WorldWideScience

Sample records for drug development competitive

  1. A dynamic perspective on pharmaceutical competition, drug development and cost effectiveness.

    Science.gov (United States)

    Refoios Camejo, Rodrigo; McGrath, Clare; Herings, Ron

    2011-04-01

    Limited healthcare budgets result in payers adopting policies at national, regional or local level to achieve allocative efficiency in drug spending. Some of these aim at creating a link between pharmaceutical prices and the value they provide by setting a cost effectiveness (CE) threshold as the maximum acceptable ratio between incremental costs and effects of new drugs. The clinical effectiveness of the comparator used in those CE analyses tends to be greater over time, whilst, due to market competition and loss of exclusivity, their price is expected to be lower. At the same time, research and development (R&D) costs increase with inflation and with efforts to address regulation towards increased safety concerns. As effective patent times decrease, a minimum price constraint raises for the new entrant. These features occur at different rates across disease areas and are expected to result in differently shaped innovation curves. In this scenario, we demonstrate that a general arbitrary threshold may prevent further efficient R&D. Investment may be withdrawn before the optimum innovation point is reached and affordable clinical effectiveness may be lost. We conclude that disease-specific characteristics are an additional consideration in CE decision rules to accommodate the particularities of innovation across disease areas.

  2. Assessing competition policy on economic development

    OpenAIRE

    Tilsa Oré

    2013-01-01

    Implementation of competition policies is one of the most recommended strategies to developing countries as a tool for achieving economic development. Using a panel dataset of over 100 countries and 7 years (from 2005-2011), I estimate the effect of competition on economic development, and also determine which of the comprehensive policy factors are the most relevant for increasing competition. A fixed effects instrumental variable approach is used. I find that competition intensity positivel...

  3. Developing Information Systems for Competitive Intelligence Support.

    Science.gov (United States)

    Hohhof, Bonnie

    1994-01-01

    Discusses issues connected with developing information systems for competitive intelligence support; defines the elements of an effective competitive information system; and summarizes issues affecting system design and implementation. Highlights include intelligence information; information needs; information sources; decision making; and…

  4. Drug Development Process

    Science.gov (United States)

    ... Device Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Step 1 Discovery and Development Discovery and Development Research for a new drug ...

  5. Synergy between Competitive Intelligence (CI), Knowledge Management (KM) and Technological Foresight (TF) as a strategic model of prospecting--the use of biotechnology in the development of drugs against breast cancer.

    Science.gov (United States)

    Canongia, Claudia

    2007-01-01

    The aim of this paper is to demonstrate the synergy between Competitive Intelligence, Knowledge Management and Technological Foresight, and to emphasize the proposal of a strategic model of data prospecting as a mechanism to support decision-making in regard to three approaches for sustainable development and innovation: technological, social and economic. The use of biotechnology in the development of drugs against breast cancer is the case study. The article shows the results of data and text mining in specialized medical and patent databases, identifying the most frequently cited drugs, as well as the authors of research, and the inventors of new technology at the beginning of the 21st century. In addition, the study includes reference to Brazilian competence in breast cancer area, the international trends in drugs for treatment of this cancer, leading international institutions and Brazilian competencies. A framework is presented, which could serve as a guide and support for the decision-making process.

  6. Molecular properties of psychopharmacological drugs determining non-competitive inhibition of 5-HT3A receptors.

    Science.gov (United States)

    Kornhuber, Johannes; Terfloth, Lothar; Bleich, Stefan; Wiltfang, Jens; Rupprecht, Rainer

    2009-06-01

    We developed a structure-property-activity relationship (SPAR)-model for psychopharmacological drugs acting as non-competitive 5-HT(3A) receptor antagonists by using a decision-tree learner provided by the RapidMiner machine learning tool. A single molecular descriptor, namely the molecular dipole moment per molecular weight (mu/MW), predicts whether or not a substance non-competitively antagonizes 5-HT-induced Na(+) currents. A low mu/MW is compatible with drug-cumulation in apolar lipid rafts. This study confirms that size-intensive descriptors allow the development of compact SPAR models.

  7. Orphan drug: Development trends and strategies.

    Science.gov (United States)

    Sharma, Aarti; Jacob, Abraham; Tandon, Manas; Kumar, Dushyant

    2010-10-01

    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.

  8. Competitive pricing within pharmaceutical classes: evidence on "follow-on" drugs in Germany 1993-2008.

    Science.gov (United States)

    Mueller, Michael T; Frenzel, Alexander

    2015-01-01

    Competition from "follow-on" drugs has been a highly controversial issue. Manufacturers launching new molecules in existing drug classes have often been criticized for inflating health systems' expenses, but it has been argued that such drugs increase therapeutic options. Economic theory suggests that follow-on drugs induce price competition. We contribute to this discussion by addressing the topic of pricing at market entry and price development in the German market. We measure determinants of price strategies of follow-on drugs using regression analyses, considering all new molecules launched in the German market from 1993 to 2008. Prices of products are standardized on defined daily dosages controlling for sales volumes based on data from the IMS Health DPM database and for the therapeutic quality of a new product using ratings by Fricke/Klaus as a proxy for innovation. We identify prices correlating with therapeutic value at market entry. While the first two molecules engage in quality competition, price discounts below the market price can be observed from the third entrant on. Price discounts are even more distinct in development races with several drugs entering the market within 2 years and in classes with a low degree of therapeutic differentiation. Prices remain relatively constant over time. This study contributes to assessments of competition in pharmaceutical markets focusing on price strategies of new market entrants. After an initial phase of market building, further follow-on products induce price competition. Largely unchanged prices after 4 years may be interpreted as quality competition and can be attributed to prices in Germany being anchor points for international price referencing.

  9. Metallomics in drug development

    DEFF Research Database (Denmark)

    Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan;

    2013-01-01

    A capillary electrophoresis inductively coupled plasma mass spectrometry method for separation of free cisplatin from liposome-encapsulated cisplatin and protein-bound cisplatin was developed. A liposomal formulation of cisplatin based on PEGylated liposomes was used as model drug formulation...... to plasma constituents in plasma samples. It was demonstrated that this approach is suitable for studies of the stability of liposome formulations as leakage of active drug from the liposomes and subsequent binding to biomolecules in plasma can be monitored. This methodology has not been reported before...... and will improve characterization of liposomal drugs during drug development and in studies on kinetics....

  10. Developing the Competitive Organization: Interventions and Strategies.

    Science.gov (United States)

    Beer, Michael; Walton, Elise

    1990-01-01

    Discusses how a competitive environment has given rise to a paradigmatic transformation in how corporations organize and manage people. Discusses the following topics: (1) the field of organization development; (2) how corporations transform their culture; (3) the role of effective change leaders; and (4) the role of the consultant. (JS)

  11. Drug resistance and antiretroviral drug development

    OpenAIRE

    Shafer, Robert W.; Jonathan M Schapiro

    2005-01-01

    As more drugs for treating HIV have become available, drug resistance profiles within antiretroviral drug classes have become increasingly important for researchers developing new drugs and for clinicians integrating new drugs into their clinical practice. In vitro passage experiments and comprehensive phenotypic susceptibility testing are used for the pre-clinical evaluation of drug resistance. Clinical studies are required, however, to delineate the full spectrum of mutations responsible fo...

  12. Drug procurement, the Global Fund and misguided competition policies

    Directory of Open Access Journals (Sweden)

    Hess Kimberly

    2009-12-01

    Full Text Available Abstract In an effort to increase competition and decrease price, the Global Fund to Fight AIDS, Tuberculosis and Malaria recently began asking some grant recipients to use international competitive bidding processes for certain drug purchases. Unfortunately, for countries like Kenya, this request has caused more harm than good. After awarding the tender for its annual supply of the anti-malarial artemether-lumefantrine to the lowest bidder, Ajanta Pharma, Kenya experienced wide stock-outs in part due to the company's inability to supply the order in full and on time. Similar problems could arise in Uganda. Despite Kenya's experience, Uganda has awarded its next tender for artemether-lumefantrine to Ajanta Pharma. Uganda is already facing wide stock-outs and risks exacerbating an already dire situation the longer it takes to fulfil the procurement contract. A tender process based primarily on price cannot account for a company's ability to consistently supply sufficient product in time.

  13. Using Sustainable Development as a Competitive Strategy

    Science.gov (United States)

    Spearman, Pat

    Sustainable development reduces construction waste by 43%, generating 50% cost savings. Residential construction executives lacking adequate knowledge regarding the benefits of sustainable development practices are at a competitive disadvantage. Drawing from the diffusion of innovation theory, the purpose of this qualitative case study was to explore knowledge acquisition within the bounds of sustainable residential construction. The purposive sample size of 11 executive decision makers fulfilled the sample size requirements and enabled the extraction of meaningful data. Participants were members of the National Home Builders Association and had experience of a minimum of 5 years in residential construction. The research question addressed how to improve knowledge acquisition relating to the cost benefits of building green homes and increase the adoption rate of sustainable development among residential builders. Data were collected via semistructured telephone interviews, field observation, and document analysis. Transcribed data were validated via respondent validation, coded into 5 initial categories aligned to the focus of the research, then reduced to 3 interlocking themes of environment, competitive advantage, and marketing. Recommendations include developing comprehensive public policies, horizontal and vertical communications networks, and green banks to capitalize sustainable development programs to improve the diffusion of green innovation as a competitive advantage strategy. Business leaders could benefit from this data by integrating sustainable development practices into their business processes. Sustainable development reduces operational costs, increases competitive advantage for builders, and reduces greenhouse gas emissions. Implications for social change increase energy independence through conservation and developing a legislative policy template for comprehensive energy strategies. A comprehensive energy strategy promotes economic development

  14. Preclinical drug development.

    Science.gov (United States)

    Brodniewicz, Teresa; Grynkiewicz, Grzegorz

    2010-01-01

    Life sciences provide reasonably sound prognosis for a number and nature of therapeutic targets on which drug design could be based, and search for new chemical entities--future new drugs, is now more than ever based on scientific principles. Nevertheless, current very long and incredibly costly drug discovery and development process is very inefficient, with attrition rate spanning from many thousands of new chemical structures, through a handful of validated drug leads, to single successful new drug launches, achieved in average after 13 years, with compounded cost estimates from hundreds of thousands to over one billion US dollars. Since radical pharmaceutical innovation is critically needed, number of new research projects concerning this area is steeply rising outside of big pharma industry--both in academic environment and in small private companies. Their prospective success will critically depend on project management, which requires combined knowledge of scientific, technical and legal matters, comprising regulations concerning admission of new drug candidates to be subjects of clinical studies. This paper attempts to explain basic rules and requirements of drug development within preclinical study period, in case of new chemical entities of natural or synthetic origin, which belong to low molecular weight category.

  15. Research on Development Mode of Foreign Competitive Basketball

    Science.gov (United States)

    Xianjiang, Zhou; Bin, Zong; Xianwu, Wu

    Adopting literature material method, survey and comparative method, the paper studies foreign competitive basketball, foreign competitive basketball on behalf of the State management system model, competitive basketball reserve personnel training and development mode system. Rely on different powers of the foreign competitive basketball from amateur to professional development; different modes of foreign competitive basketball management system; foreign competitive basketball back-up personnel training mode, the model on school training in America and other countries, mainly the club training mode in European countries; foreign model of development of competitive basketball, different from social guidance, in the combination operation mode of market regulation and government administrative intervention.

  16. [Competition between branded and generic drugs in Austria: evidence from the market for ACE inhibitors].

    Science.gov (United States)

    Mahlich, J C; Stadler, I

    2012-01-01

    The market for pharmaceuticals in Austria is highly regulated and manufacturers cannot set prices freely after patent expiration of the pioneer drug. We wanted to examine the effect of price regulation on price competition between branded and generic drugs in Austria. We examined the Austrian market for ACE inhibitors and describe competitive dynamics by means of 6 indices. We compared our results with those of Grabowski and Vernon who studied the US market. According to our analysis the competition amongst the producers of generic drugs is not great and consequently, compared to the USA, over time the prices for generic products decrease less and their market share increases less. This is due to a market-oriented system in the USA which waives most regulatory provisions. Our conclusions are in line with the findings by Danzon und Chao (2000) who argue that in a price-regulated market competitive dynamics are less strongly developed. From a politico-economic view, the necessity of price regulations in the pharmaceutical market seems questionable, as price regulations generally also cause other negative effects, such as distorted economic incentives for research and development investments. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Bushman, Mary; Morton, Lindsay; Duah, Nancy; Quashie, Neils; Abuaku, Benjamin; Koram, Kwadwo A; Dimbu, Pedro Rafael; Plucinski, Mateusz; Gutman, Julie; Lyaruu, Peter; Kachur, S Patrick; de Roode, Jacobus C; Udhayakumar, Venkatachalam

    2016-03-16

    Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.

  18. Drug development and immunotoxicity

    Institute of Scientific and Technical Information of China (English)

    SugiY; IzumM

    2002-01-01

    Immunotoxicity of drugs has to be evaluated same as other kinds of toxicities,since the functions of the immune system are vital to human survival,consisting of the protection of the body from invading pathogens and to provide immune surveillance against arising tumor cells.A given drug's effect on the immune system can be classified as (1)immuno-suppression/activation.(2)antigenicity and hypersensitivity,(3)autoimmunity.The guidance of immumotoxicity has highlighted on immuno-suppression in Harmonizing Congress among EC,USA and Japan.In this paper,the strategy and methods to evaluate immunotoxicity,mainly immuno-suppression,of the drugs will be show.complexity and variety of immuno-systems make assessment of immumotoxicity complex.The testing in rats to assess immune function is thought to be the first choice for immunotoxicity evaluation in a drug development,and then other suitable testing should be added depending on the mature of drugs.

  19. FDA relations during drug development

    OpenAIRE

    Mitchel, Jules T.

    2000-01-01

    Working closely and cooperatively with regulatory authorities during drug development is vital to successful drug development programs. In the United States, the drug development team includes not only members of the key disciplines of drug discovery, clinical research, regulatory affairs, marketing, chemistry, toxicology, and legal aspects, but also the Food and Drug Administration (FDA). New regulations encourage meetings at the pre-investigational new drug (pre-IND), end-of-phase-2, and pr...

  20. Competitive development of the agricultural enterprises France

    Directory of Open Access Journals (Sweden)

    Olena Yushkevych

    2013-05-01

    Full Text Available The stages which determine the development of agricultural enterprises in France are investigated in the article. In the course of implementation of Ukrainian-French programs of scientific and educational cooperation on the problems of the management of agricultural enterprises in State Educational Institutions training specialists (cities of Chartres and Vic–en Bigorre, France it was found that the major components of development of agricultural enterprises in France are as follows: agricultural policy, education, motivation, information and management. The problem of the diversified development in the context of transition to green economy and sustainable development is considered. It is determined that an example of competitive development of agricultural enterprises in France is the establishment and operation of professional associations, in particular, cooperatives and clusters. The priority directions of economic and ecological development of agricultural enterprises for Ukraine are offered in order to implement potential opportunities of agricultural enterprises and to relocate the resources into new kinds of agricultural and non-agricultural activities

  1. THE CHALLENGES OF GLOBAL COMPETITIVENESS: THE INSTITUTIONS AND INNOVATION DEVELOPMENT

    OpenAIRE

    Iryna TARANENKO

    2010-01-01

    The paper is devoted to the analysis of the causes of decreasing Ukraine’s global competitiveness position, and the influence of the factors: “Higher education and training”, “Innovation”, “Institutions” on the global competitiveness of Ukrainian economy. The possibilities of increasing the global competitive position of Ukraine by intensification of innovative activity, development of the set of measures on strengthening the innovative components of global competitiveness have been examined....

  2. Pedagogy for Economic Competitiveness and Sustainable Development

    Science.gov (United States)

    Sahlberg, Pasi; Oldroyd, David

    2010-01-01

    Accelerating threats to a sustainable relationship between economic growth and the capacity of the global social-ecological system to support it require that the implications of competitiveness be reassessed. Today, the capacities that underlie economic competitiveness must also be brought to bear on policy and pedagogy to prepare the coming…

  3. Pedagogy for Economic Competitiveness and Sustainable Development

    Science.gov (United States)

    Sahlberg, Pasi; Oldroyd, David

    2010-01-01

    Accelerating threats to a sustainable relationship between economic growth and the capacity of the global social-ecological system to support it require that the implications of competitiveness be reassessed. Today, the capacities that underlie economic competitiveness must also be brought to bear on policy and pedagogy to prepare the coming…

  4. 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 

  5. Microdialysis-liquid chromatographic study on competitive binding of drugs to protein

    Institute of Scientific and Technical Information of China (English)

    汪海林; 邹汉法; 张玉奎

    1997-01-01

    A new method to determine the interaction between drug and protein has been developed by utilizing the technique of microdialysis sampling with the ketoprofen and the human serum albumin (HSA) as the model of drug and protein.Two kinds of binding sites of HSA to ketoprofen have been observed.The binding constants and number of binding sites obtained by the Scatchard equation are 0.799,3.18×106 mol-1 L and 2.15,2.01×105 mol-1 L,respectively The displacement binding of drugs to HSA has also been studied.The strong displacement of competitive binding of ibuprofen with ketoprofen to HSA was observed,which means that the primary binding site of HSA to ketoprofen and that to ibuprofen are the same.However,only a weaker displacement of warfarin for the association of ketoprofen with HSA was observed,which may suggest that the primary binding site of HSA to ketoprofen is different from that to warfarin.Such a displacement effect for competitive binding of drugs to HSA was explained by the displacement model i

  6. Melatonergic drugs in development.

    Science.gov (United States)

    Carocci, Alessia; Catalano, Alessia; Sinicropi, Maria Stefania

    2014-01-01

    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.

  7. Unequal Development and Territorial Competitiveness of Network Economy

    Institute of Scientific and Technical Information of China (English)

    郭健全; 汤兵勇

    2004-01-01

    The territorial consideration is enclosed in the development of network economy and e-Business, and there is no departure of the cultivation of e-Business from the establishment of territorial competitiveness. The traditional theory of the territorial competitiveness has come across a serious impact from the Internet. So the development of Internet infrastructures and institutional environment would be something new to the theory of territorial competitiveness in the Internet era.

  8. Bioavailability and Bioequivalence in Drug Development

    OpenAIRE

    Chow, Shein-Chung

    2014-01-01

    Bioavailability is referred to as the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. The relative bioavailability in terms of the rate and extent of drug absorption is considered predictive of clinical outcomes. In 1984, the United States Food and Drug Administration (FDA) was authorized to approve generic drug products under the Drug Price Competition and Patent Term Restoration Act base...

  9. Competitive Acquisition for Part B Drugs and Biologicals

    Data.gov (United States)

    U.S. Department of Health & Human Services — Section 303 (d) of the Medicare Modernization Act (see Downloads section below) requires the implementation of a competitive acquisition program (CAP) for Medicare...

  10. Competition

    NARCIS (Netherlands)

    Boone, J.

    2000-01-01

    Competition has been modelled in the literature in a number of ways.What do these different parametrizations of competition have in common?For instance, it turns out that it is not always the case that a rise in competition reduces price cost margins, industry wide profits or concentration.All param

  11. Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a myth?

    Science.gov (United States)

    Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul

    2011-01-01

    Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

  12. Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a myth?

    Directory of Open Access Journals (Sweden)

    Constance Meiners

    Full Text Available BACKGROUND: Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. METHODS AND FINDINGS: Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. SIGNIFICANCE: In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

  13. 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...

  14. Promoting Balanced Competitiveness Strategies of Firms in Developing Countries

    CERN Document Server

    Wang, Vivienne

    2012-01-01

    Since the pioneering work of Joseph Schumpeter (1942), it has been assumed that innovations typically play a key role in firms’ competitiveness.  This assumption has been applied to firms in both developed and developing countries. However, the innovative capacities and business environments of firms in developing countries are fundamentally different from those in developed countries. It stands to reason that innovation and competitiveness models based on developed countries may not apply to developing countries.   In this volume, Vivienne Wang and Elias G. Carayannis apply both theoretical approaches and empirical analysis to explore the dynamics of innovation in developing countries, with a particular emphasis on R&D in manufacturing firms.  In so doing, they present an alternative to Michael Porter’s Competitive Advantage Model—a Competitive Position Model that focuses on incremental and adaptive innovations that are more appropriate than radical innovations for developing countries.  Their ...

  15. Competitive Pressure, Selection and Investments in Development and Fundamental Research

    NARCIS (Netherlands)

    Boone, J.

    1998-01-01

    This paper analyses the effects of competitive pressure on a firm's incentives to undertake both fundamental research and development. It presents a new framework incorporating the selection effect of product market competition, the Schumpeterian argument for monopoly power, the Nickell/Porter argum

  16. Competitive Pressure, Selection and Investments in Development and Fundamental Research

    NARCIS (Netherlands)

    Boone, J.

    1998-01-01

    This paper analyses the effects of competitive pressure on a firm's incentives to undertake both fundamental research and development. It presents a new framework incorporating the selection effect of product market competition, the Schumpeterian argument for monopoly power, the Nickell/Porter argum

  17. High Generic Drug Prices and Market Competition: A Retrospective Cohort Study.

    Science.gov (United States)

    Dave, Chintan V; Kesselheim, Aaron S; Fox, Erin R; Qiu, Peihua; Hartzema, Abraham

    2017-08-01

    Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. To determine the association between market competition levels and the change in generic drug prices in the United States. Retrospective cohort study. Prescription claims from commercial health plans between 2008 and 2013. The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl-Hirschman Index (HHI)-calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market-and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of -31.7% (95% CI, -34.4% to -28.9%), -11.8% (CI, -18.6% to -4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. Study findings may not be generalizable to drugs that became generic after 2008. Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. None.

  18. Competition.

    Science.gov (United States)

    Chambers, D W

    1997-01-01

    Our ambivalence toward competition can be traced to an unspoken preference for certain types of competition which give us an advantage over the types we value less. Four types are defined (a) pure (same rules, same objectives), (b) collaborative (same rules, shared objective), (c) market share (different rules, same objectives), and (d) market growth (different rules, value added orientation). The defining characteristics of the four types of competition are respectively: needing a referee, arguing over the spoils, differentiation and substitutability, and customer focus. Dentistry has features of all four types of competition, thus making it difficult to have a meaningful discussion or frame a coherent policy on this topic.

  19. Drug development and manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.

    2015-10-13

    X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.

  20. Competition

    NARCIS (Netherlands)

    F. Bridoux

    2014-01-01

    Competition traditionally refers to the actions that firms take in a product market to outperform rivals in attracting customers and generating revenues. Yet, competition extends beyond product markets to other arenas such as factor markets, where firms compete for resources, and the political arena

  1. New Zealand's drug development industry.

    Science.gov (United States)

    Lockhart, Michelle Marie; Babar, Zaheer-Ud-Din; Carswell, Christopher; Garg, Sanjay

    2013-09-13

    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.

  2. Melatonergic drugs in development

    OpenAIRE

    Carocci A; Catalano A; Sinicropi MS

    2014-01-01

    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 ...

  3. Competition

    Institute of Scientific and Technical Information of China (English)

    吕思思

    2007-01-01

    <正> The term competition reminds me of asoul-stirring fight between a mother monkeyand a crocodile,The crocodile caught her babywhen the baby was drinking water in a pool,Inthe end,the mother got her baby,but herbaby’s body only,She lost her child forever,just for a mouthful of water.Such is competition,cruel and merciless,But if we see the other side of the coin,we’ll

  4. MODELS OF THE 5 PORTERS COMPETITIVE FORCES METHODOLOGY CHANGES IN COMPANIES STRATEGY DEVELOPMENT ON COMPETITIVE MARKET

    Directory of Open Access Journals (Sweden)

    Sergey I Zubin

    2014-01-01

    Full Text Available There are some different types of approaches to 5 Porters Forces model development in thisarticle. Authors take up the negative attitude researcher reasons to this instrument and inputsuch changes in it, which can help to fi nd the best way to companies growing up on competitive market.

  5. Competitive intelligence and patent analysis in drug discovery.

    Science.gov (United States)

    Grandjean, Nicolas; Charpiot, Brigitte; Pena, Carlos Andres; Peitsch, Manuel C

    2005-01-01

    Patents are a major source of information in drug discovery and, when properly processed and analyzed, can yield a wealth of information on competitors activities, R&D trends, emerging fields, collaborations, among others. This review discusses the current state-of-the-art in textual data analysis and exploration methods as applied to patent analysis.:

  6. Indoor Competition Climbing as a Context for Positive Youth Development

    Directory of Open Access Journals (Sweden)

    Barry A. Garst

    2016-12-01

    Full Text Available Climbing as a competitive youth sport is rapidly expanding in both participation and popularity as it has transitioned from an unorganized recreational activity to a formalized sport with a national governing body, organized competitions, formal coaching, and team structure. In spite of this growth, little to no research has been conducted regarding indoor competition climbing as a developmental experience for youth. This study examined the contributions of indoor competition climbing to youth development outcomes based on qualitative responses collected from 623 parents and climbers (youth and adults in late Fall 2014. Themes were constructed related to climbing as a youth development experience, including: holistic development; supportive relationships; confidence and self-efficacy; and sportsmanship and character development. Holistic development, which included growth in the areas of strength and health, cognition and mental conditioning, and social skills, appears to be a hallmark of the sport of indoor competition climbing. The identified themes mapped well to the 5Cs model of positive youth development (PYD, providing evidence for the existence of the 5Cs among youth who play sports. In response to calls for intentionality in youth programming, future research examining underlying programming, coaching, and parenting mechanisms that contribute to PYD is recommended.

  7. Library performance and service competition developing strategic responses

    CERN Document Server

    White, Larry Nash

    2008-01-01

    A practice-driven and proven resource for library administrators of all types of libraries. The work describes how the library can identify the service environment factors impacting customers; strategic needs; identify library competitors; strategic abilities and service environment impacts; and use the combined results to develop proactive competitive responses that drive the service environment instead of reacting to the service environment. These strategic competitive responses would allow the library to increase the value of its service impact and effectiveness while increasing customer appreciation and the libraries advantage in the competitive service environment. Written by a highly knowledgeable practitioner from the library field Experience of the author (library and for-profit management experience) provides a hybrid/blended view of library competition and management responses from both the library and for-profit management worlds Written to applicable to all types of libraries.

  8. Site Identification by Ligand Competitive Saturation (SILCS) Simulations for Fragment-Based Drug Design

    Science.gov (United States)

    Faller, Christina E.; Raman, E. Prabhu; MacKerell, Alexander D.; Guvench, Olgun

    2015-01-01

    Fragment-based drug design (FBDD) involves screening low molecular weight molecules (“fragments”) that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind non-overlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy. The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is “soaked” in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called “FragMaps” can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine “Grid Free Energies (GFEs),” which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities. PMID:25709034

  9. Phase IV of Drug Development

    OpenAIRE

    Viraj Suvarna

    2010-01-01

    Not all Phase IV studies are post-marketing surveillance (PMS) studies but every PMS study is a phase IV study. Phase IV is also an important phase of drug development. In particular, the real world effectiveness of a drug as evaluated in an observational, non-interventional trial in a naturalistic setting which complements the efficacy data that emanates from a pre-marketing randomized controlled trial (RCT). No matter how many patients are studied pre-marketing in a controlled environment, ...

  10. SUSTAINABILITY AS A STRATEGY OF RESPONSIBLE AND COMPETITIVE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    José G. Vargas-Hernández

    2012-12-01

    Full Text Available The aim of this paper is to analyze a competitiveness strategy based on sustainability to lead the way to a model of responsible and competitive development. The analysis takes as its starting point the assumption that the maturity of a sustainable business strategy positively affects competitiveness. The used method is the critical analysis. Among other results of this analysis concludes that the current business strategy seeks a system ecologically appropriate, economically viable and socially fair to reach sustainable equilibrium. This strategy based on sustainability must be promoted by the institutions and strengthened by the capabilities and resources that each company counts on to develop advantages to foster the overall development and achieve the maximization of benefits from the tangible and intangible perspectives

  11. Competition

    CERN Multimedia

    Staff Association

    2017-01-01

    Get ready for the Easter Egg Hunt! The Staff Association is organising a competition from 10 to 21 April 2017. There are several Go Sport gift vouchers to win, with a value of 50 € each. Try your luck! Count the number of different eggs that we have hidden on our website. Then indicate your answer in the online form. To participate, you just need to be a member of the Staff Association. Winners will be randomly drawn among the correct answers.

  12. Competition

    CERN Multimedia

    Staff Association

    2016-01-01

      The Staff Association is organising a competition from 13 to 21 December 2016. There are several Go Sport vouchers to win with a value of 50 € each. Try your luck! To participate, you just have to be a member of the Staff Association and take the online quiz: https://ap-vote.web.cern.ch/content/jeu-concours-de-noel. The winners will be drawn among the correct answers.

  13. Competition

    CERN Multimedia

    Staff Association

    2016-01-01

      The Staff Association is organising a competition from April 11 to 20. There are several Go Sport gift vouchers with a value of 50 € each to win. Try your luck! To participate, you just have to be a member of the Staff Association and take the online quiz: https://ap-vote.web.cern.ch/content/jeu-concours. The winners will be drawn among the correct answers.

  14. Drug development, radiolabelled drugs and PET

    NARCIS (Netherlands)

    Vaalburg, W; Hendrikse, NH; de Vries, EFJ

    1999-01-01

    Positron emission tomography (PET) provides noninvasive in vivo quantitative pharmacokinetic and pharmacodynamic information on novel and established drugs. Because only very low amounts of the (potential) drug have to be administered, far below toxicity levels, human studies can be carried out even

  15. SUSTAINABILITY AS A STRATEGY OF RESPONSIBLE AND COMPETITIVE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    JOSÉ G. VARGAS-HERNÁNDEZ

    2012-09-01

    Full Text Available The aim of this paper is to analyze a competitiveness strategy based on sustainability to lead the way to a model ofresponsible and competitive development. The analysis takes as its starting point the assumption that the maturity of asustainable business strategy positively affects competitiveness. The used method is the critical analysis. Amongother results of this analysis concludes that the current business strategy seeks a system ecologically appropriate,economically viable and socially fair to reach sustainable equilibrium. This strategy based on sustainability must bepromoted by the institutions and strengthened by the capabilities and resources that each company counts on todevelop advantages to foster the overall development and achieve the maximization of benefits from the tangible andintangible perspectives.

  16. Software Development Offshoring Competitiveness: A Case Study of ASEAN Countries

    Science.gov (United States)

    Bui, Minh Q.

    2011-01-01

    With the success of offshoring within the American software industry, corporate executives are moving their software developments overseas. The member countries of the Association of Southeast Asian Nations (ASEAN) have become a preferred destination. However, there is a lack of published studies on the region's software competitiveness in…

  17. Software Development Offshoring Competitiveness: A Case Study of ASEAN Countries

    Science.gov (United States)

    Bui, Minh Q.

    2011-01-01

    With the success of offshoring within the American software industry, corporate executives are moving their software developments overseas. The member countries of the Association of Southeast Asian Nations (ASEAN) have become a preferred destination. However, there is a lack of published studies on the region's software competitiveness in…

  18. Strategic business planning and development for competitive health care systems.

    Science.gov (United States)

    Nauert, Roger C

    2005-01-01

    The health care industry has undergone enormous evolutionary changes in recent years. Competitive transitions have accelerated the compelling need for aggressive strategic business planning and dynamic system development. Success is driven by organizational commitments to farsighted market analyses, timely action, and effective management.

  19. Development of student engineering competitions "STUDENT FORMULA SAE» in Ukraine

    Directory of Open Access Journals (Sweden)

    Dashchenko A.F.

    2015-12-01

    Full Text Available The article deals with the direction of the educational level of students in Ukrainian higher technical educational institutions. The advantages and attractiveness of the student engineering competition "Formula Student". The evolution of the development of the Ukrainian engineering team "Formula Student" for example, the team of Odessa National Polytechnic University.

  20. 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…

  1. Sustaining Competitiveness Through product Development Activities Within Malaysian Automotive Suppliers

    Directory of Open Access Journals (Sweden)

    Norizah Mohamad

    2012-01-01

    Full Text Available The local automotive suppliers are facing a number of important challenges such asglobalisation, new requirement in market specifications and the competition brought about by theAsean Free Trade Area (AFTA agreements. In an effort to enhance the competitiveness of themanufacturing sector, the government has implemented the Second Industrial Master Plan, IMP2(1996-2005. The focus of the IMP2 is more on innovation and applications of new technologies, sothat industries can move up the value chain of their activities. Innovative capabilities achieved fromcompanies’ new product development activities have been recognized to be crucial for companies tosustain their competitiveness and organisational success. The importance of product development ismost obvious in the context of the discussion on the competitiveness of the Malaysian automotivesuppliers. The study will focus on the small medium enterprises (SMEs that make up more than 60 %of these automotive suppliers. The study is to determine the extensiveness of the suppliers’ productdevelopment activities by examining the involvement of the suppliers in customer’s productdevelopment activities. Consequently, the impact of this involvement to the competitiveness of thesuppliers is examined. The results were established based from a survey to parts and componentssuppliers of Proton, the Malaysian car national assembler. The study has shown that the SMEs wereinvolved from the early stages of the product development process that is during the design stage. Theproduct development efforts have shown to contribute towards increasing firms’ market share andfirms were also able to gain a better understanding of future product demand. A significant number ofthe suppliers have managed to penetrate the export market. Unfortunately, among the respondents,there is only one system supplier. This indicates that, either the technological capabilities of theSMEs still needed upgrading for the requirement as

  2. Sustaining Competitiveness Through product Development Activities Within Malaysian Automotive Suppliers

    Directory of Open Access Journals (Sweden)

    Norizah Mohamad

    2012-01-01

    Full Text Available The local automotive suppliers are facing a number of important challenges such asglobalisation, new requirement in market specifications and the competition brought about by theAsean Free Trade Area (AFTA agreements. In an effort to enhance the competitiveness of themanufacturing sector, the government has implemented the Second Industrial Master Plan, IMP2(1996-2005. The focus of the IMP2 is more on innovation and applications of new technologies, sothat industries can move up the value chain of their activities. Innovative capabilities achieved fromcompanies’ new product development activities have been recognized to be crucial for companies tosustain their competitiveness and organisational success. The importance of product development ismost obvious in the context of the discussion on the competitiveness of the Malaysian automotivesuppliers. The study will focus on the small medium enterprises (SMEs that make up more than 60 %of these automotive suppliers. The study is to determine the extensiveness of the suppliers’ productdevelopment activities by examining the involvement of the suppliers in customer’s productdevelopment activities. Consequently, the impact of this involvement to the competitiveness of thesuppliers is examined. The results were established based from a survey to parts and componentssuppliers of Proton, the Malaysian car national assembler. The study has shown that the SMEs wereinvolved from the early stages of the product development process that is during the design stage. Theproduct development efforts have shown to contribute towards increasing firms’ market share andfirms were also able to gain a better understanding of future product demand. A significant number ofthe suppliers have managed to penetrate the export market. Unfortunately, among the respondents,there is only one system supplier. This indicates that, either the technological capabilities of theSMEs still needed upgrading for the requirement as

  3. Drug development: portals of discovery.

    Science.gov (United States)

    Bates, Susan E; Amiri-Kordestani, Laleh; Giaccone, Giuseppe

    2012-01-01

    A British humorist said, "There is much to be said for failure. It is much more interesting than success." This CCR Focus section is aimed at identifying lessons to be learned from difficulties encountered in recent years during development of anticancer agents. Clearly, we have not found a silver bullet tyrosine kinase inhibitor against solid tumors comparable with imatinib in chronic myelogenous leukemia. Although vemurafenib for B-Raf-mutated melanoma and crizotinib for non-small cell lung cancers with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements were developed rapidly and offer hope for individualized targeted therapies, the development of agents targeting a number of other pathways has been slower and less successful. These agents include drugs for blocking the insulin-like growth factor I/insulin receptor pathways, mitotic kinase inhibitors, and Hsp90 antagonists. Several potentially useful, if not groundbreaking, agents have had setbacks in clinical development, including trastuzumab emtansine, gemtuzumab ozogamicin, and satraplatin. From experience, we have learned the following: (i) not every altered protein or pathway is a valid anticancer target; (ii) drugs must effectively engage the target; (iii) the biology of the systems we use must be very well understood; and (iv) clinical trials must be designed to assess whether the drug reached and impaired the target. It is also important that we improve the drug development enterprise to enhance enrollment, streamline clinical trials, reduce financial risk, and encourage the development of agents for niche indications. Such enormous challenges are offset by potentially tremendous gains in our understanding and treatment of cancer.

  4. COMPETITIVENESS IN SERVICES, DRIVING FORCE OF ECONOMIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    RAMONA PÎRVU

    2012-12-01

    Full Text Available The competitiveness of a nation is ensured by the profitable activity of firms. They strengthen their position in the domestic and international markets through global strategies whose purpose is to increase productivity and maintain it at a high level. For this, the company must take into account both the internal economic environment which ensures operating conditions and the external economic environment’s development. The five competitive forces determine the industry’s profitability because they configure firms’ selling prices, production costs and investments needed to be competitive in the field. The threat of new competitors limits the potential profit since they involve new production units and the opportunities for market expansion. Economic strength of the buyers and bidders attracts profits to them. Rivalry among existing competitors erodes profits by increasing costs of competition (like advertising, selling expenses or those required for research and development. The presence of substitutive goods or services limits competitors’ prices through buyers’ transfer phenomena limiting and eroding market share of industry / firm in the total production output.

  5. Drugs in development for relapsing multiple sclerosis.

    Science.gov (United States)

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral

  6. Developing a competitive advantage in the market for radiology services.

    Science.gov (United States)

    Kropf, R; Szafran, A J

    1988-01-01

    This article describes how managers of outpatient diagnostic radiology services can develop a competitive advantage by increasing the value of services to patients and referring physicians. A method is presented to identify changes to services that increase their value. The method requires the definition of the "value chains" of patients and referring physicians. Particular attention is paid to the use of information systems technology to suggest and implement service changes. A narrow range of health services was selected because the approach requires a detailed understanding of consumers and how they use services. The approach should, however, be examined carefully by managers seeking to develop a competitive advantage for a wide range of health services.

  7. Developing a new stochastic competitive model regarding inventory and price

    Science.gov (United States)

    Rashid, Reza; Bozorgi-Amiri, Ali; Seyedhoseini, S. M.

    2015-01-01

    Within the competition in today's business environment, the design of supply chains becomes more complex than before. This paper deals with the retailer's location problem when customers choose their vendors, and inventory costs have been considered for retailers. In a competitive location problem, price and location of facilities affect demands of customers; consequently, simultaneous optimization of the location and inventory system is needed. To prepare a realistic model, demand and lead time have been assumed as stochastic parameters, and queuing theory has been used to develop a comprehensive mathematical model. Due to complexity of the problem, a branch and bound algorithm has been developed, and its performance has been validated in several numerical examples, which indicated effectiveness of the algorithm. Also, a real case has been prepared to demonstrate performance of the model for real world.

  8. Competitive binding of fluoroquinolone antibiotics and some other drugs to human serum albumin: a luminescence spectroscopic study.

    Science.gov (United States)

    Seedher, Neelam; Agarwal, Pooja

    2013-01-01

    Co-administration of several drugs in multidrug therapy may alter the binding of each to human serum albumin (HSA) and hence their pharmacological activity. Thirty-two frequently prescribed drug combinations, consisting of four fluoroquinolone antibiotics and eight competing drugs, have been studied using fluorescence and circular dichroism spectroscopic techniques. Competitive binding studies on the drug combinations are not available in the literature. In most cases, the presence of competing drug decreased the binding affinity of fluoroquinolone, resulting in an increase in the concentration of free pharmacologically active drug. The competitive binding mechanism involved could be interpreted in terms of the site specificity of the binding and competing drugs. For levofloxacin, the change in the binding affinity was small because in the presence of site II-specific competing drugs, levofloxacin mainly occupied site I. A competitive interference mechanism was operative for sparfloxacin, whereas competitive interference as well as site-to-site displacement of competing drugs was observed in the case of ciprofloxacin hydrochloride. For enrofloxacin, a different behavior was observed for different combinations; site-to-site displacement and conformational changes as well as independent binding has been observed for various drug combinations. Circular dichroism spectral studies showed that competitive binding did not cause any major structural changes in the HSA molecule. Copyright © 2013 John Wiley & Sons, Ltd.

  9. STRATEGIES FOR DEVELOPING SUSTAINABLE AND COMPETITIVE CLUSTER FOR SHRIMP INDUSTRY

    Directory of Open Access Journals (Sweden)

    Anas M. Fauzi

    2012-09-01

    Full Text Available Kampung Vannamei as shrimp cluster is being developed since 2004 by PT CP Prima, tbk Surabaya through Shrimp Culture Health Management transformation technology to several traditional farmers in Gresik, Lamongan, Tuban, and Madura areas. The research objectives aims to identify and mapping of stakeholder, to analyze interaction of stakeholders, to formulate strategy from internal and external environment factors and to set priority on strategy to develop sustainable and competitive shrimp cluster in the Kampung vannamei. Primary data was collected through stakeholders’ discussion forums, questionnaires, and interviews with relevant actors. Observations to the business unit also performed to determine the production and business conditions, particularly in capturing information about the threat and challenges. While the secondary data is used in policy documents national and local area statistics, and relevant literature. Analyses were performed by using the SRI International cluster pyramid, diamond porter’s analysis, SWOT and Matrix TOWS analysis, and analytical hierarchy process. Analyses were performed by the methods discussed in qualitative and descriptive. There are 7 strategies could be implemented to develop sustainable and competitive shrimp cluster. However, it is recommended to implement the strategy base on priority, which the first priority is strategy to improve linkages between businesses in the upstream and downstream industries into multi stakeholders’ platform in shrimp industry.Keywords: Shrimp, Cluster, Competitiveness, Diamond Porter, SWOT Analysis, AHP

  10. SMEs, Competition and Entry - A developing country perspective

    DEFF Research Database (Denmark)

    Jensen, Camilla

    . The main research question is why it is so difficult for new entrepreneurs to enter markets, or in other words, why are the barriers to entry seemingly higher in developing countries? Development writers such as Hernando de Soto and Daron Acemoglu suggest that this question is closely related...... such as competition policy. The model is tested using the World Bank's BEEPS dataset which is a repeated cross section survey of firms across countries in development and transition. This data gives access to observe among other firm size and whether firms pay a bribe or not. This data is combined with Stephan Voigt...

  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 a

  12. 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

  13. Development of competitive immunoassays to hydroxyl containing fungicide metabolites.

    Science.gov (United States)

    Gough, Kevin C; Jarvis, Shila; Maddison, Ben C

    2011-01-01

    This paper describes the isolation of monoclonal antibodies and the development of competitive immunoassays to pesticide metabolites of the fungicides imazalil, carbendazim and thiabendazole. The metabolite specific hydroxyl residues were used as the reactive group with which to link the metabolite to the carrier proteins Keyhole Limpet Haemocyanin (KLH) and Bovine Serum Albumin (BSA). In each case immune responses in mice were raised and monoclonal antibodies were produced. Antibodies were developed into competitive ELISAs to the appropriate metabolite. The antibody raised to a metabolite of imazalil was optimised into a competitive ELISA format which had an assay IC50 of 7.5 μg/L and a limit of detection (LOD) of 1.1 μg/L. A single antibody isolated against the metabolite of carbendazim had assay IC50s of 3.2 and 2.7 μg/L for the metabolites of carbendazim and thiabendazole respectively with an LOD of 0.38 μg/L for both. These sensitive immunoassays may have application in the monitoring of human exposure to these fungicide residues either by occupational or non-occupational routes.

  14. Phase IV of Drug Development.

    Science.gov (United States)

    Suvarna, Viraj

    2010-04-01

    Not all Phase IV studies are post-marketing surveillance (PMS) studies but every PMS study is a phase IV study. Phase IV is also an important phase of drug development. In particular, the real world effectiveness of a drug as evaluated in an observational, non-interventional trial in a naturalistic setting which complements the efficacy data that emanates from a pre-marketing randomized controlled trial (RCT). No matter how many patients are studied pre-marketing in a controlled environment, the true safety profile of a drug is characterized only by continuing safety surveillance through a spontaneous adverse event monitoring system and a post-marketing surveillance/non-interventional study. Prevalent practice patterns can generate leads that could result in further evaluation of a new indication via the RCT route or even a signal that may necessitate regulatory action (change in labeling, risk management/minimization action plan). Disease registries are another option as are the large simple hybrid trials. Surveillance of spontaneously reported adverse events continues as long as a product is marketed. And so Phase IV in that sense never ends.

  15. Phase IV of Drug Development

    Directory of Open Access Journals (Sweden)

    Viraj Suvarna

    2010-01-01

    Full Text Available Not all Phase IV studies are post-marketing surveillance (PMS studies but every PMS study is a phase IV study. Phase IV is also an important phase of drug development. In particular, the real world effectiveness of a drug as evaluated in an observational, non-interventional trial in a naturalistic setting which complements the efficacy data that emanates from a pre-marketing randomized controlled trial (RCT. No matter how many patients are studied pre-marketing in a controlled environment, the true safety profile of a drug is characterized only by continuing safety surveillance through a spontaneous adverse event monitoring system and a post-marketing surveillance/non-interventional study. Prevalent practice patterns can generate leads that could result in further evaluation of a new indication via the RCT route or even a signal that may necessitate regulatory action (change in labeling, risk management/minimization action plan. Disease registries are another option as are the large simple hybrid trials. Surveillance of spontaneously reported adverse events continues as long as a product is marketed. And so Phase IV in that sense never ends.

  16. 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.

  17. The Development of Procedures for Identifying Competitive Behavior in Children

    Science.gov (United States)

    Mithaug, Dennis E.

    1973-01-01

    Identifies events in the competitive process that could be employed to discriminate between competition and individual, nonsocial behaviors. If a subject is working for the competitive contingency and checks his progress against another's, his behavior may be classified as competitive rather than individual, nonsocial behavior. (DP)

  18. Overseas Merger: Breakthrough of Developing Countries to Strengthen Competitiveness

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ At the beginning of this year, Lenovo Group purchased the PC business including production, marketing,research and development of worldfamous IBM with the US$1.25 billion.In this way,Lenovo Group ranks among the front three strongest of world IT industry. This made Chinese excited. Before, TCL Group purchased color TV and DVD business of famous brand Thompson France. These events proved the competitiveness of China's economy after joining WTO, though face all sorts of pressures and challenges, at the same time the world market offered the new opportunity for the development of China's economy.

  19. Indirect competitive assays on DVD for direct multiplex detection of drugs of abuse in oral fluids.

    Science.gov (United States)

    Zhang, Lingling; Li, Xiaochun; Li, Yunchao; Shi, Xiaoli; Yu, Hua-Zhong

    2015-02-03

    On-site oral fluid testing for drugs of abuse has become prominent in order to take immediate administrative action in an enforcement process. Herein, we report a DVD technology-based indirect competitive immunoassay platform for the quantitative detection of drugs of abuse. A microfluidic approach was adapted to prepare multiplex immunoassays on a standard DVD-R, an unmodified multimode DVD/Blu-Ray drive to read signal, and a free disc-quality analysis software program to process the data. The DVD assay platform was successfully demonstrated for the simultaneous, quantitative detection of drug candidates (morphine and cocaine) in oral fluids with high selectivity. The detection limit achieved was as low as 1.0 ppb for morphine and 5.0 ppb for cocaine, comparable with that of standard mass spectrometry and ELISA methods.

  20. Drug-induced liver injury and drug development: industry perspective.

    Science.gov (United States)

    Regev, Arie

    2014-05-01

    Despite intensive ongoing research, drug-induced live injury (DILI) remains a serious issue for care providers and patients, and has been a major cause of drug withdrawal and non-approval by regulatory authorities in the past 50 years. Consequently, DILI remains a major concern for the pharmaceutical industry and a leading cause for attrition during drug development. In most instances, severe DILI is an uncommon idiosyncratic reaction, which typically does not present during preclinical phases or early clinical phases of drug development. In the majority of cases, drugs that caused severe DILI in humans have not shown clear and consistent hepatotoxic signals in preclinical assessment including animal studies, cell cultures, or other methods. Despite intensive efforts to develop better biomarkers that would help in predicting DILI risk in earlier phases of drug development, such biomarkers are currently not supported by sufficient evidence and are not yet available for routine use by drug makers. Due to the lack of effective and accurate methods for prediction of idiosyncratic DILI during preclinical phases of drug development, different drug makers have adopted different approaches, which are often not supported by strong systematic evidence. Based on growing experience, it is becoming increasingly evident that milder forms of liver injury occurring during clinical development, when assessed correctly, may significantly enhance our ability to predict the drug's potential to cause more severe liver injury postmarketing. Strategies based on this concept have been adopted by many drug makers, and are being increasingly implemented during drug development. Meticulous causality assessment of individual hepatic cases and adherence to strict hepatic discontinuation rules are critical components of this approach and have to rely on thorough clinical evaluation and occasionally on assessment by liver experts experienced with DILI and drug development.

  1. Bioavailability and Bioequivalence in Drug Development.

    Science.gov (United States)

    Chow, Shein-Chung

    2014-01-01

    Bioavailability is referred to as the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. The relative bioavailability in terms of the rate and extent of drug absorption is considered predictive of clinical outcomes. In 1984, the United States Food and Drug Administration (FDA) was authorized to approve generic drug products under the Drug Price Competition and Patent Term Restoration Act based on evidence of average bioequivalence in drug absorption through the conduct of bioavailability and bioequivalence studies. This article provides an overview (from an American point of view) of definition of bioavailability and bioequivalence, Fundamental Bioequivalence Assumption, regulatory requirements, and process for bioequivalence assessment of generic drug products. Basic considerations including criteria, study design, power analysis for sample size determination, and the conduct of bioequivalence trial, and statistical methods are provided. Practical issues such as one size-fits-all criterion, drug interchangeability and scaled average criteria for assessment of highly variable drug products are also discussed.

  2. Carbohydrate drugs: current status and development prospect.

    Science.gov (United States)

    Zhang, Yan; Wang, Fengshan

    2015-04-01

    In recent years, there has been a great effort devoted to the investigation of the roles of carbohydrates in various essential biological processes and the development of carbohydrates to therapeutic drugs. This review summarizes the carbohydrate drugs which have been recorded in several pharmacopoeias, marketed, and under development. A prospect of the future development of carbohydrate drugs is discussed as well.

  3. Competitiveness as an Indicator of Sustainable Development of Tourism: Applying Destination Competitiveness Indicators to Ethiopia

    NARCIS (Netherlands)

    Wondowossen, T.A.; Nakagoshi, N.; Yukio, Y.; Jongman, R.H.G.; Dawit, A.Z.

    2014-01-01

    Competitiveness can be applied to predict the economic sustainability of tourism in destinations which has been measured in terms of leakages and linkage related to employment and income generation opportunities to the destinations. This article examines destination competitiveness of Ethiopia based

  4. Development of Competitive Gas Trading in Continental Europe

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    In this publication the IEA examines the history of major gas markets' development in OECD Europe, and explores the possible expansion of trading through the mechanism of different hubs across the region. Lessons learned from North American markets on the benefits of regulatory convergence and investor-friendly legal framework are an important part of the analysis. Competitive trading based on transparent, non-discriminatory rules in a flexible and integrated European gas market will lead to more efficiency, timely investment, and greater market resilience, therefore ensuring more security for both customers and suppliers in the long term.

  5. Competitive diffusion of new prescription drugs: The role of pharmaceutical marketing investment

    NARCIS (Netherlands)

    Ruiz Conde, Enar; Wieringa, Jaap; Leeflang, Peter

    2014-01-01

    We investigate the impact of marketing interventions on the diffusion of new products in a competitive setting. We develop a family of trial–repeat diffusion models to identify the longitudinal effects of marketing efforts, and complement this with a cross-sectional analysis to identify the between-

  6. Information needs and the role of text mining in drug development.

    Science.gov (United States)

    Roberts, Phoebe M; Hayes, William S

    2008-01-01

    Drug development generates information needs from groups throughout a company. Knowing where to look for high-quality information is essential for minimizing costs and remaining competitive. Using 1131 research requests that came to our library between 2001 and 2007, we show that drugs, diseases, and genes/proteins are the most frequently searched subjects, and journal articles, patents, and competitive intelligence literature are the most frequently consulted textual resources.

  7. SMEs, Competition and Entry - A developing country perspective

    DEFF Research Database (Denmark)

    Jensen, Camilla

    with a sizeable informal sector in developing countries and corruption. Other leading transition researchers such as Andrei Shleifer offer a variety of views on the informal sector from the romantic to the parasitic. This paper leans on the realist interpretation of de Soto grounded in institutional theory. High...... entry barriers push the entrepreneurs towards the informal sector. Whether entrepreneurs succeed in the transition towards the formal sector depends on the size of the entry barriers which are indirectly regulated both by informal institutions such as corruption and formal institutions...... such as competition policy. The model is tested using the World Bank's BEEPS dataset which is a repeated cross section survey of firms across countries in development and transition. This data gives access to observe among other firm size and whether firms pay a bribe or not. This data is combined with Stephan Voigt...

  8. Develop Intra-county Economy in the Differentiated Competition

    Institute of Scientific and Technical Information of China (English)

    Pan Xining; Xiong Qidong

    2004-01-01

    @@ Build 1 00 Ii Long Corridor in the Differentiated Competition with Mount Lushan Mount Lushan is the cultural heritage of the world, and a trump of development of tourist industry of Xingzi County. It is the key to accelerate tourism of the county. So, we should compete with Mount Lushan and develop "three springs" and long corridor to form "one corridor, ten scenery places, one hundred hotels, a thousand villas, ten thousands berths, 100,000employees, a million visitors, ten millions tax revenues, hundreds of millions of output" and stress on recreation and conferences, strengthen joint and interaction, support the markets of two places, benefits-sharing and realize win-win strategy.

  9. COMPETITIVENESS OF LEADING COMMODITIES TO SUPPORT DEVELOPING REGION OF AGROTOURISM

    Directory of Open Access Journals (Sweden)

    Murwatiningsih Murwatiningsih

    2013-10-01

    Full Text Available AbstractThe aim of the research is to seek the competitiveness of the leading commodity in Semarang city which supports the development of centre commodity in agrotourism area. The method of analysis is leading sector, scoring analysis and capacity asessment through FGD. The result of the research reveals that leading commodities are Durian, Longan, Water Apple, and Rambutan. It is found that subdistrict Gunungpati and Mangunsari are ready to be the centre of horticulture commodity because its strategic location. It is located nearby Jatibarang reservoir (potential to be a tourism village, its cultivation is relatively successful, accessable transportation, and good management. Hence, it can be the pilot project area.Key words: competitiveness, centre, commodity, horticultureJEL Classification: O20, Q10AbstrakKesejahteraan petani tidak meningkat karena daya saingnya rendah dan pengelolannya tidak optimal. Tujuan penelitian, untuk melihat daya saing komoditas unggulan Kota Semarang untuk mendukung pengembangan sentra komoditas di kawasan agrowisata. Metode analisis yaitu sektor basis, analisis scoring serta capacity assessment melalui FGD. Hasil penelitian menunjukkan komoditas yang diunggulkan di Gunungpati adalah durian, klengkeng, jambu air dan rambutan. Kelurahan Gunungpati dan Mangunsari siap dijadikan sentra komoditas hortikultura di Kecamatan Gunungpati karena letaknya strategis- dekat dengan waduk Jatibarang (dapat menjadi desa wisata, budidaya relatif lebih berhasil, transportasi dan akseptibilitas lebih mudah, pengelolaannya bagus sehingga sudah menjadi daerah percontohan.Kata Kunci: daya saing, sentra, komoditas, hortikulturJEL Classification: O20, Q10

  10. Anticonvulsant drugs, growth, and development.

    OpenAIRE

    Macardle, B M; McGowan, M E; Greene, S.A.; Miller, C.S.

    1987-01-01

    Height and stage of puberty of 67 children with epilepsy were measured before beginning treatment with anticonvulsant drugs and annually to a maximum five years' treatment. Blood concentrations of the drugs used (phenytoin, sodium valproate, carbamazepine, ethosuximide, and phenobarbitone) were monitored throughout. No significant deviation in growth patterns was detected.

  11. Towards a sustainable system of drug development.

    Science.gov (United States)

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

    2014-11-01

    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 and the pharmaceutical industry, we identified the main factors causing this system failure. Although many solutions have been suggested to fix the drug development system, we believe that a combination of reforms of the regulatory and patent systems is necessary to make drug development sustainable. These reforms must be combined with a larger, open-access role for public research institutes in the discovery, clinical evaluation and safety evaluation of new drugs.

  12. LESSONS LEARNED Biosurveillance Mobile App Development Intern Competition (Summer 2013)

    Energy Technology Data Exchange (ETDEWEB)

    Noonan, Christine F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Henry, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Corley, Courtney D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-01-14

    The purpose of the lessons learned document for the BEOWulf Biosurveillance Mobile App Development Intern Competition is to capture the project’s lessons learned in a formal document for use by other project managers on similar future projects. This document may be used as part of new project planning for similar projects in order to determine what problems occurred and how those problems were handled and may be avoided in the future. Additionally, this document details what went well with the project and why, so that other project managers may capitalize on these actions. Project managers may also use this document to determine who the project team members were in order to solicit feedback for planning their projects in the future. This document will be formally communicated with the organization and will become a part of the organizational assets and archives.

  13. 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

  14. 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

  15. Children's Development through Sports Competition: Derivative, Adjustive, Generative, and Maladaptive Approaches

    Science.gov (United States)

    Choi, Hong Suk; Johnson, Britton; Kim, Young K.

    2014-01-01

    Sports competition can play an important role for children because it contributes to developmental outcomes for a healthy lifestyle. Through sports competition, children can learn about physical, social, and cognitive skills. Sports competition can be either positive or negative in terms of development, depending on how experiences are perceived…

  16. Children's Development through Sports Competition: Derivative, Adjustive, Generative, and Maladaptive Approaches

    Science.gov (United States)

    Choi, Hong Suk; Johnson, Britton; Kim, Young K.

    2014-01-01

    Sports competition can play an important role for children because it contributes to developmental outcomes for a healthy lifestyle. Through sports competition, children can learn about physical, social, and cognitive skills. Sports competition can be either positive or negative in terms of development, depending on how experiences are perceived…

  17. Medical imaging in new drug clinical development.

    Science.gov (United States)

    Wang, Yi-Xiang; Deng, Min

    2010-12-01

    Medical imaging can help answer key questions that arise during the drug development process. The role of medical imaging in new drug clinical trials includes identification of likely responders; detection and diagnosis of lesions and evaluation of their severity; and therapy monitoring and follow-up. Nuclear imaging techniques such as PET can be used to monitor drug pharmacokinetics and distribution and study specific molecular endpoints. In assessing drug efficacy, imaging biomarkers and imaging surrogate endpoints can be more objective and faster to measure than clinical outcomes, and allow small group sizes, quick results and good statistical power. Imaging also has important role in drug safety monitoring, particularly when there is no other suitable biomarkers available. Despite the long history of radiological sciences, its application to the drug development process is relatively recent. This review highlights the processes, opportunities, and challenges of medical imaging in new drug development.

  18. COMPETITIVE INTELLIGENCE AND DEVELOPING SUSTAINABLE COMPETITIVE ADVANTAGE/LA INTELIGENCIA COMPETITIVA Y EL DESARROLLO DE UNA VENTAJA COMPETITIVA SOSTENIBLE

    National Research Council Canada - National Science Library

    Nader Seyyed Amiri; Said Shirkavand; Mahjabin Chalak; Niloufar Rezaeei

    2017-01-01

    .... This paper discusses competitive Intelligence as a means of gaining competitive advantage for Insurance companies and seeks to study Its effects on creation of sustainable competitive advantage...

  19. The increasing of competitiveness as a strategic factor for economic development

    Directory of Open Access Journals (Sweden)

    R. Neykova

    2011-10-01

    Full Text Available The competitiveness is a crucial strategic factor that characterizes the Economic development of national economy, its sectors and enterprises. In the article we have analyzed and summarized different views of different authors. We have also revealed the main characteristics and conditions that influence the increase in competitiveness through the growing globalization and Economic crisis. We have investigated the role of the Economic integration, competition and business climate as crucial factors for increasing the competitiveness.

  20. Structural Development of Finnish Universities: Achieving Competitiveness and Academic Excellence

    Science.gov (United States)

    Tirronen, Jarkko; Nokkala, Terhi

    2009-01-01

    This paper discusses strategic instruments that are used to enhance the competitiveness of Finnish universities in the context of globalisation, internationalisation and commercialisation of research and education. The Finnish higher education system is currently undergoing a major policy reform, which aims to enhance the competitiveness of…

  1. Structural Development of Finnish Universities: Achieving Competitiveness and Academic Excellence

    Science.gov (United States)

    Tirronen, Jarkko; Nokkala, Terhi

    2009-01-01

    This paper discusses strategic instruments that are used to enhance the competitiveness of Finnish universities in the context of globalisation, internationalisation and commercialisation of research and education. The Finnish higher education system is currently undergoing a major policy reform, which aims to enhance the competitiveness of…

  2. The evolving drug development landscape: from blockbusters to niche busters in the orphan drug space.

    Science.gov (United States)

    Kumar Kakkar, Ashish; Dahiya, Neha

    2014-06-01

    Strategy, Management and Health Policy Large pharmaceutical companies have traditionally focused on the development of blockbuster drugs that target disease states with large patient populations. However, with large-scale patent expirations and competition from generics and biosimilars, anemic pipelines, escalating clinical trial costs, and global health-care reform, the blockbuster model has become less viable. Orphan drug initiatives and the incentives accompanied by these have fostered renewed research efforts in the area of rare diseases and have led to the approval of more than 400 orphan products. Despite targeting much smaller patient populations, the revenue-generating potential of orphan drugs has been shown to be huge, with a greater return on investment than non-orphan drugs. The success of these "niche buster" therapeutics has led to a renewed interest from "Big Pharma" in the rare disease landscape. This article reviews the key drivers for orphan drug research and development, their profitability, and issues surrounding the emergence of large pharmaceutical firms into the orphan drug space.

  3. Recent development in novel drug delivery systems of herbal drugs

    OpenAIRE

    Mayank Chaturvedi; Manish Kumar; Amit Sinhal; Alimuddin Saifi

    2011-01-01

    Novel technologies have been developed recently for drug delivery systems. The use of herbal formulations for novel drug delivery systems is more advantageous and has more benefits compared to others. The use of liposome, ethosome, phytosomes, emulsion, microsphere, solid lipid nanoparticles of herbal formulation has enhanced the therapeutic effects of plant extracts. With the use of all these, targeted delivery of the formulation is achieved, due to which the formulation demonstrates effect ...

  4. Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

    Science.gov (United States)

    Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.

    2007-01-01

    Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

  5. Innovative drug development for infertility therapy

    NARCIS (Netherlands)

    Mannaerts, B.M.J.L.

    2013-01-01

    Innovative drug development is essential to improve therapy over time by offering better efficacy, safety and/or treatment convenience. This thesis summarizes the sequential clinical development of three innovative fertility drugs namely follitropin-b (recombinant FSH), ganirelix (GnRH antagonist)

  6. 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.

  7. Linking pseudouridine synthases to growth, development and cell competition.

    Science.gov (United States)

    Tortoriello, Giuseppe; de Celis, José F; Furia, Maria

    2010-08-01

    Eukaryotic pseudouridine synthases direct RNA pseudouridylation and bind H/ACA small nucleolar RNA (snoRNAs), which, in turn, may act as precursors of microRNA-like molecules. In humans, loss of pseudouridine synthase activity causes dyskeratosis congenita (DC), a complex systemic disorder characterized by cancer susceptibility, failures in ribosome biogenesis and telomere stability, and defects in stem cell formation. Considering the significant interest in deciphering the various molecular consequences of pseudouridine synthase failure, we performed a loss of function analysis of minifly (mfl), the pseudouridine synthase gene of Drosophila, in the wing disc, an advantageous model system for studies of cell growth and differentiation. In this organ, depletion of the mfl-encoded pseudouridine synthase causes a severe reduction in size by decreasing both the number and the size of wing cells. Reduction of cell number was mainly attributable to cell death rather than reduced proliferation, establishing that apoptosis plays a key role in the development of the loss of function mutant phenotype. Depletion of Mfl also causes a proliferative disadvantage in mosaic tissues that leads to the elimination of mutant cells by cell competition. Intriguingly, mfl silencing also triggered unexpected effects on wing patterning and cell differentiation, including deviations from normal lineage boundaries, mingling of cells of different compartments, and defects in the formation of the wing margin that closely mimic the phenotype of reduced Notch activity. These results suggest that a component of the pseudouridine synthase loss of function phenotype is caused by defects in Notch signalling.

  8. Development, use and evaluation of drugs

    DEFF Research Database (Denmark)

    Hansen, E H; Launsø, Laila

    1987-01-01

    The article presents various perspectives of drug technology and health care policy in Denmark. Drugs dominate as the most widely used treatment technology in the health care system and the use of drugs is steadily increasing. The pharmaceutical industry's development of drugs is based...... on an economic estimate of developments, expenditures, marketing costs and the anticipated share of the market. Controlled clinical trials have become the main form of documentation required by the health authorities. This method is insufficient to evaluate the (side) effects of the drugs when in actual use....... Drugs fit perfectly the technical perception of disease, a perception which prevails in the pharmaceutical industry, medical science and in the treatment of disease. This perception believes that a disease is due to an attack or dysfunction in the biological-mechanical conditions of the individual...

  9. The Impact of Skills Development on Competitiveness: Empirical Evidence from a Cross-Country Analysis

    Science.gov (United States)

    Onsomu, Eldah N.; Ngware, Moses W.; Manda, Damiano K.

    2010-01-01

    In the past half-century, most countries have emphasized the development of human capital as an instrument for economic growth, sustainable development, and improved global competitiveness. However, limited evidence exists on the link between skills development and a country's competitiveness. This paper examines the contribution and association…

  10. Indoles - A promising scaffold for drug development.

    Science.gov (United States)

    Sravanthi, T V; Manju, S L

    2016-08-25

    Generally, heterocycles occupy a prominent place in chemistry due to their wide range of applications in the fields of drug design, photochemistry, agrochemicals, dyes and so on. Among them, indole scaffolds have been found in most of the important synthetic drug molecules and paved a faithful way to develop effective targets. Privileged structures bind to multiple receptors with high affinity, thus aiding the development of novel biologically active compounds. Among the indole class of compounds, 2-arylindoles appear to be a most promising lead for drug development. The derivatives of 2-arylindoles exhibits antibacterial, anticancer, anti-oxidants, anti-inflammatory, anti-diabetic, antiviral, antiproliferative, antituberculosis activity, etc. This article would provide a clear knowledge on the wide-ranging biological activities of 2-arylindoles over the past two decades, which would be beneficial for the designing of more potent drug targets in order to compete with the existing drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Trends in Anti-Epileptic Drug Development

    Directory of Open Access Journals (Sweden)

    Lennart Gram

    1990-01-01

    Full Text Available Several avenues are being explored in the development of new anti-epileptic drugs (AEDs. For a number of years efforts have been directed towards compounds which may augment neuronal inhibition, and these efforts have resulted in the development of several valuable drugs. More recently, increased attention has been focused on the role which excitatory transmitters may play in epileptogenesis, and various substances which decrease excitation are currently being investigated at the preclinical level. Since considerable potential still resides in several of the drugs already on the market, resources have been spent on trying to modify/improve the chemical formula of some of these substances, and a number of new drugs has emerged as a result of this approach. The major accomplishments reviewed here in the development of new anti-epileptic drugs suggest that even more successful advances may be achieved in the near future.

  12. Improving the Tuberculosis Drug Development Pipeline

    OpenAIRE

    Evangelopoulos, D; McHugh, T D

    2015-01-01

    Mycobacterium tuberculosis is considered one of the most successful pathogens and multidrug-resistant tuberculosis, a disease that urgently requires new chemical entities to be developed for treatment. There are currently several new molecules under clinical investigation in the tuberculosis (TB) drug development pipeline. However, the complex lifestyle of M. tuberculosis within the host presents a barrier to the development of new drugs. In this review, we highlight the reasons that make TB ...

  13. 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 du

  14. Market Structure in the Context of Developing Competitive Strategy

    Directory of Open Access Journals (Sweden)

    Algirdas Krivka

    2011-04-01

    Full Text Available The abstract deals with the application of positioning strategies under the conditions of classical market structures. It is discovered that the assumptions of pure competition leave no space for M. Porter’s generic cost leadership and differentiation strategies to be applied. The enterprise’s actions, influencing five competitive forces and implementing generic strategies, are reasonable under the conditions of imperfect competition market structures. The game theory models, applied to oligopoly, indicate the close interaction of enterprises and interdependence of their strategic decisions: cost reduction and differentiation strategies not only increase the profit of the enterprise, implementing the strategy, but by affecting market price and residual demand decrease the competitor’s profit.Article in Lithuanian

  15. Developments and competitiveness of Mozambican chicken meat industry

    Directory of Open Access Journals (Sweden)

    Carlos Alberto de Oliveira

    2015-12-01

    Full Text Available Mozambican poultry industry might be an option to facilitate people's access to animal protein, as well as to reduce the dependence on imports of the product, bringing jobs and income forth. This study aimed to characterize and to analyze the competitiveness of poultry industry in Mozambique. Porter’s Five Forces Model, which focuses on the five strengths that shape business competition, was applied. The results show a low level of competition within the industry, a limited supply of raw material and the fact that national products are commodities and competes with strong foreign participants. Domestic demand for chicken meat is increasing, but buyers base their decision mainly on price. Challenges include establishment of governance structure and policies for poultry sector and consumer welfare. Another alternative to improve the poultry industry in Mozambique is to promote technical cooperation with other countries, such as Brazil, in order to acquire specific structures for chicken production, genetic material and adequate nutrition.

  16. Developing doctoral scientists for drug discovery: pluridimensional education required.

    Science.gov (United States)

    Janero, David R

    2013-02-01

    Research universities continue to produce new scientists capable of generating knowledge with the potential to inform disease etiology and treatment. Mounting interest of doctoral-level experimental science students in therapeutics-related research careers is discordant with the widespread lack of direct drug-discovery and development experience, let alone commercialization success, among university faculty and administrators. Likewise, the archetypical publication- and grant-fueled, principal investigator (PI)-focused academic system ("PI-stan") risks commoditization of science students pursuing their doctorates as a labor source, rendering them ill-prepared for career options related to therapeutics innovation by marginalizing their development of "beyond-the-bench" professional skills foundational to modern drug-discovery campaigns and career fluency. To militate against professionalization deficits in doctoral drug-discovery researchers, the author--a scientist-administrator-consultant with decades of discovery research and development (R&D), business, and educator experience in commercial and university settings--posits a critical need for pluridimensionality in graduate education and mentorship that extends well beyond thesis-related scientific domains/laboratory techniques to instill transferable operational-intelligence, project/people-management, and communication competencies. Specific initiatives are advocated to help enhance the doctoral science student's market competitiveness, adaptability, and navigation of the significant research, commercial, and occupational challenges associated with contemporary preclinical drug-discovery R&D.

  17. Developing selection protocols for weed competitiveness in aerobic rice

    NARCIS (Netherlands)

    Zhao, D.L.; Atlin, G.N.; Bastiaans, L.; Spiertz, J.H.J.

    2006-01-01

    Aerobic rice production systems, wherein rice is dry-sown in non-puddled soil and grown as an upland crop, offer large water savings but are subject to severe weed infestation. Weed-competitive cultivars will be critical to the adoption of aerobic rice production by farmers. Breeding

  18. A competitive co-cultivation assay for cancer drug specificity evaluation.

    Science.gov (United States)

    El Debs, Bachir W; Tschulena, Ulrich; Griffiths, Andrew D; Merten, Christoph A

    2011-09-01

    The identification of compounds that specifically inhibit or kill cancer cells without affecting cells from healthy tissues is very challenging but very important for reducing the side effects of current cancer therapies. Hence, there is an urgent need for improved assays allowing the selectivity of a given compound to be monitored directly. The authors present an assay system based on the competitive co-cultivation of an excess of cancer cells with a small fraction of noncancer human indicator cells generating a fluorescence signal. In the absence of a specific anticancer compound, the cancer cells outgrow the indicator cells and abolish the fluorescence signal. In contrast, the presence of specific anticancer drugs (such as Tyrphostin-AG1478 or PLX4720) results in the selective growth of the indicator cells, giving rise to a strong fluorescence signal. Furthermore, the authors show that the nonspecific cytotoxic compound sodium azide kills both cancer and noncancer cells, and no fluorescence signal is obtained. Hence, this assay system favors the selection of compounds that specifically target cancer cells and decreases the probability of selecting nonspecific cytotoxic molecules. Z factors of up to 0.85 were obtained, indicating an excellent assay that can be used for high-throughput screening.

  19. GLOBAL COMPETITIVENESS IN THE CONTEXT OF SUSTAINABLE DEVELOPMENT: THE ROMANIAN CASE

    Directory of Open Access Journals (Sweden)

    Cecilia – Nicoleta Jurcuț (Aniș

    2015-09-01

    Full Text Available In an increasingly open and integrated world economy, competitiveness and sustainability have become a central preoccupation of both advanced and emerging countries. Thus, the goal of this paper is to research the interconnection between the competitiveness and sustainable development factors, based on the development of the concepts and current research tendencies. Using extensive data over a period of 10 years, this study explores and tests the sign of the relationship between national competitiveness and sustainable development indicators. Our findings are the basis of developing new models describing the relationships between competitiveness, economic growth and sustainability, justified by the need of sustainable economy’s development to increase the national competitiveness, in order to attract financial resources necessary for financing the growth of the economy and economic entities.

  20. Recent advances in (therapeutic protein) drug development

    Science.gov (United States)

    Lagassé, H.A. Daniel; Alexaki, Aikaterini; Simhadri, Vijaya L.; Katagiri, Nobuko H.; Jankowski, Wojciech; Sauna, Zuben E.; Kimchi-Sarfaty, Chava

    2017-01-01

    Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016). PMID:28232867

  1. UNREALIZED COMPETITIONS OF THE 1920-1930ies IN THE CONTEXT OF THE ARCHITECTURE DEVELOPMENT PROCESS

    Directory of Open Access Journals (Sweden)

    Dudka Elena Nikolaevna

    2012-10-01

    Full Text Available Analysis of organizational and methodical issues associated with architectural competitions of the 1920-1930ss and evaluation of their results are provided in the article. The role of the architectural development and historical, cultural, social and ideological backgrounds of the architectural competitions are also covered by the author. The review of architectural competitions makes it possible to identify their impact produced on the development of the theory and practice of architecture. The period between 1920 and 1930 was marked by a quantitative and qualitative boom of architectural design competitions. Analysis of the practice of architectural competitions makes it possible to identify periods of revolutionary transformations. The most prominent buildings that date back to these periods include theatre buildings in Kharkov, Rostov-Don, Sverdlovsk; a competition for the architectural design of the Gosprom Building in Kharkov; a competition for the architectural design of the Palace of Soviets in Moscow, etc. These competitions have shaped up new approaches to volume and space-related solutions as well as architectural forms. Research of the integral process of development of approaches and/or methods of organization of architectural design competitions make it possible to identify their role as effective catalysts of architectural theory and practice.

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

    African Journals Online (AJOL)

    Development, the pharmaceutical industry has a strong incentive to ... per head on all health programmes whereas it is less than $6 in ... is loans and grants from donor countries and almost ... production capacity through technology transfer so.

  3. Membrane transporters and new drug development

    Institute of Scientific and Technical Information of China (English)

    EndoH

    2002-01-01

    Molecular biology has made it possible to identify membrane transporter molecules that transport hydrophilic endogenous and exogenous compounds across cellular membranes.Ther are two possibilities on transporters relevant to new drug development,drug targets and pharmacokinetics.Human genome database predicts that more than 10% of common diseases may be tightly related with membrane transporter dysfunction.Thus,membrane transporters would be possible molecular targets for new drug development.As an example,I will talk on our discovery of L-type amino acid transporter 1(LAT1) being oncofetal and upregulated in cancers for their rapid growth and metastasis.We provide evidence that inhibition of LAT1 functions may become novel types of anticancer tools.As another example in human pharmacokinetics,application of stable expressing cell lines of human drug transporters will be proposed including organic anion and cation transporters which are distributed in various organs including the liver and kidney.These transporters are multispecific in their substrate recognition,and better molecules to anticipate drug-drug interactions in human bodies before new drug candidates are given in clinical trials.This in vitro technique may contribute to decide suitable compounds in particular by high throughout screening strategy.

  4. Alzheimer's disease drug development: translational neuroscience strategies.

    Science.gov (United States)

    Cummings, Jeffrey L; Banks, Sarah J; Gary, Ronald K; Kinney, Jefferson W; Lombardo, Joseph M; Walsh, Ryan R; Zhong, Kate

    2013-06-01

    Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.

  5. Trial geography, pharmacogenetics, and global drug development.

    Science.gov (United States)

    Schuck, R N; Florian, J; Charlab, R; Pacanowski, M

    2015-03-01

    Drug development is increasingly global. The benefits of multiregional trials include worldwide evaluation of safety and efficacy. However, clinical practice, environmental, and genetic factors can vary across geographic regions, significantly influencing trial outcomes within a specific geographic region or the global population relative to the United States (US). Genomic technologies and research discoveries continue to advance at a remarkable pace, offering opportunities to explore intrinsic factors that could account for regional variability in drug pharmacokinetics or response.

  6. Methodology of Remote Control of Competitive Swimmers’ Individual Energetic Profile Development

    Directory of Open Access Journals (Sweden)

    Kh.A. Sanosyan

    2012-06-01

    Full Text Available The offered approach helps to estimate the correlation of swimmer’s major energetic mechanisms distantly (remotely in parallel to competition (training, basing on data, got by means of GPS and other devices. This methodology promotes efficient use of means of educational control, developed and tested before, implementing the concept of parallel control over training and competition.

  7. The Effects of Athletic Competition on Character Development in College Student Athletes

    Science.gov (United States)

    Stoll, Sharon Kay

    2012-01-01

    This article argues that there are inherent problems in athletic competition relating to character development in college student athletes. A review of the research supports the claim that athletic competitions do not build character. The author proposes ways to address this problem and provides personal observations and published research to…

  8. TRPV3 in Drug Development

    Directory of Open Access Journals (Sweden)

    Lisa M. Broad

    2016-09-01

    Full Text Available Transient receptor potential vanilloid 3 (TRPV3 is a member of the TRP (Transient Receptor Potential super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1, however, genetic mutations and use of gene knock-outs and selective pharmacological tools are helping to provide insights into its role and therapeutic potential. TRPV3 is highly expressed in skin, where it is implicated in skin physiology and pathophysiology, thermo-sensing and nociception. Gain of function TRPV3 mutations in rodent and man have enabled the role of TRPV3 in skin health and disease to be particularly well defined. Pre-clinical studies provide some rationale to support development of TRPV3 antagonists for therapeutic application for the treatment of inflammatory skin conditions, itch and pain. However, to date, only one compound directed towards block of the TRPV3 receptor (GRC15300 has progressed into clinical trials. Currently, there are no known clinical trials in progress employing a TRPV3 antagonist.

  9. 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

  10. Research on the Internationalization Trend for the Development of Worldwide Competitive Ball Games and Our Countermeasures

    Institute of Scientific and Technical Information of China (English)

    Yixin Ma

    2015-01-01

    With the progress of physical and sports industry in the world, the analysis of sport industry in China is greatly needed. In this paper, we take discussion the internationalization trend for the development of worldwide competitive ball games and our countermeasures. With the acceleration of global economic integration the frequent personnel exchanges between different countries and nations, nationalities has change.. Physical exercise is beneficial for enhancing national constitution and physique in China, and achieving higher level of national constitution and competitive application in China. Through the proposed research, we could obtain positive development of Chinese competitive ball ~ames' development and harvest.

  11. Practice of Regulatory Science (Drug Development).

    Science.gov (United States)

    Kawanishi, Toru

    2017-01-01

     The practice of regulatory science (RS) for drug development is described. In the course material for education in pharmaceutical sciences drafted by the RS Division of the Pharmaceutical Society of Japan, RS for pharmaceuticals is defined as the science of predicting, assessing, and judging the quality, efficacy, and safety of pharmaceutical products throughout their lifespan. RS is also described as an integrated science based on basic and applied biomedical sciences, including analytical chemistry, biochemistry, pharmacology, toxicology, genetics, biostatistics, epidemiology, and clinical trial methodology, and social sciences such as decision science, risk assessment, and communication science. The involvement of RS in drug development generally starts after the optimization of lead compounds. RS plays important roles governing pharmaceuticals during their entire life cycle management phase as well as the drug development phase.

  12. Steady Increase In Prices For Oral Anticancer Drugs After Market Launch Suggests A Lack Of Competitive Pressure.

    Science.gov (United States)

    Bennette, Caroline S; Richards, Catherine; Sullivan, Sean D; Ramsey, Scott D

    2016-05-01

    The cost of treating cancer has risen to unprecedented heights, putting tremendous financial pressure on patients, payers, and society. Previous studies have documented the rising prices of cancer drugs at launch, but less critical attention has been paid to the cost of these drugs after launch. We used pharmacy claims for commercially insured individuals to examine trends in postlaunch prices over time for orally administered anticancer drugs recently approved by the Food and Drug Administration (FDA). In the period 2007-13, inflation-adjusted per patient monthly drug prices increased 5 percent each year. Certain market changes also played a role, with prices rising an additional 10 percent with each supplemental indication approved by the FDA and declining 2 percent with the FDA's approval of a competitor drug. Our findings suggest that there is currently little competitive pressure in the oral anticancer drug market. Policy makers who wish to reduce the costs of anticancer drugs should consider implementing policies that affect prices not only at launch but also later.

  13. 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.

  14. Neoadjuvant breast cancer therapy and drug development.

    Science.gov (United States)

    Cortazar, Patricia; Kluetz, Paul G

    2015-11-01

    Neoadjuvant treatment of breast cancer initially was limited to patients with locally advanced breast cancer in which downstaging was necessary. Now, neoadjuvant trials have become an increasingly common way to facilitate the rapid assessment of new cancer therapies. The appeal of neoadjuvant trials is that they provide the opportunity to study translational science, tumor biomarkers, and intermediate endpoints in response to systemic therapy within a shortened period. This review summarizes the data that contribute to our understanding of the association between pathological complete response and long-term outcomes, describes the implications of drug development and accelerated approval in neoadjuvant treatment of breast cancer, and provides a perspective on future neoadjuvant drug development.

  15. 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.

  16. Pathology in drug discovery and development.

    Science.gov (United States)

    Jubb, Adrian M; Koeppen, Hartmut; Reis-Filho, Jorge S

    2014-01-01

    The rapid pace of drug discovery and drug development in oncology, immunology and ophthalmology brings new challenges; the efficient and effective development of new targeted drugs will require more detailed molecular classifications of histologically homogeneous diseases that show heterogeneous clinical outcomes. To this end, single companion diagnostics for specific drugs will be replaced by multiplex diagnostics for entire therapeutic areas, preserving tissue and enabling rapid molecular taxonomy. The field will move away from the development of new molecular entities as single agents, to which resistance is common. Instead, a detailed understanding of the pathological mechanisms of resistance, in patients and in preclinical models, will be key to the validation of scientifically rational and clinically effective drug combinations. To remain at the heart of disease diagnosis and appropriate management, pathologists must evolve into translational biologists and biomarker scientists. Herein, we provide examples of where this metamorphosis has already taken place, in lung cancer and melanoma, where the transformation has yet to begin, in the use of immunotherapies for ophthalmology and oncology, and where there is fertile soil for a revolution in treatment, in efforts to classify glioblastoma and personalize treatment. The challenges of disease heterogeneity, the regulatory environment and adequate tissue are ever present, but these too are being overcome in dedicated academic centres. In summary, the tools necessary to overcome the 'whens' and 'ifs' of the molecular revolution are in the hands of pathologists today; it is a matter of standardization, training and leadership to bring these into routine practice and translate science into patient benefit. This Annual Review Issue of the Journal of Pathology highlights the central role for pathology in modern drug discovery and development.

  17. Environmental Compliance Costs in Developed Country Agricultures: Implications for Trade and Competitiveness

    NARCIS (Netherlands)

    Fox, G.; Brouwer, F.M.

    2012-01-01

    This chapter reflects on the costs of compliance with environmental regulations and standards in agriculture in developed countries, and its implications for trade and competitiveness. It highlights the importance of enforcement mechanisms and implementation, subjects which often have been undervalu

  18. 77 FR 6479 - Leased Commercial Access; Development of Competition and Diversity in Video Programming...

    Science.gov (United States)

    2012-02-08

    ... Programming Distribution and Carriage AGENCY: Federal Communications Commission. ACTION: Final rule... carriage of video programming vendors by multichannel video programming distributors (program carriage... and Order, Leased Commercial Access; Development of Competition and Diversity in Video...

  19. Competitive capabilities among manufacturing plants in developing, emerging, and industrialized countries : A comparative analysis

    NARCIS (Netherlands)

    Schoenherr, T.; Power, D.; Narasimhan, R.; Samson, D.

    2012-01-01

    Competitive capabilities have been defined as a plant's actual performance relative to its competitors, with the most commonly investigated capabilities being quality, delivery, flexibility, and cost. However, most research in this realm has investigated capabilities within developed countries, and

  20. [Adaptive clinical study methodologies in drug development].

    Science.gov (United States)

    Antal, János

    2015-11-29

    The evolution of drug development in human, clinical phase studies triggers the overview of those technologies and procedures which are labelled as adaptive clinical trials. The most relevant procedural and operational aspects will be discussed in this overview from points of view of clinico-methodological aspect.

  1. Development of Vocational Secondary School Students Competitiveness for Studies in the European Area of Higher Education

    OpenAIRE

    Olga Dementjeva

    2012-01-01

    ABSTRACT OF THE PROMOTION THESIS DEVELOPMENT OF VOCATIONAL SECONDARY SCHOOL STUDENTS’ COMPETITIVENESS FOR STUDIES IN THE EUROPEAN AREA OF HIGHER EDUCATION The promotion thesis „Development of Vocational Secondary School Students’ Competitiveness for Studies in the European Area of Higher Education” in the field of general pedagogy of pedagogical science has been worked out by Olga Dementjeva under the supervision of Dr. chem. Professor Andrejs Rauhvargers at the Depart...

  2. 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.

  3. AUSTRALIAN COMPETITION AND CONSUMER COMMISSION v PFIZER: EVERGREENING AND MARKET POWER AS A BLOCKBUSTER DRUG GOES OFF PATENT.

    Science.gov (United States)

    Faunce, Thomas

    2015-06-01

    In Australian Competition and Consumer Commission v Pfizer Australia Pty Ltd [2015] FCA 113, the ACCC alleged that Pfizer's "Project LEAP" involved a scheme to lock pharmacists into substituting its generic version of the high sales volume anti-cholesterol drug, patent-expired atorvastatin (Lipitor), which took advantage of a substantial degree of market power for a purpose proscribed by s 46(1)(c) of the Competition and Consumer Act 2010 (Cth). The ACCC also claimed that Pfizer's actions constituted a course of exclusive dealing pursuant to s 47(1)(d) and (e) for the proscribed purpose of lessening competition. Flick J in the Federal Court of Australia, in a judgment heavy with quotations but sparse in reasoning, dismissed the ACCC's Amended Originating Application alleging abuse of market power and ordered the ACCC to pay Pfizer's costs. The ACCC has now appealed the decision. This column explores this case in the context of Pfizer's broader strategies to preserve its income globally from this high sales volume drug in the period following its patent expiration.

  4. Persistent Pharmacokinetic Challenges to Pediatric Drug Development

    Directory of Open Access Journals (Sweden)

    Daniel eSage

    2014-08-01

    Full Text Available The development of new therapeutic agents for the mitigation of pediatric disorders is largely hindered by the inability for investigators to assess pediatric pharmacokinetics (PK in healthy patients due to substantial safety concerns. Pediatric patients are a clinical moving target for drug delivery due to changes in absorption, distribution, metabolism and excretion (ADME and the potential for PK related toxicological (T events to occur throughout development. These changes in ADMET can have profound effects on drug delivery, and may lead to toxic or sub-therapeutic outcomes. Ethical, economical, logistical, and technical barriers have resulted in insufficient investigation of these changes by industrial, regulatory, and academic bodies, leading to the classification of pediatric patients as therapeutic orphans. In response to these concerns, regulatory agencies have incentivized investigation into these ontogenic changes and their effects on drug delivery in pediatric populations. The intent of this review is to briefly present a synopsis of the development changes that occur in pediatric patients, discuss the effects of these changes on ADME and drug delivery strategies, highlight the hurdles that are still being faced, and present some opportunities to overcome these challenges.

  5. 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...... stage). Cytotoxins killing cells irrespective of the phase of the cell cycle will be able to kill slowly proliferating prostate cancer cells. Lack of selectivity, however, prevents their use as systemic drugs. Prostate cancer cells secrete characteristic proteolytic enzymes, e.g. PSA and hK2......, with unusual substrate specificity. Conjugation of cytotoxins with peptides, which are selective substrates for PSA or hK2, will afford prodrugs, from which the active drug only will be released in close vicinity of the cancer cells. Based on this strategy prodrugs targeted at prostate cancer cells have been...

  6. Current scenario of drug development for leishmaniasis.

    Science.gov (United States)

    Croft, Simon L; Seifert, Karin; Yardley, Vanessa

    2006-03-01

    Although three new drugs or drug formulations, liposomal amphotericin B (AmBisome), miltefosine and paromomycin should be available for the treatment of visceral leishmaniasis (VL) within the next year, they all suffer from limitations of either cost, specific toxicities or parenteral administration. As part of research to identify better treatments for VL and cutaneous leishmaniasis (CL), alternative and potentially cheaper formulations of amphotericin B, alklyphosphocholines other than miltefosine and improved formulations of paromomycin for CL have been identified. Other drugs or compounds that have demonstrated activity in experimental rodent models of infection include licochalcone derivatives, quinoline derivatives, bisphosphonates and a maesabalide; further chemistry based upon these leads is warranted. The process for discovery and development of new antileishmanials would also benefit from improved models, for example, transfected parasites, and non invasive methods of measuring parasite load in rodent models of infection.

  7. PERFORMANCE MEASUREMENT AND COMPETITIVE STRATEGY DEVELOPMENT OF STATE-OWNED ENTERPRISES IN CHINA

    Directory of Open Access Journals (Sweden)

    Xiaosong Zheng

    2015-04-01

    Full Text Available In the increasingly competitive market, the state-owned enterprises (SOEs in China, which dominate the national economy, have to take actions to enhance their competitive advantages in response to the competition. On one hand, competitive advantage of a company has impacts on its performance. On the other hand, the enterprise needs to develop competitive strategies related to its goals. Therefore, the two elements interact with each other. However, most scholars only focus on one aspect to do research, which resulted in incomplete findings. This article summarizes the development process of performance measurement in China and Western countries, based on performance measurement theory, and points out the disadvantages of the performance measurement system of state-owned enterprises in China. In addition, competitive strategies of company are sorted out. On the basis of existing research results, the article built a performance measurement index system which is used as a theoretical tool for case study. Then, through theoretical analysis and case studies of the two state-owned enterprises in the civil airline industry (China Eastern Airlines Corporation and China Southern Airlines Corporation, this article comprehensively analyzes and compares performance measurement of the two companies and the industry environment, suggests relevant competitive strategies for both companies. Finally, this article sums up the research results and makes suggestions for performance improvement.

  8. Animal models in drug development for MRSA.

    Science.gov (United States)

    Marra, Andrea

    2014-01-01

    One of the foremost challenges of drug discovery in any therapeutic area is that of solidifying the correlation between in vitro activity and clinical efficacy. Between these is the confirmation that affecting a particular target in vivo will lead to a therapeutic benefit. In antibacterial drug discovery, there is a key advantage from the start, since the targets are bacteria-therefore, it is simple to ascertain in vitro whether a drug has the desired effect, i.e., bacterial cell inhibition or killing, and to understand the mechanism by which that occurs. The downstream criteria, whether a compound reaches the infection site and achieves appropriately high levels to affect bacterial viability, can be evaluated in animal models of infection. In this way animal models of infection can be a highly valuable and predictive bridge between in vitro drug discovery and early clinical evaluation.The Gram-positive pathogen Staphylococcus aureus causes a wide variety of infections in humans (Archer, Clin Infect Dis 26:1179-1181, 1998) and has been said to be able to infect every tissue type. Fortunately, over the years a great deal of effort has been expended toward developing infection models in rodents using this organism, with good success. This chapter will describe the advantages, methods, and outcome measurements of the rodent models most used in drug discovery for S. aureus. Mouse models will be the focus of this chapter, as they are the most economical and thus most commonly used, but a rat infection model is included as well.

  9. pH-dependent drug-drug interactions for weak base drugs: potential implications for new drug development.

    Science.gov (United States)

    Zhang, L; Wu, F; Lee, S C; Zhao, H; Zhang, L

    2014-08-01

    Absorption of an orally administered drug with pH-dependent solubility may be altered when it is coadministered with a gastric acid-reducing agent (ARA). Assessing a drug's potential for pH-dependent drug-drug interactions (DDIs), considering study design elements for such DDI studies, and interpreting and communicating study results in the drug labeling to guide drug dosing are important for drug development. We collected pertinent information related to new molecular entities approved from January 2003 to May 2013 by the US Food and Drug Administration for which clinical DDI studies with ARAs were performed. On the basis of assessments of data on pH solubility and in vivo DDIs with ARAs, we proposed a conceptual framework for assessing the need for clinical pH-dependent DDI studies for weak base drugs (WBDs). Important study design considerations include selection of ARAs and timing of dosing of an ARA relative to the WBD in a DDI study. Labeling implications for drugs having DDIs with ARAs are also illustrated.

  10. Competitive capacity of HIV-1 strains carrying M184I or Y181I drug-resistant mutations

    Institute of Scientific and Technical Information of China (English)

    LI Jue; LI Lin; LI Han-ping; ZHUANG Dao-min; LIU Si-yang; LIU Yong-jian; BAO Zuo-yi; WANG Zheng; LI Jing-yun

    2009-01-01

    Background Virus with nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcdptase inhibitors (NNRTIs) resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance. For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine (3TC) or nevirapine (NVP) resistant mutations.Methods 3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay. Results 3TC-resistant (M184I mutation) and NVP-resistant (Y181I mutation) virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages.Conclusions The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.

  11. Competition and alliances in fuel cell power train development

    Energy Technology Data Exchange (ETDEWEB)

    Schlecht, L. [Technische Universitaet Berlin (Germany). Fuel Cell and Hydrogen Research Centre

    2003-07-01

    For the realisation of the effective application and cost effectiveness of fuel cell power trains, and competitiveness with the current internal combustion engine technology, it will be necessary to either: (a) produce a large number of vehicles, (b) reduce the production costs by permanent production optimisation, or (c) introduce new materials. Learning curves, which have been derived from empirical data of past energy technologies, are initially used to provide a cost prognosis for the market launch of fuel cell power trains. Drawing on game theory the paper then describes a basic model which addresses the issue of the optimal strategy of the automotive industry, in either a monopoly or oligopoly structure. When this model's outputs are combined with the anticipated rate of fuel cell vehicles (FCVs), learning curves and network effects, from the first section of the paper we can see that if the successful market launch of FCVs is desired, an alliance structure within the automotive industry is the optimal path. (author)

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

    OpenAIRE

    Hyeong-Min Lee; Yuna Kim

    2016-01-01

    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,...

  13. The Development of Drugs against Acanthamoeba Infections.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Aqeel, Yousuf; Khan, Naveed Ahmed

    2016-11-01

    For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Targets for anti-metastatic drug development.

    Science.gov (United States)

    Stock, Anna-Maria; Troost, Gabriele; Niggemann, Bernd; Zänker, Kurt S; Entschladen, Frank

    2013-01-01

    With a constant focus on the primary tumor, the current approaches in drug development in oncology yield dismal results. However over 90 percent of cancer deaths today are due to metastasis formation and yet there is no anti-metastatic drug on the market. Tumor cell migration is the essential prerequisite for invasion and metastasis formation. It is regulated by signal substances in terms of the grade of activity and in terms of direction (chemotaxis). The latter is important for the organotropism, the localization of metastasis in certain organs. Ligands to G protein-coupled receptors, mainly chemokines and neurotransmitters, as well as ligands to receptor kinases, mainly cytokines and growth factors, form the most important group of such regulators. We provide an overview of currently available agonists and antagonists to these receptors, which have a potential as anti-metastatic targets. Moreover we provide with the example of beta-blockers, how established drugs in other indications are possibly effective and can be co-opted as such anti-metastatics. The increasing knowledge of such regulators opens new opportunities to target cancer spreading and may put forth the development of antimetastatic drugs for oncological therapy.

  15. 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.

  16. Development of a Resource Allocation Model Using Competitive Advantage

    Directory of Open Access Journals (Sweden)

    Sangwon Lee

    2016-02-01

    Full Text Available In general, during decision making or negotiations, the investor and the investee may often have different opinions which result in conflicts. So, an objective standard to mitigate potential conflicts between investors and investees should be provided since it is highly important that rational decisions must be made when choosing investments from various options. However, the models currently used come with some problems for several reasons, for instance, the arbitrariness of the evaluator, the difficulty in understanding the relationships that exist among the various investment options (that is, alternatives to investments, inconsistency in priorities, and simply providing selection criteria without detailing the proportion of investment in each option or evaluating only a single investment option at a time without considering all options. Thus, in this research, we present a project selection model which can enable reasonable resource allocation or determination of return rates by considering the core competencies for various investment options. Here, core competency is based on both performance and ability to create a competitive advantage. For this, we deduce issue-specific structural power indicators and analyze quantitatively the resource allocation results based on negotiation power. Through this, it is possible to examine whether the proposed project selection model considers core competencies or not by comparing several project selection models currently used. Furthermore, the proposed model can be used on its own, or in combination with other methods. Consequently, the presented model can be used as a quantitative criterion for determining behavioral tactics, and also can be used to mitigate potential conflicts between the investor and the investee who are considering idiosyncratic investments, determined by an interplay between power and core competency.

  17. A Case for Developing Community Drug Indicators

    Science.gov (United States)

    Loughran, Hilda; McCann, Mary Ellen

    2011-01-01

    The EU Action Plan on Drugs (2005-2008) calls for member states of the European Union to provide information on five key epidemiological indicators. These are: general population surveys, prevalence and patterns of problem drug use, drug related infectious diseases, drug related deaths and mortality of drug users, and demand for drug treatment.…

  18. Effects of Psychostimulant Drugs on Developing Brain

    Directory of Open Access Journals (Sweden)

    Ibrahim Durukan

    2013-08-01

    Full Text Available Although psychostimulants have been used for the treatment of attention deficit hyperactivity disorder for approximately 70 years, little is known about the long term effects of these drugs on developing brain. The observable effects of psychostimulants are influenced by the timing of exposure, the age of examination after drug exposure and sex. Preclinical studies point out that chronic psychostimulant exposure before adolescence cause reverse sensitization or tolerance and this leads to reduction in stimulant effectiveness in adolesecence and adulthood. Preclinical studies show the potential long term effects of psychostimulants. But it is necessary to investigate the relationship between preclinical effects and clinical practice. A developmental approach is needed to understand the impact of pediatric medications on the brain that includes assessment at multiple ages to completely characterize the long term effects of these medications. The aim of this paper is to review the effects of psychostimulants on developing brain.

  19. Opioid Peptides: Potential for Drug Development

    OpenAIRE

    Aldrich, Jane V.; McLaughlin, Jay P.

    2012-01-01

    Opioid receptors are important targets for the treatment of pain and potentially for other disease states (e.g. mood disorders and drug abuse) as well. Significant recent advances have been made in identifying opioid peptide analogs that exhibit promising in vivo activity for treatment of these maladies. This review focuses on the development and evaluation of opioid peptide analogs demonstrating activity after systemic administration, and recent clinical evaluations of opioid peptides for po...

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

    Science.gov (United States)

    2010-06-08

    ... HUMAN SERVICES Food and Drug Administration 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 Administration (FDA) is establishing a public docket...

  1. Competitive advantage in the ERP system's value-chain and its influence on future development

    Science.gov (United States)

    Johansson, Björn; Newman, Mike

    2010-02-01

    Using the resource-based view, we present a set of propositions related to enterprise resource planning (ERP) development, reflections on competitive advantage and the different roles that stakeholders play in the value-chain. This has the goal of building a foundation for future research on ERPs and how stakeholders' desire to achieve competitive advantage influence ERP development, especially when it comes to development of a more standardised or pre-customised ERP system. The propositions also act as a foundation for increasing our knowledge concerning the difficulty in developing improved ERP systems.

  2. How Increased Competition from Generic Drugs Has Affected Prices and Returns in the Pharmaceutical Industry

    Science.gov (United States)

    1998-07-01

    are also at a present discounted value in 1990 dollars. 17. Z. John Lu and William S. Comanor, Strategic Pricing of New Pharmaceuticals , Working...competed were available at a lower price. 24. Lu and Comanor, Strategic Pricing of New Pharmaceuticals . CHAPTER THREE PRICING AND COMPETITION IN

  3. Educational asymmetries in the making: Science Fair Competitions as Proxies of the Economic Development

    CERN Document Server

    Vinkovic, Dejan

    2010-01-01

    Croatia does not score well in the human development index, rate of employment, or development of the high tech sector - to mention only a few indicators that hinder good prospects for improvement. Also, Croatian high school students are at the bottom of European rankings on performance in science and mathematics and their interest in career in science is declining. Croatia needs more educated people, especially in the area of science and technology, and this can be achieved only if the youth become interested in science at an early age. Thus, science fair competitions are of an utmost importance for development of Croatia. This paper aims at investigating a relation of the Croatian counties' development index and their students' participation rates in the science fair competitions. This is done by including two development indexes in search for the relation with the counties' participation rates in biology, chemistry, physics and mathematics competition, and with a reference to a previous research on astrono...

  4. Drug Development of Therapeutic Monoclonal Antibodies.

    Science.gov (United States)

    Mould, Diane R; Meibohm, Bernd

    2016-08-01

    Monoclonal antibodies (MAbs) have become a substantial part of many pharmaceutical company portfolios. However, the development process of MAbs for clinical use is quite different than for small-molecule drugs. MAb development programs require careful interdisciplinary evaluations to ensure the pharmacology of both the MAb and the target antigen are well-understood. Selection of appropriate preclinical species must be carefully considered and the potential development of anti-drug antibodies (ADA) during these early studies can limit the value and complicate the performance and possible duration of preclinical studies. In human studies, many of the typical pharmacology studies such as renal or hepatic impairment evaluations may not be needed but the pharmacokinetics and pharmacodynamics of these agents is complex, often necessitating more comprehensive evaluation of clinical data and more complex bioanalytical assays than might be used for small molecules. This paper outlines concerns and strategies for development of MAbs from the early in vitro assessments needed through preclinical and clinical development. This review focuses on how to develop, submit, and comply with regulatory requirements for MAb therapeutics.

  5. 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......, there have been many near misses and failures in the discovery and development of headache therapeutics. Glutamate receptor antagonism whilst efficacious has central side effects and some approaches such as nitric oxide synthase inhibition, substance P antagonism and cortical spreading depression blockade...

  6. Valuation of Real Options as Competitive Prototyping in System Development

    Science.gov (United States)

    2014-07-01

    Facility (Ceylan & Ford, 2002). The National Ignition Facility ( NIF ) needed to develop slabs of laser glass to be used in the testing of nuclear...glass produced if the production technologies were feasible, were very uncertain as were costs and devel- opment schedules. Although NIF had...relationships with experienced laser glass vendors, none could guarantee successful development within the required time a priori. Therefore, the NIF program

  7. New drug development in metastatic prostate cancer.

    Science.gov (United States)

    Armstrong, Andrew J; George, Daniel J

    2008-01-01

    In 2007, drug development in castration-resistant metastatic prostate cancer (CRPC) remains challenging, due to the number of potentially viable molecular targets and clinical trials available, the lack of established surrogates for overall survival, and competing causes of mortality. This review will highlight the highest impact phase II and phase III trials of novel agents in the current CRPC landscape, and focus on both molecular targets and clinical trial designs that are more likely to demonstrate clinical benefit. The need for tissue correlative studies for target evaluation and drug mechanism is stressed to continue to advance the field and to define biomarkers that may identify patient populations that may derive a greater benefit from these molecular agents.

  8. Product development of probiotics as biological drugs.

    Science.gov (United States)

    Sutton, Ann

    2008-02-01

    Elements of product and manufacturing-process design are described for product development of live biotherapeutic biological drugs. Product design uses the history and the phenotypic and genotypic characterization of the selected strain. The quality and integrity of the selected strain can be ensured by preservation in a qualified cell-bank system. Manufacturing-process design includes step-by-step description, including the necessary process-input parameters and the expected output results. The active ingredients in the biological drug are usually manufactured using aseptic processing. The manufacture of the final dosage form of live biotherapeutics requires bioburden control or aseptic manufacture, as appropriate. Specifications for live biotherapeutics must comply with regulations for licensed biological products. Evidence of stability for the duration of the shelf life, as well as stability under the recommended conditions of use, must be provided for licensure.

  9. The professional development of workers and enterprises' competitive advantage

    Directory of Open Access Journals (Sweden)

    NICOLÁS FERNÁNDEZ LOSA

    2002-06-01

    Full Text Available This work focuses on career management. Based on life-cycle, organizational and directional-pattern perspectives of careers, a career development model is introduced. The actions that companies can take to help employees deal with these developmental tasks are highlighted. For career planning to be successful, employees, managers, and the company must all be actively involved. Finally, current career development issues including orientation and socialization, plateauing, dual career ladders, skill obsolescence, balancing work and family, job loss, and retirement are presented.

  10. Quasi-Drugs Developed in Japan for the Prevention or Treatment of Hyperpigmentary Disorders

    Directory of Open Access Journals (Sweden)

    Hideya Ando

    2010-06-01

    Full Text Available Excess production of melanin or its abnormal distribution, or both, can cause irregular hyperpigmentation of the skin, leading to melasma and age spots. To date, various quasi-drugs that prevent or improve hyperpigmentary disorders have been developed and officially approved by the Ministry of Health, Labor and Welfare of Japan. Many of these inhibit the activity of tyrosinase, an enzyme required for melanin synthesis, for example, by competitive or non-competitive inhibition of its catalytic activity, by inhibiting its maturation, or by accelerating its degradation. In this review, we categorize the quasi-drugs developed in Japan to prevent or treat hyperpigmentary disorders, or both, and discuss perspectives for future development.

  11. Development of a competition model for microbial growth in mixed culture.

    Science.gov (United States)

    Fujikawa, Hiroshi; Munakata, Kanako; Sakha, Mohammad Z

    2014-01-01

    A novel competition model for describing bacterial growth in mixed culture was developed in this study. Several model candidates were made with our logistic growth model that precisely describes the growth of a monoculture of bacteria. These candidates were then evaluated for the usefulness in describing growth of two competing species in mixed culture using Staphylococcus aureus, Escherichia coli, and Salmonella. Bacterial cells of two species grew at initial doses of 10(3), 10(4), and 10(5) CFU/g at 28ºC. Among the candidates, a model where the Lotka-Volterra model, a general competition model in ecology, was incorporated as a new term in our growth model was the best for describing all types of growth of two competitors in mixed culture. Moreover, the values for the competition coefficient in the model were stable at various combinations of the initial populations of the species. The Baranyi model could also successfully describe the above types of growth in mixed culture when it was coupled with the Gimenez and Dalgaard model. However, the values for the competition coefficients in the competition model varied with the conditions. The present study suggested that our model could be a basic model for describing microbial competition.

  12. ECO-INNOVATION AND ITS CONTRIBUTION TO SUSTAINABLE DEVELOPMENT AND COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Margareta RUSU

    2013-12-01

    Full Text Available In the context of global economy a dominant role of knowledge is the importance of human resources in the process of innovation and value creation. This paper aims to address Romania’s competitiveness in the context of global change mitigation by analyzing the counties competitiveness and eco-innovation. The efficiency-driven stage of development, which Romania is part of require specific regulatory measure in order to achieve sustainable development and competitive advantage. Analyzing the eco-innovation local needs by focusing on the SME can be seen as a solution, as they are creative in order to compensate for the lack of funding in research, development and innovation (like cluster research which is beneficial for sharing the risk and cost involved in research activities.

  13. Comparative Analysis of OECD Member Countries' Competitive Advantage in National Human Resource Development System

    Science.gov (United States)

    Oh, Hunseok; Choi, Yeseul; Choi, Myungweon

    2013-01-01

    The purpose of this study was to assess, evaluate, and compare the competitive advantages of the human resource development systems of advanced countries. The Global Human Resource Development Index was utilized for this study, since it has been validated through an expert panel's content review and analytic hierarchy process. Using a sample of 34…

  14. Assessment and Evaluation of National Human Resource Development System Competitiveness in Emerging Countries

    Science.gov (United States)

    Oh, HunSeok; Seo, DongIn; Kim, JuSeuk; Yoo, SangOk; Seong, HeeChang

    2015-01-01

    This study assessed and evaluated the competitiveness of national human resource development (NHRD) systems in emerging countries with potential for growth. The literature on emerging countries and NHRD systems was reviewed. The study developed a model mechanism with forty-one indices and nine sub-components for the NHRD system assessment in…

  15. Comparative Analysis of OECD Member Countries' Competitive Advantage in National Human Resource Development System

    Science.gov (United States)

    Oh, Hunseok; Choi, Yeseul; Choi, Myungweon

    2013-01-01

    The purpose of this study was to assess, evaluate, and compare the competitive advantages of the human resource development systems of advanced countries. The Global Human Resource Development Index was utilized for this study, since it has been validated through an expert panel's content review and analytic hierarchy process. Using a sample of 34…

  16. Comparative Analysis of OECD Member Countries' Competitive Advantage in National Human Resource Development System

    Science.gov (United States)

    Oh, Hunseok; Choi, Yeseul; Choi, Myungweon

    2013-01-01

    The purpose of this study was to assess, evaluate, and compare the competitive advantages of the human resource development systems of advanced countries. The Global Human Resource Development Index was utilized for this study, since it has been validated through an expert panel's content review and analytic hierarchy process. Using a sample…

  17. The impact of collaborations between universities and private organizations on cluster development and competitiveness in Romania

    Science.gov (United States)

    Stoicovici, D.; Bănică, M.; Ungureanu, M.; Stoicovici, M.

    2017-05-01

    While the European Union has put a lot of emphasis on cluster development due to their inherent advantages such as lower transaction costs, technological transfer and regional development, little is known about how clusters emerge and what can facilitate their competitiveness. This paper aims to study the impact of public-private cooperation between universities and organizations on cluster development and competitiveness. A literature review is employed to develop the model while 4 qualitative case studies provide the initial test of its validity. The analysis suggests that cooperating with research institutions impacts cluster development first through education of industrial staff, but also by developing innovation processes through the facilitation of the appearance of innovative ideas and also of knowledge sharing among organizations. The research has several implications both for organizations and for government officials. First of all, R&D and top management should actively seek to cooperate with research institutions both for training of their staff but also in seeking new ideas and as a way of collaborating with other organizations within the field without fear of losing competitive advantage. Second, government officials should try to create more incentives both for organizations (through for example tax returns) and for universities (extra funding or salary incentives) that can increase collaboration between these actors. This paper is the first one to asses empirically how cooperation with research institutions affect cluster competitiveness and development, especially within the developing region of Eastern Europe, Romania.

  18. Cross-Border Higher Education: Global and Local Tensions within Competition and Economic Development

    Science.gov (United States)

    Owens, Taya L.; Lane, Jason E.

    2014-01-01

    In this chapter, the authors explore various types of cross-border higher education, considering equity and quality issues within these developments. With a particular focus on international branch campuses, the authors discuss the ways in which global competition for knowledge and economic development interact with tensions at the local level.

  19. Assessment and Evaluation of National Human Resource Development System Competitiveness in Emerging Countries

    Science.gov (United States)

    Oh, HunSeok; Seo, DongIn; Kim, JuSeuk; Yoo, SangOk; Seong, HeeChang

    2015-01-01

    This study assessed and evaluated the competitiveness of national human resource development (NHRD) systems in emerging countries with potential for growth. The literature on emerging countries and NHRD systems was reviewed. The study developed a model mechanism with forty-one indices and nine sub-components for the NHRD system assessment in…

  20. Bayesian population PBPK approach for support of drug development

    OpenAIRE

    Krauß, Markus

    2016-01-01

    Low likelihood-of-approval rates of new drugs constitute a major problem in clinical development. Only one out of ten development programs entering the first clinical phase succeeds in being approved by the U.S. Food and Drug Administration (FDA) [1]. A main challenge is thereby an insufficient understanding and prediction of drug safety and efficacy, leading to the withdrawal of new drug candidates [2,3]. Here, model-based assessment of drug exposure and response can support the development ...

  1. The development and maintenance of drug addiction.

    Science.gov (United States)

    Wise, Roy A; Koob, George F

    2014-01-01

    What is the defining property of addiction? We dust off a several-decades-long debate about the relative importance of two forms of reinforcement—positive reinforcement, subjectively linked to drug-induced euphoria, and negative reinforcement, subjectively linked to the alleviation of pain—both of which figure importantly in addiction theory; each of these forms has dominated addiction theory in its time. We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement to come into play at a time when tolerance, in the form of increasing reward thresholds, appears to develop into positive reinforcement. Wise’s work has tended to focus on positive-reinforcement mechanisms that are important for establishing drug-seeking habits and reinstating them quickly after periods of abstinence, whereas Koob’s work has tended to focus on the negative-reinforcement mechanisms that become most obvious in the late stages of sustained addiction. While we tend to agree with each other about the early and late stages of addiction, we hold different views as to (i) the point between early and late at which the diagnosis of ‘addiction’ should be invoked, (ii) the relative importance of positive and negative reinforcement leading up to this transition, and (iii) the degree to which the specifics of negative reinforcement can be generalized across the range of addictive agents.

  2. Developing competitive marketing and sales strategy for HS-Eden

    OpenAIRE

    Dragusha, Cajup

    2016-01-01

    Start-ups are faced with variety of challenges and uncertainty therefore comprehensive marketing and sales strategy must be in place to make sure that limited resources are spend wisely in order to minimize uncertainty and pave a path that would lead to successful business. HS Eden is a new-start-up venture created in Lappeenranta University of Technology with an ambition to develop AMB systems for commercial use. The aim of this study was to build a marketing and sales strategy to help HS-Ed...

  3. DEVELOPMENT OF A NEW IMMUNOMODULATING DRUG TIMOFER

    Directory of Open Access Journals (Sweden)

    B. M. Kholnazarov

    2014-01-01

    Full Text Available Results of the development of an immunomodulating drug timofer based on coordination compounds isoleucyl-tryptophan dipeptide with iron (II, including the study of coordinate isoleucyl-tryptophan dipeptide with iron (II, the study of the immunostimulatory activity of the coordination compounds, the results of the preclinical and clinical studies of timotsin are presented. Method of pH titration showed that the interaction of zinc and dipeptide isoleucyltryptophan formed in solution following complex forms: [Fe (HL±]2+ (β = 1,00×1034, [Fe(HL±2]2+ (β = 6,25×1011, [Fe (HL±OH]+ (β = 4,01×1026, [Fe (L]+ (β = 8,10×1018, [Fe (L2]+ (β = 7,50×1028, [Fe (LOH]+ (β = 1,03×1029. It was shown that the immunostimulatory activity of the coordination compounds is 2 times higher than that starting dipeptide. The substance sample and standard formulation of timofer were developed and standardized. The developed immunomodulatory drug timofer showed a high therapeutic efficacy in the treatment of iron deficiency anemia patients with inflammatory processes and traumatic injuries of the maxillofacial region, with chronic inflammatory diseases of the the genitals (CMV, HSV, chlamydia, chronic endometritis, chronic salpingoopharitis, ureaplasmosis with chronic bronchitis, chronic obstructive bronchitis, bronchial asthma, pneumonia, chronic glomerulonephritis, and chronic renal failure complicated by anemia Bright, withrheumatic diseases, gynecological patients with anemia of moderate and severe degrees of severity, at surgical treatment of patients with suppurative lung disease, heart disease and chronic pericarditis operated with cardiopulmonary bypass. Timofer is registered in Tajikistan (registration number of medical drug №002866.

  4. Review: DNA microarray technology and drug development

    Directory of Open Access Journals (Sweden)

    Sana Khan

    2010-01-01

    Full Text Available On the contrary to slow and non specific traditional drug discovery methods, DNA microarray technology could accelerate the identification of potential drugs for treating diseases like cancer, AIDS and provide fruitful results in the drug discovery. The technique provides efficient automation and maximum flexibility to the researchers and can test thousand compounds at a time. Scientists find DNA microarray useful in disease diagnosis, monitoring desired and adverse outcomes of therapeutic interventions, as well as, in the selection, assessment and quality con-trol of the potential drugs. In the current scenario, where new pathogens are expected every year, DNA microarray promises as an efficient technology to detect new organisms in a short time. Classification of carcinomas at the molecular level and prediction of how various types of tumor respond to different therapeutic agents can be made possible with the use of microarray analysis. Also, microarray technique can prove instrumental in personalized medicines development by providing microarray data of a patient which could be used for identifying diseases, treatment specific to individual and trailing disease prognosis. Microarray analysis could be beneficial in the area of molecular medicines for analysis of genetic variations and functions of genes in normal individuals and diseased conditions. The technique can give satisfactory results in single nucleotide polymorphism (SNP analysis and pharmacogenomics studies. The challenges that arise with the technology are high degree of variability with data obtained, frequent up gradation of methods and machines and lack of trained manpower. Despite this, DNA micro-array promises to be the next generation sequencer which could explain how organisms evolve and adapt looking at the whole genome. In a nutshell, Microarray technology makes it possible for molecular biologists to analyze simultaneously thousands of DNA samples and monitor their

  5. Core Competitiveness as the Fundamental Guarantee for Sustainable Development of Geo-parks

    Institute of Scientific and Technical Information of China (English)

    Chenxia; SHI; Zhonghui; ZHANG

    2013-01-01

    With the booming development over the past years,geo-parks have achieved impressive progress together with a series of problems.Most importantly,geological tourism is not in prosperity.How to prosper geological tourism and achieve the sustainable development of geoparks is the top concern of workers engaged in tourism geology in China.This article discusses the problem from the perspective of core competitiveness of geo-parks,particularly from three aspects of subject,object and medium,and puts forward methods to form the core competitiveness.

  6. Crowdfunding drug development: the state of play in oncology and rare diseases.

    Science.gov (United States)

    Dragojlovic, Nick; Lynd, Larry D

    2014-11-01

    In this article, we present descriptive data on 125 crowdfunding campaigns aimed at financing research in oncology (including basic research, drug discovery, and clinical trials). We also describe five campaigns that have succeeded in raising substantial funds to support the development of treatments for ultrarare diseases. The data suggest that crowdfunding is a viable approach to supporting early proof-of-concept research that could allow researchers in oncology and rare diseases to succeed in traditional grant competitions or to attract private investment. The data also suggest that such an approach could become a valuable additional source of funding for early-stage innovators in the drug development arena.

  7. [The development of adrenal cortical hormones into drugs].

    Science.gov (United States)

    Hansen, Sven Erik

    2008-01-01

    The interplay of factors contributing to the development of adrenal cortical hormones into drugs is reviewed. Clinical research performed during long periods by the physicians T. Addison and P.S. Hench in a nearly obsessional way stimulated basic research in physiology and biochemistry of the adrenal glands. From about 1900 increasing public interest in the "new hormones"coincided with expansion in research and development in academic and industrial settings. Pharmaceutical companies developed skill by production of much demanded organ-extracts, both effective ones as insulin and preparations of questionable clinical value. In 1949 the powerful anti-inflammatory effect of the cortical hormone, cortisone was discovered. As the supply of that hormone was scanty, it had temporarily to be substituted by the adrenocorticotropic hormone (ACTH) from animal hypophyses. Thereafter development accelerated through the combined effect of many years' painstaking research on the adrenal cortical hormones, technological breakthroughs, a climate positive for bold clinical experimentation and vigorous competition among mainly American pharmaceutical companies. Within a decade prednisone, the successor of cortisone, was launched, its clinical use established and large-scale inexpensive production instituted.

  8. Innovation, competition and financial vulnerability in economic development

    Directory of Open Access Journals (Sweden)

    Leonardo Burlamaqui

    2005-04-01

    Full Text Available The financial sector has been viewed traditionally as either providing the "oil" for the "wheels of commerce" or as a parasite on the real sector of the economy where real productivity gains provide for increasing real wages and per capita incomes. The present paper takes a different route and attempts to an analysis of financial institutions on a par with the production sector of the economy. It also develops a link which amalgamates "the knowledge-based" perspective on firms' operations with Schumpeterian financial leverage to exploit productivity enhancing innovations, and Minsky's tendency towards financial fragility. The analysis also leads to some policy recommendations concerning financial regulation, risk management and financial institution's building.

  9. Competitive Advantages of Effective Relationships of Business Entities as a Basis for Economic Development of Ukraine

    Directory of Open Access Journals (Sweden)

    Butenko Nataliia V.

    2016-11-01

    Full Text Available The aim of the article is to determine the transformation of sense of relationships between business entities in the national economy as well as basic ideas and principles of forming competitive advantages of effective relationships. The objective preconditions for the transition from the confrontation strategy to relationships as a basis of interaction of business entities in the structure of the national economy are analyzed. It is determined that the weakening of the antagonistic dominant of competitive relations and the growing importance of a constructive component of partnership has become a background of the desire of business entities to establish effective relationships. The attention is focused on the trends of the cooperation and integration approach to competitive behavior, which is manifested in such forms of competitive interactions as coordination, constructive interaction and competitive collaboration in order to achieve individual and common goals of competitive relationships of the entities. The competitive advantages based on establishing long-term and effective relationships are considered. The peculiarities in the formation of the system of relationships in the insurance market are justified, in particular the causes hindering the development of relationships in the sphere of security are determined, the main partners — entities in the system of relationships in the insurance market are identified, the levels of relationships management in the insurance market are determined. Among the advantages of the use of effective relationships in the field of insurance are the following: improving the company’s image, attracting new customers, additional sales of insurance services, limiting the access of competitors’ offers, more efficient use of the advertising budget, improving the efficiency of the development of new insurance products and services, increasing the profits and value of brands, improving relations with

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

    OpenAIRE

    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 consequences of this concentration-dependent adverse drug reaction, regulatory authorities have reacted to this “pharmacoepidemic” by denying or delaying the approval of a number of new drugs and placin...

  11. 竞争情报发展及概述%Development and Overview of Competitive Intelligence

    Institute of Scientific and Technical Information of China (English)

    武经宇; 王强; 王芳

    2012-01-01

    随着科学技术的发展,竞争情报已成为诸多大型机构的长期战略资产。结合竞争情报的概念,从发展阶段、研究方法、功能、趋势等方面进行了详尽地介绍。%With development of science and technology,competitive intelligence has become long-term strategic asset to many large institutions.Combining concept of competitive intelligence,the authors introduced the content of competitive intelligence in detail from aspects of development stage,research method,function and trend.

  12. Financial Aspects of Competitiveness in the Sustainable Development of the Company

    Directory of Open Access Journals (Sweden)

    Mihail Dimitriu

    2009-06-01

    Full Text Available Competitiveness of firms is a most important problem and now the negative impact of financialcrisis bring in discussion was in which Romanian firms may survive on the Unique European market. Wethink that in present are necessary the following: 1. Increased competitiveness should not be regarded as aprocess of exploiting short-term advantages (e.g. low cost of labour, but as a process of building aneconomic structure based on capital investment and process R & D innovation; 2. Competitiveness incomplying with the legal community, or financial efforts in environmental protection, are significantsegments of the real economy of Romania can not integrate into the European Single Market; 3. Of the 6priorities of the NDP 2007-2013 (Competitiveness, Transport Infrastructure, Environment, HumanResources, Rural Development, regional development, the lowest financial allocation for Competitiveness(8.9% of total. Moreover, attracting European funds in the list is left behind to "graphics" originally made byRomania; 4. Now is a general series of vulnerabilities that lead to additional costs, such as uncertaintyregarding the sustainability and stability of policy options, solutions for restructuring and economicdevelopment, large uncertainties regarding the ability to translate words into concrete actions and establishpriorities in macroeconomic objectives and others.

  13. Developments in Diagnosis and Antileishmanial Drugs

    Directory of Open Access Journals (Sweden)

    Prachi Bhargava

    2012-01-01

    Full Text Available Leishmaniasis ranks the third in disease burden in disability-adjusted life years caused by neglected tropical diseases and is the second cause of parasite-related deaths after malaria; but for a variety of reasons, it is not receiving the attention that would be justified seeing its importance. Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1–1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. Improvements in diagnostic methods for early case detection and latest combitorial chemotherapeutic methods have given a new hope for combating this deadly disease. The cell biology of Leishmania and mammalian cells differs considerably and this distinctness extends to the biochemical level. This provides the promise that many of the parasite’s proteins should be sufficiently different from hosts and can be successfully exploited as drug targets. This paper gives a brief overview of recent developments in the diagnosis and approaches in antileishmanial drug discovery and development.

  14. [The effect of generic price competition on drug consumption and health insurance pharmaceutical expenditures in Hungary].

    Science.gov (United States)

    Répásy, Balázs; Endrei, Dóra; Zemplényi, Antal; Agoston, István; Hornyák, Lajos; Nagy, Zsolt; Csákvári, Tímea; Vajda, Réka; Boncz Imre

    2015-01-01

    The aim of our study was to analyze the Hungarian montelukast sodium drug market. We examined the effect of the appearance of generic drugs on the price and turnover of the brand-name drug, Singulair. Data derived from the nationwide pharmaceutical database of Hungarian National Health Insurance Fund Administration (2007-2014). We analized the turnover and price of the medicaments containing the active substance montelukast sodium. Accordingly our indicators were: consumer price, social insurance subsidy, patients' co-payment and days of treatment (DOT). First the generics started from a significantly lower price of 18 USD which was lower than the price of brand-name Singulair (32 USD). Then the prices of the generics started to diminish. While in 2007 the DOT was below 2 million, it increased over 10 million days by 2014. The increase of DOT was followed by the increase of health insurance subsidy until 2011. Then the amount of health insurance subsidy decreased from 10,5 million USD to 7 million USD in 2012. In 2013 and 2014 there was a further reduction, the amount of the health insurance subsidy decreased to 4,1 million USD in 2013, and in 2014 it was reduced to 2.2 million USD. Following the introduction of generic drugs, the price of the medicaments containing montelukast sodium was significantly reduced, while the days on treatment (DOT) increased. The patients' access to drugs containing montelukast sodium increased significantly. The annual health insurance subsidy was significantly reduced as well.

  15. Active controlled studies in antibiotic drug development.

    Science.gov (United States)

    Dane, Aaron

    2011-01-01

    The increasing concern of antibacterial resistance has been well documented, as has the relative lack of antibiotic development. This paradox is in part due to challenges with clinical development of antibiotics. Because of their rapid progression, untreated bacterial infections are associated with significant morbidity and mortality. As a consequence, placebo-controlled studies of new agents are unethical. Rather, pivotal development studies are mostly conducted using non-inferiority designs versus an active comparator. Further, infections because of comparator-resistant isolates must usually be excluded from the trial programme. Unfortunately, the placebo-controlled data classically used in support of non-inferiority designs are largely unavailable for antibiotics. The only available data are from the 1930s and 1940s and their use is associated with significant concerns regarding constancy and assay sensitivity. Extended public debate on this challenge has led to proposed solutions by some in which these concerns are addressed by using very conservative approaches to trial design, endpoints and non-inferiority margins, in some cases leading to potentially impractical studies. To compound this challenge, different Regulatory Authorities seem to be taking different approaches to these key issues. If harmonisation does not occur, antibiotic development will become increasingly challenging, with the risk of further decreases in the amount of antibiotic drug development. However with clarity on Regulatory requirements and an ability to feasibly conduct global development programmes, it should be possible to bring much needed additional antibiotics to patients.

  16. Chemical signatures and new drug targets for gametocytocidal drug development

    Science.gov (United States)

    Sun, Wei; Tanaka, Takeshi Q.; Magle, Crystal T.; Huang, Wenwei; Southall, Noel; Huang, Ruili; Dehdashti, Seameen J.; McKew, John C.; Williamson, Kim C.; Zheng, Wei

    2014-01-01

    Control of parasite transmission is critical for the eradication of malaria. However, most antimalarial drugs are not active against P. falciparum gametocytes, responsible for the spread of malaria. Consequently, patients can remain infectious for weeks after the clearance of asexual parasites and clinical symptoms. Here we report the identification of 27 potent gametocytocidal compounds (IC50 malaria transmission-blocking reagents.

  17. Botanicals as "new" drugs: US development.

    Science.gov (United States)

    Hoffman, Freddie Ann

    2015-11-01

    Botanicals are ingredients that can be marketed as foods, drugs, cosmetics, and medical devices in the United States. When a botanical is intended to diagnose, treat, prevent, mitigate, or cure a disease, it is considered to be a "drug". This article reviews the US regulatory requirements for botanicals as "new" drugs. An overview of the regulatory principles used to determine product category and the basic elements of an Investigational New Drug application and New Drug Application with the US Food and Drug Administration are presented. This article is part of a Special Issue entitled "Botanicals for Epilepsy".

  18. 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 conse

  19. Drugs for developing countries. Uncharitable stance from Oxfam.

    Science.gov (United States)

    Wenz, C

    1982-12-02

    Oxfam, a British charity organization, has charged multinational pharmaceutical manufacturers with encouraging overuse and misuse of drugs in developing countries. The World Health Organization (WHO) has issued a list of "essential" drugs which is being used by Bangladesh to restrict drug sales to only certain products. Despite signs of cooperation between some drug companies and WHO, Oxfam remains skeptical.

  20. Choice of the exchange policies in the developments countries: Study of the competitiveness of Tunisia

    Directory of Open Access Journals (Sweden)

    Benahji Sfaxi Hend

    2008-01-01

    Full Text Available After the collapse of the Breton Woods system, the increased fluctuations of the exchange rates pushed the developing countries to adopt exchange rate policies to avoid rocking of the balance of payments. Since 1973, Tunisia adopted fixed or intermediary exchange rate policies to support or ameliorate her competitiveness and later to balance her current account. By calculating the real effective exchange rate misalignment, we showed that this country did not achieve her goals and that amelioration of competitiveness occurred only as from the moment when she softened her exchange policies. A policy of floating exchange rate is recommended for Tunisia specially why this country is more and more open. .

  1. Theorizing Strategic Human Resource Development: Linking Financial Performance and Sustainable Competitive Advantage

    Science.gov (United States)

    Hu, Po

    2007-01-01

    This paper is to explore potential new underlying theory of strategic human resource development based on critiques of current theoretical foundations of HRD. It offers a new definition and model of Strategic HRD based on resource-based view of firm and human resource, with linkage to financial performance and competitiveness. Proposed new model…

  2. Learning from Toyota: How Action Learning Can Foster Competitive Advantage in New Product Development (NPD)

    Science.gov (United States)

    Fuchs, Barbara

    2007-01-01

    New product development and commercialization are essential to entrepreneurial growth and international competitiveness. Excellence in this area is strongly supported by individual and organizational learning efforts. By analyzing how Japanese car manufacturer Toyota organizes learning, this paper evaluates the potential of action learning to…

  3. Learning from Toyota: How Action Learning Can Foster Competitive Advantage in New Product Development (NPD)

    Science.gov (United States)

    Fuchs, Barbara

    2007-01-01

    New product development and commercialization are essential to entrepreneurial growth and international competitiveness. Excellence in this area is strongly supported by individual and organizational learning efforts. By analyzing how Japanese car manufacturer Toyota organizes learning, this paper evaluates the potential of action learning to…

  4. Knowledge management as a means of developing a firm’s competitive advantage

    Directory of Open Access Journals (Sweden)

    Tomaž Čater

    2001-01-01

    Full Text Available Knowledge management is one of the most popular themes of modern scientific literature. However, in spite of all the published research on the importance of knowledge management, there is little said about knowledge as a direct source of a firm’s competitive advantage. In the past decades, three main hypotheses on the sources of a firm’s competitive advantage were developed; namely, the industrial organization, the resource-based and the capability-based hypotheses. In this paper, we argue that the knowledge-based hypothesis can and should be considered as the fourth tantamount hypothesis on how the sources of the competitive advantage of a firm can be explained.

  5. New development of drugs against opioid addiction

    Institute of Scientific and Technical Information of China (English)

    LiJin; SuRui-bin; LuXin-qiang; LiuYin

    2004-01-01

    Opioid addiction has been a big trouble for human being for several centuries. In China, it also has become a main direct threat against national safety, society advancement, economic development and public health. Based on the national report in 2002, the number of addicts registered in due form is over 1 million, which are distributed in 2148 counties and cities in China. The real number of addicts, however, is much more than those as mentioned above. Money used for buying opioids each year in China might be over 10 billion except for other payment. Base on the statistics, 20 - 50% crimes are commited by addicts. On the other hand, drug abuse often induces contagion spread, such as tuberculosis, hepatitis and HIV disease. About 70% HIV positive subjects in China are related to drug abuse. We are very happy to see more andmore attention has been paid to the problem in our country. Recently, a program on neurobiological basis and medical biological measures of addiction has been supported by National Science and Technology Ministry as a 973 program.

  6. Review: DNA Microarray Technology and Drug Development

    Directory of Open Access Journals (Sweden)

    Sushma Drabu

    2010-01-01

    Full Text Available

    On the contrary to slow and non specific traditional drug discovery methods, DNA microarray technology could
    accelerate the identification of potential drugs for treating diseases like cancer, AIDS and provide fruitful results in
    the drug discovery. The technique provides efficient automation and maximum flexibility to the researchers and
    can test thousand compounds at a time. Scientists find DNA microarray useful in disease diagnosis, monitoring
    desired and adverse outcomes of therapeutic interventions, as well as, in the selection, assessment and quality control
    of the potential drugs. In the current scenario, where new pathogens are expected every year, DNA microarray
    promises as an efficient technology to detect new organisms in a short time. Classification of carcinomas at the
    molecular level and prediction of how various types of tumor respond to different therapeutic agents can be made
    possible with the use of microarray analysis. Also, microarray technique can prove instrumental in personalized
    medicines development by providing microarray data of a patient which could be used for identifying diseases,
    treatment specific to individual and trailing disease prognosis. Microarray analysis could be beneficial in the area
    of molecular medicines for analysis of genetic variations and functions of genes in normal individuals and diseased
    conditions. The technique can give satisfactory results in single nucleotide polymorphism (SNP analysis and
    pharmacogenomics studies. The challenges that arise with the technology are high degree of variability with data
    obtained, frequent up gradation of methods and machines and lack of trained manpower. Despite this, DNA microarray
    promises to be the next generation sequencer which could explain how organisms evolve and adapt looking
    at the whole

  7. Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools.

    Science.gov (United States)

    Issa, Naiem T; Wathieu, Henri; Ojo, Abiola; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2017-03-15

    Increased R & D spending and high failure rates exist in drug development, due in part to inadequate prediction of drug metabolism and its consequences in the human body. Hence, there is a need for computational methods to supplement and complement current biological assessment strategies. In this review, we provide an overview of drug metabolism in pharmacology, and discuss the current in vitro and in vivo strategies for assessing drug metabolism in preclinical drug development. We highlight computational tools available to the scientific community for the in silico prediction of drug metabolism, and examine how these tools have been implemented to produce drug-target signatures relevant to metabolic routes. Computational workflows that assess drug metabolism and its toxicological and pharmacokinetic effects, such as by applying the adverse outcome pathway framework for risk assessment, may improve the efficiency and speed of preclinical drug development.

  8. FDA Critical Path Initiatives: Opportunities for Generic Drug Development

    OpenAIRE

    Lionberger, Robert A.

    2008-01-01

    FDA’s critical path initiative documents have focused on the challenges involved in the development of new drugs. Some of the focus areas identified apply equally to the production of generic drugs. However, there are scientific challenges unique to the development of generic drugs as well. In May 2007, FDA released a document “Critical Path Opportunities for Generic Drugs” that identified some of the specific challenges in the development of generic drugs. The key steps in generic product de...

  9. Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin

    Science.gov (United States)

    Khodaei, Arash; Bolandnazar, Soheila; Valizadeh, Hadi; Hasani, Leila; Zakeri-Milani, Parvin

    2016-01-01

    Purpose: The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined. Methods: Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated using Scatchard plots. The same processes were conducted in the presence of NSAIDs at lower concentration of albumin and different pH conditions. To characterize the binding site of Sirolimus on albumin, the free concentration of warfarin sodium and Diazepam, site I and II specific probes, bound to albumin were measured upon the addition of increasing Sirolimus concentrations. Results: Based on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could significantly decrease the percentage of Sirolimus protein binding. The Binding reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs interactions were increased in higher pH values and also in lower albumin concentrations. Probe displacement study showed that Sirolimus may mainly bind to site I on albumin molecule. Conclusion: More considerations in co-administration of NSAIDs and Sirolimus is recommended. PMID:27478785

  10. Institutes of regional development and competitiveness in the conditions of modernization

    Directory of Open Access Journals (Sweden)

    Nadezhda Yakovlevna Kalyuzhnova

    2011-06-01

    Full Text Available This paper discusses the problem of identifying the institutions that influence the development of regions. A systematization of regional development institutions is implemented. Institutions of macro-, meso-, micro- and nano-levels of the economy affecting regional development are highlighted; at each level of the economy the institutions functioning properly and development institutions are also highlighted. The institutions are also systematically divided by type of adjustable rules. The role of institutions in the concept of regional competitiveness is examined. The indexes of regional competitiveness indicators, excluding the institutional environment of regions, are criticized. It is noted that the concept of regional competitiveness considers the region as an economic entity, which can and must prove its right to income with its economic performance, rather than capital status or informal practices of receiving transfers. Formation of the region and the competitiveness of a business entity depends on the maturity of the regional elites and their consolidation, as well as the institutional environment that encourages regional development and prevents monopoly of certain regions. The results of the quantitative analysis of the impact of institutions on the performance of regional development are presented. In particular, the influence of institutions such as corruption, small business and institutional trust is reviewed. The level of corruption is measured by the CPI index, its impact on economic growth in the sample of 12 countries that are close to Russia in terms of development, as well as at the level of Russian regions is considered. According to 2009-2010, the impact on regional development of the newly created development institutions such as foundations to promote small and medium enterprises, regional mortgage funds, special economic zones and regional venture capital funds is analyzed.

  11. 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.

  12. A new call for quality. Shifting the paradigm for development policy in Greece through competitions

    Directory of Open Access Journals (Sweden)

    Angelos Psilopoulos

    2013-12-01

    Full Text Available This paper is following up on Kouzelis, Psilopoulou and Psilopoulos (2010, where it was partly suggested that skipping architectural competitions in favour of a quantitative (i.e., fiscal approach was a prevailing paradigm for the building procurement policy in Greece at the time. Here the aim is to trace a notable shift from that paradigm by reviewing three case studies: the case of the UpTo35 competition conducted as part of a private development scheme, the case of two ideas competitions organized by architecture review GreekArchitects.gr as part of an open discourse on politics and urban issues, and finally a general turn in policy by the ‘Ministry of Environment, Energy and Climate Change including a new legislative framework aiming to establish a central role for architectural competitions in the development of public space. As these cases are studied in terms of narrative inquiry, the focus will be primarily on the incentives behind them and a proposal that they all find themselves on common ground by the narrative of simply ‘breaking with past practices’, in addition to introducing the notion of quality, not by prescribing it in qualificatory terms but rather by simply supporting and safeguarding it in both policy and will.

  13. DEVELOPMENT OF MOTOR INDUSTRY OF SVERDLOVSK REGION FROM THE POSITION OF THE INTERNATIONAL COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    A.V. Kozlov

    2007-12-01

    Full Text Available The industrial cooperation of Russia in the field of motor industry with quickly developing Asian countries with a view of increase of competitiveness of the country in the world market of cars is considered in clause. The output of Sverdlovsk region on the markets of cars of the developed countries by means of creation of joint ventures with motor-car manufacturers of the Peoples Republic of China on an example of JSC "Cars and motors of Ural " is offered.

  14. The development and maintenance of drug addiction

    National Research Council Canada - National Science Library

    Wise, Roy A; Koob, George F

    2014-01-01

    .... We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement...

  15. The Development of «Smart» Technologies as a Factor in the Competitiveness of City

    Directory of Open Access Journals (Sweden)

    Shkolnyi Oleksandr O.

    2017-06-01

    Full Text Available Results of research prove that use of «smart» technologies is one of the ways to solve the problems of city. The involvement of projects, which are aimed at the smart city development, contributes to achieving the effective management of economic resources, innovation development, and improvement of the well-being of population. The dynamic nature of «smart» cities that has been evaluated using the indicators of economic development, human capital, technological support, environmental protection, international recognition, social cohesion, transport service, regulatory mechanisms, urban planning and public administration is a prerequisite for developing the global competitive advantages. The functional spheres of the smart city project have been analyzed with emphasis on energy, transport, water supply, housing and the local government system. The example of the Metropolregion Hamburg illustrates the possibilities of strengthening competitive advantages through the «smart» logistics solutions. The need to harness the best global experience in the development of smart cities in order to enhance the global competitiveness of the domestic economy has been identified.

  16. Bayer CropScience model village project: Contributions to agricultural suppliers’ competitiveness and human development

    Directory of Open Access Journals (Sweden)

    Regina Moczadlo

    2014-12-01

    Full Text Available Bayer CropScience is carrying out a Model Village Project (MVP in rural India as part of their supply chain management and their corporate social responsibility activities. The MVP includes actions related to future business cases and higher competitiveness as well as philanthropic activities. The preparation of future business case actions aims at creating prerequisites for win-win-situations. In the long run, these prerequisites, such as long-term business relations with suppliers based on trust from both sides, can lead to a higher competitiveness of the whole supply chain and simultaneously improve human development. The impacts on the latter are evaluated using the capability approach (CA developed by Amartya Sen (2000, c1999. The case of the MVP indicates the potential of companies to contribute to human development on a strategic win-win basis. Actions have to be distinguished based on the living and financial conditions different supplier groups face. In the future, the MVP aims at assessing whether and how MNCs may be able to combine competitive enhancement with human development, provided that potential corporate risks for the villagers’ human development are also taken into account.

  17. Non-invasive radiotracer imaging as a tool for drug development.

    Science.gov (United States)

    Gibson, R E; Burns, H D; Hamill, T G; Eng, W S; Francis, B E; Ryan, C

    2000-07-01

    Non-Invasive Radiotracer Imaging (NIRI) uses either short-lived positron-emitting isotopes, such as 11C and 18F, for Positron Emis ion Tomography (PET) or single photon emitting nuclides, e.g., 123I, which provide images using planar imaging or Single-Photon Emission Computed Tomography (SPECT). These high-resolution imaging modalities provide anatomical distribution and localization of radiolabeled drugs, which can be used to generate real time receptor occupancy and off-rate studies in humans. This can be accomplished by either isotopically labeling a potential new drug (usually with 11C), or indirectly by studying how the unlabelled drug inhibits specific radioligand binding in vivo. Competitive blockade studies can be accomplished using a radiolabeled analogue which binds to the site of interest, rather than a radiolabeled version of the potential drug. Imaging, particularly PET imaging, can be used to demonstrate the effect of a drug through a biochemical marker of processes such as glucose metabolism or blood flow. NIRI as a development tool in the pharmaceutical industry is gaining increased acceptance as its unique ability to provide such critical information in human subjects is recognized. This section will review recent examples that illustrate the utility of NIRI, principally PET, in drug development, and the potential of imaging advances in the development of cancer drugs and gene therapy. Finally, we provide a brief overview of the design of new radiotracers for novel targets.

  18. 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.

  19. Study on the Development of Industry of Internet of Things Based on Competitive GEM Model in Fujian Province

    Directory of Open Access Journals (Sweden)

    Di Jun An

    2016-01-01

    Full Text Available Firstly, the basic theories of internet of things, competitive GEM model and industrial development in Fujian Province were studied in this paper. Then, the factors influencing the cultivation of industrial competitiveness of the internet of things was observed and finally the suggestions on enhancing the competitiveness of internet of things and strengthening the cultivation of talents of internet of things were put forward.

  20. TCM-based new drug discovery and development in China.

    Science.gov (United States)

    Wu, Wan-Ying; Hou, Jin-Jun; Long, Hua-Li; Yang, Wen-Zhi; Liang, Jian; Guo, De-An

    2014-04-01

    Over the past 30 years, China has significantly improved the drug development environment by establishing a series of policies for the regulation of new drug approval. The regulatory system for new drug evaluation and registration in China was gradually developed in accordance with international standards. The approval and registration of TCM in China became as strict as those of chemical drugs and biological products. In this review, TCM-based new drug discovery and development are introduced according to the TCM classification of nine categories.

  1. Effectiveness of Training and Development on Employees’ Performance and Organisation Competitiveness in the Nigerian Banking Industry

    Directory of Open Access Journals (Sweden)

    Falola, H.O.

    2014-06-01

    Full Text Available Training and development is indispensable strategic tool for enhancing employee performance and organizations keep increasing training budget on yearly basis with believe that it will earn them competitive edge. The main objective of this study is to examine the effectiveness of training and development on employees’ performance and organisation competitive advantage in the Nigerian banking industry. Descriptive research method was adopted for this study using two hundred and twenty three valid questionnaires which were completed by selected banks in Lagos State, South-West Nigeria using simple random sampling technique. The data collected were carefully analyzed using descriptive statistics to represent the raw data in a meaningful manner. The results show that strong relationship exists between training and development, employees’ performance and competitive advantage. Summary of the findings indicates that there is strong relationship between the tested dependent variable and independent construct. However, bank management should not relent in their quest to train their staff to develop new ideas that will keep improving and retaining employee performance.

  2. Forecasting development of the network of highways with hard surface with consideration of competitive advantages

    Directory of Open Access Journals (Sweden)

    Shevchuk Yaroslav V.

    2013-03-01

    Full Text Available The article uses Lotka-Volterra equations to analyse competition between the highway and railway transportation networks and competitive ability of the network with the cement concrete and asphalt concrete road coverings. Modelling the process of development by the Lotka-Volterra equations lies in selection of parameters of the model in such a manner, so that model trajectories would be very similar to approximating trends by factual data. In accordance with the results of model forecasting of development of highway and railway networks the article makes a model forecasting of development of highway and railway networks by 2080. Within the framework of the Lotka-Volterra equations, the article conducts modelling of development of earth roads and roads with hard surface and studies competition between the roads with cement concrete and asphalt concrete road coverings (type 1, on the one hand, and road-mix and bituminous macadam roads (type 2. The article establishes that earth roads do not compete with the roads with hard surface, although this type of roads was viable in the post-war period due to its cheapness.

  3. Biomarker method validation in anticancer drug development.

    Science.gov (United States)

    Cummings, J; Ward, T H; Greystoke, A; Ranson, M; Dive, C

    2008-02-01

    Over recent years the role of biomarkers in anticancer drug development has expanded across a spectrum of applications ranging from research tool during early discovery to surrogate endpoint in the clinic. However, in Europe when biomarker measurements are performed on samples collected from subjects entered into clinical trials of new investigational agents, laboratories conducting these analyses become subject to the Clinical Trials Regulations. While these regulations are not specific in their requirements of research laboratories, quality assurance and in particular assay validation are essential. This review, therefore, focuses on a discussion of current thinking in biomarker assay validation. Five categories define the majority of biomarker assays from 'absolute quantitation' to 'categorical'. Validation must therefore take account of both the position of the biomarker in the spectrum towards clinical end point and the level of quantitation inherent in the methodology. Biomarker assay validation should be performed ideally in stages on 'a fit for purpose' basis avoiding unnecessarily dogmatic adherence to rigid guidelines but with careful monitoring of progress at the end of each stage. These principles are illustrated with two specific examples: (a) absolute quantitation of protein biomarkers by mass spectrometry and (b) the M30 and M65 ELISA assays as surrogate end points of cell death.

  4. From Competition to Cooperation - Development and Practices of Open Innovation Systems

    Directory of Open Access Journals (Sweden)

    Hsiu-ling Li

    2012-06-01

    Full Text Available In this era of an innovation-driven knowledge economy, innovation is a key factor in the creation of enterprise competitiveness. With the pace of globalization gaining speed and market competition becoming more intense, an increasing number of enterprises have opted to look beyond their own laboratories and search for creativity in the outside world. In other words, the source of momentum for enterprise innovation is no longer limited to a corporation's internal organization but can be derived from the proper use of external knowledge and innovative resources. When combining internal and external creativity to foster the development of new technologies, we can create greater economic value. The rise of this form of open innovation thinking is driving the development of the innovation systems in specific countries or regions.

  5. Ethnobotany and its role in drug development.

    Science.gov (United States)

    Heinrich, M

    2000-11-01

    The botanical collections of early explorers and the later ethnobotany have played important roles in the development of new drugs for many centuries. In the middle of the last century interest in this approach had declined dramatically, but has risen again during its last decade, and new foci have developed. The systematic evaluation of indigenous pharmacopoeias in order to contribute to improved health care in marginalized regions has been placed on the agenda of international and national organizations and of NGOs. In this paper the results of various projects on Mexican Indian ethnobotany and some of the subsequent pharmacological and phytochemical studies are summarized. Medicinal plants are an important element of indigenous medical systems in Mexico. This study uses the medicinal plants in four indigenous groups of Mexican Indians-Maya, Nahua, Zapotec and Mixe-as an example. The relative importance of a medicinal plant within a culture is documented using a quantitative method and the data are compared intra- and interculturally. While the species used by the indigenous groups vary, the data indicate that there exist well-defined criteria specific for each culture, which lead to the selection of a plant as a medicine. For example, a large number of species are used for gastrointestinal illnesses by two or more of the indigenous groups. At least in this case, the multiple transfers of species and their uses within -Mexico seems to be an important reason for the widespread use of a species. Some of the data we gathered in order to evaluate the indigenous claims are also discussed, focusing on the transcription factor NF-kappaB as a molecular target. This led to the identification of sesquiterpene lactones such as parthenolide as potent and relatively specific inhibitors of this transcription factor.

  6. Joint Research and Development under US Antitrust and EU Competition Law

    DEFF Research Database (Denmark)

    Lundqvist, Björn

    made over this time to the relevant legal acts and guidelines. In doing to, the author picks up on the slow shift that has taken place in both the antitrust laws of the USA and the Competition Rules of the EU. The book concludes by discussing the necessity for a stringent attitude towards the antitrust...... establishment, and how this can be developed by reviving the concept of the ‘innovation market’....

  7. Human Resources Development and ICT Contribution to the Tourist Destination Competitiveness

    OpenAIRE

    Ramona Gruescu; Roxana Nanu; Anca Tanasie

    2009-01-01

    The paper envisages aspects concerning identification of the competitive advantage of a tourist destination from a double perspective: the critical contribution of the employees and the ICT impact on promoting and selling the destination. Research methodology includes „bottom to top” analysis of the mentioned indicators. Thus, results include the eficientisation of tourist businesses and destinations due to both human element development and ICT technologies. Two essential basis of the compet...

  8. Make it happen: business steps for competitive market positioning of SMEs in developing economy

    OpenAIRE

    Marjanova Jovanov, Tamara; Sofijanova, Elenica; Davcev, Ljupco; Temjanovski, Riste; Mitev, Goran

    2017-01-01

    This paper aims to present some of the basic business steps that SMEs in transitional economy can follow in the process of competitive market positioning. The main objective is to demonstrate that the practice of certain business activities, such as development of higher levels of market orientation, implementation of market research, marketing strategy and strategic planning can lead to better market positioning in regards to competitors and also positively affect the profitability of a comp...

  9. Development of a Compound Optimization Approach Based on Imperialist Competitive Algorithm

    Science.gov (United States)

    Wang, Qimei; Yang, Zhihong; Wang, Yong

    In this paper, an improved novel approach is developed for the imperialist competitive algorithm to achieve a greater performance. The Nelder-Meand simplex method is applied to execute alternately with the original procedures of the algorithm. The approach is tested on twelve widely-used benchmark functions and is also compared with other relative studies. It is shown that the proposed approach has a faster convergence rate, better search ability, and higher stability than the original algorithm and other relative methods.

  10. Developing the Management Competencies for Getting a Competitive Position in the Organic Food Market

    OpenAIRE

    Marian NASTASE; Mirela STOIAN; Raluca Andreea ION

    2011-01-01

    Although almost any conference tackles the issue of organic foods, we consider that this article does not fit into normal patterns of research. Our paper proposes a complex analysis in the field of organic food products. It also highlights the need of developing new competences of managers and marketers in analysing market for getting a competitive position on it. The method used is the Six Thinking Hats, devised by Edward de Bono. This method appeals to the driving creative thinking; it can ...

  11. [Centralized purchasing of essential drugs, a priority for the health care systems of developing countries].

    Science.gov (United States)

    Blaise, P; Dujardin, B; de Béthune, X; Vandenbergh, D

    1998-01-01

    Health sector reform is a key priority of many governments throughout the world. Drug supply systems are a major element of public health policy design in Africa, where 90% of drugs are imported. The WHO Essential Drugs Program and the UNICEF sponsored Bamako Initiative have, since the late 1980s, promoted the rational use of essential drugs and attempted to ensure a sustainable drug supply through the implementation of cost recovery schemes and quality assurance mechanisms in public health services. A new market for drugs is emerging within this framework and there is growing competition for its control. Government medical stores are all too often bankrupt and the private sector is expensive, catering mainly for the middle to upper classes of urban areas. An intermediate alternative. Essential Drugs Purchasing Offices (EDPOs), has been proposed to balance social objectives and economic constraints. Some of the experimental strategies have given promising results. However, their implementation raises a number of questions: What is the role of the EDPO? Should it promote public health issues in general or focus purely on drug availability? What is the most appropriate legal status? Public or private? For profit or not? How should the investment capital be structured? In drugs or in funds? With ample provision or a tight budget? How should drug purchases be managed? Where should drugs be purchased? How much? How often? According to which procedures? How should the distribution of drugs be organized? Supplying everyone? Pushing supplies or pulling purchasers in? The answers to these questions, analysis of the reasons for success and failure and the dissemination of the information gathered should identify priorities for action and future research and define a framework for expansion. These are the objectives of the "Concerted Action for the Development of EDPO in Sub-Saharan African Countries" which is supported by the European Union (DG XII).

  12. 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.

  13. Novel Pharmacometric Methods for Informed Tuberculosis Drug Development

    OpenAIRE

    Clewe, Oskar

    2016-01-01

    With approximately nine million new cases and the attributable cause of death of an estimated two millions people every year there is an urgent need for new and effective drugs and treatment regimens targeting tuberculosis. The tuberculosis drug development pathway is however not ideal, containing non-predictive model systems and unanswered questions that may increase the risk of failure during late-phase drug development. The aim of this thesis was hence to develop pharmacometric tools in or...

  14. Potential of metabolomics in preclinical and clinical drug development.

    Science.gov (United States)

    Kumar, Baldeep; Prakash, Ajay; Ruhela, Rakesh Kumar; Medhi, Bikash

    2014-12-01

    Metabolomics is an upcoming technology system which involves detailed experimental analysis of metabolic profiles. Due to its diverse applications in preclinical and clinical research, it became an useful tool for the drug discovery and drug development process. This review covers the brief outline about the instrumentation and interpretation of metabolic profiles. The applications of metabolomics have a considerable scope in the pharmaceutical industry, almost at each step from drug discovery to clinical development. These include finding drug target, potential safety and efficacy biomarkers and mechanisms of drug action, the validation of preclinical experimental models against human disease profiles, and the discovery of clinical safety and efficacy biomarkers. As we all know, nowadays the drug discovery and development process is a very expensive, and risky business. Failures at any stage of drug discovery and development process cost millions of dollars to the companies. Some of these failures or the associated risks could be prevented or minimized if there were better ways of drug screening, drug toxicity profiling and monitoring adverse drug reactions. Metabolomics potentially offers an effective route to address all the issues associated with the drug discovery and development. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Antibody Positron Emission Tomography Imaging in Anticancer Drug Development

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Williams, Simon P.; Terwisscha Van Scheltinga, Anton; Lub-de Hooge, Marjolijn N.; Schroeder, Carolien P.; Gietema, Jourik A.; Brouwers, Adrienne H.; de Vries, Elisabeth G. E.

    2015-01-01

    More than 50 monoclonal antibodies (mAbs), including several antibody-drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process,

  16. Developing Competitive Advantage in the Private Medical Services Market. The Case of Romania

    Directory of Open Access Journals (Sweden)

    Simona BASTURESCU

    2014-10-01

    Full Text Available Health was, is and will always be a top priority for a country’s stakeholders. The average health expenditure depicts an impressive variability worldwide, with Americans being the top spenders and South East Asia countries being at the bottom of the respective list. This study analyses the existing competitive advantages of the most important players in the private medical services market, in Romania. It traces their development and the factors that determine positioning strategic decisions. The competitive advantage of a business in the private medical services market is a result of a number of factors. The top three criteria of choice for a patient are doctors, medical technology and waiting time for accessing the service. The objectives of this research paper are: 1. to identify the key success factors (KSFs and the drivers of change (DC in the Romanian Medical Industry; 2. to propose a fine tuning in strategy as a response to changes in the macro and micro environment, 3. to re-evaluate existing business models and propose amendments that may lead to future sustainable competitive advantage and 4. to develop a proposition for growth strategies, business strategies and means of implementation that will lead to long term growth.

  17. ROLE OF RESOURCE-BASED ENTREPRENEURSHIP DEVELOPMENT TO INCREASE COMPETITIVENESS OF TRADITIONALLY WOVEN SARONG CREATIVE INDUSTRY

    Directory of Open Access Journals (Sweden)

    Zakiyah Z.

    2017-07-01

    Full Text Available The objectives of the study were to describe position of traditionally woven sarong creative industry in Donggala in business competition based on both internal aspects (strength and weakness and external ones (opportunity and threats, and role of resource-based entrepreneurship development to improve competitiveness of the traditionally woven sarong creative industry in Donggala. In order to meet the objectives, the study used SWOT and Moderating Regression Analysis (MRA. The findings showed that the strength of the Donggala woven sarong industry was the sarong had indigenous Central Sulawesi pattern, it was part of the rural society and was traditionally made. The weaknesses were the sarong pattern and design had yet been touched by modern technology, its color faded away easily during laundry and it was only sold in the local areas. The opportunities were the sarong may become alternative souvenir from Central Sulawesi and development of creative economy was widely discussed recently. The threat was there were various types and patterns of sarong in the market; and entrepreneurship was moderating variables between resource-based strategy and competitiveness of Donggala woven sarong creative industry; the level of significance was 0.001 and the R-Square was 0.803.

  18. The tuberculosis drug discovery and development pipeline and emerging drug targets.

    Science.gov (United States)

    Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

    2015-01-29

    The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal.

  19. Overcoming drug crystallization in electrospun fibers--Elucidating key parameters and developing strategies for drug delivery.

    Science.gov (United States)

    Seif, Salem; Franzen, Lutz; Windbergs, Maike

    2015-01-15

    For the development of novel therapeutics, uncontrolled crystallization of drugs within delivery systems represents a major challenge. Especially for thin and flexible polymeric systems such as oral films or dermal wound dressings, the formation and growth of drug crystals can significantly affect drug distribution and release kinetics as well as physical storage stability. In this context, electrospinning was introduced as a fabrication technique with the potential to encapsulate drugs within ultrafine fibers by rapid solvent evaporation overcoming drug crystallization during fabrication and storage. However, these effects could so far only be shown for specific drug-polymer combinations and an in-depth understanding of the underlying processes of drug-loaded fiber formation and influencing key parameters is still missing. In this study, we systematically investigated crystal formation of caffeine as a model drug in electrospun fibers comparing different polymers. The solvent polarity was found to have a major impact on the drug crystal formation, whereas only a minor effect was attributed to the electrospinning process parameters. Based on an in-depth understanding of the underlying processes determining drug crystallization processes in electrospun fibers, key parameters could be identified which allow for the rational development of drug-loaded electrospun fibers overcoming drug crystallization.

  20. Recent developments in genomics, bioinformatics and drug discovery to combat emerging drug-resistant tuberculosis.

    Science.gov (United States)

    Swaminathan, Soumya; Sundaramurthi, Jagadish Chandrabose; Palaniappan, Alangudi Natarajan; Narayanan, Sujatha

    2016-12-01

    Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB control. The delay in diagnosis of DR-TB leads to its increased transmission, and therefore prevalence. Recent developments in genomics have enabled whole genome sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine DR mutations rapidly from the resulting sequences. The present drug discovery and development pipeline is filled with candidate drugs which have shown efficacy against DR-TB. Furthermore, some of the FDA-approved drugs are being evaluated for repurposing, and this approach appears promising as several drugs are reported to enhance efficacy of the standard TB drugs, reduce drug tolerance, or modulate the host immune response to control the growth of intracellular M. tuberculosis. Recent developments in genomics and bioinformatics along with new drug discovery collectively have the potential to result in synergistic impact leading to the development of a rapid protocol to determine the drug resistance profile of the infecting strain so as to provide personalized medicine. Hence, in this review, we discuss recent developments in WGS, bioinformatics and drug discovery to perceive how they would transform the management of tuberculosis in a timely manner.

  1. Collaborative pre-competitive preclinical drug discovery with academics and pharma/biotech partners at Sanford|Burnham: infrastructure, capabilities & operational models.

    Science.gov (United States)

    Chung, Thomas D Y

    2014-03-01

    There has been increased concern that the current "blockbuster" model of drug discovery and development practiced by "Big Pharma" are unsustainable in terms of cost (> $1 billion/approved drug) and time to market (10 - 15 years). The recent mergers and acquisitions (M&A), shuttering of internal research programs, closure of "redundant" sites of operations, senior management turnover and continued workforce reductions among the top 10 major pharmaceutical companies reflect draconian responses to reduce costs. However, the resultant exodus of intellectual capital, loss in motivation and momentum, and exit from early stage discovery programs by pharmaceutical companies has contributed to an "innovation deficit". Disease advocacy groups, investment communities and the government are calling for new innovative business models to address this deficit. In particular they are looking towards academia and clinical trials centers to catalyze new innovations in translational research. Indeed over the last decade many academic institutions have launched drug discovery centers largely comprising high-throughput screening (HTS) to accelerate "translational" research. A major impetus for this "open innovation" effort has been the National Institutes of Health (NIH) "Roadmap" and Molecular Libraries Initiative/Program (MLI/MLP), which is in its last year, and will be transitioned into the National Center for the Advancement of Translational Sciences (NCATS). With the end of Roadmap funding, general reduction in Federal government funding and its recent sequestration, academic drug discovery centers are being challenged to become selfsustaining, adding financial value, while remaining aligned with the missions of their respective academic non-profit institutions. We describe herein, a brief history of our bi-coastal Conrad Prebys Center for Chemical Genomics (Prebys Center) at the Sanford|Burnham Medical Research Institute (SBMRI), the key components of its infrastructure, core

  2. Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives.

    Science.gov (United States)

    Cooper, Jason P; Reynolds, C Patrick; Cho, Hwangeui; Kang, Min H

    2017-06-01

    Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved drugs. Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.

  3. A development perspective on adolescent drug abuse.

    Science.gov (United States)

    Baumrind, D; Moselle, K A

    1985-01-01

    Adolescent drug use is placed in an historical and developmental perspective. Existing evidence concerning causes and consequences of adolescent drug use is inconclusive. In the absence of conclusive empirical evidence and cogent theories, we present a prima facie case against early adolescent drug use by defending six propositions which posit specific cognitive, conative, and affective negative consequences including impairment of attention and memory; developmental lag imposing categorical limitations on the level of maximum functioning available to the user in cognitive, moral and psychosocial domains; amotivational syndrome; consolidation of diffuse or negative identity; and social alienation and estrangement. We call for a program of research which could provide credible evidence to support or rebut these propositions, and thus address the factual claims underlying the sociomoral concerns of social policy planners.

  4. Assessment of pre-competitive research and development needs for industrial waste minimization

    Energy Technology Data Exchange (ETDEWEB)

    Young, J.K.; Fassbender, L.L. [Pacific Northwest Lab., Richland, WA (United States); Sen, R.K. [Sen (R.K.) and Associates, Washington, DC (United States)

    1992-02-01

    This report summarizes the findings of the first phase of a study undertaken to define a role for the Advanced Industrial Concepts (AIC) Division of the Office of Industrial Technologies (OIT) in developing waste minimization technologies for the industrial sector. The report describes the results of an industrial waste characterization based mainly on the US Environmental Protection Agency`s (EPA`s) 1989 Toxics Release Inventory (TRI) database. IN addition, it contains the results of interviews with personnel from trade associations, environmental advocacy groups, federal agencies, and industrial firms regarding pre-competitive research and development needs for industrial waste minimization. Recommendations for future AIC waste minimization activities are provided.

  5. Assessment of pre-competitive research and development needs for industrial waste minimization

    Energy Technology Data Exchange (ETDEWEB)

    Young, J.K.; Fassbender, L.L. (Pacific Northwest Lab., Richland, WA (United States)); Sen, R.K. (Sen (R.K.) and Associates, Washington, DC (United States))

    1992-02-01

    This report summarizes the findings of the first phase of a study undertaken to define a role for the Advanced Industrial Concepts (AIC) Division of the Office of Industrial Technologies (OIT) in developing waste minimization technologies for the industrial sector. The report describes the results of an industrial waste characterization based mainly on the US Environmental Protection Agency's (EPA's) 1989 Toxics Release Inventory (TRI) database. IN addition, it contains the results of interviews with personnel from trade associations, environmental advocacy groups, federal agencies, and industrial firms regarding pre-competitive research and development needs for industrial waste minimization. Recommendations for future AIC waste minimization activities are provided.

  6. 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

  7. CNS Anticancer Drug Discovery and Development Conference White Paper.

    Science.gov (United States)

    Levin, Victor A; Tonge, Peter J; Gallo, James M; Birtwistle, Marc R; Dar, Arvin C; Iavarone, Antonio; Paddison, Patrick J; Heffron, Timothy P; Elmquist, William F; Lachowicz, Jean E; Johnson, Ted W; White, Forest M; Sul, Joohee; Smith, Quentin R; Shen, Wang; Sarkaria, Jann N; Samala, Ramakrishna; Wen, Patrick Y; Berry, Donald A; Petter, Russell C

    2015-11-01

    Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric "Accelerating Drug Discovery and Development for Brain Tumors," further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. SMEs Development Strategy for Competitive and Sustainable Typical Local Snacks of Banten Province

    Directory of Open Access Journals (Sweden)

    Sawarni Hasibuan

    2015-01-01

    Full Text Available Small Medium Enterprises (SMEs for snacks in Indonesia currently has a good growth rate on one hand; but on the other hand, its level of competition is also quite high.  Growth in sales volume of the Indonesian snack industry, both in modern and traditional markets in 2012, was recorded at 10-15 percent far beyond the growth of other manufacturing industries.  However, the level of competition in the snack industry is also relatively high. Business people in the snacks sector do not only compete with fellow local business people but also with imported products, both legal and illegal.  Currently, Banten Province is indeed not known as a culinary destination with a variety of distinctively local foods. The growth  of the food industry in Banten Province is not as rapid as other manufacturing industries. However, in Banten, some types of food produced in small and medium scales (SMEs are also known.  Therefore, efforts to develop and empower typical local snack SMEs in Banten Province needs to be conducted to be able to increase its competitiveness in facing the globalization era and the ASEAN free market in 2015.  The purpose of this reseach is to map the performance profile of Banten typical local snack SMEs and to provide recommendation on SME development strategies for competitive and sustainable Banten typical local snacks.  The research method used combines the descriptive research method, IPA (Importance Performance Analysis, and SWOT analysis.  The performance level measurement for Banten typical local snack SMEs is based on stakeholder perceptions on the condition of the existing 16 attributes compared to the perception on the development expectation of each of these attributes.  Results of SWOT matrix mapping puts  the products of Banten typical local snack SMEs in quadran II.  The strategy prioritized is the quality attribute maintenance strategy for superior products, as well as product diversification to expand market share

  9. Tourism Cluster Competitiveness and Sustainability: Proposal for a Systemic Model to Measure the Impact of Tourism on Local Development

    Directory of Open Access Journals (Sweden)

    Sieglinde Kindl da Cunha

    2005-07-01

    Full Text Available This article proposes a model to measure tourism cluster impact on local development with a view to assessing tourism cluster interaction, competitiveness and sustainability impacts on the economy, society and the environment. The theoretical basis for this model is founded on cluster concept and typology adapting and integrating the systemic competitiveness and sustainability concepts within economic, social, cultural, environmental and political dimensions. The proposed model shows a holistic, multidisciplinary and multi-sector view of local development brought back through a systemic approach to the concepts of competitiveness, social equity and sustainability. Its results make possible strategic guidance to agents responsible for public sector tourism policies, as well as the strategies for competitiveness, competition, cooperation and sustainability in private companies and institutions.

  10. Competition for ligands between FGFR1 and FGFR4 regulates Xenopus neural development.

    Science.gov (United States)

    Yamagishi, Masahiro; Okamoto, Harumasa

    2010-01-01

    Cell-surface-localized receptors and their extracellular ligands usually comprise distinct families and promote diversity of signal transduction regulation. The number of available ligand molecules is often the limiting factor for receptor activation during interpretation of the signal by the responding cell. Limited ligand availability in a particular area of tissue should lead to local competition between different members of a receptor family for binding and subsequent activation. Fibroblast growth factor receptor (FGFR) 4 (FGFR4) is a less potent activator of downstream pathways than FGFR1, the major subtype of FGFR. Regional expression of Xenopus FGFR1 and FGFR4 (XFGFR1 and XFGFR4, respectively) overlap in the anterior part of prospective and developing neural tissue. In this paper we show that XFGFR1 and XFGFR4 have opposing effects on the positioning of expression domains of mid- and hindbrain markers when the expression levels of the receptors are altered. We present a line of evidence to support our hypothesis that competition between XFGFR1 and XFGFR4 for ligands is required for correct positioning of marker expression. Local competition between receptors with different potencies should provide an efficient means for a cell to interpret the ligand signal correctly, and may constitute a more general mechanism for regulating signal transduction.

  11. The possibility of coexistence and co-development in language competition: ecology-society computational model and simulation.

    Science.gov (United States)

    Yun, Jian; Shang, Song-Chao; Wei, Xiao-Dan; Liu, Shuang; Li, Zhi-Jie

    2016-01-01

    Language is characterized by both ecological properties and social properties, and competition is the basic form of language evolution. The rise and decline of one language is a result of competition between languages. Moreover, this rise and decline directly influences the diversity of human culture. Mathematics and computer modeling for language competition has been a popular topic in the fields of linguistics, mathematics, computer science, ecology, and other disciplines. Currently, there are several problems in the research on language competition modeling. First, comprehensive mathematical analysis is absent in most studies of language competition models. Next, most language competition models are based on the assumption that one language in the model is stronger than the other. These studies tend to ignore cases where there is a balance of power in the competition. The competition between two well-matched languages is more practical, because it can facilitate the co-development of two languages. A third issue with current studies is that many studies have an evolution result where the weaker language inevitably goes extinct. From the integrated point of view of ecology and sociology, this paper improves the Lotka-Volterra model and basic reaction-diffusion model to propose an "ecology-society" computational model for describing language competition. Furthermore, a strict and comprehensive mathematical analysis was made for the stability of the equilibria. Two languages in competition may be either well-matched or greatly different in strength, which was reflected in the experimental design. The results revealed that language coexistence, and even co-development, are likely to occur during language competition.

  12. TECHNOLOGY COMPETITIONS AND OLYMPIADS AMONG PUPILS AS A MEANS OF DIAGNOSTICS AND DEVELOPMENT OF THEIR GIFTEDNESS

    Directory of Open Access Journals (Sweden)

    O. V. Shatunova

    2014-01-01

    Full Text Available The research is aimed to show the significance of Technology (Handicraft lessons competitions and olimpiads (academic competitions among general education institutions pupils of the Republic of Tatarstan. The authorsnote the efficiency of these activities as the diagnostics means and improvement of natural gifted children and teenagers. Methods. The applied methods involve criteria approach to the giftedness types assessment; generalization of the advanced pedagogical theory and practice, supervision, teachership surveys and discussions with them. Results. The experience of Technology competitions and olimpiads (academiccompetitions implementation among school pupils of Kazan Federal University, Elabuga Institute is described. The research outcomes show that pupils participation in such activities not only contributes the creative potential realization but also forms sustainable interest to engineering-technical and design activitiesthat subsequently influence a graduates’ choice of high-demand majors (specialities and professions at the contemporary labour market. Additionally, the authors emphasize the objective necessity of specific teachers’ training, and formation of necessary professional skills set for successful work with gifted pupils. Scientific novelty. The research identifies a number of criteria for diagnostics of giftedness types. It is specially noted that the most important point of this phenomenon is propensity to work as the primary factor of ingenuity and talent. Practical significance. Implementation of the research outcomes can be used for further development of Technology competitions and olimpiads implementation among school pupils in high vocational education institutions that are qualified at students’ training on pedagogic majors, as well as in supplementary education establishments for children and teenagers

  13. TECHNOLOGY COMPETITIONS AND OLYMPIADS AMONG PUPILS AS A MEANS OF DIAGNOSTICS AND DEVELOPMENT OF THEIR GIFTEDNESS

    Directory of Open Access Journals (Sweden)

    O. V. Shatunova

    2015-03-01

    Full Text Available The research is aimed to show the significance of Technology (Handicraft lessons competitions and olimpiads (academic competitions among general education institutions pupils of the Republic of Tatarstan. The authorsnote the efficiency of these activities as the diagnostics means and improvement of natural gifted children and teenagers. Methods. The applied methods involve criteria approach to the giftedness types assessment; generalization of the advanced pedagogical theory and practice, supervision, teachership surveys and discussions with them. Results. The experience of Technology competitions and olimpiads (academiccompetitions implementation among school pupils of Kazan Federal University, Elabuga Institute is described. The research outcomes show that pupils participation in such activities not only contributes the creative potential realization but also forms sustainable interest to engineering-technical and design activitiesthat subsequently influence a graduates’ choice of high-demand majors (specialities and professions at the contemporary labour market. Additionally, the authors emphasize the objective necessity of specific teachers’ training, and formation of necessary professional skills set for successful work with gifted pupils. Scientific novelty. The research identifies a number of criteria for diagnostics of giftedness types. It is specially noted that the most important point of this phenomenon is propensity to work as the primary factor of ingenuity and talent. Practical significance. Implementation of the research outcomes can be used for further development of Technology competitions and olimpiads implementation among school pupils in high vocational education institutions that are qualified at students’ training on pedagogic majors, as well as in supplementary education establishments for children and teenagers

  14. 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.

  15. Do companion diagnostics make economic sense for drug developers?

    Science.gov (United States)

    Agarwal, Amit

    2012-09-15

    Drug developers are grappling with the impact of personalized medicine on their portfolios. The combination of molecular diagnostics with targeted biologic therapies has been hailed as a recent innovation with few historical analogs to guide behavior. However, if the definition of companion diagnostics is broadened to include any drug whose FDA approved label requires diagnostic testing before prescription then over 50 drugs across multiple therapeutic areas arise. Most importantly for current drug developers, these drugs represent a wide variety of market situations and with sufficient historical data to evaluate different commercialization strategies for the combination. Included in these examples are drugs which were not initially launched with companion diagnostics but were required to implement companion diagnostics after they were on the market for a period of time. The historical case studies demonstrate that companion diagnostics are neither a universal panacea nor an unmitigated disaster for drug developers but require an understanding of specific situations to determine the utility of companion diagnostics. Numerous case studies highlight how companion diagnostics have been a boon to drug developers including Iressa, statins, Soriatane, Arthrotec, Promacta, Nplate, Letairis, and Tracleer. Other examples provide lessons on how to avoid pitfalls such as Accutane, Ticlid, Tegretol, Ziagen, Actigall and Clozaril. By carefully evaluating these case studies, drug developers can gain insight on the appropriate companion diagnostic strategy to implement for their specific situation and develop the elements of a successful companion diagnostic strategy.

  16. 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.

  17. Rethinking the paradigm for the development of inhaled drugs.

    Science.gov (United States)

    Pritchard, John N

    2015-12-30

    Nebulized treatment is an important delivery option for the young, elderly, and those with severe chronic respiratory disease, but there is a lack of new nebulized drug products being produced for these patients, leading to the potential for under-treatment. This communication describes a new drug development paradigm as a timely solution to this issue. Often, drug development is initiated with nebulizers in the early stages, to provide cheaper and faster drug development, and then switched to inhaler devices in later clinical trials to address the majority of patients. However, the waste of resource on parallel development of the inhaler can be large due to the high early attrition rate of new drug development. The new paradigm uses the nebulizer to continue drug development through to market, and initiates inhaler development after completion of the riskier early phase studies. New drug safety and efficacy can be assessed faster and more efficiently by using a nebulized formulation rather than developing an inhaler. The results of calculations of expected net present value showed that the new paradigm produced higher expected net present values than the conventional model over a range of economic scenarios. This new paradigm could therefore provide improved returns on investments, as well as more modern drugs in nebulized form for those patients unable to use inhalers.

  18. 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

  19. Ex Vivo Metrics, a preclinical tool in new drug development.

    Science.gov (United States)

    Curtis, C Gerald; Bilyard, Kevin; Stephenson, Hugo

    2008-01-23

    Among the challenges facing translational medicine today is the need for greater productivity and safety during the drug development process. To meet this need, practitioners of translational medicine are developing new technologies that can facilitate decision making during the early stages of drug discovery and clinical development. Ex Vivo Metrics is an emerging technology that addresses this need by using intact human organs ethically donated for research. After hypothermic storage, the organs are reanimated by blood perfusion, providing physiologically and biochemically stable preparations. In terms of emulating human exposure to drugs, Ex Vivo Metrics is the closest biological system available for clinical trials. Early application of this tool for evaluating drug targeting, efficacy, and toxicity could result in better selection among promising drug candidates, greater drug productivity, and increased safety.

  20. Ex Vivo Metrics™, a preclinical tool in new drug development

    Directory of Open Access Journals (Sweden)

    Bilyard Kevin

    2008-01-01

    Full Text Available Abstract Among the challenges facing translational medicine today is the need for greater productivity and safety during the drug development process. To meet this need, practitioners of translational medicine are developing new technologies that can facilitate decision making during the early stages of drug discovery and clinical development. Ex Vivo Metrics™ is an emerging technology that addresses this need by using intact human organs ethically donated for research. After hypothermic storage, the organs are reanimated by blood perfusion, providing physiologically and biochemically stable preparations. In terms of emulating human exposure to drugs, Ex Vivo Metrics is the closest biological system available for clinical trials. Early application of this tool for evaluating drug targeting, efficacy, and toxicity could result in better selection among promising drug candidates, greater drug productivity, and increased safety.

  1. 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.

  2. Developing power markets - Development of market place for meeting the demand - Case India, in transition from regulated to competitive structure

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pranay; Sarkar, Prabhajit Kumar

    2010-09-15

    Power Market players of developing countries with supply deficit are exposed to a unique combination of price risk and quantity risk which is not the case with developed nations that have taken path of liberalization to open up their power markets. India has one of the largest generation capacities in the world, yet till recently the Indian Power sector was highly regulated. However, the last decade has witnessed many initiatives so as to make the sector market oriented. This paper provides opportunity for developing countries to learn from Indian experience of introducing competition in the power sector.

  3. How to Apply Sustainable Competitive Advantage for Regional Developments (Case: Ostrobothnia Region of Finland

    Directory of Open Access Journals (Sweden)

    Takala Josu

    2014-06-01

    Full Text Available Nowadays companies concern more about how to survive and extend their own business in future in their current marketplace. However, developing and prospering a region of the country is becoming more crucial question. Successful cooperation and partnership between different sectors of economy (for instance, between companies, public and academic sectors leads to the flourishing and prosperity of the region and consequently of a country. European Commission established smart specialization platform, which is a strategic approach to economic development of a region. By defining and developing of vision, competitive advantages and strategic preferences, region will determine knowledge-based potential. The purpose of this paper is to assign and define the collaboration/relations existed, how strong these relations are and what the expectations are between 3 sectors of economy: public, academic and business. Area of carrying out this research is Ostrobothnia region, however, connections in other regions of Finland and internationally is also presented. There have been chosen 3 industrial peaks from Ostrobothnia region: Energy, Fur and Boat industrial peaks. Analysis is conducted by implementing two core methods: Sense & Respond (S&R and Sustainable Competitive Advantage (SCA. The goal of this research is also to use S&R method so as to allocate efficiently resources, and to define competitive priorities in cooperation. The main results show that the most tight collaboration and partnership is observed between companies and companies in all around Finland and internationally. While concerning other relationships, companies expect to have tighter cooperation especially in Ostrobothnia and other regions of Finland.

  4. CURRENT TRENDS OF THE REGIONAL DEVELOPMENT POLICY IN THE EUROPEAN UNION. THE DEVELOPMENT OF COMPETITIVE ECONOMIC AGGLOMERATIONS OF CLUSTER TYPE

    Directory of Open Access Journals (Sweden)

    LAURA CISMAŞ

    2010-01-01

    Full Text Available The study of economic agents’ behaviour, whose nowadays tendency is togroup themselves in space as clusters, has an important place in the field of localizing industrialactivities. This is due to domestic scale economies, known as agglomerations economies.According to Edgar M. Hoover (Hoover, 1948, domestic scale economies are specific tocompanies; the economies of localizing - to a certain branch, whose companies form clusters incertain geographical arias, and the urbanization economies are specific to cities, where thereare clusters of companies from different branches. The specialty literature regarding localeconomic development, based on the idea of cluster starts from well-known economic theories,such as: agglomeration theory (Alfred Marshall, the theory of spatial localizing of industrialunits (Alfred Weber, the theory of interdependence of locations (Harold Hotelling, the diamondtheory (Michael Porter, the theory of entrepreneurship (Joseph Schumpeter, the theory ofgeographical concentration. Basically, the common point which links them are the conceptswhich occur in these theories, such as: industrial district, industrial agglomeration, spatialinterdependence, concepts which lie at the basis of the cluster idea. Clusters represent animportant instrument for promoting industrial development, innovation, competitiveness andeconomic growth. If, at the beginning, the effort to develop clusters belonged to private personsand companies, nowadays, the actors involved in their development are the governments andpublic institutions of national or regional level.The objective established within the Lisbon Strategy (2000, to make the EuropeanUnion “the most competitive and dynamic knowledge-based economy”, is tightly linked to thenew approaches of the European economic policy, to competitiveness. One of the policies isfocused on developing at the European Union level clusters in the high competitiveness fields. with an innovative character

  5. The Expanding Role of NMR in Drug Discovery and Development

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ The role of NMR in the pharmaceutical industry has changed dramatically over the last decade. Once thought of as an analytical technique used primarily to support synthetic chemistry, NMR now has an important role in the investigation of biochemical changes involved in clinical diseases and drug toxicity. It is also used extensively to elucidate the structures of drug metabolites. Data obtained using LC NMR MS and 19F NMR will be used to illustrate the utility of hyphenated methods in identifying xenobiotic metabolites as part of a drug development program. The application of NMR to the study of potential drug toxicity will also be described using the cationic, amphiphilic drugs chloroquine and amiodarone. These drugs are known to induce phospholipidosis characterized by lysosomal lamellar bodies and drug accumulation. Using a metabonomic approach, NMR spectroscopy of urine allowed the identification of a combination of urinary biomarkers of phospholipidosis.

  6. Development and trial of the drug interaction database system

    Directory of Open Access Journals (Sweden)

    Virasakdi Chongsuvivatwong

    2003-07-01

    Full Text Available The drug interaction database system was originally developed at Songklanagarind Hospital. Data sets of drugs available in Songklanagarind Hospital comprising standard drug names, trade names, group names, and drug interactions were set up using Microsoft® Access 2000. The computer used was a Pentium III processor running at 450 MHz with 128 MB SDRAM operated by Microsoft® Windows 98. A robust structured query language algorithm was chosen for detecting interactions. The functioning of this database system, including speed and accuracy of detection, was tested at Songklanagarind Hospital and Naratiwatrachanagarind Hospital using hypothetical prescriptions. Its use in determining the incidence of drug interactions was also evaluated using a retrospective prescription data file. This study has shown that the database system correctly detected drug interactions from prescriptions. Speed of detection was approximately 1 to 2 seconds depending on the size of prescription. The database system was of benefit in determining of incidence rate of drug interaction in a hospital.

  7. Nano-formulations of drugs: Recent developments, impact and challenges.

    Science.gov (United States)

    Jeevanandam, Jaison; Chan, Yen San; Danquah, Michael K

    2016-01-01

    Nano-formulations of medicinal drugs have attracted the interest of many researchers for drug delivery applications. These nano-formulations enhance the properties of conventional drugs and are specific to the targeted delivery site. Dendrimers, polymeric nanoparticles, liposomes, nano-emulsions and micelles are some of the nano-formulations that are gaining prominence in pharmaceutical industry for enhanced drug formulation. Wide varieties of synthesis methods are available for the preparation of nano-formulations to deliver drugs in biological system. The choice of synthesis methods depend on the size and shape of particulate formulation, biochemical properties of drug, and the targeted site. This article discusses recent developments in nano-formulation and the progressive impact on pharmaceutical research and industries. Additionally, process challenges relating to consistent generation of nano-formulations for drug delivery are discussed.

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

    Science.gov (United States)

    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

    2016-09-01

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale 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 multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models.

  9. Defining "innovativeness" in drug development: a systematic review.

    Science.gov (United States)

    Kesselheim, A S; Wang, B; Avorn, J

    2013-09-01

    Some observers of drug development argue that the pace of pharmaceutical innovation is declining, but others deny that contention. This controversy may be due to different methods of defining and assessing innovation. We conducted a systematic review of the literature to develop a taxonomy of methods for measuring innovation in drug development. The 42 studies fell into four main categories: counts of new drugs approved, assessments of therapeutic value, economic outcomes, and patents issued. The definition determined whether a study found a positive or negative trend in innovative drug development. Of 21 studies that relied on counts, 9 (43%) concluded that the trend for drug discovery was favorable, 11 (52%) concluded that the trend was not favorable, and 1 reached no conclusion. By contrast, of 21 studies that used other measures of innovation, 0 concluded that the trend was favorable, 8 (47%) concluded that the trend was not favorable, and 13 reached no conclusion (P = 0.03).

  10. [Strategies for pharmaceutical research and development. II. Generic drugs].

    Science.gov (United States)

    Kuchar, M

    1996-07-01

    When the patent protection is terminated, the original registered-mark preparation becomes a generic drug, which results in a decrease in its price as compared with the original pharmaceutical. The effects of changes in price relation are discussed from the viewpoint of the generic firms and the manufacturers of original preparations. The differences in the insurance system and legislative regulations of the registration of generic preparations can markedly the size influence of the share of generic drugs in the total consumption of drugs. The future development of generic drugs from a general viewpoint is discussed in relation to the contemporary extensive expiration of patent protection of drugs. The hitherto results are summed up and the topics for the present strategy of the development of generic drugs in the Research Institute for Pharmacy and Biochemistry, or in the Czech Republic, respectively are discussed.

  11. Entrepreneurship as a Competitive Development of Vocational Education: Theory and Practice

    Directory of Open Access Journals (Sweden)

    A. G. Mokronosov

    2013-01-01

    Full Text Available The paper considers the complex of economic processes in the sphere of the higher vocational education. The research is aimed at investigating, clarifying and systemizing the theoretical concepts of entrepreneur- ship in the context of the knowledge economy and rising competitiveness in the market of scientific and educational services. The research methodology basis involves the works of domestic and foreign scholars in the fields of competitive development, entrepreneurship, quasi-markets theories and self- developing organizations. The paper presents the author’s interpretation of the university entrepreneurship as the integrated and systematic process generated by the dramatic changes of socio-economic development, increasing global trends of economy intellectualization, significant proportion of scientific and educational services, and increasing role of modernization in sustaining the state welfare and stability. The university entrepreneurship is regarded as a synthesis of creative, innovative, commercial and managerial activities in the market of scientific and educational services, labor market, industrial and financial markets. The interrelation of economic and social aspects of university business is revealed including the links between the government, universities, scientific educational institutions, business community, households and other subjects of educational service market. The application of the main theoretical principles of the research concerning the higher school business vector is demonstrated by the practical activity of the Russian Vocational Pedagogical University. 

  12. Single cell analytic tools for drug discovery and development

    Science.gov (United States)

    Heath, James R.; Ribas, Antoni; Mischel, Paul S.

    2016-01-01

    The genetic, functional, or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development.1-3 In cancers, heterogeneity may be essential for tumor stability,4 but its precise role in tumor biology is poorly resolved. This challenges the design of accurate disease models for use in drug development, and can confound the interpretation of biomarker levels, and of patient responses to specific therapies. The complex nature of heterogeneous tissues has motivated the development of tools for single cell genomic, transcriptomic, and multiplex proteomic analysis. We review these tools, assess their advantages and limitations, and explore their potential applications in drug discovery and development. PMID:26669673

  13. The Development of Magnetic Drug Delivery and Disposition

    OpenAIRE

    Marszall, Michal Piotr

    2012-01-01

    Available from: http://www.intechopen.com/books/the-delivery-of-nanoparticles/the-development-of-magnetic-drug-deliveryand-disposition The process of drug delivery and disposition in the modern scientific aspect is very complex. Advances in many fields are converging to make the commercialisation of advanced drug delivery concepts possible. It integrates many disciplines, including biotechnology, medicine and pharmacology. Innovative devices should protect labile active ingredient...

  14. The Metabolism of Anticancer Drugs by the Liver: Current Approaches to the Drug Development Process.

    Science.gov (United States)

    Belka, Mariusz; Bączek, Tomasz

    2015-01-01

    The worldwide scientific community is in agreement that the activities of metabolic enzymes greatly impact the efficacies of anticancer drugs. Elucidation of the influences of these drugs on metabolism, especially that occurring in the liver, appears to be an extremely important step in the development of new anticancer drugs. Considering the continuous need to search for safe and effective chemotherapeutics, studies of the metabolism of new potent drugs are very important and should be included in the modern, innovative drug development pipeline. This article summarizes most of the current metabolic case studies involving anticancer drug development. Firstly, the impacts of diverse metabolic enzymes, particularly cytochrome P450, and the utilities of a few model in vitro enzymatic systems are described. Then, different analytical techniques, with particular emphasis on liquid chromatography- mass spectrometry detection and structural elucidation, are discussed. Finally, some computer-aided strategies for decision making in the drug design process are described. Recent advances in drug development, including microdosing, in vitro-in vivo correlation and pharmacologic audit trail, are also discussed in relation to metabolic studies.

  15. Exploring the ocean for new drug developments: Marine pharmacology

    Directory of Open Access Journals (Sweden)

    Harshad Malve

    2016-01-01

    Full Text Available Disease ailments are changing the patterns, and the new diseases are emerging due to changing environments. The enormous growth of world population has overburdened the existing resources for the drugs. And hence, the drug manufacturers are always on the lookout for new resources to develop effective and safe drugs for the increasing demands of the world population. Seventy-five percentage of earth's surface is covered by water but research into the pharmacology of marine organisms is limited, and most of it still remains unexplored. Marine environment represents countless and diverse resource for new drugs to combat major diseases such as cancer or malaria. It also offers an ecological resource comprising a variety of aquatic plants and animals. These aquatic organisms are screened for antibacterial, immunomodulator, anti-fungal, anti-inflammatory, anticancer, antimicrobial, neuroprotective, analgesic, and antimalarial properties. They are used for new drug developments extensively across the world. Marine pharmacology offers the scope for research on these drugs of marine origin. Few institutes in India offer such opportunities which can help us in the quest for new drugs. This is an extensive review of the drugs developed and the potential new drug candidates from marine origin along with the opportunities for research on marine derived products. It also gives the information about the institutes in India which offer marine pharmacology related courses.

  16. Exploring the ocean for new drug developments: Marine pharmacology

    Science.gov (United States)

    Malve, Harshad

    2016-01-01

    Disease ailments are changing the patterns, and the new diseases are emerging due to changing environments. The enormous growth of world population has overburdened the existing resources for the drugs. And hence, the drug manufacturers are always on the lookout for new resources to develop effective and safe drugs for the increasing demands of the world population. Seventy-five percentage of earth's surface is covered by water but research into the pharmacology of marine organisms is limited, and most of it still remains unexplored. Marine environment represents countless and diverse resource for new drugs to combat major diseases such as cancer or malaria. It also offers an ecological resource comprising a variety of aquatic plants and animals. These aquatic organisms are screened for antibacterial, immunomodulator, anti-fungal, anti-inflammatory, anticancer, antimicrobial, neuroprotective, analgesic, and antimalarial properties. They are used for new drug developments extensively across the world. Marine pharmacology offers the scope for research on these drugs of marine origin. Few institutes in India offer such opportunities which can help us in the quest for new drugs. This is an extensive review of the drugs developed and the potential new drug candidates from marine origin along with the opportunities for research on marine derived products. It also gives the information about the institutes in India which offer marine pharmacology related courses. PMID:27134458

  17. Project-Based Market Competition and Policy Implications for Sustainable Developments in Building and Construction Sectors

    Directory of Open Access Journals (Sweden)

    Min-Ren Yan

    2015-11-01

    Full Text Available Building and construction sectors are significant contributors to the global economy, but their energy consumption necessitates greater commitment to sustainable developments. There is therefore a growing demand for green innovation in the form of cleaner production and policies to meet the modern requirements of sustainability. However, the nature in which public work is undertaken is in an environment of project-based market competition, whereby contractors routinely bid for contracts under specific project awarding systems, and variations are accompanied with the unique scope of individual projects before the final goods or services are delivered. A comprehensive understanding of the characteristics and contractors’ behavior in systems could help to identify the leverage points of policies. This paper proposes a system dynamics model, with quantitative analysis and simulations, to demonstrate the problems of a system with different project awarding systems and ineffective market performance. The framework of market efficiency and performance measures has been proposed to evaluate the project-based competition mechanism. Managerial policy implications for market efficiency and sustainable developments can thus be systematically discussed and compared through iterative computer simulations and scenario analysis.

  18. [Development of direct competitive enzyme-linked immunosorbent assay for the determination of domoic acid].

    Science.gov (United States)

    Wang, Qian; Cheng, Jin-Ping; Gao, Li-Li; Dong, Yu; Xi, Lei

    2012-02-01

    To develop a direct competitive enzyme-linked immunosorbent assay (ELISA) for rapid detection of domoic acid concentrations, HRP (horse radish peroxidase) was successfully linked to DA using EDC. The concentration of DA was quantitatively analyzed on the basic of the specific immune responses between the DA- HRP and the monoclonal antibodies made in advance. Calibration curve were established after the optimization of reaction conditions such as the type of blocking solution, the blocking time and the incubation temperature. The results show that, the best reaction condition of the direct competitive ELISA is 1% gelatin, blocking 1 h at 37 degrees C, incubating 1 h at 37 degrees C after the monoclonal antibodies added. The detect limit is 3.58 ng x mL(-1), the coefficient of variation between the holes is below 15%, and the recovery is 80% - 120%. The whole analysis process could be completed within 1.5 h. It meets the requirements of rapid and batch detection of domoic acid. The method will have broad development prospects.

  19. The Staff Development as a Means of Enhancing the Enterprise Competitiveness

    Directory of Open Access Journals (Sweden)

    Zajtzeva Lyudmila O.

    2017-05-01

    Full Text Available The article is aimed at substantiating the importance of continuous development of staff as a means of enhancing the competitiveness of enterprise. A study on the current experience and issues of dissemination of the standard for HR management at the enterprises in Ukraine and abroad has been provided. The role of HR management in the system of competitive factors has been defined. The staff development strategies that are dependent on analysis of the internal environment and the personnel forecast of enterprise have been outlined. The need to apply both material and moral motivation to employees has been determined. The necessity to match the external conditions and the objectives of enterprise with the methods of labor incentives has been substantiated. Features of employee incentive on the basis of wage have been disclosed. There is a need to assess the quantitative and qualitative results of each employee’s individual work through the additional salaries, including in the form of various fringes, increments, lump sum remunerations, which are of a compensatory nature and allow for a significant individualization.

  20. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......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...

  1. 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...

  2. Technological Competitiveness of Ukraine under Conditions of a New Industrial Revolution and Development of Convergent Technologies

    Directory of Open Access Journals (Sweden)

    Matyushenko Igor Yu.

    2016-02-01

    Full Text Available The article considers the problem of increasing the technological competitiveness of Ukrainian enterprises under conditions of a new industrial revolution through the development and introduction of advanced converged technologies. The classification of industrial revolutions, namely, industrial, technological, information and Industry 4.0, is presented, and it has been determined that the key factor of the latter is cyber physical systems for introduction of the client-oriented “Internet of Things”. It has been justified that the formation of Industry 4.0 in developed countries will occur through advanced production technologies (APT, which main characteristics are technological substitution, automation, customization, localization and economic efficiency. It has been found that in 2020 the main priority APT will be: systems of production process control; multidimensional modeling of complex products; intelligent production systems and robotics; systems of creation and transformation (growing of material objects and 3D-printing; materials effective in creating perspective actuating devices (compositional and those that exhibit their properties in small-size structures. It has been proved that the recovery of Ukraine’s industry is not possible on the old industrial base, and the creation of a new industry based on APT of Industry 4.0 is possible in the following areas: ICT (primarily in the field of software development; new composite materials with specified properties; industrial nanobiotechnologies (biomedicine and pharmacy, new agricultural technologies; mathematical modeling for creation of intelligent production systems; space research and development (in particular, development of the first stages of heavy missiles. The necessity of elaborating state programs of competitiveness development on the basis of APT, foresight research oftechnology priorities, promoting high-tech exports in Ukraine has been substantiated.

  3. Development and Evaluation of Multiple Competitive Activities in a Synchronous Quiz Game System.

    Science.gov (United States)

    Chang, Li-Jie; Yang, Jie-Chi; Chan, Tak-Wai; Yu, Fu-Yun

    2003-01-01

    Describes the design of an online competitive learning environment that involved three basic competitive forms and 16 competitive activities to stimulate student motivation. Explains "Joyce", a system in which users can compete with either a computer agent or via the Internet. (Author/LRW)

  4. An integrated approach for developing a technology strategy framework for small- to medium-sized furniture manufacturers to improve competitiveness

    Directory of Open Access Journals (Sweden)

    Lourens, A.S.

    2013-05-01

    Full Text Available Low-technology firms, such as those found within the furniture manufacturing industry, have no framework or methodology to guide them successfully to acquire and integrate technology that enables them to operate more competitively. The aim of this article is to illustrate the development of a technology strategy framework for small- to medium-sized furniture manufacturers to assist them to improve their competitiveness. More specifically, this article presents an integrated technology strategy framework that enables management to integrate their business strategy with their technology requirements successfully, thus improving competitiveness.

  5. Tumor lymphangiogenesis and new drug development.

    Science.gov (United States)

    Dieterich, Lothar C; Detmar, Michael

    2016-04-01

    Traditionally, tumor-associated lymphatic vessels have been regarded as passive by-standers, serving simply as a drainage system for interstitial fluid generated within the tumor. However, with growing evidence that tumors actively induce lymphangiogenesis, and that the number of lymphatic vessels closely correlates with metastasis and clinical outcome in various types of cancer, this picture has changed dramatically in recent years. Tumor-associated lymphatic vessels have now emerged as a valid therapeutic target to control metastatic disease, and the first specific anti-lymphangiogenic drugs have recently entered clinical testing. Furthermore, we are just beginning to understand the whole functional spectrum of tumor-associated lymphatic vessels, which not only concerns transport of fluid and metastatic cells, but also includes the regulation of cancer stemness and specific inhibition of immune responses, opening new venues for therapeutic applications. Therefore, we predict that specific targeting of lymphatic vessels and their function will become an important tool for future cancer treatment.

  6. New drug development in digestive neuroendocrine tumors.

    Science.gov (United States)

    Durán, I; Salazar, R; Casanovas, O; Arrazubi, V; Vilar, E; Siu, L L; Yao, J; Tabernero, J

    2007-08-01

    The traditional cytotoxic agents are of limited efficacy in the treatment of neuroendocrine tumors of the gastrointestinal tract (NETs). Recent investigations have brought up a number of biological features in this family of neoplasms that could represent targets for anticancer treatment. NETs seem to have an extraordinary tumor vascularization with high expression of proangiogenic molecules such as the vascular endothelial growth factor along with overexpression of certain tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR), the insulin growth factor receptor (IGFR) and their downstream signaling pathway components (PI3K-AKT-mTOR). The rationale of an antiangiogenic approach in the treatment of NETs and the use of other pharmacological strategies such as EGFR, IGFR and mammalian target of rapamycin inhibitors are discussed. Additionally, the emerging results of recent clinical trials with these targeted drugs are presented.

  7. Drug discovery and development for neglected diseases: the DNDi model

    Directory of Open Access Journals (Sweden)

    Eric Chatelain

    2011-03-01

    Full Text Available Eric Chatelain, Jean-Robert IosetDrugs for Neglected Diseases Initiative (DNDi, Geneva, SwitzerlandAbstract: New models of drug discovery have been developed to overcome the lack of modern and effective drugs for neglected diseases such as human African trypanosomiasis (HAT; sleeping sickness, leishmaniasis, and Chagas disease, which have no financial viability for the pharmaceutical industry. With the purpose of combining the skills and research capacity in academia, pharmaceutical industry, and contract researchers, public–private partnerships or product development partnerships aim to create focused research consortia that address all aspects of drug discovery and development. These consortia not only emulate the projects within pharmaceutical and biotechnology industries, eg, identification and screening of libraries, medicinal chemistry, pharmacology and pharmacodynamics, formulation development, and manufacturing, but also use and strengthen existing capacity in disease-endemic countries, particularly for the conduct of clinical trials. The Drugs for Neglected Diseases initiative (DNDi has adopted a model closely related to that of a virtual biotechnology company for the identification and optimization of drug leads. The application of this model to the development of drug candidates for the kinetoplastid infections of HAT, Chagas disease, and leishmaniasis has already led to the identification of new candidates issued from DNDi’s own discovery pipeline. This demonstrates that the model DNDi has been implementing is working but its DNDi, neglected diseases sustainability remains to be proven.Keywords: R&D, screening, lead optimization, human African trypanosomiasis, leishmaniasis, Chagas disease, product development partnerships

  8. Developing new drugs from annals of Chinese medicine

    Directory of Open Access Journals (Sweden)

    Zhaoxiang Bian

    2012-02-01

    Full Text Available Developing new pharmaceuticals requires massive amounts of time, money and efforts. The key step is how to find a safe and effective entity for a disease condition and how to develop it as new drug effectively. Unfortunately, the FDA's rate of approving new entities has declined dramatically in the last three decades. There is a strong need to review the current strategy and to optimize process in developing new drugs, both to shorten the process and increase the success rate. Chinese medicine has used natural products to treat patients for thousands of years, and Chinese medicine practitioners have chronicled the patients and treatment methods for thousands of years. There is much information that has not yet been used. The success stories of artimisinin and arsentic trioxide are wonderful examples of how the annals of Chinese medicine can provide leads for discovering new drugs. This paper argues that the annals of Chinese medicine are valuable and describes how they can be used in modern drug discovery. The major topics addressed are: (i why Chinese medicine is a rich resource for finding new drugs; (ii how to identify a potential valuable record from Chinese medicine annals; (iii when a potential valuable record is identified from annals, how to proceed; and (iv both why and how the approach used for chemical drugs should be revised for drugs based on the historical documents related to herbal medicine. In conclusion, we argue here that the annals of Chinese medicine offer not only a rich resource for new drugs, but also several centuries of patient data with regard to safety and efficacy, that in effect represent pilot studies. Acknowledging and using these data can shorten new drug discovery time and improve efficiency of the drug development process, bringing more effective, safe drugs to market much more quickly and cheaply.

  9. How Can We Assess and Evaluate the Competitive Advantage of a Country's Human Resource Development System?

    Science.gov (United States)

    Oh, Hunseok; Ryu, Hyue-Hyun; Choi, Myungweon

    2013-01-01

    The purpose of this study was to develop an index to assess and evaluate the competitive advantage of a country's human resource development system. Based on an extensive literature review, a theoretical model of a human resource development system at the national level (named National Human Resource Development: NHRD) was constructed. The…

  10. How Can We Assess and Evaluate the Competitive Advantage of a Country's Human Resource Development System?

    Science.gov (United States)

    Oh, Hunseok; Ryu, Hyue-Hyun; Choi, Myungweon

    2013-01-01

    The purpose of this study was to develop an index to assess and evaluate the competitive advantage of a country's human resource development system. Based on an extensive literature review, a theoretical model of a human resource development system at the national level (named National Human Resource Development: NHRD) was constructed. The…

  11. CLUSTER POLICIES IN THE EUROPEAN UNION – ENGINES FOR SUSTAINABLE ECONOMIC DEVELOPMENT AND COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Popa Ion

    2013-07-01

    Full Text Available The present article wishes to present the topic of clusters and cluster policies, to highlight their status and role in the European Union and to underline their significant purpose in obtaining a sustainable economic development, and in making a more competitive and well oiled Europe. The research for this article is part of a greater goal – that of getting the answer to the question: What are clusters what and how can “they” better the performance of the regions that are part of the member states of the European Union? To do that, an inquiry into the issue was necessary, by analyzing information from multiple data sources and by drawing some conclusions, based on those informations. The conducted research was empirical, and in order to better highlight the relationship between clusters, cluster policies and economic development, a synthesis of different case studies and statistical data were used. The conclusion that was found was that strong cluster portfolios are related to (and thrive in developed countries, but interestingly enough, relationship can also be reversed (meaning that clusters cause the region they exist in to increase its performance.Also, clusters are highly prevalent from a geographical point of view, the existence of which can be seen globally, of course in different stages of development. And last, but not least, from the standpoint of national cluster policies, although all countries have programs for clusters either at national or regional level, which varies from country to country is the number and type of ministries that are responsible for implementing cluster policies. Also another factor that varies is the importance given to cluster policies. However an issue that is becoming increasingly clear is that the cluster policy is becoming more important and relevant. Therefore, the hypothesis was confirmed, there is a direct correlation between clusters, cluster policies and sustainable economic development and

  12. Phase 0 clinical trials in oncology new drug development.

    Science.gov (United States)

    Gupta, Umesh Chandra; Bhatia, Sandeep; Garg, Amit; Sharma, Amit; Choudhary, Vaibhav

    2011-01-01

    Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND) studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development.

  13. Phase 0 clinical trials in oncology new drug development

    Directory of Open Access Journals (Sweden)

    Umesh Chandra Gupta

    2011-01-01

    Full Text Available Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development.

  14. Possible causal relationships between competitive swimming in growing age and three-dimensional dentoalveolar development.

    Science.gov (United States)

    Silvestrini-Biavati, Armando; Capurro, Claudia; Ugolini, Alessandro; Butti, Andrea Carlo; Salvato, Antonino

    2013-07-26

    The aim of this study was to investigate possible links between competitive swimming during the growth phase and the development of the dentoalveolar arches. The study sample included 100 swimmers and a control group of 100 age-matched non-swimmers who had never practised swimming or related sports. Subjects who had had previous orthodontic treatment were excluded. Overjet, overbite, sagittal and transverse parameters, arch dimension, crowding and oral habits were recorded. In the swimmers, there was a significantly higher frequency of molar symmetry (P=0.04), together with a greater number of Class I subjects. The overjet in the swimmers was mainly normal, but the arch dimensions were significantly wider (+10% in the upper arch; Pcompetitive swimming during the growth phase has a favourable effect on dental arch development in the sagittal, vertical and transverse planes.

  15. Development of the competitive business in the context of environmental legislation in Croatia.

    Science.gov (United States)

    Matesić, Mirjana; Kalambura, Sanja; Bacun, Dubravka

    2014-03-01

    Environmental protection has a key role in the context of crisis management. It is not just about development of the industry of environmental protection and implementation of new ways of management in innovative solutions in solving problems. Important area of improvement is also revision of environmental legislation aiming at simplification and reduction of costs of procedures for the business. This paper discusses problems of business sector in Croatia related to transposition of demanding environmental EU regulation, it suggests improvements such as simplification of special waste management systems, of environmental impact assessments processes, environmental permitting etc. The paper considers revision of environmental protection not by lowering environmental standards, but by introducing transparent and compromising models between business and environmental protection, based on sustainable development, with control mechanisms which don't impact functioning of business sector (and its competitiveness), therefore allowing successful protection of environment and its renewable and non-renewable resources.

  16. An Analysis of Competitiveness and Government Policies Impact on Development of Cocoa Farming in Indonesia

    Directory of Open Access Journals (Sweden)

    Andi Emelda

    2014-01-01

    Full Text Available Indonesian cocoa plantations from year to year increase, on the other hand decreased cocoa production andsome government policies have been carried out in order to increase exports and tried to occupy the first rank world cocoa exporting countries.This study aims to analyze (1 comparative and competitive advantages of cocoa farming in North Luwu, (2 the impact of government policies on development of cocoa farming in North Luwu.This is a descriptive analytic study. The sampling method used was purposive sampling of 40 farmers selected. Data collected through interviews, observation and documentation. Data were analyzed using the Policy Analysis Matrix (PAM.The results showed that the value of DRC and PCR of cocoa farming is respectively 0.03 and 0.04. The impact of government policies provide incentives to develop cocoa farming in North Luwu reflected NPCI value = 1.25; NPCO = 1.12, and EPC = 1.09 are all positive values.

  17. The family bubble, achievement gap, and development as competition: media frames on youth.

    Science.gov (United States)

    O'Neil, Moira

    2009-01-01

    Identifying persistent media frames through a cognitive media analysis is an important step in the empirical measurement of public thinking about social issues. Based on a recent media analysis of racial disparities as they pertain to youth in major U.S. newspapers, this article explains three frames that were persistently evoked in media coverage of youth issues: the family bubble frame--the idea that parents are solely responsible for child outcomes; youth development as a competitive race--the idea that the overarching goal of educational and social development is to make youth more successful than their peers; and the understanding of disparities as achievement gaps. Together these frames promote individualistic understanding of social problems related to youth and limit imaginable solutions to policies that fix individuals rather than broken systems.

  18. [Competition in school nursing: the development of the nursing role and its influences].

    Science.gov (United States)

    Liu, Shiu-Chin; Yu, Shui-Chu

    2008-10-01

    This essay focuses on the competition between school nurses and the effect of such on the development of school nursing. As questions regarding the role that school nurses should play and what kind of functions they should have in school have yet to be answered, school nurses are sometimes considered as useless, with school healthcare suffering as a result. This essay first examines the development of professional school nursing in order to demonstrate the import role played by nurses in schools. Critical problems identified by the R.O.C.. School Nurses Association over the past decade in their work to secure school nurse rights and their solutions will be explained in order to underscore the contribution of school nurses and problems presently faced. Finally, the present dilemma and future direction of school nursing and nurses will be described.

  19. Antiepileptic drugs in development pipeline: A recent update

    Directory of Open Access Journals (Sweden)

    Harjeet Kaur

    2016-09-01

    Full Text Available Epilepsy is the most common neurological disorder which significantly affects the quality of life and poses a health as well as economic burden on society. Epilepsy affects approximately 70 million people in the world. The present article reviews the scientific rationale, brief pathophysiology of epilepsy and newer antiepileptic drugs which are presently under clinical development. We have searched the investigational drugs using the key words ‘antiepileptic drugs,’ ‘epilepsy,’ ‘Phase I,’ ‘Phase II’ and ‘Phase III’ in American clinical trial registers (clinicaltrials.gov, the relevant published articles using National Library of Medicine's PubMed database, company websites and supplemented results with a manual search of cross-references and conference abstracts. This review provides a brief description about the antiepileptic drugs which are targeting different mechanisms and the clinical development status of these drugs. Besides the presence of old as well as new AEDs, still there is a need of new drugs or the modified version of old drugs in order to make affected people free of seizures. An optimistic approach should be used to translate the success of preclinical testing to clinical practice. There is an urgent need to improve animal models and to explore new targets with better understanding in order to develop the novel drugs with more efficacy and safety.

  20. Combination therapy: the propitious rationale for drug development.

    Science.gov (United States)

    Phougat, Neetu; Khatri, Savita; Singh, Anu; Dangi, Mrridula; Kumar, Manish; Dabur, Rajesh; Chhillar, Anil Kumar

    2014-01-01

    Therapeutic options for many infections are extremely limited and at crisis point. We run the risk of entering a second pre-antibiotic era. There had been no miracle drug for the patients infected by resistant microbial pathogens. Most of the very few new drugs under development have problems with their toxicity, or pharmacokinetics and pharmacodynamics. We are already decades behind in the discovery, characterization and development of new antimicrobials. In that scenario, we could not imagine surviving without newer and effective antimicrobial agents. Bacteria have been the champions of evolution and are still evolving continuously, where they pose serious challenges for humans. Along with the crisis of evolving resistance, the condition is made worst by the meager drug pipeline for new antimicrobials. Despite ongoing efforts only 2 new antibiotics (Telavancin in 2009 and Ceftaroline fosamil in 2010) have been approved since 2009 pipeline status report of Infectious Disease Society of America (IDSA). Recent approval of new combination based antiviral drugs such as Stribild (combination of four drugs for HIV treatment) and Menhibrix (combination vaccine to prevent meningococcal disease and Haemophilus influenzae type b in children) proves that combination therapy is still the most promising approach to combat the ever evolving pathogens. Combination therapy involves the drug repurposing and regrouping of the existing antimicrobial agents to provide a synergistic approach for management of infectious diseases. This review article is an effort to highlight the challenges in new drug development and potential of combination drug therapy to deal with them.

  1. Orphan drug development in China - Turning challenges into opportunities.

    Science.gov (United States)

    Jin, Xiaowei; Chen, Li

    2016-11-01

    Of over 7,000 known rare diseases, only 5% currently have an available treatment option worldwide. Moreover, the vast majority of rare disease patients in China have no access to treatment due to limited availability and the lack of appropriate infrastructure in China's healthcare system. Despite increased interest in orphan drug development, drug companies in China with active programs on drugs to treat rare diseases are still limited. Hence, there is a huge unmet need in China, with over 10 million patients suffering from rare diseases. Nonetheless, this has created unprecedented opportunities for the Chinese drug development market. Life science innovation in China has recently received a healthy boost from the 13th National Five-Year Plan and from on-going reform of the China Food and Drug Administration (CFDA). Rare diseases are now recognized as a national priority with increasing governmental support, creating tremendous opportunities for both domestic and multinational drug companies. China is anticipated to play an increasingly important role in the global fight against rare diseases. To ensure future success, Chinese drug companies should leverage the valuable knowledge assembled over the past three decades by Western countries in the area of orphan drug development.

  2. Orphan drug development in China – Turning challenges into opportunities

    Science.gov (United States)

    Jin, Xiaowei; Chen, Li

    2016-01-01

    Summary Of over 7,000 known rare diseases, only 5% currently have an available treatment option worldwide. Moreover, the vast majority of rare disease patients in China have no access to treatment due to limited availability and the lack of appropriate infrastructure in China's healthcare system. Despite increased interest in orphan drug development, drug companies in China with active programs on drugs to treat rare diseases are still limited. Hence, there is a huge unmet need in China, with over 10 million patients suffering from rare diseases. Nonetheless, this has created unprecedented opportunities for the Chinese drug development market. Life science innovation in China has recently received a healthy boost from the 13th National Five-Year Plan and from on-going reform of the China Food and Drug Administration (CFDA). Rare diseases are now recognized as a national priority with increasing governmental support, creating tremendous opportunities for both domestic and multinational drug companies. China is anticipated to play an increasingly important role in the global fight against rare diseases. To ensure future success, Chinese drug companies should leverage the valuable knowledge assembled over the past three decades by Western countries in the area of orphan drug development. PMID:27904831

  3. Studies on development of controlled delivery of combination drug(s to periodontal pocket

    Directory of Open Access Journals (Sweden)

    Tiwari Gaurav

    2010-01-01

    Full Text Available Aim: The aim of this study to develop the controlled delivery of combination drug(s to periodontal pocket. Materials and Methods: In the present investigation mucoadhesive gel formulations were prepared using carboxy methylcellulose (CMC, methylcellulose (MC, hydroxyethylcellulose (HEC, polyvinylpirrolidone (PVP, polycarbophil (PC, and poloxamer. Each formulation was characterized in terms of polarizing light microscopy, gelation, gel melting, hardness, compressibility, adhesiveness, cohesiveness, syringeability, adhesion to a mucin disk, rheological studies, drug release, and antibacterial activities. Addition of CMC and PVP to the gel favored hexagonal phase formation. The gelation temperature was decreased linearly with an increasing concentration of drug(s, whereas, the melting temperature increased with the concentration of drug(s. Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion, and syringeability, yet a decreased cohesiveness. Increased time of contact between the formulation and mucin significantly increased the required force of detachment. Drug release from all formulations was non-diffusion controlled and significantly decreased as the concentration of the polymer was increased, due to the concomitant increased viscosity of the formulations and the swelling kinetics of PC, following contact with the dissolution fluid. Result: Antibacterial studies revealed that a gel with 30% HEC had a growth inhibition zone on agar with all three strains. Conclusion: Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations.

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

    Science.gov (United States)

    Mason, Matthew; Levenson, James; Quillin, John

    2017-08-01

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

  5. Anti-HIV drug development on the fast track

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ An international cooperation deal was made recently in Shanghai on developing a new anti-HIV drug based on the research results of CAS scientists and their preclinical studies,marking a breakthrough progress for China's research in the field.

  6. Research Ethics and Commercial Drug Development: When Integrity Threatens Profitability

    Directory of Open Access Journals (Sweden)

    Bélisle Pipon, Jean-Christophe

    2016-05-01

    Full Text Available This case, based on personal experiences and on those found in the literature, highlights the delicate tension faced by drug development companies having to balance research integrity and their profitability.

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

    OpenAIRE

    Cheng, Alice; Xie, Zhi

    2017-01-01

    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 ...

  8. Model-based drug development: strengths, weaknesses, opportunities, and threats for broad application of pharmacometrics in drug development.

    Science.gov (United States)

    Wetherington, Jeffrey D; Pfister, Marc; Banfield, Christopher; Stone, Julie A; Krishna, Rajesh; Allerheiligen, Sandy; Grasela, Dennis M

    2010-09-01

    Systematic implementation of model-based drug development (MBDD) to drug discovery and development has the potential to significantly increase the rate of medical breakthroughs and make available new and better treatments to patients. An analysis of the strengths, weaknesses, opportunities, and threats (ie, SWOT) was conducted through focus group discussions that included 24 members representing 8 pharmaceutical companies to systematically assess the challenges to implementing MBDD into the drug development decision-making process. The application of the SWOT analysis to the successful implementation of MBDD yielded 19 strengths, 27 weaknesses, 34 opportunities, and 22 threats, which support the following conclusions. The shift from empirical drug development to MBDD requires a question-based mentality; early, proactive planning; dynamic access to multisource data; quantitative knowledge integration; multidisciplinary collaboration; effective communication and leadership skills; and innovative, impactful application of pharmacometrics focused on enhancing quantitative decision making. The ultimate goal of MBDD is to streamline discovery and development of innovative medicines to benefit patients.

  9. Nasal drug delivery - recent developments and future prospects.

    Science.gov (United States)

    Illum, Lisbeth

    2012-07-20

    The present review sets out to discuss recent developments and prospects of absorption promoters and absorption modulator systems being developed commercially by companies specialising in nasal drug delivery of normal small molecular weight drugs and biological drugs such as peptide and proteins. The absorption promoter systems selected for discussion in this review are those with the most promising preclinical and/or clinical data and sufficient toxicology data and/or company development efforts to warrant use in marketed products i.e. CPE-215 (cyclopenta decalactone (azone)) developed by CPEX Pharma, Intravail (alkylsaccharides) developed by Aegis Therapeutics, ChiSys(TM) (chitosan) and PecSys(TM) (low methylated pectin) in development by Archimedes Pharma and CriticalSorb(TM) (polyglycol mono- and diesters of 12-hydroxystearate (70%), polyethylene glycol (30%)) developed by Critical Pharmaceuticals. Copyright © 2012. Published by Elsevier B.V.

  10. Global Alliance for Tuberculosis Drug Development

    Science.gov (United States)

    ... Inadequate Treatment Maternal and Child Health Cycle of Poverty R&D Scientific Vision Our Pipeline Developing New ... give her one! Child Survival Saving Children's Lives Childhood TB can be solved—if we choose to ...

  11. Competition between low-dose aspirin and other NSAIDs for COX-1 binding and its clinical consequences for the drugs' antiplatelet effects.

    Science.gov (United States)

    Stepensky, David; Rimon, Gilad

    2015-01-01

    NSAIDs are frequently used in modern medicine to inhibit the COX enzymes and induce analgesic, antipyretic, anti-inflammatory, and antiplatelet effects. Concomitant treatment with two or more NSAIDs can lead to their competition for binding and inhibition of the COX enzymes and altered time course of the pharmacological effects. The competition between the low-dose aspirin and other NSAIDs for binding to COX-1 is described, including the recent findings on the differences in the interaction of NSAIDs with the individual COX-1 subunits, and the clinical consequences of this drug-drug interaction. The major pharmacokinetic (PK) and pharmacodynamic (PD) factors that govern the interaction of low-dose aspirin with other NSAIDs are explained, along with the approaches for prediction of the magnitude of this interaction using mechanism-based PK-PD modeling. Concomitant administration of other NSAIDs can diminish the antiplatelet effects of low-dose aspirin, increase the risk of thromboembolic effects (heart attacks and strokes), and lead to patient morbidity and mortality. The healthcare providers and the patients are seldom aware to this clinical problem and its consequences. Despite this drug interaction, low-dose aspirin possesses high clinical safety and it is not expected to be replaced by the recently approved drugs.

  12. The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation.

    Science.gov (United States)

    Mayer, Melanie G; Rödelsperger, Christian; Witte, Hanh; Riebesell, Metta; Sommer, Ralf J

    2015-06-01

    Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains' pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as major target for

  13. The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation.

    Directory of Open Access Journals (Sweden)

    Melanie G Mayer

    2015-06-01

    Full Text Available Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains' pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as

  14. [Development of anti-cancer drugs under new renewed GCP--from the viewpoint of drug development company developer].

    Science.gov (United States)

    Ueno, T; Kobayashi, T; Inoue, K; Yanagi, Y; Yamada, Y

    1998-04-01

    During the past 7 years since the enforcement of Japan's first GCP in October 1990, various standards and guidelines have been introduced in Japan. On the other hand, the harmonization of GCP has been the subject of major discussion at ICH in order to allow the mutual acceptance of clinical data from different countries. In order to further improve the reliability and consistency of clinical data and the ethics of clinical trials in Japan, the new GCP was enforced in April 1997. A clinical study is conducted by the sponsor, but will only be successful with the collaboration of trial subjects, medical institutions, heads of medical institutions, investigators, subinvestigators, pharmacists, nurses, laboratory technicians, and other assisting staff. Before the full enforcement of the new GCP, we, as sponsors of clinical trials, carried out a survey of the current status of clinical trials centering on the reactions of medical institutions to the new GCP, future of clinical trials on anti-cancer drugs in Japan, and differences in time from clinical trials to registration in Japan, the United State and Europe. We sent a questionnaire by facsimile to 21 pharmaceutical companies which have developed or are developing anti-cancer drugs and obtained replies from 20 companies (95%) from August 25 to 30, 1997. This paper reports issues concerning clinical trials on anti-cancer drugs based on the results of our survey.

  15. The Development and Characterization of Protein-Based Stationary Phases for Studying Drug-Protein and Protein-Protein Interactions

    OpenAIRE

    Sanghvi, Mitesh; Moaddel, Ruin; Wainer, Irving W.

    2011-01-01

    Protein-based liquid chromatography stationary phases are used in bioaffinity chromatography for studying drug-protein interactions, the determination of binding affinities, competitive and allosteric interactions, as well as for studying protein-protein interactions. This review addresses the development and characterization of protein-based stationary phase, and the application of these phases using frontal and zonal chromatography techniques. The approach will be illustrated using immobili...

  16. Advances in Alzheimer's disease drug development.

    Science.gov (United States)

    Rafii, Michael S; Aisen, Paul S

    2015-03-25

    Alzheimer's disease (AD) is the foremost cause of dementia worldwide. Clinically, AD manifests as progressive memory impairment followed by a gradual decline in other cognitive abilities leading to complete functional dependency. Recent biomarker studies indicate that AD is characterized by a long asymptomatic phase, with the development of pathology occurring at least a decade prior to the onset of any symptoms. Current FDA-approved treatments target neurotransmitter abnormalities associated with the disease but do not affect what is believed to be the underlying etiology. In this review, we briefly discuss the most recent therapeutic strategies being employed in AD clinical trials, as well the scientific rationale with which they have been developed.

  17. Breaking barriers to novel analgesic drug development.

    Science.gov (United States)

    Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P; Woolf, Clifford J

    2017-08-01

    Acute and chronic pain complaints, although common, are generally poorly served by existing therapies. This unmet clinical need reflects a failure to develop novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms, and the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.

  18. Drug development: how academia, industry and authorities interact.

    Science.gov (United States)

    Garattini, Silvio; Perico, Norberto

    2014-10-01

    Unfortunately, abundant examples could be given of pitfalls in the current drug development paradigm-including in the design, conduct and evaluation of phase III clinical trials. This article discusses issues of particular relevance to clinical trials in nephrology, including the inappropriate use of placebo, publication of reports that emphasize potential treatment benefits over adverse reactions, the sometimes dubious impartiality of independent guidelines, and inadequate recruitment of elderly patients. This Perspectives article aims to highlight and summarize the flaws in the current drug development process, while suggesting a way forward that equally satisfies the requirements of academia, patients and the pharmaceutical industry. We suggest improvements to the drug development process and related legislation that intend to balance public needs with commercial aims and ensure effective drug evaluation by regulatory authorities.

  19. Precision medicine in oncology drug development: a pharma perspective.

    Science.gov (United States)

    Hollingsworth, Simon J

    2015-12-01

    A rapid expansion in precision medicine founded on the potential for durable clinical benefit through matching a drug to a predictive marker used to select patients has driven the development of targeted drugs with accompanied companion diagnostics for patient selection. Oncology has been at the forefront, with the improvements in patient survival notable. Increasing numbers of molecular subgroups require an equally increasing number (and new generation) of highly selective agents targeting inevitably lower incidence molecular segments, posing significant challenges for drug development. Innovative trial designs (umbrella or basket studies) are emerging as patient-centric approaches and public-private partnerships, cross-industry, government and non-profit sector collaborations are enabling implementation. Success will require continued innovation, new paradigms in oncology drug development and market approval and continued collaboration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Hurdles in anticancer drug development from a regulatory perspective.

    Science.gov (United States)

    Jonsson, Bertil; Bergh, Jonas

    2012-02-21

    Between January 2001 and January 2012, 48 new medicinal products for cancer treatment were licensed within the EU, and 77 new indications were granted for products already licensed. In some cases, a major improvement to existing therapies was achieved, for example, trastuzumab in breast cancer. In other cases, new fields for effective drug therapy opened up, such as in chronic myeloid leukemia, and renal-cell carcinoma. In most cases, however, the benefit-risk balance was considered to be only borderline favorable. Based on our assessment of advice procedures for marketing authorization, 'need for speed' seems to be the guiding principle in anticancer drug development. Although, for drugs that make a difference, early licensure is of obvious importance to patients, this is less evident in the case of borderline drugs. Without proper incentives and with hurdles inside and outside companies, a change in drug development cannot be expected; drugs improving benefit-risk modestly over available therapies will be brought forward towards licensure. In this Perspectives article, we discuss some hurdles to biomarker-driven drug development and provide some suggestions to overcome them.

  1. Creating Sustainable Competitive Advantage thro ugh Reputation Management: A Model Development for Restructuring Higher Education

    Directory of Open Access Journals (Sweden)

    Mesut Öncel

    2014-12-01

    Full Text Available Along with the research that has been carried out in recent years, realizing that the reputation is a measurable value has caused discussions about how to manage reputation. Although reputation management has been studied extensively by different scientists in different disciplines, there is relatively a limited number of study in the field of higher education. The aim of this research is to determine the corporate reputation management of universities at universities scale and develop a model for structuring it in universities within Turkey Higher Education system as an administrative approach. In the light of the gathered data, a model to structure the corporate reputation management for achieving a sustainable competitive strength in Turkish universities has been proposed.

  2. An industry statistician's perspective on PHC drug development.

    Science.gov (United States)

    Fridlyand, Jane; Yeh, Ru-Fang; Mackey, Howard; Bengtsson, Thomas; Delmar, Paul; Spaniolo, Greg; Lieberman, Grazyna

    2013-11-01

    In the past decade, the cost of drug development has increased significantly. The estimates vary widely but frequently quoted numbers are staggering-it takes 10-15 years and billions of dollars to bring a drug to patients. To a large extent this is due to many long, expensive and ultimately unsuccessful drug trials. While one approach to combat the low yield on investment could be to continue searching for new blockbusters, an alternative method would lead us to focus on testing new targeted treatments that have a strong underlying scientific rationale and are more likely to provide enhanced clinical benefit in population subsets defined by molecular diagnostics. Development of these new treatments, however, cannot follow the usual established path; new strategies and approaches are required for the co-development of novel therapeutics and the diagnostic. In this paper we will review, from the point of view of industry, the approaches to, and challenges of drug development strategies incorporating predictive biomarkers into clinical programs. We will outline the basic concepts behind co-development with predictive biomarkers and summarize the current regulatory paradigm. We will present guiding principles of personalized health care (PHC) development and review the statistical, strategic, regulatory and operational challenges that statisticians regularly encounter on development programs with a PHC component. Some practical recommendations for team statisticians involved in PHC drug development are included. The majority of the examples and recommendations are drawn from oncology but broader concepts apply across all therapeutic areas.

  3. Drug discovery and development for neglected diseases: the DNDi model.

    Science.gov (United States)

    Chatelain, Eric; Ioset, Jean-Robert

    2011-03-16

    New models of drug discovery have been developed to overcome the lack of modern and effective drugs for neglected diseases such as human African trypanosomiasis (HAT; sleeping sickness), leishmaniasis, and Chagas disease, which have no financial viability for the pharmaceutical industry. With the purpose of combining the skills and research capacity in academia, pharmaceutical industry, and contract researchers, public-private partnerships or product development partnerships aim to create focused research consortia that address all aspects of drug discovery and development. These consortia not only emulate the projects within pharmaceutical and biotechnology industries, eg, identification and screening of libraries, medicinal chemistry, pharmacology and pharmacodynamics, formulation development, and manufacturing, but also use and strengthen existing capacity in disease-endemic countries, particularly for the conduct of clinical trials. The Drugs for Neglected Diseases initiative (DNDi) has adopted a model closely related to that of a virtual biotechnology company for the identification and optimization of drug leads. The application of this model to the development of drug candidates for the kinetoplastid infections of HAT, Chagas disease, and leishmaniasis has already led to the identification of new candidates issued from DNDi's own discovery pipeline. This demonstrates that the model DNDi has been implementing is working but its DNDi, neglected diseases sustainability remains to be proven.

  4. Dietary Intake, Body Composition, and Menstrual Cycle Changes during Competition Preparation and Recovery in a Drug-Free Figure Competitor: A Case Study

    Science.gov (United States)

    Halliday, Tanya M.; Loenneke, Jeremy P.; Davy, Brenda M.

    2016-01-01

    Physique competitions are events in which competitors are judged on muscular appearance and symmetry. The purpose of this retrospective case study was to describe changes in dietary intake, body mass/composition, and the menstrual cycle during the 20-week competition preparation (PREP) and 20-week post competition recovery (REC) periods of a drug-free amateur female figure competitor (age = 26–27, BMI = 19.5 kg/m2). Dietary intake (via weighed food records) and body mass were assessed daily and averaged weekly. Body composition was estimated via Dual-energy X-ray absorptiometry (DXA) and 7-site skinfold measurements. Energy intake, body mass and composition, and energy availability decreased during the 20-week PREP period (changes of ~298 kcals, 5.1 kg, 6.5% body fat, and 5.4 kcal/kg fat free mass, respectively) and returned to baseline values by end of the 20-week REC period. Menstrual cycle irregularity was reported within the first month of PREP and the last menstruation was reported at week 11 of PREP. Given the potentially adverse health outcomes associated with caloric restriction, future, prospective cohort studies on the physiological response to PREP and REC are warranted in drug-free, female physique competitors. PMID:27879627

  5. 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

  6. Rate of Force Development, Muscle Architecture, and Performance in Young Competitive Track and Field Throwers.

    Science.gov (United States)

    Zaras, Nikolaos D; Stasinaki, Angeliki-Nikoletta E; Methenitis, Spyridon K; Krase, Argyro A; Karampatsos, Giorgos P; Georgiadis, Giorgos V; Spengos, Konstantinos M; Terzis, Gerasimos D

    2016-01-01

    The rate of force development (RFD) is an essential component for performance in explosive activities, although it has been proposed that muscle architectural characteristics might be linked with RFD and power performance. The purpose of the study was to investigate the relationship between RFD, muscle architecture, and performance in young track and field throwers. Twelve young track and field throwers completed 10 weeks of periodized training. Before (T1) and after (T2) training performance was evaluated in competitive track and field throws, commonly used shot put tests, isometric leg press RFD, 1 repetition maximum (1RM) strength as well as vastus lateralis architecture and body composition. Performance in competitive track and field throwing and the shot put test from the power position increased by 6.76 ± 4.31% (p Rate of force development and 1RM strength also increased (p ≤ 0.05). Vastus lateralis thickness and fascicle length increased by 5.95 ± 7.13% (p = 0.012) and 13.41 ± 16.15% (p = 0.016), respectively. Significant correlations were found at T1 and T2, between performance in the shot put tests and both RFD and fascicle length (p ≤ 0.05). Close correlations were found between RFD, muscle thickness, and fascicle length (p ≤ 0.05). Significant correlations were found between the % changes in lean body mass and the % increases in RFD. When calculated together, the % increase in muscle thickness and RFD could predict the % increase in shot put throw test from the power position (p = 0.019). These results suggest that leg press RFD may predict performance in shot put tests that are commonly used by track and field throwers.

  7. Repolarization reserve, arrhythmia and new drug development

    Directory of Open Access Journals (Sweden)

    Yang Li

    2013-05-01

    Full Text Available Repolarization-related lethal arrhythmias have led to the concept of “repolarization reserve”, which may help elucidate the relationship between K+ currents and other components of repolarization. Pharmacological manipulation as well as congenital and cardiac disease may affect repolarization and alter the repolarization reserve, leading to the development of arrhythmias. Pharmacological enhancement of outward currents or suppression of inward currents has been shown to be of therapeutic value. A number of newly found selective ion channel inhibitors or agonists have been investigated for their ability to enhance repolarization reserve and decrease the incidence of arrhythmia. In this paper we review the development, potential mechanisms, clinical application, and pharmacological significance of repolarization reserve in order to better understand, predict and prevent unexplained adverse cardiac events.

  8. Benefit-Risk Assessment in Drug Development

    DEFF Research Database (Denmark)

    Sarac, Sinan

    This thesis covers the development, testing and use of an eight-step structured method for data-driven benefit-risk assessment. The aim of this thesis was to create a tailored method for the assessment of clinical data. The focus has been on three major aspects: (i) A simple preliminary method....... In total, four pilot studies and internal workshops were conducted. The method was therefore developed in an iterative fashion. The method involves eight successive steps: 1) establishment of the decision context, 2) identification of benefit and risk criteria, 3) weighting, 4) scoring, 5) evaluation...... and supported by a qualitative framework with built-in quantitative measures. However, at the same time the method is transparent in the sense that all assumptions made in the various steps of the assessment are clearly expressed all the way to the final decision. This is important both to avoid that unreported...

  9. [Development of drug delivery systems for targeting to macrophages].

    Science.gov (United States)

    Chono, Sumio

    2007-09-01

    Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.

  10. BCS class IV drugs: Highly notorious candidates for formulation development.

    Science.gov (United States)

    Ghadi, Rohan; Dand, Neha

    2017-02-28

    BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs. A decade back, extreme examples of class IV compounds were an exception rather than the rule, yet today many drug candidates under development pipeline fall into this category. Formulation and development of an efficacious delivery system for BCS class IV drugs are herculean tasks for any formulator. The inherent hurdles posed by these drugs hamper their translation to actual market. The importance of the formulation composition and design to successful drug development is especially illustrated by the BCS class IV case. To be clinically effective these drugs require the development of a proper delivery system for both oral and per oral delivery. Ideal oral dosage forms should produce both a reasonably high bioavailability and low inter and intra subject variability in absorption. Also, ideal systems for BCS class IV should produce a therapeutic concentration of the drug at reasonable dose volumes for intravenous administration. This article highlights the various techniques and upcoming strategies which can be employed for the development of highly notorious BCS class IV drugs. Some of the techniques employed are lipid based delivery systems, polymer based nanocarriers, crystal engineering (nanocrystals and co-crystals), liquisolid technology, self-emulsifying solid dispersions and miscellaneous techniques addressing the P

  11. Development of braided drug-loaded nanofiber sutures

    Energy Technology Data Exchange (ETDEWEB)

    Hu Wen [School of Materials Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092 (China); Huang Zhengming [School of Aerospace Engineering and Applied Mechanics, Tongji University, 1239 Siping Road, Shanghai 200092 (China); Liu Xiangyang, E-mail: huangzm@tongji.edu.cn [Department of Physics, National University of Singapore, 2 Science Drive 3, 117542 (Singapore)

    2010-08-06

    The objectives of this work are twofold. Firstly, while most work on electrospinning is limited to the development of only functional materials, a structural application of electrospun nanofibers is explored. Secondly, a drug-loaded tissue suture is fabricated and its various properties are characterized. Braided drug-loaded nanofiber sutures are obtained by combining an electrospinning process with a braiding technique followed by a coating procedure. Two different electrospinning techniques, i.e. blend and coaxial electrospinning, to incorporate a model drug cefotaxime sodium (CFX-Na) into poly(L-lactic acid) (PLLA) nanofibers have been applied and compared with each other. Properties of the braided drug-loaded sutures are characterized through a variety of methods including SEM, TEM and tensile testing. The results show that the nanofibers had a preferable micromorphology. The drug was incorporated into the polymer nanofibers homogeneously, with no cross-linking. The nanofibers maintained their fibrous structures. An in vitro release study indicates that the drug-loaded nanofibers fabricated by blend electrospinning and coaxial electrospinning had a different drug release behavior. An inhibition zone experiment shows that both sutures obtained from the nanofibers of the different electrospinning techniques had favorable antibacterial properties. The drug-loaded sutures had preferable histological compatibility performance compared with commercial silk sutures in an in vivo comparative study.

  12. Clinical drugs that interact with St. John's wort and implication in drug development.

    Science.gov (United States)

    Di, Yuan Ming; Li, Chun Guang; Xue, Charlie Changli; Zhou, Shu-Feng

    2008-01-01

    St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs that have distinctive chemical structure, mechanism of action and metabolic pathways. This review highlights and updates the knowledge on clinical interactions of prescribed drugs with SJW and the implication in drug development. A number of clinically significant interactions of SJW have been identified with conventional drugs, including anticancer agents (imatinib and irinotecan), anti-HIV agents (e.g. indinavir, lamivudine and nevirapine), anti-inflammatory agents (e.g. ibuprofen and fexofenadine), antimicrobial agents (e.g. erythromycin and voriconazole), cardiovascular drugs (e.g. digoxin, ivabradine, warfarin, verapamil, nifedipine and talinolol), central nervous system agents (e.g. amitriptyline, buspirone, phenytoin, methadone, midazolam, alprazolam, and sertraline), hypoglycaemic agents (e.g. tolbutamide and gliclazide), immuno-modulating agents (e.g. cyclosporine and tacrolimus), oral contraceptives, proton pump inhibitor (e.g. omeprazole), respiratory system agent (e.g. theophylline), statins (e.g. atorvastatin and pravastatin). Both pharmacokinetic and pharmacodynamic components may play a role in the interactions of drugs with SJW. For pharmacokinetic changes of drugs by SJW, induction of cytochrome P450s (e.g. CYP2C9 and 3A4) and P-glycoprotein (P-gp) are considered the major mechanism. Thus, it is not a surprise that many drugs that interact with SJW are substrates of CYP3A4, CYP2C9 and P-gp. A comprehensive understanding of clinical drugs that interact with SJW has important implications in drug development. New drugs may be designed to minimize interactions with SJW; and new SJW formulations may be designed to avoid drug interactions. Further clinical and

  13. Weaving single photon imaging into new drug development.

    Science.gov (United States)

    Mozley, P David

    2005-01-01

    The specific aim of this review is to assess the potential contribution of single photon emitting radiopharmaceutical technologies to new drug development. For each phase of therapeutic drug development, published literature was sought that shows single photon emitters can add value by quantifying pharmacokinetics, visualizing mechanisms of drug action, estimating therapeutic safety indices, or measuring dose-dependent pharmacodynamic effects. Not any published reports were found that describe using nuclear medicine techniques to help manage the progress of a new drug development program. As a consequence, most of the case in favor of weaving single photon imaging into the process had to be built on extrapolations from studies that showed feasibility post hoc. The strongest evidence of potential value was found for drug candidates that hope to influence diseases characterized by cell proliferation or cell death, particularly in the fields of oncology, cardiology, nephrology, and inflammation. Receptor occupancy studies were observed to occasionally offer unique advantages over analogous studies with positron emission tomography (PET). Enough hard data sets were found to justify the costs of using single photon imaging in a variety of new drug development paradigms.

  14. 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.

  15. [Role of Academia in Regulatory Science for Global Drug Development].

    Science.gov (United States)

    Tsukamoto, Katsura; Takenaka, Toichi

    2016-01-01

    As diseases know no national boundaries, drug development must be designed at a global level. Drugs are highly regulated to maximize the benefits to public health, which is assessed on a regional basis. The complexity and diversity of stakeholders increase dramatically once multiple international regions are involved. Each stakeholder in drug development depends on customized criteria to make decisions for its own benefit. Thus, a huge gap exists among drug discovery researchers, developers, clinicians, patients, and regulatory bodies. With reasonable scientific evidence gathered and analyzed, mutual agreement can be reached. We believe that this important role of regulatory science and academic involvement will create harmony. By practicing diverse, innovative regulatory scientific research, academia has the potential to become the core of communication among various stakeholder groups. Furthermore, another important responsibility of academia, i.e., knowledge, provides additional aspects to the field of drug development. Those who understand regulatory science can contribute to the efficient achievement of innovative, effective, safe drugs. Thus, research and education are essential roles of academia to allow a better understanding of the balance between benefits and risks. Communication and knowledge will promote the prompt delivery of better medical products to patients in need.

  16. Drugs in development for Parkinson's disease.

    Science.gov (United States)

    Johnston, Tom H; Brotchie, Jonathan M

    2004-07-01

    Pharmacological treatment of Parkinson's disease (PD) is entering a new and exciting era. Real promise now exists for the clinical application of a large range of molecules in development that will combat different aspects and stages of the condition. These include methyl- and ethyl-esterified forms of L-dopa (etilevodopa and melevodopa), inhibitors of enzymes such as monoamine oxidase type-B (eg, rasagiline), catechol-O-methyl transferase (eg, BIA-3202) and the monoamine re-uptake mechanism (eg, brasofensine). In addition, a range of full and partial dopamine agonists (eg, sumanirole, piribedil and BP-897) and their new formulations, for example, patch delivery systems (eg, rotigotine) are being developed. We also highlight non-dopaminergic treatments that will have wide ranging applications in the treatment of PD and L-dopa-induced dyskinesia. These include alpha2 adrenergic receptor antagonists (eg, fipamezole), adenosine A2A receptor antagonists (eg, istradefylline), AMPA receptor antagonists (eg, talampanel), neuronal synchronization modulators (eg, levetiracetam) and agents that interact with serotonergic systems such as 5-hydroxytryptamine (5-HT)1A agonists (eg, sarizotan) and 5-HT2A antagonists (eg, quetiapine). Lastly, we examine a growing number of neuroprotective agents that seek to halt or even reverse disease progression. These include anti-apoptotic kinase inhibitors (eg, CEP-1347), modulators of mitochondrial function (eg, creatine), growth factors (eg, leteprinim), neuroimmunophilins (eg, V-10367), estrogens (eg, MITO-4509), c-synuclein oligomerization inhibitors (eg, PAN-408) and sonic hedgehog ligands.

  17. Myeloperoxidase: a target for new drug development?

    Science.gov (United States)

    Malle, E; Furtmüller, P G; Sattler, W; Obinger, C

    2007-11-01

    Myeloperoxidase (MPO), a member of the haem peroxidase-cyclooxygenase superfamily, is abundantly expressed in neutrophils and to a lesser extent in monocytes and certain type of macrophages. MPO participates in innate immune defence mechanism through formation of microbicidal reactive oxidants and diffusible radical species. A unique activity of MPO is its ability to use chloride as a cosubstrate with hydrogen peroxide to generate chlorinating oxidants such as hypochlorous acid, a potent antimicrobial agent. However, evidence has emerged that MPO-derived oxidants contribute to tissue damage and the initiation and propagation of acute and chronic vascular inflammatory disease. The fact that circulating levels of MPO have been shown to predict risks for major adverse cardiac events and that levels of MPO-derived chlorinated compounds are specific biomarkers for disease progression, has attracted considerable interest in the development of therapeutically useful MPO inhibitors. Today, detailed information on the structure of ferric MPO and its complexes with low- and high-spin ligands is available. This, together with a thorough understanding of reaction mechanisms including redox properties of intermediates, enables a rationale attempt in developing specific MPO inhibitors that still maintain MPO activity during host defence and bacterial killing but interfere with pathophysiologically persistent activation of MPO. The various approaches to inhibit enzyme activity of MPO and to ameliorate adverse effects of MPO-derived oxidants will be discussed. Emphasis will be put on mechanism-based inhibitors and high-throughput screening of compounds as well as the discussion of physiologically useful HOCl scavengers.

  18. Orphan regulations for orphan drug development in India

    Directory of Open Access Journals (Sweden)

    D Saikiran Reddy

    2014-01-01

    Full Text Available Through this review article an attempt has been made to put forward the challenges faced by rare disease drug development and the current scenario of orphan drug legislations in India. An orphan drug is a pharmaceutical agent that is used to treat a rare medical condition (viz., glioblastoma multiforme, nocardiosis, Tourette syndrome, etc. Developed countries such as United States (US, Europe, Japan, and Australia have laid down legal framework for combating rare diseases. A path breaking legislation was formulated by the US government way back in 1983, known as "Orphan Drugs Act (ODA." The key purpose of ODA was to incentivize R and D initiatives for such drugs to treat millions of population suffering from "orphan diseases." Though the percentage of patients suffering from "rare diseases" in India is reportedly higher than the world average, unfortunately even today such cases get little help from our government. Indian government should also encourage its domestic pharmaceutical industry to get engaged in research for orphan drugs by putting an "ODA" in place and extending financial support, and regulatory concessions like smaller and shorter clinical trials, without further delay. Thus, India could well-demonstrate that the concept of orphan drugs for orphan diseases is really not orphan in India.

  19. Development of an industrial complex for ensuring national competitiveness and economic security

    Directory of Open Access Journals (Sweden)

    A. V. Kalach

    2016-01-01

    Full Text Available Living standards depends on the state of the country’s industrial complex. In a message to Russian President Vladimir Putin's Federal Assembly was asked to implement in 2015 a national technological initiative, the development of industries of the new technological order. As a result of the predominance of the industry of the sixth technological order should occur major changes in the structure of production factors and significance. It follows the inevitability of structural changes in the system of economic institutions and mechanisms of economic security and competitiveness of the state achieve the main goal of the state program “The development of industry and increase its competitiveness” is carried out through the following the directions of sub-programs: investment goods (chemical complex development composite materials, industrial biotechnology, power engineering, machine tool industry, agricultural machinery, machinery specialized production, transport engineering; goods (light industry, children;s products industry, the automotive industry; military-industrial complex; infrastructure (development of engineering activities, industrial parks; semi-finished goods and materials (timber industry, metallurgy, industrial development of rare-earth metals. At the current pace of technological and economic development, the 6 th technological structure will come into proliferation phase in 2010–2020, and in the phase of maturity – 40-ies of XXI century. At the same time in 2020–2025 there will be a new scientific-technical and technological revolution, which will become the basis for developing, synthesizing advances in the above basic technologies. In this paper, we proposed as a tool to ensure the economic security of the state to use the acceleration system of technical development of the industrial complex.

  20. PBPK modeling and simulation in drug research and development

    OpenAIRE

    Xiaomei Zhuang; Chuang Lu

    2016-01-01

    Physiologically based pharmacokinetic (PBPK) modeling and simulation can be used to predict the pharmacokinetic behavior of drugs in humans using preclinical data. It can also explore the effects of various physiologic parameters such as age, ethnicity, or disease status on human pharmacokinetics, as well as guide dose and dose regiment selection and aid drug–drug interaction risk assessment. PBPK modeling has developed rapidly in the last decade within both the field of academia and the phar...

  1. 23 CFR 636.405 - After developing a short list, can I still establish a competitive range?

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false After developing a short list, can I still establish a competitive range? 636.405 Section 636.405 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS DESIGN-BUILD CONTRACTING Exchanges § 636.405 After developing...

  2. Reinforcement, dopamine and rodent models in drug development for ADHD.

    Science.gov (United States)

    Tripp, Gail; Wickens, Jeff

    2012-07-01

    Attention deficit hyperactivity disorder (ADHD) presents special challenges for drug development. Current treatment with psychostimulants and nonstimulants is effective, but their mechanism of action beyond the cellular level is incompletely understood. We review evidence suggesting that altered reinforcement mechanisms are a fundamental characteristic of ADHD. We show that a deficit in the transfer of dopamine signals from established positive reinforcers to cues that predict such reinforcers may underlie these altered reinforcement mechanisms, and in turn explain key symptoms of ADHD. We argue that the neural substrates controlling the excitation and inhibition of dopamine neurons during the transfer process are a promising target for future drug development. There is a need to develop animal models and behavioral paradigms that can be used to experimentally investigate these mechanisms and their effects on sensitivity to reinforcement. More specific and selective targeting of drug development may be possible through this approach.

  3. Single-cell analysis tools for drug discovery and development.

    Science.gov (United States)

    Heath, James R; Ribas, Antoni; Mischel, Paul S

    2016-03-01

    The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed.

  4. Competitive Intelligence and Regional Development within the Framework of Indonesian Provincial Autonomy

    Science.gov (United States)

    Dou, Henri; Manullang, Sri Damayanty

    2004-01-01

    Teaching methodologies and uses of competitive intelligence and competitive technical intelligence in countries where the culture and the technological level are very different from the western world cannot be implemented without a cultural understanding of the tacit local knowledge and cultural behavior of people. As an example of…

  5. International trade in services developments in light of dynamic developments in competitive environment

    Directory of Open Access Journals (Sweden)

    Anna Olefir

    2008-06-01

    Full Text Available The paper analyses theoretical grounds for determining «services», key peculiarities of international trade in services and its discrepancies from trade in goods, and determines the modern trends of development of this form of international trade according to the main types of services.

  6. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    Science.gov (United States)

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  7. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    Science.gov (United States)

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  8. Multiple soil nutrient competition between plants, microbes, and mineral surfaces: model development, parameterization, and example applications in several tropical forests

    Directory of Open Access Journals (Sweden)

    Q. Zhu

    2015-03-01

    Full Text Available Soil is a complex system where biotic (e.g., plant roots, micro-organisms and abiotic (e.g., mineral surfaces consumers compete for resources necessary for life (e.g., nitrogen, phosphorus. This competition is ecologically significant, since it regulates the dynamics of soil nutrients and controls aboveground plant productivity. Here we develop, calibrate, and test a nutrient competition model that accounts for multiple soil nutrients interacting with multiple biotic and abiotic consumers. As applied here for tropical forests, the Nutrient COMpetition model (N-COM includes three primary soil nutrients (NH4+, NO3−, and POx (representing the sum of PO43−, HPO42−, and H2PO4− and five potential competitors (plant roots, decomposing microbes, nitrifiers, denitrifiers, and mineral surfaces. The competition is formulated with a quasi-steady-state chemical equilibrium approximation to account for substrate (multiple substrates share one consumer and consumer (multiple consumers compete for one substrate effects. N-COM successfully reproduced observed soil heterotrophic respiration, N2O emissions, free phosphorus, sorbed phosphorus, and free NH4+ at a tropical forest site (Tapajos. The overall model posterior uncertainty was moderately well constrained. Our sensitivity analysis revealed that soil nutrient competition was primarily regulated by consumer-substrate affinity rather than environmental factors such as soil temperature or soil moisture. Our results imply that the competitiveness (from most to least competitive followed this order: (1 for NH4+, nitrifiers ~ decomposing microbes > plant roots, (2 for NO3−, denitrifiers ~ decomposing microbes > plant roots, (3 for POx, mineral surfaces > decomposing microbes ~ plant roots. Although smaller, plant relative competitiveness is of the same order of magnitude as microbes. We then applied the N-COM model to analyze field nitrogen and phosphorus perturbation experiments in two tropical forest

  9. Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics.

    Science.gov (United States)

    Mooij, Miriam G; Nies, Anne T; Knibbe, Catherijne A J; Schaeffeler, Elke; Tibboel, Dick; Schwab, Matthias; de Wildt, Saskia N

    2016-05-01

    Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical relevance of transporters in drug disposition and their effect in adults have been shown in drug-drug interaction and pharmacogenomic studies. Little is known, however, about the ontogeny of human membrane transporters and their roles in pediatric pharmacotherapy. As they are involved in the transport of endogenous substrates, growth and development may be important determinants of their expression and activity. This review presents an overview of our current knowledge on human membrane transporters in pediatric drug disposition and effect. Existing pharmacokinetic and pharmacogenetic data on membrane substrate drugs frequently used in children are presented and related, where possible, to existing ex vivo data, providing a basis for developmental patterns for individual human membrane transporters. As data for individual transporters are currently still scarce, there is a striking information gap regarding the role of human membrane transporters in drug therapy in children.

  10. Actors of Columbian drug trade : development and transformation

    Directory of Open Access Journals (Sweden)

    Soňa Smolíková

    2011-06-01

    Full Text Available The aim of this article is to portray the main shifts which have been taking place in Colombian drug scene since the 70’s up to the present especially in relation to actors of this business and form of their activity. At first the development of Colombian drug trade till the 80’s when two big cartels centered in Medellín and Cali arose will be briefly outlined. These cartels were able to control a great part of domestic drug trade and due to their enormous power represented serious threat to Colombian state. Thus the cartels declared open warfare with the state in the 80’s. After the cartels’ elimination in the middle of 90’s new actors represented by small drug organizations arose in Colombian drug scene. These small groups were dependent upon cooperation with foreign partners, especially with Mexican cartels. Ever more important role in drug business is played by Colombian left-wing guerilla groups which will be described in the next part of the article. The problem of right-wing paramilitary groups and their participation in Colombian drug trade will be mentioned as well.

  11. The development of an instrument to measure the self-efficacy of students participating in VEX robotics competitions

    Science.gov (United States)

    Robinson, Trevor P.

    The number of robotics competitions has steadily increased over the past 30 years. Schools are implementing robotics competitions to increase student content knowledge and interest in science, technology, engineering, and mathematics (STEM). Companies in STEM-related fields are financially supporting robotics competitions to help increase the number of students pursuing careers in STEM among other reasons. These financial supporters and school administrations are asking what the outcomes of students participating in competitive robotics are. Few studies have been conducted to investigate these outcomes. The studies that have been conducted usually compare students in robotics to students not in robotics. There have not been any studies that compare students to themselves before and after participating in robotics competitions. This may be due to the lack of available instruments to measure student outcomes. This study developed an instrument to measure the self-efficacy of students participating in VEX Robotics Competitions (VRC). The VRC is the world's largest and fastest growing robotics competition available for middle and high school students. Self-efficacy was measured because of its importance to the education community. Students with higher self-efficacy tend to persevere through difficult tasks more frequently than students with low self-efficacy. A person's self-efficacy has major influence over what interests, activities, classes, college majors, and careers he or she will pursue in life. The self-efficacy survey instrument created through this study was developed through an occupational and task analysis (OTA), and initial content and face validity was established through the OTA process. Exploratory and confirmatory factor analyses were also conducted to assist in instrument validation. The reliability was calculated using Cronbach's alpha. Face validity was established through the OTA process. Construct validity was established through the factor

  12. Professional Development Program Aimed at Physicians to Develop Drug Utilization Studies

    Directory of Open Access Journals (Sweden)

    Yacelis Dahilet Cisneros Nápoles

    2014-04-01

    Full Text Available Background: one of the deficiencies presented by physicians in their professional activity is related to the development of drug utilization studies. Objective: to design a professional development program aimed at physicians to develop drug utilization studies. Methods: an educational research was conducted at the Faculty of Medical Sciences of Cienfuegos during the 2011-2012 academic year. Theoretical methods such as the analytic-synthetic, the inductive-deductive, the historical-logical, modeling and system approach were used in the methodological and theoretical process. Results: the program aims at training physicians to develop drug utilization studies and its contents include: drug-related problems; criteria for selecting a drug in the prescription process; Pharmacoepidemiology; objectives, types of studies, characteristics and steps for the design and development of drug utilization studies; drug therapy and aspects on the selection and analysis of drug information sources. The methods are based on reflection and research itself developed by physicians during the activities for their professional development. Discussion and presentation of essays and research projects will be used to assess learning in the program, which integrates forms of professional development including specialized conferences, self-study, postgraduate courses, workshops and consultancies. Conclusions: the program serves as a reference to design the different activities required to train physicians for the development of drug utilization studies and it can be integrated in the graduate strategy of the university.

  13. 75 FR 33317 - Antibacterial Resistance and Diagnostic Device and Drug Development Research for Bacterial...

    Science.gov (United States)

    2010-06-11

    ... Development Research for Bacterial Diseases; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION.... The workshop will address antibacterial drug resistance, mechanisms of resistance, epidemiology of... Drug Evaluation and Research, Food and Drug Administration, Office of Antimicrobial Products, 10903...

  14. Development of mannosylated liposomes for bioadhesive oral drug delivery via M cells of Peyer's patches.

    Science.gov (United States)

    Pukanud, Pongthep; Peungvicha, Penchom; Sarisuta, Narong

    2009-07-01

    The aim of this study was to develop mannosylated liposomes as bioadhesive carriers for oral drug delivery. Two kinds of acyclovir (ACV)-entrapped mannosylated liposomes, i.e. ManN-ACV-lip and PAM-ACV-lip, were prepared by the use of mannosamine HCl (ManN) and p-aminophenyl-alpha-D-mannopyranoside (PAM), respectively. The mean sizes, drug entrapment efficiency, and loading capacity values of all liposomal formulations were in the ranges of 233-371 nm, 82-95%, and 42-47%, respectively. The mean size of PAM-ACV-lip was significantly smaller than those of conventional ACV liposomes and ManN-ACV-lip due to the more conical packing parameter of mannose-conjugated phospholipid. The mannosylating group grafted into bilayer membrane resulted in a decrease in drug entrapment, owing to competitive binding. The in vitro drug absorptions through everted sacs of mice ileum of both mannosylated ACV liposomes were significantly higher than those of conventional ACV liposomes or suspension.

  15. 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

  16. 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

  17. [Educative game on drugs for blind individuals: development and assessment].

    Science.gov (United States)

    Mariano, Monaliza Ribeiro; Rebouças, Cristiana Brasil de Almeida; Pagliuca, Lorita Marlena Freitag

    2013-08-01

    Study aimed to develop and assess an educational game on psychoactive drugs accessible to blind individuals, conducted in three steps: development of the educative game, evaluation by three special education experts, and assessment by twelve blind individuals. As a result, a board game called Drugs: staying clean was developed. In the Alpha version, experts made suggestions regarding the game rules and instructions and the board base, including square texture, game pieces, and Braille writing. In Beta version, we proceeded to the assessment by the blind participants, who suggested changes in the square texture and the addition of Velcro-type material to fix the counters on the board. Then, the Gamma version was played by the last pairs of blind players and was considered by them to be adequate. In the evaluation of the experts, the game was appropriate, as it allowed access to information on psychoactive drugs in a ludic and playful manner.

  18. The significance of chirality in drug design and development.

    Science.gov (United States)

    Brooks, W H; Guida, W C; Daniel, K G

    2011-01-01

    Proteins are often enantioselective towards their binding partners. When designing small molecules to interact with these targets, one should consider stereoselectivity. As considerations for exploring structure space evolve, chirality is increasingly important. Binding affinity for a chiral drug can differ for diastereomers and between enantiomers. For the virtual screening and computational design stage of drug development, this problem can be compounded by incomplete stereochemical information in structure libraries leading to a "coin toss" as to whether or not the "ideal" chiral structure is present. Creating every stereoisomer for each chiral compound in a structure library leads to an exponential increase in the number of structures resulting in potentially unmanageable file sizes and screening times. Therefore, only key chiral structures, enantiomeric pairs based on relative stereochemistry need be included, and lead to a compromise between exploration of chemical space and maintaining manageable libraries. In clinical environments, enantiomers of chiral drugs can have reduced, no, or even deleterious effects. This underscores the need to avoid mixtures of compounds and focus on chiral synthesis. Governmental regulations emphasizing the need to monitor chirality in drug development have increased. The United States Food and Drug Administration issued guidelines and policies in 1992 concerning the development of chiral compounds. These guidelines require that absolute stereochemistry be known for compounds with chiral centers and that this information should be established early in drug development in order that the analysis can be considered valid. From exploration of structure space to governmental regulations it is clear that the question of chirality in drug design is of vital importance.

  19. Management Innovations as a Condition of Competitive, Sustainable and Secure Development of the Region

    Directory of Open Access Journals (Sweden)

    Nikolay Prokofyevich Ivanov

    2016-03-01

    Full Text Available In the article within the comparative analysis the author reveals the tendencies of functioning of an economic complex in a number of regions of the South of Russia in recent years; describes the potential of modernization of economy of the Stavropol region; substantiates the influence of organizational and administrative innovations on activity and efficiency of using territorial management of institutes of economic development in practice. The author of the present research proves that realization of administrative capacity of bodies of the regional power of the Stavropol region is mainly connected with the development of production sector of the region, as well as with the monitoring and management of regional economy become the basic elements of creating the diversified, effective and competitive environment focused on creation in the region of the industrial complexes which yield the final products. The article emphasizes that organizational and administrative innovations are mostly directed on the activization of the process of regional innovative system formation, the search of more effective forms of interaction with vertically integrated companies (mega-corporations operating on the territory of the region which investment resources need to be involved in the process of modernization and restructuring of a regional economic complex.

  20. Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses.

    Directory of Open Access Journals (Sweden)

    Elena Frola

    Full Text Available The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs work together with the synaptic adhesion molecule neuroligin 2 (NL2 to regulate synapse formation in different subcellular compartments. We investigated mice ("γ2 knockdown mice" with an engineered allele of the GABAAR γ2 subunit gene which produced a mosaic expression of synaptic GABAARs in neighboring neurons, causing a strong imbalance in synaptic inhibition. Deletion of the γ2 subunit did not abolish synapse formation or the targeting of NL2 to distinct types of perisomatic and axo-dendritic contacts. Thus synaptic localization of NL2 does not require synaptic GABAARs. However, loss of the γ2 subunit caused a selective decrease in the number of axo-dendritic synapses on cerebellar Purkinje cells and cortical pyramidal neurons, whereas perisomatic synapses were not significantly affected. Notably, γ2-positive cells had increased axo-dendritic innervation compared with both γ2-negative and wild-type counterparts. Moreover heterologous synapses on spines, that are found after total deletion of GABAARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABAARs in regulating synapse development in distinct subcellular compartments, and support the hypothesis that the refinement of axo-dendritic synapses is regulated by activity-dependent competition between neighboring neurons.

  1. Development of potent selective competitive-antagonists of the melanocortin type 2 receptor.

    Science.gov (United States)

    Bouw, Elise; Huisman, Martin; Neggers, Sebastian J C M M; Themmen, Axel P N; van der Lely, A J; Delhanty, Patric J D

    2014-08-25

    Cushing's disease, a hypercortisolemic state induced by an ACTH overexpressing pituitary adenoma, causes increased morbidity and mortality. Selective antagonism of the melanocortin type 2 receptor (MC2R) may be a novel treatment modality. Five structurally related peptides with modified HFRW sites but intact putative MC2R binding sites were tested for antagonistic activity at MC1R, MC2R/MRAP, MC3R, MC4R and MC5R. Two of these peptides (GPS1573 and GPS1574) dose-dependently antagonized ACTH-stimulated MC2R activity (IC50s of 66±23 nM and 260±1 nM, respectively). GPS1573 and 1574 suppressed the Rmax but not EC50 of ACTH on MC2R, indicating non-competitive antagonism. These peptides did not antagonize α-MSH stimulation of MC1R and antagonized MC3, 4 and 5R at markedly lower potency. GP1573 and GPS1574 antagonize MC4R with IC50s of 950 nM and 3.7 μM, respectively. In conclusion, two peptide antagonists were developed with selectivity for MC2R, forming a platform for development of a medical treatment for Cushing's disease.

  2. Conceptual Principles for Developing and Regulating the Energy Policy of Ukraine at a Competitive Level

    Directory of Open Access Journals (Sweden)

    Klymchuk Oleksandr V.

    2016-02-01

    Full Text Available The article is aimed at studying the current trends of regulatory policy in the global energy market and identifying potent ways for energy efficiency growth in terms of the Ukrainian economy. An analysis of the main trends of energy policy development in the world has been carried out and a priority direction for the development of Ukrainian energy on the basis of the biofuel industry has been determined. The article substantiates actuality of the matter that one of the main directions of overcoming the energy crisis in Ukraine, along with ensuring recovery and sustainable growth of the gross domestic product, is transition to the industrial use of biofuels. The process of production and consumption of biofuels must be seen as a means to raise the level of decentralization, while ensuring energy sources. It is determined that the State must provide information support for producers of biofuels, defining their market range and encouraging beneficial business partners. Increased production of biofuels in Ukraine will serve as a fundamental factor in achieving international competitiveness of the national economy, as well as its growth on innovation basis.

  3. [Development and application of indirect competitive enzyme immunoassay for detection of neomycin in milk].

    Science.gov (United States)

    Burkin, M A; Gal'vidis, I A

    2011-01-01

    As a result of immunization of rabbits with neomycin B (N M) conjugated to periodate-oxidized transferrin, polyclonal antibodies were generated and used to develop an indirect competitive enzyme-linked immunosorbent assay (ELISA) of NM. Several heterologous conjugates, namely, glutaraldehyde (GA)-polymerized NM, gelatin-ribostamycin (sp), and gelatin-NM (ga) were used as coating antigens in different ELISA variants for quantification of NM in milk. These variants were characterized by different dynamic ranges and detection limits of 1.0, 0.1, and 0.01 ng/ml, respectively. Maximum residue level (MRL) of this antibiotic in milk accepted in the EU can be detected without any special pretreatment at a 100-fold sample dilution in the least sensitive assay variant. The mean recovery rate from NM-spiked milk containing 1.5-10% fat was 111.7% and ranged from 84 to 125.2%. We found that 57 of 106 tested milk samples contained NM at concentrations higher than 100 ng/ml. In ten percent of cases (11/1 06), the residual level of this antibiotic was greater than 500 ng/ml. In one case, the M RL was exceeded (1690 ng/ml). The assay developed in this study is specific shows no cross-reactivity with other veterinary aminoglycosides, has a good sensitivity reserve, and can serve as an effective tool to monitor the NM content in milk stuff.

  4. AN EXPLORATORY STUDY OF THE REGIONAL CONTEXT OF COMPETITIVE DEVELOPMENT IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Valentin Cojanu

    2011-06-01

    Full Text Available A recent series of EU initiatives gradually have changed the meaning of growth initiatives whereby the options of economic policy became more closely linked to the needs of development at ever smaller territorial units. The present research attempts to contribute to the discussion about the competitive potential of economic growth at territorial level.We introduce a methodological model to evaluate the conditions under which economic growth may generate opportunities leading to self -sustained economic development. The hypothesis is discussed at bothnational and regional scale and tested with a set of socio-economic variables including indicators relative to economic growth, economic functionality and spatial networks.Our findings suggest a huge potential in terms of capitalization of different types of capital (territorial, human, cultural, but also in terms of achieving mutual reinforcement of links between advanced and less advanced industries. Most of the national territory contributes insignificantly to the economic use of resourcesthrough exports and advanced manufacturing. All this means resources which do not currently contribute to economic growth. Integrating the new concepts of territorial planning is gradual, long term oriented, and with significant learning economies. The objectives to pursue can be suggested from such measures as mapping of business operations in the target area or establishing non-governmental institutions with observation and monitoring roles.

  5. Development of a human papillomavirus competitive luminex immunoassay for 9 HPV types.

    Science.gov (United States)

    Roberts, Christine; Green, Tina; Hess, Erica; Matys, Katie; Brown, Martha J; Haupt, Richard M; Luxembourg, Alain; Vuocolo, Scott; Saah, Alfred; Antonello, Joseph

    2014-01-01

    In the clinical trials of the quadrivalent human papillomavirus (qHPV) vaccine, antibodies were measured by a competitive Luminex immunoassay (HPV-4 cLIA). A nine-valent HPV (9vHPV) vaccine targeting the types in the qHPV vaccine (HPV6/11/16/18), as well as 5 of the next most frequent HPV types found in cervical cancers worldwide (HPV31/33/45/52/58) is under development. To support the 9vHPV vaccine program, a nine-multiplexed cLIA (HPV-9 cLIA) was developed. Antibody titers were determined in a competitive format, where type-specific phycoerythrin (PE)-labeled, neutralizing mAbs (mAbs-PE) compete with an individual's serum antibodies for binding to conformationally sensitive, neutralizing epitopes on the VLPs. Neutralizing antibody levels were quantitated against a reference standard - a pool of sera from 6 Rhesus macaques that were immunized with the 9vHPV vaccine. Specificity of the mAbs was assessed by measuring their individual binding capacities to the type-specific and non-type-specific VLPs at alternative concentrations of the mAbs. Antibody assignments to the HPV-9 cLIA reference standard for HPV6/11/16/18 were determined to provide for a measure of consistency in serostatus assignment between the HPV-4 and HPV-9 cLIAs. Antibody assignments to the HPV-9 reference standard for HPV31/33/45/52/58 were obtained by calibration to HPV11 using a direct binding IgG assay. For each HPV VLP type, the cross-reactivity of the mAb-PEs in the HPV-9 cLIA was <1% (i.e., the mAb-PEs result in <1% non-specific binding). The antibody concentrations assigned to the HPV-9 cLIA reference standard for types 6/11/16/18/31/33/45/52/58 were 3,817, 2,889, 23,061, 5,271, 3,942, 2,672, 1,489, 1274, and 2263 mMU/mL, respectively.

  6. Scorpion peptides: potential use for new drug development.

    Science.gov (United States)

    Hmed, Bennasr; Serria, Hammami Turky; Mounir, Zeghal Khaled

    2013-01-01

    Several peptides contained in scorpion fluids showed diverse array of biological activities with high specificities to their targeted sites. Many investigations outlined their potent effects against microbes and showed their potential to modulate various biological mechanisms that are involved in immune, nervous, cardiovascular, and neoplastic diseases. Because of their important structural and functional diversity, it is projected that scorpion-derived peptides could be used to develop new specific drugs. This review summarizes relevant findings improving their use as valuable tools for new drugs development.

  7. Scorpion Peptides: Potential Use for New Drug Development

    Directory of Open Access Journals (Sweden)

    BenNasr Hmed

    2013-01-01

    Full Text Available Several peptides contained in scorpion fluids showed diverse array of biological activities with high specificities to their targeted sites. Many investigations outlined their potent effects against microbes and showed their potential to modulate various biological mechanisms that are involved in immune, nervous, cardiovascular, and neoplastic diseases. Because of their important structural and functional diversity, it is projected that scorpion-derived peptides could be used to develop new specific drugs. This review summarizes relevant findings improving their use as valuable tools for new drugs development.

  8. 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.

  9. Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer.

    Science.gov (United States)

    Vassal, Gilles; Rousseau, Raphaël; Blanc, Patricia; Moreno, Lucas; Bode, Gerlind; Schwoch, Stefan; Schrappe, Martin; Skolnik, Jeffrey; Bergman, Lothar; Bradley-Garelik, Mary Brigid; Saha, Vaskar; Pearson, Andy; Zwierzina, Heinz

    2015-01-01

    Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders - academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be

  10. Anti-Influenza Treatment: Drugs Currently Used and Under Development.

    Science.gov (United States)

    Amarelle, Luciano; Lecuona, Emilia; Sznajder, Jacob I

    2017-01-01

    Influenza is a very common contagious disease that carries significant morbidity and mortality. Treatment with antiviral drugs is available, which if administered early, can reduce the risk of severe complications. However, many virus types develop resistance to those drugs, leading to a notable loss of efficacy. There has been great interest in the development of new drugs to combat this disease. A wide range of drugs has shown anti-influenza activity, but they are not yet available for use in the clinic. Many of these target viral components, which others are aimed at elements in the host cell which participate in the viral cycle. Modulating host components is a strategy which minimizes the development of resistance, since host components are not subject to the genetic variability of the virus. The main disadvantage is the risk of treatment-related side effects. The aim of this review is to describe the main pharmacological agents currently available and new drugs in the pipeline with potential benefit in the treatment of influenza. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Is Open Science the Future of Drug Development?

    Science.gov (United States)

    Shaw, Daniel L.

    2017-01-01

    Traditional drug development models are widely perceived as opaque and inefficient, with the cost of research and development continuing to rise even as production of new drugs stays constant. Searching for strategies to improve the drug discovery process, the biomedical research field has begun to embrace open strategies. The resulting changes are starting to reshape the industry. Open science—an umbrella term for diverse strategies that seek external input and public engagement—has become an essential tool with researchers, who are increasingly turning to collaboration, crowdsourcing, data sharing, and open sourcing to tackle some of the most pressing problems in medicine. Notable examples of such open drug development include initiatives formed around malaria and tropical disease. Open practices have found their way into the drug discovery process, from target identification and compound screening to clinical trials. This perspective argues that while open science poses some risks—which include the management of collaboration and the protection of proprietary data—these strategies are, in many cases, the more efficient and ethical way to conduct biomedical research. PMID:28356902

  12. Potential drug development candidates for human soil-transmitted helminthiases.

    Directory of Open Access Journals (Sweden)

    Piero Olliaro

    2011-06-01

    Full Text Available Few drugs are available for soil-transmitted helminthiasis (STH; the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment. While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura. In addition, drug resistance is a threat. It is therefore important to find alternatives.We searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI statements, European Public Assessment Reports (EPAR and published literature. Concomitantly, we developed a target product profile (TPP against which the products were compared.The paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files.Few of the compounds already approved for use in human or animal medicine qualify for development track decision. Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

  13. PBPK modeling and simulation in drug research and development

    Directory of Open Access Journals (Sweden)

    Xiaomei Zhuang

    2016-09-01

    Full Text Available Physiologically based pharmacokinetic (PBPK modeling and simulation can be used to predict the pharmacokinetic behavior of drugs in humans using preclinical data. It can also explore the effects of various physiologic parameters such as age, ethnicity, or disease status on human pharmacokinetics, as well as guide dose and dose regiment selection and aid drug–drug interaction risk assessment. PBPK modeling has developed rapidly in the last decade within both the field of academia and the pharmaceutical industry, and has become an integral tool in drug discovery and development. In this mini-review, the concept and methodology of PBPK modeling are briefly introduced. Several case studies were discussed on how PBPK modeling and simulation can be utilized through various stages of drug discovery and development. These case studies are from our own work and the literature for better understanding of the absorption, distribution, metabolism and excretion (ADME of a drug candidate, and the applications to increase efficiency, reduce the need for animal studies, and perhaps to replace clinical trials. The regulatory acceptance and industrial practices around PBPK modeling and simulation is also discussed.

  14. Diabetes mellitus: Exploring the challenges in the drug development process

    Directory of Open Access Journals (Sweden)

    Julius A Vaz

    2012-01-01

    Full Text Available Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

  15. Diabetes mellitus: Exploring the challenges in the drug development process.

    Science.gov (United States)

    Vaz, Julius A; Patnaik, Ashis

    2012-07-01

    Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF) estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

  16. DMEPOS Competitive Bidding

    Data.gov (United States)

    U.S. Department of Health & Human Services — The DMEPOS Competitive Bidding Program was mandated by Congress through the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). The statute...

  17. Optimization and Simulation in Drug Development - Review and Analysis

    DEFF Research Database (Denmark)

    Schjødt-Eriksen, Jens; Clausen, Jens

    2003-01-01

    We give a review of pharmaceutical R&D and mathematical simulation and optimization methods used to support decision making within the pharmaceutical development process. The complex nature of drug development is pointed out through a description of the various phases of the pharmaceutical...... development process. A part of the paper is dedicated to the use of simulation techniques to support clinical trials. The paper ends with a section describing portfolio modelling methods in the context of the pharmaceutical industry....

  18. Optimization and Simulation in Drug Development - Review and Analysis

    OpenAIRE

    Schjødt-Eriksen, Jens; Clausen, Jens

    2003-01-01

    We give a review of pharmaceutical R&D and mathematical simulation and optimization methods used to support decision making within the pharmaceutical development process. The complex nature of drug development is pointed out through a description of the various phases of the pharmaceutical development process. A part of the paper is dedicated to the use of simulation techniques to support clinical trials. The paper ends with a section describing portfolio modelling methods in the context ...

  19. Barriers to Alzheimer disease drug discovery and development in academia.

    Science.gov (United States)

    Van Eldik, Linda J; Koppal, Tanuja; Watterson, D Martin

    2002-01-01

    The drug discovery and the drug development processes represent a continuum of recursive activities that range from initial drug target identification to final Food and Drug Administration approval and marketing of a new therapeutic. Drug discovery, as its name implies, is more exploratory and less focused in many cases, whereas drug development has a clinically defined endpoint and a specific disease goal. Academia has historically made major contributions to this process at the early discovery phases. However, current trends in the organization of the pharmaceutical industry suggest an expanded role for academia in the near future. Megamergers among major pharmaceutical corporations indicate their movement toward a focus on end-stage clinical trials, manufacturing, and marketing. There has been a parallel increase in outsourcing of intermediate steps to specialty small pharmaceutical, biotechnology, and contract service companies. The new paradigm suggests that academia will play an increasingly important role at the proof-of-principle stage of basic and clinical drug discovery research, in training the future skilled work force, and in close partnerships with small pharmaceutical and biotechnology companies. However, academic drug discovery research faces a set of barriers to progress, the relative importance of which varies with the home institution and the details of the research area. These barriers fall into four general categories: (1) the historical administrative structure and environment of academia; (2) the structure and emphasis of peer review panels that control research funding by government and private agencies; (3) the organization and operation of the academic infrastructure; and (4) the structure and availability of specialized resources and information management. Selected examples of barriers to drug discovery and drug development research and training in academia are presented, as are some specific recommendations designed to minimize or

  20. DEVELOPMENT OF DOMESTIC INFUSION DRUGS BASED ON PARACETAMOL

    Directory of Open Access Journals (Sweden)

    Almakaeva L.G.

    2016-06-01

    Full Text Available The intravenous form of paracetamol compared with oral more reliably supports effective drug concentration in blood plasma that promotes a higher therapeutic effect. Recent studies have confirmed that the use of the intravenous form of paracetamol to deal with postoperative pain multimodal analgesia modes results in reducing the frequency and quantity of opioids administered , and, as a consequence, its associated side effects. The drug Paracetamol , infusion solution 10 mg / ml to 100 ml glass bottles is a drug - generic . His qualitative and quantitative composition is developed from the study of literature data about the drug - similar to " Perfalhan , 10 mg / ml solution for infusion in 100 mL " company Bristol - Myers Squibb, France and experimental work. The aim of our study is development and support of the national composition of the infusion of the drug on the basis of paracetamol, selection of excipients that provide stability of the active substances. Materials and methods. The object of the study was the substance of paracetamol manufactured by Zhejiang Kangle Pharmaceutical Co. , Ltd, China. During the work conducted qualitative and quantitative monitoring sample preparation for indicators of stability: pH content of the active ingredient , transparency, color, impurities , contamination by the methods described in the SFU [and nor- ral documentation to the drug . One potential factor of instability is the effect of paracetamol oxygen, due to the presence in the molecule of paracetamol and -NH possibility of oxidation. Results and Discussion. Paracetamol is derived atsetamina . Substance acetylation are p - aminophenol with acetic anhydride . Saturated aqueous solution has a pH of paracetamol - ment about 6 . Paracetamol is a crystalline white powder , sparingly soluble in water, soluble in 96% alcohol, very slightly soluble in metilenhloride . . Active substance enters in comparison drug in the concentration of 10 mg/ml. Stable

  1. Circular dichroism in drug discovery and development: an abridged review.

    Science.gov (United States)

    Bertucci, Carlo; Pistolozzi, Marco; De Simone, Angela

    2010-09-01

    Chirality plays a fundamental role in determining the pharmacodynamic and pharmacokinetic properties of drugs, and contributes significantly to our understanding of the mechanisms that lie behind biorecognition phenomena. Circular dichroism spectroscopy is the technique of choice for determining the stereochemistry of chiral drugs and proteins, and for monitoring and characterizing molecular recognition phenomena in solution. The role of chirality in our understanding of recognition phenomena at the molecular level is discussed here via several selected systems of interest in the drug discovery and development area. The examples were selected in order to underline the utility of circular dichroism in emerging studies of protein-protein interactions in biological context. In particular, the following aspects are discussed here: the relationship between stereochemistry and pharmacological activity--stereochemical characterization of new leads and drugs; stereoselective binding of leads and drugs to target proteins--the binding of drugs to serum albumins; conformational transitions of peptides and proteins of physiological relevance, and the stereochemical characterization of therapeutic peptides.

  2. Hemispheric Asymmetry of Development Due to Drug Exposure.

    Science.gov (United States)

    Gordon, Harold W

    2017-01-01

    A previous survey of the literature of fMRI brain activation for two risk factors, impulsivity and craving, for addiction were lateralized to the right and left hemispheres respectively. Most articles reported these findings without consideration of how lateral asymmetries might be relevant to understanding the underlying factors leading to addiction. The current survey is intended to extend these observations by demonstrating hemispheric asymmetry of development due to pre-natal or adolescent/adult exposure to drugs of abuse. Articles that reported either pre-natal or adolescent/adult exposure to drugs of abuse were collected and the hemisphere of the affected structures was tabulated to determine if, and which, drugs affected more structures in one hemisphere or the other or both together. Some drugs, notably cocaine and alcohol, differentially affected left or right hemisphere structures which significantly differed depending on whether individuals were exposed prenatally or as an adolescent/adult. Cocaine tended to affect more left hemisphere structures when exposed prenatally and significantly affected more in the right when exposed as adults. Alcohol had the reverse pattern. The difference in patterns of effect between pre-natal or adult exposure was significant for both. The results in this survey demonstrate that some drugs of abuse appear to have a right/left differential effect on structures of the brain. Further investigation into the reasons for this asymmetry may provide new insights into underlying factors of drug-seeking and addiction.

  3. [The new era of epithelium-targeted drug development].

    Science.gov (United States)

    Shimizu, Yoshimi; Nagase, Shotaro; Yagi, Kiyohito; Kondoh, Masuo

    2014-01-01

    Epithelium plays pivotal roles in biological barrier separating the inside of body and the outside environment. Ninety percent of malignant tumors are derived from epithelium. Most pathological microorganisms invade into the body from mucosal epithelium. Thus, epithelium is potential targets for drug development. Claudins (CLs), a family of tetra-transmembrane protein consisting of over 20 members, are structural and functional components of tight junction-seals in epithelium. Modulation of CL-seals enhanced mucosal absorption of drugs. CLs are often over-expressed in malignant tumors. CL-4 expression is increased in the epithelial cells covering the mucosal immune tissues. Very recently, CLs are also expected to be targets for traumatic brain injury and regenerative therapy. In this review, we overview the past, the present and the future of CLs-targeted drug development.

  4. Competitive Position of Dependent Passenger Car Maintenance Companies – Influences, Developments and Challenges in the German Market

    Directory of Open Access Journals (Sweden)

    Werdich Karl

    2015-06-01

    Full Text Available The presented paper concerns itself with passenger car maintenance companies and their competitiveness. Internal and external influences, change drivers and general changes in the companies and their organisation were identified and analysed. The influence of the development of technology and the diffusion of innovations are highlighted in particular. Under consideration of the competitiveness factors, current and future challenges for the passenger car maintenance companies were worked out. Based on these analyses, future tasks, problem statements and challenges were compiled for passenger car maintenance companies from which other subjects of scientific investigation in area of strategic and economic importance arose.

  5. Investigating the Effect of Cooperative Learning and Competitive Learning Strategies on the English Vocabulary Development of Iranian Intermediate EFL Learners

    Science.gov (United States)

    Fekri, Neda

    2016-01-01

    The current study investigated the effect of cooperative and competitive learning strategies on the acquisition of English vocabulary development by Iranian EFL intermediate learners. In addition, it explored what type of theses strategies was more effective. In such doing, utilizing an Oxford Placement Test (OPT), 45 out of 77 Iranian EFL…

  6. Investigation of the Effect of Training on the Development of High School Teachers' Attitudes towards Scientific Research and Project Competitions

    Science.gov (United States)

    Akçöltekin, Alptürk

    2016-01-01

    The main purpose of this study is to develop positive attitudes in high school teachers towards scientific research and project competitions by training them in scientific research and project preparation subjects. The study group consists of 90 high school teachers. As a result of the study, a significant difference was found in favor of…

  7. High-Technology Trade Pattern Analysis: Its Use and Application for Industry Competitiveness Response and Government Policy Development

    OpenAIRE

    Holbrook, J. A.

    1995-01-01

    The Canadian Advanced Technology Association (CATA) in collaboration with Industry Canada, sponsored a workshop on high-technology trade statistics in Ottawa, 19 October 1995. The purpose of the workshop was to review various approaches to high-technology trade pattern analysis, its use, and application for industrial competitiveness responses and government policy development.

  8. Development of indirect competitive ELISA for quantification of mitragynine in Kratom (Mitragyna speciosa (Roxb.) Korth.).

    Science.gov (United States)

    Limsuwanchote, Supattra; Wungsintaweekul, Juraithip; Keawpradub, Niwat; Putalun, Waraporn; Morimoto, Satoshi; Tanaka, Hiroyuki

    2014-11-01

    Monoclonal antibody (MAb) against mitragynine (MG), an analgesic alkaloid from Kratom leaves (Mitragyna speciosa), was produced. MG was coupled to carrier proteins employing either 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), a zero-length cross linker or a 5-carbon length glutaraldehyde cross linker. To confirm the immunogenicity, the hapten numbers were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Preparation of the MAb was accomplished by the electrofusion method. Hybridoma 1A6 that was constructed from the fusion between splenocytes of EDC/NHS conjugate immunized mice and SP2/0-Ag14 myeloma cells was selected, cloned twice and expanded. The cross-reactivities (CRs) of this MAb 1A6 with a series of indole alkaloids were 30.54%, 24.83% and 8.63% for speciogynine, paynantheine and mitraciliatine, respectively. Using this MAb, an indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed with a measurement range of 32.92-250 μg/mL. Quantitative analysis of the MG contents in plant samples by icELISA correlated well with the standard high performance liquid chromatography method (R(2)=0.994). The MAb against mitragynine provided a tool for detection of MG in Kratom preparations.

  9. Building the Competitive Advantage of a Business Entity through Brand Development

    Directory of Open Access Journals (Sweden)

    Mirjana Nedović Čabarkapa

    2010-07-01

    Full Text Available The starting point of this paper is the idea of brand. Its aim is to define the role of a brand with the purpose of the establishment of future contributions in the scope of this area, that is its influence on purchase stimulation and the establishment of a competitive advantage for a business entity in regard to other market actors. Furthermore, a brief theoretical explanation of the term brand is provided, i.e. the history of brand’s emergence, as well as a review of its elements. The many complexities during the establishment of brand are also explained. Brand has emerged as a consequence of market globalization, as well as the existence of numerous products that satisfy the same need. Its main purpose is the differentiation of products and the attempt to draw potential consumers’ attention in order to influence them to decide on the purchase of a brand product as quickly as possible. Business entities that realize the importance of creating a brand, its development and management will create all preconditions for successful, i.e. profitable operation. This way of deliberation and brand management represents the key to the business success of every business entity. It is generally considered that the market power of a brand can also be treated as an asset.

  10. Development and Creation of Competitive Advantages in the Function of Marketing Services in Financial Institutions

    Directory of Open Access Journals (Sweden)

    Fatos UKAJ

    2016-09-01

    Full Text Available The marketing of the financial services by financial institution is regarded as an easier job. This is due to the fact that, in most cases, when a client is gained, he/she remains loyal to the institution on a long term. Nowadays, taking into consideration the needs of the consumers - clients who are undergoing a constant change - financial institutions are faced with a necessity to have the required knowledge and information regarding what and how to meet the needs of their clients. Financial institutions have reached a stage of adapting their daily activities with the demands of their clients. Thus, this is due to the available information which deals with the needs of the clients, opportunities of financial institution themselves, structural changes in the services provided, and the changes in the market which includes competition. This paper will strive to present the stages of the marketing development in financial institutions through the acquisition of knowledge regarding the finances and marketing of these services. It also involves the current concept and approach towards marketing by financial institutions in Kosovo. Adopting new approaches would satisfy the client and would strengthen the position of financial institution. In addition, through this analysis, we will try to show the importance of including the concept of marketing in the operations and strategies of financial institutions for a successful business.

  11. Development of SPR Immunosensor by Indirect Competitive Method for Rapid and Highly Sensitive Salivary Cortisol Detection

    Directory of Open Access Journals (Sweden)

    Yusuke eTahara

    2014-05-01

    Full Text Available The monitoring of salivary cortisol as a key biomarker of an individual’s stress response has been increasingly focused on. This paper describes the development of a novel cortisol biosensor based on an indirect competitive method using a surface plasmon resonance (SPR immunosensor. The surface of a Au chip was modified with PEG6-COOH aromatic dialkanethiol self-assembled monolayers (SAMs and hydrocortisone 3-(O-carboxymethyl oxime (hydrocortisone 3-CMO as a cortisol analogue. A detection limit of 38 ppt range with a measurement range of 10 ppt to 100 ppb was accomplished without the incubation of a mixing solution consisting of standard cortisol and an anti-cortisol antibody, and the response time was 5 min from the sample injection. We experimentally compared our biosensor with a commercialized salivary cortisol enzyme-linked immunosorbent assay (ELISA kit using human saliva samples. It was found that the results obtained by the cortisol biosensor had a high correlation with those obtained by ELISA assay (R = 0.96. Our findings indicate the potential utility of the cortisol biosensor for on-site diagnosis and bedside point-of-care testing (POCT from bedside testing.

  12. Interspecies modulation of bacterial development through iron competition and siderophore piracy.

    Science.gov (United States)

    Traxler, Matthew F; Seyedsayamdost, Mohammad R; Clardy, Jon; Kolter, Roberto

    2012-11-01

    While soil-dwelling actinomycetes are renowned for secreting natural products, little is known about the roles of these molecules in mediating actinomycete interactions. In a previous co-culture screen, we found that one actinomycete, Amycolatopsis sp. AA4, inhibited aerial hyphae formation in adjacent colonies of Streptomyces coelicolor. A siderophore, amychelin, mediated this developmental arrest. Here we present genetic evidence that confirms the role of the amc locus in the production of amychelin and in the inhibition of S. coelicolor development. We further characterize the Amycolatopsis sp. AA4 - S. coelicolor interaction by examining expression of developmental and iron acquisition genes over time in co-culture. Manipulation of iron availability and/or growth near Amycolatopsis sp. AA4 led to alterations in expression of the critical developmental gene bldN, and other key downstream genes in the S. coelicolor transcriptional cascade. In Amycolatopsis sp. AA4, siderophore genes were downregulated when grown near S. coelicolor, leading us to find that deferrioxamine E, produced by S. coelicolor, could be readily utilized by Amycolatopsis sp. AA4. Collectively these results suggest that competition for iron via siderophore piracy and species-specific siderophores can alter patterns of gene expression and morphological differentiation during actinomycete interactions.

  13. Competition as an Effective Tool in Developing Social Marketing Programs: Driving Behavior Change through Online Activities

    Directory of Open Access Journals (Sweden)

    Corina ŞERBAN

    2011-12-01

    Full Text Available Nowadays, social marketing practices represent an important part of people’s lives. Consumers’ understanding of the need for change has become the top priority for social organizations worldwide. As a result, the number of social marketing programs has increased, making people reflect more on their behaviors and on the need to take action. Competition in social marketing can bring many benefits. The more programs initiated, the more people will start to involve in society’s problems, hereby contributing to beneficial causes. However, social organizations are in the search for competitive advantages to differentiate them on the market. This paper aims to present the role of online communication in driving competitive advantage for social organizations. Using the structural equation model, the paper describes the relations between four characteristics of the online communication: credibility, attractiveness, persuasion and promotion and then presents the correlations between these variables and website competitiveness. The resulting model shows that owning a competitive advantage in social marketing can bring many advantages to both the non-profit organization and the consumer. Therefore, the online environment can be considered a good solution for better serving consumers’ social needs. Its contribution is significant especially in programs for children and adolescents, since teenagers spend more time on the Internet than adults and are more open to using the online channels of communication. In conclusion, this article opens new opportunities for social marketers to address society’s problems and supports the integration of the online communication tools in the competition strategy.

  14. [International Partnership for Therapeutic Drug Development of NTDs by DNDi].

    Science.gov (United States)

    Yamada, Haruki; Hirabayashi, Fumiko; Brünger, Chris

    2016-01-01

    The Drugs for Neglected Diseases initiative (DNDi), with headquarters in Geneva, is a non-profit drug research and development (R&D) organization and Product Development Partnership (PDP) which was established in 2003 by 7 founding organizations such as Médecins Sans Frontières (MSF), the Pasteur Institute, The Specific Programme for Research and Training in Tropical Diseases (WHO-TDR), etc. DNDi has worked mainly on the development of new treatments for neglected tropical diseases (NTDs), which is difficult to achieve under market economy conditions. DNDi has promoted overall drug discovery research including the screening of drug candidates, hit to lead, lead optimization, pre-clinical and clinical studies in the area of infectious diseases with a focus on malaria, sleeping sickness (human African trypanosomiasis; HAT), Chagas disease, leishmaniasis, filarial diseases and pediatric formulations for HIV treatment. DNDi's achievements include the development of novel therapies based on patient needs through innovative partnerships with over 130 organizations in industry, government, academia, and public institutions around the world. To date, DNDi has registered 6 novel treatments adapted to the needs of patients in poor countries, and has another 12 novel entities in development. DNDi Japan is a Japanese non-profit organization (NPO) based on the global principles of DNDi and, as the only PDP in Japan, is supporting NTD drug discovery projects in collaboration with Japanese pharmaceutical companies, academic institutions and government agencies by utilizing Japan's excellent R&D capabilities to develop new treatments for NTDs in order to contribute to global health.

  15. From research on rare diseases to new orphan drug development

    NARCIS (Netherlands)

    Heemstra, H.E.

    2010-01-01

    Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs

  16. From research on rare diseases to new orphan drug development

    NARCIS (Netherlands)

    Heemstra, H.E.

    2010-01-01

    Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs f

  17. Open data in drug discovery and development: lessons from malaria.

    Science.gov (United States)

    Wells, Timothy N C; Willis, Paul; Burrows, Jeremy N; Hooft van Huijsduijnen, Rob

    2016-10-01

    There is a growing consensus that drug discovery thrives in an open environment. Here, we describe how the malaria community has embraced four levels of open data - open science, open innovation, open access and open source - to catalyse the development of new medicines, and consider principles that could enable open data approaches to be applied to other disease areas.

  18. Quantitative EEG Brain Mapping In Psychotropic Drug Development, Drug Treatment Selection, and Monitoring.

    Science.gov (United States)

    Itil, Turan M.; Itil, Kurt Z.

    1995-05-01

    Quantification of standard electroencephalogram (EEG) by digital computers [computer-analyzed EEG (CEEG)] has transformed the subjective analog EEG into an objective scientific method. Until a few years ago, CEEG was only used to assist in the development of psychotropic drugs by means of the quantitative pharmaco EEG. Thanks to the computer revolution and the accompanying reductions in cost of quantification, CEEG can now also be applied in psychiatric practice. CEEG can assist the physician in confirming clinical diagnoses, selecting psychotropic drugs for treatment, and drug treatment monitoring. Advancements in communications technology allow physicians and researchers to reduce the costs of acquiring a high-technology CEEG brain mapping system by utilizing the more economical telephonic services.

  19. 78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

    Science.gov (United States)

    2013-05-31

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Rheumatoid Arthritis... guidance for industry entitled ``Rheumatoid Arthritis: Developing Drug Products for Treatment.'' This... products developed as drug-device combination products. This guidance revises the guidance for...

  20. Development of modified pulsincap drug delivery system of metronidazole for drug targeting

    Directory of Open Access Journals (Sweden)

    Abraham Sindhu

    2007-01-01

    Full Text Available A modified Pulsincap dosage form of metronidazole was developed to target drug release in the colon. Bodies of hard gelatin capsules were treated with formaldehyde keeping the caps as such. Metronidazole pellets prepared by extrusion-spheronization method were incorporated into these specialized capsule shells and plugged with polymers guar gum, hydroxypropylmethylcellulose 10K, carboxymethylcellulose sodium and sodium alginate separately at concentrations 20 mg, 30 mg and 40 mg. The filled capsules were completely coated with 5% cellulose acetate phthalate to prevent variable gastric emptying. All the formulations were assayed to determine drug content and the ability of the modified Pulsincap to provide colon-specific drug delivery was assessed by in vitro drug release studies in buffer pH 1.2 for 2 h, pH 7.4 (simulated intestinal fluid for 3 h and pH 6.8 (stimulated colonic fluid for 7 h. The results indicated that significant drug release occurred only after 5 h from the start of experiment. Thus, metronidazole could be successfully colon targeted by the use of the modified Pulsincap, thereby reducing systemic side effects.

  1. EDITORIAL: Physics competitions Physics competitions

    Science.gov (United States)

    Jordens, H.; Mathelitsch, L.

    2009-11-01

    students are allowed to use any method they like, are coached by teachers, and are encouraged to ask for help from experts at research centres or universities. Finally, they must prepare a 12-minute presentation. A tournament consists of different contests. In each contest, three teams are involved: the reporting team is challenged by an opponent team to present a task. This presentation is then criticized by the opponent, pointing out merits and possible weak parts. The discussion between the two representatives of the teams is a central element of a contest. The third team acts as reviewer, giving final comments on the performances of the contesting teams. At the end, a jury grades the performances of all three teams. Then, the different roles of the teams rotate, and the students also rotate roles within the teams. The competition started in the former Soviet Union in 1988 and became international for the first time in 1994 when it was organized in Groningen, The Netherlands. In the 2008 tournament in Trogir, Croatia, teams from 24 countries participated [5]. Since this tournament is younger and less known, the national pre-selections are not as well established and numerous as for the Olympiad. Also, the training is different: in addition to developing experimental skills and physical understanding of the problems, the students must organize their performances, share work and responsibilities, and must train in the techniques of presentation and debate (in English). The winner of the tournament in Croatia was the team from Germany. Their presentation in the finals was an experimental and theoretical investigation into the Kaye effect. The students wrote up their presentation, and it is reproduced here as the second paper in this special section. Again, different in spirit and aim is 'First Step to Nobel Prize in Physics' [6]. This competition started in 1991 in Poland and encourages students to take their first steps in physics research. Students of 20 years old or

  2. 5th Antiviral Drug Discovery and Development Summit.

    Science.gov (United States)

    Blair, Wade; Perros, Manos

    2004-08-01

    The 5th Antiviral Drug Discovery and Development Summit provided an up-to-date snapshot of the ongoing developments in the area. The topics covered ranged from updates on recently launched drugs (Kaletra), Fuzeon) and new investigational inhibitors (T-1249, Reverset, UK-427857, L-870810, PA-457, remofovir, VX-950), to the discovery of new antiviral targets and advances in technologies that may provide the substrate for the next generation of therapeutics. It is apparent from the range of presentations that much of today's efforts are focused on developing new classes of HIV inhibitors (gp41, integrase), while there is also considerable progress in hepatitis C, where a number of inhibitors have or should reach proof-of-concept studies in the coming months. Here we provide the highlights of this meeting, with particular emphasis on the new developments in HIV and hepatitis C virus.

  3. New drug development for post-traumatic stress disorder.

    Science.gov (United States)

    Berlant, Jeffrey

    2003-01-01

    US FDA approval of two serotonin-selective reuptake inhibitor (SSRI) agents for post-traumatic stress disorder (PTSD) has created new opportunities for drug development. This follows many years of exploring the potential utility of several classes of psychotropic agents for this very common, yet under-recognized and under-treated disorder. This review examines some of the basic neurobiological abnormalities observed in PTSD and summarizes open and controlled drug trials for major classes of medications, including SSRIs, other antidepressants, atypical neuroleptics, noradrenergic modulators and anticonvulsants, while critically evaluating the extent of effectiveness of these agents and reviewing unmet gaps in therapeutic need.

  4. Sex Differences in the Development of the Motive to Avoid Success, Sex Role Identity, and Performance in Competitive and Non-Competitive Conditions.

    Science.gov (United States)

    Romer, Nancy

    Horner's study of the motive to avoid success (Ms) was replicated on fifth through eleventh grade males and females. Ss were given a TAT-like measure of Ms and a measure of sex role identity. They also performed a series of tasks in competitive and non-competitive conditions. No sex differences or clear age trends in Ms imagery were found;…

  5. Multiple soil nutrient competition between plants, microbes, and mineral surfaces: model development, parameterization, and example applications in several tropical forests

    Science.gov (United States)

    Zhu, Q.; Riley, W. J.; Tang, J.; Koven, C. D.

    2016-01-01

    Soil is a complex system where biotic (e.g., plant roots, micro-organisms) and abiotic (e.g., mineral surfaces) consumers compete for resources necessary for life (e.g., nitrogen, phosphorus). This competition is ecologically significant, since it regulates the dynamics of soil nutrients and controls aboveground plant productivity. Here we develop, calibrate and test a nutrient competition model that accounts for multiple soil nutrients interacting with multiple biotic and abiotic consumers. As applied here for tropical forests, the Nutrient COMpetition model (N-COM) includes three primary soil nutrients (NH4+, NO3- and POx; representing the sum of PO43-, HPO42- and H2PO4-) and five potential competitors (plant roots, decomposing microbes, nitrifiers, denitrifiers and mineral surfaces). The competition is formulated with a quasi-steady-state chemical equilibrium approximation to account for substrate (multiple substrates share one consumer) and consumer (multiple consumers compete for one substrate) effects. N-COM successfully reproduced observed soil heterotrophic respiration, N2O emissions, free phosphorus, sorbed phosphorus and NH4+ pools at a tropical forest site (Tapajos). The overall model uncertainty was moderately well constrained. Our sensitivity analysis revealed that soil nutrient competition was primarily regulated by consumer-substrate affinity rather than environmental factors such as soil temperature or soil moisture. Our results also imply that under strong nutrient limitation, relative competitiveness depends strongly on the competitor functional traits (affinity and nutrient carrier enzyme abundance). We then applied the N-COM model to analyze field nitrogen and phosphorus perturbation experiments in two tropical forest sites (in Hawaii and Puerto Rico) not used in model development or calibration. Under soil inorganic nitrogen and phosphorus elevated conditions, the model accurately replicated the experimentally observed competition among

  6. Development of biosimilars in an era of oncologic drug shortages

    Directory of Open Access Journals (Sweden)

    Li E

    2015-06-01

    Full Text Available Edward Li,1 Janakiraman Subramanian,2 Scott Anderson,3 Dolca Thomas,4 Jason McKinley,5 Ira A Jacobs4 1University of New England College of Pharmacy, Portland, ME, USA; 2Hanna Cancer Associates, Knoxville, TN, USA; 3Pfizer Inc, La Jolla, CA, USA; 4Pfizer Inc, New York, NY, USA; 5Pfizer Inc, Groton, CT, USA Abstract: Acute and chronic shortages of various pharmaceuticals and particularly of sterile injectable products are being reported on a global scale, prompting evaluation of more effective strategies to manage current shortages and development of new, high-quality pharmaceutical products to mitigate the risk of potential future shortages. Oncology drugs such as liposomal doxorubicin and 5-fluorouracil represent examples of first-choice drugs critically affected by shortages. Survey results indicate that the majority of hospitals and practicing oncologists have experienced drug shortages, which may have compromised patient safety and clinical outcomes, and increased health care costs, due to delays or changes in treatment regimens. Clinical trials evaluating novel agents in combination with standard-of-care drugs are also being affected by drug shortages. Clinical and ethical considerations on treatment objectives, drug indication, and availability of alternative options may help in prioritizing cancer patients involved in active drug shortages. The United States Food and Drug Administration and the European Medicines Agency have identified manufacturing problems, delays in supply, and lack of available active ingredients as the most frequent causes of recent or ongoing drug shortages, and have released specific guidance to monitor, manage, and reduce the risk of shortages. The upcoming loss of exclusivity for a number of anticancer biologics, together with the introduction of an abbreviated approval pathway for biosimilars, raises the question of whether these products will be vulnerable to shortages. Future supply by reliable

  7. [Post-authorization research, registries, and drug development].

    Science.gov (United States)

    Patarnello, Francesca; Recchia, Giuseppe

    2013-06-01

    In the last decade regulators, payers and health care providers tried to react to three major problems in drug development and drug use in clinical practice: the pharmaceutical R&D productivity crisis, the immaturity of benefit-risk profile for several newly approved drugs and the overall impact on economic sustainability of reimbursing new high cost drugs in their systems. The potentiality of create a continuum between the evidence requirements relevant for registration, for reimbursement and for post authorization research is clear. All different parties involved, like regulators, HTA agencies, scientific communities and manufacturers, are working to improve the knowledge profile of new drugs in order to anticipate the patient access to innovation, limiting or preventing the clinical and economical risks deriving from an incomplete safety and effectiveness profile. The Italian example of "New Drugs AIFA Registries", with or without the application of risk sharing schemes (cost sharing, pay for performance, etc.), introduced a new process and increased the sensitivity on this topic. However this might probably represents only a partial answer to the problem of how to set up the governance of coverage with evidence, drug utilization monitoring, comparative effectiveness research, outcome research programs and may be how to link them to access, pricing and reimbursement. The step change in post authorization research could be to "integrate" different sources and stakeholders in a wider and continuous approach, in a well designed and inclusive "second generation" HTA approach, where all resources (competencies, data, funding) will concur to increase the evidence profile and reduce the risks, and where any "evidence generation approach" is really compliant with the standard and rules of best research practices.

  8. Drug Discovery and Development of Antimalarial Agents: Recent Advances.

    Science.gov (United States)

    Thota, Sreekanth; Yerra, Rajeshwar

    2016-01-01

    Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.

  9. Conference report: hot topics in antibody-drug conjugate development.

    Science.gov (United States)

    Thudium, Karen; Bilic, Sanela

    2013-12-01

    American Association of Pharmaceutical Scientists National Biotechnology Conference Sheraton San Diego Hotel and Marina, San Diego, CA, USA, 19-23 May 2013 The National Biotechnology Conference, is a premier meeting for biotechnology professionals covering a broad range of hot topics in the biotechnology industry. Attracting participants from academia, industry and regulatory, this meeting features sessions that aim to address emerging subjects of interest and allows for open exchange between scientists. The 2013 conference featured leading researchers in the fields of antibody-drug conjugates (ADCs) and immunogenicity. Herein, we present a summary of the ADC hot topics, including bioanalytical and PK considerations, quantitative evaluation of the impact of immunogenicity and ADME to understand ADC drug-drug interactions, and clinical considerations for ADC development. This article aims to summarize the recommendations that were made by the speakers during various sessions throughout the conference.

  10. Schizophrenia drug discovery and development in an evolving era: are new drug targets fulfilling expectations?

    Science.gov (United States)

    Dunlop, John; Brandon, Nicholas J

    2015-02-01

    Current therapeutics for schizophrenia, the typical and atypical antipsychotic class of drugs, derive their therapeutic benefit predominantly by antagonism of the dopamine D2 receptor subtype and have robust clinical benefit on positive symptoms of the disease with limited to no impact on negative symptoms and cognitive impairment. Driven by these therapeutic limitations of current treatments and the recognition that transmitter systems beyond the dopaminergic system in particular glutamatergic transmission contribute to the etiology of schizophrenia significant recent efforts have focused on the discovery and development of novel treatments for schizophrenia with mechanisms of action that are distinct from current drugs. Specifically, compounds selectively targeting the metabotropic glutamate receptor 2/3 subtype, phosphodiesterase subtype 10, glycine transporter subtype 1 and the alpha7 nicotinic acetylcholine receptor have been the subject of intense drug discovery and development efforts. Here we review recent clinical experience with the most advanced drug candidates targeting each of these novel mechanisms and discuss whether these new agents are living up to expectations.

  11. Trends in risks associated with new drug development: success rates for investigational drugs.

    Science.gov (United States)

    DiMasi, J A; Feldman, L; Seckler, A; Wilson, A

    2010-03-01

    This study utilizes both public and private data sources to estimate clinical phase transition and clinical approval probabilities for drugs in the development pipelines of the 50 largest pharmaceutical firms (by sales). The study examined the development histories of these investigational compounds from the time point at which they first entered clinical testing (1993-2004) through June 2009. The clinical approval success rate in the United States was 16% for self-originated drugs (originating from the pharmaceutical company itself) during both the 1993-1998 and the 1999-2004 subperiods. For all compounds (including licensed-in and licensed-out drugs in addition to self-originated drugs), the clinical approval success rate for the entire study period was 19%. The estimated clinical approval success rates and phase transition probabilities differed significantly by therapeutic class. The estimated clinical approval success rate for self-originated compounds over the entire study period was 32% for large molecules and 13% for small molecules. The estimated transition probabilities were also higher for all clinical phases with respect to large molecules.

  12. New approaches in antimalarial drug discovery and development: a review

    Directory of Open Access Journals (Sweden)

    Anna Caroline C Aguiar

    2012-11-01

    Full Text Available Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria.

  13. Recent lab-on-chip developments for novel drug discovery.

    Science.gov (United States)

    Khalid, Nauman; Kobayashi, Isao; Nakajima, Mitsutoshi

    2017-02-17

    Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development. In this review, we report on the latest developments in fabrication methods and production methodologies to tailor LOC devices. A brief overview of scale-up strategies is also presented together with their potential applications in drug delivery and discovery. The impact of LOC devices on drug development and discovery has been extensively reviewed in the past. The current research focuses on fast and accurate detection of genomics, cell mutations and analysis, drug delivery, and discovery. The current research also differentiates the LOC devices into new terminology of microengineering, like organ-on-a-chip, stem cells-on-a-chip, human-on-a-chip, and body-on-a-chip. Key challenges will be the transfer of fabricated LOC devices from lab-scale to industrial large-scale production. Moreover, extensive toxicological studies are needed to justify the use of microfabricated drug delivery vehicles in biological systems. It will also be challenging to transfer the in vitro findings to suitable and promising in vivo models. For further resources related to this article, please visit the WIREs website.

  14. Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

    Science.gov (United States)

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients.

  15. Core competencies for pharmaceutical physicians and drug development scientists.

    Science.gov (United States)

    Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

    2013-01-01

    Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide.

  16. Safe procedure development to manage hazardous drugs in the workplace

    Directory of Open Access Journals (Sweden)

    Marisa Gaspar Carreño

    2017-03-01

    Full Text Available Objective: To develop a safety working procedure for the employees in the Intermutual Hospital de Levante (HIL in those areas of activity that deal with the handling of hazardous drugs (MP. Methods: The procedure was developed in six phases: 1 hazard definition; 2 definition and identification of processes and development of general correct work practices about hazardous drugs’ selection and special handling; 3 detection, selection and set of specific recommendations to handle with hazardous drugs during the processes of preparation and administration included in the hospital GFT; 4 categorization of risk during the preparation/administration and development of an identification system; 5 information and training of professionals; 6 implementation of the identification measures and prevention guidelines. Results: Six processes were detected handling HD. During those processes, thirty HD were identified included in the hospital GFT and a safer alternative was found for 6 of them. The HD were classified into 4 risk categories based on those measures to be taken during the preparation and administration of each of them. Conclusions: The development and implementation of specific safety-work processes dealing with medication handling, allows hospital managers to accomplish effectively with their legal obligations about the area of prevention and provides healthcare professional staff with the adequate techniques and safety equipment to avoid possible dangers and risks of some drugs.

  17. SMEs Development Strategy for Competitive and Sustainable Typical Local Snacks of Banten Province

    OpenAIRE

    Sawarni Hasibuan

    2015-01-01

    Small Medium Enterprises (SMEs) for snacks in Indonesia currently has a good growth rate on one hand; but on the other hand, its level of competition is also quite high.  Growth in sales volume of the Indonesian snack industry, both in modern and traditional markets in 2012, was recorded at 10-15 percent far beyond the growth of other manufacturing industries.  However, the level of competition in the snack industry is also relatively high. Business people in the snacks sector do not only com...

  18. Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European Bioanalysis Forum.

    Science.gov (United States)

    Buscher, Brigitte; Laakso, Sirpa; Mascher, Hermann; Pusecker, Klaus; Doig, Mira; Dillen, Lieve; Wagner-Redeker, Winfried; Pfeifer, Thomas; Delrat, Pascal; Timmerman, Philip

    2014-03-01

    Plasma protein binding (PPB) is an important parameter for a drug's efficacy and safety that needs to be investigated during each drug-development program. Even though regulatory guidance exists to study the extent of PPB before initiating clinical studies, there are no detailed instructions on how to perform and validate such studies. To explore how PPB studies involving bioanalysis are currently executed in the industry, the European Bioanalysis Forum (EBF) has conducted three surveys among their member companies: PPB studies in drug discovery (Part I); in vitro PPB studies in drug development (Part II); and in vivo PPB studies in drug development. This paper reflects the outcome of the three surveys, which, together with the team discussions, formed the basis of the EBF recommendation. The EBF recommends a tiered approach to the design of PPB studies and the bioanalysis of PPB samples: 'PPB screening' experiments in (early) drug discovery versus qualified/validated procedures in drug development.

  19. [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.

  20. The Challenges of Precision Oncology Drug Development and Implementation.

    Science.gov (United States)

    Hollingsworth, Simon J; Biankin, Andrew V

    2015-01-01

    The drivers of precision medicine are clear: for patients (and physicians)--more options, durable clinical benefit, reduced exposure to non-effective drugs and potential to leverage current scientific and technological advances; for the pharmaceutical industry--the potential to tackle core challenges in discovering and developing better and more efficacious medicines, to reduce rates of attrition in drug development and to reduce development costs; for healthcare systems and payers--improved efficiency through the provision of effective care and avoiding ineffective treatments. Oncology has been at the vanguard, the improvements gained in patient survival notable. However, the increasing number of molecular subgroups requires an equally increasing number (and new generation) of highly selective agents targeting inevitably lower incidence molecular segments. Innovative trial designs (umbrella/basket studies) are emerging as a patient-centric approach to drug development, and the rise in public-private partnerships, cross-industry, government and non-profit sector collaborations is enabling implementation of complex clinical trial designs. This poses significant challenges for healthcare systems and regulatory approval. Further substantial evolution of policy and processes, particularly regulatory requirements for approval for new therapeutics, are required.

  1. NIPTE: a multi-university partnership supporting academic drug development.

    Science.gov (United States)

    Gurvich, Vadim J; Byrn, Stephen R

    2013-10-01

    The strategic goal of academic translational research is to accelerate translational science through the improvement and development of resources for moving discoveries across translational barriers through 'first in humans' studies. To achieve this goal, access to drug discovery resources and preclinical IND-enabling infrastructure is crucial. One potential approach of research institutions for coordinating preclinical development, based on a model from the National Institute for Pharmaceutical Technology and Education (NIPTE), can provide academic translational and medical centers with access to a wide variety of enabling infrastructure for developing small molecule clinical candidates in an efficient, cost-effective manner.

  2. Drug-usage evaluation by disease state: developing protocols.

    Science.gov (United States)

    Enlow, M L

    1996-07-01

    The Joint Commission definition of drug-usage evaluation (DUE) also applies to DUE by disease state. The criteria for disease process selection, key processes being evaluated, methods to develop initial DUE protocols, and DUE validation and approval processes are reviewed. The treatment of community-acquired pneumonia is a disease state DUE performed at Saint Joseph Health Center in Kansas City, Missouri. The preliminary protocol was developed by a collaborative network of clinical pharmacists in the metropolitan area. Outcome measures were included in the evaluation. The results were used as baseline data in the development of a pneumonia clinical pathway.

  3. PRADO MUSEUM - SUCCESSFUL MODEL FOR RAISING COMPETITIVENESS IN THE ROMANIAN CULTURAL ORGANIZATIONS IN THE CONTEXT OF URBAN DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Răzvan-Andrei CORBOȘ

    2012-01-01

    Full Text Available The interest in the conceptual delimitation of the competitiveness of cultural organizations, as well as in identifying the sources of its growth, has increased in recent years due to the need to diversify the funding sources of this type of organization, urban development and the willingness to adapt to the requirements of customers who are more numerous and have diverse expectations. Practice shows that cultural organizations that have adopted a competitive economy vision and have applied specific management tools for increasing the organizational competitiveness, have achieved a good performance, becoming, this way, an example of managerial success story in the field. The experience of Prado Museum, one of the emblems of Madrid, falls in this direction. The substantial increase in the number of tourists, the decrease in state funding combined with the increase of proprietary financing resources, the enhancement of the national and international reputation, are just some of the positive results that prove the quality of used management. This paper presents and analysis these effects and the causes that have generated them, thus providing some possible suggestions for action for Romanian cultural organizations in order to increase their competitiveness.

  4. Evaluation, Support and Promotion of Specialists' Competitiveness Development in Modern Enterprise as Learning Organization

    Science.gov (United States)

    Katane, Irena; Kristovska, Ineta; Vjatere, Gita; Katans, Edgars

    2015-01-01

    The process of globalization and the changeability of environment nowadays demand that society ensure sustainability for itself and its lifewide environment. Therefore nowadays the paradigm of personality's and specialist's competitiveness is changing. The old paradigm is substituted by a set of new viewpoints and concepts. The issue of ensuring…

  5. Evaluation, Support and Promotion of Specialists' Competitiveness Development in Modern Enterprise as Learning Organization

    Science.gov (United States)

    Katane, Irena; Kristovska, Ineta; Vjatere, Gita; Katans, Edgars

    2015-01-01

    The process of globalization and the changeability of environment nowadays demand that society ensure sustainability for itself and its lifewide environment. Therefore nowadays the paradigm of personality's and specialist's competitiveness is changing. The old paradigm is substituted by a set of new viewpoints and concepts. The issue of ensuring…

  6. The Definition, Measurement and Development of Social Motives Underlying Cooperative and Competitive Behavior.

    Science.gov (United States)

    McClintock, Charles G.; Messick, David M.

    This research proposal supports a program in social psychology which uses a variety of game paradigms and related tasks to obtain estimates of the relative dominance of various social motives including those of maximizing own gain (individualism), joint gain (cooperation), and relative gain (competition). Numerous major studies completed or in…

  7. Strategy Development in UK Higher Education: Towards Resource-Based Competitive Advantages

    Science.gov (United States)

    Lynch, Richard; Baines, Paul

    2004-01-01

    Britain's higher education institutions (HEIs) face fundamental and unprecedented competitive pressures due to lower government funding (Cm 5735, "The Future of Higher Education," Department for Education and Skills, 2003) and a government agenda focused on a "widening participation agenda". We employ the resource-based view (RBV) of strategy…

  8. Strategy Development in UK Higher Education: Towards Resource-Based Competitive Advantages

    Science.gov (United States)

    Lynch, Richard; Baines, Paul

    2004-01-01

    Britain's higher education institutions (HEIs) face fundamental and unprecedented competitive pressures due to lower government funding (Cm 5735, "The Future of Higher Education," Department for Education and Skills, 2003) and a government agenda focused on a "widening participation agenda". We employ the resource-based view (RBV) of strategy…

  9. 78 FR 58546 - State System Development Initiative (SSDI) Grant Program; Single-Case Deviation From Competition...

    Science.gov (United States)

    2013-09-24

    ... Program; Single- Case Deviation From Competition Requirements AGENCY: Health Resources and Services Administration (HRSA), Department of Health and Human Services (HHS). ACTION: Notice of Single-Case Deviation... purpose to improve the health of all mothers and children, a key objective of the Title V MCH Block Grant...

  10. A physiome interoperability roadmap for personalized drug development.

    Science.gov (United States)

    Thomas, Simon; Wolstencroft, Katherine; de Bono, Bernard; Hunter, Peter J

    2016-04-06

    The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as '-omics'), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development.

  11. Export and Competitiveness of Indonesian Coffee Bean in International Market: Strategic Implication for the Development of Organic Coffee Bean

    Directory of Open Access Journals (Sweden)

    Bambang Drajat

    2007-07-01

    Full Text Available The performance of Indonesian coffee bean export from 1995 to 2004was not satisfactory. This implied that there were problems of the competitiveness of Indonesian coffee bean export. This study was expected to come up withsome views related with the problem. This study was aimed to analyze the competitiveness of Indonesian coffee bean export in international markets. Somepolicy implication would be derived following the conclusions. In addition,this study was aimed to deliver some arguments referring to organic coffee development as an alternative export development. Data used in this study wastime series data ranging from 1995 to 2004 supported with some primary data.The export data were analyzed descriptively and the Revealed ComparativeAdvantage (RCA Index employed to analyze the competitiveness of Indonesian coffee bean export. The results of the analysis gave some conclusions, asfollows : (1 The export of Indonesian coffee bean was product oriented notmarket oriented. (2 The Indonesian coffee bean export was characterized withlow quality with no premium price, different from that of Vietnam coffee export. (3 Besides quality, the uncompetitive Indonesian coffee export was related to market hegemony by buyers, emerging issue of Ochratoxin A. contamination and high cost economy in export. (4 The competitiveness of Indonesian coffee export was lower than those other countries, such as Columbia,Honduras, Peru, Brazil, and Vietnam. (5 Indonesia still held opportunity todevelop organic coffee for export. Some policy implications emerged from thediscussion were as follows : (1 The Government should facilitate market development through the provisions of market information and export incentives.(2 The Government should develop and applied national standard of coffeebean referring to that of international, as well as, improve processing technology equipments in the farm level for both wet and dry process. (3 Besides improving quality, the improvement

  12. Development of drugs and technology for radiation theragnosis

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hwan Jeong [Dept. of Nuclear Medicine, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of); Lee, Byung Chul [Dept. of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of); Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of); Kang, Keon Wook [Dept. of Nuclear Medicine and Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2016-06-15

    Personalized medicine is tailored medical treatment that targets the individual characteristics of each patient. Theragnosis, combining diagnosis and therapy, plays an important role in selecting appropriate patients. Noninvasive in vivo imaging can trace small molecules, antibodies, peptides, nanoparticles, and cells in the body. Recently, imaging methods have been able to reveal molecular events in cells and tissues. Molecular imaging is useful not only for clinical studies but also for developing new drugs and new treatment modalities. Preclinical and early clinical molecular imaging shows biodistribution, pharmacokinetics, mechanisms of action, and efficacy. When therapeutic materials are labeled using radioisotopes, nuclear imaging with positron emission tomography or gamma camera can be used to treat diseases and monitor therapy simultaneously. Such nuclear medicine technology is defined as radiation theragnosis. We review the current development of drugs and technology for radiation theragnosis using peptides, albumin, nanoparticles, and cells.

  13. Molecularly targeted therapy for advanced hepatocellularcarcinoma - a drug development crisis?

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Hepatocellular carcinoma is the fastest growing causeof cancer related death globally. Sorafenib, a multitargetedkinase inhibitor, is the only drug proven toimprove outcomes in patients with advanced diseaseoffering modest survival benefit. Although comprehensivegenomic mapping has improved understanding of thegenetic aberrations in hepatocellular cancer (HCC), thisknowledge has not yet impacted clinical care. The lastfew years have seen the failure of several first and secondline phase Ⅲ clinical trials of novel molecularly targetedtherapies, warranting a change in the way new therapiesare investigated in HCC. Potential reasons for thesefailures include clinical and molecular heterogeneity, trialdesign and a lack of biomarkers. This review discussesthe current crisis in HCC drug development and how weshould learn from recent trial failures to develop a moreeffective personalised treatment paradigm for patientswith HCC.

  14. Tuning HERG out: antitarget QSAR models for drug development.

    Science.gov (United States)

    Braga, Rodolpho C; Alves, Vinicius M; Silva, Meryck F B; Muratov, Eugene; Fourches, Denis; Tropsha, Alexander; Andrade, Carolina H

    2014-01-01

    Several non-cardiovascular drugs have been withdrawn from the market due to their inhibition of hERG K+ channels that can potentially lead to severe heart arrhythmia and death. As hERG safety testing is a mandatory FDArequired procedure, there is a considerable interest for developing predictive computational tools to identify and filter out potential hERG blockers early in the drug discovery process. In this study, we aimed to generate predictive and well-characterized quantitative structure-activity relationship (QSAR) models for hERG blockage using the largest publicly available dataset of 11,958 compounds from the ChEMBL database. The models have been developed and validated according to OECD guidelines using four types of descriptors and four different machine-learning techniques. The classification accuracies discriminating blockers from non-blockers were as high as 0.83-0.93 on external set. Model interpretation revealed several SAR rules, which can guide structural optimization of some hERG blockers into non-blockers. We have also applied the generated models for screening the World Drug Index (WDI) database and identify putative hERG blockers and non-blockers among currently marketed drugs. The developed models can reliably identify blockers and non-blockers, which could be useful for the scientific community. A freely accessible web server has been developed allowing users to identify putative hERG blockers and non-blockers in chemical libraries of their interest (http://labmol.farmacia.ufg.br/predherg).

  15. Phase 0 clinical trials in oncology new drug development

    OpenAIRE

    Umesh Chandra Gupta; Sandeep Bhatia; Amit Garg; Amit Sharma; Vaibhav Choudhary

    2011-01-01

    Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a visi...

  16. Assessment of competitive and mechanism-based inhibition by clarithromycin: use of domperidone as a CYP3A probe-drug substrate and various enzymatic sources including a new cell-based assay with freshly isolated human hepatocytes.

    Science.gov (United States)

    Michaud, Veronique; Turgeon, Jacques

    2010-04-01

    Clarithromycin is involved in a large number of clinically relevant drug-drug interactions. Discrepancies are observed between the magnitude of drug interactions predicted from in vitro competitive inhibition studies and changes observed clinically in the plasma levels of affected CYP3A substrates. The formation of metabolic-intermediate complexes has been proposed to explain these differences. The objectives of our study were: 1) to determine the competitive inhibition potency of clarithromycin on the metabolism of domperidone as a CYP3A probe drug using human recombinant CYP3A4 and CYP3A5 isoenzymes, human liver microsomes and cultured human hepatocytes; 2) to establish the modulatory role of cytochrome b5 on the competitive inhibition potency of clarithromycin; 3) to demonstrate the clarithromycin-induced formation of CYP450 metabolic-intermediate complexes in human liver microsomes; and 4) to determine the extent of CYP3A inhibition due to metabolic-intermediate complex formation using human liver microsomes and cultured human hepatocytes. At high concentrations (100 µM), clarithromycin had weak competitive inhibition potency towards CYP3A4 and CYP3A5. Inhibition potency was further decreased by the addition of cytochrome b5 (9-19%). Clarithromycin-induced metabolic-intermediate complexes were revealed by spectrophotometry analysis using human liver microsomes while time- and concentration-dependent mechanism-based inhibitions were quantified using isolated hepatocytes. These results indicate that mechanism-based but not competitive inhibition of CYP3As is the major underlying mechanism of drug-drug interactions observed clinically with clarithromycin. Drug interactions between clarithromycin and several CYP3A substrates are predicted to be insidious; the risk of severe adverse events should increase over time and persist for a few days after cessation of the drug.

  17. Proteomics and Its Application in Biomarker Discovery and Drug Development

    Institute of Scientific and Technical Information of China (English)

    He Qing-Yu; Chiu Jen-Fu

    2004-01-01

    Proteomics is a research field aiming to characterize molecular and cellular dynamics in protein expression and function on a global level. The introduction of proteomics has been greatly broadening our view and accelerating our path in various medical researches. The most significant advantage of proteomics is its ability to examine a whole proteome or sub-proteome in a single experiment so that the protein alterations corresponding to a pathological or biochemical condition at a given time can be considered in an integrated way. Proteomic technology has been extensively used to tackle a wide variety of medical subjects including biomarker discovery and drug development. By complement with other new technique advance in genomics and bioinformatics,proteomics has a great potential to make considerable contribution to biomarker identification and revolutionize drug development process. A brief overview of the proteomic technologies will be provided and the application of proteomics in biomarker discovery and drug development will be discussed using our current research projects as examples.

  18. Positron Emission Tomography Application to Drug Development and Research

    Science.gov (United States)

    Salvadori, Piero A.

    The research for the identification and development of new drugs represents a very complex process implying long times and massive investments. This process was not able to parallel the rate of discoveries made in the field of genomic and molecular biology and a gap created between demand of new drugs and the ability of pharmaceutical companies to select good candidates. Positron Emission Tomography, among the different Molecular Imaging modalities, could represent a new tool for the early assessment and screening of new drug candidates and, due to its physical performances and the characteristics of positron-labeled tracers, gain the role of "Biomarker" accepted by the Companies and the Regulatory Bodies of Drug Agencies. To fulfil this task PET has to exploit all of its special features such as data absolute quantification and modelling, high spatial resolution and dynamic imaging. Relevant efforts need to be directed to the careful design and validation of experimental protocols with the main goal of achieving consistency in multi- centric trials.

  19. Exosomes in development, metastasis and drug resistance of breast cancer.

    Science.gov (United States)

    Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

    2015-08-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.

  20. The competitiveness of nations and firms in a global context - implications for poverty alleviation in developing countries

    DEFF Research Database (Denmark)

    Kuada, John Ernest

    2016-01-01

    This chapter focuses attention on the human side of national and firm-level competitiveness in a dynamic global business environment. It introduces the concept of human capability development into the business economics literature, arguing that competitiveness depends on the overall capability...... of people, not only in a technical sense of having required work competencies and applying them efficiently but also on work attitude and behaviours that produce inter-human trust and collaboration. The human capability development construct is defined in terms of the following four sets of factors - (1......) the cultural and civil societal characteristics, (2) the overall institutional capabilities of the nation, (3) leadership and governance capabilities, and (4) the global orientation of individuals, organisations and the society as a whole (as well as the integration of firms and institutions within the global...

  1. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-05-21

    ... HUMAN SERVICES Food and Drug Administration Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure Research: Public Meeting AGENCY: Food and Drug... Administration (FDA) is announcing a public meeting and an opportunity for public comment on...

  2. 78 FR 63223 - Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction

    Science.gov (United States)

    2013-10-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Fibromyalgia Public Meeting on Patient-Focused Drug... public meeting entitled ``Fibromyalgia Public Meeting on Patient-Focused Drug Development''...

  3. Emerging Competitive Strategies in the Global Luxury Industry in the Perspective of Sustainable Development: the Case of Kering Group

    Directory of Open Access Journals (Sweden)

    Roberta PEZZETTI

    2016-06-01

    Full Text Available In the last years, many drivers should motivate luxury companies to engage in more sustainable practices. On the one hand, consumers seek new forms of luxury that shows respect for natural resources and human beings, yet standing by traditional factors such as quality, creativity, originality, craftsmanship and savoirfaire. The recent economic crisis has thrust the consumers towards the search for responsible luxury. In the new economic and competitive scenario, luxury brands would base their identity and image on a set of values through which they should be known and publicly judged by both clients and the market; sustainable development and corporate social responsibility strategies offer a particularly suitable platform to enrich the value-set of luxury brands. In this framework, the luxury industry is undergoing a process of self-analysis and redefinition of competitive strategies in the light of social responsibility and sustainable dimension. In order to create both financial and non-financial value, sustainable development needs to be incorporated in the core strategy of the firm and its core business. In this perspective, the paper provides an analysis of the main drivers that, in the luxury industry, are leading to a growing integration of social responsibility and sustainable development principles in the competitive strategies of luxury firms. In particular, the paper focuses on innovations emerging in the luxury industry, both at strategic and organizational levels, and provides an overview of new emerging innovative business models coherent with the principles of corporate social responsibility and sustainability. The theoretical analysis is supported by presentation of the case of the French Group Kering, which represents a pioneering example in sustainable development applied to competitive strategies and leading brand management practices.

  4. Methods for Elucidation of DNA-Anticancer Drug Interactions and their Applications in the Development of New Drugs.

    Science.gov (United States)

    Misiak, Majus; Mantegazza, Francesco; Beretta, Giovanni L

    2016-01-01

    DNA damaging agents including anthracyclines, camptothecins and platinum drugs are among most frequently used drugs in the chemotherapeutic routine. Due to their relatively low selectivity for cancer cells, administration of these drugs is associated with adverse side effects, inherent genotoxicity with risk of developing secondary cancers. Development of new drugs, which could be spared of these drawbacks and characterize by improved antitumor efficacy, remains challenging yet vitally important task. These properties are in large part dictated by the selectivity of interaction between the drug and DNA and in this way the studies aimed at elucidating the complex interactions between ligand and DNA represent a key step in the drug development. Studies of the drug-DNA interactions encompass determination of DNA sequence specificity and mode of DNA binding as well as kinetic, dynamic and structural parameters of binding. Here, we consider the types of interactions between small molecule ligands and polynucleotides, how they are affected by DNA sequence and structure, and what is their significance for the antitumor activity. Based on this knowledge, we discuss the wide array of experimental techniques available to researchers for studying drug-DNA interactions, which include absorption and emission spectroscopies, NMR, magnetic and optical tweezers or atomic force microscopy. We show, using the clinical and experimental anticancer drugs as examples, how these methods provide various types of information and at the same time complement each other to provide full picture of drug- DNA interaction and aid in the development of new drugs.

  5. Ion channels and transporters in the development of drug resistance in cancer cells

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Lambert, Ian Henry

    2014-01-01

    Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion...

  6. Tyrosine Kinase Inhibition: An Approach to Drug Development

    Science.gov (United States)

    Levitzki, Alexander; Gazit, Aviv

    1995-03-01

    Protein tyrosine kinases (PTKs) regulate cell proliferation, cell differentiation, and signaling processes in the cells of the immune system. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases can lead to inflammatory responses and to diseases such as cancer, atherosclerosis, and psoriasis. Thus, inhibitors that block the activity of tyrosine kinases and the signaling pathways they activate may provide a useful basis for drug development. This article summarizes recent progress in the development of PTK inhibitors and demonstrates their potential use in the treatment of disease.

  7. Drug Development and Challenges for Neuromuscular Clinical Trials.

    Science.gov (United States)

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases.

  8. Developing global competitiveness by assessing organized retail productivity using data envelopment analysis

    Directory of Open Access Journals (Sweden)

    Mehrotra, A.

    2009-01-01

    Full Text Available The purpose of this paper was to find out (using Regression, Data Envelopment Analysis and Sensitivity Analysis how efficiently some of the top organized India retail companies have been performing relative to each other over the years and thereby to identify factors that help increase the efficiency of a retail company. The study was conducted based on the analysis of data downloaded from Prowess database for five Indian retail companies for the time period 2000-2007. The paper is deemed to be helpful to enable Indian retail companies gain a competitive advantage in the face of increased competition being faced in the emerging organized retail sector in India. The findings brought forth Advertising and Marketing expenses as the significant performance determining factors to be paid attention to.

  9. Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

    Science.gov (United States)

    Pierce, Christopher G.; Lopez-Ribot, Jose L.

    2014-01-01

    Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751

  10. US–China Military Technological Competition and the Making of Chinese Weapons Development Strategies and Plans

    OpenAIRE

    CHEUNG, Tai Ming

    2017-01-01

    How do Chinese decision-makers and strategists view the United States todayas a military strategic competitor especially in light of the US Third Offset Strategy? This brief examines the nature, dynamics, and direction of intensifying US–China military strategic technology competition and how the Third Offset Strategy may influence implementation of Chinese strategies and plans for long-termdevelopment of its military technological and war-fighting capabilities.

  11. Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents

    Science.gov (United States)

    Liu, Yu; Wan, Wen-zhu; Li, Yan; Zhou, Guan-lian; Liu, Xin-guang

    2017-01-01

    Phosphatidylinostitol-3-kinase (PI3K) is the potential anticancer target in the PI3K/Akt/ mTOR pathway. Here we reviewed the ATP-competitive small molecule PI3K inhibitors in the past few years, including the pan Class I PI3K inhibitors, the isoform-specific PI3K inhibitors and/or the PI3K/mTOR dual inhibitors. PMID:27769061

  12. Competition as an Effective Tool in Developing Social Marketing Programs: Driving Behavior Change through Online Activities

    OpenAIRE

    Corina ŞERBAN

    2011-01-01

    Nowadays, social marketing practices represent an important part of people’s lives. Consumers’ understanding of the need for change has become the top priority for social organizations worldwide. As a result, the number of social marketing programs has increased, making people reflect more on their behaviors and on the need to take action. Competition in social marketing can bring many benefits. The more programs initiated, the more people will start to involve in society’s problems, hereby c...

  13. Industrial natural product chemistry for drug discovery and development.

    Science.gov (United States)

    Bauer, Armin; Brönstrup, Mark

    2014-01-01

    Covering: up to March 2013. In addition to their prominent role in basic biological and chemical research, natural products are a rich source of commercial products for the pharmaceutical and other industries. Industrial natural product chemistry is of fundamental importance for successful product development, as the vast majority (ca. 80%) of commercial drugs derived from natural products require synthetic efforts, either to enable economical access to bulk material, and/or to optimize drug properties through structural modifications. This review aims to illustrate issues on the pathway from lead to product, and how they have been successfully addressed by modern natural product chemistry. It is focused on natural products of current relevance that are, or are intended to be, used as pharmaceuticals.

  14. Development of a drug and alcohol information survey.

    Science.gov (United States)

    Gough, H G

    1985-04-01

    Psychological measurement in regard to using drugs, alcohol, or other substances should attend to personological, attitudinal, and informational factors. Standardized tests are available for assessing personological and attitudinal variables, but not for knowledge. To develop a test of information, 45 multiple-choice items were correlated with total and part scores in samples of 132 men and 71 women; 35 items with significant (p less than .05) coefficients and other desirable properties were retained for a Drug and Alcohol Information Survey (DAIS). For 33 male and 36 female college students participating in an intensive psychological assessment program, scores on the DAIS were positively associated with (1) ratings of modernity, sensation seeking, originality, and nonorderliness; (2) personality scales for status propensity, sociability, social presence, and rebelliousness; and (3) a nonverbal test of field-independent cognitive ability. High scorers on the DAIS also reported more frequent use of marijuana, alcohol, and tobacco than did students with low scores.

  15. Developing the function of human resource management with a view to building competitive advantage of enterprises in Bosnia and Herzegovina

    Directory of Open Access Journals (Sweden)

    Adisa Delić

    2014-12-01

    Full Text Available Contemporary business environment generates hyper changes and hyper competition, which is why enterprises are challenged to search for new sources to preserve and build competitive advantage in the global marketplace. In the theory and practice of management, the general view is that people and their knowledge are becoming a fundamental value in modern enterprises, and that successful human resource management is an important determinant of competitiveness. However, the importance of having specific knowledge and skills in the enterprises in Bosnia and Herzegovina (BiH is still not recognized and human resources of these enterprises are not treated in accordance with their importance. Therefore, the objective of this paper is to point to the state and prospects of human resource development in the enterprises in BiH in the context of improving their competitiveness. This paper includes the results of one part of the empirical research covering 120 enterprises from BiH. The research was conducted in order to identify and analyze the situation in the field of key phases of human resource management in these enterprises (job analysis, human resource planning, management and selection of human resources, training and human resource development, evaluation of work performance, selection and implementation of the reward system, and management of human resource fluctuation. Based on the results, it can be concluded that the human resource management in these enterprises is underdeveloped when viewed as a special managerial function or business function, but also when treated as a separate modern business orientation in which people and their knowledge are the key value in the enterprise. The study results also show inadequate organizational treatment of human resource management in the enterprises in BiH, considering that managers’ awareness about the importance of establishing a department of human resources in these enterprises is still not

  16. Clustering as a determinant of development the competitive pharmaceutical industry - example of Nutribiomed cluster

    Directory of Open Access Journals (Sweden)

    Anna Skowrońska

    2015-04-01

    Full Text Available Continuous improvement and follow the technology seems to be particularly important in terms of health. Given the epidemiological trends is necessary to develop advanced technologies in the medical and pharmaceutical industries. Only innovative solutions offer a chance for a battle with disease, for example, with tumors which are one of the leading causes of death in Europe. This approach perfectly illustrates the strategy known as open innovation, according to which companies should learn from external sources by combining complementary ideas for its ongoing operations. The pharmaceutical industry has a significant impact on the functioning of not only the economy, but it is also closely linked to the health sector, and thus affects the level and quality of life of societies. In this context it becomes particularly important to seek solutions that will ensure the free flow of knowledge and access to highly specialized techniques, which in turn have a positive impact on the health of citizens. Analysis of the functioning of the pharmaceutical clusters is based on case study cluster Nutribiomed. The results achieved in many areas of activity confirm the legitimate use of the structure of the group of highly specialized industry, which is the drug market and indicates a number of benefits associated with the operation as part of its structure.

  17. Tought on Knowledge Competition Strategies for Enterprise Sustainable Development%企业可持续发展的知识竞争战略思考

    Institute of Scientific and Technical Information of China (English)

    郎诵真; 朱晓峰; 周晓明

    2000-01-01

    Based on a discussion on the connotation and affecting factors of enterprise sustainable development,this article proposes knowledge competition strategies for enterprises to adapt themselves to the coming of knowledge-based economy and national sustainable development.

  18. Sex, gender, and pharmaceutical politics: From drug development to marketing.

    Science.gov (United States)

    Fisher, Jill A; Ronald, Lorna M

    2010-08-01

    Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing. This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials. The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals. The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome. Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and

  19. Socio-hydrologic modeling to understand and mediate the competition for water between agriculture development and environmental health: Murrumbidgee River Basin, Australia

    NARCIS (Netherlands)

    Van Emmerik, T.H.M.; Li, Z.; Sivapalan, M.; Pande, S.; Kandasamy, J.; Savenije, H.H.G.; Chanan, A.; Vigneswaran, S.

    2014-01-01

    Competition for water between humans and ecosystems is set to become a flash point in the coming decades in many parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling the development of

  20. Socio-hydrologic modeling to understand and mediate the competition for water between agriculture development and environmental health: Murrumbidgee River Basin, Australia (discussion paper)

    NARCIS (Netherlands)

    Van Emmerik, T.H.M.; Li, Z.; Sivapalan, M.; Pande, S.; Kandasamy, J.; Savenije, H.H.G.; Chanan, A.; Vigneswaran, S.

    2014-01-01

    Competition for water between humans and ecosystems is set to become a flash point in the coming decades in many parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling the development of

  1. Socio-hydrologic modeling to understand and mediate the competition for water between agriculture development and environmental health: Murrumbidgee River Basin, Australia

    NARCIS (Netherlands)

    Van Emmerik, T.H.M.; Li, Z.; Sivapalan, M.; Pande, S.; Kandasamy, J.; Savenije, H.H.G.; Chanan, A.; Vigneswaran, S.

    2014-01-01

    Competition for water between humans and ecosystems is set to become a flash point in the coming decades in many parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling the development of effec

  2. Socio-hydrologic modeling to understand and mediate the competition for water between agriculture development and environmental health: Murrumbidgee River Basin, Australia (discussion paper)

    NARCIS (Netherlands)

    Van Emmerik, T.H.M.; Li, Z.; Sivapalan, M.; Pande, S.; Kandasamy, J.; Savenije, H.H.G.; Chanan, A.; Vigneswaran, S.

    2014-01-01

    Competition for water between humans and ecosystems is set to become a flash point in the coming decades in many parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling the development of effec

  3. 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.

  4. 78 FR 43209 - Narcolepsy Public Meeting on Patient-Focused Drug Development

    Science.gov (United States)

    2013-07-19

    ... HUMAN SERVICES Food and Drug Administration Narcolepsy Public Meeting on Patient-Focused Drug... public comment on Patient-Focused Drug Development for narcolepsy. Patient-Focused Drug Development is... narcolepsy on daily life as well as the available therapies for narcolepsy. DATES: The public meeting will...

  5. 78 FR 58313 - Fibromyalgia Public Meeting on Patient-Focused Drug Development

    Science.gov (United States)

    2013-09-23

    ... HUMAN SERVICES Food and Drug Administration Fibromyalgia Public Meeting on Patient-Focused Drug... public comment on Patient-Focused Drug Development for fibromyalgia. Patient-Focused Drug Development is... fibromyalgia on daily life as well as the available therapies for fibromyalgia. DATES: The public meeting...

  6. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-08-02

    ... HUMAN SERVICES Food and Drug Administration Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure Research; Reopening of Comment Period AGENCY: Food and Drug... Virus (HIV) Patient-Focused Drug Development and HIV Cure Research,'' published in the Federal...

  7. Diagnostics of intellectual potential of development of foreign economic activity of enterprises of the Kharkiv region for ensuring their competitiveness

    Directory of Open Access Journals (Sweden)

    Vasyurenko Volodymyr O.

    2013-03-01

    Full Text Available The article studies the essence of the “intellectual potential” notion and establishes that one should understand intellectual potential as potential (not actualised at present knowledge, information, experience of personnel, organisational abilities and information channels, which are used by an enterprise in its production and innovation activity for ensuring economic security and competitiveness. It shows that conditionally the intellectual potential of enterprise development could be divided into two main components: human potential and organisational potential. In order to ensure competitiveness of foreign economic activity (FEA of enterprises, the article offers to diagnose the state of their intellectual potential of development. Moreover, the article offers to consider this procedure of diagnostics as a process of controlling the correspondence of the vector of development of intellectual potential of an enterprise in general and its components. The article develops conceptual provisions of diagnostics of the state of intellectual potential of enterprise development and conducts a diagnostics of the state of intellectual potential of enterprise development at enterprises of the real sector of economy, namely, at the engineering enterprises of the Kharkiv region, which are engaged in foreign economic activity. The article calculates an integral indicator of the state of intellectual potential of development of FEA of enterprises of the Kharkiv region.

  8. Political Failures and Intergovernmental Competition

    Directory of Open Access Journals (Sweden)

    Jean Hindriks

    2012-01-01

    Full Text Available In normative public economics, intergovernmental competition is usually viewed as harmful. Although empirical support for this position does not abound, market integration has intensified competition among developed countries. In this paper we argue that when assessing welfare effects of intergovernmental competition for various forms of political failures (the public choice critique, the outcome is ambiguous and competition can be welfare improving.

  9. Methodological issues in clinical drug development for essential tremor.

    Science.gov (United States)

    Carranza, Michael A; Snyder, Madeline R; Elble, Rodger J; Boutzoukas, Angelique E; Zesiewicz, Theresa A

    2012-01-01

    Essential tremor (ET) is one of the most common tremor disorders in the world. Despite this, only two medications have received Level A recommendations from the American Academy of Neurology to treat it (primidone and propranolol). Even though these medications provide relief to a large group of ET patients, up to 50% of patients are non-responders. Additional medications to treat ET are needed. This review discusses some of the methodological issues that should be addressed for quality clinical drug development in ET.

  10. War In Developing Drugs: A Case Study In Connection

    Directory of Open Access Journals (Sweden)

    Sourav Sarkar

    2015-03-01

    Full Text Available Truly someone said that “Necessity is the mother of invention”. Scientific evolution always comes with sociological need and temporary crisis in our daily life. The invention of fire, wheel for transportation, paper for documentation, each and every scientific invention is associated with some sociological need. Even these words are very true for discovery of medicines. It was until the starting of twentieth century i.e. the world war, which caused proper things and brought sufficient human attention towards the need of developing new medicines (Drugs and medicinal techniques. In this article we shall try to reveal the very history with a strong emphasis on the chronological sequence.

  11. Drugs in development for toxoplasmosis: advances, challenges, and current status

    Directory of Open Access Journals (Sweden)

    Alday PH

    2017-01-01

    Full Text Available P Holland Alday,1 Joseph Stone Doggett1,2 1Division of Infectious Diseases, Oregon Health & Science University, 2Portland Veterans Affairs Medical Center, Portland, OR, USA Abstract: Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. Keywords: Toxoplasma gondii, therapeutics, preclinical medicine, experimental medicine, mechanism of action, Apicomplexa

  12. Drugs in development for toxoplasmosis: advances, challenges, and current status

    Science.gov (United States)

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

    Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168

  13. Competition driven by retinal waves promotes morphological and functional synaptic development of neurons in the superior colliculus.

    Science.gov (United States)

    Furman, Moran; Xu, Hong-Ping; Crair, Michael C

    2013-09-01

    Prior to eye opening, waves of spontaneous activity sweep across the developing retina. These "retinal waves," together with genetically encoded molecular mechanisms, mediate the formation of visual maps in the brain. However, the specific role of wave activity in synapse development in retino-recipient brain regions is unclear. Here we compare the functional development of synapses and the morphological development of neurons in the superior colliculus (SC) of wild-type (WT) and transgenic (β2-TG) mice in which retinal wave propagation is spatially truncated (Xu HP, Furman M, Mineur YS, Chen H, King SL, Zenisek D, Zhou ZJ, Butts DA, Tian N, Picciotto MR, Crair MC. Neuron 70: 1115-1127, 2011). We use two recently developed brain slice preparations to examine neurons and synapses in the binocular vs. mainly monocular SC. We find that retinocollicular synaptic strength is reduced whereas the number of retinal inputs is increased in the binocular SC of β2-TG mice compared with WT mice. In contrast, in the mainly monocular SC the number of retinal inputs is normal in β2-TG mice, but, transiently, synapses are abnormally strong, possibly because of enhanced activity-dependent competition between local, "small" retinal wave domains. These findings demonstrate that retinal wave size plays an instructive role in the synaptic and morphological development of SC neurons, possibly through a competitive process among retinofugal axons.

  14. Data-driven battery product development: Turn battery performance into a competitive advantage.

    Energy Technology Data Exchange (ETDEWEB)

    Sholklapper, Tal [Voltaiq, Inc.

    2016-04-19

    Poor battery performance is a primary source of user dissatisfaction across a broad range of applications, and is a key bottleneck hindering the growth of mobile technology, wearables, electric vehicles, and grid energy storage. Engineering battery systems is difficult, requiring extensive testing for vendor selection, BMS programming, and application-specific lifetime testing. This work also generates huge quantities of data. This presentation will explain how to leverage this data to help ship quality products faster using fewer resources while ensuring safety and reliability in the field, ultimately turning battery performance into a competitive advantage.

  15. On the early and developed stages of surface condensation: competition mechanism between interfacial and condensate bulk thermal resistances

    Science.gov (United States)

    Sun, Jie; Wang, Hua Sheng

    2016-10-01

    We use molecular dynamics simulation to investigate the early and developed stages of surface condensation. We find that the liquid-vapor and solid-liquid interfacial thermal resistances depend on the properties of solid and fluid, which are time-independent, while the condensate bulk thermal resistance depends on the condensate thickness, which is time-dependent. There exists intrinsic competition between the interfacial and condensate bulk thermal resistances in timeline and the resultant total thermal resistance determines the condensation intensity for a given vapor-solid temperature difference. We reveal the competition mechanism that the interfacial thermal resistance dominates at the onset of condensation and holds afterwards while the condensate bulk thermal resistance gradually takes over with condensate thickness growing. The weaker the solid-liquid bonding, the later the takeover occurs. This competition mechanism suggests that only when the condensate bulk thermal resistance is reduced after it takes over the domination can the condensation be effectively intensified. We propose a unified theoretical model for the thermal resistance analysis by making dropwise condensation equivalent to filmwise condensation. We further find that near a critical point (contact angle being ca. 153°) the bulk thermal resistance has the least opportunity to take over the domination while away from it the probability increases.

  16. Alzheimer's disease drug development based on Computer-Aided Drug Design.

    Science.gov (United States)

    Zeng, Huahui; Wu, Xiangxiang

    2016-10-04

    Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the excessive deposition of amyloids in the brain. The pathological features mainly include the extracellular amyloid plaques and intracellular neurofibrillary tangles, which are the production of amyloid precursor protein (APP) processed by the α-, β- and γ-secretases. Based on the amyloid cascade hypotheses of AD, a large number of amyloid-β agents and secretase inhibitors against AD have been recently developed by using computational methods. This review article describes pathophysiology of AD and the structure of the Aβ plaques, β- and γ-secretases, and discusses the recent advances in the development of the amyloid agents for AD therapy and diagnosis by using Computer-Aided Drug Design approach.

  17. Medication development of ibogaine as a pharmacotherapy for drug dependence.

    Science.gov (United States)

    Mash, D C; Kovera, C A; Buck, B E; Norenberg, M D; Shapshak, P; Hearn, W L; Sanchez-Ramos, J

    1998-05-30

    The potential for deriving new psychotherapeutic medications from natural sources has led to renewal interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

  18. A fuzzy model for achieving lean attributes for competitive advantages development using AHP-QFD-PROMETHEE

    Science.gov (United States)

    Roghanian, E.; Alipour, Mohammad

    2014-06-01

    Lean production has become an integral part of the manufacturing landscape as its link with superior performance and its ability to provide competitive advantage is well accepted among academics and practitioners. Lean production helps producers in overcoming the challenges organizations face through using powerful tools and enablers. However, most companies are faced with restricted resources such as financial and human resources, time, etc., in using these enablers, and are not capable of implementing all these techniques. Therefore, identifying and selecting the most appropriate and efficient tool can be a significant challenge for many companies. Hence, this literature seeks to combine competitive advantages, lean attributes, and lean enablers to determine the most appropriate enablers for improvement of lean attributes. Quality function deployment in fuzzy environment and house of quality matrix are implemented. Throughout the methodology, fuzzy logic is the basis for translating linguistic judgments required for the relationships and correlation matrix to numerical values. Moreover, for final ranking of lean enablers, a multi-criteria decision-making method (PROMETHEE) is adopted. Finally, a case study in automotive industry is presented to illustrate the implementation of the proposed methodology.

  19. MILITARY COMPETITION BETWEEN FRIENDS? HEGEMONIC DEVELOPMENT AND MILITARY SPENDING AMONG EIGHT WESTERN DEMOCRACIES, 1920-1938

    Directory of Open Access Journals (Sweden)

    Jari Eloranta

    2001-01-01

    Full Text Available This article explores the complicated phenomenon of military spending among a sample of eight Western democracies in the interwar period by analyzing especially the possibility of economic and/or military competition between the Western Great Powers and the ensuing impacts on the smaller states included here. The hegemonic paradigm suggested by e.g. Paul Kennedy predicts that the economic leader in a system will increasingly invest on maintaining security; thus eventually bringing economic growth to a halt. The military spending patterns respective of economic growth at first seem to suggest that not only the totalitarian states, as is the traditional view, but also the UK and France stepped in to fill the void created by the lack of American leadership. However, the military expenditures of these nations were too low to warrant the conclusion that they had any impact on their respective economic performance. This result is also verified here by employing Granger non-causality tests between the military spending and economic growth variables. Moreover, regression analysis on the military spending variables for the UK and France points towards competition on the level. The smaller states, respectively, seemed to follow the UK and France fairly closely in their military spending decisions.

  20. Development of a Noncontact Kickboxing Circuit Training Protocol That Simulates Elite Male Kickboxing Competition.

    Science.gov (United States)

    Ouergui, Ibrahim; Houcine, Nizar; Marzouki, Hamza; Davis, Philip; Zaouali, Monia; Franchini, Emerson; Gmada, Nabil; Bouhlel, Ezzedine

    2015-12-01

    The aim of this study was to verify whether the specific kickboxing circuit training protocol (SKCTP) could reproduce kickboxing combat's hormonal, physiological, and physical responses. Twenty athletes of regional and national level volunteered to participate in the study (mean ± SD, age: 21.3 ± 2.7 years; height: 170 ± 0.5 cm; body mass: 73.9 ± 13.9 kg). After familiarization, SKCTP was conducted 1 week before a kickboxing competition. Cortisol, testosterone, growth hormone (GH), blood lactate [La], and glucose concentrations, as well as the Wingate upper-body test and countermovement jump (CMJ) performances were measured before and after SKCTP and combat. Heart rate (HR) and rating of perceived exertion (RPE) were measured throughout rounds (R) R1, R2, and R3. Testosterone, GH, glucose, [La], HR, RPE, and CMJ did not differ among the 2 conditions (p > 0.05). However, Cortisol was higher for competition (p = 0.038), whereas both peak (p = 0.003) and mean power (p kickboxing training, as well as a specific assessment tool to be used by kickboxing coaches to quantify kickboxers' fitness levels, when physiological parameters responses to the test are measured.

  1. Development of an indirect competitive ELISA for simultaneous detection of enrofloxacin and ciprofloxacin

    Institute of Scientific and Technical Information of China (English)

    Hai-tang ZHANG; Jin-qing JIANG; Zi-liang WANG; Xin-yao CHANG; Xing-you LIU; San-hu WANG; Kun ZHAO; Jin-shan CHEN

    2011-01-01

    Modified 1-ethyl-3-(3-dimethylaminopropy) carbodiimide (EDC) method was employed to synthesize the artificial antigen of enrofloxacin (ENR),and New Zealand rabbits were used to produce anti-ENR polyclonal antibody (pAb).Based on the checkerboard titration,an indirect competitive enzyme-linked immunosorbent assay (ELISA) standard curve was established.This assay was sensitive and had a linear range from 0.6 to 148.0 μg/kg (R2=0.9567),with the half maximal inhibitory concentration (IC50) and limit of detection (LOD) values of 9.4 μg/kg and 0.2 μg/kg,respectively.Of all the competitive analogues,the produced pAb exhibited a high cross-reactivity to ciprofioxacin (CIP) (87%),the main metabolite of ENR in tissues.After optimization,the matrix effects can be ignored using a 10-fold dilution in beef and 20-fold dilution in pork.The overall recoveries and coefficients of variation (CVs) were in the ranges of 86%-109% and 6.8%-13.1%,respectively.It can be concluded that the established ELISA method is suitable for simultaneous detection of ENR and CIP in animal tissues.

  2. Polymer-Drug Conjugates: Recent Development in Clinical Oncology

    OpenAIRE

    Li, Chun; Wallace, Sidney

    2008-01-01

    Targeted drug delivery aims to increase the therapeutic index by making more drug molecules available at the diseased sites while reducing systemic drug exposure. In this update, we provide an overview of polymer-drug conjugates that have advanced into the clinical trials. These systems use synthetic water-soluble polymers as the drug carriers. The preclinical pharmacology and recent data in clinical trials with poly(L-glutamic acid)-paclitaxel (PG-TXL) are discussed first. This is followed b...

  3. Interdisciplinary researches for potential developments of drugs and natural products

    Directory of Open Access Journals (Sweden)

    Arunrat Chaveerach

    2017-04-01

    Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

  4. Drugs in early clinical development for the treatment of osteosarcoma.

    Science.gov (United States)

    Heymann, Marie-Françoise; Brown, Hannah K; Heymann, Dominique

    2016-11-01

    Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.

  5. Recombinant drug development, regulation, and commercialization: an Indian industry perspective.

    Science.gov (United States)

    Sahoo, Niharika; Manchikanti, Padmavati

    2011-04-01

    The Indian biopharmaceutical sector comprises nearly 40 companies that manufacture and/or market 14 recombinant drugs that account for nearly 50 products. Among these, 22 companies have manufacturing facilities in India. The aim of the present study was to analyze the patenting trends, commercialization, and regulatory system for biopharmaceuticals in India. Representatives from 19 such biopharmaceutical companies were interviewed on aspects related to regulatory compliance, manufacturing, commercialization, and innovation in order to understand the challenges faced by them in the current regulatory and patent system. The study revealed that 94% of the companies have filed patents and 52% are developing new biologic entities in areas such as diabetes mellitus, cancer, and congestive heart diseases. Forty-two percent of the companies consider delays in regulatory approval to be a major constraint for biopharmaceutical industry development. Almost all are of the opinion that uniform guidelines across countries would help to prevent delays in the commercialization of products. A high proportion of representatives of the biopharmaceutical industry in India identified that elaboration of regulatory guidelines, defined submission requirements, and drug approval timelines are vital to the growth of the biopharmaceutical industry. © 2011 Adis Data Information BV. All rights reserved.

  6. Titanium MEMS Technology Development for Drug Delivery and Microfluidic Applications

    Science.gov (United States)

    Khandan, Omid

    The use of microelectromechanical systems (MEMS) technology in medical and biological applications has increased dramatically in the past decade due to the potential for enhanced sensitivity, functionality, and performance associated with the miniaturization of devices, as well as the market potential for low-cost, personalized medicine. However, the utility of such devices in clinical medicine is ultimately limited due to factors associated with prevailing micromachined materials such as silicon, as it poses concerns of safety and reliability due to its intrinsically brittle properties, making it prone to catastrophic failure. Recent advances in titanium (Ti) micromachining provides an opportunity to create devices with enhanced safety and performance due to its proven biocompatibility and high fracture toughness, which causes it to fail by means of graceful, plasticity-based deformation. Motivated by this opportunity, we discuss our efforts to advance Ti MEMS technology in two ways: 1) Through the development of titanium-based microneedles (MNs) that seek to provide a safer, simpler, and more efficacious means of ocular drug delivery, and 2) Through the advancement of Ti anodic bonding for future realization of robust microfluidic devices for photocatalysis applications. As for the first of these thrusts, we show that MN devices with in-plane geometry and through-thickness fenestrations that serve as drug reservoirs for passive delivery via diffusive transport from fast-dissolving coatings can be fabricated utilizing Ti deep reactive ion etching (Ti DRIE). Our mechanical testing and finite element analysis (FEA) results suggest that these devices possess sufficient stiffness for reliable corneal insertion. Our MN coating studies show that, relative to solid MNs of identical shank dimension, fenestrated devices can increase drug carrying capacity by 5-fold. Furthermore, we demonstrate that through-etched fenestrations provide a protective cavity for delivering

  7. Drug development and government policy%试谈药物研发与政府管理政策

    Institute of Scientific and Technical Information of China (English)

    叶仙蓉

    2012-01-01

    本文通过分析不同时期与药物研发密切相关的科技管理政策与药品审批、知识产权等制度的演变过程,认为新药研发的发展离不开国家政策的引导和支持.同时提出新时期下,国家级科研院所开展创新药物研发过程中需要关注以下几方面的问题:新药研发项目的确立应当围绕国家需求和临床需求,应重视对治疗某些重大疾病新的作用机制与新靶点的理论探索,应充分利用国家的特殊政策和支撑条件以加快研发速度,研发过程中需要一个高水平的研发核心小组负责综合分析,统筹安排,同时根据国内外情况变化与研发的进展,适时申请专利、科研计划项目以及新药注册,争取开发出具有国际竞争力的创新药物.%The author analyzed the changes in different periods of science and technology, management, administration of drug approval and intellectual property; then concluded that the new drug development in China can not be separated from national policy guidance and support. In the future, the national drug development institutions should pay attention to following issues when researching and developing a new drug. The new drug development project should be met the requirement of the country and the clinical therapy. The national drug development institutions should pay more attention to the new mechanism and new target for the treatment of some important disease , and should fully use the national policy and nationally supported hardware to accelerate the new drug development process. In the development process, a senior expert group is necessary to comprehensively analyze the results and control the progress of the project. In the meantime, it should be determined when to apply the patent, national research project and new drug registration according to the changing siluation of the in-/out-of the country and the progress of the project, in order to develop an international competitive new drug.

  8. Competitive Intelligence.

    Science.gov (United States)

    Bergeron, Pierrette; Hiller, Christine A.

    2002-01-01

    Reviews the evolution of competitive intelligence since 1994, including terminology and definitions and analytical techniques. Addresses the issue of ethics; explores how information technology supports the competitive intelligence process; and discusses education and training opportunities for competitive intelligence, including core competencies…

  9. Identifying the Right Disease Targets to Develop Better Drugs, Faster | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... JavaScript on. Identifying the Right Disease Targets to Develop Better Drugs, Faster Past Issues / Spring 2014 Table ... a-dozen pharmaceutical companies are now racing to develop drugs that lower cholesterol by blocking PCSK9. Are ...

  10. [Internet and nursing: development of a site on drug administration].

    Science.gov (United States)

    da Silva, F B; Cassiani, S H; Zem-Mascarenhas, S H

    2001-01-01

    This study identified existent sites in the internet about Administration of Medications and developed and evaluated a specific site of this thematic. Of the 158 existent and available sites in the database of the Alta Vista search, 17 of these presented some relationship with pharmacology, marketing and information about drugs, technologies and rules of the medication. After that a site was developed and named The process of Administration of Medications in focus which goal was to present investigations conducted by a group about the following topics: errors, technology, complications, study group and the team. The evaluation of this site was made by 2 analyst of systems, 2 computer science technicians and 4 nursing professors and it showed that the quality of the pages, the time of answer, the link, images and content were considered between excellent and satisfactory.

  11. 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.

  12. STRATEGIC MANAGEMENT OF URBAN TOURISM IN ALBANIA - THE POTENTIAL ROLE OF URBAN TOURISM IN COMPETITIVE DEVELOPMENT OF ALBANIA DESTINATION

    Directory of Open Access Journals (Sweden)

    Fioralba VELA

    2008-06-01

    Full Text Available In this paper, the main objective is to introduce the role of urban tourism as a potential form of tourism in the competitive development of the Albanian destination and the role of urban tourism to the community of the Albanian urban areas and the problems related to this development. For the purpose of the study, it’s needed to define the criteria of the study and the organization of the Albanian cities that offers the greatest possibilities to develop the urban tourism as a competitive form of tourism development. These criteria are: the evidence of the heritage historical patrimony, the evidence of the culinary patrimony, the evidence of the technical patrimony, the evidence of the hospitality patrimony, the evidence of the transport’s situation, the evidence of the cultural patrimony, the evidence of leisure structures, various services. The analyses used enable the author to come on interesting conclusions.

  13. Competition, mortality, and development of spatial patterns in two Cantabrian populations of Fagus sylvatica L. (Fagaceae

    Directory of Open Access Journals (Sweden)

    Fernández Prieto, José Antonio

    2000-06-01

    Full Text Available In this paper the spatial patterns of size and mortality of European beech (Fagus sylvatica L. were analy sed in two deciduous forest plots of Northern Spain. ¿i general terms, radial growth of F. sylvatica yields a direct relationship with size and an inverse relation with intraspecific competition while tree mortality seems be related to intraspecific competition. In the overall even-aged population, a lack of a recognisable structure in tree-size distribution, a small-scale regularity of survivors, and a regular pattern of dominant trees was noticed. This is a consequence of intense intraspecific competition at local level. In the old-growth plot, the wide repulsión between small and large beeches yields a specific spatial structure in tree-size distribution, showing even-sized groups of trees in different stages. Mortality in this plot occurs mainly within the dense group of small trees, which produces a broad regular pattern among the live beech trees. The random spatial pattern of dominant beeches seems to be characteristic of old-growth forests and could be a consequence of either self-thinning processes or exogenous factors.En el presente trabajo se analizan las distribuciones espaciales de tamaño y mortalidad en poblaciones de haya (Fagus sylvatica L. incluidas en dos parcelas de bosque atlántico. En general, el crecimiento radial de F. sylvatica es directamente proporcional al tamaño e inversamente proporcional a la competencia intraespecífica, mientras que la mortalidad parece estar condicionada por competencia con individuos de la misma especie. La población formada sobre todo por árboles coetáneos presenta características espaciales indicativas de una intensa competencia intraespecífica entre árboles vecinos, como lo son la ausencia de una distribución ordenada de tamaños, regularidad local de los árboles vivos y un patrón regular en los árboles dominantes. La población incluida en bosque maduro presenta una

  14. Assessment of drug metabolism enzyme and transporter pharmacogenetics in drug discovery and early development: perspectives of the I-PWG.

    Science.gov (United States)

    Brian, William; Tremaine, Larry M; Arefayene, Million; de Kanter, Ruben; Evers, Raymond; Guo, Yingying; Kalabus, James; Lin, Wen; Loi, Cho-Ming; Xiao, Guangqing

    2016-04-01

    Genetic variants of drug metabolism enzymes and transporters can result in high pharmacokinetic and pharmacodynamic variability, unwanted characteristics of efficacious and safe drugs. Ideally, the contributions of these enzymes and transporters to drug disposition can be predicted from in vitro experiments and in silico modeling in discovery or early development, and then be utilized during clinical development. Recently, regulatory agencies have provided guidance on the preclinical investigation of pharmacogenetics, for application to clinical drug development. This white paper summarizes the results of an industry survey conducted by the Industry Pharmacogenomics Working Group on current practice and challenges with using in vitro systems and in silico models to understand pharmacogenetic causes of variability in drug disposition.

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

    OpenAIRE

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

    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 w...

  16. 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

    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...

  17. 78 FR 33851 - Lung Cancer Patient-Focused Drug Development; Public Meeting

    Science.gov (United States)

    2013-06-05

    ... No. FDA-2013-N-0596] Lung Cancer Patient-Focused Drug Development; Public Meeting AGENCY: Food and... Patient-Focused Drug Development for lung cancer. Patient-Focused Drug Development is part of FDA's... cancer on daily life as well as the available therapies for lung cancer. DATES: The public meeting...

  18. 75 FR 65495 - Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability

    Science.gov (United States)

    2010-10-25

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for...

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

    Science.gov (United States)

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

    2017-02-03

    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.

  20. Multicriteria Decision Analysis to Develop Effective Sustainable Development Strategies for Enhancing Competitive Advantages: Case of the TFT-LCD Industry in Taiwan

    Directory of Open Access Journals (Sweden)

    Iuan-Yuan Lu

    2016-07-01

    Full Text Available In the Internet of Things era, panel displays play a major role in human life, because humans frequently use liquid crystal displays to monitor their electrical devices. The display industry creates remarkable economic output, but every manufacturing process inevitably has some undesirable effects on the environment. With the increasing awareness of environmental protection, balanced development is necessary to address the emerging market trends. However, short-sighted manufacturing corporations that focus solely on financial performance can achieve only short-term profits. The purpose of this study was to develop the most effective sustainable improvement strategies that can enhance competitive advantages in real-world situations. The proposed method combines the balanced scorecard and a new hybrid modified multiple attribute decision-making model which together adopt the DEMATEL technique to construct the influential network relation map and develop the DEMATEL-based ANP with the VIKOR method to deliver strategies that integrate environmental sustainability and competitive advantage. Finally, a real-world case study applying the proposed method to the cases of liquid crystal display manufacturers was conducted. Then, this paper discusses the effective use of natural resources, development of enterprises, and sustainable competitive advantage in this context. Various manufacturers, communities, and stakeholders can benefit from the coopetition solutions explained by the proposed method.