified rational buyer auction for procurement of ancillary services utilizing participation matrix

    International Nuclear Information System (INIS)

    Jamalzadeh, R.; Ardehali, M.M.; Rashidinejad, M.

    2008-01-01

    The rational buyer auction is based on a simultaneous auction that is the redesigned auction mechanism for ancillary services by the California independent system operator (CAISO). The incentive for the rational buyer auction is CAISO's intent to adopt a common sense rule of substituting higher-quality lower-cost services for lower-quality higher-cost services, when it results in reduced total procurement cost. For the purposes of designing a desirable auction where the minimum cost for the objective function as well as prevention of price reversal are achieved, either the payment cost in marginal pricing auction must be lowered or price reversal in rational buyer auction must be avoided. The objectives of this study are (a) to develop a newly proposed 'modified rational buyer' auction that does not allow price reversal and (b) to propose and validate a solution procedure that is based on participation matrix and discrete programming. The validation of the proposed solution procedure is accomplished through examination of two case studies available in the literature. Based on the first case study data, it is shown that the newly developed modified rational buyer auction avoids price reversal occurrence, while the total payment of ISO is increased by 5.8%, as compared with rational buyer auction. Also in comparison with marginal pricing auction, the ISO payment is lowered by 38.8%, when the newly developed modified rational buyer auction is utilized. For future work, it is recommended that the application of the modified rational buyer auction to joint dispatch of energy and ancillary services is investigated

  4. The Influence of Big (Clinical) Data and Genomics on Precision Medicine and Drug Development.

    Science.gov (United States)

    Denny, Joshua C; Van Driest, Sara L; Wei, Wei-Qi; Roden, Dan M

    2018-03-01

    Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications. New biomedical informatics and machine-learning approaches advance the ability to interpret clinical information, enabling identification of complex phenotypes and subpopulations of patients. We review the recent history of use of "big data" from EHR-based cohorts and biobanks supporting these activities. Future studies using EHR data, other information sources, and new methods will promote a foundation for discovery to more rapidly advance precision medicine. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  5. Love and rationality: on some possible rational effects of love

    Directory of Open Access Journals (Sweden)

    Gustavo Ortiz-Millán

    Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.

  6. Changes in Rational Economic Behavior Model, Caused By the Development of E-Commerce

    Directory of Open Access Journals (Sweden)

    Menzeleev Ilya, A.

    2016-03-01

    Full Text Available In the paper the author examines the origins of rationality concept and its transformation within the framework of economic science. According to the author, rationality is a fundamental concept both for philosophy and for economics. Changes in rational economic behavior model significantly effect on informal institutes (in short-term perspective and on formal institutes (in long-term period. In the paper it is said about significant changes taking place with humanity right now. Today it becomes more and more difficult to describe human behavior by uniform concept of rationality. Now people live in a world that is developing unprecedentedly fast, with the usage of incredible amount of information, countless tasks and social contacts. The development of the Internet and IT tools facilitate this process. Already since the midtwentieth century advertising and marketing has been influencing people’s lifestyle like politics or news. Media resources brands today are comparable to the resources of some political parties or even TV channels what means that advertising today is one of the main factors affecting consumers ' minds and their behavioral model, main feature of which is the premise of rationality or justification of actions. The author analyzes the changes of models of rationality over time and, above all, the changes caused by the development of Internet marketing and its tools for monitoring user activity and the impact on decision making in the Network. In conclusion a number of recommendations is given, which can help consumers to save an independence in making decisions in the Internet environment.

  7. Rational management of epilepsy.

    Science.gov (United States)

    Viswanathan, Venkataraman

    2014-09-01

    Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country.

  8. Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design

    Science.gov (United States)

    Basith, Shaherin; Cui, Minghua; Macalino, Stephani J. Y.; Park, Jongmi; Clavio, Nina A. B.; Kang, Soosung; Choi, Sun

    2018-01-01

    The primary goal of rational drug discovery is the identification of selective ligands which act on single or multiple drug targets to achieve the desired clinical outcome through the exploration of total chemical space. To identify such desired compounds, computational approaches are necessary in predicting their drug-like properties. G Protein-Coupled Receptors (GPCRs) represent one of the largest and most important integral membrane protein families. These receptors serve as increasingly attractive drug targets due to their relevance in the treatment of various diseases, such as inflammatory disorders, metabolic imbalances, cardiac disorders, cancer, monogenic disorders, etc. In the last decade, multitudes of three-dimensional (3D) structures were solved for diverse GPCRs, thus referring to this period as the “golden age for GPCR structural biology.” Moreover, accumulation of data about the chemical properties of GPCR ligands has garnered much interest toward the exploration of GPCR chemical space. Due to the steady increase in the structural, ligand, and functional data of GPCRs, several cheminformatics approaches have been implemented in its drug discovery pipeline. In this review, we mainly focus on the cheminformatics-based paradigms in GPCR drug discovery. We provide a comprehensive view on the ligand– and structure-based cheminformatics approaches which are best illustrated via GPCR case studies. Furthermore, an appropriate combination of ligand-based knowledge with structure-based ones, i.e., integrated approach, which is emerging as a promising strategy for cheminformatics-based GPCR drug design is also discussed. PMID:29593527

  9. Risk control and rational recreation: A qualitative analysis of synthetic drug use among young urbanites in China.

    Science.gov (United States)

    Lin, Shaozhen; Zhang, Yong-an

    2014-07-01

    To fight against the rapid growth of synthetic drugs, the Chinese government has strengthened the controls and regulation, incorporated synthetic drugs into the new detoxification system, and changed the inconsistent governance of synthetic and traditional drugs. This, however, has not stopped the spread of synthetic drugs among young urbanites. While scholars have focused on the loopholes and defects of specific drug control regulations, ethnographic inquiries illustrate how and why control does not work, or is even resisted by young drug users. In-depth qualitative interviews were conducted with 28 individuals aged between 20 and 35, recruited from a cohort of synthetic drug users in a Shanghai drug rehabilitation centre. Audio-recorded interviews elicited accounts of their daily experiences of drug use as well as their perspectives on the impact of the government's new drug control policies. The main themes voiced by our respondents include: (1) synthetic drugs are not addictive, and are used to feel 'high'; (2) synthetic drugs are used to achieve their goals, which are otherwise impossible through mainstream means; (3) users are confident that they will be able to manage the use of synthetic drugs without harm to themselves; (4) their worries concern administrative punishment rather than consequences to health. The participants of this study did not support the government's attempts to control the use of synthetic drugs. They viewed their use as rational recreation under the perceived boundaries of 'acceptable risks'. Even in the context of severe control, synthetic drugs have strong appeal to youths. Drug policy should acknowledge the experiences of users and consider the socio-cultural contexts of youth drug-taking. The personal experience of participants could help improve the Chinese Drug Control Act and regulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. [Theoretical and practical considerations in rational polytherapy for epilepsy].

    Science.gov (United States)

    Rajna, Péter

    2011-11-30

    Author analyses the consideration of rational polytherapy for epilepsy. Among the theoretical aspects he points the different effect of seizure inhibitory drugs on the epilepsy models but didn't find data enough for the basis of any successful combination. Combinations of compounds having different way of action are more promising. Rational polytherapy can serve also the epileptic patients' tailored therapy in the daily routine. There have already been some proved synergisms concerning drug interactions. Based on detailed analysis of side effects a possibility occurs for neutralization of side effects when anticonvulsants with side effects of opposite nature are combined. Considering both the side effect profiles and the different (somatic and psychic) habits of the patients we can create a special list of favourable combinations. Co-morbid states and their treatments play a significant role in the application of rational polytherapy. Combination of anticonvulsants of lower potential but without drug-interactions can be the choice in these cases. The non-epileptic indications of the anticonvulsants can also be utilized in polymorbid patients. Based on the theoretical and practical considerations the author defines the ten-step-cognitive-preparation-process in planning the optimal (poly)therapy. On speculative basis he suggests eight beneficial versions of seizure inhibitory rational polytherapy.

  11. On rationally supported surfaces

    DEFF Research Database (Denmark)

    Gravesen, Jens; Juttler, B.; Sir, Z.

    2008-01-01

    We analyze the class of surfaces which are equipped with rational support functions. Any rational support function can be decomposed into a symmetric (even) and an antisymmetric (odd) part. We analyze certain geometric properties of surfaces with odd and even rational support functions....... In particular it is shown that odd rational support functions correspond to those rational surfaces which can be equipped with a linear field of normal vectors, which were discussed by Sampoli et al. (Sampoli, M.L., Peternell, M., Juttler, B., 2006. Rational surfaces with linear normals and their convolutions...... with rational surfaces. Comput. Aided Geom. Design 23, 179-192). As shown recently, this class of surfaces includes non-developable quadratic triangular Bezier surface patches (Lavicka, M., Bastl, B., 2007. Rational hypersurfaces with rational convolutions. Comput. Aided Geom. Design 24, 410426; Peternell, M...

  12. What are the arguments for and against rational therapy for epilepsy?

    Science.gov (United States)

    Barker-Haliski, Melissa; Sills, Graeme J; White, H Steve

    2014-01-01

    Although more than a dozen new anti-seizure drugs (ASDs) have entered the market since 1993, a substantial proportion of patients (~30 %) remain refractory to current treatments. Thus, a concerted effort to identify and develop new therapies that will help these patients continues. Until this effort succeeds, it is reasonable to re-assess the use of currently available therapies and to consider how these therapies might be utilized in a more efficacious manner. This applies to the selection of monotherapies in newly-diagnosed epilepsy, but perhaps, more importantly, to the choice of combination treatments in otherwise drug-refractory epilepsy. Rational polytherapy is a concept that is predicated on the combination of drugs with complementary mechanisms of action (MoAs) that work synergistically to maximize efficacy and minimize the potential for adverse events. Furthermore, rational polytherapy requires a detailed understanding of the MoA subclasses amongst available ASDs and an appreciation of the empirical evidence that supports the use of specific combinations. The majority of ASDs can be loosely categorized into those that target neurotransmission and network hyperexcitability, modulate intrinsic neuronal properties through ion channels, or possess broad-spectrum efficacy as a result of multiple mechanisms. Within each of these categories, there are discrete pharmacological profiles that differentiate individual ASDs. This chapter will consider how knowledge of MoA can help guide therapy in a rational manner, both in the selection of monotherapies for specific seizure types and syndromes, but also in the choice of drug combinations for patients whose epilepsy is not optimally controlled with a single ASD.

  13. Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

    Science.gov (United States)

    Germovsek, Eva; Barker, Charlotte I S; Sharland, Mike; Standing, Joseph F

    2018-04-19

    Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies.

  14. Development of a Preventive HIV Vaccine Requires Solving Inverse Problems Which Is Unattainable by Rational Vaccine Design

    Directory of Open Access Journals (Sweden)

    Marc H. V. Van Regenmortel

    2018-01-01

    Full Text Available Hypotheses and theories are essential constituents of the scientific method. Many vaccinologists are unaware that the problems they try to solve are mostly inverse problems that consist in imagining what could bring about a desired outcome. An inverse problem starts with the result and tries to guess what are the multiple causes that could have produced it. Compared to the usual direct scientific problems that start with the causes and derive or calculate the results using deductive reasoning and known mechanisms, solving an inverse problem uses a less reliable inductive approach and requires the development of a theoretical model that may have different solutions or none at all. Unsuccessful attempts to solve inverse problems in HIV vaccinology by reductionist methods, systems biology and structure-based reverse vaccinology are described. The popular strategy known as rational vaccine design is unable to solve the multiple inverse problems faced by HIV vaccine developers. The term “rational” is derived from “rational drug design” which uses the 3D structure of a biological target for designing molecules that will selectively bind to it and inhibit its biological activity. In vaccine design, however, the word “rational” simply means that the investigator is concentrating on parts of the system for which molecular information is available. The economist and Nobel laureate Herbert Simon introduced the concept of “bounded rationality” to explain why the complexity of the world economic system makes it impossible, for instance, to predict an event like the financial crash of 2007–2008. Humans always operate under unavoidable constraints such as insufficient information, a limited capacity to process huge amounts of data and a limited amount of time available to reach a decision. Such limitations always prevent us from achieving the complete understanding and optimization of a complex system that would be needed to achieve a truly

  15. Menopause: developing a rational treatment plan.

    Science.gov (United States)

    Vitiello, Danielle; Naftolin, Frederick; Naftoilin, Frederick; Taylor, Hugh S

    2007-12-01

    In recent years, growing importance has been afforded to assisting women in coping with the menopausal transition. Menopause is a normal stage of development and a woman's attitude toward this transition embodies biological, psychological and social influences. An enlarging body of conflicting data concerning menopausal hormone therapy (MHT) demands reassessment of established paradigms of disease prevention and menopausal health. Currently, a woman's decision to participate in or abstain from menopausal HT is personal. It involves not only consideration of risk stratification of potential harm and benefit, but also involves her expectations and attitudes toward perceived physical and emotional changes associated with this change. Through the use of extensive patient history, quality-of-life questionnaires and powerful biological profiling, we may be able to develop a rational approach to menopausal HT that safely guides our patients through this transition.

  16. CONTRIBUTIONS TO RATIONAL APPROXIMATION,

    Science.gov (United States)

    Some of the key results of linear Chebyshev approximation theory are extended to generalized rational functions. Prominent among these is Haar’s...linear theorem which yields necessary and sufficient conditions for uniqueness. Some new results in the classic field of rational function Chebyshev...Furthermore a Weierstrass type theorem is proven for rational Chebyshev approximation. A characterization theorem for rational trigonometric Chebyshev approximation in terms of sign alternation is developed. (Author)

  17. Guidelines for Rational Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  18. Development of rations for the enhanced survival of salmon

    International Nuclear Information System (INIS)

    Ewing, R.D.; Lagasse, J.P.

    1990-12-01

    The nutritional quality of feed plays an important role in determining the health and ''fitness'' of smolts. Commercial fish meal, the major source of protein in salmon rations, may be reduced in quality from poor drying techniques during manufacture. Dietary stress in the hatchery may result. This investigation tests the hypothesis that protein quality of fish rations can influence the survival of smolts and the ultimate return of adults. The test involves a comparison between performances of coho (Oncorhynchus kisutch) and chinook salmon (O. tshawytscha) reared on rations containing very high quality protein derived from vacuum dried meals and those of fish reared on commercial rations, with commercial fish meal as a source of protein. Survival and return of several brood years of test and control fish are used to measure the influence of ration on survival. This report includes recovery data from these marked fish collected 1982 through September 1990

  19. Uso racional de medicamentos: uma abordagem econômica para tomada de decisões Rational drug use: an economic approach to decision making

    Directory of Open Access Journals (Sweden)

    Daniel Marques Mota

    2008-04-01

    Full Text Available O artigo aborda o uso racional de medicamentos (URM sob um ponto de vista da economia. O URM, para ser implementado, implica custos e envolve a apropriação de conhecimentos e mudanças de conduta de diversos agentes. A dificuldade na adoção da prática do URM pode estar relacionada a problemas de escassez, assimetria de informação, informação incompleta, incertezas nas decisões clínicas, externalidades, preço-tempo, incentivos para prescritores e dispensadores, preferências dos prescritores e utilidade marginal. Assim, cabe às autoridades sanitárias, entre outras entidades, regular, reduzir e controlar essas falhas que poderão introduzir ineficiências na assistência farmacêutica, bem como produzir riscos à vida humana.The present article approaches rational drug use (RDU from the economical point of view. The implementation of RDU implies in costs and involves acquisition of knowledge and behavioral changes of several agents. The difficulties in implementing RDU may be due to shortage problems, information asymmetry, lack of information, uncertain clinical decisions, externalities, time-price, incentives for drug prescribers and dispensers, drug prescriber preferences and marginal utility. Health authorities, among other agencies, must therefore regularize, rationalize and control drug use to minimize inefficiency in pharmaceutical care and to prevent exposing the population to unnecessary health risks.

  20. Developing and Testing Rational Models of Message Design.

    Science.gov (United States)

    O'Keefe, Barbara J.

    1992-01-01

    Responds to an article in the same issue regarding research methods for conversational cognition. Argues for a noncognitive view of rational models in communication research. Sets out an analysis of the kinds of claims made by rational models of message design. Discusses the implications of this analysis for studies of the cognitive processes…

  1. Prescribing Pattern of Oral Antihyperglycaemic Drugs, Rationality and Adherence to American Diabetes Association (ADA) Treatment Guidelines among Type 2 Diabetes Mellitus (T2DM) Postmenopausal Women.

    Science.gov (United States)

    Sharma, Sudhaa; Tandon, Vishal R; Roshi; Mahajan, Annil

    2016-01-01

    Oral antihyperglycaemic prescription trends keep on changing and thus the drug prescription trend study may prove to be powerful exploratory tool for health care providers. To investigate trends in prescriptions of oral antihyperglycaemic drugs (OHDs) among postmenopausal women suffering from T2DM in India and evaluate the rationality and adherence to ADA treatment guidelines. An observational, cross-sectional descriptive prescription audit (n=500) was carried. Postmenopausal women were interviewed in their local language using pre-tested pre validated questionnaire after verbal informed consent at a teaching tertiary care hospital of north India. Oral antihyperglycaemic drugs (OHDs) drugs were categorized as per the pharmacological classification. Adherence to available clinical practice guidelines/recommendations issued under American Diabetes Association (ADA) 2015 Guidelines as well as rationality of these prescriptions were assessed using WHO Guide to Good Prescribing. Mean age of the study population was 58.14±12.86. Mean duration since menopause was 5.3 years and of T2DM was 9.5 years. A 93.4% of the prescriptions had only OHDs whereas 6.6% of the prescriptions had various insulin preprations + OHDs (pADA treatment guidelines was observed.

  2. Development and validation of a smoking rationalization scale for male smokers in China.

    Science.gov (United States)

    Huang, Xinyuan; Fu, Wenjie; Zhang, Haiying; Li, Hong; Li, Xiaoxia; Yang, Yong; Wang, Fan; Gao, Junling; Zheng, Pinpin; Fu, Hua; Ding, Ding; Chapman, Simon

    2017-07-01

    The purpose of this study is to develop a smoking rationalization scale for Chinese male smokers. A total of 35 focus groups and 19 one-on-one interviews were conducted to collect items of the scale. Exploratory factor analyses and confirmatory factor analyses were conducted to identify the underlying structure of the scale. Results found a 26-item scale within six dimensions (smoking functional beliefs, risk generalization beliefs, social acceptability beliefs, safe smoking beliefs, self-exempting beliefs, and quitting is harmful beliefs). The scale showed acceptable validity and reliability. Results highlight that smoking rationalization is common among Chinese male smokers, and some beliefs of smoking rationalization seem to be peculiar to China.

  3. Refolding of proteins from inclusion bodies: rational design and recipes.

    Science.gov (United States)

    Basu, Anindya; Li, Xiang; Leong, Susanna Su Jan

    2011-10-01

    The need to develop protein biomanufacturing platforms that can deliver proteins quickly and cost-effectively is ever more pressing. The rapid rate at which genomes can now be sequenced demands efficient protein production platforms for gene function identification. There is a continued need for the biotech industry to deliver new and more effective protein-based drugs to address new diseases. Bacterial production platforms have the advantage of high expression yields, but insoluble expression of many proteins necessitates the development of diverse and optimised refolding-based processes. Strategies employed to eliminate insoluble expression are reviewed, where it is concluded that inclusion bodies are difficult to eliminate for various reasons. Rational design of refolding systems and recipes are therefore needed to expedite production of recombinant proteins. This review article discusses efforts towards rational design of refolding systems and recipes, which can be guided by the development of refolding screening platforms that yield both qualitative and quantitative information on the progression of a given refolding process. The new opportunities presented by light scattering technologies for developing rational protein refolding buffer systems which in turn can be used to develop new process designs armed with better monitoring and controlling functionalities are discussed. The coupling of dynamic and static light scattering methodologies for incorporation into future bioprocess designs to ensure delivery of high-quality refolded proteins at faster rates is also discussed.

  4. Antimicrobial Drugs in Fighting against Antimicrobial Resistance

    OpenAIRE

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i....

  5. The Role of Neoadjuvant Trials in Drug Development for Solid Tumors.

    Science.gov (United States)

    Funt, Samuel A; Chapman, Paul B

    2016-05-15

    The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

    Directory of Open Access Journals (Sweden)

    Nir Qvit

    2016-04-01

    Full Text Available Parasitic diseases cause ∼500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase and TRACK (Trypanosoma receptor for activated C-kinase. We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase, may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. Keywords: Chagas disease, Leishmaniasis, Peptide, LACK, TRACK, Scaffold protein

  7. Adolescent rationality.

    Science.gov (United States)

    Moshman, David

    2013-01-01

    Adolescents are commonly seen as irrational, a position supported to varying degrees by many developmentalists, who often appeal to recent research on adolescent brains. Careful review of relevant evidence, however, shows that (1) adults are less rational than is generally assumed, (2) adolescents (and adults) are categorically different from children with respect to the attainment of advanced levels of rationality and psychological functioning, and (3) adolescents and adults do not differ categorically from each other with respect to any rational competencies, irrational tendencies, brain structures, or neurological functioning. Development often continues in adolescence and beyond but categorical claims about adolescents as distinct from adults cannot be justified. A review of U.S. Supreme Court decisions concerning intellectual freedom, reproductive freedom, and criminal responsibility shows ongoing ambivalence and confusion about the rationality of adolescents. Developmental theory and research suggest that adolescents should be conceptualized as young adults, not immature brains, with important implications for their roles, rights, and responsibilities.

  8. Viagra: : A success story for rationing?

    NARCIS (Netherlands)

    Klein, R.; Sturm, H.

    2002-01-01

    The 1998 launch of Viagra prompted widespread fears about the budgetary consequences for insurers and governments, all the more so since Viagra was only the first of a new wave of so-called lifestyle drugs. The fears have turned out to be greatly exaggerated. This paper analyzes the rationing

  9. TRPV1: A Target for Rational Drug Design

    Directory of Open Access Journals (Sweden)

    Vincenzo Carnevale

    2016-08-01

    Full Text Available Transient Receptor Potential Vanilloid 1 (TRPV1 is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX. Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures.

  10. Comparison of a rational vs. high throughput approach for rapid salt screening and selection.

    Science.gov (United States)

    Collman, Benjamin M; Miller, Jonathan M; Seadeek, Christopher; Stambek, Julie A; Blackburn, Anthony C

    2013-01-01

    In recent years, high throughput (HT) screening has become the most widely used approach for early phase salt screening and selection in a drug discovery/development setting. The purpose of this study was to compare a rational approach for salt screening and selection to those results previously generated using a HT approach. The rational approach involved a much smaller number of initial trials (one salt synthesis attempt per counterion) that were selected based on a few strategic solubility determinations of the free form combined with a theoretical analysis of the ideal solvent solubility conditions for salt formation. Salt screening results for sertraline, tamoxifen, and trazodone using the rational approach were compared to those previously generated by HT screening. The rational approach produced similar results to HT screening, including identification of the commercially chosen salt forms, but with a fraction of the crystallization attempts. Moreover, the rational approach provided enough solid from the very initial crystallization of a salt for more thorough and reliable solid-state characterization and thus rapid decision-making. The crystallization techniques used in the rational approach mimic larger-scale process crystallization, allowing smoother technical transfer of the selected salt to the process chemist.

  11. History of Economic Rationalities

    DEFF Research Database (Denmark)

    This book concentrates upon how economic rationalities have been embedded into particular historical practices, cultures, and moral systems. Through multiple case-studies, situated in different historical contexts of the modern West, the book shows that the development of economic rationalities...... takes place in the meeting with other regimes of thought, values, and moral discourses. The book offers new and refreshing insights, ranging from the development of early economic thinking to economic aspects and concepts in the works of classical thinkers such as Thomas Hobbes, John Locke and Karl Marx......, to the role of economic reasoning in contemporary policies of art and health care. With economic rationalities as the read thread, the reader is offered a unique chance of historical self-awareness and recollection of how economic rationality became the powerful ideological and moral force that it is today....

  12. Two Concepts of Rationality

    Directory of Open Access Journals (Sweden)

    Danny Frederick

    2010-02-01

    Full Text Available The dominant tradition in Western philosophy sees rationality as dictating. Thus rationality may require that we believe the best explanation and simple conceptual truths and that we infer in accordance with evident rules of inference. I argue that, given what we know about the growth of knowledge, this authoritarian concept of rationality leads to absurdities and should be abandoned. I then outline a libertarian concept of rationality, derived from Popper, which eschews the dictates and which sees a rational agent as one who questions, criticises, conjectures and experiments. I argue that, while the libertarian approach escapes the absurdities of the authoritarian, it requires two significant developments and an important clarification to be made fully consistent with itself.

  13. [Rational motivation of drug injection and prostitution].

    Science.gov (United States)

    Beauchamp, Sylvie

    2003-01-01

    Homeless drug users and prostitutes constitute a population at risk for contracting and propagating AIDS. This study aims at understanding the paradox related to drug injection and prostitution among 21 homeless from Montreal. These behaviors are studied following the picoeconomic paradox of an apprehended desire. The results show that these homeless see drug injection as a self-reward motivated by imaginary emotional object, in spite of the known and dreaded consequences. Prostitution is described as a self-investment accessory to drug injection. This study concludes with reflections on AIDS prevention programs in relation with the needs of the homeless.

  14. Standby Gasoline Rationing Plan. Contingency gasoline rationing regulations

    Energy Technology Data Exchange (ETDEWEB)

    1979-02-01

    The Economic Regulatory Administration issues final rules with respect to standby gasoline rationing. The plan is designed for and would be used only in the event of a severe gasoline shortage. The plan provides that eligibility for ration allotments will be primarily on the basis of motor vehicle registrations. DOE will mail government ration checks to the parties named in a national vehicle registration file to be maintained by DOE. Ration recipients may cash these checks for ration coupons at various designated coupon issuance points. Retail outlets and other suppliers will be required to redeem the ration coupons received in exchange for gasoline sold. Supplemental gas will be given to high-priority activities. A ration banking system will be established with two separate and distinct of ration accounts: retail outlets and other suppliers will open redemption accounts for the deposit of redeemed ration rights; and individuals or firms may open ration rights accounts, which will operate in much the same manner as monetary checking accounts. A white market will be permitted for the sale of transfer of ration rights. A percentage of the total ration rights to be issued will be reserved for distribution to the states as a State Ration Reserve, to be used by the states primarily for the relief of hardship. A National Ration Reserave will also be established. All sections of the Standby Gasoline Rationing Regulations are analyzed. (MCW)

  15. Rational Risk-Benefit Decision-Making in the Setting of Military Mefloquine Policy.

    Science.gov (United States)

    Nevin, Remington L

    2015-01-01

    Mefloquine is an antimalarial drug that has been commonly used in military settings since its development by the US military in the late 1980s. Owing to the drug's neuropsychiatric contraindications and its high rate of inducing neuropsychiatric symptoms, which are contraindications to the drug's continued use, the routine prescribing of mefloquine in military settings may be problematic. Due to these considerations and to recent concerns of chronic and potentially permanent psychiatric and neurological sequelae arising from drug toxicity, military prescribing of mefloquine has recently decreased. In settings where mefloquine remains available, policies governing prescribing should reflect risk-benefit decision-making informed by the drug's perceived benefits and by consideration both of the risks identified in the drug's labeling and of specific military risks associated with its use. In this review, these risks are identified and recommendations are made for the rational prescribing of the drug in light of current evidence.

  16. Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

    NARCIS (Netherlands)

    Witte, W.E.; Wong, Y.C.; Nederpelt, I.; Heitman, L.H.; Danhof, M.; Graaf, van der P.H.; Gilissen, R.A.; de, Lange E.C.

    2016-01-01

    INTRODUCTION Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target

  17. Drug policy constellations: A Habermasian approach for understanding English drug policy.

    Science.gov (United States)

    Stevens, Alex; Zampini, Giulia Federica

    2018-07-01

    It is increasingly accepted that a view of policy as a rational process of fitting evidence-based means to rationally justified ends is inadequate for understanding the actual processes of drug policy making. We aim to provide a better description and explanation of recent English drug policy decisions. We develop the policy constellation concept from the work of Habermas, in dialogue with data from two contemporary debates in English policy; on decriminalisation of drug possession and on recovery in drug treatment. We collect data on these debates through long-term participant observation, stakeholder interviews (n = 15) and documentary analysis. We show the importance of social asymmetries in power in enabling structurally advantaged groups to achieve the institutionalisation of their moral preferences as well as the reproduction of their social and economic power through the deployment of policies that reflect their material interests and normative beliefs. The most influential actors in English drug policy come together in a 'medico-penal constellation', in which the aims and practices of public health and social control overlap. Formal decriminalisation of possession has not occurred, despite the efforts of members of a challenging constellation which supports it. Recovery was put forward as the aim of drug treatment by members of a more powerfully connected constellation. It has been absorbed into the practice of 'recovery-oriented' drug treatment in a way that maintains the power of public health professionals to determine the form of treatment. Actors who share interests and norms come together in policy constellations. Strategic action within and between constellations creates policies that may not take the form that was intended by any individual actor. These policies do not result from purely rational deliberation, but are produced through 'systematically distorted communication'. They enable the most structurally favoured actors to institutionalise

  18. Orphan drugs: trends and issues in drug development.

    Science.gov (United States)

    Rana, Proteesh; Chawla, Shalini

    2018-04-12

    Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

  19. Rationality of limited rationality : some aggregate implications

    OpenAIRE

    Uri M. Possen; Mikko Puhakka

    1994-01-01

    In this paper we let economic agents choose whether to become fully rational or stay boundedly rational. Boundedly rational agents are less sophisticated in their information processing abilities. It is costly to acquire information needed to become fully rational, and thus not all agents are willing to incur those costs. We then explore the aggregate effects of endogenizing the decision whether the agent should or should not become fully rational in handling information. Since fully and boun...

  20. Definition of rational antiepileptic polypharmacy.

    Science.gov (United States)

    Wilder, B J; Homan, R W

    1996-01-01

    Rational polypharmacy is in its earliest stages of development and will require substantial additional development to realize its full potential. Indeed, despite the powerful appeal of the concept, clinical proof is not yet available that RP is superior to monotherapy. Important questions need to be addressed: 1. Will RP control seizures more effectively than monotherapy? 2. What data are needed to develop RP for a specific patient? 3. Will RP be cost effective? 4. Can RP be developed which will treat or prevent epilepsy while controlling seizures? Possible approaches to these questions could include: 1. The development of a data base for prospective use to monitor patients being treated at Epilepsy Centers using RP principles. 2. Use the data obtained from the above to construct more specific studies to compare identified combination therapies with monotherapy. 3. Prospectively compare in a placebo controlled, blinded study, the effect of the combination of an anti-ictal medication and a laboratory proven antiepileptic drug for prevention of the development of epilepsy in an at risk population such as head trauma or stroke.

  1. Medicinal chemistry inspired fragment-based drug discovery.

    Science.gov (United States)

    Lanter, James; Zhang, Xuqing; Sui, Zhihua

    2011-01-01

    Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Strategy selection as rational metareasoning.

    Science.gov (United States)

    Lieder, Falk; Griffiths, Thomas L

    2017-11-01

    Many contemporary accounts of human reasoning assume that the mind is equipped with multiple heuristics that could be deployed to perform a given task. This raises the question of how the mind determines when to use which heuristic. To answer this question, we developed a rational model of strategy selection, based on the theory of rational metareasoning developed in the artificial intelligence literature. According to our model people learn to efficiently choose the strategy with the best cost-benefit tradeoff by learning a predictive model of each strategy's performance. We found that our model can provide a unifying explanation for classic findings from domains ranging from decision-making to arithmetic by capturing the variability of people's strategy choices, their dependence on task and context, and their development over time. Systematic model comparisons supported our theory, and 4 new experiments confirmed its distinctive predictions. Our findings suggest that people gradually learn to make increasingly more rational use of fallible heuristics. This perspective reconciles the 2 poles of the debate about human rationality by integrating heuristics and biases with learning and rationality. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Aspects of physicians' attitudes towards the rational use of drugs at a training and research hospital: a survey study.

    Science.gov (United States)

    Filiz Basaran, Nesrin; Akici, Ahmet

    2013-08-01

    The rational use of drugs (RUD) is primarily the responsibility of physicians. The aim of this study was to investigate whether physicians are aware of RUD principles and how they apply them in daily medical practice. A total 136 physicians working at the Kartal Training and Research Hospital in Istanbul were enrolled in the study between February and March 2012. A face-to-face interview was conducted with physicians to assess their knowledge and attitude regarding RUD. A large majority of the physicians declared that consultation time was insufficient (84 %). The data obtained from the survey indicate that 54 % of the enrolled physicians monitored the therapeutic outcome and that 27 % found the information given to the patient to be sufficient. Participating physicians stated that the less known characteristics of the drugs they prescribed were drug interactions, traceability in market, and price. The most preferred reference source was Vademecum (a drug guideline prepared by the private sector). Two major factors contributing to prescribing patterns were "self study" and "observation of teachers" at clinical training. There was a significant difference between internists-surgeons and residents-specialists in the number of prescribed drugs per prescription (p change in managerial practices within the healthcare system. The other, more essential explanation is education; consequently, serious consideration should be given to including effective clinical pharmacotherapy training and RUD courses in the medical education curriculum.

  4. Development of rationalized system treating floor drain

    International Nuclear Information System (INIS)

    Nakamura, Yasuyuki; Serizawa, Kenichi; Komatsu, Akihiro; Shimizu, Takayuki

    1998-01-01

    Radioactive liquid wastes generated at BWR plants are collected and treated as required. These days, however, generation of floor drain has deceased and HFF (Hollow Fiber Filter) has experienced a wide applicability to several kinds of liquid wastes. We should consider that the floor drain can be mixed and diluted with equipment drain and be purified by HFF. That enables some of the sumps and long priming pipes to be combined. From this point of view, we have developed a highly rationalized waste liquid system. We have evaluated the applicability of this system after an investigation into the generation and properties of floor drain and equipment drain at the latest BWR'S and an on-site test at a typical BWR. (author)

  5. DEVELOPMENT OF DOMESTIC INFUSION DRUGS BASED ON PARACETAMOL

    Directory of Open Access Journals (Sweden)

    Almakaeva L.G.

    2016-06-01

    aqueous solution decreases in acidic and alkaline environments where paratse - tamol gradually destroyed to acetic acid or p - aminophenol To prevent oxidation of the drug administered antioxidant - sodium metabisulfite in concentrations generally 1.0 g / l. In order to prevent the negative - tive impact of oxygen on paracetamol solution 10 mg / mL drug preparation was conducted under nitrogen gas protection . It is established that the use of nitrogen gas protection affects the quality of the drug. Prepared sample preparation without nitrogen gas protection did not meet project MKYA in terms of " 4 - aminophenol " and " color ", besides a slight tendency pH change and reducing quantitative content of active ingredient. Therefore, the production of the drug " Paracetamol , infusion solution 10 mg / ml. in bottles of 100 ml " necessary solution prepared bubbling nitrogen for 20 minutes. It is established that the use of nitrogen gas protection affects the quality of the drug. the manufacture of the drug " Paracetamol , infusion solution 10 mg / ml. in bottles of 100 ml " necessary solution prepared bubbling nitrogen for 20 minutes. Calculated theoretical osmolarity of the drug- 299,47 мОsм / l. Solution osmolarity close to osmolarity of blood, which is an important criterion when used in injection therapy. Conclusions. Theoretically grounded and experimentally confirmed rational composition drug infusion composition based on paracetamol. Selected auxiliaries and processing methods in the preparation of the solution , prevents oxidation of the main active ingredient , and also provide the optimum level of osmolarity solution. Results of this development are used during compile of registration dossier of preparation, analytical and technological normative documents on his production and control of quality of intermediate products and prepared products.

  6. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  7. In silico pharmacology for a multidisciplinary drug discovery process.

    Science.gov (United States)

    Ortega, Santiago Schiaffino; Cara, Luisa Carlota López; Salvador, María Kimatrai

    2012-01-01

    The process of bringing new and innovative drugs, from conception and synthesis through to approval on the market can take the pharmaceutical industry 8-15 years and cost approximately $1.8 billion. Two key technologies are improving the hit-to-drug timeline: high-throughput screening (HTS) and rational drug design. In the latter case, starting from some known ligand-based or target-based information, a lead structure will be rationally designed to be tested in vitro or in vivo. Computational methods are part of many drug discovery programs, including the assessment of ADME (absorption-distribution-metabolism-excretion) and toxicity (ADMET) properties of compounds at the early stages of discovery/development with impressive results. The aim of this paper is to review, in a simple way, some of the most popular strategies used by modelers and some successful applications on computational chemistry to raise awareness of its importance and potential for an actual multidisciplinary drug discovery process.

  8. Towards a Rational Kingdom in Africa: Knowledge, Critical Rationality and Development in a Twenty-First Century African Cultural Context

    Directory of Open Access Journals (Sweden)

    Lawrence Ogbo Ugwuanyi

    2018-03-01

    Full Text Available This paper seeks to locate the kind of knowledge that is relevant for African development in the twenty-first century African cultural context and to propose the paradigm for achieving such knowledge. To do this, it advances the view that the concept of twenty-first century in an African context must be located with the colonial and post-colonial challenges of the African world and applied to serve the African demand. Anchored on this position, the paper outlines and critiques the wrong assumption on which modern state project was anchored in post-colonial Africa and its development dividend to suggest that this is an outcome of a wrong knowledge design that is foundational to the state project and which the project did not address. It proposes a shift in the knowledge paradigm in Africa and suggests critical self-consciousness as a more desirable knowledge design for Africa. It applies the term ‘rational kingdom’ (defined as a community of reason marked by critical conceptual self-awareness driven by innovation and constructivism to suggest this paradigm. ‘Innovation’ is meant as the application of reason with an enlarged capacity to anticipate and address problems with fresh options and ‘constructivism’ is meant as the disposition to sustain innovation by advancing an alternative but more reliable worldview that can meet the exigencies of modernity in an African cultural context. The paper then proceeds to outline the nature of the rational kingdom and its anticipated gains and outcomes. It applies the method of inductive reasoning to advance its position. To do this it invokes selected but crucial areas of African life to locate how the developmental demands of these aspects of life suggest a critical turn in African rationality.

  9. Strategies to enhance rational use of antibiotics in hospital : a guideline by the German Society for Infectious Diseases

    NARCIS (Netherlands)

    de With, K.; Allerberger, F.; Amann, S.; Apfalter, P.; Brodt, H. -R.; Eckmanns, T.; Fellhauer, M.; Geiss, H. K.; Janata, O.; Krause, R.; Lemmen, S.; Meyer, E.; Mittermayer, H.; Porsche, U.; Presterl, E.; Reuter, S.; Sinha, B.; Strauss, R.; Wechsler-Foerdoes, A.; Wenisch, C.; Kern, W. V.

    In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was

  10. Optimization of self nanoemulsifying drug delivery system for poorly water-soluble drug using response surface methodology

    DEFF Research Database (Denmark)

    Ren, Shan; Mu, Huiling; Alchaer, Fadi

    2013-01-01

    impact of excipients on the performance of formulations as well as the fate of drug. The aim of this study was to rationalize the SNEDDS development procedure and to get a better understanding on the role of excipients on the SNEDDS. The formulations consist of soybean oil or rapeseed oil, Cremophor...

  11. Toward a Rational View of Hallucinogenic Drugs.

    Science.gov (United States)

    McGlothlin, William H.

    The enactment of California's "LSD Bill" is presented as an example of poor judgment in drug legislation on the state level. An appraisal of the nonmedical use of hallucinogens centering around the types of users, and the results of drug use, shows that the principal social impact of hallucinogens is on the personalities and values of the users.…

  12. Integrated Teaching of Structure-Based Drug Design and Biopharmaceutics: A Computer-Based Approach

    Science.gov (United States)

    Sutch, Brian T.; Romero, Rebecca M.; Neamati, Nouri; Haworth, Ian S.

    2012-01-01

    Rational drug design requires expertise in structural biology, medicinal chemistry, physiology, and related fields. In teaching structure-based drug design, it is important to develop an understanding of the need for early recognition of molecules with "drug-like" properties as a key component. That is, it is not merely sufficient to teach…

  13. Fiber sources for complete calf starter rations.

    Science.gov (United States)

    Murdock, F R; Wallenius, R W

    1980-11-01

    Complete calf starter rations containing either 1) alfalfa hay, 2) cottonseed hulls, or 3) alfalfa-beet pulp as sources of fiber were fed to Holstein heifer calves at two locations on a limited milk program from 3 days to 12 wk of age. Rations were isonitrogenous and similar in content of crude fiber and acid detergent fiber. Although growth and development were normal on all rations, calves fed the cottonseed hull ration consumed more starter and gained more body weight than calves fed the other sources of fiber. The similarity of feed efficiencies, rumen pH, and molar ratios of volatile fatty acids between rations indicated no appreciable differences in rumen development or function. The growth response of calves fed the cottonseed hull ration appeared to be a result of better ration acceptability for which no reason was evident. Calves raised at Puyallup gained more body weight than calves at Pullman, and these gains were made more efficiently. These location effects may be related to seasonal differences and greater demands for production of body heat. Although the incidence of scours was less for calves fed alfalfa hay starter, the incidence and severity of bloat were higher for that ration.

  14. Can rational models be good accounts of developmental change? The case of language development at two time scales.

    Science.gov (United States)

    Dawson, Colin R; Gerken, LouAnn

    2012-01-01

    Rational models of human perception and cognition have allowed researchers new ways to look at learning and the ability to make inferences from data. But how good are such models at accounting for developmental change? In this chapter, we address this question in the domain of language development, focusing on the speed with which developmental change takes place, and classifying different types of language development as either fast or slow. From the pattern of fast and slow development observed, we hypothesize that rational learning processes are generally well suited for handling fast processes over small amounts of input data. In contrast, we suggest that associative learning processes are generally better suited to slow development, in which learners accumulate information about what is typical of their language over time. Finally, although one system may be dominant for a particular component of language learning, we speculate that both systems frequently interact, with the associative system providing a source of emergent hypotheses to be evaluated by the rational system and the rational system serving to highlight which aspects of the learner's input need to be processed in greater depth by the associative system.

  15. Intervention research in rational use of drugs : a review

    NARCIS (Netherlands)

    Le Grand, A; Van Hogerzeil, H; Haaijer-Ruskamp, FM; LeGrand, A.

    Many studies have been done to document drug use patterns, and indicate that overprescribing, multi-drug prescribing, misuse of drugs, use of unnecessary expensive drugs and overuse of antibiotics and injections are the most common problems of irrational drug use by prescribers as well as consumers.

  16. FUNCTIONAL SUBCLONE PROFILING FOR PREDICTION OF TREATMENT-INDUCED INTRA-TUMOR POPULATION SHIFTS AND DISCOVERY OF RATIONAL DRUG COMBINATIONS IN HUMAN GLIOBLASTOMA

    Science.gov (United States)

    Reinartz, Roman; Wang, Shanshan; Kebir, Sied; Silver, Daniel J.; Wieland, Anja; Zheng, Tong; Küpper, Marius; Rauschenbach, Laurèl; Fimmers, Rolf; Shepherd, Timothy M.; Trageser, Daniel; Till, Andreas; Schäfer, Niklas; Glas, Martin; Hillmer, Axel M.; Cichon, Sven; Smith, Amy A.; Pietsch, Torsten; Liu, Ying; Reynolds, Brent A.; Yachnis, Anthony; Pincus, David W.; Simon, Matthias; Brüstle, Oliver; Steindler, Dennis A.; Scheffler, Björn

    2016-01-01

    Purpose Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. Experimental Design Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and inter-individual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacological sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. Results Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential anti-glioblastoma compounds. A more comprehensive intra-tumoral analysis revealed that stable genetic and phenotypic characteristics of co-existing subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacological profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. Conclusions Our data provide a previously unrecognized strategy for revealing functional consequences of intra-tumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. PMID:27521447

  17. Development and aging of decision-making rationality under risk framework

    OpenAIRE

    Han-hui LIU; Yan-yan AN; Hui-min LI; Zhen WEI; Xing-ting ZHU; Hui-jie LI

    2014-01-01

    Background Humans often display irrational choice and decision-making due to the frame effect. However, it is unclear whether this irrational choice and decision-making will increase during the aging process. Methods The present research explored development and aging of risky-seeking and rational decision-making with 232 younger adults and 120 older adults. The experiment was a 2 (Age:younger adult and old adult) × 2 (Frame: positive and negative) × 2 (Relevance: lower level and higher level...

  18. Quantitative decisions in drug development

    CERN Document Server

    Chuang-Stein, Christy

    2017-01-01

    This book offers a high-level treatise of evidence-based decisions in drug development. Because of the inseparable relationship between designs and decisions, a good portion of this book is devoted to the design of clinical trials. The book begins with an overview of product development and regulatory approval pathways. It then discusses how to incorporate prior knowledge into study design and decision making at different stages of drug development. The latter include selecting appropriate metrics to formulate decisions criteria, determining go/no-go decisions for progressing a drug candidate to the next stage and predicting the effectiveness of a product. Lastly, it points out common mistakes made by drug developers under the current drug-development paradigm. The book offers useful insights to statisticians, clinicians, regulatory affairs managers and decision-makers in the pharmaceutical industry who have a basic understanding of the drug-development process and the clinical trials conducted to support dru...

  19. A neuroeconomic theory of rational addiction and nonlinear time-perception.

    Science.gov (United States)

    Takahashi, Taiki

    2011-01-01

    Neuroeconomic conditions for "rational addiction" (Becker & Murphy 1988) have been unknown. This paper derived the conditions for "rational addiction" by utilizing a nonlinear time-perception theory of "hyperbolic" discounting, which is mathematically equivalent to the q-exponential intertemporal choice model based on Tsallis' statistics. It is shown that (i) Arrow-Pratt measure for temporal cognition corresponds to the degree of irrationality (i.e., Prelec's "decreasing impatience" parameter of temporal discounting) and (ii) rationality in addicts is controlled by a nondimensionalization parameter of the logarithmic time-perception function. Furthermore, the present theory illustrates the possibility that addictive drugs increase impulsivity via dopaminergic neuroadaptation without increasing irrationality. Future directions in the application of the model to studies in neuroeconomics are discussed.

  20. Drug and therapeutics committees in Danish hospitals: a survey of organization, activities and drug selection procedures

    DEFF Research Database (Denmark)

    Plet, H. T.; Hallas, J.; Nielsen, Gitte S.

    2013-01-01

    To implement rational pharmacotherapy in hospitals, it is important to develop, implement and evaluate hospital drug formularies (HDFs). A report from Denmark recommended standardizing activities of the drug and therapeutics committees (DTCs) in Denmark, but little is known about their current...... organization. The aim of the study was to describe the organization of DTCs in Denmark, how HDFs are developed and implemented, and to what extent policies that support the use of HDFs exist. A questionnaire was developed based on previous research and guidelines and contained 20 questions, which were divided...... of the meetings lasted between 1 and 2.5 hr. Eight (89%) DTCs developed HDFs, policies and guidelines (P&Gs) that supported the use of HDFs. Eight (89%) had established criteria for inclusion of drugs on the HDFs, and seven had developed criteria for generic substitution and therapeutic interchange. The number...

  1. Biochemical markers of bone turnover in the clinical development of drugs for osteoporosis and metastatic bone disease: potential uses and pitfalls.

    Science.gov (United States)

    Cremers, Serge; Garnero, Patrick

    2006-01-01

    Biochemical markers of bone turnover are used increasingly during the clinical development of drugs for the treatment of metabolic bone diseases such as Paget's disease, osteoporosis and cancer that has metastasised to the bone. However, assessing the optimal value of these markers is often complicated, and such an assessment is an obvious prerequisite for rational use of the markers and, consequently, potential improvement of clinical drug development. Biochemical markers of bone turnover are substances in the blood or urine that are produced or released during bone remodelling. They provide semiquantitative information on bone remodelling, and are often the most adequate tool to describe the pharmacodynamics of the drug. Their use has increased considerably because of dose-effect relationships that have been seen with certain drugs, but also because they have proven relationships with clinical outcomes in several metabolic bone diseases. However, there is a lack of information on the kinetics of these markers, and the immunoassays that are frequently used in their monitoring often measure a mixture of fragments rather than a single molecular entity. For drug development it should also be realised that different markers, but also different assays for the same marker, may provide different results, considerably limiting the ability to compare results. In postmenopausal osteoporosis, relationships have been shown between several biochemical markers of bone turnover, and either fracture risk and/or the antifracture efficacy of drugs. Such relationships can be used for the development of drugs with similar mechanisms of action, but also for the development of these drugs for closely related indications, such as corticosteroid-induced osteoporosis. In both of these instances, data on effects on biochemical markers of bone turnover are usually employed in combination with information about effects on bone mineral density. However, the relationships of these parameters

  2. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

  3. Panning for SNuRMs: using cofactor profiling for the rational discovery of selective nuclear receptor modulators.

    Science.gov (United States)

    Kremoser, Claus; Albers, Michael; Burris, Thomas P; Deuschle, Ulrich; Koegl, Manfred

    2007-10-01

    Drugs that target nuclear receptors are clinically, as well as commercially, successful. Their widespread use, however, is limited by an inherent propensity of nuclear receptors to trigger beneficial, as well as adverse, pharmacological effects upon drug activation. Hence, selective drugs that display reduced adverse effects, such as the selective estrogen receptor modulator (SERM) Raloxifene, have been developed by guidance through classical cell culture assays and animal trials. Full agonist and selective modulator nuclear receptor drugs, in general, differ by their ability to recruit certain cofactors to the receptor protein. Hence, systematic cofactor profiling is advancing into an approach for the rationally guided identification of selective NR modulators (SNuRMs) with improved therapeutic ratio.

  4. Rationalization: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    Rationalization was studied by Sigmund Freud and was specifically labeled by Ernest Jones. Rationalization ought to be differentiated from rational, rationality, logical analysis, etc. On the one hand, rationalization is considered a defense mechanism, on the other hand, rationality is not. Haan has done much work with self-report inventories and…

  5. Rational pharmacotherapy training for fourth-year medical students.

    Science.gov (United States)

    Gelal, Ayse; Gumustekin, Mukaddes; Arici, M Aylin; Gidener, Sedef

    2013-01-01

    In this study we aimed to evaluate the impact of Rational Pharmacotherapy (RPT) course program, reinforced by video footages, on the rational pharmacotherapy skills of the students. RPT course program has been conducted in Dokuz Eylul University School of Medicine since 2008/9. The course has been organised in accordance with World Health Organisation (WHO) Good Prescribing Guide. The aim of the course was to improve the problem solving skills (methodology for selection of the (p)ersonel-drug, prescription writing and informing patient about his illness and drugs) and communication skills of students. The impact of the course has been measured by pre/post-test design by an objective structured clinical examination (OSCE). In academic year 2010/11, to further improve OSCE score of the students we added doctor-patient communication video footages to the RPT course programme. During training, the students were asked to evaluate the doctor-patient communication and prescription on two video footages using a checklist followed by group discussions. Total post-test OSCE score was significantly higher for 2010/11 academic year students (n = 147) than it was for 2009/10 year students (n = 131). The 2010/11 academic year students performed significantly better than the 2009/10 academic year students on four steps of OSCE. These steps were "defining the patient's problem", "specifying the therapeutic objective", "specifying the non-pharmacological treatment" and "choosing a (drug) treatment, taking all relevant patient characteristics into account". The present study demonstrated that the implementation of video footages and group discussions to WHO/Good Prescribing Method improved the fourth-year medical students' performance in rational pharmacotherapy skills.

  6. From rational creatures to the rational Creator: ancient and patristic analogies of the “fine-tuning” argument

    Directory of Open Access Journals (Sweden)

    Alexey Fokin

    2017-12-01

    Full Text Available In this article the author deals with the proofs of the existence of God, based on the fact of the presence of rational beings in the world. These proofs can be found in Greek and Roman Classical philosophy and early Patristics, and can be viewed as an analogue of the modern “fine-tuning argument”. The author considers the origins and development of this argument in the Greek and Roman philosophy: in Socrates, Plato, Cicero, Sextus Empiricus, and especially the Stoics, who gave to the argument a logical form, based on the relationship between “the parts and the whole”: if the world as a whole produces and contains rational beings as its parts, it should also be rational or contain a rational principle that generates all its parts and governs them, just as human soul governs human body. The correction of this argument was proposed by Sextus Empiricus, who introduced the concept of "spermatic logoi", or rational principles, to explain the generation of the rational beings by the world, so that if the world contains the spermatic logoi of rational and living beings, then the world as a whole is also rational. The author also investigates the reception of the argument based on the existence of rational beings in the world in Latin Patristics: in Minucius Felix, Tertullian and especially Lactantius, in whom this argument has reached the climax of its development. At the same time it was shown, that the ancient argument has undergone a transformation from the postulation of the rationality of the world as a whole or its equation with God himself to a genuine proof of the existence of the one God who is the Creator both of the world and human beings, superior to the both as the all-powerful and transcendent Mind.

  7. Rational Decision Making as Performative Praxis: Explaining Rationality's Éternel Retour

    OpenAIRE

    Cabantous, L.; Gond, J-P.

    2011-01-01

    Organizational theorists built their knowledge of decision making through a progressive critique of rational choice theory. Their positioning towards rationality, however, is at odds with the observation of rationality persistence in organizational life. This paper addresses this paradox. It proposes a new perspective on rationality that allows the theorizing of the production of rational decisions by organizations. To account for rationality's éternel retour, we approach rational decision ma...

  8. Interpolation of rational matrix functions

    CERN Document Server

    Ball, Joseph A; Rodman, Leiba

    1990-01-01

    This book aims to present the theory of interpolation for rational matrix functions as a recently matured independent mathematical subject with its own problems, methods and applications. The authors decided to start working on this book during the regional CBMS conference in Lincoln, Nebraska organized by F. Gilfeather and D. Larson. The principal lecturer, J. William Helton, presented ten lectures on operator and systems theory and the interplay between them. The conference was very stimulating and helped us to decide that the time was ripe for a book on interpolation for matrix valued functions (both rational and non-rational). When the work started and the first partial draft of the book was ready it became clear that the topic is vast and that the rational case by itself with its applications is already enough material for an interesting book. In the process of writing the book, methods for the rational case were developed and refined. As a result we are now able to present the rational case as an indepe...

  9. Metabonomics and drug development.

    Science.gov (United States)

    Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann

    2015-01-01

    Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.

  10. Self-Reported Rationing Behavior Among US Physicians: A National Survey.

    Science.gov (United States)

    Sheeler, Robert D; Mundell, Tim; Hurst, Samia A; Goold, Susan Dorr; Thorsteinsdottir, Bjorg; Tilburt, Jon C; Danis, Marion

    2016-12-01

    Rationing is a controversial topic among US physicians. Understanding their attitudes and behaviors around rationing may be essential to a more open and sensible professional discourse on this important but controversial topic. To describe rationing behavior and associated factors among US physicians. Survey mailed to US physicians in 2012 to evaluate self-reported rationing behavior and variables related to this behavior. US physicians across a full spectrum of practice settings. A total of 2541 respondents, representing 65.6 % of the original mailing list of 3872 US addresses. The study was a cross-sectional analysis of physician attitudes and self-reported behaviors, with neutral language representations of the behaviors as well as an embedded experiment to test the influence of the word "ration" on perceived responsibility. Overall percentage of respondents reporting rationing behavior in various contexts and assessment of attitudes toward rationing. In total, 1348 respondents (53.1 %) reported having personally refrained within the past 6 months from using specific clinical services that would have provided the best patient care, because of health system cost. Prescription drugs (n = 1073 [48.3 %]) and magnetic resonance imaging (n = 922 [44.5 %]) were most frequently rationed. Surgical and procedural specialists were less likely to report rationing behavior (adjusted odds ratio [OR] [95 % CI], 0.8 [0.9-0.9] and 0.5 [0.4-0.6], respectively) compared to primary care. Compared with small or solo practices, those in medical school settings reported less rationing (adjusted OR [95 % CI], 0.4 [0.2-0.7]). Physicians who self-identified as very or somewhat liberal were significantly less likely to report rationing (adjusted OR [95 % CI], 0.7 [0.6-0.9]) than those self-reporting being very or somewhat conservative. A more positive opinion about rationing tended to align with greater odds of rationing. More than one-half of respondents engaged in

  11. Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Hyeong-Min Lee

    2016-01-01

    Full Text Available Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.

  12. RATIONAL APPROXIMATIONS TO GENERALIZED HYPERGEOMETRIC FUNCTIONS.

    Science.gov (United States)

    Under weak restrictions on the various free parameters, general theorems for rational representations of the generalized hypergeometric functions...and certain Meijer G-functions are developed. Upon specialization, these theorems yield a sequency of rational approximations which converge to the

  13. Drugs and development: the global impact of drug use and trafficking on social and economic development.

    Science.gov (United States)

    Singer, Merrill

    2008-12-01

    Locating development efforts within the context of globalism and global drug capitalism, this article examines the significant health and social impact both legal and illegal drugs have on international development efforts. The paper takes on an issue that is generally overlooked in the development debate and is not much addressed in the current international development standard, the Millennium Development Goals, and yet is one that places serious constraints on the ability of underdeveloped nations to achieve improvement. The relationship between psychotropic or "mind/mood altering" drugs and sustainable development is rooted in the contribution that the legal and illegal drug trade makes to a set of barriers to development, including: (1) interpersonal crime and community violence; (2) the corruption of public servants and the disintegration of social institutions; (3) the emergence of new or enhanced health problems; (4) the lowering of worker productivity; (5) the ensnarement of youth in drug distribution and away from productive education or employment; (6) the skewing of economies to drug production and money laundering. The paper emphasizes the need for new approaches for diminishing the burden placed by drugs on development.

  14. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  15. Rationalizing the Promotion of Non-Rational Behaviors in Organizations.

    Science.gov (United States)

    Smith, Peter A. C.; Sharma, Meenakshi

    2002-01-01

    Organizations must balance rational/technical efficiency and emotions. Action learning has been proven to be effective for developing emotional openness in the workplace. Facilitators of action learning should draw upon the disciplines of counseling, Gestalt, psychodynamics, and Eastern philosophies. (Contains 23 references.) (SK)

  16. The procedure of new drug application and the philosophy of critical rationalism or the limits of quality assurance with good clinical practice.

    Science.gov (United States)

    Högel, J; Gaus, W

    1999-12-01

    K.R. Popper's philosophy of critical rationalism is concerned with the detection and removal of error. Fundamental contradictions exist between Popper's theory of knowledge and the present-day practice of the clinical investigation of new drugs. Currently, the public authorities concerned with the licensing of drugs pass judgment on trials, which are closely linked by the one-sponsor problem: the assertions made by the sponsor are not independently confirmed. This lack leads to excessive documentation and to costly monitoring and auditing, which are intended to ensure the credibility of results. In Popper's view, confirmatory trials, independent of the sponsor and supervised by the regulatory bodies, would be a better way to achieve reliable knowledge. The consequence would, among other things, be a reorganization of phase III of the clinical investigation of new drugs by dividing it into independent parts, one under the control of the sponsor and one under the control of the public authority. The implementation of this suggestion would lead to a more scientific manner of dealing with new drugs and to savings in terms of unproductive measures during the application process.

  17. CREDIT RATIONING AND SME DEVELOPMENT IN BOTSWANA ...

    African Journals Online (AJOL)

    None

    have the negative effect of stifling the growth of potential firms, thereby .... credit market may explain the credit rationing behaviour of banks to ... derive policy implications to enhance access to bank credit by SMEs. 4. ..... The main challenges to SMEs identified by the study were non-payment of outstanding ... This decision is.

  18. THE HICKSIAN RATIONAL CONSUMER

    OpenAIRE

    Manuel FERNÁNDEZ-GRELA

    2005-01-01

    The aim of this paper is to trace the evolution of the concept of ''rational consumer'' in Hicks's writings. After being one of the pioneers in the introduction of rationality assumptions about consumer behaviour in economic models, Hicks gradually developed a sceptical view about some of the uses to which those assumptions were put into. The focus of the paper is on continuity in Hicksian views, providing a picture of gradual changes in the long series of Hicks's works

  19. Drug development in neuropsychopharmacology.

    Science.gov (United States)

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  20. Rationality in Society

    NARCIS (Netherlands)

    Flache, Andreas; Dijkstra, Jacob; Wright, James D.

    2015-01-01

    Contemporary theories of rational behavior in human society augment the orthodox model of rationality both by adding various forms of bounded rationality and relaxing the assumptions of self-interest and materialistic preferences. This entry discusses how these extensions of the theory of rational

  1. Love and rationality: on some possible rational effects of love

    Directory of Open Access Journals (Sweden)

    Gustavo Ortiz-Millán

    2007-01-01

    Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.Neste artigo defendo a idéia de que, em vez de perturbar a racionalidade, como a concepção do senso comum o faz, o amor pode, na verdade, ajudar-nos a desenvolver modos racionais de pensar e agir. Dou bons argumentos para o amor romântico ou erótico, uma vez que esse é o tipo de amor que é mais freqüentemente associado à irracionalidade no agir e no pensar. Argumento que esse tipo de amor pode fazer-nos desenvolver formas epistêmicas e práticas de racionalidade. Com base em uma análise de suas tendências características para a ação, argumento que o amor pode ajudar-nos a desenvolver uma forma instrumental de racionalidade para se determinar o melhor meio de atingir o objeto de amor. Ele também pode limitar o número de considerações práticas que podem ajudar-nos a atingir os nossos objetivos. Finalmente, o amor pode gerar modos racionais de formação de crenças ao estruturar os parâmetros considerados na percepção e na aten

  2. New Zealand’s Drug Development Industry

    Directory of Open Access Journals (Sweden)

    Christopher Carswell

    2013-09-01

    Full Text Available The pharmaceutical industry’s profitability depends on identifying and successfully developing new drug candidates while trying to contain the increasing costs of drug development. It is actively searching for new sources of innovative compounds and for mechanisms to reduce the enormous costs of developing new drug candidates. There is an opportunity for academia to further develop as a source of drug discovery. The rising levels of industry outsourcing also provide prospects for organisations that can reduce the costs of drug development. We explored the potential returns to New Zealand (NZ from its drug discovery expertise by assuming a drug development candidate is out-licensed without clinical data and has anticipated peak global sales of $350 million. We also estimated the revenue from NZ’s clinical research industry based on a standard per participant payment to study sites and the number of industry-sponsored clinical trials approved each year. Our analyses found that NZ’s clinical research industry has generated increasing foreign revenue and appropriate policy support could ensure that this continues to grow. In addition the probability-based revenue from the out-licensing of a drug development candidate could be important for NZ if provided with appropriate policy and financial support.

  3. Orphan drug: Development trends and strategies

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2010-01-01

    Full Text Available The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model - niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases.

  4. Fragment-based drug discovery using rational design.

    Science.gov (United States)

    Jhoti, H

    2007-01-01

    Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

  5. A Rational Approach to Rational Suicide.

    Science.gov (United States)

    Richman, Joseph

    1992-01-01

    Describes suicide as reaction to internal and external sources of stress and the impact of life events. Notes that, in the elderly, these situations are prevalent in many who are not suicidal. Contends that much more is written about rational suicide than its alternative (rational nonsuicide). Reviews reasons for this and suggests rational…

  6. Decision Making: Rational, Nonrational, and Irrational.

    Science.gov (United States)

    Simon, Herbert A.

    1993-01-01

    Describes the current state of knowledge about human decision-making and problem-solving processes, explaining recent developments and their implications for management and management training. Rational goal-setting is the key to effective decision making and accomplishment. Bounded rationality is a realistic orientation, because the world is too…

  7. Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

    International Nuclear Information System (INIS)

    Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

    2012-01-01

    In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

  8. Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies.

    Science.gov (United States)

    Manoharan, Prabu; Vijayan, R S K; Ghoshal, Nanda

    2010-10-01

    The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

  9. Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies

    Science.gov (United States)

    Manoharan, Prabu; Vijayan, R. S. K.; Ghoshal, Nanda

    2010-10-01

    The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables ( X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

  10. Rational Asymmetric Development, Piketty and Poverty in Africa

    Directory of Open Access Journals (Sweden)

    Simplice A. Asongu

    2016-12-01

    Full Text Available An April 2015 World Bank report on the Millennium Development Goal poverty target has revealed that extreme poverty has been decreasing in all regions of the world with the exception of Africa. This study extends the implications of Thomas Piketty’s celebrated literature from developed countries to the nexus between developed nations and African countries by building on responses from Rogoff (2014 and Stiglitz (2014, post Washington Consensus paradigms and underpinnings from SolowSwan and Boyce-Fofack-Ndikumana. The central argument presented is that the inequality problem is at the heart of rational asymmetric development between rich and poor countries. Piketty has shown that inequality increases when the return on capital is higher than the growth rate, because the poor cannot catch-up with the rich. We argue that when the return on political economy (or capitalism fuelled illicit capital flight is higher than the growth rate in African countries, inequality in development increases and Africa may not catch-up with the developed world. As an ideal solution, Piketty has proposed progressive income taxation based on automatic exchange of bank information. The ideal analogy proposed in tackling the spirit of African poverty is a comprehensive commitment to fighting illicit capital flight based on this. Hence, contrary to theoretical underpinnings of exogenous growth models, catch-up may not be so apparent. Implications for the corresponding upward bias in endogenous development and catch-up literature are discussed.

  11. Self-deception as pseudo-rational regulation of belief.

    Science.gov (United States)

    Michel, Christoph; Newen, Albert

    2010-09-01

    Self-deception is a special kind of motivational dominance in belief-formation. We develop criteria which set paradigmatic self-deception apart from related phenomena of auto-manipulation such as pretense and motivational bias. In self-deception rational subjects defend or develop beliefs of high subjective importance in response to strong counter-evidence. Self-deceivers make or keep these beliefs tenable by putting prima-facie rational defense-strategies to work against their established standards of rational evaluation. In paradigmatic self-deception, target-beliefs are made tenable via reorganizations of those belief-sets that relate relevant data to target-beliefs. This manipulation of the evidential value of relevant data goes beyond phenomena of motivated perception of data. In self-deception belief-defense is pseudo-rational. Self-deceivers will typically apply a dual standard of evaluation that remains intransparent to the subject. The developed model of self-deception as pseudo-rational belief-defense is empirically anchored. So, we hope to put forward a promising candidate. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Positron emission tomography in drug development

    International Nuclear Information System (INIS)

    Rubin, R. H.; Fischman, A. J.

    1997-01-01

    There are four kinds of measurements that can be carried out with positron emission tomography (PET) that can contribute significantly to the process of drug development: pharmacodynamic measurement of tissue metabolism influenced by a given drug; precise measurements of tissue blood flow; tissue pharmacokinetics of a given drug following administration of a particular dose; and the temporal course of ligand-receptor interaction. One or more of these measurements can greatly improve the decision making involved in determining the appropriate dose of a drug, the clinical situations in which a drug might be useful, and the linkage of pharmacokinetics with pharmacodynamics, which is at the heart of effective drug development. The greater the potential of a particular compound as a therapeutic agent, the greater the potential for PET to contribute to the drug development process

  13. Development of decommissioning recycle simulator for the rational reuse of dismantled wastes

    International Nuclear Information System (INIS)

    Sakata, Eichi; Ozaki, Sachio; Hironaga, Michihiko; Nishiuchi, Tatsuo

    2002-01-01

    An expert system having a faculty of furnishing motivations for decommissioning planners to establish a rational recycle scenario has been developed and named 'recycle simulator'. This paper presents both a summarized configuration and an algorithm of the proposed system and indicates content of required data-bases and their mutual relations. Finally an instance applying the 'recycle simulator' pointed out some important factors in the reuse of demolished concrete. (author)

  14. THE ROLE OF P-GLYCOPROTEIN IN RATIONAL PHARMACOTHERAPY IN CARDIOLOGY

    Directory of Open Access Journals (Sweden)

    A. V. Shulkin

    2015-09-01

    Full Text Available On the basis of the analysis of published data the role of P-glycoprotein, carrier protein, in rational pharmacotherapy in cardiology was shown on the example of its substrates – digoxin, antiplatelet agents and anticoagulants. Determination of C3435T polymorphism of multidrug resistance gene (MDR1, encoding P-glycoprotein, in pharmacotherapy with digoxin, antiplatelet drugs (clopidogrel tikagrelol, prasugrel and anticoagulants (dabigatran etexilate, rivaroxaban, edoxaban is not feasible in routine practice. Drug in- teractions have clinical implications for the efficacy and safety of pharmacotherapy in coadministration of these drugs with P-glycoprotein substrates, inducers and inhibitors.

  15. Rational development of radiopharmaceuticals for HIV-1

    International Nuclear Information System (INIS)

    Lau, Chuen-Yen; Maldarelli, Frank; Eckelman, William C.; Neumann, Ronald D.

    2014-01-01

    The global battle against HIV-1 would benefit from a sensitive and specific radiopharmaceutical to localize HIV-infected cells. Ideally, this probe would be able to identify latently infected host cells containing replication competent HIV sequences. Clinical and research applications would include assessment of reservoirs, informing clinical management by facilitating assessment of burden of infection in different compartments, monitoring disease progression and monitoring response to therapy. A “rational” development approach could facilitate efficient identification of an appropriate targeted radiopharmaceutical. Rational development starts with understanding characteristics of the disease that can be effectively targeted and then engineering radiopharmaceuticals to hone in on an appropriate target, which in the case of HIV-1 (HIV) might be an HIV-specific product on or in the host cell, a differentially expressed gene product, an integrated DNA sequence specific enzymatic activity, part of the inflammatory response, or a combination of these. This is different from the current approach that starts with a radiopharmaceutical for a target associated with a disease, mostly from autopsy studies, without a strong rationale for the potential to impact patient care. At present, no targeted therapies are available for HIV latency, although a number of approaches are under study. Here we discuss requirements for a radiopharmaceutical useful in strategies targeting persistently infected cells. The radiopharmaceutical for HIV should be developed based on HIV biology, studied in an animal model and then in humans, and ultimately used in clinical and research settings

  16. Drug residues recovered in feed after various feedlot mixer truck cleanout procedures.

    Science.gov (United States)

    Van Donkersgoed, Joyce; Sit, Dan; Gibbons, Nicole; Ramogida, Caterina; Hendrick, Steve

    2010-01-01

    A study was conducted to determine the effectiveness of two methods of equipment cleanout, sequencing or flushing, for reducing drug carryover in feedlot mixer trucks. Feed samples were collected from total mixed rations before and after various feed mixer equipment cleanout procedures. Medicated rations contained either 11 ppm of tylosin or 166 or 331 ppm of chlortetracycline. There were no differences between sequencing and flushing or between flushing with dry barley and flushing with barley silage in the median proportion of drug recovered in the next ration. A larger drug reduction was achieved using flush material at a volume of 10 versus 5% of the mixer capacity and mixing the flush material for 3 versus 4 min. Regardless of the drug or prescription concentrations in the total mixed rations or the equipment cleanout procedure used, concentrations of chlortetracycline and tylosin recovered were very low.

  17. One For All? Hitting multiple Alzheimer’s Disease targets with one drug

    Directory of Open Access Journals (Sweden)

    Rebecca Ellen Hughes

    2016-04-01

    Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

  18. Success rates for product development strategies in new drug development.

    Science.gov (United States)

    Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

    2016-04-01

    While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

  19. Drug Design and Emotion

    Science.gov (United States)

    Folkers, Gerd; Wittwer, Amrei

    2007-11-01

    "Geteiltes Leid ist halbes Leid." The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. Though subjective, mental and physical states can be shared. Visual perception of suffering may be important but also narrative description plays a role, all our senses are mixing in. It is hypothetized that literature, art and humanities allow this overlap. A change of mental states can lead to empirically observable effects as it is the case for the effect of role identity or placebo on pain perception. Antidepressants and other therapeutics are another choice to change the mental and bodily states. Their development follows today's notion of "rationality" in the design of therapeutics and is characterized solely by an atomic resolution approach to understand drug activity. Since emotional states and physiological states are entangled, given the difficulty of a physical description of emotion, the future rational drug design should encompass mental states as well.

  20. Choice, internal consistency, and rationality

    OpenAIRE

    Aditi Bhattacharyya; Prasanta K. Pattanaik; Yongsheng Xu

    2010-01-01

    The classical theory of rational choice is built on several important internal consistency conditions. In recent years, the reasonableness of those internal consistency conditions has been questioned and criticized, and several responses to accommodate such criticisms have been proposed in the literature. This paper develops a general framework to accommodate the issues raised by the criticisms of classical rational choice theory, and examines the broad impact of these criticisms from both no...

  1. Population and Drugs

    OpenAIRE

    Feberová, Beata

    2008-01-01

    PEOPLE AND DRUGS II. Author: Križanová L. Tutor: Práznovcová L. Dept. of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Czech Republic Background: It is necessary to rationalize the system of funding of health service. One of the ways how to achieve this aim is monitoring of drug prescription and patient's financial participation on the therapy. Aim of study: Observation and analysis of drug prescription aimed at the prescription of the drug...

  2. Ethics of rationing of nursing care.

    Science.gov (United States)

    Rooddehghan, Zahra; Yekta, Zohreh Parsa; Nasrabadi, Alireza N

    2016-09-21

    Rationing of various needed services, for example, nursing care, is inevitable due to unlimited needs and limited resources. Rationing of nursing care is considered an ethical issue since it requires judgment about potential conflicts between personal and professional values. The present research sought to explore aspects of rationing nursing care in Iran. This study applied qualitative content analysis, a method to explore people's perceptions of everyday life phenomena and interpret the subjective content of text data. Data collection was performed through in-depth, unstructured, face-to-face interviews with open-ended questions. The study population included Iranian nurses of all nursing positions, from clinical nurses to nurse managers. Purposive sampling was employed to select 15 female and 3 male nurses (11 clinical nurses, 3 supervisors, 1 matron, 1 nurse, and 2 members of the Nursing Council) working in hospitals of three cities in Iran. The study protocol was approved by Tehran University of Medical Sciences (91D1302870). Written informed consent was also obtained from all participants. According to the participants, rationing of nursing care consisted of two categories, that is, causes of rationing and consequences of rationing. The first category comprised three subcategories, namely, patient needs and demands, routinism, and VIP patients. The three subcategories forming the second category were missed nursing care, patient dissatisfaction, and nurses' feeling of guilt. Levels at which healthcare practices are rationed and clarity of the rationing are important structural considerations in the development of an equal, appropriate, and ethical healthcare system. Moreover, the procedure of rationing is critical as it not only influences people's lives but also reflects the values that dominate in the society. Therefore, in order to minimize the negative consequences of rationing of nursing care, further studies on the ethical dimensions of this phenomenon

  3. Establishing a Drug Rehabilitation Center in a Prison Setting.

    Science.gov (United States)

    Page, Richard C.

    The implementation of a drug treatment center in a prison environment is described. Such topics as the program initiation, selection of residents, early program operation are discussed. Program activities such as regular group counseling and rational therapy were developed to assist residents in the resolution of personal problems and interactions…

  4. P-glycoprotein recognition of substrates and circumvention through rational drug design.

    Science.gov (United States)

    Raub, Thomas J

    2006-01-01

    It is now well recognized that membrane efflux transporters, especially P-glycoprotein (P-gp; ABCB1), play a role in determining the absorption, distribution, metabolism, excretion, and toxicology behaviors of some drugs and molecules in development. An investment in screening structure-activity relationship (SAR) is warranted in early discovery when exposure and/or target activity in an in vivo efficacy model is not achieved and P-gp efflux is identified as a rate-limiting factor. However, the amount of investment in SAR must be placed into perspective by assessing the risks associated with the intended therapeutic target, the potency and margin of safety of the compound, the intended patient population(s), and the market competition. The task of rationally designing a chemistry strategy for circumventing a limiting P-gp interaction can be daunting. The necessity of retaining biological potency and metabolic stability places restrictions on what can be done, and the factors for P-gp recognition of substrates are complicated and poorly understood. The parameters within the assays that affect overall pump efficiency or net efflux, such as passive diffusion, membrane partitioning, and molecular interaction between pump and substrate, should be understood when interpreting data sets associated with chemistry around a scaffold. No single, functional group alone is often the cause, but one group can accentuate the recognition points existing within a scaffold. This can be likened to a rheostat, rather than an on/off switch, where addition or removal of a key group can increase or decrease the pumping efficiency. The most practical approach to de-emphasize the limiting effects of P-gp on a particular scaffold is to increase passive diffusion. Efflux pumping efficiency may be overcome when passive diffusion is fast enough. Eliminating, or substituting with fewer, groups that solvate in water, or decreasing their hydrogen bonding capacity, and adding halogen groups can

  5. A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

    Science.gov (United States)

    Li, Jun; Nekka, Fahima

    2013-02-21

    The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Pragmatics & rationality.

    OpenAIRE

    Allott, N. E.

    2007-01-01

    This thesis is about the reconciliation of realistic views of rationality with inferential-intentional theories of communication. Grice (1957 1975) argued that working out what a speaker meant by an utterance is a matter of inferring the speaker's intentions on the presumption that she is acting rationally. This is abductive inference: inference to the best explanation for the utterance. Thus an utterance both rationalises and causes the interpretation the hearer constructs. Human rationality...

  7. What does systems biology mean for drug development?

    Science.gov (United States)

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

    The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with

  8. Baseline rationing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    The standard problem of adjudicating conflicting claims describes a situation in which a given amount of a divisible good has to be allocated among agents who hold claims against it exceeding the available amount. This paper considers more general rationing problems in which, in addition to claims...... to international protocols for the reduction of greenhouse emissions, or water distribution in drought periods. We define a family of allocation methods for such general rationing problems - called baseline rationing rules - and provide an axiomatic characterization for it. Any baseline rationing rule within...... the family is associated with a standard rule and we show that if the latter obeys some properties reflecting principles of impartiality, priority and solidarity, the former obeys them too....

  9. Rationing with baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    2013-01-01

    We introduce a new operator for general rationing problems in which, besides conflicting claims, individual baselines play an important role in the rationing process. The operator builds onto ideas of composition, which are not only frequent in rationing, but also in related problems...... such as bargaining, choice, and queuing. We characterize the operator and show how it preserves some standard axioms in the literature on rationing. We also relate it to recent contributions in such literature....

  10. Rational Emotive Education

    Science.gov (United States)

    Knaus, William

    1977-01-01

    Rational Emotive Education--an outgrowth of theories developed by Albert Ellis--is a teaching design of mental health concepts and problem-solving activities designed to help students to approach and cope with their problems through experiential learning, via a structured, thematic sequence of emotive education lessons. (MJB)

  11. Towards a sustainable system of drug development

    NARCIS (Netherlands)

    Moors, Ellen H.M.; Cohen, Adam F.; Schellekens, Huub

    2014-01-01

    Drug development has become the exclusive activity of large pharmaceutical companies. However, the output of new drugs has been decreasing for the past decade and the prices of new drugs have risen steadily, leading to access problems for many patients. By analyzing the history of drug development

  12. A Comparative Analysis of Two Software Development Methodologies: Rational Unified Process and Extreme Programming

    Directory of Open Access Journals (Sweden)

    Marcelo Rafael Borth

    2014-01-01

    Full Text Available Software development methodologies were created to meet the great market demand for innovation, productivity, quality and performance. With the use of a methodology, it is possible to reduce the cost, the risk, the development time, and even increase the quality of the final product. This article compares two of these development methodologies: the Rational Unified Process and the Extreme Programming. The comparison shows the main differences and similarities between the two approaches, and highlights and comments some of their predominant features.

  13. Ananyeva Rational antibiotic use in rheumatology

    Directory of Open Access Journals (Sweden)

    Boris Sergeyevich Belov

    2012-06-01

    Full Text Available To control infections and infectious complications is one of the most urgent challenges in medicine under present-day conditions. At the same time, rational therapy with anti-infective drugs occupies a highly importance place. In rheumatology, the necessity of using antibiotics is associated with at least two factors, such as eradication of a pathogen trigger (an infectious agent that triggers the immunopathological mechanisms of inflammation and treatment of comorbid infection. The paper gives information on etiological agents and detailed antimicrobial therapy regimens for the major infections observed in modern rheumatology.

  14. Ananyeva Rational antibiotic use in rheumatology

    Directory of Open Access Journals (Sweden)

    Boris Sergeyevich Belov

    2012-01-01

    Full Text Available To control infections and infectious complications is one of the most urgent challenges in medicine under present-day conditions. At the same time, rational therapy with anti-infective drugs occupies a highly importance place. In rheumatology, the necessity of using antibiotics is associated with at least two factors, such as eradication of a pathogen trigger (an infectious agent that triggers the immunopathological mechanisms of inflammation and treatment of comorbid infection. The paper gives information on etiological agents and detailed antimicrobial therapy regimens for the major infections observed in modern rheumatology.

  15. Inaugurating Rationalization: Three Field Studies Find Increased Rationalization When Anticipated Realities Become Current.

    Science.gov (United States)

    Laurin, Kristin

    2018-04-01

    People will often rationalize the status quo, reconstruing it in an exaggeratedly positive light. They will even rationalize the status quo they anticipate, emphasizing the upsides and minimizing the downsides of sociopolitical realities they expect to take effect. Drawing on recent findings on the psychological triggers of rationalization, I present results from three field studies, one of which was preregistered, testing the hypothesis that an anticipated reality becoming current triggers an observable boost in people's rationalizations. San Franciscans rationalized a ban on plastic water bottles, Ontarians rationalized a targeted smoking ban, and Americans rationalized the presidency of Donald Trump, more in the days immediately after these realities became current compared with the days immediately before. Additional findings show evidence for a mechanism underlying these behaviors and rule out alternative accounts. These findings carry implications for scholarship on rationalization, for understanding protest behavior, and for policymakers.

  16. Realization theory for rational systems: Minimal rational realizations

    NARCIS (Netherlands)

    J. Nemcová (Jana); J.H. van Schuppen (Jan)

    2010-01-01

    htmlabstractThe study of realizations of response maps is a topic of control and system theory. Realization theory is used in system identification and control synthesis. A minimal rational realization of a given response map p is a rational realization of p such that the dimension of its state

  17. Many faces of rationality: Implications of the great rationality debate for clinical decision‐making

    Science.gov (United States)

    Elqayam, Shira

    2017-01-01

    Abstract Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people “should” or “ought to” make their decisions) and descriptive theories of decision‐making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence‐based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision‐making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret‐based rationality, pragmatic/substantive rationality, and meta‐rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is “rational” behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context‐poor situations, such as policy decision‐making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision

  18. Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

    International Nuclear Information System (INIS)

    Makin, Guy; Dive, Caroline

    2001-01-01

    Drug resistance is a fundamental problem in the treatment of most common human cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcoming drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signalling, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan et al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-mediated survival signalling, and offers the potential for targeted adjuvant therapy as a means of overcoming drug resistance

  19. Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures.

    Science.gov (United States)

    Gertsch, Jürg

    2011-07-01

    For centuries the science of pharmacognosy has dominated rational drug development until it was gradually substituted by target-based drug discovery in the last fifty years. Pharmacognosy stems from the different systems of traditional herbal medicine and its "reverse pharmacology" approach has led to the discovery of numerous pharmacologically active molecules and drug leads for humankind. But do botanical drugs also provide effective mixtures? Nature has evolved distinct strategies to modulate biological processes, either by selectively targeting biological macromolecules or by creating molecular promiscuity or polypharmacology (one molecule binds to different targets). Widely claimed to be superior over monosubstances, mixtures of bioactive compounds in botanical drugs allegedly exert synergistic therapeutic effects. Despite evolutionary clues to molecular synergism in nature, sound experimental data are still widely lacking to support this assumption. In this short review, the emerging concept of network pharmacology is highlighted, and the importance of studying ligand-target networks for botanical drugs is emphasized. Furthermore, problems associated with studying mixtures of molecules with distinctly different pharmacodynamic properties are addressed. It is concluded that a better understanding of the polypharmacology and potential network pharmacology of botanical drugs is fundamental in the ongoing rationalization of phytotherapy. © Georg Thieme Verlag KG Stuttgart · New York.

  20. 75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs

    Science.gov (United States)

    2010-06-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0247] Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug...

  1. Use of SPring-8 in drug development

    International Nuclear Information System (INIS)

    Nishijima, Kazumi

    2006-01-01

    Protein structure analysis consortium was established by 21 drug companies and has analyzed protein structures using the beam line BL32B2 of SPring-8 since September in 2002. Outline of the protein structure analysis consortium, contribution of SPring-8 to drug development, and the present status and future of use of SPring-8 are stated. For examples of structure analysis, the human nuclear enzyme (PARP-1) fragment complex crystal structure, human ISG20, human dipeptidine peptidase IV, human cMDH, chromatin binding human nuclear enzyme complex, change of structure of each step of tyrosine activation of bacteria tyrosine tRNA synthetase are described. Contribution of analysis of protein structure and functions to drug development, development process of new drug, drug screening using compounds database on the basis of the three dimensional structure of receptor active site, genome drug development, and the effects of a target drug on the market are explained. (S.Y.)

  2. Many faces of rationality: Implications of the great rationality debate for clinical decision-making.

    Science.gov (United States)

    Djulbegovic, Benjamin; Elqayam, Shira

    2017-10-01

    Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people "should" or "ought to" make their decisions) and descriptive theories of decision-making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence-based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision-making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret-based rationality, pragmatic/substantive rationality, and meta-rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is "rational" behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context-poor situations, such as policy decision-making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision-making, whereas in the context

  3. Pharmacogenomics to Revive Drug Development in Cardiovascular Disease.

    Science.gov (United States)

    Dubé, Marie-Pierre; de Denus, Simon; Tardif, Jean-Claude

    2016-02-01

    Investment in cardiovascular drug development is on the decline as large cardiovascular outcomes trials require considerable investments in time, efforts and financial resources. Pharmacogenomics has the potential to help revive the cardiovascular drug development pipeline by providing new and better drug targets at an earlier stage and by enabling more efficient outcomes trials. This article will review some of the recent developments highlighting the value of pharmacogenomics for drug development. We discuss how genetic biomarkers can enable the conduct of more efficient clinical outcomes trials by enriching patient populations for good responders to the medication. In addition, we assess past drug development programs which support the added value of selecting drug targets that have established genetic evidence supporting the targeted mechanism of disease. Finally, we discuss how pharmacogenomics can provide valuable evidence linking a drug target to clinically relevant outcomes, enabling novel drug discovery and drug repositioning opportunities.

  4. Refining stability and dissolution rate of amorphous drug formulations

    DEFF Research Database (Denmark)

    Grohganz, Holger; Priemel, Petra A; Löbmann, Korbinian

    2014-01-01

    Introduction: Poor aqueous solubility of active pharmaceutical ingredients (APIs) is one of the main challenges in the development of new small molecular drugs. Additionally, the proportion of poorly soluble drugs among new chemical entities is increasing. The transfer of a crystalline drug to its...... and on the interaction of APIs with small molecular compounds rather than polymers. Finally, in situ formation of an amorphous form might be an option to avoid storage problems altogether. Expert opinion: The diversity of poorly soluble APIs formulated in an amorphous drug delivery system will require different...... approaches for their stabilisation. Thus, increased focus on emerging techniques can be expected and a rational approach to decide the correct formulation is needed....

  5. Standby Gasoline Rationing Plan

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-06-01

    The final rules adopted by the President for a Standby Gasoline Rationing Plan are presented. The plan provides that eligibility for ration allotments will be determined primarily on the basis of motor vehicle registrations, taking into account historical differences in the use of gasoline among states. The regulations also provide authority for supplemental allotments to firms so that their allotment will equal a specified percentage of gasoline use during a base period. Priority classifications, i.e., agriculture, defense, etc., are established to assure adequate gasoline supplies for designated essential services. Ration rights must be provided by end-users to their suppliers for each gallon sold. DOE will regulate the distribution of gasoline at the wholesale level according to the transfer by suppliers of redeemed ration rights and the gasoline allocation regulations. Ration rights are transferable. A ration banking system is created to facilitate transfers of ration rights. Each state will be provided with a reserve of ration rights to provide for hardship needs and to alleviate inequities. (DC)

  6. Rationality in discovery : a study of logic, cognition, computation and neuropharmacology

    NARCIS (Netherlands)

    Bosch, Alexander Petrus Maria van den

    2001-01-01

    Part I Introduction The specific problem adressed in this thesis is: what is the rational use of theory and experiment in the process of scientific discovery, in theory and in the practice of drug research for Parkinson’s disease? The thesis aims to answer the following specific questions: what is:

  7. The Emotional and Moral Basis of Rationality

    Science.gov (United States)

    Boostrom, Robert

    2013-01-01

    This chapter explores the basis of rationality, arguing that critical thinking tends to be taught in schools as a set of skills because of the failure to recognize that choosing to think critically depends on the prior development of stable sentiments or moral habits that nourish a rational self. Primary among these stable sentiments are the…

  8. Pharmaco-epidcemiology of drugs utilised for cataract surgery in a government medical college and hospital.

    Science.gov (United States)

    Biswas, Supreeti; Mondal, Kanchan Kumar; Halder, Sujash; Sarkar, Sougat Sourendra; Maiti, Tamoghna; Lahiri, Saibendu Kumar; Haldar, Swaraj

    2010-12-01

    Prescription audit is a powerful tool for rational prescription. To evaluate pharmaco-epidemiology of drugs utilised for cataract surgery, a retrospective study was conducted in the department of pharmacology, RG Kar Medical College, Kolkata. Data from bed head tickets of one year, available in medical record section, were collected in case report forms and analysed. Utilisation pattern of drugs like dosage form, dose, route and frequency of administration and duration of therapy were audited. Drug prescription versus therapeutic indication was also evaluated. Price of the prescribed drugs was evaluated for rationality towards cost-effective prescription. For 848 cases of cataract surgery, drugs were prescribed pre-, per- and post-operatively. Different fluoroquinolone antibiotics, anti-inflammatory and mydriatic-cycloplegic agents were prescribed. High or low cost drugs were prescribed both in generic (52%) and brand (48%) names. Few Latin abbreviations were used in directions. Different parameters and study results were discussed from various aspects to explore their social impacts. Though prescription pattern was almost rational, some parts need improvement. Healthcare provider should be aware of cost-effectiveness of the prescribed drugs for the benefit of patients to provide a rational prescription.

  9. Momentum effect in stocks’ returns between the rational and the behavioural financial theories: Proposition of the progressive rationality

    Directory of Open Access Journals (Sweden)

    Faten Zoghlami

    2013-01-01

    Full Text Available     The puzzling momentum strategies’ payoffs defied the rational financial theory asserting the stocks returns’ unpredictability. Moreover, the momentum effect persist the main stocks returns’ anomaly escaping any risk-based explanation. The resilience of this phenomenon had favoured the development of behavioural financial field, which breaks with the investor’ full rationality hypothesis. This paper attempts to reconcile between the rational and behavioural financial theories, through the introduction of the progressive rationality concept. Especially, we argue that recognizing the temporary inappropriate investors’ reactions; can resolve the puzzling momentum anomaly. To fulfil our objective, we identify the appropriate autoregressive level that captures the significant autocorrelations involved by the investors’ over and under reactions. Then, we explore the profitability of the 6/6 momentum strategy implemented on the adjusted stocks’ returns. The adjusted momentum strategy is still profitable but no longer puzzling, since the related excess return is henceforth fully captured by a β and a size effect.Key words: Tunisian momentum effect, the rational finance theory, the behavioural finance theory, the three-factorial model and the autoregressive process.

  10. Obesity and Pediatric Drug Development.

    Science.gov (United States)

    Vaughns, Janelle D; Conklin, Laurie S; Long, Ying; Zheng, Panli; Faruque, Fahim; Green, Dionna J; van den Anker, John N; Burckart, Gilbert J

    2018-05-01

    There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed for statements addressing obesity in pediatric patients. Forty-five drugs studied in pediatric patients under the FDA Amendments Act were found to have statements and key words in the medical and clinical pharmacology reviews and labels related to obesity. Forty-four products were identified similarly with pediatric studies under FDASIA. Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only 4 labels. We conclude that there is little information presently available to provide guidance related to dosing in obese pediatric patients. Moving forward, regulators, clinicians, and the pharmaceutical industry should consider situations in drug development in which the inclusion of obese patients in pediatric trials is necessary to facilitate the safe and effective use of new drug products in the obese pediatric population. © 2018, The American College of Clinical Pharmacology.

  11. The Irish Cost-Effectiveness Threshold: Does it Support Rational Rationing or Might it Lead to Unintended Harm to Ireland's Health System?

    Science.gov (United States)

    O'Mahony, James F; Coughlan, Diarmuid

    2016-01-01

    Ireland is one of the few countries worldwide to have an explicit cost-effectiveness threshold. In 2012, an agreement between government and the pharmaceutical industry that provided substantial savings on existing medications set the threshold at €45,000/quality-adjusted life-year (QALY). This replaced a previously unofficial threshold of €20,000/QALY. According to the agreement, drugs within the threshold will be granted reimbursement, whereas those exceeding it may still be approved following further negotiation. A number of drugs far exceeding the threshold have been approved recently. The agreement only applies to pharmaceuticals. There are four reasons for concern regarding Ireland's threshold. The absence of an explicit threshold for non-drug interventions leaves it unclear if there is parity in willingness to pay across all interventions. As the threshold resembles a price floor rather than a ceiling, in principle it only offers a weak barrier to cost-ineffective interventions. It has no empirical basis. Finally, it is probably too high given recent estimates of a threshold for the UK based on the cost effectiveness of services forgone of approximately £13,000/QALY. An excessive threshold risks causing the Irish health system unintended harm. The lack of an empirically informed threshold means the policy recommendations of cost-effectiveness analysis cannot be considered as fully evidence- based rational rationing. Policy makers should consider these issues and recent Irish legislation that defined cost effectiveness in terms of the opportunity cost of services forgone when choosing what threshold to apply once the current industry agreement expires at the end of 2015

  12. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  13. Fostering Non-Cognitive Development of Underrepresented Students through Rational Emotive Behavior Therapy: Recommendations for School Counselor Practice

    Science.gov (United States)

    Warren, Jeffrey M.; Hale, Robyn W.

    2016-01-01

    The non-cognitive factors (NCFs) endorsed by Sedlacek (2004) appear to align with the core values of rational emotive behavior therapy (REBT). This article explores theoretical and empirical evidence that suggests REBT fosters the development of NCFs. School counselors can promote non-cognitive development by embedding REBT throughout direct and…

  14. CIME-CIRM course Rationality Problems in Algebraic Geometry

    CERN Document Server

    Pirola, Gian

    2016-01-01

    Providing an overview of the state of the art on rationality questions in algebraic geometry, this volume gives an update on the most recent developments. It offers a comprehensive introduction to this fascinating topic, and will certainly become an essential reference for anybody working in the field. Rationality problems are of fundamental importance both in algebra and algebraic geometry. Historically, rationality problems motivated significant developments in the theory of abelian integrals, Riemann surfaces and the Abel–Jacobi map, among other areas, and they have strong links with modern notions such as moduli spaces, Hodge theory, algebraic cycles and derived categories. This text is aimed at researchers and graduate students in algebraic geometry.

  15. RATIONAL-IRRATIONAL ELECTORAL PREFERENCES, ALTRUISM AND EXPRESSIVE BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Mihai Ungureanu

    2015-01-01

    Full Text Available Caplan (2000, 2001, 2006 proposed the rational-irrationality model arguing that irrationality is a good as any other, whose consumption is maximized in relation to its costs and benefits. Applying this model to the problem of electoral behavior Caplan implies that voters ‘afford’ many irrational beliefs, because the lack of individual decisiveness renders vote as a consequenceless act. This paper contributes to the development of knowledge by analyzing the compatibility of rational irrationality with active electoral behavior. Two important arguments are being proposed: First, Wittman’s (2008 intuition that rational irrationality is incompatible with voting could be supported only about a particular type of altruism, which Caplan actually seems to reject. Second, rational irrationality seems to be compatible with expressive motivations, reinforcing the conclusion that rational-irrational individuals are active voters in mass elections.

  16. A more rational approach to new-product development.

    Science.gov (United States)

    Bonabeau, Eric; Bodick, Neil; Armstrong, Robert W

    2008-03-01

    Companies often treat new-product development as a monolithic process, but it can be more rationally divided into two parts: an early stage that focuses on evaluating prospects and eliminating bad bets, and a late stage that maximizes the remaining candidates' market potential. Recognizing the value of this approach, Eli Lilly designed and piloted Chorus, an autonomous unit dedicated solely to the early stage. This article demonstrates how segmenting development in this way can speed it up and make it more cost-effective. Two classes of decision-making errors can impede NPD, the authors say. First, managers often ignore evidence challenging their assumptions that projects will succeed. As a result, many projects go forward despite multiple red flags; some even reach the market, only to fail dramatically after their introduction. Second, companies sometimes terminate projects prematurely because people fail to conduct the right experiments to reveal products' potential. Most companies promote both kinds of errors by focusing disproportionately on late-stage development; they lack the early, truth-seeking functions that would head such errors off. In segmented NPD, however, the early-stage organization maintains loyalty to the experiment rather than the product, whereas the late-stage organization pursues commercial success. Chorus has significantly improved NPD efficiency and productivity at Lilly. Although the unit absorbs just one-tenth of Lilly's investment in early-stage development, it delivers a substantially greater fraction of the molecules slated for late Phase II trials--at almost twice the speed and less than a third of the cost of the standard process, sometimes shaving as much as two years off the usual development time.

  17. Drug discovery and developments in developing countries ...

    African Journals Online (AJOL)

    the major burden being in developing countries. Many of ... The driving force for drug discovery and development by pharmaceutical firms ... world and particularly in the third world countries ..... GFHR (2000) Global Forum for Health Research:.

  18. Normative and descriptive rationality: from nature to artifice and back

    Science.gov (United States)

    Besold, T. R.; Uckelman, S. L.

    2018-03-01

    Rationality plays a key role in both the study of human reasoning and Artificial Intelligence (AI). Certain notions of rationality have been adopted in AI as guides for the development of intelligent machines and these notions have been given a normative function. The notions of rationality in AI are often taken to be closely related to conceptions of rationality in human contexts. In this paper, we argue that the normative role of rationality differs in the human and artificial contexts. While rationality in human-focused fields of study is normative, prescribing how humans ought to reason, the normative conception in AI is built on a notion of human rationality which is descriptive, not normative, in the human context, as AI aims at building agents which reason as humans do. In order to make this point, we review prominent notions of rationality used in psychology, cognitive science, and (the history of) philosophy, as well as in AI, and discuss some factors that contributed to rationality being assigned the differing normative statuses in the differing fields of study. We argue that while 'rationality' is a normative notion in both AI and in human reasoning, the normativity of the AI conception of 'rationality' is grounded in a descriptive account of human rationality.

  19. Rational points, rational curves, and entire holomorphic curves on projective varieties

    CERN Document Server

    Gasbarri, Carlo; Roth, Mike; Tschinkel, Yuri

    2015-01-01

    This volume contains papers from the Short Thematic Program on Rational Points, Rational Curves, and Entire Holomorphic Curves and Algebraic Varieties, held from June 3-28, 2013, at the Centre de Recherches Mathématiques, Université de Montréal, Québec, Canada. The program was dedicated to the study of subtle interconnections between geometric and arithmetic properties of higher-dimensional algebraic varieties. The main areas of the program were, among others, proving density of rational points in Zariski or analytic topology on special varieties, understanding global geometric properties of rationally connected varieties, as well as connections between geometry and algebraic dynamics exploring new geometric techniques in Diophantine approximation.

  20. Towards a classification of rational Hopf algebras

    International Nuclear Information System (INIS)

    Fuchs, J.; Ganchev, A.; Vecsernyes, P.

    1994-02-01

    Rational Hopf algebras, i.e. certain quasitriangular weak quasi-Hopf *-algebras, are expected to describe the quantum symmetry of rational field theories. In this paper methods are developed which allow for a classification of all rational Hopf algebras that are compatible with some prescribed set of fusion rules. The algebras are parametrized by the solutions of the square, pentagon and hexagon identities. As examples, we classify all solutions for fusion rules with not more than three sectors, as well as for the level three affine A 1 (1) fusion rules. We also establish several general properties of rational Hopf algebras and present a graphical description of the coassociator in terms of labelled tetrahedra. The latter construction allows to make contact with conformal field theory fusing matrices and with invariants of three-manifolds and topological lattice field theory. (orig.)

  1. Rational Multiparty Computation

    OpenAIRE

    Wallrabenstein, John Ross

    2014-01-01

    The field of rational cryptography considers the design of cryptographic protocols in the presence of rational agents seeking to maximize local utility functions. This departs from the standard secure multiparty computation setting, where players are assumed to be either honest or malicious. ^ We detail the construction of both a two-party and a multiparty game theoretic framework for constructing rational cryptographic protocols. Our framework specifies the utility function assumptions neces...

  2. [Change in drug resistance of Staphylococcus aureus].

    Science.gov (United States)

    Lin, Yan; Liu, Yan; Luo, Yan-Ping; Liu, Chang-Ting

    2013-11-01

    To analyze the change in drug resistance of Staphylococcus aureus (SAU) in the PLA general hospital from January 2008 to December 2012, and to provide solid evidence to support the rational use of antibiotics for clinical applications. The SAU strains isolated from clinical samples in the hospital were collected and subjected to the Kirby-Bauer disk diffusion test. The results were assessed based on the 2002 American National Committee for Clinical Laboratory Standards (NCCLS) guidelines. SAU strains were mainly isolated from sputum, urine, blood and wound excreta and distributed in penology, neurology wards, orthopedics and surgery ICU wards. Except for glycopeptide drugs, methicillin-resistant Staphylococcus aureus (MRSA) had a higher drug resistance rate than those of the other drugs and had significantly more resistance than methicillin-sensitive Staphylococcus aureus (MSSA) (P resistance, we discovered a gradual increase in drug resistance to fourteen test drugs during the last five years. Drug resistance rate of SAU stayed at a higher level over the last five years; moreover, the detection ratio of MRSA keeps rising year by year. It is crucial for physicians to use antibiotics rationally and monitor the change in drug resistance in a dynamic way.

  3. Rationality and Integration in a Family Childrearing Decision.

    Science.gov (United States)

    Diana, Mark S.

    This paper illuminates how concepts of rationality developed by Diesing in l962 are reflected in parents' childrearing decisions. After examining technical (TR), economic (ER), social (SR), legal (LR), and political (PR) rationalities or decision-making styles, consideration is given to integrative effects and the influence of parents' friends and…

  4. Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics.

    Science.gov (United States)

    Pulley, Jill M; Shirey-Rice, Jana K; Lavieri, Robert R; Jerome, Rebecca N; Zaleski, Nicole M; Aronoff, David M; Bastarache, Lisa; Niu, Xinnan; Holroyd, Kenneth J; Roden, Dan M; Skaar, Eric P; Niswender, Colleen M; Marnett, Lawrence J; Lindsley, Craig W; Ekstrom, Leeland B; Bentley, Alan R; Bernard, Gordon R; Hong, Charles C; Denny, Joshua C

    2017-04-01

    The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics.

  5. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  6. Rational choice in field archaelology

    Directory of Open Access Journals (Sweden)

    Cătălin Pavel

    2011-11-01

    Full Text Available In the present article I attempt to apply advances in the study of instrumental and epistemic rationality to field archaeology in order to gain insights into the ways archaeologists reason. The cognitive processes, particularly processes of decision making, that enable archaeologists to conduct the excavation in the trench have not been adequately studied so far. I take my cues from two different bodies of theory. I first inquire into the potential that rational choice theory (RCT may have in modeling archaeological behaviour, and I define subjective expected utility, which archaeologists attempt to maximize, in terms of knowledge acquisition and social gain. Following Elster’s criticism of RCT, I conclude that RCT’s standards for rational action do not correspond with those ostensibly used in field archaeology, but that instrumental rationality has a prominent role in the “archaeological experiment”. I further explore if models proposed as reaction to RCT may account for archaeological decision making. I focus on fast and frugal heuristics, and search for archaeological illustrations for some of the cognitive biases that are better documented in psychological literature. I document confirmation and congruence biases, the endowment effect, observer-expectancy bias, illusory correlation, clustering illusion, sunk cost bias, and anchoring, among others and I propose that some of these biases are used as cognitive tools by archaeologists at work and retain epistemic value. However, I find formal logic to be secondary in the development of archaeological reasoning, with default logic and defeasible logic being used instead. I emphasize scientific knowledge as an actively negotiated social product of human inquiry, and conclude that to describe rationality in field archaeology a bounded rationality model is the most promising avenue of investigation.

  7. Rational Behavior Skills: A Teaching Sequence for Students with Emotional Disabilities.

    Science.gov (United States)

    Patton, Patricia Lucey

    1995-01-01

    Rational behavior training is a proactive teaching model concerned with helping students with behavior disorders or serious emotional disturbances develop rational thinking and appropriate social skills. Describes a seven-session sequence for teaching rational behavior skills in a middle school setting. Pre- and posttest data revealed significant…

  8. Optimization of fodder rations for intensive development of cattle-breeding in an radioactive contaminated zone

    International Nuclear Information System (INIS)

    Stolyarov, G.V.

    1999-01-01

    It has been calculated some variants of the optimal structure of milk cow herd's fodder rations in a radioactive contaminated zone in dependence of the contamination density. Rations were balanced in primary nutritive including digestible protein. It has been determined their costs and specific radioactivity of cesium-137. These fodder rations can be recommended to the farms of the Gomel Region suffered from the Chernobyl nuclear power station explosion

  9. [New drug development by innovative drug administration--"change" in pharmaceutical field].

    Science.gov (United States)

    Nagai, T

    1997-11-01

    New drug development can be made by providing products of higher "selectivity for the drug" for medical treatment. There are two ways for the approach to get higher "selectivity of drug": 1) discovery of new compounds with high selectivity of drug; 2) innovation of new drug administration, that is new formulation and/or method with high selectivity of drug by integration and harmonization of various hard/soft technologies. An extensive increase of biological information and advancement of surrounding science and technology may modify the situation as the latter overcomes the former in the 21 century. As the science and technology in the 21 century is said to be formed on "3H", that is, 1. hybrid; 2. hi-quality; 3. husbandry, the new drug development by innovative drug administration is exactly based on the science and technology of 3H. Its characteristic points are interdisciplinary/interfusion, international, of philosophy/ethics, and systems of hard/hard/heart. From these points of view, not only the advance of unit technology but also a revolution in thinking way should be "must" subjects. To organize this type of research well, a total research activity such as ROR (research on research) might take an important and efficient role. Here the key words are the "Optimization technology" and "Change in Pharmaceutical Fields." As some examples of new drug innovation, our trials on several topical mucosal adhesive dosage forms and parenteral administration of peptide drugs such as insulin and erythropoietin will be described.

  10. Enhancing Rationality: Heuristics, Biases, and The Critical Thinking Project

    Directory of Open Access Journals (Sweden)

    Mark Battersby

    2016-07-01

    Full Text Available Abstract: This paper develops four related claims: 1. Critical thinking should focus more on decision making, 2. the heuristics and bias literature developed by cognitive psychologists and behavioral economists provides many insights into human irrationality which can be useful in critical thinking instruction, 3. unfortunately the “rational choice” norms used by behavioral economists to identify “biased” decision making narrowly equate rational decision making with the efficient pursuit of individual satisfaction; deviations from these norms should not be treated as an irrational bias, 4. a richer, procedural theory of rational decision making should be the basis for critical thinking instruction in decision making.

  11. Irrational Rationality of Terrorism

    Directory of Open Access Journals (Sweden)

    Robert Nalbandov

    2013-12-01

    Full Text Available The present article deals with the ontological problem of applying the rational choice frameworks to the study of terrorism. It testing the application of the rational choice to the “old” (before the end of the Cold War and the “new” (after the end of the Cold War terrorisms. It starts with analyzing the fundamentals of rationality and applies it at two levels: the individual (actors and group (collective via two outlooks: tactical (short-term and strategic (long-term. The main argument of the article is that while the “old” terrorism can be explained by the rational choice theory its “new” version represents a substantial departure from rationality.

  12. Rational points on elliptic curves

    CERN Document Server

    Silverman, Joseph H

    2015-01-01

    The theory of elliptic curves involves a pleasing blend of algebra, geometry, analysis, and number theory. This book stresses this interplay as it develops the basic theory, thereby providing an opportunity for advanced undergraduates to appreciate the unity of modern mathematics. At the same time, every effort has been made to use only methods and results commonly included in the undergraduate curriculum. This accessibility, the informal writing style, and a wealth of exercises make Rational Points on Elliptic Curves an ideal introduction for students at all levels who are interested in learning about Diophantine equations and arithmetic geometry. Most concretely, an elliptic curve is the set of zeroes of a cubic polynomial in two variables. If the polynomial has rational coefficients, then one can ask for a description of those zeroes whose coordinates are either integers or rational numbers. It is this number theoretic question that is the main subject of this book. Topics covered include the geometry and ...

  13. Rational Unified Process

    OpenAIRE

    Kopal, Nils

    2016-01-01

    In this German seminar paper, which was written in the year 2011 at the University of Duisburg for a Bachelor Colloquium in Applied computer science, we show a brief overview of the Rational Unified Process (RUP). Thus, interested students or generally interested people in software development gain a first impression of RUP. The paper includes a survey and overview of the underlying process structure, the phases of the process, its workflows, and describes the always by the RUP developers pos...

  14. Lying for Strategic Advantage: Rational and Boundedly Rational Misrepresentation of Intentions

    OpenAIRE

    Crawford, Vincent P.

    2001-01-01

    Starting from Hendricks and McAfee's (2000) example of the Allies' decision to feint at Calais and attack at Normandy on D-Day, this paper models misrepresentation of intentions to competitors or enemies. Allowing for the possibility of bounded strategic rationality and rational players' responses to it yields a sensible account of lying via costless, noiseless messages. In many cases the model has generically unique pure-strategy sequential equilibria, in which rational players exploit bound...

  15. A survey on the factors influencing the pattern of medicine's use: Concerns on irrational use of drugs.

    Science.gov (United States)

    Soleymani, Fatemeh; Ahmadizar, Fariba; Meysamie, Alipasha; Abdollahi, Mohammad

    2013-04-01

    Pharmacists have a remarkable role in rational use of drugs by dissemination of drug information to guide patients, physicians, and policy makers. The present study was undertaken to evaluate the pharmacists' view point about the main factors affecting current drug use pattern regarding rational drug use and the most effective strategies for improving and promoting rational drug use among pharmacists. In a cross-sectional survey, pre-designed questionnaires were filled in convenient sampling by pharmacists who had attended the congress of rational drug use in Tehran, Iran. A total of 144 pharmacists with the average age of 40.78 years old were enrolled to the study. Data indicated that the most priorities in irrational use of drugs from pharmacists' view point were lack of appropriate cooperation and communication between physicians and pharmacists (39%), pharmacists' low tariff and economic issues (34%), lack of public knowledge about drug usage (45%), and lack of supervisory regulations on pharmacy practice (15.8%). In this study, lack of public knowledge and awareness about appropriate use of medicines was the most important element from pharmacists' viewpoint in occurrence of irrational drug use. Dissemination of information and compiling of diverse strategies in education, management, regulation, and finance can be very efficient due to a strong relationship between drug policies and performance of regulations and supervisions as well as drug services.

  16. Substantiation of the active ingredients rational concentration of ointment for treatment of allergic dermatitis complicated by fungal infection

    Directory of Open Access Journals (Sweden)

    O. A. Rukhmakova

    2015-08-01

    Full Text Available Aim. Due to the rapid growth of number of allergic skin diseases complicated by secondary fungal infection, creation of new drugs with an integrated anti-allergic and anti-fungal action for their local treatment is especially important. Methods and results. In the process of developing an ointment under conventional name “Allergolik” microbiological studies have been conducted to determine its rational composition. Concentrations of licorice root extract, terbinafine hydrochloride and lavender essential oil have been substantiated as parts of the studied medication. Study of acute toxicity of the developed dosage form has set that it belongs to the IV class of low-toxic substances due to the standard classification of K.K. Sidorova. Conclusion. This testifies the correctness of the choice of drug active ingredients and their concentrations.

  17. Rational use of medicines - Indian perspective!

    Science.gov (United States)

    Mohanta, G P; Manna, P K

    2015-01-01

    India, the largest democracy in the world, is with a federal structure of 29 states and 7 union territories. With a population of more than 1.2 billion, resource is always a constraint and so is in the health system too. In the federal structure, providing healthcare is largely the responsibility of state governments. Medicines are important component of health care delivery system and quality care is dependent on the availability and proper use of quality medicines. In spite of being known as pharmacy of the third world, poor access to medicines in the country is always a serious concern. Realizing the need of quality use of medicines, several initiatives have been initiated. As early as 1994, seeds of rational use of medicines were sown in the country with two initiatives: establishment of a civil society, Delhi Society for Promoting Rational Use of Drugs (DSPURD) and establishment of government agency in Tamil Nadu, a southern state, called Tamil Medical Services Corporation Limited (TNMSCL). DSPUD was in official association with World Health Organization Country Office for implementing essential medicine programme in the country for two biennia. In addition to organizing sensitising and training programme for healthcare professionals throughout the country, it looked after the procurement and appropriate use of medicines in Delhi government health facilities. TNMSCL has made innovations in medicine management including procurement directly from manufacturers as a part of pooled procurement, establishing warehouses with modern storage facilities and Information Technology enabled management of whole process. TNMSCL Model is now replicated in almost the entire country and even in some small other countries as it is successful in improving access to medicines.The National Government and the State Governments have developed strategies to promote rational use of medicines as a part of improving access and quality care in public health facilities. National

  18. [Chapter 2. Transitions in drug-discovery technology and drug-development in Japan (1980-2010)].

    Science.gov (United States)

    Sakakibara, Noriko; Yoshioka, Ryuzo; Matsumoto, Kazuo

    2014-01-01

    In 1970s, the material patent system was introduced in Japan. Since then, many Japanese pharmaceutical companies have endeavored to create original in-house products. From 1980s, many of the innovative products were small molecular drugs and were developed using powerful medicinal-chemical technologies. Among them were antibiotics and effective remedies for the digestive organs and circulatory organs. During this period, Japanese companies were able to launch some blockbuster drugs. At the same time, the pharmaceutical market, which had grown rapidly for two decades, was beginning to level off. From the late 1990s, drug development was slowing down due to the lack of expertise in biotechnology such as genetic engineering. In response to the circumstances, the research and development on biotechnology-based drugs such as antibody drugs have become more dynamic and popular at companies than small molecule drugs. In this paper, the writers reviewed in detail the transitions in drug discovery and development between 1980 and 2010.

  19. Overview of Biomarkers and Surrogate Endpoints in Drug Development

    Directory of Open Access Journals (Sweden)

    John A. Wagner

    2002-01-01

    Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

  20. Determinants of Actor Rationality

    DEFF Research Database (Denmark)

    Ellegaard, Chris

    Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer-supplier...... relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

  1. How to manage enterprise? From creation to rational continuation

    NARCIS (Netherlands)

    Hans Broekhuis; Louise van Weerden

    2009-01-01

    There is a difference between enterprise and management. Enterprise is about creation and management is the rational continuation of enterprise. Being rational comes natural to entrepreneurs, but a good entrepreneur has to develop both aspects. To achieve this is an important aspect of management

  2. Rationality and institutions : an inquiry into the normative implications of rational choice theory

    OpenAIRE

    Engelen, Bart

    2007-01-01

    I aim to analyze in this dissertation what a desirable basic institutional structure looks like from the perspective of rationality. While the main topic is thus normative in nature, I start by clarifying in the first part what the notion of rationality exactly entails. I do so by focusing explicitly on the economic conception of rationality, according to which a rational individual is motivated to serve his self-interest on the basis of cost-benefit calculations. Such a Homo Economicus is ch...

  3. Antimalarial Drug: From its Development to Deface.

    Science.gov (United States)

    Barik, Tapan Kumar

    2015-01-01

    Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of vaccine development for malaria, till now, no effective vaccine is available for use and hence only antimalarial drugs remain our best hope for both treatment and prevention of malaria. However, emergence and spread of drug resistance has been a major obstacle for the success of malaria elimination globally. This review will summarize the information related to antimalarial drugs, drug development strategies, drug delivery through nanoparticles, few current issues like adverse side effects of most antimalarial drugs, non availability of drugs in the market and use of fake/poor quality drugs that are hurdles to malaria control. As we don't have any other option in the present scenario, we have to take care of the existing tools and make them available to almost all malaria affected area.

  4. Rationing medical education.

    African Journals Online (AJOL)

    This paper discussed the pros and cons of the application of rationing to medical education and the different ... Different types of rationing exist in healthcare professional education. ... state-of-the-art resources, technology and tutors con-.

  5. Molecular science for drug development and biomedicine.

    Science.gov (United States)

    Zhong, Wei-Zhu; Zhou, Shu-Feng

    2014-11-04

    With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of "Molecular Science for Drug Development and Biomedicine", in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine.[...].

  6. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

    Directory of Open Access Journals (Sweden)

    Jan eStenvang

    2013-12-01

    Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

  7. The target invites a foe: antibody-drug conjugates in gynecologic oncology.

    Science.gov (United States)

    Campos, Maira P; Konecny, Gottfried E

    2018-02-01

    Antibody-drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and noncleavable linkers are currently being investigated in clinical trials. A number of novel target antigens are currently being validated in ongoing clinical trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3, protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most ADCs currently in clinical development, dose-limiting toxicities appear to be unrelated to the targeted antigen but more tightly associated with the payload. Rational drug design involving optimization of the antibody, the linker and the conjugation chemistry is aimed at improving the therapeutic index of new ADCs. Antibody-drug conjugates can increase the efficacy and decrease the toxicity of their payloads in comparison with traditional cyctotoxic agents. A better and quicker translation of recent scientific advances in the field of ADCs into rational clinical trials for patients diagnosed with ovarian, endometrial or cervical cancer could create real improvements in tumor response, survival and quality of life for our patients.

  8. Rationality problem for algebraic tori

    CERN Document Server

    Hoshi, Akinari

    2017-01-01

    The authors give the complete stably rational classification of algebraic tori of dimensions 4 and 5 over a field k. In particular, the stably rational classification of norm one tori whose Chevalley modules are of rank 4 and 5 is given. The authors show that there exist exactly 487 (resp. 7, resp. 216) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 4, and there exist exactly 3051 (resp. 25, resp. 3003) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 5. The authors make a procedure to compute a flabby resolution of a G-lattice effectively by using the computer algebra system GAP. Some algorithms may determine whether the flabby class of a G-lattice is invertible (resp. zero) or not. Using the algorithms, the suthors determine all the flabby and coflabby G-lattices of rank up to 6 and verify that they are stably permutation. The authors also show that the Krull-Schmidt theorem for G-...

  9. Development and Optimization of controlled drug release ...

    African Journals Online (AJOL)

    The aim of this study is to develop and optimize an osmotically controlled drug delivery system of diclofenac sodium. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active drugs. Drug delivery from these systems, to a large extent, is independent of the physiological factors ...

  10. Rational Approximations to Rational Models: Alternative Algorithms for Category Learning

    Science.gov (United States)

    Sanborn, Adam N.; Griffiths, Thomas L.; Navarro, Daniel J.

    2010-01-01

    Rational models of cognition typically consider the abstract computational problems posed by the environment, assuming that people are capable of optimally solving those problems. This differs from more traditional formal models of cognition, which focus on the psychological processes responsible for behavior. A basic challenge for rational models…

  11. Horizonte de racionalidade acerca da dependência de drogas nos serviços de saúde: implicações para o tratamento The horizon of rationality about drug dependency in health services: implications to the treatments

    Directory of Open Access Journals (Sweden)

    Daniela Ribeiro Schneider

    2010-05-01

    Full Text Available O artigo refere-se à discussão de pesquisa baseada em metodologia de análise de conteúdo, cuja meta é explicitar o horizonte de racionalidade dos serviços de atenção aos usuários de álcool e outras drogas na Região da Grande Florianópolis, objetivando contribuir no estabelecimento de parâmetros qualitativos na avaliação de serviços de saúde. Verificou-se a existência de concepção hegemônica acerca do fenômeno da dependência de drogas e do modo de intervenção no fenômeno, síntese de racionalidades diversas e, algumas vezes, contraditórias entre si. Tal concepção centra seu modelo na noção de doença, na meta da abstinência, no busca do controle sobre a adição, operando dispositivos médico-terapêuticos e morais. Nas raízes desta concepção, encontra-se uma perspectiva subjetivista, moralista e psicopatologizante, constituindo-se em visão ahistórica e pouco crítica da produção social em torno do uso de drogas, pautada numa racionalidade de predomínio metafísico, ainda que mesclado com outras racionalidades como a científica. Discute-se a importância de correlacionar o "horizonte de racionalidade" dos serviços de saúde com a problemática da eficácia e eficiência dos tratamentos na área da dependência de drogas.This article refers to the research discussion based on methodology of content analysis, which aims at making explicit the horizon of rationality of the services provided for alcohol users and other drugs in the Great Florianópolis region, to contribute to the establishment of qualitative parameters in the evaluation of health services. It was verified that there is a hegemonic conception about the drugs dependence phenomenon as well as the way to intervene in this phenomenon, synthesis of different and, sometimes, contradictory rationalities. The model of this conception is based on the notion of disease, on the pursue for abstinence, on the struggle to control de addiction, operating

  12. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review

    Directory of Open Access Journals (Sweden)

    Olliaro P

    2004-01-01

    Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent

  13. Method Development for Clinical Comprehensive Evaluation of Pediatric Drugs Based on Multi-Criteria Decision Analysis: Application to Inhaled Corticosteroids for Children with Asthma.

    Science.gov (United States)

    Yu, Yuncui; Jia, Lulu; Meng, Yao; Hu, Lihua; Liu, Yiwei; Nie, Xiaolu; Zhang, Meng; Zhang, Xuan; Han, Sheng; Peng, Xiaoxia; Wang, Xiaoling

    2018-04-01

    Establishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the 'Clinical Comprehensive Evaluation System for Pediatric Drugs' (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process. An evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers). By applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust. An evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful

  14. [Generic drugs: good or bad? Physician's knowledge of generic drugs and prescribing habits].

    Science.gov (United States)

    García, A J; Martos, F; Leiva, F; Sánchez de la Cuesta, F

    2003-01-01

    In this article we analyze the responses of 1220 Spanish physicians who participated in a survery about generic drugs. A previously validated questionnaire was sent to physicians through the Spanish Medical Councils of the different provinces. Four items were analyzed: what doctors know about generic drugs (knowledge); physicians' prescribing habits concerning these drugs (attitude and professional competence); how prescription of generic drugs effects pharmaceutical costs amd, finally, what doctors believe a generic drug should be. The influence of physician-related variables (age, type of contract, specialty, workload, etc.) on prescribing of generic drugs was also analyzed. In view of the results, we believe that to rationalize expenditure through and appropriate policy on generic drugs Spanish health authorities should offer more and better training and information (clear and independent) about what generic drugs are.

  15. The worldwide trend of using botanical drugs and strategies for developing global drugs.

    Science.gov (United States)

    Ahn, Kyungseop

    2017-03-01

    Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development. [BMB Reports 2017; 50(3): 111-116].

  16. Principles of ration formulation for ruminants

    International Nuclear Information System (INIS)

    Jayasuriya, M.C.N.

    2002-01-01

    Feeding standards as practiced in developed countries could be misleading when non-conventional feed resources are used in formulating rations for ruminant livestock in developing countries. They tend to reject the poor quality feeds that are available in vast quantities. The non-availability of good quality forage throughout the year and the need to optimise the efficiency of utilisation of locally available feed resources have lead to the application of basic nutritional principles when considering ration formulation. The alternative approach to the use of feeding standards would be to ensure that the production system matches the available resources. The development of feed supplementation strategies based on locally available feed resources require the understanding of the relative roles and nutrient needs of the two-compartment system represented by the micro-organisms in the rumen and the host animal. (author)

  17. Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

    Science.gov (United States)

    Subramaniam, B; Claudius, J S

    1990-03-08

    Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

  18. Nuclear imaging drug development tools

    International Nuclear Information System (INIS)

    Buchanan, L.; Jurek, P.; Redshaw, R.

    2007-01-01

    This article describes the development of nuclear imaging as an enabling technology in the pharmaceutical industry. Molecular imaging is maturing into an important tool with expanding applications from validating that a drug reaches the intended target through to market launch of a new drug. Molecular imaging includes anatomical imaging of organs or tissues, computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound.

  19. Modeling chemical reactions for drug design.

    Science.gov (United States)

    Gasteiger, Johann

    2007-01-01

    Chemical reactions are involved at many stages of the drug design process. This starts with the analysis of biochemical pathways that are controlled by enzymes that might be downregulated in certain diseases. In the lead discovery and lead optimization process compounds have to be synthesized in order to test them for their biological activity. And finally, the metabolism of a drug has to be established. A better understanding of chemical reactions could strongly help in making the drug design process more efficient. We have developed methods for quantifying the concepts an organic chemist is using in rationalizing reaction mechanisms. These methods allow a comprehensive modeling of chemical reactivity and thus are applicable to a wide variety of chemical reactions, from gas phase reactions to biochemical pathways. They are empirical in nature and therefore allow the rapid processing of large sets of structures and reactions. We will show here how methods have been developed for the prediction of acidity values and of the regioselectivity in organic reactions, for designing the synthesis of organic molecules and of combinatorial libraries, and for furthering our understanding of enzyme-catalyzed reactions and of the metabolism of drugs.

  20. Assessment of indicators for hospital drug formulary non-adherence

    NARCIS (Netherlands)

    Fijn, R; Lenderink, AW; Egberts, ACG; Brouwers, JRBJ; De Jong-Van DenBerg, LTW

    Background: Translation of rational drug therapy into practice remains an international problem. Although pharmacotherapeutic treatment guidelines (PTGs) as managerial tools are favoured over hospital drug formularies (HDFs), the latter are still applied in most hospitals. HDF enforcement often

  1. Optimal public rationing and price response.

    Science.gov (United States)

    Grassi, Simona; Ma, Ching-To Albert

    2011-12-01

    We study optimal public health care rationing and private sector price responses. Consumers differ in their wealth and illness severity (defined as treatment cost). Due to a limited budget, some consumers must be rationed. Rationed consumers may purchase from a monopolistic private market. We consider two information regimes. In the first, the public supplier rations consumers according to their wealth information (means testing). In equilibrium, the public supplier must ration both rich and poor consumers. Rationing some poor consumers implements price reduction in the private market. In the second information regime, the public supplier rations consumers according to consumers' wealth and cost information. In equilibrium, consumers are allocated the good if and only if their costs are below a threshold (cost effectiveness). Rationing based on cost results in higher equilibrium consumer surplus than rationing based on wealth. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Counterfeit drugs and medical devices in developing countries

    Directory of Open Access Journals (Sweden)

    Glass BD

    2014-03-01

    Full Text Available Beverley D GlassSchool of Pharmacy and Molecular Sciences, James Cook University, Townsville, QLD, AustraliaAbstract: The World Health Organization has reported that counterfeit medicines potentially make up more than 50% of the global drug market, with a significant proportion of these fake products being encountered in developing countries. This occurrence is attributed to a lack of effective regulation and a weak enforcement capacity existing in these countries, with an increase in this trade resulting from the growing size and sophistication of drug counterfeiters. In addition, due to both cost and lack of availability of medicines, consumers in developing countries are more likely to seek out these inexpensive options. The World Health Organization is mindful of the impact of counterfeit drugs on consumer confidence in health care systems, health professionals, the supply chain, and genuine suppliers of medicines and medical devices. Antibiotics, antituberculosis drugs, and antimalarial and antiretroviral drugs are frequently targeted, with reports of 60% of the anti-infective drugs in Asia and Africa containing active pharmaceutical ingredients outside their pharmacopoeial limits. This has obvious public health implications of increasing drug resistance and negating all the efforts that have already gone into the provision of medicines to treat these life threatening conditions in the developing world. This review, while focusing on counterfeit medicines and medical devices in developing countries, will present information on their impact and how these issues can be addressed by regulation and control of the supply chain using technology appropriate to the developing world. The complexity of the problem will also be highlighted in terms of the definition of counterfeit and substandard medicines, including gray pharmaceuticals. Although this issue presents as a global public health problem, outcomes in developing countries where counterfeit

  3. Exploring rationality in schizophrenia

    DEFF Research Database (Denmark)

    Revsbech, Rasmus; Mortensen, Erik Lykke; Owen, Gareth

    2015-01-01

    Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Meth...... differences became non-significant. Conclusions When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality.......Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Method...... Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence...

  4. Respect for rational autonomy.

    Science.gov (United States)

    Walker, Rebecca L

    2009-12-01

    The standard notion of autonomy in medical ethics does not require that autonomous choices not be irrational. The paper gives three examples of seemingly irrational patient choices and discusses how a rational autonomy analysis differs from the standard view. It then considers whether a switch to the rational autonomy view would lead to overriding more patient decisions but concludes that this should not be the case. Rather, a determination of whether individual patient decisions are autonomous is much less relevant than usually considered in determining whether health care providers must abide by these decisions. Furthermore, respect for rational autonomy entails strong positive requirements of respect for the autonomy of the person as a rational decision maker. The rationality view of autonomy is conceptually stronger than the standard view, allows for a more nuanced understanding of the practical moral calculus involved in respecting patient autonomy, and promotes positive respect for patient autonomy.

  5. Geometry of minimal rational curves on Fano manifolds

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, J -M [Korea Institute for Advanced Study, Seoul (Korea, Republic of)

    2001-12-15

    This lecture is an introduction to my joint project with N. Mok where we develop a geometric theory of Fano manifolds of Picard number 1 by studying the collection of tangent directions of minimal rational curves through a generic point. After a sketch of some historical background, the fundamental object of this project, the variety of minimal rational tangents, is defined and various examples are examined. Then some results on the variety of minimal rational tangents are discussed including an extension theorem for holomorphic maps preserving the geometric structure. Some applications of this theory to the stability of the tangent bundles and the rigidity of generically finite morphisms are given. (author)

  6. From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers.

    Science.gov (United States)

    MacEwan, Sarah R; Chilkoti, Ashutosh

    2017-06-06

    The molecular complexity and heterogeneity of cancer has led to a persistent, and as yet unsolved, challenge to develop cures for this disease. The pharmaceutical industry focuses the bulk of its efforts on the development of new drugs, but an alternative approach is to improve the delivery of existing drugs with drug carriers that can manipulate when, where, and how a drug exerts its therapeutic effect. For the treatment of solid tumors, systemically delivered drug carriers face significant challenges that are imposed by the pathophysiological barriers that lie between their site of administration and their site of therapeutic action in the tumor. Furthermore, drug carriers face additional challenges in their translation from preclinical validation to clinical approval and adoption. Addressing this diverse network of challenges requires a systems engineering approach for the rational design of optimized carriers that have a realistic prospect for translation from the laboratory to the patient. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Embodying rationality

    OpenAIRE

    Mastrogiorgio, Antonio; Petracca, Enrico

    2016-01-01

    The current notions of bounded rationality in economics share distinctive features with Simon’s original notion, which still influences the theoretical and experimental research in the fields of choice, judgment, decision making, problem solving, and social cognition. All these notions of bounded rationality are in fact equally rooted in the information-processing approach to human cognition, expressing the view that reasoning is disembodied and that it can be reduced to the processing of abs...

  8. Drug Treatment Centers in Afghanistan: Creating a Participatory Approach to Tackling the Drug Trade

    Science.gov (United States)

    2012-12-01

    Oxford Economic Papers 61, no. 1 (2009): 12. 16 community referral system for social services would increase the actors involved, introduce new...rationalized the use of prescription drugs as an emotional and physical crutch . Many chose opium, because it is less costly, being unaware that the...208. 41 continue to use legal and illegal drugs as an emotional crutch . In fact, pharmaceutical use is heavily linked to poverty. Health costs

  9. CoPs Facing Rationalization: The Politics of Community Reproduction

    Science.gov (United States)

    Kilskar, Stine Skaufel; Ingvaldsen, Jonas A.; Valle, Nina

    2018-01-01

    Purpose: This paper aims to explore the relationship between the contemporary forms of manufacturing rationalization and the reproduction of communities of practice (CoPs) centred on tasks and craft. Building on critical literature highlighting the tensions between CoPs and rationalization, this paper aims to develop a nuanced account of how CoPs…

  10. Capital Requirements and Credit Rationing

    OpenAIRE

    Itai Agur

    2010-01-01

    This paper analyzes the trade-off between financial stability and credit rationing that arises when increasing capital requirements. It extends the Stiglitz-Weiss model of credit rationing to allow for bank default. Bank capital structure then matters for lending incentives. With default and rationing endogenous, optimal capital requirements can be analyzed. Introducing bank financiers, the paper also shows that uninsured funding raises the sensitivity of rationing to capital requirements. In...

  11. Surrogacy in antiviral drug development

    Science.gov (United States)

    Shaunak, Sunil; Davies, Donald S

    2002-01-01

    The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therapeutic intervention have started to give way to the use of an increasing number of surrogate markers. Using a combination of these markers, it is now possible to measure and monitor the pathogen as well as the host's response. Nowhere is this better exemplified in virology than in the field of AIDS. We have utilized the advances in pathogenesis and new antiretroviral drug development to: develop a new class of drugs which block the entry of HIV-1 into cells.develop a new approach for effectively delivering these drugs to those tissues in which most viral replication takes place. Over the last 10 years, our work has progressed from concept to clinical trial. Our laboratory based evaluation of the new molecules developed as well as our clinical evaluation of their safety and efficacy have had to respond and adapt to the rapid changes taking place in AIDS research. This paper discusses the problems encountered and the lessons learnt. PMID:12100230

  12. DEVELOPMENT AND REGISTRATION OF CHIRAL DRUGS

    NARCIS (Netherlands)

    WITTE, DT; ENSING, K; FRANKE, JP; DEZEEUW, RA

    1993-01-01

    In this review we describe the impact of chirality on drug development and registration in the United States, Japan and the European Community. Enantiomers may have differences in their pharmacological profiles, and, therefore, chiral drugs ask for special analytical and pharmacological attention

  13. [Rationalization and rationing at the bedside. A normative and empirical status quo analysis].

    Science.gov (United States)

    Strech, D

    2014-02-01

    The topic of bedside rationing is increasingly discussed in Germany. Further need for clarification exists for the question how bedside rationing (e.g., in the area of overcare) can be justified despite coexistent inefficiencies. This paper outlines and analyses the relationship of waste avoidance and rationing from an ethical perspective. Empirical findings regarding the status quo of bedside rationing and rationalization are presented. These normative and empirical explorations will then be further specified regarding opportunities for future physician-driven activities to tackle overuse. The self-government partners in Germany should communicate more explicitly within their communities and to the public how and with which benchmarks they aim to reduce inefficient health care (overuse) in an appropriate manner. Physician-driven activities such as the "Choosing Wisely®" initiative in the USA could provide a first step to raise the awareness for overuse among physicians as well as in the public.

  14. Development of rational pay factors based on concrete compressive strength data

    Science.gov (United States)

    2008-06-01

    This research project addresses the opportunity to contain the escalating costs of concrete materials in construction projects. Both statistical process control and rational acceptance criteria show that quality improvement and cost savings can be ac...

  15. [Historical development of vaccines. Introduction: Hazards and rationality in the vaccinal approach].

    Science.gov (United States)

    Moulin, A M

    1995-01-01

    The aim of this paper is to introduce the one hundred years of vaccination that has passed since Louis Pasteur first coined this generic term. According to the late Jonas Salk, vaccinology is a science encompassing all aspects of vaccine from its conception in the laboratory to its production by companies and its application and distribution in the field. In this historical survey I explore how vaccination never consisted of a simple and uniform application of a rational model, but rather diverged along various pathways, several of which were discarded in retrospect as being hazardous, and I analyse the ongoing interplay between rational and inventive thinking.

  16. Rational BRDF.

    Science.gov (United States)

    Pacanowski, Romain; Salazar Celis, Oliver; Schlick, Christophe; Granier, Xavier; Poulin, Pierre; Cuyt, Annie

    2012-11-01

    Over the last two decades, much effort has been devoted to accurately measuring Bidirectional Reflectance Distribution Functions (BRDFs) of real-world materials and to use efficiently the resulting data for rendering. Because of their large size, it is difficult to use directly measured BRDFs for real-time applications, and fitting the most sophisticated analytical BRDF models is still a complex task. In this paper, we introduce Rational BRDF, a general-purpose and efficient representation for arbitrary BRDFs, based on Rational Functions (RFs). Using an adapted parametrization, we demonstrate how Rational BRDFs offer 1) a more compact and efficient representation using low-degree RFs, 2) an accurate fitting of measured materials with guaranteed control of the residual error, and 3) efficient importance sampling by applying the same fitting process to determine the inverse of the Cumulative Distribution Function (CDF) generated from the BRDF for use in Monte-Carlo rendering.

  17. Echinocandins for candidemia: a rational choice

    Directory of Open Access Journals (Sweden)

    Francesco Menichetti

    2013-08-01

    Full Text Available Among antifungal drugs, echinocandins (micafungin, caspofungin and anidulafungin represent a rational choice for the first-line therapy of candidemia/invasive candidiasis in critically ill patients. Among other properties characterizing echinocandins, it’s important to emphasize the broad spectrum of activity, the fungicidal activity against the majority of Candida spp., and the activity against the biofilm. Furthermore, echinocandins show greater efficacy than conventional amphotericin B and fluconazole, and similar efficacy to liposomal amphotericin B (but they are less toxic. Finally, echinocandins are recommended at the highest level of evidence (AI for the treatment of invasive candidiasis by IDSA and ESCMID guidelines.http://dx.doi.org/10.7175/rhc.v4i2s.872

  18. Rationality, perception, and the all-seeing eye.

    Science.gov (United States)

    Felin, Teppo; Koenderink, Jan; Krueger, Joachim I

    2017-08-01

    Seeing-perception and vision-is implicitly the fundamental building block of the literature on rationality and cognition. Herbert Simon and Daniel Kahneman's arguments against the omniscience of economic agents-and the concept of bounded rationality-depend critically on a particular view of the nature of perception and vision. We propose that this framework of rationality merely replaces economic omniscience with perceptual omniscience. We show how the cognitive and social sciences feature a pervasive but problematic meta-assumption that is characterized by an "all-seeing eye." We raise concerns about this assumption and discuss different ways in which the all-seeing eye manifests itself in existing research on (bounded) rationality. We first consider the centrality of vision and perception in Simon's pioneering work. We then point to Kahneman's work-particularly his article "Maps of Bounded Rationality"-to illustrate the pervasiveness of an all-seeing view of perception, as manifested in the extensive use of visual examples and illusions. Similar assumptions about perception can be found across a large literature in the cognitive sciences. The central problem is the present emphasis on inverse optics-the objective nature of objects and environments, e.g., size, contrast, and color. This framework ignores the nature of the organism and perceiver. We argue instead that reality is constructed and expressed, and we discuss the species-specificity of perception, as well as perception as a user interface. We draw on vision science as well as the arts to develop an alternative understanding of rationality in the cognitive and social sciences. We conclude with a discussion of the implications of our arguments for the rationality and decision-making literature in cognitive psychology and behavioral economics, along with suggesting some ways forward.

  19. HUMAN REASON AND SOCIAL RATIONALITY IN ION UNGUREANU’S THINKING

    Directory of Open Access Journals (Sweden)

    LUCIEN V. CONSTANTIN

    2014-12-01

    Full Text Available Ion Ungureanu is one of the most important sociologists Romania has had in the last half a century. Leader of his generation, he contributed to the development of the paradigms of sociological thinking and he analyzed fundamental concepts of sociological theory. This study aims to expose comparatively and critically one of the most significant contributions of Ion Ungureanu – the concept of social rationality. Unlike Max Weber and Vilfredo Pareto, Ion Ungureanu makes the important distinction between human rationality and social rationality. Struck by this shortcoming, more or less, the two conceptions end up supporting the thesis of human and social action of landed irrationality, like V. Pareto or by opening the path to this irrationality, like Max Weber, taking into consideration the fact that comprehension and knowledge of the meaning of the action, condition of the possibility of initiation of a rational action, can seldom be known by the social actors. With Ion Ungureanu, the rationality of social action is understood through multiple criteria, depending on six ontological dimensions of social existence – social development, economic growth, social participation, social responsibility, social education and social rationality, each containing two aspects. All of these form what the Romanian sociologist calls “the generalized model of social rationality”, a theoretical referential that allows the optimization of social life

  20. Is It Rational to Assume that Infants Imitate Rationally? A Theoretical Analysis and Critique

    Science.gov (United States)

    Paulus, Markus

    2012-01-01

    It has been suggested that preverbal infants evaluate the efficiency of others' actions (by applying a "principle of rational action") and that they imitate others' actions rationally. The present contribution presents a conceptual analysis of the claim that preverbal infants imitate rationally. It shows that this ability rests on at least three…

  1. [Development of antituberculous drugs: current status and future prospects].

    Science.gov (United States)

    Tomioka, Haruaki; Namba, Kenji

    2006-12-01

    Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are

  2. Preclinical experimental models of drug metabolism and disposition in drug discovery and development

    Directory of Open Access Journals (Sweden)

    Donglu Zhang

    2012-12-01

    Full Text Available Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.

  3. [Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

    Science.gov (United States)

    Li, Yuanyuan; Xie, Yanming

    2011-10-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

  4. Bounded rationality alters the dynamics of paediatric immunization acceptance.

    Science.gov (United States)

    Oraby, Tamer; Bauch, Chris T

    2015-06-02

    Interactions between disease dynamics and vaccinating behavior have been explored in many coupled behavior-disease models. Cognitive effects such as risk perception, framing, and subjective probabilities of adverse events can be important determinants of the vaccinating behaviour, and represent departures from the pure "rational" decision model that are often described as "bounded rationality". However, the impact of such cognitive effects in the context of paediatric infectious disease vaccines has received relatively little attention. Here, we develop a disease-behavior model that accounts for bounded rationality through prospect theory. We analyze the model and compare its predictions to a reduced model that lacks bounded rationality. We find that, in general, introducing bounded rationality increases the dynamical richness of the model and makes it harder to eliminate a paediatric infectious disease. In contrast, in other cases, a low cost, highly efficacious vaccine can be refused, even when the rational decision model predicts acceptance. Injunctive social norms can prevent vaccine refusal, if vaccine acceptance is sufficiently high in the beginning of the vaccination campaign. Cognitive processes can have major impacts on the predictions of behaviour-disease models, and further study of such processes in the context of vaccination is thus warranted.

  5. Bounded Rationality and Budgeting

    OpenAIRE

    Ibrahim, Mukdad

    2016-01-01

    This article discusses the theory of bounded rationality which had been introduced by Herbert Simon in the 1950s. Simon introduced the notion of bounded rationality stating that while decision-makers strive for rationality, they are limited by the effect of the environment, their information process capacity and by the constraints on their information storage and retrieval capabilities. Moreover, this article tries to specifically blend this notion into budgeting, using the foundations of inc...

  6. Developing Essential Understanding of Rational Numbers for Teaching Mathematics in Grades 3-5. Essential Understandings

    Science.gov (United States)

    Clarke, Carne; Fisher, William; Marks, Rick; Ross, Sharon; Zbiek, Rose Mary

    2010-01-01

    This book focuses on essential knowledge for teachers about rational numbers. It is organized around four big ideas, supported by multiple smaller, interconnected ideas--essential understandings. Taking teachers beyond a simple introduction to rational numbers, the book will broaden and deepen their mathematical understanding of one of the most…

  7. Open source drug discovery--a new paradigm of collaborative research in tuberculosis drug development.

    Science.gov (United States)

    Bhardwaj, Anshu; Scaria, Vinod; Raghava, Gajendra Pal Singh; Lynn, Andrew Michael; Chandra, Nagasuma; Banerjee, Sulagna; Raghunandanan, Muthukurussi V; Pandey, Vikas; Taneja, Bhupesh; Yadav, Jyoti; Dash, Debasis; Bhattacharya, Jaijit; Misra, Amit; Kumar, Anil; Ramachandran, Srinivasan; Thomas, Zakir; Brahmachari, Samir K

    2011-09-01

    It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Rational accountability and rational autonomy in academic practice: An extended case study of the communicative ethic of interdisciplinary science

    Science.gov (United States)

    Robertson, Susan Margaret

    The dissertation investigates the interaction of rational accountability and rational autonomy in interdisciplinary science within the lifeworld of the university. It focuses on the cultural, social and motivational forces that university researchers draw on, and develop, to constitute and regulate interdisciplinary science. Findings are analyzed within an applied critical social theory framework that attends to the interaction of instrumental and communicative rational action within the public spaces that constitute the lifeworld of the university as a public sphere in society. The research raises questions of how academics practice interdisciplinary science and how these practices relate to the reproduction of the regulative ideal of the university as a community that practices public reason. The conceptual framework informing the research is Habermas' (1984) theory of communicative action. Using Burawoy's (1991) extended case study method as an operational strategy, two modes of constituting and regulating interdisciplinary science were found. Instrumental rational modes dominated in social contexts of interdisciplinary science where consensus on the normative goals and purposes of rational academic action were pre-existing and pre-supposed by participants. Communicative rational modes dominated in social contexts of interdisciplinary science where the normative goals and purposes of rational academic action entered a contested domain. Endorsements for interdisciplinary science policies are coinciding with demands for increased accountability and relevance of Canada's university system. At the same time that the university system must respond to external demands, it must reproduce itself as a public institution open to the discursive redemption of factual and normative validity claims. The study found that academics participate in, but also contest the instrumental regulation of academic inquiry and conduct by using their constitutional autonomy and freedom to

  9. Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast.

    Directory of Open Access Journals (Sweden)

    Elke Ericson

    2008-08-01

    Full Text Available To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac interfered with establishment of cell polarity, cyproheptadine (Periactin targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol and pimozide (Orap. Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.

  10. Community attitudes toward rationing ARVs: a qualitative study of justice and equity.

    Science.gov (United States)

    Rennie, Stuart

    2006-12-01

    Medical rationing of anti-retroviral therapies (ARVs) may conflict with the right to health, but rationing is nevertheless a reality in developing countries. In this article, which is based on a poster presentation at the conference, Stuart Rennie presents the preliminary findings of a study on community attitudes towards rationing ARVs in the Democratic Republic of Congo (DRC).

  11. Rational valuations

    Directory of Open Access Journals (Sweden)

    Georg Spielthenner

    2007-01-01

    Full Text Available Valuations are ubiquitous. We may be for or against genetically modified food; we find some politicians irresponsible; we prefer Beethoven to rock ‘n’ roll or vice versa; some enjoy bird-watching while others find it boring; and we may think that we have to tighten up on green-house gas emissions. Valuing is pervasive and often we are not even aware that we are valuing. However, many of ourvaluations are ill grounded and rationally defective. They are frequently based on misinformation, sloppy thinking, prejudice, and are biased in many ways as psychological research shows. For this reason there is widespread agreement among phi-losophers that we need an account of substantive valuational rationality, both for the theory of practical reasoning and for ethics as well. My main objectin this paper is to outline such an account and to present a principle that allows a non-technical rational criticism of valuations

  12. Rational emotions.

    Science.gov (United States)

    Meshulam, Meir; Winter, Eyal; Ben-Shakhar, Gershon; Aharon, Itzhak

    2012-01-01

    We present here the concept of rational emotions: Emotions may be directly controlled and utilized in a conscious, analytic fashion, enabling an individual to size up a situation, to determine that a certain "mental state" is strategically advantageous and adjust accordingly. Building on the growing body of literature recognizing the vital role of emotions in determining decisions, we explore the complementary role of rational choice in choosing emotional states. Participants played the role of "recipient" in the dictator game, in which an anonymous "dictator" decides how to split an amount of money between himself and the recipient. A subset of recipients was given a monetary incentive to be angry at low-split offers. That subset demonstrated increased physiological arousal at low offers relative to high offers as well as more anger than other participants. These results provide a fresh outlook on human decision-making and contribute to the continuing effort to build more complete models of rational behavior.

  13. Rational use and interpretation of urine drug testing in chronic opioid therapy.

    Science.gov (United States)

    Reisfield, Gary M; Salazar, Elaine; Bertholf, Roger L

    2007-01-01

    Urine drug testing (UDT) has become an essential feature of pain management, as physicians seek to verify adherence to prescribed opioid regimens and to detect the use of illicit or unauthorized licit drugs. Results of urine drug tests have important consequences in regard to therapeutic decisions and the trust between physician and patient. However, reliance on UDT to confirm adherence can be problematic if the results are not interpreted correctly, and evidence suggests that many physicians lack an adequate understanding of the complexities of UDT and the factors that can affect test results. These factors include metabolic conversion between drugs, genetic variations in drug metabolism, the sensitivity and specificity of the analytical method for a particular drug or metabolite, and the effects of intentional and unintentional interferants. In this review, we focus on the technical features and limitations of analytical methods used for detecting drugs or their metabolites in urine, the statistical constructs that are pertinent to ordering UDT and interpreting test results, and the application of these concepts to the clinical monitoring of patients maintained on chronic opioid therapy.

  14. Models for Rational Number Bases

    Science.gov (United States)

    Pedersen, Jean J.; Armbruster, Frank O.

    1975-01-01

    This article extends number bases to negative integers, then to positive rationals and finally to negative rationals. Methods and rules for operations in positive and negative rational bases greater than one or less than negative one are summarized in tables. Sample problems are explained and illustrated. (KM)

  15. Cyborg pantocrator: international relations theory from decisionism to rational choice.

    Science.gov (United States)

    Guilhot, Nicolas

    2011-01-01

    International relations theory took shape in the 1950s in reaction to the behavioral social science movement, emphasizing the limits of rationality in a context of high uncertainty, weak rules, and the possibility of lethal conflict. Yet the same discipline rapidly developed "rational choice" models applied to foreign policy decision making or nuclear strategy. This paper argues that this transformation took place almost seamlessly around the concept of "decision." Initially associated with an antirationalist or "decisionist" approach to politics, the sovereign decision became the epitome of political rationality when it was redescribed as "rational choice," thus easing the cultural acceptance of political realism in the postwar years. © 2011 Wiley Periodicals, Inc.

  16. Drug development: from concept to marketing!

    Science.gov (United States)

    Tamimi, Nihad A M; Ellis, Peter

    2009-01-01

    Drug development is an expensive, long and high-risk business taking 10-15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product's safety continues beyond the initial drug approval through post-marketing monitoring of adverse events. Copyright 2009 S. Karger AG, Basel.

  17. Application of propensity scores to explore the effect of public reporting of medicine use information on rational drug use in China: a quasi-experimental design.

    Science.gov (United States)

    Zhang, Xiaopeng; Wang, Lijun; Zhang, Xinping

    2014-11-11

    Transparency has become a hottest topic and a growing movement in the health care system worldwide. This study used a quasi-experimental design method to explore whether public reporting of medicine use information can improve rational drug use. 20 township hospitals and 274 doctors of City Y in Hubei Province, China were divided into the intervention and control groups on the basis of their characteristics. In the intervention group, the values and rankings of the average expenditure per prescription, percentage of prescriptions requiring antibiotics and percentage of prescriptions requiring injections of each hospital and doctor were publicly released to patients and doctors in an appropriate format monthly. Data were gathered both four months before and after the intervention. Propensity score matching (PSM) was used to minimize the observed covariate (gender, age, experience, education level, title, and monthly income) differences in the doctors' characteristics. 108 pairs of doctors were obtained after PSM. Chi-square test and t-test were employed to explore the effect of public reporting of medicine use information on rational drug use. The study was approved by the Committee of Tongji Medical College, Hua Zhong University of Science and Technology (IORG No: IORG0003571). In baseline, the average expenditure per prescription of the 274 doctors was 42.82 RMB yuan (USD 6.97), the percentage of prescriptions requiring antibiotics was 63.00%, and the percentage of prescriptions requiring injections was 70.79%, all higher than the average of Hubei Province and the standard recommended by WHO. Before the intervention all the three indicators were all comparable (p > 0.05), whereas after the intervention, a significant difference (p < 0.05) was found for the percentage of prescriptions requiring injections between the intervention (64.66%) and control groups (70.52%). Irrational drug use remains a policy issue in township hospitals in the study area. We demonstrated

  18. Are security analysts rational? a literature review

    OpenAIRE

    Peixinho, Rúben; Coelho, Luís; Taffler, Richard J.

    2005-01-01

    Rational choice theory and bounded rationality constitute the basis for the discussion in several areas regarding human rationality. In finance, this discussion has been made between traditional finance and behavioural finance approach, which have different perspectives concerning market agents’ rationality. This paper reviews several studies addressing rationality among security analysts. The analysis shows that analysts’systematic optimism seems to be inconsistent with rationality....

  19. Has molecular imaging delivered to drug development?

    Science.gov (United States)

    Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.

    2017-10-01

    Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  20. Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-β-Glucuronide.

    Science.gov (United States)

    Varma, Manthena V S; Lin, Jian; Bi, Yi-an; Kimoto, Emi; Rodrigues, A David

    2015-07-01

    Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8) inhibitor for clinical investigation by the U.S. Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex; its major circulating metabolite, gemfibrozil 1-O-β-glucuronide (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and metabolite also behave as moderate inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and repaglinide) by employing both static mechanistic and dynamic physiologically based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of the observed values, respectively, when incorporating the interaction potential of both gemfibrozil and its 1-O-β-glucuronide. Moreover, the PBPK model was able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin, and repaglinide under control and gemfibrozil treatment conditions. Analyses suggest that Gem-Glu is the major contributor to the DDIs, and its exposure needed to bring about complete inactivation of CYP2C8 is only a fraction of that achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex interactions of gemfibrozil can be quantitatively rationalized, and the learnings from this analysis can be applied in support of future predictions of gemfibrozil DDIs. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Multiscale Modeling in the Clinic: Drug Design and Development

    Energy Technology Data Exchange (ETDEWEB)

    Clancy, Colleen E.; An, Gary; Cannon, William R.; Liu, Yaling; May, Elebeoba E.; Ortoleva, Peter; Popel, Aleksander S.; Sluka, James P.; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M.

    2016-02-17

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

  2. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...... and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development...

  3. Autogenerator-based modelling framework for development of strategic games simulations: rational pigs game extended.

    Science.gov (United States)

    Fabac, Robert; Radošević, Danijel; Magdalenić, Ivan

    2014-01-01

    When considering strategic games from the conceptual perspective that focuses on the questions of participants' decision-making rationality, the very issues of modelling and simulation are rarely discussed. The well-known Rational Pigs matrix game has been relatively intensively analyzed in terms of reassessment of the logic of two players involved in asymmetric situations as gluttons that differ significantly by their attributes. This paper presents a successful attempt of using autogenerator for creating the framework of the game, including the predefined scenarios and corresponding payoffs. Autogenerator offers flexibility concerning the specification of game parameters, which consist of variations in the number of simultaneous players and their features and game objects and their attributes as well as some general game characteristics. In the proposed approach the model of autogenerator was upgraded so as to enable program specification updates. For the purpose of treatment of more complex strategic scenarios, we created the Rational Pigs Game Extended (RPGE), in which the introduction of a third glutton entails significant structural changes. In addition, due to the existence of particular attributes of the new player, "the tramp," one equilibrium point from the original game is destabilized which has an influence on the decision-making of rational players.

  4. Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence.

    Science.gov (United States)

    Ersche, Karen D; Turton, Abigail J; Chamberlain, Samuel R; Müller, Ulrich; Bullmore, Edward T; Robbins, Trevor W

    2012-09-01

    Not everyone who takes drugs becomes addicted, but the likelihood of developing drug addiction is greater in people with a family history of drug or alcohol dependence. Relatively little is known about how genetic risk mediates the development of drug dependence. By comparing the phenotypic profile of individuals with and without a family history of addiction, the authors sought to clarify the extent to which cognitive dysfunction and personality traits are shared by family members--and therefore likely to have predated drug dependence--and which aspects are specific to drug-dependent individuals. The authors assessed cognitive function and personality traits associated with drug dependence in stimulant-dependent individuals (N=50), their biological siblings without a history of drug dependence (N=50), and unrelated healthy volunteers (N=50). Cognitive function was significantly impaired in the stimulant-dependent individuals across a range of domains. Deficits in executive function and response control were identified in both the stimulant-dependent individuals and in their non-drug-dependent siblings. Drug-dependent individuals and their siblings also exhibited elevated anxious-impulsive personality traits relative to healthy comparison volunteers. Deficits in executive function and response regulation as well as anxious-impulsive personality traits may represent endophenotypes associated with the risk of developing cocaine or amphetamine dependence. The identification of addiction endophenotypes may be useful in facilitating the rational development of therapeutic and preventive strategies.

  5. Rational Multi-curve Models with Counterparty-risk Valuation Adjustments

    DEFF Research Database (Denmark)

    Crépey, Stéphane; Macrina, Andrea; Nguyen, Tuyet Mai

    2016-01-01

    We develop a multi-curve term structure set-up in which the modelling ingredients are expressed by rational functionals of Markov processes. We calibrate to London Interbank Offer Rate swaptions data and show that a rational two-factor log-normal multi-curve model is sufficient to match market da...... with regulatory obligations. In order to compute counterparty-risk valuation adjustments, such as credit valuation adjustment, we show how default intensity processes with rational form can be derived. We flesh out our study by applying the results to a basis swap contract....... with accuracy. We elucidate the relationship between the models developed and calibrated under a risk-neutral measure Q and their consistent equivalence class under the real-world probability measure P. The consistent P-pricing models are applied to compute the risk exposures which may be required to comply...

  6. Pharmacist's contribution to the promotion of access and rational use of essential medicines in SUS.

    Science.gov (United States)

    Melo, Daniela Oliveira de; Castro, Lia Lusitana Cardozo de

    2017-01-01

    to describe the pharmaceutical inclusion process in a Basic Health Unit multidisciplinary team and evaluate results related to rational use and promotion of access to essential medicines. This is a descriptive, cross-sectional study conducted in a primary care health unit in the city of São Paulo. Pharmacist's activities were evaluated regarding the service structure and organization and prescribing quality improvement, guidance method creation, and implementation of clinical pharmacy service. Data measured before and after the interventions and between 2010 and 2011 were analyzed using Pearson´s chi-square test with a significance level of 5%, and odds ratio. Pharmacist's activities had statistically significant result in drug shortage reduction; prescribing quality improvement associated with an increased proportion of prescriptions met; decrease in the total of prescribed drugs among patients receiving pharmacotherapeutic follow-up and, comparing the years 2010 and 2011, changes in the pharmacotherapy recommendations have gained increased acceptance level. Pharmacist's activities may effectively provide rational use and promotion of access to essential medicines.

  7. Drug Advertising and Health Habit

    OpenAIRE

    Toshiaki Iizuka; Ginger Zhe Jin

    2005-01-01

    We examine the effect of direct-to-consumer advertising (DTCA) of drug treatment on an important health habit, physical exercise. By learning the existence of a new drug treatment via DTCA, rational consumers may become careless about maintaining healthy lifestyles. Using the National Health Insurance Survey (NHIS) and MSA-level DTCA data, we find that the DTCA related to four chronic conditions -- diabetes, high cholesterol, over weight, and hypertension -- reduce the likelihood of engaging ...

  8. [Exploration and demonstration study on drug combination from clinical real world].

    Science.gov (United States)

    Xie, Yan-ming; Wang, Lian-xin; Wang, Yong-yan

    2014-09-01

    Drug combination is extensive in the clinical real world,which is an important part and the inherent requirements of the post-marketing evaluation of traditional Chinese medicine (TCM). The key issues and technology include multi-domain and multi-disciplinary such as the rationality, efficacy and safety evaluation of combination drug starting from clinical real world, study on component in vivo and mechanism of combination drug, the risk/benefit assessment and cost-benefit evaluation of combination drug and so on. The topic has been studied as clinical demonstration on combination therapy of variety of diseases such as coronary heart disease, stroke, insomnia, depression, hepatitis, herpes zoster, psoriasis and ectopic pregnancy. Meanwhile, multi-disciplinary dynamic innovation alliance of clinical drug combination has been presented, which can promote the academic development and improving service ability and level of TCM.

  9. Physical stabilization of low-molecular-weight amorphous drugs in the solid state: a material science approach.

    Science.gov (United States)

    Qi, Sheng; McAuley, William J; Yang, Ziyi; Tipduangta, Pratchaya

    2014-07-01

    Use of the amorphous state is considered to be one of the most effective approaches for improving the dissolution and subsequent oral bioavailability of poorly water-soluble drugs. However as the amorphous state has much higher physical instability in comparison with its crystalline counterpart, stabilization of amorphous drugs in a solid-dosage form presents a major challenge to formulators. The currently used approaches for stabilizing amorphous drug are discussed in this article with respect to their preparation, mechanism of stabilization and limitations. In order to realize the potential of amorphous formulations, significant efforts are required to enable the prediction of formulation performance. This will facilitate the development of computational tools that can inform a rapid and rational formulation development process for amorphous drugs.

  10. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles—A Platform for Drug Development

    Directory of Open Access Journals (Sweden)

    Henrika Wickström

    2017-11-01

    Full Text Available Mesoporous silica nanoparticles (MSNs have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV and poorly permeable (BCS class III, IV drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI surface functionalized MSNs, as well as drug-free and drug-loaded MSN–PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  11. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

    Science.gov (United States)

    Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

    2017-11-21

    Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  12. Rationalization of water consumption in paper industry

    Directory of Open Access Journals (Sweden)

    Žarković Darja

    2004-01-01

    Full Text Available The subject of this paper was to consider the possibilities of economical paper production with rationalization of water consumption. In accordance with the principles of viable development. The pulp & paper industry has had to face global market needs and strict regulation concerning the environment. The basic motive was to provide consistent and high product quality, which is competitive on the market. The pulp & paper industry is one of the largest consumers and pollutants of natural resources. In that light, the rationalization of raw material, water, energy and chemicals consumption with minimization of environmental impact is essential. The European directive on environmental protection obliges producers of pulp & paper to decrease the volume of wastewater and to increase the efficiency treatment. Pulp and paper industry in Serbia and Montenegro will also be faced with the demands for environmental protection. Numerous examples of water consumption rationalization and improvement of water quality in the pulp & paper industry could be found in different literature sources. It is necessary to increase water system closure and implement up-to-date treatment methods. The possibilities for water consumption rationalization, in a real system the paperboard mill UMKA, were examined.

  13. Limited rationality and strategic interaction

    DEFF Research Database (Denmark)

    Fehr, Ernst; Tyran, Jean-Robert

    2008-01-01

    Much evidence suggests that people are heterogeneous with regard to their abilities to make rational, forward-looking decisions. This raises the question as to when the rational types are decisive for aggregate outcomes and when the boundedly rational types shape aggregate results. We examine...... this question in the context of a long-standing and important economic problem: the adjustment of nominal prices after an anticipated monetary shock. Our experiments suggest that two types of bounded rationality-money illusion and anchoring-are important behavioral forces behind nominal inertia. However......, depending on the strategic environment, bounded rationality has vastly different effects on aggregate price adjustment. If agents' actions are strategic substitutes, adjustment to the new equilibrium is extremely quick, whereas under strategic complementarity, adjustment is both very slow and associated...

  14. Rationality and complexity in the work of Elinor Ostrom

    Directory of Open Access Journals (Sweden)

    Arturo Lara

    2015-09-01

    Full Text Available What role does the theory of rational choice play in the scientific evolution of the work of Elinor Ostrom? Ostrom accepts, rejects, and makes critical improvements to the prior achievements of the theory of rational choice, in the pursuit of a “creative synthesis.” She proposes that this theory can be used i to study not only competitive situations involving the exchange of private goods, but also social dilemmas; ii to construct a syntax and grammar of institutions; iii to develop a broader concept of rationality; and iv to integrate this theory into a realistic concept of individuals and social structures.

  15. Development Considerations for Nanocrystal Drug Products.

    Science.gov (United States)

    Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

  16. Development of anti-inflammatory drugs - the research and development process.

    Science.gov (United States)

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  17. The Development and Validation of the Rational and Intuitive Decision Styles Scale.

    Science.gov (United States)

    Hamilton, Katherine; Shih, Shin-I; Mohammed, Susan

    2016-01-01

    Decision styles reflect the typical manner by which individuals make decisions. The purpose of this research was to develop and validate a decision style scale that addresses conceptual and psychometric problems with current measures. The resulting 10-item scale captures a broad range of the rational and intuitive styles construct domain. Results from 5 independent samples provide initial support for the dimensionality and reliability of the new scale, as demonstrated by a clear factor structure and high internal consistency. In addition, our results show evidence of convergent and discriminant validity through expected patterns of correlations across decision-making individual differences and the International Personality Item Pool (IPIP) Big Five traits. Research domains that would benefit from incorporating the concept of decision styles are discussed.

  18. Low hanging fruit in infectious disease drug development.

    Science.gov (United States)

    Kraus, Carl N

    2008-10-01

    Cost estimates for developing new molecular entities (NME) are reaching non-sustainable levels and coupled with increasing regulatory requirements and oversight have led many pharmaceutical sponsors to divest their anti-microbial development portfolios [Projan SJ: Why is big Pharma getting out of anti-bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug development: implications for the future.Clin Infect Dis 2004, 38:1279-1286]. Operational issues such as study planning and execution are significant contributors to the overall cost of drug development that can benefit from the leveraging of pre-randomization data in an evidence-based approach to protocol development, site selection and patient recruitment. For non-NME products there is even greater benefit from available data resources since these data may permit smaller and shorter study programs. There are now many available open source intelligence (OSINT) resources that are being integrated into drug development programs, permitting an evidence-based or 'operational epidemiology' approach to study planning and execution.

  19. Psychology and the Rationality of Emotion.

    Science.gov (United States)

    Clore, Gerald L

    2011-04-01

    Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome.

  20. Psychology and the Rationality of Emotion*

    OpenAIRE

    Clore, Gerald L.

    2011-01-01

    Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome.

  1. Testing bounded rationality against full rationality in job changing behavior

    OpenAIRE

    Contini, Bruno; Morini, Matteo

    2007-01-01

    In this paper we question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers' performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new ...

  2. Testing Bounded Rationality Against Full Rationality in Job Changing Behavior

    OpenAIRE

    Bruno Contini

    2008-01-01

    In this paper I question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers’ performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new o...

  3. METHODOLOGY OF DOMESTIC STUDIES OF MEDICINAL DRUGS NEED AND THEIR CONSUMPTION

    Directory of Open Access Journals (Sweden)

    N. B. Dryomova

    2015-01-01

    Full Text Available At the current development stage of Russian healthcare rational use of limited financial resources for the fullest satisfaction of population's need in medicinal drugs acquires a special importance. Therefore, the issue about knowledge of experts in determination of need in drugs and evaluation of the consumption, as well as methods applied for these scientific and practical tasks resolution has a critical character. The purpose of our work is to characterize the development of research methodology of medicinal drugs need and their consumption in Russia. We have revealed the dynamics and tendencies of analyzed scientific direction development, leading scientists, principal methods, and study objects using scientometric methods of content-analysis and scientific works calculation (dissertations autoab-stracts. We have established the fact of significant change of methodology beginning with 2000 comparing with a period 1970-1980s. According to authors' opinion this was conditioned by objective need in problem solving connected with pharmaceutical support in the frameworks of state guarantees.

  4. Psychology and the Rationality of Emotion*

    Science.gov (United States)

    Clore, Gerald L.

    2014-01-01

    Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome. PMID:25125770

  5. Rational Thinking and Cognitive Sophistication: Development, Cognitive Abilities, and Thinking Dispositions

    Science.gov (United States)

    Toplak, Maggie E.; West, Richard F.; Stanovich, Keith E.

    2014-01-01

    We studied developmental trends in 5 important reasoning tasks that are critical components of the operational definition of rational thinking. The tasks measured denominator neglect, belief bias, base rate sensitivity, resistance to framing, and the tendency toward otherside thinking. In addition to age, we examined 2 other individual difference…

  6. Delays in clinical development of neurological drugs in Japan.

    Science.gov (United States)

    Ikeda, Masayuki

    2017-06-28

    The delays in the approval and development of neurological drugs between Japan and other countries have been a major issue for patients with neurological diseases. The objective of this study was to analyze factors contributing to the delay in the launching of neurological drugs in Japan. We analyzed data from Japan and the US for the approval of 42 neurological drugs, all of which were approved earlier in the US than in Japan, and examined the potential factors that may cause the delay of their launch. Introductions of the 42 drugs in Japan occurred at a median of 87 months after introductions in the US. The mean review time of new drug applications for the 20 drugs introduced in Japan in January 2011 or later (15 months) was significantly shorter than that for the other 22 drugs introduced in Japan in December 2010 or earlier (24 months). The lag in the Japan's review time behind the US could not explain the approval delays. In the 31 of the 42 drugs, the application data package included overseas data. The mean review time of these 31 drugs (17 months) was significantly shorter than that of the other 11 drugs without overseas data (26 months). The mean approval lag behind the US of the 31 drugs (78 months) was also significantly shorter than that of the other 11 drugs (134 months). These results show that several important reforms in the Japanese drug development and approval system (e.g., inclusion of global clinical trial data) have reduced the delays in the clinical development of neurological drugs.

  7. DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

    Science.gov (United States)

    A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

  8. 75 FR 13081 - Fisheries off West Coast States; Pacific Coast Groundfish Fishery; Trawl Rationalization Program

    Science.gov (United States)

    2010-03-18

    ... West Coast States; Pacific Coast Groundfish Fishery; Trawl Rationalization Program AGENCY: National... proposed Trawl Rationalization Program. We are interested in feedback concerning proposed regulations to... Pacific Fishery Management Council (Council) has been developing a trawl rationalization program that...

  9. The rational parts of one-loop QCD amplitudes I: The general formalism

    International Nuclear Information System (INIS)

    Xiao Zhiguang; Yang Gang; Zhu Chuanjie

    2006-01-01

    A general formalism for computing only the rational parts of one-loop QCD amplitudes is developed. Starting from the Feynman integral representation of the one-loop amplitude, we use tensor reduction and recursive relations to compute the rational parts directly. Explicit formulas for the rational parts are given for all bubble and triangle integrals. Formulas are also given for box integrals up to two-mass-hard boxes which are the needed ingredients to compute up to 6-gluon QCD amplitudes. We use this method to compute explicitly the rational parts of the 5- and 6-gluon QCD amplitudes in two accompanying papers

  10. Max Weber's Types of Rationality: Cornerstones for the Analysis of Rationalization Processes in History.

    Science.gov (United States)

    Kalberg, Stephen

    1980-01-01

    Explores rationality in Max Weber's works and identifies four types of rationality which play major roles in his writing--practical, theoretical, substantive, and formal. Implications for society and education are discussed. (DB)

  11. Significance and challenges of stereoselectivity assessing methods in drug metabolism

    Directory of Open Access Journals (Sweden)

    Zhuowei Shen

    2016-02-01

    Full Text Available Stereoselectivity in drug metabolism can not only influence the pharmacological activities, tolerability, safety, and bioavailability of drugs directly, but also cause different kinds of drug–drug interactions. Thus, assessing stereoselectivity in drug metabolism is of great significance for pharmaceutical research and development (R&D and rational use in clinic. Although there are various methods available for assessing stereoselectivity in drug metabolism, many of them have shortcomings. The indirect method of chromatographic methods can only be applicable to specific samples with functional groups to be derivatized or form complex with a chiral selector, while the direct method achieved by chiral stationary phases (CSPs is expensive. As a detector of chromatographic methods, mass spectrometry (MS is highly sensitive and specific, whereas the matrix interference is still a challenge to overcome. In addition, the use of nuclear magnetic resonance (NMR and immunoassay in chiral analysis are worth noting. This review presents several typical examples of drug stereoselective metabolism and provides a literature-based evaluation on current chiral analytical techniques to show the significance and challenges of stereoselectivity assessing methods in drug metabolism.

  12. Machine learning in the rational design of antimicrobial peptides.

    Science.gov (United States)

    Rondón-Villarreal, Paola; Sierra, Daniel A; Torres, Rodrigo

    2014-01-01

    One of the most important public health issues is the microbial and bacterial resistance to conventional antibiotics by pathogen microorganisms. In recent years, many researches have been focused on the development of new antibiotics. Among these, antimicrobial peptides (AMPs) have raised as a promising alternative to combat antibioticresistant microorganisms. For this reason, many theoretical efforts have been done in the development of new computational tools for the rational design of both better and effective AMPs. In this review, we present an overview of the rational design of AMPs using machine learning techniques and new research fields.

  13. Recent trends for drug lag in clinical development of oncology drugs in Japan: does the oncology drug lag still exist in Japan?

    Science.gov (United States)

    Maeda, Hideki; Kurokawa, Tatsuo

    2015-12-01

    This study exhaustively and historically investigated the status of drug lag for oncology drugs approved in Japan. We comprehensively investigated oncology drugs approved in Japan between April 2001 and July 2014, using publicly available information. We also examined changes in the status of drug lag between Japan and the United States, as well as factors influencing drug lag. This study included 120 applications for approval of oncology drugs in Japan. The median difference over a 13-year period in the approval date between the United States and Japan was 875 days (29.2 months). This figure peaked in 2002, and showed a tendency to decline gradually each year thereafter. In 2014, the median approval lag was 281 days (9.4 months). Multiple regression analysis identified the following potential factors that reduce drug lag: "Japan's participation in global clinical trials"; "bridging strategies"; "designation of priority review in Japan"; and "molecularly targeted drugs". From 2001 to 2014, molecularly targeted drugs emerged as the predominant oncology drug, and the method of development has changed from full development in Japan or bridging strategy to global simultaneous development by Japan's taking part in global clinical trials. In line with these changes, the drug lag between the United States and Japan has significantly reduced to less than 1 year.

  14. The concept of rational suicide.

    Science.gov (United States)

    Mayo, D J

    1986-05-01

    Suicide has been condemned in our culture in one way or another since Augustine offered theological arguments against it in the sixth century. More recently, theological condemnation has given way to the view that suicidal behavior must always be symptomatic of emotional disturbance and mental illness. However, suicide has not always been viewed so negatively. In other times and cultures, it has been held that circumstances might befall a person in which suicide would be a perfectly rational course of action, in the same sense that any other course of action could be rational: that it could be sensible, i.e., defensible by good reasons, or that it could be in keeping with the agent's fundamental interests. Indiscriminate use of modern life-sustaining technologies has renewed interest in the possibility of rational suicide. Today proponents of rational suicide tend to equate the rationality of suicide with the competence of the decision to commit suicide.

  15. The rational expectations equilibrium inventory model theory and applications

    CERN Document Server

    1989-01-01

    This volume consists of six essays that develop and/or apply "rational expectations equilibrium inventory models" to study the time series behavior of production, sales, prices, and inventories at the industry level. By "rational expectations equilibrium inventory model" I mean the extension of the inventory model of Holt, Modigliani, Muth, and Simon (1960) to account for: (i) discounting, (ii) infinite horizon planning, (iii) observed and unobserved by the "econometrician" stochastic shocks in the production, factor adjustment, storage, and backorders management processes of firms, as well as in the demand they face for their products; and (iv) rational expectations. As is well known according to the Holt et al. model firms hold inventories in order to: (a) smooth production, (b) smooth production changes, and (c) avoid stockouts. Following the work of Zabel (1972), Maccini (1976), Reagan (1982), and Reagan and Weitzman (1982), Blinder (1982) laid the foundations of the rational expectations equilibrium inve...

  16. RATGRAPH: Computer Graphing of Rational Functions.

    Science.gov (United States)

    Minch, Bradley A.

    1987-01-01

    Presents an easy-to-use Applesoft BASIC program that graphs rational functions and any asymptotes that the functions might have. Discusses the nature of rational functions, graphing them manually, employing a computer to graph rational functions, and describes how the program works. (TW)

  17. The establishment and expansion of an innovative centre for rational pharmacotherapy--determinants and challenges.

    Science.gov (United States)

    Kardakis, Therese; Tomson, Göran; Wettermark, Björn; Brommels, Mats; Godman, Brian; Bastholm-Rahmner, Pia

    2015-01-01

    The regional Board of Health in Stockholm, Sweden, established the Pharmacotherapy Centre (PTC) to enhance the rational use of medicines. The PTC initiated computerised decision support systems and developed a range of electronic service products to sustain rational prescribing. However, knowledge about which determinants have supported or hindered the sustainability of this type of healthcare organisation is limited. This study aims to identify and explore determinants that support or challenge the development and sustainability of the PTC organisation, as well as investigate the key elements of their implementation efforts. An in-depth interview study among key informants involved in the establishment of the PTC organisation was conducted. Data were analysed using qualitative content analysis. Findings suggest that determinants enabling the development and expansion of this organisation include the presence of innovative characteristics among the PTC leadership and the ability of leaders to nurture visionary innovation in others, as well as the instigation of informal social networks and to identify end-user needs. Challenges included an ambiguous relationship to the pharmaceutical industry, an underestimation of the innovation-system fit and to undertake systematic evaluation of created impact by the organisation. Although prescriber use of electronic service products and adherence to an essential drug list increased over time, it remains difficult to identify methods required for demonstrating patient effects. Whereas some determinants enabled the successful expansion of the PTC organisation, others served to substantially hinder it. The determinants identified can pave the way for systematic investigations into organisational change and development research in the pharmaceutical field. Copyright © 2013 John Wiley & Sons, Ltd.

  18. F-theory and all things rational: surveying U(1) symmetries with rational sections

    International Nuclear Information System (INIS)

    Lawrie, Craig; Schäfer-Nameki, Sakura; Wong, Jin-Mann

    2015-01-01

    We study elliptic fibrations for F-theory compactifications realizing 4d and 6d supersymmetric gauge theories with abelian gauge factors. In the fibration these U(1) symmetries are realized in terms of additional rational section. We obtain a universal characterization of all the possible U(1) charges of matter fields by determining the corresponding codimension two fibers with rational sections. In view of modelling supersymmetric Grand Unified Theories, one of the main examples that we analyze are U(1) symmetries for SU(5) gauge theories with 5̄ and 10 matter. We use a combination of constraints on the normal bundle of rational curves in Calabi-Yau three- and four-folds, as well as the splitting of rational curves in the fibers in codimension two, to determine the possible configurations of smooth rational sections. This analysis straightforwardly generalizes to multiple U(1)s. We study the flops of such fibers, as well as some of the Yukawa couplings in codimension three. Furthermore, we carry out a universal study of the U(1)-charged GUT singlets, including their KK-charges, and determine all realizations of singlet fibers. By giving vacuum expectation values to these singlets, we propose a systematic way to analyze the Higgsing of U(1)s to discrete gauge symmetries in F-theory.

  19. "Leaky" Rationality: How Research on Behavioral Decision Making Challenges Normative Standards of Rationality.

    Science.gov (United States)

    Keys, Daniel J; Schwartz, Barry

    2007-06-01

    For more than 30 years, decision-making research has documented that people often violate various principles of rationality, some of which are so fundamental that theorists of rationality rarely bother to state them. We take these characteristics of decision making as a given but argue that it is problematic to conclude that they typically represent departures from rationality. The very psychological processes that lead to "irrational" decisions (e.g., framing, mental accounting) continue to exert their influence when one experiences the results of the decisions. That is, psychological processes that affect decisions may be said also to "leak" into one's experience. The implication is that formal principles of rationality do not provide a good enough normative standard against which to assess decision making. Instead, what is needed is a substantive theory of rationality-one that takes subjective experience seriously, considers both direct and indirect consequences of particular decisions, considers how particular decisions fit into life as a whole, and considers the effects of decisions on others. Formal principles may play a role as approximations of the substantive theory that can be used by theorists and decision makers in cases in which the formal principles can capture most of the relevant considerations and leakage into experience is negligible. © 2007 Association for Psychological Science.

  20. Popper, Rationality and the Possibility of Social Science

    Directory of Open Access Journals (Sweden)

    Danny Frederick

    2013-02-01

    Full Text Available Social science employs teleological explanations which depend upon the rationality principle, according to which people exhibit instrumental rationality. Popper points out that people also exhibit critical rationality, the tendency to stand back from, and to question or criticise, their views. I explain how our critical rationality impugns the explanatory value of the rationality principle and thereby threatens the very possibility of social science. I discuss the relationship between instrumental and critical rationality and show how we can reconcile our critical rationality with the possibility of social science if we invoke Popper’s conception of limited rationality and his indeterminism.

  1. Rational drug use in acute pancreatitis: Case report

    Directory of Open Access Journals (Sweden)

    Rosić Nikola

    2011-01-01

    Full Text Available Acute pancreatitis is a sudden inflammation of pancreas where its enzymes autodigest the gland. Two main causes of acute pancreatitis are alcoholism and billiar calculosis. Treatment consists of preventing dehydration, analgesia, decrease of pancreatic exocrine function, enteral nutritional support , respiratory and renal function support and surgery. The patient presents with abdominal pain that lasts for few days and is followed by vomiting. Laboratory tests first revealed abnormal values of blood count and pancreas enzymes (leucocytes -19,7 x 109/L, hematocrit - 0,32, amylase - 52569 IU/L, lypase - 4750 IU/L, CRP - 152 IU/L, albumins - 25 g/L, followed by abnormal values of liver enzymes (AST - 80 IU/L, ALT - 127 IU/L, GGT - 362 IU/L. Further diagnostic procedures showed billiary calculosis, pleural effusion and acute pancreatitis with ascites. No surgery was performed, due to the lack of infect ion and the signs of the patient going into recovery. It was observed that not all diagnostic procedures that exist in the protocol of treatment, such as ERCP or biopsy of pancreatic t issue with microbiological investigation, were performed. Considering the rules of rat ional drug therapy, as well as the protocols that are to be applied in Clinical center 'Kragujevac' in Kragujevac, it was observed that some drugs (antibiotics and albumin were not used in a proper manner, i.e. in compliance with the protocol, which increased the cost of the treatment without improving the patient health or shortening the hospital stay.

  2. Casebook on rationalization of power use

    International Nuclear Information System (INIS)

    1986-06-01

    This book introduces the cases on rationalization of power use, which is divided into four parts. The first part refers the goal of rational use of energy and the result. The second part deals with the excellent cases on rationalization of domestic power use, which list the name of the company, hotel and factory according to the field such as building, textile and food. The third part contains the outstanding cases on rationalization of foreign power use, which were listed by the specific way to reduce electricity use each section. The fourth part is comprised of two chapters, which deals with the cases of domestic technical data and foreign technical data for rational use of energy.

  3. Public and private health-care financing with alternate public rationing rules.

    Science.gov (United States)

    Cuff, Katherine; Hurley, Jeremiah; Mestelman, Stuart; Muller, Andrew; Nuscheler, Robert

    2012-02-01

    We develop a model to analyze parallel public and private health-care financing under two alternative public sector rationing rules: needs-based rationing and random rationing. Individuals vary in income and severity of illness. There is a limited supply of health-care resources used to treat individuals, causing some individuals to go untreated. Insurers (both public and private) must bid to obtain the necessary health-care resources to treat their beneficiaries. Given individuals' willingnesses-to-pay for private insurance are increasing in income, the introduction of private insurance diverts treatment from relatively poor to relatively rich individuals. Further, the impact of introducing parallel private insurance depends on the rationing mechanism in the public sector. We show that the private health insurance market is smaller when the public sector rations according to need than when allocation is random. Copyright © 2010 John Wiley & Sons, Ltd.

  4. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  5. Accessing external innovation in drug discovery and development.

    Science.gov (United States)

    Tufféry, Pierre

    2015-06-01

    A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. In this review, the authors look at a number of external innovation opportunities. These include increased interactions with academia via academic centers of excellence/innovation centers, better communication on projects using crowdsourcing or social media and new models centered on external providers such as built-to-buy startups or virtual pharmaceutical companies. The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.

  6. Fragment-based drug discovery as alternative strategy to the drug development for neglected diseases.

    Science.gov (United States)

    Mello, Juliana da Fonseca Rezende E; Gomes, Renan Augusto; Vital-Fujii, Drielli Gomes; Ferreira, Glaucio Monteiro; Trossini, Gustavo Henrique Goulart

    2017-12-01

    Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area. In this article, we discuss the basic Fragment-Based Drug Discovery process, brief successful ideas of general applications and show a landscape of its use in NDs, encouraging the implementation of this strategy as an interesting way to optimize the development of new drugs to NDs. © 2017 John Wiley & Sons A/S.

  7. Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

    Science.gov (United States)

    Sun, Qihang

    Nanocarriers can minimize the side effects and improve therapeutic efficacy of anticancer drugs. Although some success has been achieved via active or passive drug delivery to tumor cells, the known nanocarriers are far from satisfying therapeutic efficacy expectations. This is because they usually fail in one of the four crucial requirements, that is, to retain drug in blood circulation but release it reliably in tumor cells and to be stealthy in transport in circulation and tumor tissue but sticky upon arrival at the tumor cell. Therefore, the goal of this work is to fabricate nanoassemblies of dendrimers and lipids to address all these challenges. Particularly, nanoassemblies designed and prepared in this work are illustrated to improve the tumor tissue penetration. Examples of dendrimers synthesized in this work are water-insoluble, pH-dependent water-insoluble and water-soluble biodegradable polyester dendrimers. These dendrimers are shown to be encapsulated by commonly used fusogenic and long-circulating lipids to form reliable nanoassemblies. The dendrimer/lipid nanocarriers are used to demonstrate a cascade drug delivery. They are expected to be stable in circulation, due to their appropriately large size, but to release the drug-loaded dendrimers in tumor tissue. The released dendrimers carrying drugs are much smaller and hence expected to have a much deeper penetration throughout the tumor tissue.

  8. Relation of knowledge and level of education to the rationality of self-medication on childhood diarrhea on the Code River banks in Jogoyudan, Jetis, Yogyakarta

    Science.gov (United States)

    Dania, H.; Ihsan, M. N.

    2017-11-01

    Self-medication as an alternative is used to reduce the severity of diarrhea. Optimal treatment can be done by increasing the rationalization of self-medication on diarrhea. This can be achieved with good knowledge about self-medication, which is in turn influenced by level of education. The aim of this study was to determine the relationship of knowledge and education level to rationality of self-medication on childhood diarrhea around the Code River in Jogoyudan, Jetis, Yogyakarta. The study was conducted by cross-sectional analytical observational design. The subjects were mothers who had children aged 2-11 years who had experienced diarrhea and had self-medication. Questionnaires were used to assess the rationality of self-medication on children's diarrhea by the parents. The respondents were askeds to fill out about indications, right drugs, doses, time intervals and periods of drug administration. Data were analyzed using chi- square. It was showed that of 40 respondents, 14 respondents (35%) performed rational self-medication on children's diarrhea and 26 respondents (65%). did not rationalize the treatment. The results of a bivariate test obtained a chi-square value of 9.808 (> 3.841) and a p value of 0.002 ( 3.841) and a p value of 0.000 (<0.05) on relationship between knowledge and rationality of self- medication. The conclusion of this study is that there is a correlation between knowledge and level of education and rationality of self-medication on childhood diarrhea on the Code River banks in Jogoyudan, Jetis, Yogyakarta.

  9. Mind the gap : predicting cardiovascular risk during drug development

    NARCIS (Netherlands)

    Chain, Anne S. Y.

    2012-01-01

    Cardiovascular safety issues, specifically drug-induced QT/QTc-interval prolongation, remain a major cause of drug attrition during clinical development and is one of the main causes for post-market drug withdrawals accounting for 15-34% of all drug discontinuation. Given the potentially fatal

  10. Drug policy, harm and human rights: a rationalist approach.

    Science.gov (United States)

    Stevens, Alex

    2011-05-01

    It has recently been argued that drug-related harms cannot be compared, so making it impossible to choose rationally between various drug policy options. Attempts to apply international human rights law to this area are valid, but have found it difficult to overcome the problems in applying codified human rights to issues of drug policy. This article applies the rationalist ethical argument of Gewirth (1978) to this issue. It outlines his argument to the 'principle of generic consistency' and the hierarchy of basic, nonsubtractive and additive rights that it entails. It then applies these ideas to drug policy issues, such as whether there is a right to use drugs, whether the rights of drug 'addicts' can be limited, and how different harms can be compared in choosing between policies. There is an additive right to use drugs, but only insofar as this right does not conflict with the basic and nonsubtractive rights of others. People whose freedom to choose whether to use drugs is compromised by compulsion have a right to receive treatment. They retain enforceable duties not to inflict harms on others. Policies which reduce harms to basic and nonsubtractive rights should be pursued, even if they lead to harms to additive rights. There exists a sound, rational, extra-legal basis for the discussion of drug policy and related harms which enables commensurable discussion of drug policy options. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Rationing medical education | Walsh | African Health Sciences

    African Journals Online (AJOL)

    Even though some stakeholders in medical education might be taken aback at the prospect of rationing, the truth is that rationing has always occurred in one form or another in medical education and in healthcare more broadly. Different types of rationing exist in healthcare professional education. For example rationing may ...

  12. Improving clinical drug development regulatory procedures for anticonvulsants

    Directory of Open Access Journals (Sweden)

    Janković Slobodan

    2015-01-01

    Full Text Available Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the noninferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.

  13. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

    Science.gov (United States)

    Hamilton, Gregory S

    2015-09-01

    Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  14. Por que o uso racional de medicamentos deve ser uma prioridade? Why rational drug use must be a priority?

    Directory of Open Access Journals (Sweden)

    Daniela Silva de Aquino

    2008-04-01

    Full Text Available A Organização Mundial de Saúde diz que há uso racional de medicamentos quando pacientes recebem medicamentos apropriados para suas condições clínicas, em doses adequadas às suas necessidades individuais, por um período adequado e ao menor custo para si e para a comunidade. Porém, o que se observa, mostra uma realidade bastante diferente. Pelo menos 35% dos medicamentos adquiridos no Brasil são feitos através de automedicação. Os medicamentos respondem por 27% das intoxicações no Brasil e 16% dos casos de morte por intoxicações são causados por medicamentos. Além disso, 50% de todos os medicamentos são prescritos, dispensados ou usados inadequadamente, e os hospitais gastam de 15 a 20% de seus orçamentos para lidar com as complicações causadas pelo mau uso dos mesmos. A proposta de alívio imediato do sofrimento, como em um passe de mágica, é um apelo atraente, mas tem seu preço. Este preço nem sempre se restringe ao desembolso financeiro e pode ser descontado na própria saúde. Os requisitos para o uso racional de medicamentos são muito complexos e envolvem uma série de variáveis, em um encadeamento lógico. Para que sejam cumpridos, devem contar com a participação de diversos atores sociais: pacientes, profissionais de saúde, legisladores, formuladores de políticas públicas, indústria, comércio, governo.According to the World Health Organization, rational drug use means that patients receive medicines appropriate to their clinical needs, in doses that meet their individual requirements, for an adequate period of time, and at the lowest cost to them and their community. However, as far as one can see, the reality is very different. In Brazil, at least, 35% of medicines are purchased for self-medication. Medicaments are responsible for 27% of intoxications in Brazil and for 16% of deaths due to poisoning are caused by medicaments. Moreover, 50% of medicaments are prescribed, dispensed or used inappropriately

  15. Models of bounded rationality under certainty

    NARCIS (Netherlands)

    Rasouli, S.; Timmermans, H.J.P.; Rasouli, S.; Timmermans, H.J.P.

    2015-01-01

    Purpose This chapter reviews models of decision-making and choice under conditions of certainty. It allows readers to position the contribution of the other chapters in this book in the historical development of the topic area. Theory Bounded rationality is defined in terms of a strategy to simplify

  16. Towards Rational Decision-Making in Secondary Education.

    Science.gov (United States)

    Cohn, Elchanan

    Without a conscious effort to achieve optimum resource allocation, there is a real danger that educational resources may be wasted. This document uses input-output analysis to develop a model for rational decision-making in secondary education. (LLR)

  17. Effects of Rational-Emotive Therapy, Rational Role Reversal, and Rational-Emotive Imagery on the Emotional Adjustment of Community Mental Health Center Patients.

    Science.gov (United States)

    Lipsky, Marc J.; And Others

    1980-01-01

    Results showed that rational-emotive therapy (RET), with the addition of rational role reversal, produced significantly better results than did relaxation training and support or no contact. This was the first study to demonstrate the efficacy of RET with multisymptomatic applicants to a community mental health center. (Author/BEF)

  18. A qualitative examination of the effects of international counter-drug interdictions.

    Science.gov (United States)

    Toth, Alexander G; Mitchell, Ojmarrh

    2018-05-01

    The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations. The findings indicate that sporadic counter-drug interdictions do not a have permanent deterrent effect on transnational drug smuggling operations. However, these types of law enforcement operations produce temporary alterations in drug trafficking, as traffickers adopted a variety of methods to thwart the efforts of law enforcement-often by relying on information acquired from corrupt local law enforcement. The results also indicate that while interdiction operations displaced trafficking activities (temporally, spatially, and methodological), there is little evidence that drug traffickers responded to such operations by moving into new areas (i.e., malign spatial displacement). Sporadic international drug interdiction programs do little to deter drug trafficking organizations (DTOs) from engaging in their illicit trade. Instead, DTOs adjust in a calculating manner to these operations to ensure that their illegal products reach consumer marketplaces, which is congruent with the rational choice theoretical perspective. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Veterinary Medicine Needs New Green Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Pierre-Louis TOUTAIN

    2016-08-01

    Full Text Available Given that: (1 the worldwide consumption of antimicrobial drugs (AMDs used in food-producing animals will increase over the coming decades; (2 the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR of animal origin; (3 alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed green antibiotics, having minimal ecological impact on the animal commensal and environmental microbiomes.We first explain why animal and human commensal microbiota comprise a turnstile exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s. For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem.

  20. Argumentation, rationality, and psychology of reasoning

    Directory of Open Access Journals (Sweden)

    David Godden

    2015-05-01

    Full Text Available This paper explicates an account of argumentative rationality by articulating the common, basic idea of its nature, and then identifying a collection of assumptions inherent in it. Argumentative rationality is then contrasted with dual-process theories of reasoning and rationality prevalent in the psychology of reasoning. It is argued that argumentative rationality properly corresponds only with system-2 reasoning in dual-process theories. This result challenges the prescriptive force of argumentative norms derives if they derive at all from their descriptive accuracy of our cognitive capacities. In response, I propose an activity-based account of reasoning which retains the assumptions of argumentative rationality while recontextualizing the relationship between reasoning as a justificatory activity and the psychological states and processes underlying that activity.

  1. The intersection of stress, drug abuse and development.

    Science.gov (United States)

    Thadani, Pushpa V

    2002-01-01

    Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

  2. Challenges in developing drugs for primary headaches

    DEFF Research Database (Denmark)

    Schytz, Henrik Winther; Hargreaves, Richard; Ashina, Messoud

    2017-01-01

    This review considers the history of drug development in primary headaches and discusses challenges to the discovery of innovative headache therapeutics. Advances in headache genetics have yet to translate to new classes of therapeutics and there are currently no clear predictive human biomarkers...... for any of the primary headaches that can guide preventative drug discovery and development. Primary headache disorder subtypes despite common phenotypic presentation are undoubtedly heterogeneous in their pathophysiology as judged by the variability of response to headache medicines. Sub......, despite having promising effects in basic pain models, have not delivered efficacy in the clinic. Future efforts may triage novel physiological mediators using human experimental models of headache pain to support drug discovery strategies that target active pathways pharmacologically....

  3. [Development of new drugs: opportunities and benefits for Peru].

    Science.gov (United States)

    Bayona, Andrés; Fajardo, Natalia

    2012-01-01

    The development of innovative drugs allows coming up with new medicines to prevent and better treat illnesses. This improves people's quality of life and makes it more productive. Therefore, the mission of pharmaceutical research is to develop safe and effective drugs. Clinical trials allow the evaluation of the safety and efficacy profiles of new medicines, medical devices and diagnostic tests. Research and development (R&D) of new drugs is a long and costly process, where out of every 5000 to 10000 new components that enter preclinical testing, only one is approved. Compared to 2011, drug development has increased by 7.6%. According to ClinicalTrials.gov, 5% of the trials take place in Latin America, and Peru is in the fifth position. On the other hand, according to the Global Competitiveness Report issued by the World Economic Forum, Peru ranks 61st, its biggest challenges being the functioning of its public institutions, investment in R&D and technological capacity. The complexity of drug R&D results in a search for competitive places to develop clinical trials. Clinical Research is a humanized industry due to its ethical platform, stated in the guidelines of good clinical practices. This industry demands our country to develop a differentiating value that contributes to the development of knowledge and its competitiveness.

  4. Ethnically diverse pluripotent stem cells for drug development.

    Science.gov (United States)

    Fakunle, Eyitayo S; Loring, Jeanne F

    2012-12-01

    Genetic variation is an identified factor underlying drug efficacy and toxicity, and adverse drug reactions, such as liver toxicity, are the primary reasons for post-marketing drug failure. Genetic predisposition to toxicity might be detected early in the drug development pipeline by introducing cell-based assays that reflect the genetic and ethnic variation of the expected treatment population. One challenge for this approach is obtaining a collection of suitable cell lines derived from ethnically diverse populations. Induced pluripotent stem cells (iPSCs) seem ideal for this purpose. They can be obtained from any individual, can be differentiated into multiple relevant cell types, and their self-renewal capability makes it possible to generate large quantities of quality-controlled cell types. Here, we discuss the benefits and challenges of using iPSCs to introduce genetic diversity into the drug development process. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Rational Thinking in School-Based Practice

    Science.gov (United States)

    Clark, Mary Kristen; Flynn, Perry

    2011-01-01

    Purpose: We reflect on Alan Kamhi's (2011) prologue on balancing certainty and uncertainty as it pertains to school-based practice. Method: In schools, rational thinking depends on effective team processes, much like professional learning communities. We consider the conditions that are required for rational thinking and how rational team dialogue…

  6. Off-label use of psychotropic drugs beyond officially approved indications in Colombia

    Directory of Open Access Journals (Sweden)

    Paola Marcela Fletscher-Covaleda

    2017-07-01

    Conclusions: Psychotropic drugs in Bogotá are used, to a great extent, as off-label in indications other than those officially approved. Thus, it is important to strengthen education and control to achieve a rational, effective and safe use of drugs.

  7. Revising Rationality: The Use of "Nudge" Approaches in Neoliberal Education Policy

    Science.gov (United States)

    Bradbury, Alice; McGimpsey, Ian; Santori, Diego

    2013-01-01

    This article argues that the concept of rationality is undergoing significant revision in UK education policy-making, influenced by developments in several academic fields. This article focuses on the take up of behavioural economics in policy as one aspect of this revision of the concept of rationality, discussing how this has happened and its…

  8. Rational approximations for tomographic reconstructions

    International Nuclear Information System (INIS)

    Reynolds, Matthew; Beylkin, Gregory; Monzón, Lucas

    2013-01-01

    We use optimal rational approximations of projection data collected in x-ray tomography to improve image resolution. Under the assumption that the object of interest is described by functions with jump discontinuities, for each projection we construct its rational approximation with a small (near optimal) number of terms for a given accuracy threshold. This allows us to augment the measured data, i.e., double the number of available samples in each projection or, equivalently, extend (double) the domain of their Fourier transform. We also develop a new, fast, polar coordinate Fourier domain algorithm which uses our nonlinear approximation of projection data in a natural way. Using augmented projections of the Shepp–Logan phantom, we provide a comparison between the new algorithm and the standard filtered back-projection algorithm. We demonstrate that the reconstructed image has improved resolution without additional artifacts near sharp transitions in the image. (paper)

  9. Determinants of the range of drugs prescribed in general practice: a cross-sectional analysis.

    NARCIS (Netherlands)

    Bakker, D.H. de; Coffie, D.S.V.; Heerdink, E.R.; Dijk, L. van; Groenewegen, P.P.

    2007-01-01

    BACKGROUND: Current health policies assume that prescribing is more efficient and rational when general practitioners (GPs) work with a formulary or restricted drugs lists and thus with a limited range of drugs. Therefore we studied determinants of the range of drugs prescribed by general

  10. Rationality in Machiavelli and in Kant

    Directory of Open Access Journals (Sweden)

    Vadim Chaly

    2016-11-01

    Full Text Available The paper contains interpretation and comparative analysis of Machiavelli’s and Kant’s conceptions on rationality as two prime examples of “realist” and “idealist” modes of agency. Kantian model of rationality is viewed as an augmentation of the Machiavellian one, not an opposition to it. To elaborate the point, Robert Aumann’s model of act-rationality and rulerationality is applied to the two philosophical models. Kantian practical reason is interpreted as an addition to Aumann’s instrumental rationality, providing rules for rules, or “rule-rule-rationality”.

  11. A meta-analysis of the relationship between rational beliefs and psychological distress.

    Science.gov (United States)

    Oltean, Horea-Radu; David, Daniel Ovidiu

    2018-06-01

     Rational emotive behavior therapy (REBT) model of psychological health assumes that rational beliefs cause functional emotions and adaptive behavior, but the presumed role of rational beliefs as protective factor against psychological distress/disorders is still in debate. An important step in validating an evidence-based therapy is to investigate the underling theoretical assumptions. Thus, the aim of the present meta-analysis is to investigate the direction and magnitude of the relationship between rational beliefs and psychological distress.  Our search identified 26 studies that met our criteria. We evaluated the effect size using the random-effects model and we tested the moderator role of several variables. The overall results revealed a medium negative association between rational beliefs and psychological distress, r = -0.31. The strongest association was found for unconditional acceptance beliefs (r = -0.41). The results add empirical evidence for the underling theory of REBT and revealed that the strength of the association between rational beliefs and distress is robust for a wide range of emotional problems. Therefore, rational beliefs could be a trans-diagnostic protective factor against distress. Moreover, results emphasized that rational beliefs type is an important factor, suggesting an increased focus in therapy on the developing of unconditional acceptance and self-acceptance beliefs. © 2017 Wiley Periodicals, Inc.

  12. Effective Entrepreneurial Choice: The Role of Rationality and Non-Rationality in Three Entrepreneurs Success Stories

    OpenAIRE

    Chong, Anne Michele, Siang Yoon

    2007-01-01

    Good entrepreneurship is important for economic growth and productivity in any modern economy. The purpose of this dissertation is to research how good entrepreneurial decisions are made. In theory, optimal or rational decision making means choosing the best alternative in response to the problem. However, in reality, people do not act rationally because they often cannot make rational choices. The reason is that people do not have enough brain power, time or resources to process the compl...

  13. AGC kinases, mechanisms of regulation ‎and innovative drug development.

    Science.gov (United States)

    Leroux, Alejandro E; Schulze, Jörg O; Biondi, Ricardo M

    2018-02-01

    The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation. In the present review, we update the knowledge of the mechanisms of regulation of different AGC kinases. The conformation of the catalytic domain of many AGC kinases is regulated allosterically through the modulation of the conformation of a regulatory site on the small lobe of the kinase domain, the PIF-pocket. The PIF-pocket acts like an ON-OFF switch in AGC kinases with different modes of regulation, i.e. PDK1, PKB/Akt, LATS and Aurora kinases. In this review, we make emphasis on how the knowledge of the molecular mechanisms of regulation can guide the discovery and development of small allosteric modulators. Molecular probes stabilizing the PIF-pocket in the active conformation are activators, while compounds stabilizing the disrupted site are allosteric inhibitors. One challenge for the rational development of allosteric modulators is the lack of complete structural information of the inhibited forms of full-length AGC kinases. On the other hand, we suggest that the available information derived from molecular biology and biochemical studies can already guide screening strategies for the identification of innovative mode of action molecular probes and the development of selective allosteric drugs for the treatment of human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Suicide: rationality and responsibility for life.

    Science.gov (United States)

    Ho, Angela Onkay

    2014-03-01

    Death by suicide is widely held as an undesirable outcome. Most Western countries place emphasis on patient autonomy, a concept of controversy in relation to suicide. This paper explores the tensions between patients' rights and many societies' overarching desire to prevent suicide, while clarifying the relations between mental disorders, mental capacity, and rational suicide. A literature search was conducted using search terms of suicide and ethics in the PubMed and LexisNexis Academic databases. Article titles and abstracts were reviewed and deemed relevant if the paper addressed topics of rational suicide, patient autonomy or rights, or responsibility for life. Further articles were found from reference lists and by suggestion from preliminary reviewers of this paper. Suicidal behaviour in a person cannot be reliably predicted, yet various associations and organizations have developed standards of care for managing patients exhibiting suicidal behaviour. The responsibility for preventing suicide tends to be placed on the treating clinician. In cases where a person is capable of making treatment decisions--uninfluenced by any mental disorder--there is growing interest in the concept of rational suicide. There is much debate about whether suicide can ever be rational. Designating suicide as an undesirable event that should never occur raises the debate of who is responsible for one's life and runs the risk of erroneously attributing blame for suicide. While upholding patient rights of autonomy in psychiatric care is laudable, cases of suicidality warrant a delicate consideration of clinical judgment, duty of care, and legal obligations.

  15. The role of globalization in drug development and access to orphan drugs: orphan drug legislation in the US/EU and in Latin America.

    Science.gov (United States)

    Arnold, Renée J G; Bighash, Lida; Bryón Nieto, Alejandro; Tannus Branco de Araújo, Gabriela; Gay-Molina, Juan Gabriel; Augustovski, Federico

    2015-01-01

    Compared to a decade ago, nearly three times as many drugs for rare diseases are slated for development. This article addresses the market access issues associated with orphan drug status in Europe and the United States in contrast to the legislation in five Latin American (LA) countries that have made strides in this regard--Mexico, Brazil, Colombia, Chile and Argentina. Based on the success of orphan drug legislation in the EU and US, LA countries should strive to adopt similar strategies with regard to rare diseases and drug development. With the implementation of new targeted regulations, reimbursement strategies, and drug approvals, accessibility to treatment will be improved for people afflicted with rare diseases in these developing countries.

  16. Brivaracetam: a rational drug discovery success story

    Science.gov (United States)

    Rogawski, M A

    2008-01-01

    Levetiracetam, the α-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a ∼90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity in animal seizure models. Recent phase II clinical trials demonstrating that brivaracetam is efficacious and well tolerated in the treatment of partial onset seizures have validated the strategy of the discovery programme. Brivaracetam is among the first clinically effective AEDs to be discovered by optimization of pharmacodynamic activity at a molecular target. PMID:18552880

  17. Rational use of blood glucose test strips for self-monitoring in patients with diabetes mellitus: Economic impact in the Portuguese healthcare system.

    Science.gov (United States)

    Risso, Teresa; Furtado, Cláudia

    2017-12-01

    Self-monitoring of blood glucose is important for diabetes management in insulin-treated patients, but its effectiveness in patients treated with oral glucose lowering drugs only is not fully supported by current evidence. This paper aims to characterise the prescription patterns of blood glucose test strips (BGTS) in Portugal and estimate the potential cost-savings from the rational use of BGTS. A retrospective analysis of the Portuguese database of electronic medical prescriptions to assess the patterns of BGTS prescription. The database was searched for prescription, from 01 January 2016 to 31 December 2016, of insulin and other antidiabetics, as well as the associated prescriptions of BGTS. 894,637 patients were prescribed antidiabetic medicines during 2016, 82.7% of which were prescribed oral glucose lowering drugs only. BGTS were prescribed to 456,179 patients, being more frequently prescribed in insulin-treated patients. Still, 42.8% of patients treated with oral glucose lowering drugs only were also prescribed BGTS, with large proportion of those being prescribed antidiabetic drugs with lower risk of causing hypoglycaemia and, even so, >200 BGTS/year. Several scenarios for a more rational use of BGTS were estimated to result in cost-savings of up to €9.5 million per year. BGTS were prescribed to more than a third of patients treated with oral glucose lowering drugs only, despite accumulating evidence of their limited effectiveness in this population, resulting in substantial economic burden to the healthcare system. Given the estimated potential cost-savings, rational use of BGTS should be encouraged in Portugal. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Phase II clinical development of new drugs

    CERN Document Server

    Ting, Naitee; Ho, Shuyen; Cappelleri, Joseph C

    2017-01-01

    This book focuses on how to appropriately plan and develop a Phase II program, and how to design Phase II clinical trials and analyze their data. It provides a comprehensive overview of the entire drug development process and highlights key questions that need to be addressed for the successful execution of Phase II, so as to increase its success in Phase III and for drug approval. Lastly it warns project team members of the common potential pitfalls and offers tips on how to avoid them.

  19. Development of a Rational Design Space for Optimizing Mixing Conditions for Formation of Adhesive Mixtures for Dry-Powder Inhaler Formulations.

    Science.gov (United States)

    Sarkar, Saurabh; Minatovicz, Bruna; Thalberg, Kyrre; Chaudhuri, Bodhisattwa

    2017-01-01

    The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and AstraZeneca fine lactose in high-shear and low-shear double cone blenders was systematically investigated. Process variables impacting the mixing performance were evaluated for both blenders. The performance of the blenders with respect to the mixing time, press-on forces, static charging, and abrasion of carrier fines was monitored, and for some of the parameters, distinct differences could be detected. A comparison table is presented, which can be used as a guidance to enable rational choice of blender and process parameters based on the user requirements. Segregation of adhesive mixtures during hopper discharge was also investigated. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  1. Discrete Choice and Rational Inattention

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Melo, Emerson; de Palma, André

    2017-01-01

    This paper establishes a general equivalence between discrete choice and rational inattention models. Matejka and McKay (2015, AER) showed that when information costs are modelled using the Shannon entropy, the result- ing choice probabilities in the rational inattention model take the multinomial...... logit form. We show that when information costs are modelled using a class of generalized entropies, then the choice probabilities in any rational inattention model are observationally equivalent to some additive random utility discrete choice model and vice versa. This equivalence arises from convex...

  2. Rationalization of work of leaders of physical-sports organizations

    Directory of Open Access Journals (Sweden)

    Galina Putiatina

    2016-02-01

    Full Text Available Purpose: to create the main ways of rationalization of the work of heads of physical-sports organizations in the structure of their scientific organization of the work. Material & Methods: the content of the administrative activity of representatives of the system of the regional government of the sphere of physical culture and sport of the Kharkov area, and also directors of sports schools of Kharkov (57 respondents are generalized. Methods – the analysis of references, the organizational analysis, the organizational diagnosis, the poll (questioning, the methods of mathematical statistics. Results: the essence and the content of rationalization of the administrative work in the sphere of physical culture and sport are considered. The integrated approach to certain objects of rationalization of the administrative work is established in physical-sports organizations. Conclusions: the main ways of rationalization of the work of heads of physical-sports organizations are: the organization of work concerning the development of motivational mechanisms of the activity of heads; the increase of the economic appeal of work; the formation of ideology of a healthy lifestyle.

  3. Rational top and its classical r-matrix

    International Nuclear Information System (INIS)

    Aminov, G; Arthamonov, S; Smirnov, A; Zotov, A

    2014-01-01

    We construct a rational integrable system (the rational top) on a co-adjoint orbit of SL N Lie group. It is described by the Lax operator with spectral parameter and classical non-dynamical skew-symmetric r-matrix. In the case of the orbit of minimal dimension the model is gauge equivalent to the rational Calogero–Moser (CM) system. To obtain the results we represent the Lax operator of the CM model in two different factorized forms—without spectral parameter (related to the spinless case) and another one with the spectral parameter. The latter gives rise to the rational top while the first one is related to generalized Cremmer–Gervais r-matrices. The gauge transformation relating the rational top and CM model provides the classical rational version of the IRF-Vertex correspondence. From the geometrical point of view it describes the modification of SL(N,C)-bundles over degenerated elliptic curve. In view of the Symplectic Hecke Correspondence the rational top is related to the rational spin CM model. Possible applications and generalizations of the suggested construction are discussed. In particular, the obtained r-matrix defines a class of KZB equations. (paper)

  4. Development of a brazilian nanoencapsulated drug for schistosomiasis treatment

    Directory of Open Access Journals (Sweden)

    Laís Bastos da Fonseca

    2013-11-01

    Full Text Available Schistosomiasis is a parasitic disease that, according to the World Health Organization, constitutes a major public health problem associated with severe morbidity, mostly children in preschool age. The administration of drugs in children always constitutes a difficult task, especially when formulations are not developed specifically for pediatric use, when high doses of drug are required and the drug has a bitter taste, as in the case of praziquantel. Polymer nanoparticles are promising systems for development of encapsulated drugs with low water solubility and bitter taste, due to the good physical and chemical stability, adequate biocompatibility and simple manufacturing processes. Moreover, they can enhance the bioavailabili-ty and reduce variability of treatment among patients. Poly (methyl methacrylate doped with praziquantel was produced through a miniemulsion polymerization pro-cess to compose a pediatric pharmaceutical suspension. Nanoparticles were cha-racterized in terms of physico-chemical properties, toxicological properties and biological activity in mice, being concluded that obtained results were satisfactory. The results were encapsulation rate around 90%, absence of chemical interaction drug - polymer and the presence of biological activity. A collaborative approach was used for this development, involving national partnerships and independent funding mechanisms, a powerful pathway for development of drugs for neglected diseases.

  5. Hot-spot analysis for drug discovery targeting protein-protein interactions.

    Science.gov (United States)

    Rosell, Mireia; Fernández-Recio, Juan

    2018-04-01

    Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

  6. Rational design of nanomaterials for water treatment

    KAUST Repository

    Li, Renyuan

    2015-08-26

    The ever-increasing human demand for safe and clean water is gradually pushing conventional water treatment technologies to their limits and it is now a popular perception that the solutions to the existing and future water challenges will highly hinge upon the further development of nanomaterial sciences. The concept of rational design emphasizes ‘design-for-purpose’ and it necessitates a scientifically clear problem definition to initiate the nanomaterial design. The field of rational design of nanomaterials for water treatment has experienced a significant growth in the past decade and is poised to make its contribution in creating advanced next-generation water treatment technologies in the years to come. Within the water treatment context, this review offers a comprehensive and in-depth overview of the latest progress of the rational design, synthesis and applications of nanomaterials in adsorption, chemical oxidation and reduction reactions, membrane-based separation, oil/water separation, and synergistic multifunctional all-in-one nanomaterials/nanodevices. Special attention is paid on chemical concepts of the nanomaterial designs throughout the review.

  7. Adolescent Identity: Rational vs. Experiential Processing, Formal Operations, and Critical Thinking Beliefs.

    Science.gov (United States)

    Klaczynski, Paul A.; Fauth, James M.; Swanger, Amy

    1998-01-01

    The extent to which adolescents rely on rational versus experiential information processing was studied with 49 adolescents administered multiple measures of formal operations, two critical thinking questionnaires, a measure of rational processing, and a measure of ego identity status. Implications for studies of development are discussed in terms…

  8. Lessons from Learning to Have Rational Expectations

    OpenAIRE

    Lindh, Thomas

    1989-01-01

    This paper reviews a growing literature investigating how economic agents may learn rational expectations. Fully rational learning requires implausible initial information assumptions, therefore some form of bounded rationality has come into focus. Such learning models often converge to rational expectations equilibria within certain bounds. Convergence analysis has been much simplified by methods from adaptive control theory. Learning stability as a correspondence principle show some promise...

  9. Drug development against tuberculosis: Impact of alkaloids.

    Science.gov (United States)

    Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K

    2017-09-08

    Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Drug development for airway diseases: looking forward

    NARCIS (Netherlands)

    Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F.

    2015-01-01

    Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations

  11. Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

    Science.gov (United States)

    Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

    2006-08-10

    optimize the rate of drug dissolution and permeation. A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug and excipients. Advances in experimental and computational methodologies will be helpful in shortening the processing time from formulation design to clinical use. This paper aims to review the developments in the buccal adhesive drug delivery systems to provide basic principles to the young scientists, which will be useful to circumvent the difficulties associated with the formulation design.

  12. Cost-effectiveness analysis of microdose clinical trials in drug development.

    Science.gov (United States)

    Yamane, Naoe; Igarashi, Ataru; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

    2013-01-01

    Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.

  13. Otic drug delivery systems: formulation principles and recent developments.

    Science.gov (United States)

    Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

    2018-04-25

    Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

  14. Rationing hepatitis C treatment in the context of austerity policies in France and Cameroon: A transnational perspective on the pharmaceuticalization of healthcare systems.

    Science.gov (United States)

    Chabrol, Fanny; David, Pierre-Marie; Krikorian, Gaëlle

    2017-08-01

    New powerful drugs against hepatitis C can cure the disease, but they are not widely distributed because their exorbitant prices are destabilizing healthcare systems in both African and European countries. This article takes access to hepatitis C treatments since 2013 in France and in Cameroon as a lens to analyze the rationing of pharmaceutical treatments in relation to recent transformations of health systems. Access to these treatments is analyzed thanks to ethnographic observation and interviews lead in Paris and Yaoundé, with patients, associations, health professionals and public health experts. In Cameroon, rationing takes place through various layers of socio-economic restrictions, and no patient organization advocates for hepatitis treatment. In France, access to hepatitis C treatments has become politicized, and collective mobilizations have denounced rationing as a threat to the promise of universal social security. In this study, we examine Africa's long experience with rationing in the context of structural adjustment, and we bring together experiences in France and Cameroon. This article analyses the phenomenon of the pharmaceuticalization of healthcare systems, that is to say the growing use of pharmaceuticals in healthcare systems, by documenting the social and political construction of scarcity. Indeed, whereas pharmaceuticalization is a concept that has often been used in situations of drugs abundance, a parallel analysis of rationing highlights a political economy of pharmaceuticals that shapes public health debates and policies according to an economy of scarcity, especially in times of austerity. Copyright © 2017. Published by Elsevier Ltd.

  15. Computational Amphiphilic Materials for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naresh eThota

    2015-10-01

    Full Text Available Amphiphilic materials can assemble into a wide variety of morphologies and have emerged as a novel class of candidates for drug delivery. Along with a large number of experiments reported, computational studies have been also conducted in this field. At an atomistic/molecular level, computations can facilitate quantitative understanding of experimental observations and secure fundamental interpretation of underlying phenomena. This review summarizes the recent computational efforts on amphiphilic copolymers and peptides for drug delivery. Atom-resolution and time-resolved insights are provided from bottom-up to microscopically elucidate the mechanisms of drug loading/release, which are indispensable in the rational screening and design of new amphiphiles for high-efficacy drug delivery.

  16. Rational-number comparison across notation: Fractions, decimals, and whole numbers.

    Science.gov (United States)

    Hurst, Michelle; Cordes, Sara

    2016-02-01

    Although fractions, decimals, and whole numbers can be used to represent the same rational-number values, it is unclear whether adults conceive of these rational-number magnitudes as lying along the same ordered mental continuum. In the current study, we investigated whether adults' processing of rational-number magnitudes in fraction, decimal, and whole-number notation show systematic ratio-dependent responding characteristic of an integrated mental continuum. Both reaction time (RT) and eye-tracking data from a number-magnitude comparison task revealed ratio-dependent performance when adults compared the relative magnitudes of rational numbers, both within the same notation (e.g., fractions vs. fractions) and across different notations (e.g., fractions vs. decimals), pointing to an integrated mental continuum for rational numbers across notation types. In addition, eye-tracking analyses provided evidence of an implicit whole-number bias when we compared values in fraction notation, and individual differences in this whole-number bias were related to the individual's performance on a fraction arithmetic task. Implications of our results for both cognitive development research and math education are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. Should informed consent be based on rational beliefs?

    Science.gov (United States)

    Savulescu, J; Momeyer, R W

    1997-10-01

    Our aim is to expand the regulative ideal governing consent. We argue that consent should not only be informed but also based on rational beliefs. We argue that holding true beliefs promotes autonomy. Information is important insofar as it helps a person to hold the relevant true beliefs. But in order to hold the relevant true beliefs, competent people must also think rationally. Insofar as information is important, rational deliberation is important. Just as physicians should aim to provide relevant information regarding the medical procedures prior to patients consenting to have those procedures, they should also assist patients to think more rationally. We distinguish between rational choice/action and rational belief. While autonomous choice need not necessarily be rational, it should be based on rational belief. The implication for the doctrine of informed consent and the practice of medicine is that, if physicians are to respect patient autonomy and help patients to choose and act more rationally, not only must they provide information, but they should care more about the theoretical rationality of their patients. They should not abandon their patients to irrationality. They should help their patients to deliberate more effectively and to care more about thinking rationally. We illustrate these arguments in the context of Jehovah's Witnesses refusing life-saving blood transfusions. Insofar as Jehovah's Witnesses should be informed of the consequences of their actions, they should also deliberate rationally about these consequences.

  18. Open source biotechnology : A drug for developing countries' health problems?

    NARCIS (Netherlands)

    Schellekens, M.H.M.

    2008-01-01

    In developing countries, many people suffer from diseases for which there are no drugs or for which drugs exist that they cannot afford because they are too expensive. The advent of genomics has sparked the idea that new drugs can be more easily developed and that genomics thus could lessen the

  19. Challenges in orphan drug development and regulatory policy in China.

    Science.gov (United States)

    Cheng, Alice; Xie, Zhi

    2017-01-18

    While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

  20. [Data-mining characteristics of adverse drug reactions and pharmacovi-gilance of Chinese patent drugs including Aconitum herbs].

    Science.gov (United States)

    Zhang, Xiao-Meng; Li, Fan; Zhang, Bing; Chen, Xiao-Fen; Piao, Jing-Zhu

    2018-01-01

    The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication

  1. Research Article Antimalarial Drugs for Pediatrics - Prescribing and ...

    African Journals Online (AJOL)

    Erah

    2011-03-23

    Mar 23, 2011 ... is a need to institute measures to ensure rational prescribing, dispensing and use of antimalarial drugs in pediatrics. ... facilities, strategies to control behaviour in the private sector are ..... changes were implemented in 2006 in.

  2. [Effect of psychotropic drugs on activity of anticonvulsants in maximal electroshock test].

    Science.gov (United States)

    Alikina, N A; Tregubov, A L; Kotegov, V P

    2010-08-01

    The effect ofpsychotropic drugs on the pharmacological properties of anticonvulsants was studied on white mice under maximal electroshock (ME) test conditions. Changes in the anticonvulsant effect of phenobarbital, diphenin, carbamazepine, hexamidine were traced upon their joint administration with psychotropic drugs, including piracetam, aminalon, amitriptyline, imizine, levomepromazine, and lithium oxybutyrate. An important result of research is the fact, that in no one of combinations the basic pharmacological effect of anticonvulsants was decreased. Based on the results of experiments, the most rational combinations of anticonvulsants with psychotropic preparations were revealed as manifested in the ME test. As criterion of rational combination was the increase in the activity of anticonvulsants and reduction of their toxicity in combination or at least invariance of this parameter. Rational combinations include (i) phenobarbital with piracetam, amitriptyline, levomepromazine, and lithium oxybutyrate; (ii) carbamazepine with piracetam; and (iii) hexamidine with amitriptyline, levomepromazine and imizine.

  3. Racism in United States: Drug Legislation and the Trade-Off Behind It

    Science.gov (United States)

    Heiligman, Avron C.

    1978-01-01

    This paper attempts to show that drug legislation in the United States has been the result of racial discrimination as rationalized by labeling specific target populations deviant. The author suggests that organized medicine can also be linked to the controlling measures of drug legislation. (Author)

  4. Product differentiation under bounded rationality

    NARCIS (Netherlands)

    Vermeulen, B.; Poutré, La J.A.; Kok, de A.G.; Pyka, A.; Handa, H.; Ishibuchi, H.; Ong, Y.-S.; Tan, K.-C.

    2015-01-01

    We study product differentiation equilibria and dynamics on the Salop circle under bounded rationality. Due to bounded rationality, firms tend to agglomerate in pairs. Upon adding a second tier of component suppliers, downstream assemblers may escape pairwise horizontal agglomeration. Moreover, we

  5. Effectiveness of an educational feedback intervention on drug prescribing in dental practice.

    Science.gov (United States)

    Rauniar, G P; Das, B P; Manandhar, T R; Bhattacharya, S K

    2012-01-01

    Irrational use of drugs as well as inappropriate and over drug prescribing leads to unnecessary expenditures and emergence of resistant bacterial strains. Feedback intervention on drug prescribing habits and face to face educational intervention of prescription audit would be effective in rationalizing prescribing practices. To measure the impact of educational feedback intervention on the prescribing behavior of dental surgeons. Prospective audit of twelve hundred outpatients prescriptions in dental OPD at BPKIHS of those dental surgeon who attended the educational intervention session was collected randomly by trained persons on customized data collection sheet before and after educational intervention. A total 1200 prescription were collected, 300 before and 300 after intervention period at the internal of one month, three months and six months. Majority of the prescriptions (39.33%) contained four drugs but after intervention, prescriptions contained mostly one drug, 73% in first month, 78.67% in third month and 65.34% in six month. Mean number of drugs per prescription after intervention were decreased. There was increased number of generic names of drugs after intervention. Amoxicillin, Metronidazole, Chlorhexidine, Povidone iodine gargle, Nimesulide, Ibuprofen, Ibuprofen + paracetamol, and Paracetamol were most commonly prescribed by dental prescribers before and after intervention. Selection of antimicrobial was done on empirical basis which was correct because Amoxicillin concentration reaches effectively in gingival crevicular fluid and Metronidazole covered effectively against anaerobic bacteria were found in orodental infection. The uses of topical anti-infective preparation as irrigants of choice that can kill majority of micro-organisms found is root canal and dental tubules and minimize systemic use of antimicrobials. Nimesulide prescribing needs to be rationalized. Feedback educational intervention of prescription audit is effective to improve their

  6. An evaluation of rational-emotive imagery as a component of rational-emotive therapy in the treatment of test anxiety.

    Science.gov (United States)

    Hymen, S P; Warren, R

    1978-06-01

    This study evaluated the efficacy of rational-emotive imagery as a component of rational-emotive therapy in reduction of college students' test anxiety. 11 volunteers met for 6 1-hr. group treatment sessions over a 3-wk. period. After 2 initial treatment sessions subjects were randomly assigned to groups given either rational-emotive therapy with rational-emotive imagery or rational-emotive therapy without imagery. Contrary to predictions, improvement between groups on self-report and performance measures was nonsignificant. Failure to obtain differences was attributed to similarities in content of treatment sessions and short treatment time. Combined groups reported significant improvement on all dependent measures. Although the study did not yield the predicted benefits of the imagery, results lend further support to the efficacy of rational-emotive therapy procedures in the reduction of test anxiety.

  7. Emotional and rational disease acceptance in patients with depression and alcohol addiction

    Directory of Open Access Journals (Sweden)

    Matthiessen Peter F

    2008-01-01

    Full Text Available Abstract Background The concept of a rational respectively emotional acceptance of disease is highly valued in the treatment of patients with depression or addiction. Due to the importance of this concept for the long-term course of disease, there is a strong interest to develop a tool to identify the levels and factors of acceptance. We thus intended to test an instrument designed to assess the level of positive psychological wellbeing and coping, particularly emotional disease acceptance and life satisfaction Methods In an anonymous cross-sectional survey enrolling 115 patients (51% female, 49% male; mean age 47.6 ± 10.0 years with depression and/or alcohol addiction, the ERDA questionnaire was tested. Results Factor analysis of the 29-item construct (Cronbach's alpha = 0.933 revealed a 4-factor solution, which explained 59.4% of variance: (1 Positive Life Construction, Contentedness and Well-Being; (2 Conscious Dealing with Illness; (3 Rejection of an Irrational Dealing with Disease; (4 Disease Acceptance. Two factors could be ascribed to a rational, and two to an emotional acceptance. All factors correlated negatively with Depression and Escape, while several aspects of Life Satisfaction" (i.e. myself, overall life, where I live, and future prospects correlated positively. The highest factor scores were found for the rational acceptance styles (i.e. Conscious Dealing with Illness; Disease Acceptance. Emotional acceptance styles were not valued in a state of depression. Escape from illness was the strongest predictor for several acceptance aspects, while life satisfaction was the most relevant predictor for "Positive Life Construction, Contentedness and Well-Being". Conclusion The ERDA questionnaire was found to be a reliable and valid assessment of disease acceptance strategies in patients with depressive disorders and drug abuses. The results indicate the preferential use of rational acceptance styles even in depression. Disease acceptance

  8. Emotional and rational disease acceptance in patients with depression and alcohol addiction.

    Science.gov (United States)

    Büssing, Arndt; Matthiessen, Peter F; Mundle, Götz

    2008-01-21

    The concept of a rational respectively emotional acceptance of disease is highly valued in the treatment of patients with depression or addiction. Due to the importance of this concept for the long-term course of disease, there is a strong interest to develop a tool to identify the levels and factors of acceptance. We thus intended to test an instrument designed to assess the level of positive psychological wellbeing and coping, particularly emotional disease acceptance and life satisfaction In an anonymous cross-sectional survey enrolling 115 patients (51% female, 49% male; mean age 47.6 +/- 10.0 years) with depression and/or alcohol addiction, the ERDA questionnaire was tested. Factor analysis of the 29-item construct (Cronbach's alpha = 0.933) revealed a 4-factor solution, which explained 59.4% of variance: (1) Positive Life Construction, Contentedness and Well-Being; (2) Conscious Dealing with Illness; (3) Rejection of an Irrational Dealing with Disease; (4) Disease Acceptance. Two factors could be ascribed to a rational, and two to an emotional acceptance. All factors correlated negatively with Depression and Escape, while several aspects of Life Satisfaction" (i.e. myself, overall life, where I live, and future prospects) correlated positively. The highest factor scores were found for the rational acceptance styles (i.e. Conscious Dealing with Illness; Disease Acceptance). Emotional acceptance styles were not valued in a state of depression. Escape from illness was the strongest predictor for several acceptance aspects, while life satisfaction was the most relevant predictor for "Positive Life Construction, Contentedness and Well-Being". The ERDA questionnaire was found to be a reliable and valid assessment of disease acceptance strategies in patients with depressive disorders and drug abuses. The results indicate the preferential use of rational acceptance styles even in depression. Disease acceptance should not be regarded as a coping style with an attitude

  9. [Alternatives to the drug research and development model].

    Science.gov (United States)

    Velásquez, Germán

    2015-03-01

    One-third of the global population lacks access to medications; the situation is worse in poor countries, where up to 50% of the population lacks access. The failure of current incentive systems based in intellectual property to offer the necessary pharmaceutical products, especially in the global south, is a call to action. Problems related to drug access cannot be solved solely through improvements or modifications in the existing incentive models. The intellectual property system model does not offer sufficient innovation for developing countries; new mechanisms that effectively promote innovation and drug access simultaneously are needed. A binding international agreement on research and development, negotiated under the auspices of the World Health Organization, could provide an adequate framework for guaranteeing priority-setting, coordination, and sustainable financing of drugs at reasonable prices for developing countries.

  10. Challenges in the clinical development of new antiepileptic drugs.

    Science.gov (United States)

    Franco, Valentina; French, Jacqueline A; Perucca, Emilio

    2016-01-01

    Despite the current availability in the market of over two dozen antiepileptic drugs (AEDs), about one third of people with epilepsy fail to achieve complete freedom from seizures with existing medications. Moreover, currently available AEDs have significant limitations in terms of safety, tolerability and propensity to cause or be a target for clinically important adverse drug interactions. A review of the evidence shows that there are many misperceptions about the viability of investing into new therapies for epilepsy. In fact, there are clear incentives to develop newer and more efficacious medications. Developing truly innovative drugs requires a shift in the paradigms for drug discovery, which is already taking place by building on greatly expanded knowledge about the mechanisms involved in epileptogenesis, seizure generation, seizure spread and development of co-morbidities. AED development can also benefit by a review of the methodology currently applied in clinical AED development, in order to address a number of ethical and scientific concerns. As discussed in this article, many processes of clinical drug development, from proof-of-concept-studies to ambitious programs aimed at demonstrating antiepileptogenesis and disease-modification, can be facilitated by a greater integration of preclinical and clinical science, and by application of knowledge acquired during decades of controlled epilepsy trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Rationing in health systems: A critical review.

    Science.gov (United States)

    Keliddar, Iman; Mosadeghrad, Ali Mohammad; Jafari-Sirizi, Mehdi

    2017-01-01

    Background: It is difficult to provide health care services to all those in need of such services due to limited resources and unlimited demands. Thus, priority setting and rationing have to be applied. This study aimed at critically examining the concept of rationing in health sector and identifying its purposes, influencing factors, mechanisms, and outcomes. Methods: The critical interpretive synthesis methodology was used in this study. PubMed, Cochrane, and Proquest databases were searched using the related key words to find related documents published between 1970 and 2015. In total, 161 published reports were reviewed and included in the study. Thematic content analysis was applied for data analysis. Results: Health services rationing means restricting the access of some people to useful or potentially useful health services due to budgetary limitation. The inherent features of the health market and health services, limited resources, and unlimited needs necessitate health services rationing. Rationing can be applied in 4 levels: health care policy- makers, health care managers, health care providers, and patients. Health care rationing can be accomplished through fixed budget, benefit package, payment mechanisms, queuing, copayments, and deductibles. Conclusion: This paper enriched our understanding of health services rationing and its mechanisms at various levels and contributed to the literature by broadly conceptualizing health services rationing.

  12. Filozofická reflexe omezené racionality (Philosophical Reflection of Bounded Rationality

    Directory of Open Access Journals (Sweden)

    Michal Müller

    2017-03-01

    Full Text Available Research of rationality represents area of interaction between philosophy and economics. Development of neuroscience and advances in scientific research lead to another common characteristic – gradual loss of competence to comment on results of scientific research. This article describes development of the concept of economic rationality and makes an effort to deal with the following question: Can philosophy play useful role in contemporary discussions about the nature of decision-making and rationality? The authors conclude that philosophy itself does not have any extraordinary method which is able to ensure an exclusive position within the contemporary research. The role of philosophy consists in analyzing arguments, explanations of terms, in the search for ethical consequences, or in the preparation of social sciences to naturalization through critical evaluation of obsolete approaches that are inconsistent with the findings of natural science.

  13. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  14. Indian aspects of drug information resources and impact of drug information centre on community.

    Science.gov (United States)

    Chauhan, Nitesh; Moin, Sabeeya; Pandey, Anushree; Mittal, Ashu; Bajaj, Umakant

    2013-04-01

    Drug information centre refer to facility specially set aside for, and specializing in the provision of drug information and related issues. The purpose of drug information center is to provide authentic individualized, accurate, relevant and unbiased drug information to the consumers and healthcare professionals regarding medication related inquiries to the nation for health care and drug safety aspects by answering their call regarding the all critical problems on drug information, their uses and their side effects. Apart from that the center also provides in-depth, impartial source of crucial drug information to meet the needs of the practicing physicians, pharmacists and other health care professionals to safeguard the health, financial and legal interests of the patient and to broaden the pharmacist role visible in the society and community. The service should include collecting, reviewing, evaluating, indexing and distributing information on drugs to health workers. Drug and poisons information centers are best established within major teaching hospitals. This allows access to clinical experience, libraries, research facilities and educational activities. Information present in the current paper will not only enlighten the role of drug information center but also focused on the rational use of drug.

  15. Indian aspects of drug information resources and impact of drug information centre on community

    Directory of Open Access Journals (Sweden)

    Nitesh Chauhan

    2013-01-01

    Full Text Available Drug information centre refer to facility specially set aside for, and specializing in the provision of drug information and related issues. The purpose of drug information center is to provide authentic individualized, accurate, relevant and unbiased drug information to the consumers and healthcare professionals regarding medication related inquiries to the nation for health care and drug safety aspects by answering their call regarding the all critical problems on drug information, their uses and their side effects. Apart from that the center also provides in-depth, impartial source of crucial drug information to meet the needs of the practicing physicians, pharmacists and other health care professionals to safeguard the health, financial and legal interests of the patient and to broaden the pharmacist role visible in the society and community. The service should include collecting, reviewing, evaluating, indexing and distributing information on drugs to health workers. Drug and poisons information centers are best established within major teaching hospitals. This allows access to clinical experience, libraries, research facilities and educational activities. Information present in the current paper will not only enlighten the role of drug information center but also focused on the rational use of drug.

  16. Analysis of clinical drug-drug interaction data to predict uncharacterized interaction magnitudes between antiretroviral drugs and co-medications.

    Science.gov (United States)

    Stader, Felix; Kinvig, Hannah; Battegay, Manuel; Khoo, Saye; Owen, Andrew; Siccardi, Marco; Marzolini, Catia

    2018-04-23

    Despite their high potential for drug-drug-interactions (DDI), clinical DDI studies of antiretroviral drugs (ARVs) are often lacking, because the full range of potential interactions cannot feasibly or pragmatically be studied, with some high-risk DDI studies also ethically difficult to undertake. Thus, a robust method to screen and to predict the likelihood of DDIs is required.We developed a method to predict DDIs based on two parameters: the degree of metabolism by specific enzymes such as CYP3A and the strength of an inhibitor or inducer. These parameters were derived from existing studies utilizing paradigm substrates, inducers and inhibitors of CYP3A, to assess the predictive performance of this method by verifying predicted magnitudes of changes in drug exposure against clinical DDI studies involving ARVs.The derived parameters were consistent with the FDA classification of sensitive CYP3A substrates and the strength of CYP3A inhibitors and inducers. Characterized DDI magnitudes (n = 68) between ARVs and co-medications were successfully quantified meaning 53%, 85% and 98% of the predictions were within 1.25-fold (0.80 - 1.25), 1.5-fold (0.66 - 1.48) and 2-fold (0.66 - 1.94) of the observed clinical data. In addition, the method identifies CYP3A substrates likely to be highly or conversely minimally impacted by CYP3A inhibitors or inducers, thus categorizing the magnitude of DDIs.The developed effective and robust method has the potential to support a more rational identification of dose adjustment to overcome DDIs being particularly relevant in a HIV-setting giving the treatments complexity, high DDI risk and limited guidance on the management of DDIs. Copyright © 2018 American Society for Microbiology.

  17. Research on Bounded Rationality of Fuzzy Choice Functions

    Directory of Open Access Journals (Sweden)

    Xinlin Wu

    2014-01-01

    Full Text Available The rationality of a fuzzy choice function is a hot research topic in the study of fuzzy choice functions. In this paper, two common fuzzy sets are studied and analyzed in the framework of the Banerjee choice function. The complete rationality and bounded rationality of fuzzy choice functions are defined based on the two fuzzy sets. An assumption is presented to study the fuzzy choice function, and especially the fuzzy choice function with bounded rationality is studied combined with some rationality conditions. Results show that the fuzzy choice function with bounded rationality also satisfies some important rationality conditions, but not vice versa. The research gives supplements to the investigation in the framework of the Banerjee choice function.

  18. Impact of Drug Metabolism/Pharmacokinetics and Their Relevance upon Taxus-based Drug Development.

    Science.gov (United States)

    Hao, Da-Cheng; Ge, Guang-Bo; Wang, Ping; Yang, Ling

    2018-05-22

    Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. DDIs significantly impact the PK/pharmacodynamics performance of taxanes and co-administered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus -involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial tothe translation of bench findings to the clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Protein Complex Production from the Drug Discovery Standpoint.

    Science.gov (United States)

    Moarefi, Ismail

    2016-01-01

    Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.

  20. Focusing on changing clinical practice to enhance rational prescribing--collaboration and networking enable comprehensive approaches.

    Science.gov (United States)

    Helin-Salmivaara, Arja; Huupponen, Risto; Klaukka, Timo; Hoppu, Kalle

    2003-10-01

    Most western societies are enhancing rational pharmacotherapy to get best value for the constantly increasing expenditure on drugs. Government bodies and the medical profession took joint responsibility for the education programme for rational prescribing, launched in Finland at the end of the 1990s. The goals were to enhance critical thinking, and when appropriate, change prescribing behaviour. Various approaches that included evidence-based continuing medical education (CME), implementing clinical guidelines, delivering information, and providing prescribing feedback were used simultaneously. The commitment of the stakeholders and participants has been strong and the approaches have succeeded even though there is no clear outcome measure. The Government has recently decided to continue and widen the process, which started as a pilot programme, on a tight budget.

  1. Perestroika in pharma: evolution or revolution in drug development?

    Science.gov (United States)

    FitzGerald, Garret A

    2010-01-01

    New-drug approvals have remained roughly constant since 1950, while the cost of drug development has soared. It seems likely that a more modular approach to drug discovery and development will evolve, deriving some features from the not-for-profit sector. For this to occur, we must address the deficit in human capital with expertise in both translational medicine and therapeutics and also in regulatory science; utilize regulatory reform to incentivize innovation and the expansion of the precompetitive space; and develop an informatics infrastructure that permits the global, secure, and compliant sharing of heterogeneous data across academic and industry sectors. These developments, likely prompted by the perception of crisis rather than opportunity, will require linked initiatives among academia, the pharmaceutical industry, the US National Institutes of Health, and the US Food and Drug Administration, along with a more adventurous role for venture capital. A failure to respond threatens the United States' lead in biomedical science and in the development and regulation of novel therapeutics. 2010 Mount Sinai School of Medicine.

  2. New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.

    Science.gov (United States)

    Lienhardt, Christian; Raviglione, Mario; Spigelman, Mel; Hafner, Richard; Jaramillo, Ernesto; Hoelscher, Michael; Zumla, Alimuddin; Gheuens, Jan

    2012-05-15

    For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.

  3. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

  4. Drug delivery across length scales.

    Science.gov (United States)

    Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

    2018-02-20

    Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

  5. Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

    Science.gov (United States)

    Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

    2018-01-01

    Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

  6. Laser dynamics of asynchronous rational harmonic mode-locked fiber soliton lasers

    International Nuclear Information System (INIS)

    Jyu, Siao-Shan; Jiang, Guo-Hao; Lai, Yinchieh

    2013-01-01

    Laser dynamics of asynchronous rational harmonic mode-locked (ARHM) fiber soliton lasers are investigated in detail. In particular, based on the unique laser dynamics of asynchronous mode-locking, we have developed a new method for determining the effective active modulation strength in situ for ARHM lasers. By measuring the magnitudes of the slowly oscillating pulse timing position and central frequency, the effective phase modulation strength at the multiplication frequency of rational harmonic mode-locking can be accurately inferred. The method can be a very useful tool for developing ARHM fiber lasers. (paper)

  7. Rational and Mechanistic Perspectives on Reinforcement Learning

    Science.gov (United States)

    Chater, Nick

    2009-01-01

    This special issue describes important recent developments in applying reinforcement learning models to capture neural and cognitive function. But reinforcement learning, as a theoretical framework, can apply at two very different levels of description: "mechanistic" and "rational." Reinforcement learning is often viewed in mechanistic terms--as…

  8. Macroeconomics after Two Decades of Rational Expectations.

    Science.gov (United States)

    McCallum, Bennett T.

    1994-01-01

    Discusses real business cycle analysis, growth theory, and other economic concepts in the context of the rational expectations revolution in macroeconomics. Focuses on post-1982 research. Concludes that the rejuvenation of growth analysis is an encouraging development because it could lead to changes in welfare policy. (CFR)

  9. The basics of preclinical drug development for neurodegenerative disease indications.

    Science.gov (United States)

    Steinmetz, Karen L; Spack, Edward G

    2009-06-12

    Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and

  10. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    Science.gov (United States)

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  11. Using Rational-Emotive Therapy to Prevent Classroom Problems.

    Science.gov (United States)

    Webber, Jo; Coleman, Maggie

    1988-01-01

    Teachers are encouraged to utilize rational-emotive therapy to prevent and deal with classroom behavior problems. Rational-emotive therapy is defined, the ABC model of rational thinking briefly explained, types of irrational thinking identified, and suggestions for becoming a rational thinker are offered. Classroom examples are given. (DB)

  12. [Rationalization, rationing, prioritization: terminology and ethical approaches to the allocation of limited resources in hematology/oncology].

    Science.gov (United States)

    Winkler, Eva

    2011-01-01

    The field of oncology with its numerous high-priced innovations contributes considerably to the fact that medical progress is expensive. Additionally, due to the demographic changes and the increasing life expectancy, a growing number of cancer patients want to profit from this progress. Since resources are limited also in the health system, the fair distribution of the available resources urgently needs to be addressed. Dealing with scarcity is a typical problem in the domain of justice theory; therefore, this article first discusses different strategies to manage limited resources: rationalization, rationing, and prioritization. It then presents substantive as well as procedural criteria that assist in the just distribution of effective health benefits. There are various strategies to reduce the utilization of limited resources: Rationalization means that efficiency reserves are being exhausted; by means of rationing, effective health benefits are withheld due to cost considerations. Rationing can occur implicitly and thus covertly, e.g. through budgeting or the implementation of waiting periods, or explicitly, through transparent rules or policies about healthcare coverage. Ranking medical treatments according to their importance (prioritization) is often a prerequisite for rationing decisions. In terms of requirements of justice, both procedural and substantive criteria (e.g. equality, urgency, benefit) are relevant for the acceptance and quality of a decision to limit access to effective health benefits. Copyright © 2011 S. Karger AG, Basel.

  13. Navigating the poverty of heroin addiction treatment and recovery opportunity in Kenya: access work, self-care and rationed expectations.

    Science.gov (United States)

    Rhodes, Tim; Ndimbii, James; Guise, Andy; Cullen, Lucy; Ayon, Sylvia

    2015-01-01

    Drawing on the analyses of qualitative interview accounts of people who inject heroin in Kenya, we describe the narration of addiction treatment access and recovery desire in conditions characterised by a 'poverty of drug treatment opportunity'. We observe the performance of addiction recovery narrative in the face of heavy social constraints limiting access to care. Fee-based residential rehabilitation ('rehab') is the only treatment locally available and inaccessible to most. Its recovery potential is doubted, given normative expectations of relapse. Treating drug use is a product of tightly bounded agency. Individuals enact strategies to maximise their slim chances of treatment access ('access work'), develop self-care alternatives when these fail to materialise and ration their care expectations. The use of rehab as a primary means of respite and harm reduction rather than recovery and the individuation of care in the absence of an enabling recovery environment are key characteristics of drug treatment experience. The recent incorporation of 'harm reduction' into policy discourses may trouble the primacy of recovery narrative in addiction treatment and in how treatment desires are voiced. The diversification of drug treatments in combination with social interventions enabling their access are fundamental.

  14. Drugs' development in acute heart failure: what went wrong?

    Science.gov (United States)

    Teneggi, Vincenzo; Sivakumar, Nithy; Chen, Deborah; Matter, Alex

    2018-05-08

    Acute heart failure (AHF) is a major burden disease, with a complex physiopathology, unsatisfactory diagnosis, treatment and a very poor prognosis. In the last two decades, a number of drugs have progressed from preclinical to early and late clinical development, but only a few of them have been approved and added to a stagnant pharmacological armamentarium. We have reviewed the data published on drugs developed for AHF since early 2000s, trying to recognise factors that have worked for a successful approval or for the stoppage of the program, in an attempt to delineate future trajectories for AHF drug development. Our review has identified limitations at both preclinical and clinical levels. At the preclinical level, the major shortcoming is represented by animal models looking at short-term endpoints which do not recapitulate the complexity of the human disease. At the clinical level, the main weakness is given by the disconnect between short-term endpoints assessed in the early stage of drug development, and medium-long-term endpoints requested in Phase 3 for regulatory approval. This is further amplified by the lack of validation and standardisation of short- and long-term endpoints; absence of predictive biomarkers; conduct of studies on heterogeneous populations; and use of different eligibility criteria, time of assessments, drug schedules and background therapies. Key goals remain a better understanding of AHF and the construction of a successful drug development program. A reasonable way to move forward resides in a strong collaboration between main stakeholders of therapeutic innovation: scientific community, industry and regulatory agencies.

  15. Cyclodextrins in drug carrier systems.

    Science.gov (United States)

    Uekama, K; Otagiri, M

    1987-01-01

    One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.

  16. PHARMACOTHERAPY OF ACUTE STENOSING LARYNGOTRACHEITIS. WHAT DRUGS ARE DATA-BASED?

    Directory of Open Access Journals (Sweden)

    L. M. Ogorodova

    2012-01-01

    Full Text Available Acute stenosing laryngotracheitis is the most common cause of the upper respiratory tract obstruction in children at the age of 6 months to 6 years old. It is the rapidly occurring syndrome, consisting of barking cough, hoarseness, stridor. The disease can be associated with development of respiratory failure and asphyxia, so pediatricians and emergency care doctors must be well aware of rational pharmacotherapy of this condition. The review contains the descriptions of the drugs, which efficacy is confirmed by convincing evidence database. 

  17. An active role for machine learning in drug development

    Science.gov (United States)

    Murphy, Robert F.

    2014-01-01

    Due to the complexity of biological systems, cutting-edge machine-learning methods will be critical for future drug development. In particular, machine-vision methods to extract detailed information from imaging assays and active-learning methods to guide experimentation will be required to overcome the dimensionality problem in drug development. PMID:21587249

  18. A two-pronged approach in leishmaniasis drug development in ...

    African Journals Online (AJOL)

    Nancy Kamau

    Trouiller P; Olliaro P; Torreele E;. Orbinski J; Laing R and Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet. 2002; 359: 2188–94. 9. Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public-private partnerships.

  19. A New Drug Release Method in Early Development of Transdermal Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Bing Cai

    2012-01-01

    Full Text Available In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release. In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture levels (29, 57, 198 μL cm−2 were evaluated. The synthetic skin simulators were collected after 1, 2, 3, 4, 6, and 24 hours and extracted with pH 1.0 hydrochloric acid solution. The drug concentrations in the extractions were measured by isocratic reverse phase high-pressure liquid chromatography. The results showed that, with the increasing moisture level on the synthetic skin simulator, the drug release rate increased. In comparison with the conventional USP method, the drug release results performed by the new method were in more correlation to the release rate claimed in the product label. This new method could help to differentiate the drug release rates among assorted formulations of transdermal drug delivery systems in the early stage of development.

  20. Prodrug Strategy in Drug Development

    Directory of Open Access Journals (Sweden)

    Hajnal Kelemen

    2016-09-01

    Full Text Available Prodrugs are chemically modified derivatives introduced in therapy due to their advantageous physico-chemical properties (greater stability, improved solubility, increased permeability, used in inactive form. Biological effect is exerted by the active derivatives formed in organism through chemical transformation (biotransformation. Currently, 10% of pharmaceutical products are used as prodrugs, nearly half of them being converted to active form by hydrolysis, mainly by ester hydrolysis. The use of prodrugs aims to improve the bioavailability of compounds in order to resolve some unfavorable characteristics and to reduce first-pass metabolism. Other objectives are to increase drug absorption, to extend duration of action or to achieve a better tissue/organ selective transport in case of non-oral drug delivery forms. Prodrugs can be characterized by chemical structure, activation mechanism or through the presence of certain functional groups suitable for their preparation. Currently we distinguish in therapy traditional prodrugs prepared by chemical derivatisation, bioprecursors and targeted delivery systems. The present article is a review regarding the introduction and applications of prodrug design in various areas of drug development.

  1. Rational reconstructions of modern physics

    CERN Document Server

    Mittelstaedt, Peter

    2013-01-01

    Newton’s classical physics and its underlying ontology are loaded with several metaphysical hypotheses that cannot be justified by rational reasoning nor by experimental evidence. Furthermore, it is well known that some of these hypotheses are not contained in the great theories of Modern Physics, such as the theory of Special Relativity and Quantum Mechanics. This book shows that, on the basis of Newton’s classical physics and by rational reconstruction, the theory of Special Relativity as well as Quantum Mechanics can be obtained by partly eliminating or attenuating the metaphysical hypotheses. Moreover, it is shown that these reconstructions do not require additional hypotheses or new experimental results. In the second edition the rational reconstructions are completed with respect to General Relativity and Cosmology. In addition, the statistics of quantum objects is elaborated in more detail with respect to the rational reconstruction of quantum mechanics. The new material completes the approach of t...

  2. Rational Choice and the Framing of Decisions.

    Science.gov (United States)

    1986-05-29

    survival in a competitive environment , and a minority of rational individuals can sometimes impose rationality on the whole market. Third, the...intuitive appeal of the axioms of rational choice makes it plausible that the theory derived from these axioms should provide an acceptable account of choice...rn-use U? RATIONAL CHOICE AMD THE FINNING OF KCISIOUS(U mi/ STANFORD UNIV CR A TYERSEY ET AL. 29 NAYN4-S4-K-S61SWICLASS IF lED FO 5/10S IL EEEEEEEE

  3. Intergroup conflict and rational decision making.

    Science.gov (United States)

    Martínez-Tur, Vicente; Peñarroja, Vicente; Serrano, Miguel A; Hidalgo, Vanesa; Moliner, Carolina; Salvador, Alicia; Alacreu-Crespo, Adrián; Gracia, Esther; Molina, Agustín

    2014-01-01

    The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict -associated with indicators of the activation of negative feelings (negative affect state and heart rate)- has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making.

  4. Intergroup Conflict and Rational Decision Making

    Science.gov (United States)

    Martínez-Tur, Vicente; Peñarroja, Vicente; Serrano, Miguel A.; Hidalgo, Vanesa; Moliner, Carolina; Salvador, Alicia; Alacreu-Crespo, Adrián; Gracia, Esther; Molina, Agustín

    2014-01-01

    The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict –associated with indicators of the activation of negative feelings (negative affect state and heart rate)– has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making. PMID:25461384

  5. Intergroup conflict and rational decision making.

    Directory of Open Access Journals (Sweden)

    Vicente Martínez-Tur

    Full Text Available The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict -associated with indicators of the activation of negative feelings (negative affect state and heart rate- has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making.

  6. Rational Behavior Training: A Seven Lesson Sequence for Teaching Rational Behavior Skills to Students with Social and Emotional Disabilities.

    Science.gov (United States)

    Patton, Patricia Lucey

    This seven lesson curriculum sequence is designed to help teachers teach principles of Rational Behavior Training (RBT) which targets thinking behaviors, feeling behaviors, and behavioral responses to the environment. The program is appropriate for students with social and emotional disabilities and also develops reading, writing, spelling,…

  7. The varieties of religious development in adulthood: a longitudinal investigation of religion and rational choice.

    Science.gov (United States)

    McCullough, Michael E; Enders, Craig K; Brion, Sharon L; Jain, Andrea R

    2005-07-01

    The authors used growth mixture models to study religious development during adulthood (ages 27-80) in a sample of individuals who were identified during childhood as intellectually gifted. The authors identified 3 discrete trajectories of religious development: (a) 40% of participants belonged to a trajectory class characterized by increases in religiousness until midlife and declines in later adulthood; (b) 41% of participants belonged to a trajectory class characterized by very low religiousness in early adulthood and age-related decline; and (c) 19% of participants belonged to a trajectory class characterized by high religiousness in early adulthood and age-related increases. Gender, strength of religious upbringing, number of children, marrying, and agreeableness predicted membership in the trajectory classes. Results were largely consistent with the rational choice theory of religious involvement.

  8. Quasi-Birth-and-Death Processes with Rational Arrival Process Components

    DEFF Research Database (Denmark)

    Bean, Nigel G.; Nielsen, Bo Friis

    to develop an analytic method for such a process, that parallels the analysis of a traditional QBD. We demonstrate the analysis by considering a queue where the arrival process and the sequence of service times are derived from two different RAPs that are not just Markovian Arrival processes. We also...... introduce an element of correlation between the arrival process and the sequence of service times.......In this paper we introduce the concept of a Quasi-Birth-and-Death process (QBD) with Rational Arrival Process components. We use the physical interpretation of a Rational Arrival Process (RAP), developed by Asmussen and Bladt, to consider such a Markov process. We exploit this interpretation...

  9. LEGO-inspired drug design: Discovery of novel fungal Plasma membrane H+-ATPase (Pma1) inhibitors from small molecule libraries: An introduction of HFSA-SBS_DOS-RD strategy in drug discovery

    DEFF Research Database (Denmark)

    Tung, Truong Thanh; Dao, Trong Tuan; Palmgren, Michael B.

    to extracellular, this enzyme generates a transmembrane electrochem. gradient, as a consequence, fungi can uptake nutrients by secondary transport systems. Until now, only low resoln. of protein structure has been reported, and notably there a no report of co-crystal structure of Pma1 with inhibitors. Therefore......-oriented synthesis (SBS_DOS) and rational design (RD), so called HFSA-SBS_DOS-RD strategy in drug discovery and development process. Using HFSA-SBS_DOS-RD, our group successfully designed, synthesized, and performed SAR studies of novel compds. potent Pma1 inhibitors. An expeditious, high yield and scalable...... microwave-assisted synthesis was developed and applied for synthesis of library compds. To our delight, ours compd. libraries were able to inhibit Pma1 activity and growth inhibitory activity of C. albican and S. cerevisiae revealed the most promising example for future development of antifungal drugs...

  10. Rational customs clearance technology choice

    OpenAIRE

    Shramenko, N.; Andriets, V.

    2008-01-01

    Issues concerning cargo delivery efficiencyincrease by choice of rational customs clearance technology have been considered. Three possible variants of customs clearance andmethods which allow to define the most rational version of cargo delivery in international road communication based on main efficiency criteria for definite distance have been presented.

  11. Kant on empiricism and rationalism

    OpenAIRE

    Vanzo, Alberto

    2013-01-01

    This paper aims to correct some widely held misconceptions concerning Kant's role in the formation of a widespread narrative of early modern philosophy. According to this narrative, which dominated the English-speaking world throughout the twentieth century, the early modern period was characterized by the development of two rival schools: René Descartes's, Baruch Spinoza's, and G. W. Leibniz's rationalism; and John Locke's, George Berkeley's, and David Hume's empiricism. Empiricists and rati...

  12. Cognitive Rationality and Its Logic-Mathematical Language

    Science.gov (United States)

    Masalova, Svetlana

    2012-01-01

    The article deals with the cognitive (flexible) rationality, combining rational and irrational moments of the scientific search of the cognizing subject. Linguo-cognitive model of the concept as the flexible regulative rationality reveals the activity of the cognitive processes and the mentality of the epistemological-ontic subject, its leading…

  13. Developing drugs for the developing world: an economic, legal, moral, and political dilemma.

    Science.gov (United States)

    Resnik, D B

    2001-05-01

    This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on (1) the prospects for a reasonable profit and (2) the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry's efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and

  14. Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents.

    Science.gov (United States)

    Speck-Planche, Alejandro; Kleandrova, Valeria V; Luan, Feng; Cordeiro, M Natália D S

    2012-08-01

    The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoinformatics has played a decisive role, including Quantitative-Structure-Activity Relationship (QSAR) techniques. However, until now, there is no methodology able to predict anti-CRC activity of compounds against more than one CRC cell line, which should constitute the principal goal. In an attempt to overcome this problem we develop here the first multi-target (mt) approach for the virtual screening and rational in silico discovery of anti-CRC agents against ten cell lines. Here, two mt-QSAR classification models were constructed using a large and heterogeneous database of compounds. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. Some fragments were extracted from the molecules and their contributions to anti-CRC activity were calculated using mt-QSAR-LDA model. Several fragments were identified as potential substructural features responsible for the anti-CRC activity and new molecules designed from those fragments with positive contributions were suggested and correctly predicted by the two models as possible potent and versatile anti-CRC agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development.

    Science.gov (United States)

    Kunz, Meik; Liang, Chunguang; Nilla, Santosh; Cecil, Alexander; Dandekar, Thomas

    2016-01-01

    The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure-activity relationships.Database URL:http://drumpid.bioapps.biozentrum.uni-wuerzburg.de. © The Author(s) 2016. Published by Oxford University Press.

  16. Drug development for neurodevelopmental disorders

    DEFF Research Database (Denmark)

    Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E

    2018-01-01

    Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal ge......, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led...... to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has...... been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical...

  17. Rationalization of activity cliffs of a sulfonamide inhibitor of DNA methyltransferases with induced-fit docking.

    Science.gov (United States)

    Medina-Franco, José L; Méndez-Lucio, Oscar; Yoo, Jakyung

    2014-02-21

    Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure-activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of 'activity cliffs', e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

  18. Rationalization of Activity Cliffs of a Sulfonamide Inhibitor of DNA Methyltransferases with Induced-Fit Docking

    Directory of Open Access Journals (Sweden)

    José L. Medina-Franco

    2014-02-01

    Full Text Available Inhibitors of human DNA methyltransferases (DNMT are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure–activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of ‘activity cliffs’, e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

  19. Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane

    International Nuclear Information System (INIS)

    Sibeko, B; Pillay, V; Choonara, Y E; Khan, R A; Danckwerts, M P; Modi, G; Iyuke, S E; Naidoo, D

    2009-01-01

    The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 deg. C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

  20. Technique on rationalization of using electricity and cases

    International Nuclear Information System (INIS)

    1988-04-01

    This book deals with rationalization of using electric and cases. It is divided into four parts. The first part introduces necessity and of progression rationalization of using electric. The second part describes the technique on rationalization of using electric with management of electric energy. The third part depicts domestic cases of rationalization on using of electric such as substation and motor. The last part also introduces foreign cases of rationalization on using of electric with measure of generator circuit, design of motor, design of lighting and design of other equipment.

  1. Adolescent Brain Development and Drugs

    Science.gov (United States)

    Winters, Ken C.; Arria, Amelia

    2011-01-01

    Research now suggests that the human brain is still maturing during adolescence. The developing brain may help explain why adolescents sometimes make decisions that are risky and can lead to safety or health concerns, including unique vulnerabilities to drug abuse. This article explores how this new science may be put to use in our prevention and…

  2. A discussion of theoretical and practical rationality

    Energy Technology Data Exchange (ETDEWEB)

    Wahlstroem, B. [Technical Research Centre of Finland, Espoo (Finland). VTT Automation

    1999-12-01

    Theoretical rationality as defined in Expected Utility Theory and amended with other considerations gives a good basis for decision making. One should however always keep in mind that practical rationality often is far more complicated. People use their everyday experience when placed before new problems and this may lead to apparently irrational choices which on a closer scrutiny may be completely rational. Theories in human decision making unfortunately becomes untestable, firstly because a theory taking all considerations into account would be to complex to be practical and secondly because the data needed to test the theory cannot be collected. The benefit of EUT is that it is simple and straightforward as compared with competing theories. In the natural sciences rationality is often seen simply as a problem of optimisation. This view is practical, but it has to include also psychological and sociological considerations. The apparent controversy between natural and behavioural sciences could at least in principle be resolved by a better understanding of the complexity of human rationality. The human mind does not work in isolation, but it is adapted to a social community and a continuously changing environment. Understanding all components of human rationality is a challenge which cannot be solved on a short term basis. An important part of human rationality is connected to the intricate balance between individual and societal utility. The human mind has over thousands of years learnt to resolve that balance, but in the modern society there are decisions which may not be solvable with an intuitive approach and a strategy of trial and error. For these decisions more solid theories of rationality will be needed. EUT can in spite of its dismerits be used as the backbone for such a theory, but it has to be extended with better explanations of both individual and social rationality. If this understanding of the practical aspects of human rationality can be reached

  3. A discussion of theoretical and practical rationality

    International Nuclear Information System (INIS)

    Wahlstroem, B.

    1999-01-01

    Theoretical rationality as defined in Expected Utility Theory and amended with other considerations gives a good basis for decision making. One should however always keep in mind that practical rationality often is far more complicated. People use their everyday experience when placed before new problems and this may lead to apparently irrational choices which on a closer scrutiny may be completely rational. Theories in human decision making unfortunately becomes untestable, firstly because a theory taking all considerations into account would be to complex to be practical and secondly because the data needed to test the theory cannot be collected. The benefit of EUT is that it is simple and straightforward as compared with competing theories. In the natural sciences rationality is often seen simply as a problem of optimisation. This view is practical, but it has to include also psychological and sociological considerations. The apparent controversy between natural and behavioural sciences could at least in principle be resolved by a better understanding of the complexity of human rationality. The human mind does not work in isolation, but it is adapted to a social community and a continuously changing environment. Understanding all components of human rationality is a challenge which cannot be solved on a short term basis. An important part of human rationality is connected to the intricate balance between individual and societal utility. The human mind has over thousands of years learnt to resolve that balance, but in the modern society there are decisions which may not be solvable with an intuitive approach and a strategy of trial and error. For these decisions more solid theories of rationality will be needed. EUT can in spite of its dismerits be used as the backbone for such a theory, but it has to be extended with better explanations of both individual and social rationality. If this understanding of the practical aspects of human rationality can be reached

  4. A Development of Hybrid Drug Information System Using Image Recognition

    Directory of Open Access Journals (Sweden)

    HwaMin Lee

    2015-04-01

    Full Text Available In order to prevent drug abuse or misuse cases and avoid over-prescriptions, it is necessary for medicine taker to be provided with detailed information about the medicine. In this paper, we propose a drug information system and develop an application to provide information through drug image recognition using a smartphone. We designed a contents-based drug image search algorithm using the color, shape and imprint of drug. Our convenient application can provide users with detailed information about drugs and prevent drug misuse.

  5. The basics of preclinical drug development for neurodegenerative disease indications

    Directory of Open Access Journals (Sweden)

    Spack Edward G

    2009-06-01

    Full Text Available Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s. Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot

  6. Application of PBPK modelling in drug discovery and development at Pfizer.

    Science.gov (United States)

    Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

    2012-01-01

    Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

  7. Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth

    Science.gov (United States)

    Al-Ali, Hassan; Lee, Do-Hun; Danzi, Matt C.; Nassif, Houssam; Gautam, Prson; Wennerberg, Krister; Zuercher, Bill; Drewry, David H.; Lee, Jae K.; Lemmon, Vance P.; Bixby, John L.

    2016-01-01

    Mammalian Central Nervous System (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multi-target drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds’ kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth, as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology, was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line, as well as targets recently shown to mediate drug resistance. PMID:26056718

  8. Drug design: Insights from atomistic simulations

    International Nuclear Information System (INIS)

    Collu, F.; Spiga, E.; Kumar, A.; Hajjar, E.; Vargiu, A.V.; Ceccarelli, M.; Ruggerone, P.

    2009-01-01

    Computer simulations have become a widely used and powerful tool to study the behaviour of many-particle and many-interaction systems and processes such as nucleic acid dynamics, drug-DNA interactions, enzymatic processes, membrane, antibiotics. The increased reliability of computational techniques has made possible to plane a bottom-up approach in drug design, i.e. designing molecules with improved properties starting from the knowledge of the molecular mechanisms. However, the in silico techniques have to face the fact that the number of degrees of freedom involved in biological systems is very large while the time scale of several biological processes is not accessible to standard simulations. Algorithms and methods have been developed and are still under construction to bridge these gaps. Here we review the activities of our group focussed on the time-scale bottleneck and, in particular, on the use of the meta dynamics scheme that allows the investigation of rare events in reasonable computer time without reducing the accuracy of the calculation. In particular, we have devoted particular attention to the characterization at microscopic level of translocation of antibiotics through membrane pores, aiming at the identification of structural and dynamical features helpful for a rational drug design.

  9. Deep Play. Rationality in the Life World with Special Reference to Sailing

    Science.gov (United States)

    Goold, Patrick

    2014-01-01

    In an essay on the rationality of play, the author characterizes rationality by the three distinct demands it makes on the individual--demands for autonomy, solidarity, and integrity. He develops each of these as they apply to the sport of sailing, using the example of two deep-ocean expeditions to arrive at a concept of deep play he sees as one…

  10. Coping More Effectively Through Rational Self-Counseling.

    Science.gov (United States)

    Rogers, George W., Jr.

    1981-01-01

    Rational Self-Counseling, a variation of rational-emotive therapy, is a self-help therapeutic technique in which students are encouraged to be responsible for their own behavior and emotions. The primary function of self-counseling is to evaluate whether thoughts are rational. A list of questions which students might ask themselves is presented.…

  11. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  12. Freedom and Rationality : Rousseau on Citizenship

    OpenAIRE

    Salvat, Christophe

    2008-01-01

    This paper deals with Rousseau's idea of freedom in terms of rationality and deliberation. It gives support to Berlin's interpretation of the general will as a rational and objective will but dismisses the idea that Rousseau's theory necessarily leads to authoritarianism. The general will, publicly expressed by the law, may be defined as the rational and self-regarding will agents would have if put in an independent and objective state, i.e. the state of nature. The general and the particular...

  13. Reappraisal of Rational Choice Theory

    Directory of Open Access Journals (Sweden)

    Katalin Martinas

    2013-01-01

    Full Text Available The value of rational choice theory (RCT for the social sciences has long been contested. Much time has been spent by economists and critics on the pervasive but elusive concept of rationality. The critiques mainly challenge the basis of the utility theorem. Several articles on the misuse of mathematics in economics have already appeared in the literature. As N. Bouleau stated, “On several occasions, however, one feels that the criticism is that the math is being misused and should be developed in some other direction (e.g. a statistical analysis of the financial tendencies that polarize wealth and income, or a study of the positive feedback mechanisms, etc.. This leaves certain dissatisfaction – on a philosophical level.” The aim of this paper is to present a decision theory, yields intention (logos and valuation (existence. Here we present a new mathematical representation of RCT, which leads to a dynamic economic theory. We discuss the philosophical or meta-economical problems, which are needed for the successful applications of mathematics.

  14. Quasi-Birth-and-Death Processes with Rational Arrival Process Components

    DEFF Research Database (Denmark)

    Bean, Nigel G.; Nielsen, Bo Friis

    2010-01-01

    This paper introduces the concept of a Quasi-Birth-and-Death process (QBD) with Rational Arrival Process (RAP) components. We use the physical interpretation of the prediction process of the RAP, developed by Asmussen and Bladt, and develop an analysis that parallels the analysis of a traditional...... QBD. Further, we present an algorithm for the numerical evaluation of the matrix G. As an example, we consider two queues where the arrival process and the sequence of service times are taken from two dependent RAPs, that are not Markovian Arrival Processes......This paper introduces the concept of a Quasi-Birth-and-Death process (QBD) with Rational Arrival Process (RAP) components. We use the physical interpretation of the prediction process of the RAP, developed by Asmussen and Bladt, and develop an analysis that parallels the analysis of a traditional...

  15. Neuroimaging in nuclear medicine: drug addicted brain

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yong-An; Kim, Dae-Jin [The Catholic University of Korea, Seoul (Korea, Republic of)

    2006-02-15

    Addiction to illicit drugs in one of today's most important social issues. Most addictive drugs lead to irreversible parenchymal changes in the human brain. Neuroimaging data bring to light the pharmacodynamics and pharmacokinetics of the abused drugs, and demonstrate that addiction is a disease of the brain. Continuous researches better illustrate the neurochemical alterations in brain function, and attempt to discover the links to consequent behavioral changes. Newer hypotheses and theories follow the numerous results, and more rational methods of approaching therapy are being developed. Substance abuse is on the rise in Korea, and social interest in the matter as well. On the other hand, diagnosis and treatment of drug addiction is still very difficult, because how the abused substance acts in the brain, or how it leads to behavioral problems in not widely known. Therefore, understanding the mechanism of drug addiction can improve the process of diagnosing addict patients, planning therapy, and predicting the prognosis . Neuroimaging approaches by nuclear medicine methods are expected to objectively judge behavioral and neurochemical changes, and response to treatment. In addition, as genes associated with addictive behavior are discovered, functional nuclear medicine images will aid in the assessment of individuals. Reviewing published literature on neuroimaging regarding nuclear medicine is expected to be of assistance to the management of drug addict patients. What's more, means of applying nuclear medicine to the care of drug addict patients should be investigated further.

  16. Neuroimaging in nuclear medicine: drug addicted brain

    International Nuclear Information System (INIS)

    Chung, Yong-An; Kim, Dae-Jin

    2006-01-01

    Addiction to illicit drugs in one of today's most important social issues. Most addictive drugs lead to irreversible parenchymal changes in the human brain. Neuroimaging data bring to light the pharmacodynamics and pharmacokinetics of the abused drugs, and demonstrate that addiction is a disease of the brain. Continuous researches better illustrate the neurochemical alterations in brain function, and attempt to discover the links to consequent behavioral changes. Newer hypotheses and theories follow the numerous results, and more rational methods of approaching therapy are being developed. Substance abuse is on the rise in Korea, and social interest in the matter as well. On the other hand, diagnosis and treatment of drug addiction is still very difficult, because how the abused substance acts in the brain, or how it leads to behavioral problems in not widely known. Therefore, understanding the mechanism of drug addiction can improve the process of diagnosing addict patients, planning therapy, and predicting the prognosis . Neuroimaging approaches by nuclear medicine methods are expected to objectively judge behavioral and neurochemical changes, and response to treatment. In addition, as genes associated with addictive behavior are discovered, functional nuclear medicine images will aid in the assessment of individuals. Reviewing published literature on neuroimaging regarding nuclear medicine is expected to be of assistance to the management of drug addict patients. What's more, means of applying nuclear medicine to the care of drug addict patients should be investigated further

  17. Interest Groups' Influence over Drug Pricing Policy Reform in South Korea

    Science.gov (United States)

    Chung, Woojin

    2005-01-01

    In 1999, the Korean government made a drug pricing policy reform to improve the efficiency and transparency of the drug distribution system. Yet, its policy formation process was far from being rational. Facing harsh resistance from various interest groups, the government changed its details into something different from what was initially investigated and planned. So far, little evidence supports any improvement in Korea's drug distribution system. Instead, the new drug pricing policy has deteriorated Korea's national health insurance budget, indicating a heavier economic burden for the general public. From Korea's experience, we may draw some lessons for the future development of a better health care system. As a society becomes more pluralistic, the government should come out of authoritarianism and thoroughly prepare in advance for resistance to reform, by making greater efforts to persuade strong interest groups while informing the general public of potential benefits of the reform. Additionally, facing developing civic groups, the government should listen but not rely too much on them at the final stage of the policy formation. Many of the civic groups lack expertise to evaluate the details of policy and tend to act in a somewhat emotional way. PMID:15988802

  18. Interest groups' influence over drug pricing policy reform in South Korea.

    Science.gov (United States)

    Chung, Woo Jin; Kim, Han Joong

    2005-06-30

    In 1999, the Korean government made a drug pricing policy reform to improve the efficiency and transparency of the drug distribution system. Yet, its policy formation process was far from being rational. Facing harsh resistance from various interest groups, the government changed its details into something different from what was initially investigated and planned. So far, little evidence supports any improvement in Korea's drug distribution system. Instead, the new drug pricing policy has deteriorated Korea's national health insurance budget, indicating a heavier economic burden for the general public. From Korea's experience, we may draw some lessons for the future development of a better health care system. As a society becomes more pluralistic, the government should come out of authoritarianism and thoroughly prepare in advance for resistance to reform, by making greater efforts to persuade strong interest groups while informing the general public of potential benefits of the reform. Additionally, facing developing civic groups, the government should listen but not rely too much on them at the final stage of the policy formation. Many of the civic groups lack expertise to evaluate the details of policy and tend to act in a somewhat emotional way.

  19. The influence of peer affiliation and student activities on adolescent drug involvement.

    Science.gov (United States)

    Jenkins, J E

    1996-01-01

    This study examined the importance of students' academic performance level and extracurricular activities as predictors of drug involvement relative to peer influence. Social development theory provided the theoretical rational for the study. Data were obtained from 2,229 randomly selected students in the eighth, tenth, and twelfth grades from seventeen school districts in northeastern Ohio. At all three grade levels, involvement in extracurricular activities and academic level were significantly correlated with students' gateway and hard drug use. Consistent with prior research, the strongest correlate of gateway and hard drug use across all grade levels was affiliation with drug-using friends. Having a job after school was marginally related to self-reported gateway drug use at grade level ten. Multiple regression analysis revealed that extracurricular involvement and academic performance level make small, but unique contributions to the prediction of adolescents' gateway drug use beyond affiliation with drug-using peers at all three grade levels. The findings of this study suggest that students' academic performance and extracurricular involvements are significantly related to adolescent gateway and hard drug use, but have less predictive significance relative to peer relationships.

  20. Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

    Science.gov (United States)

    Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

    2013-01-01

    The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

  1. The rational maps Fλ(z)

    Indian Academy of Sciences (India)

    It is proved that the rational maps in the family {z → zm +λ/zd : λ ∈ C\\{0}} for integers m, d ≥ 2 ... The problem of the existence of Herman rings of a rational map has been studied by. Lyubich in [9] ..... Surveys 41(4) (1986) 35–95. [10] Milnor J ...

  2. Heterogeneity and the (de)stabilizing role of rationality

    International Nuclear Information System (INIS)

    Cavalli, Fausto; Naimzada, Ahmad; Pireddu, Marina

    2015-01-01

    Highlights: • We analyze Cournot oligopolies with heterogeneous firms of generic size. • Rational and naive players are considered. • Stability with respect to oligopoly composition is studied. • In some settings, increasing the rational firms fraction introduces instability. - Abstract: In this paper we study oligopolies of generic size consisting of heterogeneous firms, which adopt best response adjustment mechanisms with either perfect foresight (rational firms) or static expectations (naive firms). Assuming an isoelastic demand function and possibly different marginal costs for the two groups of firms, we focus on the local stability of the Nash equilibrium. We show that, with respect to the oligopoly composition, described in terms of the fraction of rational firms, different scenarios are possible. We find that a high rationality degree may not always guarantee stability, in particular when rational firms have sufficiently larger marginal costs. In fact, in this situation, increasing the fraction of rational firms can even introduce instability. Besides the usual scenarios in which replacing some naive firms with rational ones leads to a stabilization of (or at least keeps unchanged) the dynamics, we provide a family of situations, characterized by costs ratio favorable to naive firms, in which equilibrium loses its stability when naive firms are replaced by rational ones. The results we present are both analytical and simulative.

  3. Use of biomarkers in ALS drug development and clinical trials.

    Science.gov (United States)

    Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

    2015-05-14

    The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. [Significance of re-evaluation and development of Chinese herbal drugs].

    Science.gov (United States)

    Gao, Yue; Ma, Zengchun; Zhang, Boli

    2012-01-01

    The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

  5. Précis of bayesian rationality: The probabilistic approach to human reasoning.

    Science.gov (United States)

    Oaksford, Mike; Chater, Nick

    2009-02-01

    According to Aristotle, humans are the rational animal. The borderline between rationality and irrationality is fundamental to many aspects of human life including the law, mental health, and language interpretation. But what is it to be rational? One answer, deeply embedded in the Western intellectual tradition since ancient Greece, is that rationality concerns reasoning according to the rules of logic--the formal theory that specifies the inferential connections that hold with certainty between propositions. Piaget viewed logical reasoning as defining the end-point of cognitive development; and contemporary psychology of reasoning has focussed on comparing human reasoning against logical standards. Bayesian Rationality argues that rationality is defined instead by the ability to reason about uncertainty. Although people are typically poor at numerical reasoning about probability, human thought is sensitive to subtle patterns of qualitative Bayesian, probabilistic reasoning. In Chapters 1-4 of Bayesian Rationality (Oaksford & Chater 2007), the case is made that cognition in general, and human everyday reasoning in particular, is best viewed as solving probabilistic, rather than logical, inference problems. In Chapters 5-7 the psychology of "deductive" reasoning is tackled head-on: It is argued that purportedly "logical" reasoning problems, revealing apparently irrational behaviour, are better understood from a probabilistic point of view. Data from conditional reasoning, Wason's selection task, and syllogistic inference are captured by recasting these problems probabilistically. The probabilistic approach makes a variety of novel predictions which have been experimentally confirmed. The book considers the implications of this work, and the wider "probabilistic turn" in cognitive science and artificial intelligence, for understanding human rationality.

  6. Rationality and the Logic of Good Reasons.

    Science.gov (United States)

    Fisher, Walter R.

    This paper contends that the rationality of the logic of good reasons is constituted in its use. To support this claim, the paper presents an analysis of the relationship between being reasonable and being rational. It then considers how following the logic of good reasons leads to rationality in the behavior of individuals and groups; the latter…

  7. Reflection of successful anticancer drug development processes in the literature.

    Science.gov (United States)

    Heinemann, Fabian; Huber, Torsten; Meisel, Christian; Bundschus, Markus; Leser, Ulf

    2016-11-01

    The development of cancer drugs is time-consuming and expensive. In particular, failures in late-stage clinical trials are a major cost driver for pharmaceutical companies. This puts a high demand on methods that provide insights into the success chances of new potential medicines. In this study, we systematically analyze publication patterns emerging along the drug discovery process of targeted cancer therapies, starting from basic research to drug approval - or failure. We find clear differences in the patterns of approved drugs compared with those that failed in Phase II/III. Feeding these features into a machine learning classifier allows us to predict the approval or failure of a targeted cancer drug significantly better than educated guessing. We believe that these findings could lead to novel measures for supporting decision making in drug development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Rational Unified Process jako metodika vývoje softwaru

    OpenAIRE

    Rytíř, Vladimír

    2008-01-01

    Cílem této práce je seznámit se s procesem vývoje softwaru dle vybraných metodik s hlavním zaměřením na metodiku Rational Unified Process od firmy IBM. Incepční a elaborační fáze této metody také aplikuji na praktickém  příkladě. Goal of my work is to introduce software development process metods specialized to Rational Unified Process metod from IBM. I aplicate inception and elaboration phases of RUP on practical example. B

  9. Rationality, mental causation and social sciences

    OpenAIRE

    Mladenović Ivan

    2009-01-01

    The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.

  10. Physiological responses to rational-emotive self-verbalizations.

    Science.gov (United States)

    Master, S; Gershman, L

    1983-12-01

    This study tested Albert Ellis' Rational Emotive Therapy (RET) theory which predicts that cognitive beliefs, not the stimulus situation, generate human emotions. According to RET, emotions created by rational beliefs are adaptive, while irrational beliefs result in an unadaptive anxiety level. Results demonstrated that at high levels of problem relevance there was (1) a significantly greater GSR in direct response to the stimulus situation, and also to irrational statements, than to rational and control statements, and (2) no significant difference between rational and neutral control statements. The authors argue that these results are more parsimoniously explained by conditioning theory than by RET theory.

  11. [Does the public sector have an independent research role in the development of drugs?].

    Science.gov (United States)

    Poulsen, Henrik Enghusen; Grønlykke, Thor Buch

    2003-04-14

    Exclusively private companies do drug development. The State contributes with education of academics and basic research constituting the basis of half of the drugs developed by the private companies. The Danish private drug research amounts to six billion DKK per year, corresponding to the estimated price of the development of one new drug. The development shows a negative tendency. There are doubts about the scientific credibility, the number of new drugs is declining, drug development costs are rising, and the competitiveness in Europe is declining compared with the one of The United States. Continued improvement of Danish drug development can be achieved by stimulation of the public research related to drug development.

  12. Pharmacogenomics and its potential impact on drug and formulation development.

    Science.gov (United States)

    Regnstrom, Karin; Burgess, Diane J

    2005-01-01

    Recent advances in genomic research have provided the basis for new insights into the importance of genetic and genomic markers during the different stages of drug development. A new field of research, pharmacogenomics, which studies the relationship between drug effects and the genome, has emerged. Structural pharmacogenomics maps the complete DNA sequences of whole genomes (genotypes) including individual variations, and functional pharmacogenomics assesses the expression levels of thousands of genes in one single experiment. Together, these two areas of pharmacogenomics have generated massive databases, which have become a challenge for the research field of informatics and have fostered a new branch of research, bioinformatics. If skillfully used, the databases generated by pharmacogenomics together with data mining on the Web promise to improve the drug development process in a variety of areas: identification of drug targets, evaluation of toxicity, classification of diseases, evaluation of formulations, assessment of drug response and treatment, post-marketing applications, and development of personalized medicines.

  13. Towards a Characterization of Rational Expectations

    OpenAIRE

    Itai Arieli

    2008-01-01

    R. J. Aumann and J. H. Drèze (2008) define a rational expectation of a player i in a game G as the expected payo of some type of i in some belief system for G in which common knowledge of rationality and common priors obtain. Our goal is to characterize the set of rational expectations in terms of the game's payoff matrix. We provide such a characterization for a specific class of strategic games, called semi-elementary, which includes Myerson's "elementary" games.

  14. The Development Impact of the Illegality of Drug Trade

    OpenAIRE

    Keefer, Philip; Loayza, Norman V.; Soares, Rodrigo R.

    2008-01-01

    This paper reviews the unintended consequences of the war on drugs, particularly for developing countries, and weighs them against the evidence regarding the efficacy of prohibition to curb drug use and trade. It reviews the available evidence and presents new results that indicate that prohibition has limited effects on drug prevalence and prices, most likely indicating a combination of i...

  15. Influences on the prescribing of new drugs.

    Science.gov (United States)

    Tobin, Luke; de Almedia Neto, Abelio C; Wutzke, Sonia; Patterson, Craig; Mackson, Judith; Weekes, Lynn; Williamson, Margaret

    2008-01-01

    The aim of this study was to identify the factors that influence prescribing of new drugs among general practitioners, endocrinologists and psychiatrists. Four focus groups were conducted with GPs, endocrinologists and psychiatrists on sources of awareness and influences on prescribing of new drugs. Pharmaceutical companies were the most important source for becoming aware of new drugs. There were many influences on the decision to prescribe a new drug, the most important being efficacy, safety, cost and advantage over existing therapies. Endocrinologists placed greater emphasis on evidence from clinical trials and scientific conferences, and psychiatrists and GPs placed more weight on pharmaceutical representatives, colleagues and specialists. New drug prescribing occurs in a complex environment with many influences. Effective interventions to promote rational, safe and effective prescribing of new drugs will need to be cognisant of these factors.

  16. Do national drug policies influence antiretroviral drug prices? Evidence from the Southern African Development community.

    Science.gov (United States)

    Liu, Yao; Galárraga, Omar

    2017-03-01

    The efficacy of low- and middle-income countries’ (LMIC) national drug policies in managing antiretroviral (ARV) pharmaceutical prices is not well understood. Though ARV drug prices have been declining in LMIC over the past decade, little research has been done on the role of their national drug policies. This study aims to (i) analyse global ARV prices from 2004 to 2013 and (ii) examine the relationship of national drug policies to ARV prices. Analysis of ARV drug prices utilized data from the Global Price Reporting Mechanism from the World Health Organization (WHO). Ten of the most common ARV drugs (first-line and second-line) were selected. National drug policies were also assessed for 12 countries in the South African Development Community (SADC), which self-reported their policies through WHO surveys. The best predictor of ARV drug price was generic status—the generic versions of 8 out of 10 ARV drugs were priced lower than branded versions. However, other factors such as transaction volume, HIV prevalence, national drug policies and PEPFAR/CHAI involvement were either not associated with ARV drug price or were not consistent predictors of price across different ARV drugs. In the context of emerging international trade agreements, which aim to strengthen patent protections internationally and potentially delay the sale of generic drugs in LMIC, this study shines a spotlight on the importance of generic drugs in controlling ARV prices. Further research is needed to understand the impact of national drug policies on ARV prices.

  17. Rational inattention or rational overreaction?

    DEFF Research Database (Denmark)

    Browning, Martin; Hansen, Lars Gårn; Smed, Sinne

    We investigate differences in how consumers of fish react to health information in the mass media. We specify a dynamic empirical model that allows for heterogeneity in all basic parameters of consumer behavior as well as in how consumers react to information. We estimate the model using a unique...... houshold panel tracking consumption, prices, news stories and media habits over 24 quarters. We fi nd that the consumers most likely to be ’rationally ignorant’ of health effects react more dramatically to health news than the consumers who most likely are well informed....

  18. Bounded rationality alters the dynamics of paediatric immunization acceptance

    Science.gov (United States)

    Oraby, Tamer; Bauch, Chris T.

    2015-01-01

    Interactions between disease dynamics and vaccinating behavior have been explored in many coupled behavior-disease models. Cognitive effects such as risk perception, framing, and subjective probabilities of adverse events can be important determinants of the vaccinating behaviour, and represent departures from the pure “rational” decision model that are often described as “bounded rationality”. However, the impact of such cognitive effects in the context of paediatric infectious disease vaccines has received relatively little attention. Here, we develop a disease-behavior model that accounts for bounded rationality through prospect theory. We analyze the model and compare its predictions to a reduced model that lacks bounded rationality. We find that, in general, introducing bounded rationality increases the dynamical richness of the model and makes it harder to eliminate a paediatric infectious disease. In contrast, in other cases, a low cost, highly efficacious vaccine can be refused, even when the rational decision model predicts acceptance. Injunctive social norms can prevent vaccine refusal, if vaccine acceptance is sufficiently high in the beginning of the vaccination campaign. Cognitive processes can have major impacts on the predictions of behaviour-disease models, and further study of such processes in the context of vaccination is thus warranted. PMID:26035413

  19. The role of radiolabelled compounds in preclinical drug development

    International Nuclear Information System (INIS)

    Hawkins, D.R.

    1988-01-01

    The role of radiolabelled compounds in the development of new drugs is discussed, with particular reference to their use in toxicological, metabolic and pharmacokinetic studies for the pre-clinical safety evaluation of new drugs. (U.K.)

  20. A Trojan horse in drug development

    DEFF Research Database (Denmark)

    Christensen, Søren Brøgger; Skytte, Dorthe Mondrup; Denmeade, Samuel R

    2009-01-01

    Available chemotherapeutics take advantage of the fast proliferation of cancer cells. Consequently slow growth makes androgen refractory prostate cancer resistant towards available drugs. No treatment is available at the present, when the cancer has developed metastases outside the prostate (T4 s...

  1. Antimicrobial drug use and related management practices among Ontario swine producers.

    OpenAIRE

    Dunlop, R H; McEwen, S A; Meek, A H; Friendship, R A; Clarke, R C; Black, W D

    1998-01-01

    A mail survey of swine producers in Ontario was undertaken during 1991 to describe the types, frequency, and motives for antimicrobial use. Two hundred operations that marketed fewer than 350 hogs per year, and 800 that marketed more than 350 per year were sent questionnaires, 63% of which were completed and returned. Most operations (86%) added antimicrobials to starter (weanling pig) rations, while fewer (29%) added these drugs to finisher pig rations. The most commonly used antimicrobials ...

  2. Rationality, mental causation and social sciences

    Directory of Open Access Journals (Sweden)

    Mladenović Ivan

    2009-01-01

    Full Text Available The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.

  3. Pandemic ventilator rationing and appeals processes.

    Science.gov (United States)

    Patrone, Daniel; Resnik, David

    2011-06-01

    In a severe influenza pandemic, hospitals will likely experience serious and widespread shortages of patient pulmonary ventilators and of staff qualified to operate them. Deciding who will receive access to mechanical ventilation will often determine who lives and who dies. This prospect raises an important question whether pandemic preparedness plans should include some process by which individuals affected by ventilator rationing would have the opportunity to appeal adverse decisions. However, the issue of appeals processes to ventilator rationing decisions has been largely neglected in state pandemic planning efforts. If we are to devise just and effective plans for coping with a severe influenza pandemic, more attention to the issue of appeals processes for pandemic ventilator rationing decisions is needed. Arguments for and against appeals processes are considered, and some suggestions are offered to help efforts at devising more rational pandemic preparedness plans.

  4. Many faces of rationality: Implications of the great rationality debate for clinical decision-making

    OpenAIRE

    Djulbegovic, B.; Elqayam, Shira

    2017-01-01

    open access article Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings fromThe Great Rationality Debate from t...

  5. Commitment-based action: Rational choice theory and contrapreferential choice

    Directory of Open Access Journals (Sweden)

    Radovanović Bojana

    2014-01-01

    Full Text Available This paper focuses on Sen’s concept of contrapreferential choice. Sen has developed this concept in order to overcome weaknesses of the rational choice theory. According to rational choice theory a decision-maker can be always seen as someone who maximises utility, and each choice he makes as the one that brings to him the highest level of personal wellbeing. Sen argues that in some situations we chose alternatives that bring us lower level of wellbeing than we could achieve if we had chosen some other alternative available to us. This happens when we base our decisions on moral principles, when we act out of duty. Sen calls such action a commitment-based action. When we act out of commitment we actually neglect our preferences and thus we make a contrapreferential choice, as Sen argues. This paper shows that, contrary to Sen, a commitment-based action can be explained within the framework of rational choice theory. However, when each choice we make can be explained within the framework of rational choice theory, when in everything we do maximisation principle can be loaded, then the variety of our motives and traits is lost, and the explanatory power of the rational choice theory is questionable. [Projekat Ministarstva nauke Republike Srbije, br. 47009: Evropske integracije i društveno-ekonomske promene privrede Srbije na putu ka EU i br. 179015: Izazovi i perspektive strukturnih promena u Srbiji: Strateški pravci ekonomskog razvoja i usklađivanje sa zahtevima EU

  6. Managing antiepileptic drugs during pregnancy and lactation

    DEFF Research Database (Denmark)

    Sabers, Anne; Tomson, Torbjörn

    2009-01-01

    PURPOSE OF REVIEW: This review discusses data on the pharmacokinetics of antiepileptic drugs (AEDs) in pregnancy and lactation, and the clinical consequences thereof, thus providing a basis for a rational management of AEDs during pregnancy and lactation. RECENT FINDINGS: Studies have confirmed...... of AEDs in pregnancy and during lactation is important to enable optimal treatment. Gestation induced alterations in pharmacokinetics vary with the AED but also between patients and are difficult to predict. Therapeutic drug monitoring is, therefore, advisable during pregnancy and the use...... of the individual patient's optimal prepregnancy drug level is recommended as reference. Breastfeeding is in general safe but needs appropriate observation of the nursing infant....

  7. . MODERN EDUCATION: FROM RATIONALITY TO REASONABLENESS

    Directory of Open Access Journals (Sweden)

    O. S. Anisimov

    2014-01-01

    Full Text Available The paper deals with the problem of modern education development and criticizes a pragmatic attitude to education. Based on the retrospective historical analysis, the author maintains that educational systems are generally focused on fostering the pragmatic intellect rather than reasoning, which leads to a superficial world perception, and undermines personal analytical potential and capability of strategic problem solving. Concentration on rationality is unlikely to provide a way out of the world crisis. In the author’s view, education demands both the deep and solid comprehension of existential concepts and the reference to the “absolute spirit” of Confucius, Plato, Kant and Hegel. The research is aimed at justifying the civilizational paradigm of education on the basis of Hegelian fundamental ideas of intellectual perception with the emphasis on reasonability instead of rationality. As the most adequate implementation instrument, the author suggests a game simulating technique that combines the benefits of philosophical, scientific and methodological thinking.

  8. 78 FR 68459 - Medical Device Development Tools; Draft Guidance for Industry, Tool Developers, and Food and Drug...

    Science.gov (United States)

    2013-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1279] Medical Device Development Tools; Draft Guidance for Industry, Tool Developers, and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

  9. Generalized NLS hierarchies from rational W algebras

    International Nuclear Information System (INIS)

    Toppan, F.

    1993-11-01

    Finite rational W algebras are very natural structures appearing in coset constructions when a Kac-Moody subalgebra is factored out. The problem of relating these algebras to integrable hierarchies of equations is studied by showing how to associate to a rational W algebra its corresponding hierarchy. Two examples are worked out, the sl(2)/U(1) coset, leading to the Non-Linear Schroedinger hierarchy, and the U(1) coset of the Polyakov-Bershadsky W algebra, leading to a 3-field representation of the KP hierarchy already encountered in the literature. In such examples a rational algebra appears as algebra of constraints when reducing a KP hierarchy to a finite field representation. This fact arises the natural question whether rational algebras are always associated to such reductions and whether a classification of rational algebras can lead to a classification of the integrable hierarchies. (author). 19 refs

  10. Identification of necessary and sufficient conditions for real non-negativeness of rational matrices

    International Nuclear Information System (INIS)

    Saeed, K.

    1982-12-01

    The necessary and sufficient conditions for real non-negativeness of rational matrices have been identified. A programmable algorithm is developed and is given with its computer flow chart. This algorithm can be used as a general solution to test the real non-negativeness of rational matrices. The computer program assures the feasibility of the suggested algorithm. (author)

  11. Divergence and convergence of commercial and scientific priorities in drug development: The case of Zelmid, the first SSRI antidepressant.

    Science.gov (United States)

    Mulinari, Shai

    2015-08-01

    Based on a realist conceptualization of interests, this paper explores how commercial and scientific priorities appear to have converged and diverged during the development of the antidepressant Zelmid. The drug represents the first of the selective serotonin reuptake inhibitors (SSRIs) to reach the market. Zelmid was synthesized in 1971 and launched by the Swedish firm Astra in 1982, but subsequently withdrawn the next year because of adverse neurological effects. This paper draws on in-depth interviews with scientists representing both industry and academia who had high-level involvement in various phases of the project (experimental, pre-clinical and clinical), as well as on textual sources such as scientific articles and memoirs. Zelmid was a product of mechanism-based or "rational" drug discovery from the early 1960s and the associated intermingling of science and commerce. It is argued that both scientists and the pharmaceutical company shared an interest in embracing mechanism-based drug discovery because it simultaneously promised medico-scientific advances and profits. However, the intermingling of science and commerce also strained the relationship between scientific and commercial priorities further along the trajectory of the drug; for example, concerning issues such as dosage strategy and drug use in primary care, where corporate management allegedly took decisions contrary to the recommendations of both academic and company scientists. On such occasions the asymmetry in power became apparent in scientists' narratives: commercial considerations trumped those of science since, ultimately, decisions rest with management, not with scientists. In addition, temporality appears to be associated with the divergence of commercial and scientific priorities. While rare during experimental and pre-clinical phases, divergence was concentrated downstream to the clinical testing and post-marketing phases. It is hypothesized that a similar pattern of convergence and

  12. The use of 'Omics technology to rationally improve industrial mammalian cell line performance.

    Science.gov (United States)

    Lewis, Amanda M; Abu-Absi, Nicholas R; Borys, Michael C; Li, Zheng Jian

    2016-01-01

    Biologics represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 being in this class. Furthermore, health authority approval of biologics in the immuno-oncology space is expected to transform treatment of patients with debilitating and deadly diseases. The growing importance of biologics in the healthcare field has also resulted in the recent approvals of several biosimilars. These recent developments, combined with pressure to provide treatments at lower costs to payers, are resulting in increasing need for the industry to quickly and efficiently develop high yielding, robust processes for the manufacture of biologics with the ability to control quality attributes within narrow distributions. Achieving this level of manufacturing efficiency and the ability to design processes capable of regulating growth, death and other cellular pathways through manipulation of media, feeding strategies, and other process parameters will undoubtedly be facilitated through systems biology tools generated in academic and public research communities. Here we discuss the intersection of systems biology, 'Omics technologies, and mammalian bioprocess sciences. Specifically, we address how these methods in conjunction with traditional monitoring techniques represent a unique opportunity to better characterize and understand host cell culture state, shift from an empirical to rational approach to process development and optimization of bioreactor cultivation processes. We summarize the following six key areas: (i) research applied to parental, non-recombinant cell lines; (ii) systems level datasets generated with recombinant cell lines; (iii) datasets linking phenotypic traits to relevant biomarkers; (iv) data depositories and bioinformatics tools; (v) in silico model development, and (vi) examples where these approaches have been used to rationally improve cellular processes. We critically assess relevant and state of the art research

  13. 77 FR 60622 - New Animal Drugs; Change of Sponsor's Address; Monensin; Spinosad; Tilmicosin

    Science.gov (United States)

    2012-10-04

    ... swine the sole ration for respiratory disease 21-day period, associated with beginning Actinobacillus... dairy cattle: For 14 days to provide the control of 12.5 milligrams/ bovine respiratory kilogram/head... drug residues least 10 percent of in milk. This drug the animals in the product is not group. approved...

  14. Drug Development for Metastasis Prevention.

    Science.gov (United States)

    Fontebasso, Yari; Dubinett, Steven M

    2015-01-01

    Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors.

  15. Melatonergic drugs in development

    Directory of Open Access Journals (Sweden)

    Carocci A

    2014-09-01

    Full Text Available Alessia Carocci,1 Alessia Catalano,1 Maria Stefania Sinicropi2 1Department of Pharmacy–Drug Sciences, University of Bari Aldo Moro, Bari, 2Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy Abstract: Melatonin (N-acetyl-5-methoxytryptamine is widely known as "the darkness hormone". It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review. Keywords: MT1/MT2 ligands, circadian rhythms, melatonin 

  16. Lying for the Greater Good: Bounded Rationality in a Team

    Directory of Open Access Journals (Sweden)

    Oktay Sürücü

    2014-10-01

    Full Text Available This paper is concerned with the interaction between fully and boundedly rational agents in situations where their interests are perfectly aligned. The cognitive limitations of the boundedly rational agent do not allow him to fully understand the market conditions and lead him to take non-optimal decisions in some situations. Using categorization to model bounded rationality, we show that the fully rational agent can nudge, i.e., he can manipulate the information he sends and decrease the expected loss caused by the boundedly rational agent. Assuming different types for the boundedly rational agent, who differ only in the categories used, we show that the fully rational agent may learn the type of the boundedly rational agent along their interaction. Using this additional information, the outcome can be improved and the amount of manipulated information can be decreased. Furthermore, as the length of the interaction increases the probability that the fully rational agent learns the type of the boundedly rational agent grows

  17. Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review

    Science.gov (United States)

    Csermely, Peter; Korcsmáros, Tamás; Kiss, Huba J.M.; London, Gábor; Nussinov, Ruth

    2013-01-01

    Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The “central hit strategy” selectively targets central node/edges of the flexible networks of infectious agents or cancer cells to kill them. The “network influence strategy” works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach. PMID:23384594

  18. Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.

    Science.gov (United States)

    Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin

    2015-01-01

    Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections.

  19. Anti-influenza drugs: the development of sialidase inhibitors.

    Science.gov (United States)

    von Itzstein, Mark; Thomson, Robin

    2009-01-01

    Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza, and subsequently Tamiflu, has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important. An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.

  20. Rational Choice and Developmental Influences on Recidivism Among Adolescent Felony Offenders.

    Science.gov (United States)

    Fagan, Jeffrey; Piquero, Alex R

    2007-12-01

    Recent case law and social science both have claimed that the developmental limitations of adolescents affect their capacity for control and decision making with respect to crime, diminishing their culpability and reducing their exposure to punishment. Social science has focused on two concurrent adolescent developmental influences: the internalization of legal rules and norms that regulate social and antisocial behaviors, and the development of rationality to frame behavioral choices and decisions. The interaction of these two developmental processes, and the identification of one domain of socialization and development as the primary source of motivation or restraint in adolescence, is the focus of this article. Accordingly, we combine rational choice and legal socialization frameworks into an integrated, developmental model of criminality. We test this framework in a large sample of adolescent felony offenders who have been interviewed at six-month intervals for two years. Using hierarchical and growth curve models, we show that both legal socialization and rational choice factors influence patterns of criminal offending over time. When punishment risks and costs are salient, crime rates are lower over time. We show that procedural justice is a significant antecedent of legal socialization, but not of rational choice. We also show that both mental health and developmental maturity moderate the effects of perceived crime risks and costs on criminal offending.