Zapatero Miguel, Pablo
The so-called 'TRIPS flexibilities' restated in 2001 by the World Trade Organization's Doha Declaration on TRIPS and Public Health offer a variety of policy avenues for promoting global price-based competition for essential medicines, and thus for improving access to affordable medicines in the developing world. In recent years, developing countries and international organisations alike have begun to explore the potentialities of global generic markets and competition generally, and also of using compulsory licensing to remedy anti-competitive practices (e.g. excessive pricing) through TRIPS-compatible antitrust enforcement. These and other 'pro-competitive' TRIPS flexibilities currently available provide the critical leverage and policy space necessary to improve access to affordable medicines in the developing world.
ELENA MĂDĂLINA OPRIȚESCU
Full Text Available The development and diversification of the economic activities, the stimulation of investments both in the public sector, but mainly in the private one, the reduction of unemployment, the improvement of living standards are just some of the concepts aimed at by the regional development. The main method which can lead to a balanced development of the regions is financing them differentially so that the underdeveloped regions would obtain proportionally more funds that the developed ones. At a region level, the main objective is represented by the more accelerated growth of the less developed regions, in an effort to diminish the inter-regional and intra-regional development disparities. A key role is played by the sustainable economic growth concept, while also analyzing the competitiveness at a regional level, as well as the main development factors.
Ensure that judges receive specialized training in competition law . .... ensure good coverage and quality of service; banks are subject to prudential and other .... vendors who offer the best value do the most business and the customers benefit.
Kolber, Michael A
Most physicians that treat individuals with HIV-1 disease are able to successfully suppress viral replication with the pharmacologic armamentarium available today. For the majority of patients this results in immune reconstitution and improved quality of life. However, a large fraction of these patients have transient elevations in their viral burden and even persistence of low-level viremia. In fact, many individuals whose viral load is suppressed to < 50 c/ml have evidence of low-level viral replication. The impact of low-level viremia and persistent viral replication is an area of significant study and interest owing to the potential for the development of drug resistance mutations. Here the fundamental question is whether and perhaps what factors provide a venue for the development of resistant virus. The concern is clearly the eventual progression of disease with the exhaustion of treatment options. The purpose of this review is to evaluate the current literature regarding the effect of low-level viremia on the development of drug resistance mutations. Herein, we discuss the impact of different levels of viral suppression on the development of mutations. In addition, we look at the role that resistance and fitness play in determining the survival of a breakthrough mutation within the background of drug.
Daryono Soebagyo; Triyono Triyono; Yuli Tri Cahyono
This study was conducted to identify regional competitiveness in some areas of Central Java. Regional competitiveness became one of the issues in regional development policy since the enactment of local autonomy.Measurement of regional competitiveness has been mostly done through ranking as a benchmark the competitiveness of the region. Mapping regional competitiveness in Indonesia has been made to all counties and cities, which shows the competitiveness ranking of each region. Competitivenes...
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…
Chriqui, Vincent; Bergougnoux, Jean; Hossie, Gaelle; Beeker, Etienne; Buba, Johanne; Delanoe, Julien; Ducos, Geraldine; Hilt, Etienne; Rigard-Cerison, Aude; Teillant, Aude; Auverlot, Dominique; Martinez, Elise; Dambrine, Fabrice; Roure, Francoise
By letter dated 27 April 2011, the Director General of the Centre for Strategic Analysis, Vincent Chriqui, confided to Jean Bergougnoux, honorary president of the SNCF, Honorary General Director of EDF, the task of animating a reflection Prospective Technological Studies of the sectors of energy, transport and construction. This synthesis report, prepared with the assistance of rapporteurs Centre for Strategic Analysis, attempts to summarize and put into perspective all the work which show these specific reports. Admittedly some very complex issues still need supplements. It may therefore be useful to extend this work in a number of areas. Beyond its role in the competitiveness of a country, technological innovation is essential to provide appropriate responses to the challenges of our commitment to sustainable development in terms of economic growth, preservation of the environmental and social progress. Mission for Prospective Technological conducted by the Centre for Strategic Analysis has sought to clarify this dual problem by proposing a long-term vision for the energy, transport and construction. For each technology studied, it has attempted to assess both the possible contribution to sustainable development and the competitive potential of our country on the international scene. His work, chaired by Jean Bergougnoux have reviewed the technological advances that may occur in the coming decades in the sectors concerned. They examined the conditions for integration of these advances in systems and subsystems existing (or create) and the conditions of a mature technical, economic but also social. Wherever possible, two time horizons were identified: a medium-term horizon, 2030, for which we have a fairly clear vision of future developments and long-term horizon, 2050, which allows to consider jumps Scientists are still uncertain. Finally, the mission is interested in four transverse technologies involved consistently in the three study areas, which are likely to
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.
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.
Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain
Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one.
Koch, Gilbert; Jusko, William J; Schropp, Johannes
We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.
de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F
Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.
Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.
... Forum : Competition and Regulatory Implementation Issues in Developing Countries ... create challenges that influence the operation of regulatory institutions. ... IWRA/IDRC webinar on climate change and adaptive water management.
Ghana has a relatively good international reputation with respect to political stability and macroeconomic reforms. However, its success with developing the private sector and attracting investment has at best been mixed. Therefore the new government that came into power in 2001 proclaimed a "Golden Age of Business". Competitiveness and private sector development are closely interlinked. On the one hand the factors that influence the competitiveness of a country are a precondition for private...
Full Text Available The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model - niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases.
Despite the preponderance of economic theory and research which argues to the contrary, the notion that national economies stand in a fundamentally competitive relationship with one another remains surprisingly widespread. In recent years, some of the most influential impetus for this misperception has come from Michael Porter's conceptualization of "the competitive advantage of nations" in relation to economic development and date theory. It is argued that Porter neither proposes nor demonst...
Mueller, Michael T; Frenzel, Alexander
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.
Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann
Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.
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
Mahlich, J C; Stadler, I
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.
Couverture du livre Finance and Competitiveness in Developing Countries. Editor(s):. José M. ... Ils se penchent sur les enjeux clés internationaux comme les preuves de l'impact de la variabilité du taux de change sur le commerce, les tendances des prêts bancaires, ainsi que l'ouverture du commerce et le développement.
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.
Kwon, Hye-Young; Kim, Hyungmin; Godman, Brian; Reich, Michael R
A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.
Full Text Available Da`wah – usually spelt dakwah in Indonesian – has been an important aspect of Islam from its very birth. Since the late nineteenth century, however, as a result of political and social transformations it has taken new forms. In one form or others, da`wah has been practised by a large variety of Islamic movements and organizations. Although complementary to each other in certain cases, in others their relations have rather been characterized by competition for authority and power, not only between various da`wah organizations, but also, through these organizations, between regimes, categories of religious and social leaders, and social categories of Muslims. For this reason, da`wah has had important dimensions beyond the domain of religion proper. Moreover, da`wah has been connected to political and social causes such as the struggle against communism and Christianity – sometimes emulating them in certain respects – and community development. Quite a few da`wah initiatives, state-sponsored or non-governmental, have taken transnational scopes. Indonesian dakwah has shared most of the above features. This article, analyzing dakwah in Indonesia, confirms their existence and adds to their understanding. It substantiates theories on the objectification of Islam in modern societies: the spread of mass education has led to the fragmentation of religious understanding, which has stimulated a fierce competition for religious authority and the control of religious institutions and organizations. Just as in many other Muslim-majority countries, in Indonesia the state has played a prominent role in the development of mass education, the ensuing competition for religious authority, as well as the functionalization of religion. As was the case elsewhere, in Indonesia dakwah has had important dimensions beyond the religious domain. On the other hand, Indonesian dakwah has shown a number of particularities. In order to illustrate the combination of
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
Carocci, Alessia; Catalano, Alessia; Sinicropi, Maria Stefania
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.
Jan 1, 2008 ... This has brought about many changes in the economies of developing ... touching on issues of globalization, consumer welfare, cartels and monopolies ... citizens can promote and practice to limit the impact of such practices.
1 janv. 2008 ... This has brought about many changes in the economies of developing ... and an effective marketplace, touching on issues of globalization, ... and the policies that governments and citizens can promote and practice to limit the ...
Sahlberg, Pasi; Oldroyd, David
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…
Competitive intelligence (CI) is the process of developing actionable foresight regarding competitive dynamics and non-market factors that can ... It is a relevant tool for strategic decision making which in return impacts national ... archives, resource centers, etc are yet to realize their position as Competitive Intelligent Agents.
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 argument for competitive pressure and the infant industry argument for protection. The key insight is that the effects of competitive pressure on a firm's incentives to innovate depend on the firm's eff...
Barnes, Michael R; Harland, Lee; Foord, Steven M; Hall, Matthew D; Dix, Ian; Thomas, Scott; Williams-Jones, Bryn I; Brouwer, Cory R
Pharmaceutical research and development is facing substantial challenges that have prompted the industry to shift funding from early- to late-stage projects. Among the effects is a major change in the attitude of many companies to their internal bioinformatics resources: the focus has moved from the vigorous pursuit of intellectual property towards exploration of pre-competitive cross-industry collaborations and engagement with the public domain. High-quality, open and accessible data are the foundation of pre-competitive research, and strong public-private partnerships have considerable potential to enhance public data resources, which would benefit everyone engaged in drug discovery. In this article, we discuss the background to these changes and propose new areas of collaboration in computational biology and chemistry between the public domain and the pharmaceutical industry.
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...
Using detailed trade and firm-level financial data, the authors demonstrate, ... This book examines the link between finance and competitiveness at the macro and sectoral levels in ... Asian outlook: New growth dependent on new productivity.
The experience of these countries suggests that high productivity and competitiveness .... Fluctuations in the terms of trade and, hence, in the availability of foreign ...... plying mills), 3312 (wooden and cane containers), 3521 (paints, varnishes, ...
... Preclinical Research Preclinical Research Drugs undergo laboratory and animal testing to answer basic questions about safety. More Information ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products
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...
Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul
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.
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.
... molecule that contains genetic instructions to make proteins. Delivery of CFTR-encoded mRNA would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation. This drug is delivered via inhalation. Editas This program is ...
Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.
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.
Dave, Chintan V; Kesselheim, Aaron S; Fox, Erin R; Qiu, Peihua; Hartzema, Abraham
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.
Alexey. A. Sidorov
Full Text Available Factors and possible consequences of transatlantic integration are elaborated in the article. An overview of the history of transatlantic cooperation is provided. The author highlights the paramount goal of Transatlantic Trade and Investment Partnership (TTIP - strengthening the positions of its parties in the world economy against the backdrop of global competition. Stalemate in Doha round of WTO trade negotiations as well as depressed state of the European economy also contributed to transatlantic integration. Validity of the EU Commission conclusion on TTIP benefits is examined. Results of TTIP econometric modelling are critically assessed. Problems of the EU-US non-tariff liberalization are analyzed. Efficiency of the EU and US labor markets is compared. Low competitiveness of the EU in comparison to the USA and underlying risks for TTIP economic growth and employment are outlined. High unemployment, difficulties of manufacturing (including high-tech industries thereof recovery, adverse general business situation in the EU are among such risks. Various modes of regulatory cooperation and possibility of their adoption in TTIP are considered. Harmonization, erga omnes mutual recognition of regulations, bilateral mutual recognition of regulations, mutual recognition of conformity testing are distinguished. Possible implications of the modes of regulatory cooperation on TTIP members competitiveness, competition with emerging economies and global standard setting are examined. Conflict of TTIP goals and motivations is revealed. The existence of economic factors of transatlantic integration as well as overestimation of TTIP benefits (primarily for the EU economy is concluded.
Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan
in plasma. A detection limit of 41 ng/mL of platinum and a precision of 2.1 % (for 10 µg/mL of cisplatin standard) were obtained. Simultaneous measurements of phosphorous and platinum allows the simultaneous monitoring of the liposomes, liposome-encapsulated cisplatin, free cisplatin and cisplatin bound...... 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...
Buchanan, L.; Jurek, P.; Redshaw, R.
This article describes the development of nuclear imaging as an enabling technology in the pharmaceutical industry. Molecular imaging is maturing into an important tool with expanding applications from validating that a drug reaches the intended target through to market launch of a new drug. Molecular imaging includes anatomical imaging of organs or tissues, computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound.
To describe alternative policies aimed at encouraging price competition in generic drug markets in countries with strict price regulation, and to present some case studies drawn from the European experience. Systematic literature review of articles and technical reports published after 1999. The shortcomings in consumer price competition observed in some European generic markets, including Spain, may be reduced through three types of public reimbursement or financing reforms: policies aimed at improving the design of current maximum reimbursement level policies; policies aimed at monitoring competitive prices in order to reimburse real acquisition cost to pharmacies; and, more radical and market-oriented policies such as competitive tendering of public drug purchases. The experience of recent reforms adopted in Germany, Belgium, Holland, Norway, and Sweden offers a useful guide for highly price-regulated European countries, such as Spain, currently characterized by limited consumer price competition and the high discounts offered to pharmacy purchases. Direct price regulation and/or the generic reference pricing systems used to reduce generic drug prices in many European countries can be successfully reformed by adopting measures more closely aimed at encouraging consumer price competition in generic drug markets. Copyright 2009 SESPAS. Published by Elsevier Espana. All rights reserved.
Vaughns, Janelle D; Conklin, Laurie S; Long, Ying; Zheng, Panli; Faruque, Fahim; Green, Dionna J; van den Anker, John N; Burckart, Gilbert J
There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed for statements addressing obesity in pediatric patients. Forty-five drugs studied in pediatric patients under the FDA Amendments Act were found to have statements and key words in the medical and clinical pharmacology reviews and labels related to obesity. Forty-four products were identified similarly with pediatric studies under FDASIA. Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only 4 labels. We conclude that there is little information presently available to provide guidance related to dosing in obese pediatric patients. Moving forward, regulators, clinicians, and the pharmaceutical industry should consider situations in drug development in which the inclusion of obese patients in pediatric trials is necessary to facilitate the safe and effective use of new drug products in the obese pediatric population. © 2018, The American College of Clinical Pharmacology.
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 ...
the major burden being in developing countries. Many of ... The driving force for drug discovery and development by pharmaceutical firms ... world and particularly in the third world countries ..... GFHR (2000) Global Forum for Health Research:.
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
Bridoux, F.; Vodosek, M.; Den Hartog, D.N.; McNett, J.M.
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
Full Text Available The aim of this research is to study the comparative advantage and papaya competitive and to design its development model by using the approach of local base agriculture development. This research uses survey method. The resulting research shows that papaya is a base commodity that has comparative advantage and competitive. The development papaya in the district of Sukabumi is quite good bases on eight superior creations. But in order to be the main sector in economic development and has a competition, the development of papaya must concern to its influence factors. In supporting papaya development as a competitive local superior commodity, it needs to be done some efforts are as follows: (1 increase a skillful worker; (2 improve business management; (3 increase papaya productivity by using technology and study papaya planted technology in specific local superior commodity; (4 develop the involvement of the business relation; (5 provide market information and information technology network; and (6 improve infrastructures.
Grandjean, Nicolas; Charpiot, Brigitte; Pena, Carlos Andres; Peitsch, Manuel C
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.: © 2005 Elsevier Ltd . All rights reserved.
Full Text Available This paper discusses the central features of so-called ‘site allocation competitions’, as organized by the City of Helsinki Real Estate Department (Kiinteistövirasto in Finnish. Site allocation competitions are developer competitions where the municipality sells or leases plots of land to developers or contractors, but where the ‘bidding’ is based on competing on the basis of architectural and urban quality factors. The focus in this paper is on the Finnish context, but as its legal framework is constituted by European competition law. In these competitions the proprietor expects the contractor or developer to create a design team and in turn the proprietor receives multiple proposals for a site without really paying for them. It seems important to examine this rather new type of architectural competition, as it is often an integral part of important large projects in terms of both financial investments and architectural design. It also constitutes a new tool in the practices of urban planning. The present study is explorative, based mainly on a close study and analysis of written material, such as reports, as well as three interviews with experienced organizers. The aim of the paper is to clarify the concept of developer competition, and discuss its possible benefits and problems. The core issue in the study is how architectural quality is produced within the legal framework, as well as to discuss the relation of the developer competition to the aims of urban planning and professional agents.
Poulsen, Henrik Enghusen; Grønlykke, Thor Buch
Exclusively private companies do drug development. The State contributes with education of academics and basic research constituting the basis of half of the drugs developed by the private companies. The Danish private drug research amounts to six billion DKK per year, corresponding to the estimated price of the development of one new drug. The development shows a negative tendency. There are doubts about the scientific credibility, the number of new drugs is declining, drug development costs are rising, and the competitiveness in Europe is declining compared with the one of The United States. Continued improvement of Danish drug development can be achieved by stimulation of the public research related to drug development.
Feldman, Roger; Lobo, Félix
We take on two subjects of controversy among economists-advertising and trademarks-in the context of the market for generic drugs. We outline a model in which trademarks for drug names reduce search costs but increase product differentiation. In this particular framework, trademarks may not benefit consumers. In contrast, the generic names of drugs or "International Nonproprietary Names" (INN) have unquestionable benefits in both economic theory and empirical studies. We offer a second model where advertising of a brand-name drug creates recognition for the generic name. The monopoly patent-holder advertises less than in the absence of a competitive spillover.
The aim of privatization in developed countries is to encourage competition in generation and supply of power whereas the focus of developing economies is to bridge the demand supply gap by addition of capacity. However, there needs to be a reconciliation between these two apparently having conflicting objectives even in case of developing economies. In competitive power markets it is necessary that rules of the game are identified in advance and followed uniformly by all players. Existence of a ''referee'' would be necessary to regulate the game so as to ensure fair play. The regulatory institution would serve this purpose and work as a stimulator to development of privatization and competitive power markets in developing economies. Consumer interests should be of upper-most priority in the mind while establishing power markets and regulatory institutions, particularly as market forces are unfavorable to consumer interests in power shortage conditions. As competition fosters, gradually market forces take over and the ''harsh'' regulator would convert itself to a ''silent vigil referee'' so as to ensure genuine competition. The debate of deregulation vs. regulation will continue but the show must go on for building of an increasingly sound, competitive and vibrant power sector in the interest of end use consumers. The planned and phased restructuring though a delayed process is a preferred process and India is fully determined to achieve this
Faller, Christina E; Raman, E Prabhu; MacKerell, Alexander D; Guvench, Olgun
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 nonoverlapping 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.
Sergey I Zubin
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.
RAMONA PÎRVU; MARIA DANATIE ENESCU
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 beca...
Bayona, Andrés; Fajardo, Natalia
The development of innovative drugs allows coming up with new medicines to prevent and better treat illnesses. This improves people's quality of life and makes it more productive. Therefore, the mission of pharmaceutical research is to develop safe and effective drugs. Clinical trials allow the evaluation of the safety and efficacy profiles of new medicines, medical devices and diagnostic tests. Research and development (R&D) of new drugs is a long and costly process, where out of every 5000 to 10000 new components that enter preclinical testing, only one is approved. Compared to 2011, drug development has increased by 7.6%. According to ClinicalTrials.gov, 5% of the trials take place in Latin America, and Peru is in the fifth position. On the other hand, according to the Global Competitiveness Report issued by the World Economic Forum, Peru ranks 61st, its biggest challenges being the functioning of its public institutions, investment in R&D and technological capacity. The complexity of drug R&D results in a search for competitive places to develop clinical trials. Clinical Research is a humanized industry due to its ethical platform, stated in the guidelines of good clinical practices. This industry demands our country to develop a differentiating value that contributes to the development of knowledge and its competitiveness.
Many developing countries have adopted market-oriented reforms as a part of the globalization and liberalization process. However, due to market distortions, the need to ensure proper access to essential services requires effective regulation. Accordingly, developing countries are legislating or revising their ...
This article will provide vital insights, acquired in a recent study with eight manufacturing companies, to guide the development of a human resource development strategy. This study was a pilot for a larger study, planned for the fall of 1995 with 50 manufacturing companies randomly chosen from the Directory of Massachusetts High Technology Companies.
Silva, E.; Wu, Y.; Ojiako, U.
At the level of the firm, three major parameters are found to influence the ability of SMEs to develop risk management competencies; these are enterprise risk management, internal control, and risk culture.
White, Larry Nash
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.
Winters, Ken C.; Arria, Amelia
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…
Rosenfeld, Stuart A.
In the past, economic development in the rural United States, particularly in the rural South, relied principally on the attractiveness of a low-wage work force to mass-production manufacturing industries. Now however, the viability of the traditional mass-production economy's organizational structure and operating procedures has been eroded by…
... the National Research Council (CONICET) in Buenos Aires. Rohinton Medhora is Vice-President of Programs at Canada's International Development Research Centre. He has published primarily in the areas of monetary integration and central banking and holds a doctorate in economics from the University of Toronto.
Bushnell, Mary Ellen; Heller, Donald
The experience of the Massachusetts Institute of Technology in adopting a cost-recovery strategy for systems development is described, providing information of use to all managers. Issues addressed include establishing revenue goals, marketing and promotion, contracting with clients, and time accounting and billing. (Author/MSE)
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.
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.
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.
José G. Vargas-Hernández
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
Grunert, Klaus G.; Hildebrandt, Lutz
others or what are successful strategies to outperform a competitor. In the beginning of strategic management research, the theoretical background for explaining the strategic behaviour of firms and business units was not very sophisticated. Most studies were purely exploratory and in general, small......Since the early days of strategic management research scientists and managers have tried to find general rules for developing successful business strategies. Numerous articles have been published based on studies that explore research questions like: why are some competitors more profitable than......-scale case studies were the bases to generate assumptions on the causes of business success. A fundamental breakthrough towards a broader theoretical basis for strategic planning was the adoption of concepts and research methods from economic theory in the seventies of the last century. For more than 20...
Wildenhaus, Kevin J.
This article reviews the historical development of female participation in sports, then identifies the unique issues associated with women's struggles for athletic acceptance and competitive excellence. Topics discussed include talent recognition and development, sex roles and socialization, physiology and maturation, coaching the female athlete,…
Shaunak, Sunil; Davies, Donald S
The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therapeutic intervention have started to give way to the use of an increasing number of surrogate markers. Using a combination of these markers, it is now possible to measure and monitor the pathogen as well as the host's response. Nowhere is this better exemplified in virology than in the field of AIDS. We have utilized the advances in pathogenesis and new antiretroviral drug development to: develop a new class of drugs which block the entry of HIV-1 into cells.develop a new approach for effectively delivering these drugs to those tissues in which most viral replication takes place. Over the last 10 years, our work has progressed from concept to clinical trial. Our laboratory based evaluation of the new molecules developed as well as our clinical evaluation of their safety and efficacy have had to respond and adapt to the rapid changes taking place in AIDS research. This paper discusses the problems encountered and the lessons learnt. PMID:12100230
Bui, Minh Q.
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…
Fontebasso, Yari; Dubinett, Steven M
Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors.
This presentation provided an explanation of the concept of regulated rates in the natural gas industry, including cost based rates, tariff defined services, tariff defined terms and conditions, discounting and capacity release. Definition of competitive alternatives, such as negotiated rates and negotiated terms and conditions, was included. Additional alternatives, comprising revisions to capacity release programs and further unbundling of the natural gas industry, were also examined. A section on market competition dealt with the development of market centers and hubs, the impact of new pipeline projects as well as recontracting and decontracting. Under the heading of 'Maximizing Value' were discussed issues such as seasonally adjusted contract quantities and seasonally adjusted rates. Other competitive issues, such as access to alternative supplies and alternative markets, quality of customer relations, and timing of contract expirations, also received attention
Full Text Available The purpose of the paper is to analyze historical trends and development prospects of the European chemical industry competitiveness. It is concluded that the chemical industry is one of the EU’s most successful spheres, boasting €527 billion in sales in 2013, making it the second-largest global manufacture. Methodology. To explain the competitiveness of the EU chemical branch in the global market, it is proposed the constant-market share methodology to chemical exports coupled with econometric analysis. Results. The constant market share (CMS approach to assessing competitiveness, developed in the 1970 s for analysis of trade, is based on the principle that changes in the geographic and product structures of exports will affect a country’s export growth relative to that of the world, and that is way its global export market share. There were analyzed the EU biggest exporters (Germany, France, Italy, UK, Spain, Netherlands, Belgium, Poland, the USA, Japan; China, India, Saudi Arabia, Brazil. Practical implication. The analysis presents the results of competitiveness assessment in a different way, showing the average annual growth rate of EU and world chemical exports in the top section and then decomposing the gap between the two into that thanks to growth dynamics (structure effect and competitive effect. It is defined a lot of factors that are important to industrial competitiveness. On the cost side, in many industries labor is a large enough share of overall production costs that international differences in salaries can have a large bearing on competitiveness. Costs are also affected by a variety of government policies. It is also defined that innovation is one of the most important factors, which opens up new opportunities both in terms of new products and more efficient processes for manufacturing existing products. Value/originality. Given analysis helps to understand the causes and factors that have an impact on the European
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
Moors, Ellen H.M.; Cohen, Adam F.; Schellekens, Huub
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
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.
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.
Kolomiets Ganna M.
Full Text Available The article considers the qualitative changes of the national competitive advantages as derivatives of the evolution of technological modes in the global business environment; the role of both the formal and the informal institutions in their development and implementation has been analyzed. With this in mind, topical in the development of competitive advantages will be improving the formal institutions in conjunction with the informal: recognition and use of the positive potential of the national values and attitudes. High adaptatibility towards turbulence of the economic environment, desire and capability to master new knowledge, technologies, fulfill one’s own abilities in the native country, should define the focus and content of transformations of the formal institutions. Results of the analysis show that nowadays a value shift is going on, attitudes are being changed, which suggests that there’s a necessity to understand that disposition of power institutions, mistrust to authorities can significantly slow down transformations in the direction of «competitive advantages – competitiveness»
Kruglova Olga Valentinovna
Full Text Available Scientific approaches and the methodical tools, allowing to form the strategic capacity of the commercial organizations taking into account its innovative component which in turn allows to define possibilities of the company with an acceptable accuracy are considered, and in the subsequent to consider and use them when developing competitive strategy of the development. These calculations are approved at the enterprises of the Nizhny Novgorod Region and proved the practical and economic importance.
Falvey, Rod; La Chimia, Annamaria; Morrissey, Oliver; Zgovu, Evious
Measures to support Competition Policy and enhance the efficiency of Public Procurement can enhance the impact of regional integration agreements. The first part addresses Competition Policy - measures employed by government to ensure a fair competitive market environment. Competition policy aims to ensure that markets remain competitive (through anti-trust or anti-cartel enforcement) or become competitive (through liberalisation). For a variety of reasons, competition is often restricted in ...
Full Text Available This study analyzes the effects of institutional structure on the international competitiveness of developed countries econometrically by employing a “Panel Data Analysis” with a sample of 21 developed countries and 23 institutional variables for the period 2000-2011. The results of the analysis indicate that while judicial independence, protection of intellectual property rights, integrity of the juridical system, marginal tax, political freedoms, black market exchange rate, restrictions on foreign investment, private sector’s share in the banking system, hiring-minimum wage, and hiring-dismissal have a positive effect; the nature of legal arrangements, government spending, transfers and subsidies, civil liberties, tariffs, regulations regarding trade barriers, collective bargaining, and military tutelage have a negative effect on the international competitiveness of developed countries.
Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal ge......, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led...... to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has...... been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical...
Valentina Fedorovna Lapo
Full Text Available The author considers the problem of competition between regions for investments. It is hypothesized that the presence of legislative stimulating benefits in a particular region, ceteris paribus, promotes investment flows in forest projects from other regions and is an instrumentl of inter-regional competition. To test the hypotheses the researcher uses a modified model with spatial weighted exogenous variables in order to assess the spatial effects. The obtained estimates indicate the presence of spatial effects, both negative (an inter-regional competition for investment and positive (agglomeration effects. The author argues that the process of inter-regional competition for investment in projects on forest development is caused by benefits under taxes and payments into the regional budget, regulation of pricing (including actions by natural and local monopolies and depreciation policy and solutions to put some forest projects in the list of priority ones. Along with this, the paper identifies agglomeration effects induced by a number of benefits: direct dealings in investment by financing or property contribution, subsidies, state guarantees, credit security and partial payment of interest
Tylkowski, Bartosz; Jastrząb, Renata; Odani, Akira
Platinum compounds represent one of the great success stories of metals in medicine. Following the unexpected discovery of the anticancer activity of cisplatin (Fig. 1) in 1965 by Prof. Rosenberg , a large number of its variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. Although cisplatin has been in use for over four decades, new and more effective platinum-based therapeutics are finally on the horizon. A wide introduction to anticancer studies is given by the authors of the previous chapter. This chapter aims at providing the readers with a comprehensive and in-depth understanding of recent developments of platinum anticancer drugs and to review the state of the art. The chapter is divided into two parts. In the first part we present a historical aspect of platinum and its complexes, while in the second part we give an overview of developments in the field of platinum anticancer agents.
The aim of this study is to develop and optimize an osmotically controlled drug delivery system of diclofenac sodium. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active drugs. Drug delivery from these systems, to a large extent, is independent of the physiological factors ...
Rotaru, Ioan; Bilegan, I.C.; Jelev, Adrian
At present a trend manifests world wide toward promoting nuclear power, for increasing its performances, toward maintaining competitiveness and sustaining the programs of development and application of advanced nuclear technologies. These objectives will be achieved by improving: operation performances; management of life-cycle, quality management; technical infrastructure; human resource performances; international cooperation for developing innovative nuclear technologies; technologies and applications of advanced reactors. Fostering the Romanian nuclear power on the basis of CANDU 6 type rectors, the developing in Romania of an advanced industrial infrastructure, the economical, environmental and social aspects and their interplay with nuclear power development are the main subjects presented in this work
Rana, Proteesh; Chawla, Shalini
Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.
Rashid, Reza; Bozorgi-Amiri, Ali; Seyedhoseini, S. M.
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.
Kropf, R; Szafran, A J
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.
Ertek, Gürdal; Ertek, Gurdal
Information visualization is the growing field of computer science that aims at visually mining data for knowledge discovery. In this paper, a data mining framework and a novel information visualization scheme is developed and applied to the domain of higher education. The presented framework consists of three main types of visual data analysis: Discovering general insights, carrying out competitive benchmarking, and planning for High School Relationship Management (HSRM). In this paper the f...
Anas M. Fauzi
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
Ruiz Conde, Enar; Wieringa, Jaap; Leeflang, Peter
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
In the United States electric utilities are using competitive bidding programs to procure power supplies from non-utility generators and, in some cases, to establish contracts with energy service companies for the implementation of demand-side management projects. Such programs are viewed as a path to efficient contracts in the private power industry. But bidding programs are complex, subject to pitfalls, and are developing very quickly. This paper reports on that development as of the early 1990s and, as an illustration, briefly describes and analyzes the bidding program of an electric utility in the State of New York. (author). 2 tabs
Full Text Available In the paper are investigated the regional competitiveness and the territorial aspects of industry in Serbia. There are analyzed the key recent movement in industrial development of Serbia and macrolocational factors and territorial organization of industry. The research of possible structural changes of industry and identification of its key development sectors is the important component of territorial development analysis in Serbia. This paper points to the kinds and types of industrial zones and industrial parks as fundamental models of regional and urban development of that activity with critical retrospection on the industrial zones in Serbia (greenfield and brownfield industrial locations. There are shown results of evaluation the regional competitiveness from a stand-point of possibilities of industrial development on the regional level (NUTS 3 by comparative analyses and Spider method. Results are used as one of the bases for making preliminary draft of territorial development scenario of this activity in Serbia and for the possible alocation of the future industrial zones and industrial parks in region level.
To descriptively analyze the policy environment surrounding the Polish generic medicines retail market. The policy analysis was based on an international literature review. Also, a simulation exercise was carried out to compute potential savings from substituting generic for originator medicines in Poland using IMS Health pharmaceutical intelligence data. Poland has a mature, high-volume, low-value generic medicines market, primarily driven by the establishment of the reference price at the price of the cheapest medicine in combination with pricing regulation and the low level of medicine prices. The practice of discounting in the distribution chain implies that the National Health Fund and patients do not capture the potential savings from a generic medicines market where companies compete on price. This high-volume market has benefited in the past from the limited availability of originator medicines and a short data exclusivity period, even though there are no incentives for physicians to prescribe generic medicines and a financial disincentive for pharmacists to dispense generic medicines. Increased generic substitution would be expected to reduce public expenditure on originator medicines by 21%. To develop a competitive and sustainable market, Poland needs to consider moving away from competition by discount to competition by price. This could be achieved by replacing maximum distribution margins by fixed margins. Also, Poland may wish to raise reference prices as a temporary measure to boost market entry for medicine classes with few generic medicines.
Craik, D.; Munro, S.
The use of nuclear magnetic resonance (NMR) spectroscopy for structural and conformational studies on drug molecules, the three-dimensional investigation of proteins structure and their interactions with ligands are discussed. In-vivo NMR studies of the effects of drugs on metabolism in perfused organs and whole animals are also briefly presented. 5 refs., ills
Wondowossen, T.A.; Nakagoshi, N.; Yukio, Y.; Jongman, R.H.G.; Dawit, A.Z.
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
Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.
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.
Protein structure analysis consortium was established by 21 drug companies and has analyzed protein structures using the beam line BL32B2 of SPring-8 since September in 2002. Outline of the protein structure analysis consortium, contribution of SPring-8 to drug development, and the present status and future of use of SPring-8 are stated. For examples of structure analysis, the human nuclear enzyme (PARP-1) fragment complex crystal structure, human ISG20, human dipeptidine peptidase IV, human cMDH, chromatin binding human nuclear enzyme complex, change of structure of each step of tyrosine activation of bacteria tyrosine tRNA synthetase are described. Contribution of analysis of protein structure and functions to drug development, development process of new drug, drug screening using compounds database on the basis of the three dimensional structure of receptor active site, genome drug development, and the effects of a target drug on the market are explained. (S.Y.)
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
Barik, Tapan Kumar
Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of vaccine development for malaria, till now, no effective vaccine is available for use and hence only antimalarial drugs remain our best hope for both treatment and prevention of malaria. However, emergence and spread of drug resistance has been a major obstacle for the success of malaria elimination globally. This review will summarize the information related to antimalarial drugs, drug development strategies, drug delivery through nanoparticles, few current issues like adverse side effects of most antimalarial drugs, non availability of drugs in the market and use of fake/poor quality drugs that are hurdles to malaria control. As we don't have any other option in the present scenario, we have to take care of the existing tools and make them available to almost all malaria affected area.
Rubin, R. H.; Fischman, A. J.
There are four kinds of measurements that can be carried out with positron emission tomography (PET) that can contribute significantly to the process of drug development: pharmacodynamic measurement of tissue metabolism influenced by a given drug; precise measurements of tissue blood flow; tissue pharmacokinetics of a given drug following administration of a particular dose; and the temporal course of ligand-receptor interaction. One or more of these measurements can greatly improve the decision making involved in determining the appropriate dose of a drug, the clinical situations in which a drug might be useful, and the linkage of pharmacokinetics with pharmacodynamics, which is at the heart of effective drug development. The greater the potential of a particular compound as a therapeutic agent, the greater the potential for PET to contribute to the drug development process
Breno Barros Telles do Carmo; Dmontier Pinheiro Aragão; Heráclito Lopes Jaguaribe Pontes; Bruno Magalhães Ribeiro; Marcos Ronaldo Albertin
The new global market competitiveness considerer the competition between productive chains (PC) or supply chains, not just between enterprises. In this case, it can be observed collaboration and cooperation enterprises that dispute with others productives chain. The PC competitiveness can be impaired if is subject by inhibitors factors, that can impairer the performance. This paper analyses these competitiveness factors inhibitors in biodiesel productive chain (CPB) in semi-arid area: exporte...
Mitola, J.P. [Unicom Thermal Technologies, Chicago, IL (United States)
In two year`s time, Unicorn Thermal Technologies has grown into one of the largest district cooling systems of 25,000 tons with a 1996 plan to grow to 40,000 tons. This growth is attributed to the development and implementation of a marketing and sales plan based on thorough market research and innovative marketing and sales strategies, and the consistent implementation of those strategies. The beginning of the sales effort was focused around the company`s first district cooling facility, However, it quickly grew into a much broader vision as market acceptance increased. Although the district energy industry has often based its message on being a low cost energy provider, market research and early sales experience indicated that customers choose district cooling as a value added service. As customers began to reserve capacity in the first plant, the idea that district cooling is a value added service and not a commodity energy product was continually reinforced through marketing communications. Although this analysis is a review of developing a district energy system in a competitive urban market, it purposely avoids a long winded discussion of head to head competition.
Sheingold, Steven; Nguyen, Nguyen Xuan
This study estimates the effects of generic competition, increased cost-sharing, and benefit practices on utilization and spending for prescription drugs. We examined changes in Medicare price and utilization from 2007 to 2009 of all drugs in 28 therapeutic classes. The classes accounted for 80% of Medicare Part D spending in 2009 and included the 6 protected classes and 6 classes with practically no generic competition. All variables were constructed to measure each drug relative to its class at a specific plan sponsor. We estimated that the shift toward generic utilization had cut in half the rate of increase in the price of a prescription during 2007-2009. Specifically, the results showed that (1) rapid generic penetration had significantly held down costs per prescription, (2) copayment and other benefit practices shifted utilization to generics and favored brands, and (3) price increases were generally greater in less competitive classes of drugs. In many ways, Part D was implemented at a fortuitous time; since 2006, there have been relatively few new blockbuster drugs introduced, and many existing high-volume drugs used by beneficiaries were in therapeutic classes with multiple brands and generic alternatives. Under these conditions, our paper showed that plan sponsors have been able to contain costs by encouraging use of generics or drugs offering greater value within therapeutic classes. It is less clear what will happen to future Part D costs if a number of new and effective drugs for beneficiaries enter the market with no real competitors.
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
Dzhabbarova N. O.
Full Text Available presented challenges and stages of the development process of marketing strategies for competitive agricultural enterprises, consider a system of competitive strategies are disclosed function to ensure their implementation.
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.
Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.
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.
Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F.
Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations
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)
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.
Algirdas Krivka; Romualdas Ginevičius
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 oligo...
Buehler, Benno; Coublucq, Daniel; Hariton, Cyril; Langus, Gregor; Valletti, Tommaso
The Directorate General for Competition at the European Commission enforces competition law in the areas of antitrust, merger control, and state aids. This year's article provides first a general presentation of the role of the Chief Competition Economist's team and surveys the main achievements of the Directorate General for Competition over 2016/2017. The article then reviews the economic work undertaken in one merger case between Dow/DuPont, which raised specific issues related to innovation, as well as in an antitrust case on parity clauses related to Amazon e-books.
Zhong, Wei-Zhu; Zhou, Shu-Feng
With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of "Molecular Science for Drug Development and Biomedicine", in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine.[...].
Tirronen, Jarkko; Nokkala, Terhi
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…
Feb 7, 2011 ... That's more than the Gross Domestic Product [GDP] of Tanzania in 2002.” ... to prevent foreign or domestic firms from engaging in anti-competitive behaviour. ... Taimoon Stewart is an advisor on trade and competition issues at the ... European consultancy specializing in political and regulatory issues.
Choi, Hong Suk; Johnson, Britton; Kim, Young K.
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…
WITTE, DT; ENSING, K; FRANKE, JP; DEZEEUW, RA
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
Full Text Available Competitive advantage is a relative feature, evaluated in respect of other competing enterprises. The gaining of sustainable competitive advantage is conditioned by knowledge of own performance and the results of the competitive environment. SMEs have limited opportunities to obtain such information on their own. The method of mutual benchmarking changes this situation by introducing the collaborative network. The aim of the cooperation is to support each of the group members to achieve sustainable competitive advantage, which is the result of a conscious strategy, and not only a matter of chance. This cooperation is based on the collecting and processing of data and sharing information through a common IT platform: for example, a group of Polish SMEs was shown how to implement such a common IT solution and how to provide the information preparing within the proposed service. The whole is a complete proposal for effective support of creating a competitive strategy in SMEs.
Conclusion: The developed system is capable of releasing the drug after a 4-h lag period. However ... concentration would be at its maximum level, ... spheronizer (Caleva MBS, UK)operating at .... capsules show that the color intensity of the.
Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul
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 internat...
Lisa M. Broad
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.
Full Text Available The paper specifies basic stages of developing and realizing the strategy of enhancing competitiveness of enterprises and represents an appropriate algorithm. The study analyzes the economic indexes and results of the activity of the agrarian enterprises in Kherson region and provides competitive strategies of efficient development of agrarian enterprises with different levels of competitiveness and specifies the ways of realizing them which will contribute to the optimal use of the available strategic potential
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
Carlos Alberto de Oliveira
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.
Full Text Available The article considers modern trends in the development of the global economy, the dynamics of the activity of the domestic economy. The statistical data of the share of loss-making enterprises on the domestic market are analyzed. The importance of competitiveness and financial stability of enterprises in modern conditions is considered, the relationship between competitiveness and financial stability is indicated. The notion of financial competitiveness is formulated. Financial competitiveness is analyzed from the point of view of enterprise management and on the parameters for assessing the financial stability of enterprises. Methods for assessing the financial competitiveness of enterprises have been identified. The primary calculation of financial competitiveness indicators for PJSC “SF Almaz” was carried out based on the selected methods. The analysis of the obtained calculation results is carried out. Methods are proposed to ensure financial competitiveness of Russian companies.
Hoang, U; Luna, P; Russell, P; Bergonzi-King, L; Ashton, J; McCarthy, C; Donovan, H; Inman, P; Seminog, O; Botchway, S
Film competitions can be a helpful method to understand issues of quality in health films. In this paper, we describe the development and use of explicit quality criteria to identify the 'best' films for the first ever international public health film competition. A film selection committee encompassing a range of stakeholders was compiled. The committee drew up 10 explicit quality criteria to judge films drawing upon other film festival's selection criteria. These criteria were then applied to a broad range of health-related films entered into a film competition to select the 'best' film to screen. Eighty-four films from 20 different countries were submitted to the public health film competition. The originality of the subject covered by the film, the public health importance of the issue and story-telling approach in the film were found to be the most discriminatory criteria to select films. Selection of health films for festivals can be undertaken using explicit quality criteria. There are a number of advantages to such an approach; however, explicit selection involves a large commitment of resources from film festival organizers and there is further research required to test the validity of the quality criteria applied to health-related films.
Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M
Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.
Zhao, D.L.; Atlin, G.N.; Bastiaans, L.; Spiertz, J.H.J.
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
Full Text Available In this paper, we explore the pricing and greenness issues of two competitive firms without and with consumer heterogeneity. We derive and compare the optimal solutions and profits employed by firms under different scenarios. Then, we identify the effects of consumer heterogeneity under different competition intensities. The analytical results reveal that if market competition is at a relatively low level, we find that: (i when the greenness sensitivity of consumers with no preference is sufficiently small, more consumers have high environmental awareness, and companies easily achieve their environmental goals as well as economic goals; (ii when the greenness sensitivity of consumers with no preference is at a medium level, as the fraction of consumers with high environmental awareness increases, and the firm might achieve economic goals at the cost of reducing environmental goals; and (iii when the greenness sensitivity of consumers with no preference is at a high level, the fraction of consumers with high environmental awareness increases, but firms might have more difficulty achieving their environmental and economic goals. On the other hand, if the market competition is at a relatively high level, the presence of consumer heterogeneity can help improve environmental goals, but make achievement of economic goals difficult.
promoted by major donors and international organisations as part of the ... ownership and control in the South African economy. The new ... The effects of competition policy in South Africa, and selected .... costs and multiproduct firms. ..... While consistent with profit maximisation, import parity pricing is inefficient in terms.
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.
Tamimi, Nihad A M; Ellis, Peter
Drug development is an expensive, long and high-risk business taking 10-15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product's safety continues beyond the initial drug approval through post-marketing monitoring of adverse events. Copyright 2009 S. Karger AG, Basel.
Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F
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
Ting, Naitee; Ho, Shuyen; Cappelleri, Joseph C
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.
Bennette, Caroline S; Richards, Catherine; Sullivan, Sean D; Ramsey, Scott D
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. Project HOPE—The People-to-People Health Foundation, Inc.
Cecilia – Nicoleta Jurcuț (Aniș
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.
Schytz, Henrik Winther; Hargreaves, Richard; Ashina, Messoud
This review considers the history of drug development in primary headaches and discusses challenges to the discovery of innovative headache therapeutics. Advances in headache genetics have yet to translate to new classes of therapeutics and there are currently no clear predictive human biomarkers...... for any of the primary headaches that can guide preventative drug discovery and development. Primary headache disorder subtypes despite common phenotypic presentation are undoubtedly heterogeneous in their pathophysiology as judged by the variability of response to headache medicines. Sub......, despite having promising effects in basic pain models, have not delivered efficacy in the clinic. Future efforts may triage novel physiological mediators using human experimental models of headache pain to support drug discovery strategies that target active pathways pharmacologically....
Christensen, Søren Brøgger; Skytte, Dorthe Mondrup; Denmeade, Samuel R
Available chemotherapeutics take advantage of the fast proliferation of cancer cells. Consequently slow growth makes androgen refractory prostate cancer resistant towards available drugs. No treatment is available at the present, when the cancer has developed metastases outside the prostate (T4 s...
Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.
Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.
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.
On 17 March 2000, the World Trade Organization upheld the provision in Canada's patent laws that allows generic drug manufacturers to develop (but not sell) their cheaper versions of patented medicines before the 20-year patients expire. The decision prevents pharmaceutical companies from enjoying market monopolies beyond their patent terms, avoiding what would otherwise be even lengthier delays in the sale of cheaper, generic drugs in Canada. This decision is of significance not only to Canada, but also to other WTO member countries and to all individuals who use pharmaceutical products. However, the decision is not all positive: the WTO also ruled that Canada is violating international agreements by letting generic manufacturers stockpile their versions of patented drugs before patents expire. This article explains the issues, the arguments, and the decision.
Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin
Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections.
Full Text Available Many studies have been investigating determinants of the company's competitive strategy. Nevertheless, there have insufficient studies conducted to investigate the determinants of competitive strategy on banking industry, particularly on Local development banks (LDBS. This study is aimed at filling in the literature. This study surveyed top executives of twenty-six local development banks in Indonesia and employed PLS approach to answer the research questions. The result shows that three groups of variables, i.e., innovation management, company resource management, and adoption of technology influence the development of competitive strategy in local development banks.
... Development Initiative (SSDI) Grant Program; Single- Case Deviation From Competition Requirements AGENCY...). ACTION: Notice of Single-Case Deviation from Competition Requirements for the Maternal and Child Health... and quality data that is timely. SUPPLEMENTARY INFORMATION: Intended Recipient of the Award...
Hoerger, Thomas J.; Meadow, Ann
Competitive bidding to derive Medicare fees promises several advantages over administered fee systems. The authors show how incentives for cost savings, quality, and access can be incorporated into bidding schemes, and they report on a study of the clinical laboratory industry conducted in preparation for a bidding demonstration. The laboratory industry is marked by variable concentration across geographic markets and, among firms themselves, by social and economic heterogeneity. The authors conclude that these conditions can be accommodated by available bidding design options and by careful selection of bidding markets. PMID:10180003
Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao
Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.
In Australian Competition and Consumer Commission v Pfizer Australia Pty Ltd  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.
Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K
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.
Pedan, Alex; Wu, Hongsheng
This article examines the impact of direct-to-physician, direct-to-consumer, and other marketing activities by pharmaceutical companies on a mature drug category which is in the later stage of its life cycle and in which generics have accrued a significant market share. The main objective of this article is to quantitatively estimate the impact of pharmaceutical promotions on physician prescribing behavior for three different statin brands, after controlling for factors such as patient, physician and physician practice characteristics, generic pressure, et cetera. Using unique panel data of physicians, combined with patient pharmacy prescription records, the authors developed a physician level generalized linear regression model. The generalized estimating equations method was used to account for within physician serial correlations and estimate physician population averaged effects. The findings reveal that even though on average the marketing efforts affect the brand share positively, the magnitude of the effects is very brand specific. Generally, each statin brand has its own trend and because of this, the best choice of predictors for one brand could be suboptimal for another.
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0247] Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug...
SHAULSKA L.V.; SEREDA G.V.; SHKURAT M.Y.
The most strong competition in the labor market is in the segment of young people without work experience. The paper is devoted to the development of perspective directions of the enhance the competitiveness of specialists with higher education, developing their socio-emotional, cognitive skills "soft skills". On the basis of the analysis of the definition "competence" the authors substantiate the necessity of development within higher education personal characteristics (socio-emotional and c...
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.
Full Text Available This paper deals with the issue of the management cycle of Competitive Intelligence. The author describes the process of Competitive Intelligence in Czech corporate management. He concludes that in most cases, the Competitive Intelligence operations are directed by the top management, and the attention of Competitive Intelligence is being paid to Key Intelligence Topics (KIT. The Competitive Intelligence is then focused on the output of strategic analyses, complemented in some cases with a summary (synthesis of acquired intelligence plus some signal intelligence (SIGINT. The results of the Competitive Intelligence produced in such a way are actually the outputs mostly applicable in operational management and mostly unsuitable for strategic management. However, top managers abroad almost invariably need the data relevant to the future situation since their decisions are of strategic nature. The following section of the paper is devoted to the conceptual solution of Competitive Intelligence, i.e. the Competitive Intelligence objectives linked with the development strategy of the corporation. Here the author arrives at three basic development strategies: a. the corporation desires status quo, i.e. to keep its market position as it is, b. the corporation is out to expand, and c. the corporation intends not only to keep its existing and dominant market position but strives for its long-term dominance to last.
Young, G.C.; Ellis, W.J.
A history of the use of AMS in GSK studies spanning the last 8 years (1998-2005) is presented, including use in pilot studies through to clinical, animal and in vitro studies. A brief summary of the status of GSK's in-house AMS capability is outlined and views on the future of AMS in GSK are presented, including potential impact on drug development and potential advances in AMS technology
Full Text Available The aim of the study is to reveal molecular mechanisms of possible activity modulation of antimicrobial bis-quaternary ammonium compounds (BQAC and aspirin (ASP through noncovalent competitive complexation under their combined introduction into the model systems with membrane phospholipids. Methods. Binary and triple systems containing either decamethoxinum or ethonium, or thionium and aspirin, as well as dipalmitoyl-phosphatidylcholine (DPPC have been investigated by electrospray ionization mass spectrometry. Results. Basing on the analysis of associates recorded in the mass spectra, the types of nonocovalent complexes formed in the systems studied were determined and the supposed role of the complexation in the BQAC and ASP activity modulation was discussed. The formation of associates of BQAC dications with ASP anion is considered as one of the possible ways of deactivation of ionic forms of the medications. The formation of stable complexes of BQAC with DPPC and ASP with DPPC in binary systems as well as the complexes distribution in triple-components systems BQAC:ASP:DPPC point to the existence of competition between drugs of these two types for the binding to DPPC. Conclusions. The results obtained point to the competitive complexation in the model molecular systems containing the BQAC, aspirin and membrane phospholipids. The observed phenomenon testifies to the possibility of modulating the activity of bisquaternary antimicrobial agents and aspirin under their combined usage, due to the competition between the drugs for binding to the target membrane phospholipid molecules and also due to the formation of stable noncovalent complexes between BQAC and ASP.
O. N. Dmitriev
Full Text Available A number of problem questions of formation of strategy of development of administrative potential of the modern Russian enterprise which realization provides competitive advantages of the enterprise in its mutual relations with counterparts is considered.
Ou, C.X.J.; Chan, K.C.C.
Much recent effort has been put into developing effective electronic markets. However, the research has mainly focused on institutional trust-building mechanisms. Practically, sellers lack guidelines in shaping competitive edges in electronic markets where institutional mechanisms have been applied
Wagner, H N
Regulatory applications for imaging biomarkers will expand in proportion to the validation of specific parameters as they apply to individual questions in the management of disease. This validation is likely to be applicable only to a particular class of drug or a single mechanism of action. Awareness among the world's regulatory authorities of the potential for these emerging technologies is high, but so is the cost to the sponsor (including the logistics of including images in a dossier), and therefore the pharmaceutical industry must evaluate carefully the potential benefit of each technology for its drug development programs, just as the authorities must consider carefully the extent to which the method is valid for the use to which the applicant has put it. For well-characterized tracer systems, it may be possible to design inexpensive cameras that make rapid assessments.
Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes
Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...
Akhmadyar, N S; Khairulin, B E; Amangeldy-Kyzy, S; Ospanov, M A
One of the main problems of drug provision of multidisciplinary hospitals is the necessity to improve the efficiency of budget spending. Despite the efforts undertaken in Kazakhstan for improving the mechanism of drug distribution (creation of the Kazakhstan National Formulary, Unified National Health System, the handbook of medicines (drugs) costs in the electronic register of inpatients (ERI), having a single distributor), the number of unresolved issues still remain."National Medical Holding" JSC (NMH) was established in 2008 and unites 6 innovational healthcare facilities with up to 1431 beds (700 children and 731 adults), located in the medical cluster - which are "National Research Center for Maternal and Child Health" JSC (NRCMC), "Republic Children's Rehabilitation Center" JSC (RCRC), "Republican Diagnostic Center" JSC (RDC), "National Centre for Neurosurgery" JSC (NCN), "National Research Center for Oncology and Transplantation" JSC (NRCOT) and "National Research Cardiac Surgery Center" JSC (NRCSC). The main purpose of NMH is to create an internationally competitive "Hospital of the Future", which will provide the citizens of Kazakhstan and others with a wide range of medical services based on advanced medical technology, modern hospital management, international quality and safety standards. These services include emergency care, outpatient diagnostic services, obstetrics and gynecology, neonatal care, internal medicine, neurosurgery, cardiac surgery, transplantation, cancer care for children and adults, as well as rehabilitation treatment. To create a program of development of a drug formulary of NMH and its subsidiaries. In order to create drug formularies of NMH, analytical, software and statistical methods were used.AII subsidiary organizations of NMH (5 out of 6) except for the NRCOT have been accredited by Joint Commission International (JCI) standards, which ensure the safety of patients and clinical staff, by improving the technological
Wise, Roy A; Koob, George F
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.
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...
Johnston, Laura A
Studies in Drosophila and mammals have made it clear that genetic mutations that arise in somatic tissues are rapidly recognized and eliminated, suggesting that cellular fitness is tightly monitored. During development, damaged, mutant, or otherwise unfit cells are prevented from contributing to the tissue and are instructed to die, whereas healthy cells benefit and populate the animal. This cell selection process, known as cell competition, eliminates somatic genetic heterogeneity and promotes tissue fitness during development. Yet cell competition also has a dark side. Super competition can be exploited by incipient cancers to subvert cellular cooperation and promote selfish behavior. Evidence is accumulating that MYC plays a key role in regulation of social behavior within tissues. Given the high number of tumors with deregulated MYC, studies of cell competition promise to yield insight into how the local environment yields to and participates in the early stages of tumor formation.
Cline, Richard R; Mott, David A
Several proposals for adding a prescription drug benefit to the Medicare program rely on consumer choice and market forces to promote efficiency. However, little information exists regarding: 1) the extent of price sensitivity for such plans among Medicare beneficiaries, or 2) the extent to which drug-only insurance plans using various cost-control mechanisms might experience adverse selection. Using data from a survey of elderly Wisconsin residents regarding their likely choices from a menu of hypothetical drug plans, we show that respondents are likely to be price sensitive with respect to both premiums and out-of-pocket costs but that selection problems may arise in these markets. Outside intervention may be necessary to ensure the feasibility of a market-based approach to a Medicare drug benefit.
Faller, Christina E.; Raman, E. Prabhu; MacKerell, Alexander D.; Guvench, Olgun
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 ...
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.
The paper develops a simple model for a developing country with a dual economic structure. The model is a further theoretical extension and empirical work to an earlier published book chapter on the same topic. The abstract was updated after presentation at the conference in Gold Coast, Australia....... 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...... 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...
Johansson, Björn; Newman, Mike
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.
Dubé, Marie-Pierre; de Denus, Simon; Tardif, Jean-Claude
Investment in cardiovascular drug development is on the decline as large cardiovascular outcomes trials require considerable investments in time, efforts and financial resources. Pharmacogenomics has the potential to help revive the cardiovascular drug development pipeline by providing new and better drug targets at an earlier stage and by enabling more efficient outcomes trials. This article will review some of the recent developments highlighting the value of pharmacogenomics for drug development. We discuss how genetic biomarkers can enable the conduct of more efficient clinical outcomes trials by enriching patient populations for good responders to the medication. In addition, we assess past drug development programs which support the added value of selecting drug targets that have established genetic evidence supporting the targeted mechanism of disease. Finally, we discuss how pharmacogenomics can provide valuable evidence linking a drug target to clinically relevant outcomes, enabling novel drug discovery and drug repositioning opportunities.
Full Text Available This article is devoted to analysis of interdependence and correlation between competition and competitiveness, and competition’s consequences. The author analysed some authors’ visions on competitiveness, and common features between theories of competition and competitiveness. Using the synthetic indicator elaborated by author has been evaluated the competitiveness of domestic goods on the internal and external market. At the end of this article, the author has developed proposals to increase competitiveness.
Chain, Anne S. Y.
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
Caplan, M.; Thompson, T.S. [MZ Consulting Inc., ON (Canada)
Nuclear power plants are large infrastructure projects that require government support and approval. This paper will highlight and contrast the larger, mostly government-desired, nuclear program localization objectives with the more utility-specific requirements for successful project implementation. Governments are concerned about sustainable industrial development, particularly manufacturing, and job creation while utilities are focused on delivering reliable electricity to consumers at the lowest cost. Numerous countries emphasize local content as a key requirement when procuring a station. For countries like China and Korea that have large programs, their strategy has been to localize to the point of having their own indigenous design. However, developing a workable localization strategy that truly benefits the local economy for others including existing nuclear markets like Canada, the UK, South Africa and Brazil as well as in newly developing markets such as Vietnam and Malaysia is more challenging. These countries may not look to indigenize a new design, rather they would localize elements of the nuclear program that best fit their strengths. The paper will discuss the issues related to developing successful localization and industrialization strategies in a changing nuclear world. (author)
Caplan, M.; Thompson, T.S.
Nuclear power plants are large infrastructure projects that require government support and approval. This paper will highlight and contrast the larger, mostly government-desired, nuclear program localization objectives with the more utility-specific requirements for successful project implementation. Governments are concerned about sustainable industrial development, particularly manufacturing, and job creation while utilities are focused on delivering reliable electricity to consumers at the lowest cost. Numerous countries emphasize local content as a key requirement when procuring a station. For countries like China and Korea that have large programs, their strategy has been to localize to the point of having their own indigenous design. However, developing a workable localization strategy that truly benefits the local economy for others including existing nuclear markets like Canada, the UK, South Africa and Brazil as well as in newly developing markets such as Vietnam and Malaysia is more challenging. These countries may not look to indigenize a new design, rather they would localize elements of the nuclear program that best fit their strengths. The paper will discuss the issues related to developing successful localization and industrialization strategies in a changing nuclear world. (author)
hedge technology investment risk (Benaroch, 2001), and application to design modularity (Baldwin & Clark, 2000), research and development resource...Valuation Models assume that: (a) future asset behavior and value conform to well-defined processes, (b) markets are complete and arbitrage opportunities
Lee, Seungmin; Lee, Keunchul; Kwon, Sungho
This preliminary study developed pre-performance routines for tenpin bowlers and instructed them. To develop the routine, the situations before throwing the ball were divided into four phases; participants were examined through interviews and observations. This study used an A-B design; the A stage included the development of the routines for 3 wk., while the B stage included the instruction and two evaluations of the routine consistency. Practice was implemented for 4 hr. per day for 9 wk. The participants noted they understood the developed routine easily and experienced an atmosphere similar to that of a competition during training through the routines. They found it difficult to practice the relaxation phase, but emphasized that the relaxation phase was helpful. Consistent routines were associated with an improved mental state and performance in a competition. This study suggests that pre-performance routines stabilize the mental state of the athletes, apparently giving them a competitive advantage.
Kiyosawa, Naoki; Manabe, Sunao
Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.
The essential ingredients of sustainable development are economics and efficiency in the use of energy and materials, and in the prevention, disposal and recycling of wastes. Nuclear power will continue to be an important means of electricity generation for the foreseeable future but the extent to which this will be the case depends on the nuclear industry resolving public concerns over environmental, health and safety risks, and competing successfully with other generating technologies. In the final analysis, the future of nuclear power will be determined primarily by economic considerations. (UK)
Rocío Ramírez Ibagon
Full Text Available The present document describes the experiences obtained from the initiation of the Basic Development for Reconstruction of Social Abilities with Emphasis on Peaceful Co-Existence Programme. The programme includes young people who have enrolled in the National Reinsertion Programme to obtain their Secundary school Degree. It offers a profile of the population, a recount of the reasons why children and young people participate in armed conflict and also describes the reasons that influence their return. Finally, the paper makes mention of the alms and achievements of said experiences.
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...
This article covers the competitive intelligence content and five characteristics, and on the American Competitive intelligence Outstanding Company's place situation, shows fully the competitive intelligence constructs the core competitive power regarding the enterprise to have the significant function, Its contribution has already hold the pivotal status in the world famous enterprise. It is an important cornerstone for enterprises which construct the core competitive power. Along with the enterprise competition environment rapid change, the competitive intelligence importance suddenly to reveal day by day. Just like the world richest family Microsoft Corporation president Bill. Gates asserted that, How to collect, How to analysis, how to manage and how to use information, lt will decide the enterprise victory and loss. And unified the enterprise scientific research production the special details, take 'To develop the SF_6 New Product' to introduce as the example how did the enterprise competition intelligence, as well as how did the information development and using in it. (author)
Carmen B. Rosa
Full Text Available Photovoltaic (PV power generation is embedded in a globally competitive environment. This characteristic forces PV power plants to perform most processes relevant for their competitiveness with maximum efficiency. From managers’ point of view, the evaluation of solar energy performance from installed plants is justified to indicate their level of organizational competitiveness, which supports the decision-making process. This manuscript purposes a computational tool that graphically presents the level of competitiveness of PV power plants units based on performance indicators. This tool was developed by using the Key Performance Indicators (KPIs concept, which represents a set of measures focusing on the most critical aspects for the success of the organizations. The KPIs encompass four Fundamental Viewpoints (FV: Strategic Alliances, Solar Energy Monitoring, Management and Strategic Processes, and Power Generation Innovations. These four FVs were deployed on 26 Critical Success Factors (CSFs and 39 KPIs. Sequentially, the tool was applied in four solar generation plants, where three presented an organizational competitiveness global level “potentially competitive”. The proposed computational tool allows managers to assess the degree of organization competitiveness as well as aid in prospecting of future scenarios and decision-making.
Retail competition as the cornerstone of a competitive electricity marketplace was the subject of the seventh in the series of policy discussion papers developed at the Market Design Conference. Concern was expressed that because of the complexities involved in market design and technical implementation, the retail competition may lag behind other elements of the implementation of the new market design. A variety of key issues were debated, including the role of physical versus financial contracts, the form of retail competition and financial settlement systems in the short term, the requirement to separate 'competitive' (metering, billing, maintenance, consumer education) from non-competitive' (the transmission wires) services and the role of municipal electric utilities. It was agreed that the IMO should play an important role in defining and enforcing the separation of services, and that as a general rule, the development of policy in this area should be guided by the principle of maximizing the potential for competition
Full Text Available The purpose of this study is to analyze SME clusters competitiveness based on 9 factors. Those 9 factors of competitiveness are raw materials, labour, product prices, markets, technology, investment, management, and economic and socio-cultural base. The development of SMEs is a part of long-term economic development to attain a balanced economic structure. Nevertheless, the gaps of resource potential, infrastructure and market lead to disproportional dispersion of location as well as industrial lethargy. Regional economic development is defined as a process where the Academic, Business, Community and Government (ABCG manage the existing resources and establish an interrelationship among them to run the economy at regional level. There are seven clusters of SMEs in Sragen regency including featured products of the region. This study investigated the competitiveness of three clusters of SMEs, namely batik cluster, convection cluster and furniture cluster based on the Criteria of Regional Superior Products (PUD. The expected objectives of this study were to determine the contribution of batik fashion, convection and furniture clusters to GRDP, poverty, and development of cluster area/location as well as to provide inputs for the prevailing policy related to the improvement of competitiveness of SMEs clusters. The inputs include the recommendation for the local government to prioritize the policy for the development of batik cluster competitiveness particularly on labor, raw material, management and pricing. In convection cluster, the priority of development policy should be preoccupied on technology, market, investment and economic base. Meanwhile, the socio-cultural aspects must be prioritized for the development of furniture cluster competitiveness. Data was analyzed by using Analytic Hierarchy Process (AHP and Topsis Analysis.
Full Text Available The purpose of this study was to develop the new wheel-chair which had the function to drive straight by one-hand operation. To perform this purpose, the driving force transmission axis (DFTA which had transmitted the driving force from the one side of wheel to another side of that was developed. The wheel-chair could drive straight by one-hand operation by the DFTA. The large torque, however, was generated in the DFTA, because the DFTA transmitted the driving force from the one side of wheel to another side by the axis of small diameter. Furthermore, the shear stress in the DFTA generated by this torque would lead to the DFTA break. The shear stress in the DFTA was calculated to examine the axial strength and durability. On the DETA of the wheelchair, the maximum shear stress calculated from the torque in driving was 39.53 MP and this was defined as the standard of the demand specifications as a strength and durability of the DFTA.
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.
Oh, HunSeok; Seo, DongIn; Kim, JuSeuk; Yoo, SangOk; Seong, HeeChang
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…
Oh, Hunseok; Choi, Yeseul; Choi, Myungweon
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…
Owens, Taya L.; Lane, Jason E.
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.
Stoicovici, D.; Bănică, M.; Ungureanu, M.; Stoicovici, M.
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.
Phadke, Amol Anant
This dissertation explores issues related to competition in and regulation of electricity sectors in developing countries on the backdrop of fundamental reforms in their electricity sectors. In most cases, electricity sector reforms promoted privatization based on the rationale that it will lower prices and improve quality. In Chapter 2, I analyze this rationale by examining the stated capital cost of independent (private) power producer's (IPPs) power projects in eight developing countries and find that the stated capital cost of projects selected via competitive bidding is on an average about 40% to 60% lower than that of the projects selected via negotiations, which, I argue, represents the extent to which the costs of negotiated projects are overstated. My results indicate that the policy of promoting private sector without an adequate focus on improving competition or regulation has not worked in most cases in terms of getting competitively priced private sector projects. Given the importance of facilitating effective competition or regulation, In Chapter 3, I examine the challenges and opportunities of establishing a competitive wholesale electricity market in a developing country context. I model a potential wholesale electricity market in Maharashtra (MH) state, India and find that it would be robustly competitive even in a situation of up-to five percent of supply shortage, when opportunities for demand response are combined with policies such as divestiture and requiring long-term contracts. My results indicate that with appropriate policies, some developing countries could establish competitive wholesale electricity markets. In Chapter 4, I focus on the demand side and analyze the cost effectiveness of improving end-use efficiency in an electricity sector with subsidized tariffs and electricity shortages and show that they offer the least expensive way of reducing shortages in Maharashtra State, India. In Chapter 5, I examine the costs of reducing carbon
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.
In developing countries, many people suffer from diseases for which there are no drugs or for which drugs exist that they cannot afford because they are too expensive. The advent of genomics has sparked the idea that new drugs can be more easily developed and that genomics thus could lessen the
Butenko Nataliia V.
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
Full Text Available Personalized medicine aims is to supply the proper drug to the proper patient within the right dose. Pharmacogenomics (PGx is to recognize genetic variants that may influence drug efficacy and toxicity. All things considered, the fields cover a wide area, including basic drug discovery researches, the genetic origin of pharmacokinetics and pharmacodynamics, novel drug improvement, patient genetic assessment and clinical patient administration. At last, the objective of Pharmacogenomics is to anticipate a patient’s genetic response to a particular drug as a way of presenting the best possible medical treatment. By predicting the drug response of an individual, it will be possible to increase the success of therapies and decrease the incidence of adverse side effect.
The role of radiolabelled compounds in the development of new drugs is discussed, with particular reference to their use in toxicological, metabolic and pharmacokinetic studies for the pre-clinical safety evaluation of new drugs. (U.K.)
Okolnishnikova Irina Yurievna
Full Text Available The aim of the research is the development of theoretical approaches to the study of the essence and structure of the resource potential of entrepreneurship in the context of the development strategy of the competitive advantages in business structure. As the research methodology the complex of principles and tools of system and axiological approaches is used. According to the results of the conducted research, possessing the scientific novelty, the conceptual apparatus is clarified and the author's definition of the resource potential of the enterprise is given, a model of the resource potential structure in commercial organization is analyzed and the mechanism of strategy formation for sustainable competitive advantages provision of the organization on the basis of the effective use of its resource potential is identified. Area of application of the research results is the control of competitiveness in general and resource potential of entrepreneurial structures, in particular at all levels of the socio-economic system of society.
Full Text Available In the article the problem of advancing the international competitiveness of industry has been highlighted in the context of the impact on getting out the crises in the country and forming preconditions for economic growth. The study is based on an empirical basis of metallurgical industries of Ukraine, which has traditionally focused largely on international markets. The advancing international competitiveness of these enterprises is particularly topical and important for getting over the crisis and forming a trajectory of economic development of the country. The system of the factors has been represented and analysed, the priorities for advancing the international competitiveness of metallurgical industryJSC "Zaporizhstar.Recommendations to improve the competitiveness of the analysed enterprise have been formulated and common priorities for improving the international competitiveness of steel companies determining the possibility of positive impact on getting over the crisis and economic development at the level of companies, as well as at the level of Ukraine’s economy have been identified.
L. A. Tsvetkova
The analysis of prospects of introduction of the developments related to blokcheyn in the world and in Russia has been made. Key investors and beneficiaries in the development of blockchain technologies were identified. High competitiveness of Russian developments, unique staffing, and favorable climatic conditions for the development of blockade technologies in the Russian Federation were noted. The patent activity in the world has been analyzed and the place of Russia on the patent landscap...
Liu, Yao; Galárraga, Omar
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.
Munck, Christian; Gumpert, Heidi; Nilsson Wallin, Annika
the genomes of all evolved E. coli lineages, we identified the mutational events that drive the differences in drug resistance levels and found that the degree of resistance development against drug combinations can be understood in terms of collateral sensitivity and resistance that occurred during...... adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance......Resistance arises quickly during chemotherapeutic selection and is particularly problematic during long-term treatment regimens such as those for tuberculosis, HIV infections, or cancer. Although drug combination therapy reduces the evolution of drug resistance, drug pairs vary in their ability...
More than half of the drugs approved to treat cancer come from a natural product or a natural product prototype. Scientists in NCI-Frederick's Natural Products Branch are exploring ways to harness chemicals produced by marine invertebrates, other animals, plants, and microbes for cancer drug discovery.
Hansen, E H; Launsø, Laila
. Drugs offer a standard solution to health problems independent of the individuals' social life. Thus drugs become a tool which function in agreement with the disintegrated and achievement-orientated approach to disease as it is organized today. In general the statements in this article are not limited...
Anderson, Neal; Gernaey, Krist V; Jamison, Timothy F; Kircher, Manfred; Wiles, Charlotte; Leadbeater, Nicholas E; Sandford, Graham; Richardson, Paul
Against a backdrop of a struggling economic and regulatory climate, pharmaceutical companies have recently been forced to develop new ways to provide more efficient technology to meet the demands of a competitive drug industry. This issue, coupled with an increase in patent legislation and a rising generics market, makes these themes common issues in the growth of drug development. As a consequence, the importance of process chemistry and scale-up has never been more under the spotlight. Future Medicinal Chemistry wishes to share the thoughts and opinions of a variety of experts from this field, discussing issues concerning the use of flow chemistry to optimize drug development, the potential regulatory and environmental challenges faced with this, and whether the academic and industrial sectors could benefit from a more harmonized system relevant to process chemistry.
Full Text Available While the oceans cover more than 70% of the Earth’s surface, marine derived microbial natural products have been largely unexplored. The marine environment is a habitat for many unique microorganisms, which produce biologically active compounds (“bioactives” to adapt to particular environmental conditions. For example, marine surface associated microorganisms have proven to be a rich source for novel bioactives because of the necessity to evolve allelochemicals capable of protecting the producer from the fierce competition that exists between microorganisms on the surfaces of marine eukaryotes. Chemically driven interactions are also important for the establishment of cross-relationships between microbes and their eukaryotic hosts, in which organisms producing antimicrobial compounds (“antimicrobials”, may protect the host surface against over colonisation in return for a nutrient rich environment. As is the case for bioactive discovery in general, progress in the detection and characterization of marine microbial bioactives has been limited by a number of obstacles, such as unsuitable culture conditions, laborious purification processes, and a lack of de-replication. However many of these limitations are now being overcome due to improved microbial cultivation techniques, microbial (meta- genomic analysis and novel sensitive analytical tools for structural elucidation. Here we discuss how these technical advances, together with a better understanding of microbial and chemical ecology, will inevitably translate into an increase in the discovery and development of novel drugs from marine microbial sources in the future.
Full Text Available A thorough analysis of competitive factors of functional foods has made it possible to develop an algorithm for assessing the competitive factors of functional food products, with respect to their essential consumer features — quality, safety and functionality. Questionnaires filled in by experts and the published results of surveys of consumers from different countries were used to help select the essential consumer features in functional foods. A “desirability of consumer features” model triangle, based on functional bread and bakery products, was constructed with the use of the Harrington function.
This fascinating new book dissects, from a Competition law perspective, how Research and Development collaborations operate under both US and EU antitrust law. Analyzing the evolution of this innovation landscape from the 1970s to the present day, Blomqvist details the modifications and amendments...... 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...
Benahji Sfaxi Hend
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. .
Full Text Available The article discusses first the differences between market economic models, socialist or planned economies, and economies controlled by monopolies or cartels, to make the case for competition supervision. Subsequently it argues for a broad approach to competition super-vision - beyond a narrow view of antitrust law. The second part of the paper discusses monopoly or dominant position and the criteria to measure them. It reviews the reasons for merger control as a preventive step against monopoly or dominant position. Finally it discusses the issues related to collusion in the form of cartels and how to detect them. The third part of the paper focuses on the best ways for developing and transition countries to introduce or reinforce comprehensive competition supervision: Functioning institutions and how they have to be empowered and structured; priorities to be set; how competition oversight has to be embedded in the legal system, including court review; and why effective enforcement is so important and how it can be promoted. In an annex** there are links to some 75 countries which have newly introduced competition laws in the past 25 years and their legislative materials. Finally, there are links to another 30 countries which have substantially revised their legislative bases in the same time frame.
... Commercial Access; Development of Competition and Diversity in Video Programming Distribution and Carriage... contained in the Second Report and Order, FCC 11-119, pertaining to carriage of video programming vendors by multichannel video programming distributors (program carriage rules). This notice is consistent with the Secord...
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…
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…
Ulrich, Schulze-Konig Tim
Full text: Radiocarbon has a huge potential as a tracer for metabolism studies in humans. By using Accelerator Mass Spectrometry (AMS) for its detection, a unique sensitivity is reached reducing required radiation doses to a negligible level. Until recently, a widespread use of AMS in biomedical research was impeded by the high complexity of the instrument, time-consuming sample preparation, and a limited availability of measurement capacity. Over the last few years, tremendous progress has been achieved in the reduction of size and complexity of AMS instruments. It allowed designing a compact AMS system, dubbed BioMICADAS to address the needs of biomedical users. For more than two years, this system is in successful operation at a commercial service provider for the pharmaceutical industry. A further drastic simplification of radiocarbon mass spectrometers seems possible and could establish a regular usage of this technology in drug development. However, to reach this goal a better integration of AMS into the workflow of bioanalytical laboratories will be necessary. For this purpose, CO 2 accepting ion sources may be a key, since they enable an almost automated sample preparation. The status of radiocarbon AMS in biomedical research and its perspective will be discussed
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.
This study was conducted to theoretically develop and empirically test a structural equation model of tourism destination competitiveness from the tourism stakeholders'perspective. The proposed hypotheses that attempted to identify the structural relationships among the five constructs in the model were examined through a series of analyses in LISREL: 1) perceived tourism development impacts, 2) environmental attitudes, 3) place attachment, 4) development preferences about destination attract...
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.
Keefer, Philip; Loayza, Norman V.; Soares, Rodrigo R.
This paper reviews the unintended consequences of the war on drugs, particularly for developing countries, and weighs them against the evidence regarding the efficacy of prohibition to curb drug use and trade. It reviews the available evidence and presents new results that indicate that prohibition has limited effects on drug prevalence and prices, most likely indicating a combination of i...
Richter, Wolf S.
The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)
De Mello Sant Ana, Paulo Henrique; De Martino Jannuzzi, Gilberto; Valdir Bajay, Sergio
For the last 20 years, countless countries have been carrying out structural reforms in the natural gas industry, trying to achieve efficiency and economic rationality with the introduction of competition. The objective of the paper is to present an approach to the development of competition and infrastructure of the Brazilian natural gas industry. This approach is based on a market projection to 2011, on the international experience and on the characteristics of the Brazilian market, infrastructure and regulatory framework. Possible impacts of the proposed measures are also provided. According to the market projection carried out in this paper, in 2011 there will be a possible surplus of natural gas in the country, which includes a dependence diminishing of the Bolivian gas supply. This gas surplus, allied to an upcoming Gas Law and the trade liberalization in the states of Sao Paulo and Rio de Janeiro, can stimulate the development of competition, if some changes that proposed in this paper are made in the current Gas Bills. The approach proposed herein seeks to stimulate non-discriminatory open access, focused on information transparency and tariff regulation to help the development of infrastructure and competition. (author)
Full Text Available Today, in the era of knowledge economy a competitive advantage is based on technological development and innovation, as well as the exploitation of potential opportunities and possibilities for whose implementation knowledge is necessary. Constant investment in human capital increases productivity, employment and receives a direct source of innovation and longterm competitiveness. Human resources and their knowledge are the key to success for the economy and businesses, while incompetent workforce is one of the most important brake in their business. Development of competition in the domestic and international market, it became imperative for the development of a modern economy. In fact, knowledge is the capitalization of innovation through the creation of new products, services, processes, or labels, but that has no value and significance, if is not commercialized in the market. The aim of this paper is to show the level of competitiveness of the Serbian economy, measurable changes that occur in this direction and degree of easiness of doing business in Serbia, which should contribute to an increase in labor productivity.
Park, Kevin; Williams, Dominic P.; Naisbitt, Dean J.; Kitteringham, Neil R.; Pirmohamed, Munir
Adverse drug reactions (ADRs) are a significant human health problem. Any organ system can be affected, including the liver, skin and kidney. Drug-induced liver injury is the most frequent reason for the withdrawal of an approved drug from the market, and it also accounts for up to 50% of cases of acute liver failure. The clinical picture is often diverse, even for the same drug. Mild, asymptomatic effects occur at a relatively high frequency with a number of drugs. Idiosyncratic toxicity is rare but potentially life-threatening. Many serious ADRs that occur in man are unpredictable from routine pathology and clinical chemistry in laboratory animals and are therefore poorly understood. The drug metabolist can determine the propensity of a novel chemical entity to either accumulate in the hepatocyte or undergo bioactivation in numerous model systems, from expressed enzymes, genetically engineered cells to whole animals. Bioactivation can be measured using trapping experiments with model nucleophiles or by measurement of non-specific covalent binding. The chemistry of the process is defined and the medicinal chemist can address the issue by seeking a metabolically stable pharmacophore to replace the potential toxicophore. However, we require a more fundamental understanding of the role of drug chemistry and biochemistry in ADRs. This requires knowledge of the ultimate toxin, signalling in cell defense and the sequence of molecular events, which ultimately lead to cell and tissue damage. It is imperative that such studies have a clinical level, but then translated into laboratory-based molecular studies. This will provide a deeper understanding of potential toxicophores for drug design and define candidate genes for pharmacogenomic approaches to individualized medicines
Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development. [BMB Reports 2017; 50(3): 111-116].
Nadezhda Yakovlevna Kalyuzhnova
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.
Reichert, Janice M; Milne, Christopher-Paul
Recently, well-publicized reports by Public Citizen and the Joint Economic Committee (JEC) of the US Congress questioned the role of the drug industry in the discovery and development of therapeutically important drugs. To gain a better understanding of the relative roles of the public and private sectors in pharmaceutic innovation, the Tufts Center for the Study of Drug Development evaluated the underlying National Institutes of Health (NIH) and academic research cited in the Public Citizen and JEC reports and performed its own assessment of the relationship between the private and public sectors in drug discovery and development of 21 "impact" drugs. We found that, ultimately, any attempt to measure the relative contribution of the public and private sectors to the research and development (R&D) of therapeutically important drugs by output alone, such as counting publications or even product approvals, is flawed. Several key factors (eg, degree of uncertainty, expected market value, potential social benefit) affect investment decisions and determine whether public or private sector funds, or both, are most appropriate. Because of the competitiveness and complexity of today's R&D environment, both sectors are increasingly challenged to show returns on their investment and the traditional boundaries separating the roles of the private and public research spheres have become increasingly blurred. What remains clear, however, is that the process still starts with good science and ends with good medicine.
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.
Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor
During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.
Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.
Rodriguez E, Wilken; Bejarano B, Hernan; Villazon A, Hernando
The new materials have a growing importance in the national development, and most of the industrialized countries are investing big supreme in the development of these, due to their great strategic paper in the global economic interaction. The present article seeks to give a general vision of the participation of these materials in the world economy as alternative factor of competition, keeping primarily in mind the conservation of the environment and the permanent search of the total quality
Full Text Available This paper deals with the essential features determining the role of innovation in developing economies by examining the structure of innovation measures. The economic growth and competitiveness of developing economies are powerfully connected to its innovation status. The purpose of this paper is to examine the significance of innovation in driving economic growth per capita and competitiveness in selected developing economies. In order to determine the interconnection among the variables of innovation, competitiveness, and growth, assorted methodological measurement instruments have been applied. The data were collected from both primary and secondary sources. The results suggest the importance of specific innovation dimensions for prospective economic growth in developing economies. The identical measures responsible for fragile innovation are associated to the low composite measures of innovation accomplishment. This demonstrates the enormous disparity concentrated in every innovation aspect over time, specifically in innovation output and enterprise performances between the developing economies and the EU-28 average measures. The research results indicate the usage of appropriate economic instruments in diminishing the problems that developing economies are currently dealing with.
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
Baumrind, D; Moselle, K A
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.
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
It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.
Shelomentsev, A. G.; Medvedev, M. A.; Isaichik, K. F.; Dyomina, M. I.; Berg, I. A.; Kit, M.
This paper discusses comparative analysis of trajectories in the development of participating countries of the Eurasian Economic Union (EAEC) in a two-dimensional phase space. The coordinates in the space is represented by the value of a dynamic variable that is a key indicator of the country's development, and the rate of its relative growth. This allows for construction of a ternary classification diagram describing competitive behavior strategies of countries in question. The comparative analysis was run for two primary factors: the size of investment in the main capital and R&D spendings. The authors carried out analysis and identification of competitive strategies for the behavior of the EAEC countries, as well as he proposed conclusions and recommendations on improving the policy of economic development.
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.
Shkolnyi Oleksandr O.
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.
Full Text Available At the end of the 20th century, the economic structure was changed fundamentally in some countries. It was mostly related to the growth of global competition. One of the consequences of this process was the decline in manufacturing production in developed countries and in the post-Soviet countries. The purpose of this article is to define the meaning and consequences of the decline in manufacturing production in developed countries and in post-Soviet countries on the example of Ukraine. Methodology. This study is based on some general theoretical approaches such as analysis and synthesis, induction and deduction, etc. Also, statistical analysis was used for discovering some economic trends. Structural analysis was helpful for examining shifts in economic structure. Correlation between different facts, which is crucial for the understanding of the transformation of manufacturing, was identified by applying the systems approach. The aim of the article is to reveal the impact of global competition on the state of manufacturing and to define the manufacturing development trend. Results of this research showed that the decline in the rate of profit causes the transformation of economic structure. Global competition made the production of some goods in developed countries less profitable due to the relatively high costs. The ability to transfer labour-intensive production to developing countries transformed economic structure in developed countries. It was the reason for a sharp decline in manufacturing production, which caused some economic and social problems. Post-Soviet countries had serious economic and social problems too. Liberalization of trade made these countries face with global competition. This competition revealed extremely weak competitive positions of a great range of products. There was a massive decline in manufacturing production in Ukraine. This study proves that the transformation of manufacturing is far from the end. First of all
Kooistra, Albert J.; Volkamer, Andrea
Kinases are among the most studied drug targets in industry and academia, due to their involvement in a majority of cellular processes and, upon dysregulation, in a variety of diseases including cancer, inflammation, and autoimmune disorders. The high interest in this druggable protein family
Full Text Available Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.
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.
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.
The development of renewable energy in markets with competition at wholesale and retail levels poses challenges not present in areas served by vertically-integrated utilities. The intermittent nature of some renewable energy resources impact reliability, operations, and market prices, in turn affecting all market participants. Meeting renewable energy goals may require coordination among many market players. These challenges may be successfully overcome by imposing goals, establishing trading mechanisms, and implementing operational changes in competitive markets. This strategy has contributed to Texas' leadership among all US states in non-hydro renewable energy production. While Texas has been largely successful in accommodating over 9000 MW of wind power capacity, this extensive reliance upon wind power has also created numerous problems. Higher levels of operating reserves must now be procured. Market prices often go negative in the proximity of wind farms. Inaccurate wind forecasts have led to reliability problems. Five billion dollars in transmission investment will be necessary to facilitate further wind farm projects. Despite these costs, wind power is generally viewed as a net benefit. - Research Highlights: → Texas rapidly emerged as a leader in renewable energy development. → This state's experiences demonstrate that the right combination of policies to lead to rapid renewable energy development in a region with a very competitive electricity market. → Wind power development has lead to various operational challenges.
Di Jun An
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.
Trouiller P; Olliaro P; Torreele E;. Orbinski J; Laing R and Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet. 2002; 359: 2188–94. 9. Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public-private partnerships.
Murphy, Robert F.
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
Full Text Available The success of the economy of each country is determined by its innovation development. The purpose of the paper is to investigate the essence of innovation potential and its role in providing the national economy’s competitiveness under the conditions of technological changes on the example of the European Union developed countries. The subject of research is the innovation potential of Austria and Germany. Methodology. The study is based on a comparative analysis of approaches to determination and evaluation of innovation potential in specialized economic literature. Analysis and synthesis and the system approach were used to outline the entity of innovation potential, to explore and structure its elements in the context of providing the national economy’s competitiveness. The quality and quantity analysis were used to discover general characteristics of the EU countries’ innovation development, special aspects of the national innovation systems of Austria and Germany, the role of innovation potential in the national economies competitiveness of these countries. The method of mathematical modelling in economics, in particular, regression analysis based on annual data for the period from 1995 to 2015, was applied to assess the impact of innovation potential on the Austria and Germany competitiveness. The absolute value of GDP and the share of export of goods and services in GDP are used as a dependent variable. Elements that characterize the country’s innovation potential were used as independent variables: the share of researchers in R&D of total population, the share of labour force with advanced education of total working-age population with advanced education, expenditure on tertiary education as a percentage of GDP, R&D expenditure as a percentage of GDP, patent applications as a percentage of total population. Results of the survey of theoretical works showed that the most multifaceted and comprehensive approach to determining the
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.
New drug development can be made by providing products of higher "selectivity for the drug" for medical treatment. There are two ways for the approach to get higher "selectivity of drug": 1) discovery of new compounds with high selectivity of drug; 2) innovation of new drug administration, that is new formulation and/or method with high selectivity of drug by integration and harmonization of various hard/soft technologies. An extensive increase of biological information and advancement of surrounding science and technology may modify the situation as the latter overcomes the former in the 21 century. As the science and technology in the 21 century is said to be formed on "3H", that is, 1. hybrid; 2. hi-quality; 3. husbandry, the new drug development by innovative drug administration is exactly based on the science and technology of 3H. Its characteristic points are interdisciplinary/interfusion, international, of philosophy/ethics, and systems of hard/hard/heart. From these points of view, not only the advance of unit technology but also a revolution in thinking way should be "must" subjects. To organize this type of research well, a total research activity such as ROR (research on research) might take an important and efficient role. Here the key words are the "Optimization technology" and "Change in Pharmaceutical Fields." As some examples of new drug innovation, our trials on several topical mucosal adhesive dosage forms and parenteral administration of peptide drugs such as insulin and erythropoietin will be described.
Marjanova, Tamara Jovanov; Sofijanova, Elenica; Davcev, Ljupco; Temjanovski, Riste
The main purpose of this paper is to verify the significance of the implementation of competition orientation (CO) as a part of market orientation for the financial performance of the entrepreneurial small and medium – sized companies in a developing economy. The objectives are: 1. To measure the level of each of the variables of the scale (CO 1: The management continuously analyses the strengths and weaknesses of the competitors; CO 2: We regularly use information about our competitors in st...
Ramona Gruescu; Roxana Nanu; Anca Tanasie
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...
Heinemann, Fabian; Huber, Torsten; Meisel, Christian; Bundschus, Markus; Leser, Ulf
The development of cancer drugs is time-consuming and expensive. In particular, failures in late-stage clinical trials are a major cost driver for pharmaceutical companies. This puts a high demand on methods that provide insights into the success chances of new potential medicines. In this study, we systematically analyze publication patterns emerging along the drug discovery process of targeted cancer therapies, starting from basic research to drug approval - or failure. We find clear differences in the patterns of approved drugs compared with those that failed in Phase II/III. Feeding these features into a machine learning classifier allows us to predict the approval or failure of a targeted cancer drug significantly better than educated guessing. We believe that these findings could lead to novel measures for supporting decision making in drug development. Copyright © 2016 Elsevier Ltd. All rights reserved.
Cheng, Alice; Xie, Zhi
While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.
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.
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.
Ирина Юрьевна Окольнишникова
Full Text Available The aim of the research is the development of theoretical approaches to the study of the essence and structure of the resource potential of entrepreneurship in the context of the development strategy of the competitive advantages in business structure.As the research methodology the complex of principles and tools of system and axiological approaches is used.According to the results of the conducted research, possessing the scientific novelty, the conceptual apparatus is clarified and the author's definition of the resource potential of the enterprise is given, a model of the resource potential structure in commercial organization is analyzed and the mechanism of strategy formation for sustainable competitive advantages provision of the organization on the basis of the effective use of its resource potential is identified.Area of application of the research results is the control of competitiveness in general and resource potential of entrepreneurial structures, in particular at all levels of the socio-economic system of society.DOI: http://dx.doi.org/10.12731/2218-7405-2013-2-39
Sheppard, Jeremy M; Nimphius, Sophia; Haff, Greg G; Tran, Tai T; Spiteri, Tania; Brooks, Hedda; Slater, Gary; Newton, Robert U
Appropriate and valid testing protocols for evaluating the physical performances of surfing athletes are not well refined. The purpose of this project was to develop, refine, and evaluate a testing protocol for use with elite surfers, including measures of anthropometry, strength and power, and endurance. After pilot testing and consultation with athletes, coaches, and sport scientists, a specific suite of tests was developed. Forty-four competitive junior surfers (16.2 ± 1.3 y, 166.3 ± 7.3 cm, 57.9 ± 8.5 kg) participated in this study involving a within-day repeated-measures analysis, using an elite junior group of 22 international competitors (EJG), to establish reliability of the measures. To reflect validity of the testing measures, a comparison of performance results was then undertaken between the EJG and an age-matched competitive junior group of 22 nationally competitive surfers (CJG). Percent typical error of measurement (%TEM) for primary variables gained from the assessments ranged from 1.1% to 3.0%, with intraclass correlation coefficients ranging from .96 to .99. One-way analysis of variance revealed that the EJG had lower skinfolds (P = .005, d = 0.9) than the CJG, despite no difference in stature (P = .102) or body mass (P = .827). The EJG were faster in 15-m sprint-paddle velocity (P < .001, d = 1.3) and had higher lower-body isometric peak force (P = .04, d = 0.7) and superior endurance-paddling velocity (P = .008, d = 0.9). The relatively low %TEM of these tests in this population allows for high sensitivity to detect change. The results of this study suggest that competitively superior junior surfers are leaner and possess superior strength, paddling power, and paddling endurance.
Song, Yan; Dhodda, Raj; Zhang, Jun; Sydor, Jens
In the recent past, we have seen an increase in the outsourcing of bioanalysis in pharmaceutical companies in support of their drug development pipeline. This trend is largely driven by the effort to reduce internal cost, especially in support of late-stage pipeline assets where established bioanalytical assays are used to analyze a large volume of samples. This article will highlight our perspective of how bioanalytical laboratories within pharmaceutical companies can be developed into the best partner in the advancement of drug development pipelines with high-quality support at competitive cost.
Mello, Juliana da Fonseca Rezende E; Gomes, Renan Augusto; Vital-Fujii, Drielli Gomes; Ferreira, Glaucio Monteiro; Trossini, Gustavo Henrique Goulart
Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area. In this article, we discuss the basic Fragment-Based Drug Discovery process, brief successful ideas of general applications and show a landscape of its use in NDs, encouraging the implementation of this strategy as an interesting way to optimize the development of new drugs to NDs. © 2017 John Wiley & Sons A/S.
Pulley, Jill M; Shirey-Rice, Jana K; Lavieri, Robert R; Jerome, Rebecca N; Zaleski, Nicole M; Aronoff, David M; Bastarache, Lisa; Niu, Xinnan; Holroyd, Kenneth J; Roden, Dan M; Skaar, Eric P; Niswender, Colleen M; Marnett, Lawrence J; Lindsley, Craig W; Ekstrom, Leeland B; Bentley, Alan R; Bernard, Gordon R; Hong, Charles C; Denny, Joshua C
The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics.
Regnstrom, Karin; Burgess, Diane J
Recent advances in genomic research have provided the basis for new insights into the importance of genetic and genomic markers during the different stages of drug development. A new field of research, pharmacogenomics, which studies the relationship between drug effects and the genome, has emerged. Structural pharmacogenomics maps the complete DNA sequences of whole genomes (genotypes) including individual variations, and functional pharmacogenomics assesses the expression levels of thousands of genes in one single experiment. Together, these two areas of pharmacogenomics have generated massive databases, which have become a challenge for the research field of informatics and have fostered a new branch of research, bioinformatics. If skillfully used, the databases generated by pharmacogenomics together with data mining on the Web promise to improve the drug development process in a variety of areas: identification of drug targets, evaluation of toxicity, classification of diseases, evaluation of formulations, assessment of drug response and treatment, post-marketing applications, and development of personalized medicines.
Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng
Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.
Thomas, N.; Rades, T.; Müllertz, A.
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...
This synthesis reports a comprehensive study (October 2013) for ADEME, the French office for energy management and sustainable development, which presents an assessment of the present structure of the solar thermal sector in France (and overseas territories): main actors, Research and Development activities, qualification and certification of equipment, distribution, design and education aspects, installation, etc. In the second and third parts of the report, the demand and the perception of the offer by clients are assessed, followed by a presentation of the sector cost structure and a comparison of various competitive systems. In the last part of the synthesis, a diagnostic of the sector is exposed, with propositions and recommendations
Alemayehu, Demissie; Berger, Marc L
The explosion of data sources, accompanied by the evolution of technology and analytical techniques, has created considerable challenges and opportunities for drug development and healthcare resource utilization. We present a systematic overview these phenomena, and suggest measures to be taken for effective integration of the new developments in the traditional medical research paradigm and health policy decision making. Special attention is paid to pertinent issues in emerging areas, including rare disease drug development, personalized medicine, Comparative Effectiveness Research, and privacy and confidentiality concerns.
Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...
Dragojlovic, Nick; Lynd, Larry D
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. Copyright © 2014 Elsevier Ltd. All rights reserved.
O. V. Shatunova
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
Sieglinde Kindl da Cunha
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.
Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M
Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.
Full Text Available Mesoporous silica nanoparticles (MSNs have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV and poorly permeable (BCS class III, IV drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI surface functionalized MSNs, as well as drug-free and drug-loaded MSN–PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.
Yun, Jian; Shang, Song-Chao; Wei, Xiao-Dan; Liu, Shuang; Li, Zhi-Jie
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.
Ashford C. Chea
The paper looks at the development experience of East Asia and draws lessons for Sub-Saharan Africa in building global competitiveness. It starts with a historical perspective of both regions’ developmental trajectories. This is followed by an analysis of the causes of East Asia’s superior economic performance and development and SSA underdevelopment. The article also draws policy lessons from East Asia development strategies for SSA global competitiveness. The paper ends with a presentation ...
Fakunle, Eyitayo S; Loring, Jeanne F
Genetic variation is an identified factor underlying drug efficacy and toxicity, and adverse drug reactions, such as liver toxicity, are the primary reasons for post-marketing drug failure. Genetic predisposition to toxicity might be detected early in the drug development pipeline by introducing cell-based assays that reflect the genetic and ethnic variation of the expected treatment population. One challenge for this approach is obtaining a collection of suitable cell lines derived from ethnically diverse populations. Induced pluripotent stem cells (iPSCs) seem ideal for this purpose. They can be obtained from any individual, can be differentiated into multiple relevant cell types, and their self-renewal capability makes it possible to generate large quantities of quality-controlled cell types. Here, we discuss the benefits and challenges of using iPSCs to introduce genetic diversity into the drug development process. Copyright © 2012 Elsevier Ltd. All rights reserved.
Tomioka, Haruaki; Namba, Kenji
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are
developed, tested and used. Standardised diagrams for the visualisation of results from the assessment have been established, and different diagrams have been developed for different scenarios. For the visualisation of results from single and/or multiple similar trial assessments, tornado-like diagrams were...
Bélisle Pipon, Jean-Christophe
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.
Kumar, Pranay; Sarkar, Prabhajit Kumar
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.
Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam
Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.
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.
Jones, L. III.
This paper examines the current level of competition in the electric industry in the context of the history of the industry and the development of electric markets in other counties. The topics of the paper include competition in the history of the American electric industry, the current state of competition, the competitive situation in Texas, competition in other electric markets, and competitive changes in the US market
Full Text Available In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release. In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture levels (29, 57, 198 μL cm−2 were evaluated. The synthetic skin simulators were collected after 1, 2, 3, 4, 6, and 24 hours and extracted with pH 1.0 hydrochloric acid solution. The drug concentrations in the extractions were measured by isocratic reverse phase high-pressure liquid chromatography. The results showed that, with the increasing moisture level on the synthetic skin simulator, the drug release rate increased. In comparison with the conventional USP method, the drug release results performed by the new method were in more correlation to the release rate claimed in the product label. This new method could help to differentiate the drug release rates among assorted formulations of transdermal drug delivery systems in the early stage of development.
The electric utility industry is in the beginning throes of a transformation from a cost-based regulated structure to a more market based less regulated system. Traditional unit commitment and economic dispatch methodologies can continue to provide reliable least-cost solutions, providing they are modified to accommodate a larger sphere of market participants. This paper offers a method for an entity such as an Independent System Operator (ISO) to solicit and evaluate bids for developing a spot priced electric market by replicating existing utility practices that are effective and efficient, while creating an open and equitable competitive marketplace for electricity
Siddiqui, Ruqaiyyah; Aqeel, Yousuf; Khan, Naveed Ahmed
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. O...
Danilo Icaza Ortiz
Full Text Available This paper is a review of the competition regime works of various authors, published under the auspices of the University of the Hemispheres and the Corporation for Studies and Publications. Analyzes the structure, the general concepts, case law taken for development. Includes comments on the usefulness of this work for the study of competition law and the contribution to the lawyers who want to practice in this branch of economic law.
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
A. G. Mokronosov
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.
The current external environment of information work has undergone profound changes. The world competition in Military fields, the development of national economy and the applications of high-technologies put forward higher requirements to intelligence work. Under the environment of global information integration, 'eyes and ears' roles of nuclear scientific and technical information will be more highlighted. In this context, we believe that the way of nuclear sci-tech information development should be focused on comprehensive research and be based on the building of information resources and advanced information technology methods, forming an integrated service system with capabilities of rapid resources, decision support, information assurance and sustainable development. The goal of nuclear sci-tech information development should be to serve the development of nuclear power and the popularization and application of nuclear technology in the fields of national economy, to implement the strategy of 'integrated intelligence support', to ensure the formation of rapid response capability, to enhance capabilities of decision support and science and technology development guidance, to build digital information resources and to constantly promote the research on network collaboration. This paper analyzes the characteristics of nuclear sci-tech information under new competitive environment, describes the ideas and goals of its development and proposes the way to achieve these goals. In order to provide the information support and service with the characteristics of rapid response, high quality and high efficiency, the paper also puts forward that under the new environment, we should optimize the service system, extend service functions, transform service mode, speed up the transformation on intelligence work, adjust and optimize business content and structure, promote business process re-engineering, and pay equal attention to 'ensuring demands' and 'guiding the future
Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P; Woolf, Clifford J
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.
Talmaciu Ana Maria
Full Text Available In the new innovation economy, national competitiveness is an expression of the quality of the human capital and of the capacity to attract and retain the talent. In this paper, we propose to verify the link between the national competitiveness and the human capital, measured by the public expenditure on tertiary education and by the public expenditure on research and development. The research methodology uses the Panel Data method for Central and Eastern European countries by analyzing data on competitiveness scores in the Europe 2020 Report 2014, the Human Development Index 2015, the Global Competitiveness Report 2016 and those on public expenditure on tertiary education and by the public expenditure on research and development, corresponding to the period 2010-2014. The objectives of this paper are: synthesis of theoretical delimitations on competitiveness, highlighting the relationship between national competitiveness and human capital, testing this relationship for the case of Central and Eastern European countries. The results show a significant and a positive relation, indicating that investment in education and research contributes significantly to increasing the national competitiveness. The obtained results draw attention to the fact that Central and Eastern Europe countries need to initiate measures to reduce the drain-brain phenomenon and to create a favorable socio-economic context for retaining and attracting the talent.
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
Zhang, Ping; Brusic, Vladimir
Mathematical modeling enables: the in silico classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silico pre-screened drug targets can be validated by a small number of carefully selected experiments. This review discusses the basics of mathematical modeling in cancer drug discovery and development. The topics include in silico discovery of novel molecular drug targets, optimization of immunotherapies, personalized medicine and guiding preclinical and clinical trials. Breast cancer has been used to demonstrate the applications of mathematical modeling in cancer diagnostics, the identification of high-risk population, cancer screening strategies, prediction of tumor growth and guiding cancer treatment. Mathematical models are the key components of the toolkit used in the fight against cancer. The combinatorial complexity of new drugs discovery is enormous, making systematic drug discovery, by experimentation, alone difficult if not impossible. The biggest challenges include seamless integration of growing data, information and knowledge, and making them available for a multiplicity of analyses. Mathematical models are essential for bringing cancer drug discovery into the era of Omics, Big Data and personalized medicine.
Thitinan, Sumalee; McConville, Jason T
To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.
Li Nansheng; Ren Xiaorong
with the enterprise competitive environment rapid change, the importance of competitive intelligence becomes suddenly to reveal day by day. The patent is one of the most important information sources of competitive intelligence. This article describes the present status of the enterprise patent work, proposes the patent work strategy, point out that if it wants to enhance the enterprise competitive power, it will pay attention to the patent work. (authors)
Zajtzeva Lyudmila O.
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.
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.
Matyushenko Igor Yu.
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.
Laís Bastos da Fonseca
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.
Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert
The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.
Huang, Wei; Whittaker, Kelly; Zhang, Huihua; Wu, Jian; Zhu, Si-Wei; Huang, Ruo-Pan
Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. In this review, some technical aspects of antibody array development and the various platforms currently available will be addressed; however, the main focus will be on the discussion of antibody array technologies and their applications in drug discovery. Aspects of the drug discovery process, including target identification, mechanisms of drug resistance, molecular mechanisms of drug action, drug side effects, and the application in clinical trials and in managing patient care, which have been investigated using antibody arrays in recent literature will be examined and the relevance of this technology in progressing this process will be discussed. Protein profiling with antibody array technology, in addition to other applications, has emerged as a successful, novel approach for drug discovery because of the well-known importance of proteins in cell events and disease development.
Thadani, Pushpa V
Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.
In 1999 about 16% of the world's electricity was produced by nuclear power, and the total worldwide operating experience of nuclear power plants was over 9200 reactor-years. Some 16 countries are dependent on nuclear power for more than 25% of their electricity generation. In some countries deregulation of the electricity market has either happened or is currently ongoing, while in others it is planned for the future. Nevertheless, many countries are already facing open electricity markets and operating costs are under unprecedented pressure, with competition expected to come soon to the nuclear industry worldwide. To a certain extent, however, the industry has already prepared or is currently preparing to face competition. This report is primarily intended for nuclear power plant and utility managers. It discusses the means and principal issues for the development of the nuclear economic performance international system (NEPIS), which should enhance nuclear power plant competitiveness. The following issues are addressed: The major transformations occurring in the electricity generation industry that require reductions in operations and maintenance costs at nuclear utilities; The methods that nuclear plant management use to identify and justify the economic optimum level of a plant and its use of resources; The value of collecting cost and performance data and the analysis techniques that use that data; The cost data required to be collected; The difficulty of collecting data with existing cost accounting systems; The new cost accounting and collection systems that will be required, The cost effectiveness of the overall process. This report also presents the preliminary results of a pilot project that was established to collect cost data on a few nuclear power plants and was used to verify the adequacy of the definitions and terminology set for NEPIS
Li, Jing; Yu, Fei; Chen, Yi; Oupický, David
Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809
Halliday, Tanya M.; Loenneke, Jeremy P.; Davy, Brenda M.
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
Franco, Valentina; French, Jacqueline A; Perucca, Emilio
Despite the current availability in the market of over two dozen antiepileptic drugs (AEDs), about one third of people with epilepsy fail to achieve complete freedom from seizures with existing medications. Moreover, currently available AEDs have significant limitations in terms of safety, tolerability and propensity to cause or be a target for clinically important adverse drug interactions. A review of the evidence shows that there are many misperceptions about the viability of investing into new therapies for epilepsy. In fact, there are clear incentives to develop newer and more efficacious medications. Developing truly innovative drugs requires a shift in the paradigms for drug discovery, which is already taking place by building on greatly expanded knowledge about the mechanisms involved in epileptogenesis, seizure generation, seizure spread and development of co-morbidities. AED development can also benefit by a review of the methodology currently applied in clinical AED development, in order to address a number of ethical and scientific concerns. As discussed in this article, many processes of clinical drug development, from proof-of-concept-studies to ambitious programs aimed at demonstrating antiepileptogenesis and disease-modification, can be facilitated by a greater integration of preclinical and clinical science, and by application of knowledge acquired during decades of controlled epilepsy trials. Copyright © 2015 Elsevier Ltd. All rights reserved.
Hao, Da-Cheng; Ge, Guang-Bo; Wang, Ping; Yang, Ling
Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. DDIs significantly impact the PK/pharmacodynamics performance of taxanes and co-administered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus -involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial tothe translation of bench findings to the clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
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.
Oh, Hunseok; Ryu, Hyue-Hyun; Choi, Myungweon
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…
Matesić, Mirjana; Kalambura, Sanja; Bacun, Dubravka
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.
Lungu, Ion; Manicu, Maria; Caraca, Lusine
The political and economical transformation, followed by institutional changes occurring all over the world has led to the creation of new relationships in the electricity sector, a segment playing a vital role in the economical and social development of a country. Thus, the energy sector planning and the strict control of the state used as a means to ensure the energy security have been largely rejected. In most countries, the state has given up its price control practice on activities that were deemed competitive, subsidies have been significantly reduced or eliminated, and barriers hindering the energy trading have been eased or removed. The process of removing state intervention from the electricity markets is in full progress and is achieved through deep structural reforms covering two directions: privatisation of large state-owned companies, on one hand and, on the other hand, restructuring the industrial branches that are network-dependent. These branches are mainly restructured through separation of monopolistic activities from competitive activities, concurrently with the invalidation and/or amendment of the legislation referring to the granting of energy efficiency incentives in the sector. The paper addresses the following items: - Energy markets regulatory framework within EU; - Internal electricity market regulation in the context of the 2003/54 EC Directive; Romania engaged itself in this effort to restructuring its electricity sector. The process started in 1998 and aimed at ensuring the supply of electricity and heat under conditions of quality, fair prices and mitigated environmental impact
Marrer, Estelle; Dieterle, Frank
Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.
A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. In this review, the authors look at a number of external innovation opportunities. These include increased interactions with academia via academic centers of excellence/innovation centers, better communication on projects using crowdsourcing or social media and new models centered on external providers such as built-to-buy startups or virtual pharmaceutical companies. The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.
Managing biodiversity for sustainable and competitive ecotourism destinations requires a basic understanding of the principles of biology, which are poorly understood in tropical developing countries, including Indonesia. This paper describes the current status of tourism in Indonesia, identifies environment and biodiversity vulnerability in tourism destinations, and explores the challenges of the biological field in supporting ecotourism development. This review found that tourism, especially nature-based and ecotourism, has grown significantly in Indonesia, and the contribution of Indonesian biodiversity has been identified as significant. Threats to biodiversity, however, are found in nature-based tourism destinations. Issues related to pollution, exotic plant species invasion, habitat changes and degradation, habitat loss, and wildlife disturbance are widely reported, indicating the importance of such issues in destination management. Pollution is found in both terrestrial and aquatic ecosystems. Water pollution is an important issue among lakes and rivers. To date, there are few assessments of the impact of tourism activities on aquatic ecosystems, resulting in the management of aquatic ecosystems facing numerous difficulties. These studies identify the invasive plants found, which become a crucial problem in many nature-based tourism destinations, and which significantly contribute to a reduction in the existence of many flora-fauna in a wild habitat. Habitat changes and degradation are mostly influenced by tourism infrastructure development. Massive infrastructure development often leads to habitat loss, which is a crucial step in local biodiversity extinction. Increasing and uncontrolled visitor behaviors influence animal behavior changes, which is recognized as a dangerous phenomenon affecting animal survival in the future. An agenda for future integrative biological research is needed to improve resource management, to increase sustainability and the
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.
Jeevanandam, Jaison; Chan, Yen San; Danquah, Michael K
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. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
Luo, Yao; Wang, Ling
The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Prausnitz, Mark R.; Bommarius, Andreas S.
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.…
Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the
Steinmetz, Karen L; Spack, Edward G
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
Spack Edward G
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
Full Text Available Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the noninferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.
Melanie G Mayer
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
One-third of the global population lacks access to medications; the situation is worse in poor countries, where up to 50% of the population lacks access. The failure of current incentive systems based in intellectual property to offer the necessary pharmaceutical products, especially in the global south, is a call to action. Problems related to drug access cannot be solved solely through improvements or modifications in the existing incentive models. The intellectual property system model does not offer sufficient innovation for developing countries; new mechanisms that effectively promote innovation and drug access simultaneously are needed. A binding international agreement on research and development, negotiated under the auspices of the World Health Organization, could provide an adequate framework for guaranteeing priority-setting, coordination, and sustainable financing of drugs at reasonable prices for developing countries.
Milne, Christopher-Paul; Ni, Wendi
Social media has transformed how people interact with one another through the Internet, and it has the potential to do the same for orphan drug development. Currently, social media influences the orphan drug development process in the following three ways: assisting the study of orphan diseases, increasing the awareness of orphan disease, and playing a vital role in clinical trials. However, there are some caveats to the utilization of social media, such as the need to protect patient privacy by adequately de-identifying personal health information, assuring consistent quality and representativeness of the data, and preventing the unblinding of patient group assignments. Social media has both potential for improving orphan drug development and pitfalls, but with proper oversight on the part of companies, support and participation of patients and their advocacy groups, and timely guidance from regulatory authorities, the positives outweigh the negatives for this powerful and patient-centric tool. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.
Olga Victorovna Kandyba
Full Text Available The relevance of the inclusion of the universities competitions in accordance with WorldSkills Russia standards (hereinafter – WSR is determined by the problematic situation that has developed in the higher education system and the modern requirements of the tourist industry labor market for graduates. Universities competitions in accordance with international standards are a new direction in the WSR movement, which can enhance the status of vocational education. This is the first experience in Russia, which, first, requires reflection, understanding and, accordingly, acceptance by the university teaching community of the WSR movement itself. Secondly, the conducted competitions have revealed a number of problems that must be solved on the way to effective implementation of WSR standards in the educational process. The article presents the matrix of professional competencies, compiled on the basis of the Federal State Educational Standard of the Higher Professional Education in “Tourism” training area 43.03.02 and the Skill WSR “Tourism” standards. On the basis of the developed matrix of competences, the correlation between the professional competencies of HPE FSES and competencies shown in the modules of the Skill WSR “Tourism” is revealed. Purpose Conducting a comparative analysis of the competencies of the HPE FSES in “Tourism” training area with competencies based on the modules of the competition task of the WSR Championship. Methodology In the article methods of included observation, peer review and comparative analysis were used. Results A comparative analysis of the competencies of the HPE FSES in “Tourism” training area with competencies necessary to complete the modules of the competition task of the WSR competition is conducted, recommendations on the expansion of the elements of the competition tasks for the university championship WSR are given. Practical implications The results obtained should be used to
L. A. Tsvetkova
Full Text Available The analysis of prospects of introduction of the developments related to blokcheyn in the world and in Russia has been made. Key investors and beneficiaries in the development of blockchain technologies were identified. High competitiveness of Russian developments, unique staffing, and favorable climatic conditions for the development of blockade technologies in the Russian Federation were noted. The patent activity in the world has been analyzed and the place of Russia on the patent landscape in the field of blockchain technologies has been determined. It is shown that, to date, the weak position of Russian developers in the global patent landscape in the field of blockchain is not critical due to the high level of uncertainty in matters of protectability of the proposed blockchain algorithms. Special attention was paid to the delayed, perhaps shortterm, readiness of residents of industrially developed countries to expand in the global space of intellectual property associated with the blockchain as soon as the patentability of the proposed solutions is proved. It is concluded that the next 2–3 years should be considered as a “window of opportunity” to form the prerequisites for Russia’s technological leadership in the cluster of block-technologies.
Wenqiang Liu; Xiliang Zhang; Lin Gan
This paper presents an overview of the development of wind power in China. The factors that affect the directions of wind power development are analyzed. It examines the economics of wind farm development and compares it with conventional energy sources. The major constraints in wind technology development, and defects of the current policies, are discussed. It points out that wind power development should be subject to rational policy change and institutional adjustment. It discusses the incentive mechanisms and institutional frameworks for future development. Particular importance is attributed to market incentives for wind power to reach the objectives of industrialization and commercialization. A number of cost-competitive incentive measures and policies are recommended: (i) introducing market based mechanisms through standard power purchase agreement; (ii) establishing effective investment policies and regulations to attract private investment; (iii) promoting localization of wind turbine production; (iv) adjusting tax and subsidy policies; and (v) reforming governmental institutions to make clear rules and responsibilities for policymaking, and enhancing communication/coordination between relevant government agencies in order to formulate uniform and effective policies. (Author)
Bhatter, Purva; Chatterjee, Anirvan; D'souza, Desiree; Tolani, Monica; Mistry, Nerges
Background Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global tuberculosis control. A significant fitness cost has been associated with DR strains from specific lineages. Evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of MDR TB. The aim of this study was to evaluate the fitness of MDR TB strains, from a TB endemic region of western India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU in the presence of drug susceptible strains from the same lineages. Methodology Drug susceptible strains from a single lineage were mixed with drug resistant strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG, S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb) strains was evaluated using the difference in growth rates obtained by using the CFU assay system. Conclusion/Significance While MANU were most fit amongst the drug susceptible strains of the 3 lineages, only Beijing MDR strains were found to grow in the presence of any of the competing drug susceptible strains. A disproportionate increase in Beijing MDR could be an alarm for an impending epidemic in this locale. In addition to particular non synonymous substitutions, the competing strains in an environment may impact the fitness of circulating drug resistant strains. PMID:22479407
... principles of the economic system in the United States, including seminars on the economic institutions in... Competition for the Cooperative Civic Education and Economic Education Exchange Program; Notice Inviting.... Funding Opportunity Description Purpose of Program: The Cooperative Civic Education and Economic Education...
In May 2006, the Danish Government presented a report on promoting environmentally effective technology and established a number of innovative partnerships. The partnerships intend to strengthen public-private cooperation between the state, industry, universities and venture capital to accelerate innovation for a number of green technologies. The partnership for wind energy is called Megavind. Megavind's strategy for offshore wind describes the offshore challenges and suggests research, development and demonstration (RD and D) priorities to enable offshore wind power become to competitive with other energy technologies. The strategy lists key recommendations as well as key thematic priorities and for each of these a number of RD and D priorities. Under each thematic priority references are made to the European Strategic Energy Technology plan (SET-plan), which prioritises offshore wind RD and D in Europe. (LN)
Kraus, Carl N
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.
Julius A Vaz
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.
Vaz, Julius A; Patnaik, Ashis
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.
Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E
Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.
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.
Sanchez-Rexach, Eva; Meaurio, Emilio; Sarasua, Jose-Ramon
Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings. Copyright © 2017 Elsevier B.V. All rights reserved.
Teneggi, Vincenzo; Sivakumar, Nithy; Chen, Deborah; Matter, Alex
Acute heart failure (AHF) is a major burden disease, with a complex physiopathology, unsatisfactory diagnosis, treatment and a very poor prognosis. In the last two decades, a number of drugs have progressed from preclinical to early and late clinical development, but only a few of them have been approved and added to a stagnant pharmacological armamentarium. We have reviewed the data published on drugs developed for AHF since early 2000s, trying to recognise factors that have worked for a successful approval or for the stoppage of the program, in an attempt to delineate future trajectories for AHF drug development. Our review has identified limitations at both preclinical and clinical levels. At the preclinical level, the major shortcoming is represented by animal models looking at short-term endpoints which do not recapitulate the complexity of the human disease. At the clinical level, the main weakness is given by the disconnect between short-term endpoints assessed in the early stage of drug development, and medium-long-term endpoints requested in Phase 3 for regulatory approval. This is further amplified by the lack of validation and standardisation of short- and long-term endpoints; absence of predictive biomarkers; conduct of studies on heterogeneous populations; and use of different eligibility criteria, time of assessments, drug schedules and background therapies. Key goals remain a better understanding of AHF and the construction of a successful drug development program. A reasonable way to move forward resides in a strong collaboration between main stakeholders of therapeutic innovation: scientific community, industry and regulatory agencies.
Tsukamoto, Katusra; Carroll, Kelly A; Onishi, Taku; Matsumaru, Naoki; Brasseur, Daniel; Nakamura, Hidefumi
A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P 15% after 2008. Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and
Radu Riana Iren; Necsulescu Ecaterina
Blue ocean strategy challenges companies to emerge in the middle of the fierce competition that is by creating undisputed market areas which result in competition to become irrelevant. Only, instead of dividing the existing market demand, blue ocean strategy refers to a growing demand and to eliminate competition. Blue Ocean opportunities have always existed and have been explored as the universe expanded business. This expansion is the foundation of economic growth.
In the actual context of economic globalization, the competitiveness has a crucial importance for all the countries. But due to which factors and to what extent takes place the creation and improvement of it? This paper traces the role of the private sector in creating and sustaining international competitiveness, it summarizes three determinants of international competitiveness (productivity, innovation and clusters) and traces their impact on it. The main argument of this paper is that thes...
Serkan Kilic; Gokhan Senol
Retailing is a dynamic and complex sector that offers wide range of products and services to consumers. This sector which includes different types of enterprises, has an important position within the supply chain. Food retailing has also a big potential within retailing sector. On the other hand, an intensive competition exists in food retailing. Taking place in the competitive market, food retailers attempt to gain a competitive advantage against their rivals with their geographic location,...
Full text. Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the Gl tract, the depth of penetration of a nebulized solution into the lung, or the residence time of a drug on the cornea. By using the gamma camera to image the in vivo distribution of pharmaceutical formulations radio labelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Example will be shown of studies which examine the rate of transit of orally-administered formulations through the GI tract, as well as describing the development of devices for specific targeting of drugs to the colon. Data will also demonstrate the effectiveness of devices such as spacers in pulmonary drug delivery, in both normal volunteers, and in asthmatic subjects. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers
Schjødt-Eriksen, Jens; Clausen, Jens
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 develo...... 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....
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
Chen, Jie; Zhao, Naiqing
As the second largest pharmaceutical market with a great potential for future growth, China has drawn much attention from the global pharmaceutical community. With an increasing government investment in biomedical research, the domestic biopharmaceutical (biotechnological) companies in China are turning their attention to the development of innovative medicines and targeting the global market. To introduce innovative products to Chinese patients sooner, to improve the efficiency of its review and approval processes, and to harmonize its regulatory science with international standards, the China Food and Drug Administration (CFDA) has initiated a series of major changes to its policies and regulations. This paper presents a snapshot of China's pharmaceutical market, and research and development status, and introduces technical guidelines pertaining to clinical trials and new drug applications. The recent wave of ground-breaking reforms in CFDA's regulatory science is discussed. Examples of clinical trials and new drug applications are provided throughout the discussion.
FitzGerald, Garret A
New-drug approvals have remained roughly constant since 1950, while the cost of drug development has soared. It seems likely that a more modular approach to drug discovery and development will evolve, deriving some features from the not-for-profit sector. For this to occur, we must address the deficit in human capital with expertise in both translational medicine and therapeutics and also in regulatory science; utilize regulatory reform to incentivize innovation and the expansion of the precompetitive space; and develop an informatics infrastructure that permits the global, secure, and compliant sharing of heterogeneous data across academic and industry sectors. These developments, likely prompted by the perception of crisis rather than opportunity, will require linked initiatives among academia, the pharmaceutical industry, the US National Institutes of Health, and the US Food and Drug Administration, along with a more adventurous role for venture capital. A failure to respond threatens the United States' lead in biomedical science and in the development and regulation of novel therapeutics. 2010 Mount Sinai School of Medicine.
Malysheva, Tatiana V.; Shinkevich, Alexey I.; Kharisova, Guzyal M.; Nuretdinova, Yuliya V.; Khasyanov, Oleg R.; Nuretdinov, Ildar G.; Zaitseva, Natalia A.; Kudryavtseva, Svetlana S.
The purpose of this article is to develop methodological approaches to the production effectiveness’s evaluating and products competitiveness’s level estimation to identify risk groups according to the products and producers, to propose targeted measures manufacturers’ support, to activate innovative development and minimize potential social impacts. The leading method to study this problem is the method of constructing the matrix of the producers’ efficiency and the commodities’ competitiven...
Hojsgaard, Diego H; Martínez, Eric J; Quarin, Camilo L
Meiotic and apomictic reproductive pathways develop simultaneously in facultative aposporous species, and compete to form a seed as a final goal. This developmental competition was evaluated in tetraploid genotypes of Paspalum malacophyllum in order to understand the low level of sexuality in facultative apomictic populations. Cyto-embryology on ovules, flow cytometry on seeds and progeny tests by DNA fingerprinting were used to measure the relative incidence of each meiotic or apomictic pathway along four different stages of the plant's life cycle, namely the beginning and end of gametogenesis, seed formation and adult offspring. A high variation in the frequencies of sexual and apomictic pathways occurred at the first two stages. A trend of radical decline in realized sexuality was then observed. Sexual and apomictic seeds were produced, but the efficiency of the sexual pathway dropped drastically, and exclusively clonal offspring remained. Both reproductive pathways are unstable at the beginning of development, and only the apomictic one remains functional. Key factors reducing sexuality are the faster growth and parthenogenetic development in the aposporous pathway, and an (epi)genetically negative background related to the extensive gene de-regulation pattern responsible for apomixis. The effects of inbreeding depression during post-fertilization development may further decrease the frequency of effective sexuality. No claim to original US government works. New Phytologist © 2012 New Phytologist Trust.
A. V. Kalach
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.
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
Recently, many urban public universities have seen a drastic increase in competition. This project integrates Schumpeter's economic theories from 70 years ago with current strategic management theory in order to provide a framework for strategic response to that competition. This article explores all possible combinations of the high-low quality…
Dou, Henri; Manullang, Sri Damayanty
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…
Donald R. Zak; Mark E. Kubiske; Kurt S. Pregitzer; Andrew J. Burton
Plant growth responses to rising atmospheric CO2 and O3 vary among genotypes and between species, which could plausibly influence the strength of competitive interactions for soil N. Ascribable to the size-symmetric nature of belowground competition, we reasoned that differential growth responses to CO2...
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.
Full Text Available During the post-war period, natural resource production has often been associated withperipheralization in the world-economy. This paper seeks to demonstrate that this associationdoes not hold when examined from a long-term perspective, and explains the conditions underwhich natural resource production can support upward economic mobility in the world-system.First, this paper provides evidence that the production of cash crops and resource extraction hasnot always equaled peripheralization in the world-economy, as demonstrated by, among otherthings, the upward economic mobility of the United States, Canada, Australia and New Zealandduring the nineteenth century. It then puts forth a new hypothesis that the existence ofopportunities for raw material producing countries depends on whether the hegemonic regime ofaccumulation at a given time structures the economy in a way that is either complementary orcompetitive to the economic development of raw material producing countries. By examining theBritish centered regime of accumulation during the nineteenth century, we find that it wascomparatively complementary to economic development in raw material producing countrieswhereas the twentieth century United States centered regime was comparatively competitive withraw material producers. Based on a comparison with Britain and the United States, the paperalso suggests that Chinas increasingly central role in the world-economy may be comparativelycomplementary to economic development in raw material producing countries.
Nicolás, Leticia; Martínez-Gómez, Margarita; Hudson, Robyn; Bautista, Amando
Interest has been growing in the influence siblings may have on individual development. While mammalian research has tended to emphasize competition among siblings for essential but often limited resources such as the mother's milk, there is also evidence of mutual benefits to be had from sibling presence, most notably for altricial young in enhanced thermoregulatory efficiency. In the present study we asked whether littermates of an altricial mammal, the domestic rabbit, might gain other developmental benefits from sibling presence. From postnatal days 1 to 25 we raised rabbit pups either together with their littermates or alone except for the brief, once daily nursing characteristic of this species, while controlling for litter size and ambient nest box temperature. At weaning on Day 25 the young were then transferred to individual cages. Before weaning, we found that pups raised separately from their littermates obtained less milk, and showed lower weight gain and slower development of the ability to maintain body equilibrium than their litter-raised sibs. This was the case even though the two groups did not differ in birth weight or in the ratio of converting milk into body mass in their temperature-controlled nest boxes. Postweaning, the isolation-raised animals were also less successful in competing for food and water when tested after deprivation than their litter-raised sibs. The present study adds to the growing evidence of the influence, in this case positive, that sibs (or half sibs) may have in shaping one another's development. © 2010 Wiley Periodicals, Inc.
... Competitive Auction for Solar Energy Development on Public Lands in the State of Colorado AGENCY: Bureau of...) application and a plan of development for solar energy projects on approximately 3,705 acres of public land in... designated Solar Energy Zones (SEZ): Los Mogotes East SEZ and De Tilla Gulch SEZ. Applications for solar...
Yamkova S. P.
Full Text Available the article explains the importance of the development of innovation as the economic competitiveness of regions of Russia. Considered term innovation potential of the region. The problems of development of innovative potential of the region and ways to solve them.
Nagano, Kazuya; Tsutsumi, Yasuo
Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony-stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. It is difficult to identify proteins useful as therapeutic seeds or targets. Another problem in using bioactive proteins is pleiotropic actions through receptors, making it hard to elicit desired effects without side effects. Additionally, bioactive proteins have poor therapeutic effects owing to degradation by proteases and rapid excretion from the circulatory system. Therefore, it is essential to establish a series of novel drug delivery systems (DDS) to overcome these problems. Here, we review original technologies in DDS. First, we introduce antibody proteomics technology for effective selection of proteins useful as therapeutic seeds or targets and identification of various kinds of proteins, such as cancer-specific proteins, cancer metastasis-related proteins, and a cisplatin resistance-related protein. Especially Ephrin receptor A10 is expressed in breast tumor tissues but not in normal tissues and is a promising drug target potentially useful for breast cancer treatment. Moreover, we have developed a system for rapidly creating functional mutant proteins to optimize the seeds for therapeutic applications and used this system to generate various kinds of functional cytokine muteins. Among them, R1antTNF is a TNFR1-selective antagonistic mutant of TNF and is the first mutein converted from agonist to antagonist. We also review a novel polymer-conjugation system to improve the in vivo stability of bioactive proteins. Site-specific PEGylated R1antTNF is uniform at the molecular level, and its bioactivity is similar to that of unmodified R1antTNF. In the future, we hope that many innovative protein drugs will be
von Itzstein, Mark; Thomson, Robin
Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza, and subsequently Tamiflu, has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important. An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.
Garbayo, E; Ansorena, E; Blanco-Prieto, M J
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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Lappin, Graham; Noveck, Robert; Burt, Tal
Introduction Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. Areas covered The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. Expert opinion Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date. PMID:23550938
Feduccia, Allison A; Holland, Julie; Mithoefer, Michael C
Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug "Ecstasy." MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.
Kuada, John Ernest
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...
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...
Klymchuk Oleksandr V.
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.
Nikolay Prokofyevich Ivanov
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.
Schmidt, Brian J; Papin, Jason A; Musante, Cynthia J
A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. Copyright © 2012 Elsevier Ltd. All rights reserved.
Hilpert, Reinhold; Bauer, Christian; Binder, Florian; Grol, Michael; Hallermayer, Klaus; Josel, Hans-Peter; Klein, Christian; Maier, Josef; Makower, Alexander; Oberpriller, Helmut; Ritter, Josef
In a joint project of Deutsche Aerospace, Boehringer Mannheim and the University of Potsdam portable devices for the detection of illegal drugs, based on biosensor technology, are being developed. The concept enrichment of the drug from the gas phase and detection by immunological means. This publication covers the development of specific antibodies and various detection procedures. Antibodies with a high affinity for cocaine have been developed with the aid of specially synthesized immunogens. A competitive detection procedure with biosensors based on optical grating couplers and applying particulate labels has been established, showing a lower detection limit of 10-10 mol/l for cocaine. Additionally, a combination of a displacement-immunoreactor and an enzymatically amplified electrode was investigated, which at present still suffers from insufficient sensitivity of the immunoreactor. An alternative, fleece-matrix based test procedure, where enrichment and detection steps are integrated in a single unit, is promising in terms of simplicity and sensitivity. A simple swab-test for the detection of cocaine at surfaces has been developed, which has a lower detection limit of about 10 ng and which can be performed within one minute.
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
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. PMID:23986704
Marisa Gaspar Carreño
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.
Full Text Available 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 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 Learning Outcomes 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.
Sakakibara, Noriko; Yoshioka, Ryuzo; Matsumoto, Kazuo
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.
Karlsson, Oskar; Hanrieder, Jörg
During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.
Long, Marcus John Curtis; Aye, Yimon
This Perspective delineates how redox signaling affects the activity of specific enzyme isoforms and how this property may be harnessed for rational drug design. Covalent drugs have resurged in recent years and several reports have extolled the general virtues of developing irreversible inhibitors. Indeed, many modern pharmaceuticals contain electrophilic appendages. Several invoke a warhead that hijacks active-site nucleophiles whereas others take advantage of spectator nucleophilic side chains that do not participate in enzymatic chemistry, but are poised to bind/react with electrophiles. The latest data suggest that innate electrophile sensing-which enables rapid reaction with an endogenous signaling electrophile-is a quintessential resource for the development of covalent drugs. For instance, based on recent work documenting isoform-specific electrophile sensing, isozyme non-specific drugs may be converted to isozyme-specific analogs by hijacking privileged first-responder electrophile-sensing cysteines. Because this approach targets functionally relevant cysteines, we can simultaneously harness previously untapped moonlighting roles of enzymes linked to redox sensing. Copyright © 2017 Elsevier Ltd. All rights reserved.
Gaspar Carreño, Marisa; Achau Muñoz, Rubén; Torrico Martín, Fátima; Agún Gonzalez, Juan José; Sanchez Santos, Jose Cristobal; Cercos Lletí, Ana Cristina; Ramos Orozco, Pedro
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). 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. 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. 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. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Firdaus, Anton; Hamsal, Mohammad
This research about how PT KHI make an improvement in Business model by offering EPC (Engineering, Procurement & Construction) services to costumer to gain a better profit margin. Research result suggests PT KHI to improve its Business Model in order to enhance sustainable competitive advantage. Many competitors have the same business model in industry. PT KHI should offer different business model to stay ahead and winning the competition. The research result indicate based on current con...
Mirjana Nedović Čabarkapa
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.
Traxler, Matthew F; Seyedsayamdost, Mohammad R; Clardy, Jon; Kolter, Roberto
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. © 2012 Blackwell Publishing Ltd.
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.
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.
Full Text Available 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.
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)
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.
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.
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…
Carrier, Felix; Banayan, David; Boley, Randy; Karnik, Niranjan
As the classification of mental disorders advances towards a disease model as promoted by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC), there is hope that a more thorough neurobiological understanding of mental illness may allow clinicians and researchers to determine treatment efficacy with less diagnostic variability. This paradigm shift has presented a variety of ethical issues to be considered in the development of psychiatric drugs. These challenges are not limited to informed consent practices, industry funding, and placebo use. The consideration for alternative research models and quality of research design also present ethical challenges in the development of psychiatric drugs. The imperatives to create valid and sound research that justify the human time, cost, risk and use of limited resources must also be considered. Clinical innovation, and consideration for special populations are also important aspects to take into account. Based on the breadth of these ethical concerns, it is particularly important that scientific questions regarding the development of psychiatric drugs be answered collaboratively by a variety of stakeholders. As the field expands, new ethical considerations will be raised with increased focus on genetic markers, personalized medicine, patient-centered outcomes research, and tension over funding. We suggest that innovation in trial design is necessary to better reflect practices in clinical settings and that there must be an emphasized focus on expanding the transparency of consent processes, regard for suicidality, and care in working with special populations to support the goal of developing sound psychiatric drug therapies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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
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. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
Jarosławski, Szymon; Toumi, Mondher; Auquier, Pascal; Dussart, Claude
In wealthy nations, non-profit drug R&D has been proposed to reduce the prices of medicines. We sought to review the ethical and economic issues concerning non-profit drug R&D companies, and the possible impact that their pricing strategy may have on the innovation efforts from for-profit companies targeting the same segment of the pharmaceutical market. There are two possible approaches to pricing drugs developed by non-profit R&D programs: pricing that maximises profits and "affordable" pricing that reflects the cost of manufacturing and distribution, plus a margin that ensures sustainability of the drug supply. Overall, the non-profits face ethical challenges - due to the lack of resources, they are unable to independently commercialize their products on a large scale; however, the antitrust law does not permit them to impose prices on potential licensees. Also, reduced prices for the innovative products may result in drying the for-profit R&D in the area.
Johnston, Tom H; Brotchie, Jonathan M
The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.
Jordens, H.; Mathelitsch, L.
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 . 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' . This competition started in 1991 in Poland and encourages students to take their first steps in physics research. Students of 20 years old or
Kunz, Meik; Liang, Chunguang; Nilla, Santosh; Cecil, Alexander; Dandekar, Thomas
The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure-activity relationships.Database URL:http://drumpid.bioapps.biozentrum.uni-wuerzburg.de. © The Author(s) 2016. Published by Oxford University Press.
Hoffmann, Else Kay; Lambert, Ian Henry
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 i...
...] Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability AGENCY... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 21, rm...
Fu, Sihai; Feng, Mei; Xiong, Yan
The value of snake venom polypeptides in clinical application has drawn extensive attention, and the development of snake polypeptides into new drugs with anti-tumor, anti-inflammatory, antithrombotic, analgesic or antihypertensive properties has become the recent research hotspot. With the rapid development of molecular biology and biotechnology, the mechanisms of snake venom polypeptides are also gradually clarified. Numerous studies have demonstrated that snake venom polypeptides exert their pharmacological effects by regulating ion channels, cell proliferation, apoptosis, intracellular signaling pathway, and expression of cytokine as well as binding to relevant active sites or receptors.
Jackson, Nicole; Czaplewski, Lloyd; Piddock, Laura J V
Antibiotic (antibacterial) resistance is a serious global problem and the need for new treatments is urgent. The current antibiotic discovery model is not delivering new agents at a rate that is sufficient to combat present levels of antibiotic resistance. This has led to fears of the arrival of a 'post-antibiotic era'. Scientific difficulties, an unfavourable regulatory climate, multiple company mergers and the low financial returns associated with antibiotic drug development have led to the withdrawal of many pharmaceutical companies from the field. The regulatory climate has now begun to improve, but major scientific hurdles still impede the discovery and development of novel antibacterial agents. To facilitate discovery activities there must be increased understanding of the scientific problems experienced by pharmaceutical companies. This must be coupled with addressing the current antibiotic resistance crisis so that compounds and ultimately drugs are delivered to treat the most urgent clinical challenges. By understanding the causes of the failures and successes of the pharmaceutical industry's research history, duplication of discovery programmes will be reduced, increasing the productivity of the antibiotic drug discovery pipeline by academia and small companies. The most important scientific issues to address are getting molecules into the Gram-negative bacterial cell and avoiding their efflux. Hence screening programmes should focus their efforts on whole bacterial cells rather than cell-free systems. Despite falling out of favour with pharmaceutical companies, natural product research still holds promise for providing new molecules as a basis for discovery.
Leong, Ruby; Zhao, Hong; Reaman, Gregory; Liu, Qi; Wang, Yaning; Stewart, Clinton F; Burckart, Gilbert
Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population. Therefore, the development of drug dosing in pediatric oncology patients represents a special challenge. Potential approaches to pediatric dosing in oncology patients include extrapolation of efficacy from adult studies in those few cases where the disease is similar, inclusion of adolescent patients in adult trials when possible, and bridging the adult dose to the pediatric dose. An analysis of the recommended phase 2 dose for 40 molecularly targeted agents in pediatric patients provides some insight into current practices. Increased knowledge of tumor biology and efforts to identify and validate molecular targets and genetic abnormalities that drive childhood cancers can lead to increased opportunities for precision medicine in the treatment of pediatric cancers. © 2017, The American College of Clinical Pharmacology.
Forray, Carlos; Buller, Raimund
In spite of the significant impact that the serendipitous discovery of drugs with antipsychotic properties had on the care of patients with psychotic disorders, there are significant challenges when aiming at therapeutic goals such as remission, recovery, improved health-related quality of life and functioning. The efficacy and effectiveness of existing antipsychotic drugs fail to address the full spectrum of symptoms and functional deficits that currently prevent patients with psychotic disorders from achieving fulfilling lives. The study of the pharmacological mechanism of action has increased our knowledge on molecular targets and brain circuits related to the antipsychotic properties of this drug class. However, our understanding of how these molecular targets and brain circuits relate to other aspects of disease pathophysiology like cognitive impairment and negative symptoms is incomplete although these are significant clinical unmet needs. Currently, there is still an important knowledge gap between psychopathology and pathophysiology in schizophrenia research. This may have contributed to some recent costly failures of large clinical development programs for drugs targeted at glutamatergic function and nicotinic receptors. The lack of success of these pharmacological approaches to achieve clinical validation raises important questions concerning the underlying hypothesis that guided the choice of molecular targets, and about the predictive validity of translational models that supported the rationale for testing these drugs in clinical studies. From a clinical perspective there is a need to more strongly consider the disease heterogeneity linked to the use of the current diagnostic classification of subjects and to the validity of the psychopathological constructs and assessments that are used to assess clinical outcomes. A paradigm shift in the development of drugs for schizophrenia is needed. This will require among other addressing: the shortcomings of a
Vanessa Strüver, MSc
Conclusions: Both theoretically expected and actually reported benefits in the majority of the included publications emphasized the importance of individual patient benefits from drug development rather than the collective benefits to society in general. The authors of these publications emphasized the right of each individual patient or subject to look for and expect some personal benefit from participating in a clinical trial rather than considering societal benefit as a top priority. From an ethical point of view, the benefits each individual patient receives from his or her participation in a clinical trial might also be seen as a societal benefit, especially when the drug or device tested, if approved for marketing, would eventually be made available for other similar patients from the country in which the clinical trial was conducted.
Full Text Available Developments in genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians The ability to molecularly characterize of human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials.In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from a new regimen.
Kraus, Virginia B
The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.
Fisher, Jill A; Ronald, Lorna M
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
Competition and co-operation appear in many different social venues. The author gives a variety of examples of co-operative behaviour in economics, politics, research, and everyday life activities such as sports. These four diverse examples illustrate the variety of forms that co-operation may take such as tacit co-operation, incremental co-operation, deep co-operation, etc. The links with the form of democracy (adversary democracy or consensual democracy) are also pointed. However, as with so many other things in life, the key is to the question of co-operation or competition is balance. Co-operation and competition are dialectical opposites. They create and maintain and define each other; they each are incomplete without the other
Mead, Walter J.; Sorensen, Philip Edward
The oil and gas resources of the Outer Continental Shelf represent one of America's largest publicly-owned assets. Through 1978, OCS oil and gas leases had yielded \\$40.5 billion in gross production value and produced over \\$28.3 billion in direct revenue to the federal government.Policies and procedures for managing the oil and gas resources of the OCS were established by Congress in the Outer Continental Shelf Lands Act of 1953. The Department of Interior was given the central responsibility for carrying out this management role in the 1953 Act; this responsibility has been re-established in the 1978 Amendments to the OCS Lands Act. As stated in the 1978 legislation, the goals of OCS management are to:...preserve, protect and develop oil and natural gas resources in a manner which is consistent with the need (A) to make such resources available to meet the Nation's energy needs as rapidly as possible... (C) to insure the public a fair and equitable return on the resources of the Outer Continental Shelf, and (D) to preserve and maintain free enterprise competition.As part of its continuing effort to monitor the effectiveness of federal policies relating to OCS oil and gas resources, the Conservation Division of U.S. Geological Survey, Department of Interior, has sponsored the research which is the basis for the present report. The objectives of the research have been to determine the extent to which the historical policies of OCS management have resulted in achievement of the goals set forth by Congress in the section quoted above.
Full Text Available Schistosomiasis, one of the world's greatest neglected tropical diseases, is responsible for over 280,000 human deaths per annum. Praziquantel, developed in the 1970s, has high efficacy, excellent tolerability, few and transient side effects, simple administration procedures and competitive cost and it is currently the only recommended drug for treatment of human schistosomiasis. The use of a single drug to treat a population of over 200 million infected people appears particularly alarming when considering the threat of drug resistance. Quantitative, objective and validated methods for the screening of compound collections are needed for the discovery of novel anti-schistosomal drugs.The present work describes the development and validation of a luminescence-based, medium-throughput assay for the detection of schistosomula viability through quantitation of ATP, a good indicator of metabolically active cells in culture. This validated method is demonstrated to be fast, highly reliable, sensitive and automation-friendly. The optimized assay was used for the screening of a small compound library on S. mansoni schistosomula, showing that the proposed method is suitable for a medium-throughput semi-automated screening. Interestingly, the pilot screening identified hits previously reported to have some anti-parasitic activity, further supporting the validity of this assay for anthelminthic drug discovery.The developed and validated schistosomula viability luminescence-based assay was shown to be successful and suitable for the identification of novel compounds potentially exploitable in future schistosomiasis therapies.
Maeda, Hideki; Kurokawa, Tatsuo
This study exhaustively and historically investigated the status of drug lag for oncology drugs approved in Japan. We comprehensively investigated oncology drugs approved in Japan between April 2001 and July 2014, using publicly available information. We also examined changes in the status of drug lag between Japan and the United States, as well as factors influencing drug lag. This study included 120 applications for approval of oncology drugs in Japan. The median difference over a 13-year period in the approval date between the United States and Japan was 875 days (29.2 months). This figure peaked in 2002, and showed a tendency to decline gradually each year thereafter. In 2014, the median approval lag was 281 days (9.4 months). Multiple regression analysis identified the following potential factors that reduce drug lag: "Japan's participation in global clinical trials"; "bridging strategies"; "designation of priority review in Japan"; and "molecularly targeted drugs". From 2001 to 2014, molecularly targeted drugs emerged as the predominant oncology drug, and the method of development has changed from full development in Japan or bridging strategy to global simultaneous development by Japan's taking part in global clinical trials. In line with these changes, the drug lag between the United States and Japan has significantly reduced to less than 1 year.
cancer drug screening and cancer drug development. At the NCI, for example, the old in vivo mouse screen using mouse lymphomas has been shelved; it discovered compounds with some activity in lymphomas, but not the common solid tumors of adulthood. It has been replaced with an initial in vitro screen of some sixty cell lines, representing the common solid tumors-ovary, G.I., lung, breast, CNS, melanoma and others. The idea was to not only discover new drugs with specific anti-tumor activity but also to use the small volumes required for in vitro screening as a medium to screen for new natural product compounds, one of the richest sources of effective chemotherapy. The cell line project had an unexpected dividend. The pattern of sensitivity in the panel predicted the mechanism of action of unknown compounds. An antifolate suppressed cell growth of the different lines like other antifolates, anti-tubulin compounds suppressed like other anti-tubulins, and so on. It now became possible, at a very early stage of cancer drug screening, to select for drugs with unknown-and potentially novel-mechanisms of action. The idea was taken to the next logical step, and that was to characterize the entire panel for important molecular properties of human malignancy: mutations in the tumor suppressor gene p53, expression of important oncogenes like ras or myc, the gp170 gene which confers multiple drug resistance, protein-specific kinases, and others. It now became possible to use the cell line panel as a tool to detect new drugs which targeted a specific genetic property of the tumor cell. Researchers can now ask whether a given drug is likely to inhibit multiple drug resistance or kill cells which over-express specific oncogenes at the earliest phase of drug discovery. In this issue of The Oncologist, Tom Connors celebrates the fiftieth anniversary of cancer chemotherapy. His focus is on the importance of international collaboration in clinical trials and the negative impact of
The development of the British gas industry shows that structural changes at one industrial stage may have effects on the other stages and that competition at one stage (commercial stage) may be limited by the way the other stages are structured. The conditions of regulation in the gas industry, the development at its different stages, and its present structure are described. The effects of commercial restructuring on gas exploration and gas lifting, gas transport and gas storage are analyzed. (orig./UA) [de
Full Text Available the article presents ways of development of a technological platform of the Russian economy and a role of new technologies and «human factor» in providing its competitiveness at a post-industrial stage. The author offers: education systems development, use of channels of the international migration of a skilled labor force, forming of the national market of new technologies, enhancement of interaction with the world market of new technologies.
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...
Liu, Bing-Mi, E-mail: email@example.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Zhang, Jun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Bai, Chong-Liang [Centre for Molecular Science and Engineering, Northeastern University, Shenyang 110819 (China); Wang, Xin; Qiu, Xin-Zhi; Wang, Xiao-Li; Ji, Hui [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Liu, Bin, E-mail: firstname.lastname@example.org [Department of Pharmacy, Liaoning University, Shenyang 110036 (China)
The effects of three kinds of flavonoids, quercetin, rutin and baicalin, on the binding of ticagrelor to human serum albumin (HSA) were systematically investigated using fluorescence, UV–vis absorption and circular dichroism (CD) spectroscopic techniques. The results indicated that ticagrelor strongly quenched the HSA fluorescence by the style of static quenching and non-radiation energy transferring as a result of the HSA–ticagrelor complex formation, while the presence of flavonoids could not change the quenching mechanism. Ticagrelor could spontaneously bind in site I on HSA with high affinity, and this binding process was mainly driven by both hydrophobic forces and hydrogen bonding. The significantly decreased binding affinity and the unchanged binding mode and distance between ticagrelor and HSA indicated that that flavonoids could compete against ticagrelor in site I, and baicalin was the most effective competitor. The conformation investigation of HSA further confirmed the flavonoid/ticagrelor competitive binding mechanism. - Highlights: • Ticagrelor could spontaneously bind in subdomain IIA (site I) on HSA with high affinity. • The presence of flavonoids could not change the quenching mechanism. • The presence of flavonoids significantly decreased the binding affinity of ticagrelor with HSA. • Flavonoids could compete against ticagrelor in site I. • Baicalin was the most effective competitor among the three flavonoids.
Liu, Bing-Mi; Zhang, Jun; Bai, Chong-Liang; Wang, Xin; Qiu, Xin-Zhi; Wang, Xiao-Li; Ji, Hui; Liu, Bin
The effects of three kinds of flavonoids, quercetin, rutin and baicalin, on the binding of ticagrelor to human serum albumin (HSA) were systematically investigated using fluorescence, UV–vis absorption and circular dichroism (CD) spectroscopic techniques. The results indicated that ticagrelor strongly quenched the HSA fluorescence by the style of static quenching and non-radiation energy transferring as a result of the HSA–ticagrelor complex formation, while the presence of flavonoids could not change the quenching mechanism. Ticagrelor could spontaneously bind in site I on HSA with high affinity, and this binding process was mainly driven by both hydrophobic forces and hydrogen bonding. The significantly decreased binding affinity and the unchanged binding mode and distance between ticagrelor and HSA indicated that that flavonoids could compete against ticagrelor in site I, and baicalin was the most effective competitor. The conformation investigation of HSA further confirmed the flavonoid/ticagrelor competitive binding mechanism. - Highlights: • Ticagrelor could spontaneously bind in subdomain IIA (site I) on HSA with high affinity. • The presence of flavonoids could not change the quenching mechanism. • The presence of flavonoids significantly decreased the binding affinity of ticagrelor with HSA. • Flavonoids could compete against ticagrelor in site I. • Baicalin was the most effective competitor among the three flavonoids.
Landvatter, S.W.; Heys, J.R.; Garner, K.T.; Mack, J.F.; Senderoff, S.G.; Shu, A.Y.; Villani, A.J.; Saunders, D.
Radiolabelled drugs play a vital role in the development of new pharmaceuticals including application in drug discovery, pre-clinical development and clinical development. The synthesis of these pharmaceuticals in tritium or carbon-14 labelled form poses many challenges for the synthetic organic chemist. The actual choice of synthetic route must take into account the small scale, limited choice and high cost of labelled precursors, and the positioning of the label into a metabolically stable position. There are, however, a number of synthetic strategies available for overcoming these constraints. Although in some C-14 syntheses the requisite labelled raw material can be purchased and the existing synthesis adapted for labelling, frequently the synthetic challenge is the synthesis of a structurally simple, yet commercially unavailable, labelled precursor (e.g., γ-butyrolactone-[2- 14 C], cyclohexanone-[ 3 H], CuCN-[ 14 C], 2-furancarboxaldehyde-[ 14 C]). Another useful strategy in C-14 synthesis is the conversion of an advanced intermediate, or perhaps the unlabelled product itself, into a precursor which can then be reconverted into the labelled version of the intermediate. Occasionally, a new total synthesis must be developed. In addition to these strategies, tritium labelling can uniquely take advantage of exchange labelling techniques, synthesis and reduction of unsaturated precursors, or tritium-halogen replacement reactions. Examples of these strategies and use of the labelled products are discussed
Dobchev, Dimitar A; Pillai, Girinath G; Karelson, Mati
Machine learning (ML) computational methods for predicting compounds with pharmacological activity, specific pharmacodynamic and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties are being increasingly applied in drug discovery and evaluation. Recently, machine learning techniques such as artificial neural networks, support vector machines and genetic programming have been explored for predicting inhibitors, antagonists, blockers, agonists, activators and substrates of proteins related to specific therapeutic targets. These methods are particularly useful for screening compound libraries of diverse chemical structures, "noisy" and high-dimensional data to complement QSAR methods, and in cases of unavailable receptor 3D structure to complement structure-based methods. A variety of studies have demonstrated the potential of machine-learning methods for predicting compounds as potential drug candidates. The present review is intended to give an overview of the strategies and current progress in using machine learning methods for drug design and the potential of the respective model development tools. We also regard a number of applications of the machine learning algorithms based on common classes of diseases.
Lee, Andrew M.; Pasquato, Antonella; Kunz, Stefan
Hemorrhagic fevers caused by arenaviruses are among the most devastating emerging human diseases. Considering the number of individuals affected, the current lack of a licensed vaccine, and the limited therapeutic options, arenaviruses are arguably among the most neglected tropical pathogens and the development of efficacious anti-arenaviral drugs is of high priority. Over the past years significant efforts have been undertaken to identify novel potent inhibitors of arenavirus infection. High throughput screening of small molecule libraries employing pseudotype platforms led to the discovery of several potent and broadly active inhibitors of arenavirus cell entry that are effective against the major hemorrhagic arenaviruses. Mechanistic studies revealed that these novel entry inhibitors block arenavirus membrane fusion and provided novel insights into the unusual mechanism of this process. The success of these approaches highlights the power of small molecule screens in antiviral drug discovery and establishes arenavirus membrane fusion as a robust drug target. These broad screenings have been complemented by strategies targeting cellular factors involved in productive arenavirus infection. Approaches targeting the cellular protease implicated in maturation of the fusion-active viral envelope glycoprotein identified the proteolytic processing of the arenavirus glycoprotein precursor as a novel and promising target for anti-arenaviral strategies.
Kawabata, Thomas T; Evans, Ellen W
The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.
Chajbullinova, A.; Votýpka, Jan; Sádlová, J.; Kvapilová, K.; Seblova, V.; Kreisinger, J.; Jirků, Milan; Sanjoba, C.; Gantuya, S.; Matsumoto, Y.; Volf, P.
Roč. 5, OCT 2 (2012) ISSN 1756-3305 Institutional support: RVO:60077344 Keywords : Leishmania turanica * L. major * mixed infections * competition * genetic exchange * vector competence * Phlebotomus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.246, year: 2012 http://www.parasitesandvectors.com/content/5/1/219
May 17, 2011 ... 09.15 – 10.45 Session 1: The general case for alliance building ... relationship between corporate governance and a firm's competitive behaviour, ... Spencer Weber Waller, Director, Institute of Consumer Anti-Trust Studies, Loyola University ... tools for enforcement: the case of the remittance transfer market.
Katane, Irena; Kristovska, Ineta; Vjatere, Gita; Katans, Edgars
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…
Carlin, Anna; Manson, Daniel P.; Zhu, Jake
With the projected higher demand for Network Systems Analysts and increasing computer crime, network security specialists are an organization's first line of defense. The principle function of this paper is to provide the evolution of Collegiate Cyber Defense Competitions (CCDC), event planning required, soliciting sponsors, recruiting personnel…
The Chinese gas market is facing four key challenges and the government is elaborating responses which will have implications for the Chinese and world energy markets: - Enabling the development of gas demand in order to fight against the issue of air pollution which is particularly strong in the big coast cities of the East and South-East of the country. This means replacing coal and oil by cleaner energy sources, including natural gas for which demand is booming. In such a young market, everything needs to be put in place: from the construction of LNG terminals to the sale and installation of gas stoves. The price of gas needs to be competitive for the market to develop. - Securing supplies: As national production is struggling to follow the rise in demand and as shale gas - of which China owns the second largest reserves in the world - is still a distant dream, this country is more and more reliant on imports. For evident energy security reasons, China diversifies its supplies at the maximum level and develops new energy partnerships. Four importing routes are favoured: LNG transported by ships, the West axis with Central Asia, the South axis with Burma and the new North-East axis with Russia. These imports, which amounted to 53 bcm in 2013, may triple by 2020. Even though China managed to negotiate a favourable price with Russia and its LNG importing price is lower than the one of Japan - thanks to its first LNG importing contracts signed in the early 2000 - imports are expensive, in particular for a country used to producing or importing coal at a very low cost. Up to now, the price at which gas is sold could not cover the import price and this system is not sustainable. - Developing national production: Despite important gas reserves - in particular for unconventional gas (shale gas, tight gas, CBM) - production in China is still not much developed in comparison with its potential and the growth opportunities are significant. Making the best of this potential
Borry, Pascal; Caulfield, Timothy; Estivill, Xavier; Loland, Sigmund; McNamee, Michael; Knoppers, Bartha Maria
Through the widespread availability of location-identifying devices, geolocalisation could potentially be used to place athletes during out-of-competition testing. In light of this debate, the WADA Ethics Panel formulated the following questions: (1) should WADA and/or other sponsors consider funding such geolocalisation research projects?, (2) if successful, could they be proposed to athletes as a complementary device to Anti-Doping Administration and Management System to help geolocalisation and reduce the risk of missed tests? and (3) should such devices be offered on a voluntary basis, or is it conceivable that they would be made mandatory for all athletes in registered testing pools? In this position paper, the WADA Ethics Panel concludes that the use of geolocalisation could be useful in a research setting with the goal of understanding associations between genotype, phenotype and environment; however, it recognises that the use of geolocalisation as part of or as replacement of whereabouts rules is replete with ethical concerns. While benefits remain largely hypothetical and minimal, the potential invasion of privacy and the data security threats are real. Considering the impact on privacy, data security issues, the societal ramifications of offering such services and various pragmatic considerations, the WADA Ethics Panel concludes that at this time, the use of geolocalisation should neither be mandated as a tool for disclosing whereabouts nor implemented on a voluntary basis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Knowles, Richard Graham
The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.
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.
Alday, P Holland; Doggett, Joseph Stone
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.
Japan Atomic Energy Research Institute started the public competition research and development on nuclear science and technology in 1998, and closed it in 2003. This report describes the system of the competition research and development, application situations, R and D subjects adopted, evaluation findings, outputs produced, achievements and problems, as a summative report of practice of the system for six years. (author)
Japan Atomic Energy Research Institute started the public competition research and development on software for computational science and engineering in 1997, and closed it in 2002. This report describes the system of the competition research and development, application situations, R and D subjects adopted, evaluation findings, outputs produced, achievements and problems, as a summative report of practice of the system for six years. (author)
... different competition is going on: the National Football League (NFL) vs. drug use. Read More » 92 Comments ... Future survey highlights drug use trends among the Nation’s youth for marijuana, alcohol, cigarettes, e-cigarettes (e- ...
Alderman, Christopher P
To describe the development, implementation, and initial evaluation of a paperless drug and therapeutics bulletin that is distributed by electronic mail from the pharmacy department of an Australian teaching hospital. A standardized format for the bulletin was designed and approved in February 2001. The aim of the bulletin is to facilitate the timely dissemination of concise, factual information about issues of current interest in therapeutics, drug safety, and the cost-effective use of medicines. A simple and attractive graphic design was chosen, and the hospital's clinical pharmacists and drug information staff developed an initial bank of content during the period immediately preceding the launch. The bulletin is presented as a 1-page, read-only file in Word for Windows format and was initially distributed by electronic mail to all users of the hospital's computerized communication network. As the popularity of the bulletin increased, healthcare practitioners from outside of the hospital began to request permission for inclusion on the circulation list, and the content was frequently forwarded by E-mail to workers in other hospitals and community-based settings. The bulletin is now distributed to pharmacists around Australia via 2 separate moderated discussion lists, one of which provides an archive site for previous editions. Healthcare workers in Singapore, the US, Canada, and New Zealand also receive the bulletin, which is now also abstracted by a major Australian pharmacy journal. A readership survey (also electronically distributed) was used to seek feedback after the publication of the first 12 editions. Readers indicated a high level of satisfaction with the content, format, and frequency of distribution of the materials. Although the concept and execution of this project was relatively simple, an extensive literature review did not reveal any previously published reports describing this type of approach to the distribution of a pharmacy bulletin. The
Mash, Deborah C; Kovera, Craig A; Buck, Billy E; Norenberg, Michael D; Shapshak, Paul; Hearn, W Lee; Sanchez-Ramos, Juan
The potential for deriving new psychotherapeutic medications from natural sources has led to renewed 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 the 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.
Mash, D C; Kovera, C A; Buck, B E; Norenberg, M D; Shapshak, P; Hearn, W L; Sanchez-Ramos, J
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.
Schrattenholz, André; Soskić, Vukić
regard to a new focus on agents that modulate multiple targets simultaneously. Targeting cellular function as a system rather than on the level of the single protein molecule significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards "systemic" drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data and extraction of "screenable" information from biological systems essentially ruled by deterministic chaotic processes on a background of individual stochasticity.
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.
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.
Coleman, Robert A
Today's drug discovery and development paradigm is not working, and something needs to be done about it. There is good reason to believe that a move away from reliance on animal surrogates for human subjects in the Pharma Industry's R&D programmes could provide an important step forward. However, no serious move will be made in that direction until there is some hard evidence that it will be rewarded with improved productivity outcomes. The Safer Medicines Trust are proposing that a study be undertaken, involving a range of drugs that have been approved for human use, but have subsequently proved to have limitations in terms of safety and/or efficacy. The aim is to determine the efficiency of a battery of human-based test methods to identify a compound's safety and efficacy profiles, and to compare this with that of the more traditional, largely animal-based methods that were employed in their original development. Should such an approach prove more reliable, the authorities will be faced with important decisions relating to the role of human biological test data in regulatory submissions, while the Pharma Industry will be faced with the key logistical issue of how to acquire the human biomaterials necessary to make possible the routine application of such test methods. 2009 FRAME.
Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee
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.
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.
Tedjalaksana, Retta Margaretta; Aldianto, Leo
Every development demand a change, include in business world. Small businesses that are still using traditional management system face a challenge to maintaining the business continuity and facing competition in this modern era. Soybean Store Hadijanto Trisno, a hereditary business is facing some issues in running the business, which are company doesn't have functional division, lack of workers and transport during peak hours, and no database system. Those business issues are explored throu...
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.
Hamilton, Gregory S
Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Wang, Xiang; Ju, Wei
The topic of the thesis is improving the competitiveness of the case company. We will regard Suguo as the case compamy. We focused on a Chinese local convenience store, and compared it in four perspectives with an international convenience store which has already entered the Chinese market successfully. The four perspectives are market perspective, customer perspective, management perspective, and decorative style perspective. In addition, we created a strategic map on the basis of the consum...
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...
Pantri Heriyati; Ign. Heruwasto; Sari Wahyuni
Malaysia is opening parts of its services to greater foreign participation due to globalization. Local banks have since consolidated a decade ago and foreign banks expanding their businesses in local markets have intensified the competition. As a result, credit card adoption is getting more challenging to marketers. Hence effective marketing strategies are important. The theoretical model of the paper is based on the buyer behaviour model by Kotler and Armstrong (1999). The ...
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
Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M
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.
Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U
Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.
Arnold, Renée J G; Bighash, Lida; Bryón Nieto, Alejandro; Tannus Branco de Araújo, Gabriela; Gay-Molina, Juan Gabriel; Augustovski, Federico
Compared to a decade ago, nearly three times as many drugs for rare diseases are slated for development. This article addresses the market access issues associated with orphan drug status in Europe and the United States in contrast to the legislation in five Latin American (LA) countries that have made strides in this regard--Mexico, Brazil, Colombia, Chile and Argentina. Based on the success of orphan drug legislation in the EU and US, LA countries should strive to adopt similar strategies with regard to rare diseases and drug development. With the implementation of new targeted regulations, reimbursement strategies, and drug approvals, accessibility to treatment will be improved for people afflicted with rare diseases in these developing countries.
...] Draft Guidance for Industry on Complicated Urinary Tract Infections: Developing Drugs for Treatment... Urinary Tract Infections: Developing Drugs for Treatment.'' The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of complicated urinary tract infections (c...
Jensen, Kasper; Ni, Yueqiong; Panagiotou, Gianni
therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present...... view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in Drug-Bank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing......Recent research has demonstrated that consumption of food -especially fruits and vegetables-can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful...
Lowrence, Rene Christena; Raman, Thiagarajan; Makala, Himesh V; Ulaganathan, Venkatasubramanian; Subramaniapillai, Selva Ganesan; Kuppuswamy, Ashok Ayyappa; Mani, Anisha; Chittoor Neelakantan, Sundaresan; Nagarajan, Saisubramanian
Multi drug resistant (MDR) pathogens pose a serious threat to public health since they can easily render most potent drugs ineffective. Efflux pump inhibitors (EPI) can be used to counter the MDR phenotypes arising due to increased efflux. In the present study, a series of dithiazole thione derivatives were synthesized and checked for its antibacterial and efflux pump inhibitory (EPI) activity. Among 10 dithiazole thione derivatives, real-time efflux studies revealed that seven compounds were potent EPIs relative to CCCP. Zebrafish toxicity studies identified four non-toxic putative EPIs. Both DTT3 and DTT9 perturbed membrane potential and DTT6 was haemolytic. Among DTT6 and DTT10, the latter was less toxic as evidenced by histopathology studies. Since DTT10 was non-haemolytic, did not affect the membrane potential, and was least toxic, it was chosen further for in vivo study, wherein DTT10 potentiated effect of ciprofloxacin against clinical strain of MRSA and reduced bacterial burden in muscle and skin tissue of infected zebrafish by ~ 1.7 and 2.5 log fold respectively. Gene expression profiling of major efflux transport proteins by qPCR revealed that clinical isolate of MRSA, in the absence of antibiotic, upregulated NorA, NorB and MepA pump, whereas it downregulates NorC and MgrA relative to wild-type strain of Staphylococcus aureus. In vitro studies with NorA mutant strains and substrate profiling revealed that at higher concentrations DTT10 is likely to function as a competitive inhibitor of NorA efflux protein in S. aureus, whereas at lower concentrations it might inhibit ciprofloxacin efflux through NorB and MepA as implied by docking studies. A novel non-toxic, non-haemolytic dithiazole thione derivative (DTT10) was identified as a potent competitive inhibitor of NorA efflux pump in S. aureus using in silico, in vitro and in vivo studies. This study also underscores the importance of using zebrafish infection model to screen and evaluate putative EPI for
Jardim, Denis L; de Melo Gagliato, Débora; Giles, Francis J; Kurzrock, Razelle
Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR . ©2017 American Association for Cancer Research.
Minias, Alina; Brzostek, Anna; Dziadek, Jaroslaw
Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated proteins as targets for the development of new antitubercular compounds. We discuss data, including gene expression data, that highlight the importance of DNA repair genes during the pathogenic cycle as well as after exposure to antimicrobials currently in use. Specifically, we report experiments on determining the essentiality of DNA repair-related genes. We report the availability of protein crystal structures and summarize discovered protein inhibitors. Further, we describe phenotypes of available gene mutants of M. tuberculosis and model organisms Mycobacterium bovis and Mycobacterium smegmatis. We summarize experiments regarding the role of DNA repair-related proteins in pathogenesis and virulence performed both in vitro and in vivo during the infection of macrophages and animals. We detail the role of DNA repair genes in acquiring mutations, which influence the rate of drug resistance acquisition. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Full Text Available Abstract Recent advances in genomic sequencing and omics-based capabilities are uncovering tremendous therapeutic opportunities and rapidly transforming the field of cancer medicine. Molecularly targeted agents aim to exploit key tumor-specific vulnerabilities such as oncogenic or non-oncogenic addiction and synthetic lethality. Additionally, immunotherapies targeting the host immune system are proving to be another promising and complementary approach. Owing to substantial tumor genomic and immunologic complexities, combination strategies are likely to be required to adequately disrupt intricate molecular interactions and provide meaningful long-term benefit to patients. To optimize the therapeutic success and application of combination therapies, systematic scientific discovery will need to be coupled with novel and efficient clinical trial approaches. Indeed, a paradigm shift is required to drive precision medicine forward, from the traditional “drug-centric” model of clinical development in pursuit of small incremental benefits in large heterogeneous groups of patients, to a “strategy-centric” model to provide customized transformative treatments in molecularly stratified subsets of patients or even in individual patients. Crucially, to combat the numerous challenges facing combination drug development—including our growing but incomplete understanding of tumor biology, technical and informatics limitations, and escalating financial costs—aligned goals and multidisciplinary collaboration are imperative to collectively harness knowledge and fuel continual innovation.
Full Text Available The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.
Resnik, D B
This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on (1) the prospects for a reasonable profit and (2) the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry's efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and
Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.
Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426
Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L
Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.
Jambou, Ronan; Le Bras, Jacques; Randrianarivelojosia, Milijaona
Artemisinin combination therapy (ACT) paves the way for new opportunities to eliminate malaria in the tropics. However, the huge increase of ACT consumption raises major concerns about their availability over the next few years. At the same time a decrease in their efficacy has already been reported. Alongside the deployment of multifocal control programs, the process ranging from artemisia crop production to accreditation of new ACT combinations urgently needs to be strengthened to supply sufficient quantities of high-quality drugs. New suppliers will have the opportunity to enter this market to develop new formulations, and bioequivalence studies are required to validate these new formulations. It is thus crucial for national malaria control teams to be able to better scrutinize the dossier of these new formulations. Copyright © 2010 Elsevier Ltd. All rights reserved.
Full Text Available Drug development has been globalized, and multi-regional clinical trial (MRCT for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017.
Farhana Abu Bakar
Full Text Available Alphaviruses are enveloped, positive single-stranded RNA viruses, typically transmitted by arthropods. They often cause arthralgia or encephalitic diseases in infected humans and there is currently no targeted antiviral treatment available. The re-emergence of alphaviruses in Asia, Europe, and the Americas over the last decade, including chikungunya and o’nyong’nyong viruses, have intensified the search for selective inhibitors. In this review, we highlight key molecular determinants within the alphavirus replication complex that have been identified as viral targets, focusing on their structure and functionality in viral dissemination. We also summarize recent structural data of these viral targets and discuss how these could serve as templates to facilitate structure-based drug design and development of small molecule inhibitors.
Khalily, Muhammad Tahir
This paper describes moves towards the coordination of efforts to respond to the worsening drug abuse situation in Pakistan which affects all segments of society. The efforts reported seek to rectify inconsistencies in treatment policy resulting in unsatisfactory outcomes. Examples of collaborative strategies with encouraging results need further underpinning and expansion. There is, however, a lack of realization at the policy level of the need to effect changes in treatment formulated on a consistent and evidence-based approach. Policy has therefore been reviewed and proposals made for a comprehensive treatment strategy in line with international best practices to deal with this problem effectively and efficiently. Establishment of an addiction study centre at university level to continue professional and academic development is suggested.
Van Ha NGUYEN; Xavier GALIEGUE
Vietnam has been very successful for the last two decades, since the adoption of “Doi moi” in 1986. Over the last two decades, an economic growth rate in Vietnam has been one of the highest worldwide (with GDP growing by respectively 8% per year). The increase of the Vietnamese share of world trade is the highest of all major Asian exporters (including China) since the mid-1990s. « Why is Vietnam so competitive with respect to other Asian exporters? » This paper considers Vietnam's competitiv...
Sholklapper, Tal [Voltaiq, Inc.
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.
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1279] Medical Device Development Tools; Draft Guidance for Industry, Tool Developers, and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...
Allan, M C
To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part I of this series provides a background for the discussion of drug safety by defining the basic terms and showing the flow of safety information through a pharmaceutical company. The customers for adverse drug event data are identified to provide a basis for providing quality service. The development of a drug product is briefly reviewed to show the evolution of safety data. Drug development and safety are defined by federal regulations. These regulations are developed by the FDA with information from pharmaceutical manufacturers. The intent of the regulations and the accompanying guidelines is described. An illustration from the news media is cited to show an alternative, positive approach to handling an adverse event report. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text and additional readings are presented in an appendix. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction ;of the components
Roghanian, E.; Alipour, Mohammad
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.
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.
The objective of this work is to validate the technical targets in the governmental hydrogen energy road-map of Japan by analyzing market penetration of fuel cell vehicle(FCV)s and effects of fuel price and carbon tax on it from technology competition point of view. In this analysis, an energy system model of Japan based on MARKAL is used. The results of the analysis show that hydrogen FCVs could not have cost-competitiveness until 2030 without carbon tax, including the governmental actual plan of carbon tax. However, as the carbon tax rate increases, instead of conventional vehicles including gasoline hybrid electric vehicle, hydrogen FCVs penetrate to the market earlier and more. By assuming higher fuel price and severer carbon tax rate, market share of hydrogen FCVs approaches to the governmental goal. This suggests that cheaper vehicle cost and/or hydrogen price than those targeted in the road-map is required. At the same time, achievement of the technical targets in the road-map also allows to attain the market penetration target of hydrogen FCVs in some possible conditions. (authors)
Baldwin, Aaron David
The use of polymers as biomaterials has evolved over the past several decades, encompassing an expanding synthetic toolbox and many bio-mimetic approaches. Both synthetic and natural polymers have been used as components for biomaterials as their unique chemical structures can provide specific functions for desired applications. Of these materials, heparin, a highly sulfated naturally occurring polysaccharide, has been investigated extensively as a core component in drug delivery platforms and tissue engineering. The goal of this work was to further explore the use of heparin via conjugation with synthetic polymers for applications in drug delivery. We begin by investigating low molecular weight heparin (LMWH), a depolymerized heparin that is used medicinally in the prevention of thrombosis by subcutaneous injection or intravenous drip. Certain disease states or disorders require frequent administration with invasive delivery modalities leading to compliance issues for individuals on prolonged therapeutic courses. To address these issues, a long-term delivery method was developed for LMWH via subcutaneous injection of in situ hydrogelators. This therapy was accomplished by chemical modification of LMWH with maleimide functionality so that it may be crosslinked into continuous hydrogel networks with four-arm thiolated polyethylene glycol (PEG-SH). These hydrogels degrade via hydrolysis over a period of weeks and release bioactive LMWH with first-order kinetics as determined by in vitro and in vivo models, thus indicating the possibility of an alternative means of heparin delivery over current accepted methodologies. Evaluation of the maleimide-thiol chemistries applied in the LMWH hydrogels revealed reversibility for some conjugates under reducing conditions. Addition chemistries, such as maleimide-thiol reactions, are widely employed in biological conjugates and are generally accepted as stable. Here we show that the resulting succinimide thioether formed by the
Bergeron, Pierrette; Hiller, Christine A.
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…
Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei
Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.
Full Text Available Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.
Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M
Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, ptransdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.
Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.
Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615
Sardar, Samra; Andersson, Åsa
Development of novel drugs for treatment of chronic inflammatory diseases is to a large extent dependent on the availability of good experimental in vivo models in order to perform preclinical tests of new drugs and for the identification of novel drug targets. Here, we review a number of existing...... of in vivo models during development of anti-rheumatic drugs; from Methotrexate to various antibody treatments, to novel drugs that are, or have recently been, in clinical trials. For novel drugs, we have explored websites for clinical trials. Although one Rheumatoid Arthritis in vivo model cannot mirror...
This document examines competitiveness in the developing world. Chapters 1 through 3, which are largely conceptual, examine the following topics: the concept of competitiveness and why it is important; market-stimulating technology policies in developing countries, and the relationship between import liberalization and industrial performance.…
Sahlgren, C.M.; Meinander, A.; Zhang, H.; Cheng, F.; Preis, Maren; Xu, C.; Salminen, T.A.; Toivola, D.M.; Abankwa, D.; Rosling, A.; Karaman, D.Ş.; Salo-Ahen, O.M.H.; Österbacka, R.; Eriksson, J.E.; Willför, S.; Petre, I.; Peltonen, J.; Leino, R.; Johnson, M.; Rosenholm, J.; Sandler, N.
Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic
...] Draft Guidance for Industry on Pulmonary Tuberculosis: Developing Drugs for Treatment; Availability...) is announcing the availability of a draft guidance for industry entitled ``Pulmonary Tuberculosis... of antimycobacterial drugs for the treatment of pulmonary tuberculosis. This guidance applies to the...
El-Kattan, Ayman F; Varma, Manthena V; Steyn, Stefan J; Scott, Dennis O; Maurer, Tristan S; Bergman, Arthur
To assess the utility of Extended Clearance Classification System (ECCS) in understanding absorption, distribution, metabolism, and elimination (ADME) attributes and enabling victim drug-drug interaction (DDI) predictions. A database of 368 drugs with relevant ADME parameters, main metabolizing enzymes, uptake transporters, efflux transporters, and highest change in exposure (%AUC) in presence of inhibitors was developed using published literature. Drugs were characterized according to ECCS using ionization, molecular weight and estimated permeability. Analyses suggested that ECCS class 1A drugs are well absorbed and systemic clearance is determined by metabolism mediated by CYP2C, esterases, and UGTs. For class 1B drugs, oral absorption is high and the predominant clearance mechanism is hepatic uptake mediated by OATP transporters. High permeability neutral/basic drugs (class 2) showed high oral absorption, with metabolism mediated generally by CYP3A, CYP2D6 and UGTs as the predominant clearance mechanism. Class 3A/4 drugs showed moderate absorption with dominant renal clearance involving OAT/OCT2 transporters. Class 3B drugs showed low to moderate absorption with hepatic uptake (OATPs) and/or renal clearance as primary clearance mechanisms. The highest DDI risk is typically seen with class 2/1B/3B compounds manifested by inhibition of either CYP metabolism or active hepatic uptake. Class 2 showed a wider range in AUC change likely due to a variety of enzymes involved. DDI risk for class 3A/4 is small and associated with inhibition of renal transporters. ECCS provides a framework to project ADME profiles and further enables prediction of victim DDI liabilities in drug discovery and development.
Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F; Ries, Markus
Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.
Future Plan: • Construction cost evaluation of PGSFR and commercial SFR; – Component based capital cost evaluation of PGSFR is undergoing and will be completed by the first half of 2014; – Component cost is only based on the experience from that of LWR; • Cost Benefit Analysis of Future Nuclear Energy Mix; – With revised National Energy Plan (as of 2013); – Near-term: Benefit from LWR spent fuel recycling: - In Korean law, Share of Expense for spent fuel disposal is reserved as 0.4M$ per a LWR spent fuel assembly (as of 2003); – Long-term: Competitive power plant to LWR with self sustainable feature; • Revision of commercial SFR conceptual design; – Less constraint in material (fuel, cladding) irradiation experience; – More innovative features as long-term goal
Ioana Ancuţa IANCU
Full Text Available In the literature there are studies that deal with intermediaries in banking services (especially, mutual funds and pensions, insurance, real estate, etc. Most of them focus on subjects like investor behaviour, ethical issues and market manipulation. In this paper we intend to observe the stages in the evolution of the Financial Investment Services Companies (SSIF between 1995-2016 in relation with the number of transactions, the volume of traded shares, the number of issuing companies as well as the economic and political situation of our country. Moreover, our study shows that the number of SSIF's is little affected by economic crises or declines and is rather influenced by the annual net incomes of the population. Basically, SSIF’s are in constant competition with the rest of the financial institutions, banks being a good example.
Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors
Schneider, Lon S
The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
G. Z. Efimova
, risk and adventures. At the same time, uncompetitive respondents try to be “simple and modest, not to attract attention to themselves”; focused on abidance by rules; avoid condemnation by the people surrounding them.Triple, and sometimes, fivefold gap between some indicators received on the basis of response for different block questions of the questionnaire among competitive and noncompetitive students, demonstrates formation of essentially various vital strategy.Practical significance. The emphasized factors of the formation of competitive orientations and criteria of competitiveness evaluation can provide a framework for the development of organizational and managerial decisions in the system of professional education.
Nales, D.A.; Kozarewicz, Piotr; Aylward, Brian; de Vries, Rutger; Egberts, Toine C G; Rademaker, Carin M A; Schobben, Alfred F A M
The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed
van Riet-Nales, Diana A.; Kozarewicz, Piotr; Aylward, Brian; de Vries, Rutger; Egberts, Toine C G; Rademaker, Carin M A; Schobben, Alfred F A M
The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed
Konstantin V. Kovtsev
Full Text Available The article presents the main components of the university’s image as a tool of social partnership development. It focuses on the issues of forming a positive image of the university. The most preferable approaches to image formation are identified. It is proposed to consider the system of social partnership as a specific translator for opinions about the institution that transfers from partners and individuals, who are accepted for internal affairs of the university’s activities due to partner structures on a general public and consumer audience of high school. The author offers to improve the image of university developed of social partnership. The university’s activities for development of its brand which can be implemented by using the approaches described in the paper are considered. The article contains developed image-building mechanisms which make it possible to get bonuses for participation in the partnership structure by partners and which promote the competitiveness of the university.
John W. Olney
Full Text Available Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed Fetal Alcohol Spectrum Disorder (FASD, which may include craniofacial malformations, structural pathology in the brain, and a variety of long-term neuropsychiatric disturbances. There is compelling evidence that exposure to alcohol during early embryogenesis (4th week of gestation can cause excessive death of cell populations that are essential for normal development of the face and brain. While this can explain craniofacial malformations and certain structural brain anomalies that sometimes accompany FASD, in many cases these features are absent, and the FASD syndrome manifests primarily as neurobehavioral disorders. It is not clear from the literature how alcohol causes these latter manifestations. In this review we will describe a growing body of evidence documenting that alcohol triggers widespread apoptotic death of neurons and oligodendroglia (OLs in the developing brain when administered to animals, including non-human primates, during a period equivalent to the human third trimester of gestation. This cell death reaction is associated with brain changes, including overall or regional reductions in brain mass, and long-term neurobehavioral disturbances. We will also review evidence that many drugs used in pediatric and obstetric medicine, including general anesthetics (GAs and anti-epileptics (AEDs, mimic alcohol in triggering widespread apoptotic death of neurons and OLs in the third trimester-equivalent animal brain, and that human children exposed to GAs during early infancy, or to AEDs during the third trimester of gestation, have a significantly increased incidence of FASD-like neurobehavioral disturbances. These findings provide evidence that exposure of the developing human brain to GAs in early infancy, or to alcohol or AEDs in late gestation, can cause FASD-like neurodevelopmental disability syndromes. We propose that the mechanism by which
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.
Bhunu, C. P.
Homelessness and drug-misuse are known to exist like siamese twins. We present a model to capture the dynamics in the growth in the number of homeless (street kids and street adults) and drug misusers. The reproduction numbers of the model are determined and analyzed. Results from this study suggests that adult peer pressure plays a more significant role in the growth of drug-misuse and the number of street kids. This result suggests that in resource constrained settings intervention strategies should be tailor made to target adults whose behaviour influence others to misuse drugs and abuse children. Furthermore, numerical simulations show that homelessness and drug-misuse positively enhances, the growth of each other. Thus, to effectively control these two social problems require strategies targeting both of them.
The international community's commitment to halve by 2015 the HIV transmission among people who inject drugs has not only been largely missed, instead new HIV infections have increased by 30%. Moreover, drug injection remains one of the drivers of new HIV infections due to punitive responses and lack of harm reduction resourcing. In the midst of this situation, adolescents are a forgotten component of the global response to illegal drugs and their link with HIV infection. The Sustainable Development Goals (SDGs) present an opportunity to achieve the global objective of ending AIDS among adolescents who use drugs, by addressing the structural vulnerabilities they face be they economic, social, criminal, health-related or environmental. The implementation of the SDGs presents an opportunity to address the horizontal nature of drug policy and to efficiently address the drugs-adolescents-HIV risk nexus. Adolescent-focused drug policies are linked to goals 1, 3, 4, 10, 16 and 17. Goals 3 and 16 are the most relevant; the targets of the latter link to the criminalization of drug use and punitive policy environments and their impact on adolescents' health and HIV transmission risks. Moreover, it presents an opportunity to include adolescent needs that are missing in the three drug control conventions (1961, 1971 and 1988), and link them with the provisions of the Convention on the Rights of the Child (1989). Finally, the six principles to deliver on sustainable development are also an opportunity to divert adolescents who use drugs away from criminalization and punitive environments in which their vulnerability to HIV is greater. Addressing HIV among adolescents who use drugs is an extremely complex policy issue depending on different sets of binding and non-binding commitments, interventions and stakeholders. The complexity requires a horizontal response provided by the SDGs framework, starting with the collection of disaggregated data on this specific subgroup. Ending
Wu, Jian-Sheng; Zheng, Wei-Shi; Lai, Jian-Huang
Kernel competitive learning has been successfully used to achieve robust clustering. However, kernel competitive learning (KCL) is not scalable for large scale data processing, because (1) it has to calculate and store the full kernel matrix that is too large to be calculated and kept in the memory and (2) it cannot be computed in parallel. In this paper we develop a framework of approximate kernel competitive learning for processing large scale dataset. The proposed framework consists of two parts. First, it derives an approximate kernel competitive learning (AKCL), which learns kernel competitive learning in a subspace via sampling. We provide solid theoretical analysis on why the proposed approximation modelling would work for kernel competitive learning, and furthermore, we show that the computational complexity of AKCL is largely reduced. Second, we propose a pseudo-parallelled approximate kernel competitive learning (PAKCL) based on a set-based kernel competitive learning strategy, which overcomes the obstacle of using parallel programming in kernel competitive learning and significantly accelerates the approximate kernel competitive learning for large scale clustering. The empirical evaluation on publicly available datasets shows that the proposed AKCL and PAKCL can perform comparably as KCL, with a large reduction on computational cost. Also, the proposed methods achieve more effective clustering performance in terms of clustering precision against related approximate clustering approaches. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available The Chinese Belt and Road Initiative will open new trade routes between China and the European Union (EU and increase competition pressures on smaller EU member states. This article ranks where states like Estonia stand internationally in terms of innovativeness (and consequent competitiveness by conducting an econometric study of patent development, education policy and research and development (R&D expenditure policy. The authors claim that small member states such as Estonia should follow the example of countries such as Germany and adopt policies which focus more on increased public spending on R&D and innovation in public universities of science and technology, and raise support for high tech startups with a strong focus on international patenting. Member States must go further and subsidise R&D activities by focusing, inter alia, on filing of foreign patents such as triadic patents.
María de la Caridad Veloso Pérez
Full Text Available The proposal to the problematic solution dealt with in the present investigation is constituted by competitive sport activities, which respond to its totality to the integral diagnosis and therefore, to the individual and group characteristics of the selected students as it is shown, being of this form in the heat of correspondence with their real necessities. This activities were developed during the partaking sport time and three stages framed during the course to the competitions. Its organization was based on the same principles on which the Program of the Special Olympic Games is fomented, extracting from the quarries of the base sport the sport talent, it is for that reason so important the work of preparation and participation in the bases, as from the whole scale practice it is that the quality is obtained or the sport talent within the ample range of sport disciplines. The work's objective is to apply competitive sport activities to improve the participation of late mental development children in the systematic training. These activities, proposed as solution, were very effective, since it was obtained a favorable atmosphere in all the school in students, teachers, specialists, family, community, making possible these children to improved their participation in the systematic training, their technical level improved a lot and, mainly, they demonstrated that the sport is one of the fundamental routes to the formation of values in this population group. The results thrown by the investigation are considered valuable since it is the base for the profit of good results in the competence.
Snyder, Kristen M; Reaman, Gregory; Avant, Debbie; Pazdur, Richard
The Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children. A search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric-specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table. Fifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use. WRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Copyright © 2013 Wiley Periodicals, Inc.