WorldWideScience

Sample records for advancing drug innovation

  1. Protein Innovations Advance Drug Treatments, Skin Care

    Science.gov (United States)

    2012-01-01

    Dan Carter carefully layered the sheets of tracing paper on the light box. On each sheet were renderings of the atomic components of an essential human protein, one whose structure had long been a mystery. With each layer Carter laid down, a never-before-seen image became clearer. Carter joined NASA s Marshall Space Flight Center in 1985 and began exploring processes of protein crystal growth in space. By bouncing intense X-rays off the crystals, researchers can determine the electron densities around the thousands of atoms forming the protein molecules, unveiling their atomic structures. Cultivating crystals of sufficient quality on Earth was problematic; the microgravity conditions of space were far more accommodating. At the time, only a few hundred protein structures had been mapped, and the methods were time consuming and tedious. Carter hoped his work would help reveal the structure of human serum albumin, a major protein in the human circulatory system responsible for ferrying numerous small molecules in the blood. More was at stake than scientific curiosity. Albumin has a high affinity for most of the world s pharmaceuticals, Carter explains, and its interaction with drugs can change their safety and efficacy. When a medication enters the bloodstream a cancer chemotherapy drug, for example a majority of it can bind with albumin, leaving only a small percentage active for treatment. How a drug interacts with albumin can influence considerations like the necessary effective dosage, playing a significant role in the design and application of therapeutic measures. In spite of numerous difficulties, including having no access to microgravity following the 1986 Space Shuttle Challenger disaster, the image Carter had hoped to see was finally clarifying. In 1988, his lab had acquired specialized X-ray and detection equipment a tipping point. Carter and his colleagues began to piece together albumin s portrait, the formation of its electron densities coalescing on

  2. Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

    Science.gov (United States)

    Hanna, Debra; Romero, Klaus; Schito, Marco

    2017-03-01

    The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.

  3. A new prize system for drug innovation.

    Science.gov (United States)

    Gandjour, Afschin; Chernyak, Nadja

    2011-10-01

    We propose a new prize (reward) system for drug innovation which pays a price based on the value of health benefits accrued over time. Willingness to pay for a unit of health benefit is determined based on the cost-effectiveness ratio of palliative/nursing care. We solve the problem of limited information on the value of health benefits by mathematically relating reward size to the uncertainty of information including information on potential drug overuse. The proposed prize system offers optimal incentives to invest in research and development because it rewards the innovator for the social value of drug innovation. The proposal is envisaged as a non-voluntary alternative to the current patent system and reduces excessive marketing of innovators and generic drug producers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. International Conference on Advanced Computing for Innovation

    CERN Document Server

    Angelova, Galia; Agre, Gennady

    2016-01-01

    This volume is a selected collection of papers presented and discussed at the International Conference “Advanced Computing for Innovation (AComIn 2015)”. The Conference was held at 10th -11th of November, 2015 in Sofia, Bulgaria and was aimed at providing a forum for international scientific exchange between Central/Eastern Europe and the rest of the world on several fundamental topics of computational intelligence. The papers report innovative approaches and solutions in hot topics of computational intelligence – advanced computing, language and semantic technologies, signal and image processing, as well as optimization and intelligent control.

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

    Science.gov (United States)

    Nagai, T

    1997-11-01

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

  6. Continuous innovation in the drug life cycle

    NARCIS (Netherlands)

    Langedijk, J.

    2016-01-01

    Patients may benefit from new uses for old drugs. Competent authorities such as the European Medicines Agency evaluate the quality, efficacy and safety of a medicinal product for the use in a well-defined therapeutic indication. Innovations may continue upon the approval, for example through the

  7. [Challenges and strategies of drug innovation].

    Science.gov (United States)

    Guo, Zong-Ru; Zhao, Hong-Yu

    2013-07-01

    Drug research involves scientific discovery, technological inventions and product development. This multiple dimensional effort embodies both high risk and high reward and is considered one of the most complicated human activities. Prior to the initiation of a program, an in-depth analysis of "what to do" and "how to do it" must be conducted. On the macro level, market prospects, capital required, risk assessment, necessary human resources, etc. need to be evaluated critically. For execution, drug candidates need to be optimized in multiple properties such as potency, selectivity, pharmacokinetics, safety, formulation, etc., all with the constraint of finite amount of time and resources, to maximize the probability of success in clinical development. Drug discovery is enormously complicated, both in terms of technological innovation and organizing capital and other resources. A deep understanding of the complexity of drug research and our competitive edge is critical for success. Our unique government-enterprise-academia system represents a distinct advantage. As a new player, we have not heavily invested in any particular discovery paradigm, which allows us to select the optimal approach with little organizational burden. Virtue R&D model using CROs has gained momentum lately and China is a global leader in CRO market. Essentially all technological support for drug discovery can be found in China, which greatly enables domestic R&D efforts. The information technology revolution ensures the globalization of drug discovery knowledge, which has bridged much of the gap between China and the developed countries. The blockbuster model and the target-centric drug discovery paradigm have overlooked the research in several important fields such as injectable drugs, orphan drugs, and following high quality therapeutic leads, etc. Prejudice against covalent ligands, prodrugs, nondrug-like ligands can also be taken advantage of to find novel medicines. This article will

  8. Market entry, power, pharmacokinetics: what makes a successful drug innovation?

    Science.gov (United States)

    Alt, Susanne; Helmstädter, Axel

    2018-02-01

    Depending on the timing of market entry, radical innovations can be distinguished from incremental innovations. Whereas a radical innovation typically is the first available derivative of a drug class, incremental innovations are launched later and show a certain benefit compared with the radical innovation. Here, we use historical market data relating to pharmacokinetic (PK), pharmacodynamic (PD), and other drug-related properties to investigate which derivatives within certain drug classes have been most successful on the market. Based on our investigations, we suggest naming the most successful drugs 'overtaking innovation', because they often exceed the market share of all the other derivatives. Seven drug classes showed that the overtaking innovation is never a radical innovation, but rather an early incremental innovation, with advantages in manageability and/or tolerance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. [Innovative therapeutic strategies for intravesical drug administration].

    Science.gov (United States)

    Moch, C; Salmon, D; Rome, P; Marginean, R; Pivot, C; Colombel, M; Pirot, F

    2013-05-01

    Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Advanced materials and processing for drug delivery: the past and the future.

    Science.gov (United States)

    Zhang, Ying; Chan, Hon Fai; Leong, Kam W

    2013-01-01

    Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Challenges to Value-Enhancing Innovation in Health Care Delivery: Commonalities and Contrasts with Innovation in Drugs and Devices.

    Science.gov (United States)

    Garber, Steven; Gates, Susan M; Blume-Kohout, Margaret E; Burgdorf, James R; Wu, Helen

    2012-01-01

    Limiting the growth of health care costs while improving population health is perhaps the most important and difficult challenge facing U.S. health policymakers. The role of innovation in advancing these social goals is controversial, with many seeing innovation as a major cause of cost growth and many others viewing innovation as crucial for improving the quality of care and health outcomes. The authors argue that mitigating the tension between improving health and controlling costs requires more-nuanced perspectives on innovation. More specifically, they argue that policymakers should carefully distinguish between innovative activities that are worth their social costs and activities that are not worth their social costs and try to encourage the former and discourage the latter. The article considers innovation in drugs, devices, and methods of delivering health care, with particular attention to delivery.

  12. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

    Directory of Open Access Journals (Sweden)

    Nicholas Ekow Thomford

    2018-05-01

    Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug

  13. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

    Science.gov (United States)

    Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

    2018-05-25

    The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review

  14. Advancement in integrin facilitated drug delivery.

    Science.gov (United States)

    Arosio, Daniela; Casagrande, Cesare

    2016-02-01

    The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. Copyright © 2015

  15. Advancing innovation in health care leadership: a collaborative experience.

    Science.gov (United States)

    Garcia, Victor H; Meek, Kevin L; Wilson, Kimburli A

    2011-01-01

    The changing framework of today's health care system requires leaders to be increasingly innovative in how they approach their daily functions and responsibilities. Sustaining and advancing a level of innovation that already exists can be challenging for health care administrators with the demands of time and resource limitations. Using collaboration to bring new-age teaching and disciplines to front-line leadership, one hospital was able to reinvigorate a culture of innovation through multiple levels and disciplines of the organization. The Innovation Certification Course provided nursing leaders and other managers' an evidence-drive approach, new principles and useful strategies of innovative leadership and graduate program education.

  16. Accessing external innovation in drug discovery and development.

    Science.gov (United States)

    Tufféry, Pierre

    2015-06-01

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

  17. Advances in buccal drug delivery.

    Science.gov (United States)

    Birudaraj, Raj; Mahalingam, Ravichandran; Li, Xiaoling; Jasti, Bhaskara R

    2005-01-01

    The buccal route offers an attractive alternative for systemic drug delivery of drugs because of better patient compliance, ease of dosage form removal in emergencies, robustness, and good accessibility. Use of buccal mucosa for drug absorption was first attempted by Sobrero in 1847, and since then much research was done to deliver drugs through this route. Today, research is more focused on the development of suitable delivery devices, permeation enhancement, and buccal delivery of drugs that undergo a first-pass effect, such as cardiovascular drugs, analgesics, and peptides. In addition, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity. In this review, the anatomy and physiology of buccal mucosa, followed by discussion of recent literature on the buccal permeation enhancement, and pathways of enhancement for various molecules are detailed. In addition, bioadhesion theories from historic perspective and current status are discussed. The various dosage forms on the market and in different stages of development are also reviewed.

  18. Open Innovation at NASA: A New Business Model for Advancing Human Health and Performance Innovations

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth E.; Keeton, Kathryn E.

    2014-01-01

    This paper describes a new business model for advancing NASA human health and performance innovations and demonstrates how open innovation shaped its development. A 45 percent research and technology development budget reduction drove formulation of a strategic plan grounded in collaboration. We describe the strategy execution, including adoption and results of open innovation initiatives, the challenges of cultural change, and the development of virtual centers and a knowledge management tool to educate and engage the workforce and promote cultural change.

  19. Challenges to value-enhancing innovation in health care delivery: commonalities and contrasts with innovation in drugs and devices

    National Research Council Canada - National Science Library

    Garber, Steven

    2011-01-01

    .... health policymakers. The role of innovation in advancing these social goals is controversial, with many seeing innovation as a major cause of cost growth and many others viewing innovation as crucial for improving...

  20. SMART POLYMERS: INNOVATIONS IN NOVEL DRUG DELIVERY

    OpenAIRE

    Apoorva Mahajan; Geeta Aggarwal

    2011-01-01

    Smart polymers are attracting the researchers for development of novel drug delivery systems. Importance of smart polymers is rising day by day as these polymers undergo large reversible, physical or chemical changes in response to small changes in the environmental conditions such as pH, temperature, dual- stimuli, light and phase transition. Smart polymers are representing promising means for targeted drug delivery, enhanced drug delivery, gene therapy, actuator stimuli and protein folders....

  1. Something new every day: defining innovation and innovativeness in drug therapy.

    Science.gov (United States)

    Aronson, Jeffrey K

    2008-01-01

    The word "innovation" comes from the Latin noun innovatio, derived from the verb innovare, to introduce [something] new. It can refer either to the act of introducing something new or to the thing itself that is introduced. In terms of commerce, it is defined in the Oxford English Dictionary as "the action of introducing a new product into the market; a product newly brought on to the market," a definition that illustrates both aspects of the word's meaning. "Innovativeness" is the property of being an innovation. Here I identify several different types of innovativeness in drug therapy, including structural, pharmacological or pharmacodynamic, pharmaceutical, and pharmacokinetic innovativeness, and I stress the over-riding importance of clinical innovativeness, which should result in a better benefit to harm balance at an affordable cost.

  2. Antiviral Information Management System (AIMS): a prototype for operational innovation in drug development.

    Science.gov (United States)

    Jadhav, Pravin R; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra

    2010-09-01

    This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques.

  3. Innovation strategies for generic drug companies: moving into supergenerics.

    Science.gov (United States)

    Ross, Malcolm S F

    2010-04-01

    Pharmaceutical companies that market generic products generally are not regarded as innovators, but rather as companies that produce copies of originator products to be launched at patent expiration. However, many generics companies have developed excellent scientific innovative skills in an effort to circumvent the defense patents of originator companies. More patents per product, in terms of both drug substances (process patents and polymorph patents) and formulations, are issued to generics companies than to companies that are traditionally considered to be 'innovators'. This quantity of issued patents highlights the technical knowledge and skill sets that are available in generics companies. In order to adopt a completely innovative model (ie, the development of NCEs), a generics company would require a completely new set of skills in several fields, including a sufficient knowledge base, project and risk management experience, and capability for clinical data evaluation. However, with relatively little investment, generics companies should be able to progress into the so-called 'supergeneric' drug space - an area of innovation that reflects the existing competencies of both innovative and generics companies.

  4. Innovations in Advanced Materials and Metals Manufacturing Project (IAM2)

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Elizabeth [Columbia River Economic Development Council, Vancouver, WA (United States)

    2017-01-06

    This project, under the Jobs and Innovation Accelerator Challenge, Innovations in Advanced Materials and Metals Manufacturing Project, contracted with Cascade Energy to provide a shared energy project manager engineer to work with five different companies throughout the Portland metro grant region to implement ten energy efficiency projects and develop a case study to analyze the project model. As a part of the project, the energy project manager also looked into specific new technologies and methodologies that could change the way energy is consumed by manufacturers—from game-changing equipment and technology to monitor energy use to methodologies that change the way companies interact and use their machines to reduce energy consumption.

  5. 76 FR 23543 - The Jobs and Innovation Accelerator Challenge; a Coordinated Initiative To Advance Regional...

    Science.gov (United States)

    2011-04-27

    ... Jobs and Innovation Accelerator Challenge; a Coordinated Initiative To Advance Regional Competitiveness... Federal resources to support regional innovation and sustainable economic prosperity. Knowing that regional innovation clusters provide a globally proven approach for developing economic prosperity, this...

  6. Industry Perspectives on Market Access of Innovative Drugs: The Relevance for Oncology Drugs

    OpenAIRE

    Pauwels, Kim; Huys, Isabelle; Casteels, Minne; Simoens, Steven

    2016-01-01

    Key Points - Representatives of the pharmaceutical industry call for a broader recognition of value within the assessment and appraisal of innovative drugs - Focus on value within the assessment and appraisal of drugs is jeopardized by financial drives as the side of industry and at the side of the payers - A well–considered value-framework, with attention for patient reported outcomes, societal preferences and dynamic approach on the drug life cycle, needs to be incorporated in ass...

  7. Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines.

    Science.gov (United States)

    Schito, Marco; Migliori, Giovanni Battista; Fletcher, Helen A; McNerney, Ruth; Centis, Rosella; D'Ambrosio, Lia; Bates, Matthew; Kibiki, Gibson; Kapata, Nathan; Corrah, Tumena; Bomanji, Jamshed; Vilaplana, Cris; Johnson, Daniel; Mwaba, Peter; Maeurer, Markus; Zumla, Alimuddin

    2015-10-15

    Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Alka Lohani

    2014-01-01

    Full Text Available Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs.

  9. Innovations and Advances in Computer, Information, Systems Sciences, and Engineering

    CERN Document Server

    Sobh, Tarek

    2013-01-01

    Innovations and Advances in Computer, Information, Systems Sciences, and Engineering includes the proceedings of the International Joint Conferences on Computer, Information, and Systems Sciences, and Engineering (CISSE 2011). The contents of this book are a set of rigorously reviewed, world-class manuscripts addressing and detailing state-of-the-art research projects in the areas of  Industrial Electronics, Technology and Automation, Telecommunications and Networking, Systems, Computing Sciences and Software Engineering, Engineering Education, Instructional Technology, Assessment, and E-learning.

  10. Some Recent Advances in Transdermal Drug Delivery Systems ...

    African Journals Online (AJOL)

    Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

  11. Advanced design cultures long-term perspective and continuous innovation

    CERN Document Server

    2015-01-01

    This book describes new thinking and practice in Advanced Design (ADD) – design that is not merely highly developed but anticipates the future by envisioning novel products and processes. The focus is especially on the front end of innovation and the search for solutions in complex pioneering processes using design-related tools and practices. The book opens by describing these tools, the approaches that characterize ADD, and its historical dimension. Specific fields in which ADD has flourished are then examined, exploring the dynamics between research and design. The coverage ranges from transportation, lighting, and electrical appliances through to business networks, technology parks, and the development of ground-breaking materials. AdvanceDesign is the name of the research group at the Politecnico di Milano (Italy’s largest technical university) of which the authors are members. It was chosen to reflect both the “advanced”, tangible dimension of design in terms of modern product development, mater...

  12. Promoting Value, Affordability, and Innovation in Cancer Drug Treatment - The Rising Cost of Cancer Drugs: Impact on Patients and Society

    Science.gov (United States)

    Innovative new drugs have improved outcomes for many cancer patients. But spending on cancer drugs has increased dramatically in recent years, placing a burden on cancer patients and a strain on health system and societal resources.

  13. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative

  14. New perspectives on innovative drug discovery: an overview.

    Science.gov (United States)

    Pan, Si Yuan; Pan, Shan; Yu, Zhi-Ling; Ma, Dik-Lung; Chen, Si-Bao; Fong, Wang-Fun; Han, Yi-Fan; Ko, Kam-Ming

    2010-01-01

    Despite advances in technology, drug discovery is still a lengthy, expensive, difficult, and inefficient process, with a low rate of success. Today, advances in biomedical science have brought about great strides in therapeutic interventions for a wide spectrum of diseases. The advent of biochemical techniques and cutting-edge bio/chemical technologies has made available a plethora of practical approaches to drug screening and design. In 2010, the total sales of the global pharmaceutical market will reach 600 billion US dollars and expand to over 975 billion dollars by 2013. The aim of this review is to summarize available information on contemporary approaches and strategies in the discovery of novel therapeutic agents, especially from the complementary and alternative medicines, including natural products and traditional remedies such as Chinese herbal medicine.

  15. Industry perspectives on market access of innovative drugs

    Directory of Open Access Journals (Sweden)

    Kim ePauwels

    2016-06-01

    Full Text Available This study presents industry perspectives on the challenges related to market access of innovative drugs in general and oncology drugs in specific. Fifteen interviews were conducted with representatives of pharmaceutical companies and industry associations. Interviewees call for a broader recognition of value within the assessment and appraisal of drugs. According to interviewees, focus on value is jeopardized by the lack of a common value definition across Europe, poor availability and validity of value measures and cost-saving measures such as external reference price setting and cost-effectiveness analysis at the side of the payers. Centralized assessment of relative-effectiveness at European level would provide a common value estimate across member states, independent of financial drivers. Empirical evidence on patient reported outcomes and societal preferences is however essential in the development of a value definition. Furthermore, value-based pricing would imply a dynamic approach where the price is differentiated across indications and across the lifecycle of the drug, especially in fields such as oncology. Financial drivers however also threat the application of value-based pricing at the side of the industry, making value-based profitability a more appropriate term.

  16. International conference on Advances in Intelligent Control and Innovative Computing

    CERN Document Server

    Castillo, Oscar; Huang, Xu; Intelligent Control and Innovative Computing

    2012-01-01

    In the lightning-fast world of intelligent control and cutting-edge computing, it is vitally important to stay abreast of developments that seem to follow each other without pause. This publication features the very latest and some of the very best current research in the field, with 32 revised and extended research articles written by prominent researchers in the field. Culled from contributions to the key 2011 conference Advances in Intelligent Control and Innovative Computing, held in Hong Kong, the articles deal with a wealth of relevant topics, from the most recent work in artificial intelligence and decision-supporting systems, to automated planning, modelling and simulation, signal processing, and industrial applications. Not only does this work communicate the current state of the art in intelligent control and innovative computing, it is also an illuminating guide to up-to-date topics for researchers and graduate students in the field. The quality of the contents is absolutely assured by the high pro...

  17. Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

    Science.gov (United States)

    Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

    2011-02-01

    The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

  18. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  19. Innovation Training within the Australian Advanced Manufacturing Industry

    Science.gov (United States)

    Donovan, Jerome Denis; Maritz, Alex; McLellan, Andrew

    2013-01-01

    Innovation has emerged as a core driver for the future profitability and success of the manufacturing sector, and increasingly both governments and the private sector are examining ways to support the development of innovation capabilities within organisations. In this research, we have evaluated a government-funded innovation training course…

  20. Recent Advances in Ocular Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Shinobu Fujii

    2011-01-01

    Full Text Available Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient’s and doctor’s convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

  1. Recent Advances in Drug-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Naoko Inomata

    2012-01-01

    Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

  2. Recent advances in targeted drug therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    FAN Yongqiang

    2018-02-01

    Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

  3. Advancing drug availability-experiences from Africa.

    Science.gov (United States)

    Powell, Richard A; Kaye, Richard Mugula; Ddungu, Henry; Mwangi-Powell, Faith

    2010-07-01

    International health and drug regulatory authorities acknowledge that analgesics (especially opioids) are insufficiently available for pain management in many countries. In Africa, reported morphine consumption is far below the global mean, with multiple factors hampering opioid supply. Since 2006, the African Palliative Care Association has hosted three regional drug availability workshops across the continent to address this issue. Using an interactive format, the workshops have identified country-specific barriers to opioid and other essential medication accessibility before supporting participants to develop action plans to address recognized impediments. Despite multiple challenges, a number of successes have arisen from the implementation of the plans. However, key issues remain, including the introduction of supportive policy environments, effective educational initiatives, and measures to address supply-chain obstacles impeding drug availability. Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  4. Recent Advances in Drug Development and Regulatory Science in China.

    Science.gov (United States)

    Chen, Jie; Zhao, Naiqing

    2018-01-01

    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.

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

    Science.gov (United States)

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

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ji Young Yhee

    2016-09-01

    Full Text Available Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD, cystic fibrosis (CF, idiopathic pulmonary fibrosis (IPF, and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed.

  7. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    Science.gov (United States)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  8. From generic to biosimilar drugs: why take an innovative pace?

    Directory of Open Access Journals (Sweden)

    Fereshteh Barei

    2012-12-01

    Full Text Available BACKGROUND: The transition of the generic/biotechnology industry to innovation by investing in innovative R&D will enhance business expertise in biopharmaceutical development and manufacturing. The major impact of this evolution is on patient access to treatment and savings for the health care systems. OBJECTIVES: The aim of this paper is to investigate the innovative aspect of biosimilar and biobetter products, manufactured by some big generic companies. We will also try to explore the innovative business strategy, implementing this high risk product differentiation policy. METHODS: This qualitative research is conducted by a series of interviews with CEOs, physicians, and academics in different countries. The qualitative data obtained were analyzed by Nvivo9.2 software. A literature review has also contributed to our key findings. RESULTS: The results show that switching into biosimilars/biobetters is an innovative strategic choice, approved by some big generic pharmaceutical companies. The biosimilar/biobetter products can be considered innovative because of their value added quality. CONCLUSION: Expanding the product portfolio to biosimilars/biobetter can be considered as a long run strategy in the innovative business plans aiming to ensure the market access. Patients and their access to better treatments are major components of these innovative business models.

  9. Reply to "transforming oncology care": advancing value, accessing innovation.

    Science.gov (United States)

    Paradis, Rebecca

    2015-09-01

    Alternative payment models in oncology are already successfully standardizing care, curbing costs, and improving the patient experience. Yet, it is unclear whether decision makers are adequately considering patient access to innovation when creating these models, which could have severe consequences for a robust innovation ecosystem and the lives of afflicted patients. The suggested chart includes recommendations on: Allowing for the adoption of new, promising therapies; Promoting the measurement of patient-centered outcomes; and Providing support for personalized medicine.

  10. An improved approach to measuring drug innovation finds steady rates of first-in-class pharmaceuticals, 1987-2011.

    Science.gov (United States)

    Lanthier, Michael; Miller, Kathleen L; Nardinelli, Clark; Woodcock, Janet

    2013-08-01

    For more than a decade, industry analysts and policy makers have raised concerns about declining pharmaceutical innovation, citing declining numbers of new molecular entities (NMEs) approved in the United States each year. Yet there is little consensus on whether this is the best measure of "innovation." We examined NME approvals during 1987-2011 and propose the three distinct subcategories of NMEs--first-in-class, advance-in-class, and addition-to-class--to provide more nuanced and informative insights into underlying trends. We found that trends in NME approvals were largely driven by addition-to-class, or "me too," drug approvals, while first-in-class approvals remained fairly steady over the study period. Moreover, the higher proportion of first-in-class drug approvals over the most recent decade is an encouraging sign of the health of the industry as a whole.

  11. Drumming: An Innovative Alternative for Drug Addicted Individuals

    Science.gov (United States)

    Hill, John C.; Hains, Bryan; Ricketts, Kristina

    2017-01-01

    Drug abuse has been a persistent problem within the United States. Among the nation, Kentucky ranks third in drug overdose and drug mortality rates, with numbers quadrupling from 1999 to 2010. Recent statistics indicate drug offenders account or a significant portion of individuals within the criminal justice system, directly affecting the…

  12. Diterpenes: Advances in Neurobiological Drug Research.

    Science.gov (United States)

    Islam, Md Torequl; da Silva, Claucenira Bandeira; de Alencar, Marcus Vinícius Oliveira Barros; Paz, Márcia Fernanda Correia Jardim; Almeida, Fernanda Regina de Castro; Melo-Cavalcante, Ana Amélia de Carvalho

    2016-06-01

    A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action-wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro-protection, anti-epileptic, anxiolytic, anti-Alzheimer's disease, anti-Parkinson's disease, anti-cerebral ischemia, anti-neuropathic pain, anti-neuro-inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Advanced drug delivery approaches against periodontitis.

    Science.gov (United States)

    Joshi, Deeksha; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

  14. Open innovation in early drug discovery: roadmaps and roadblocks.

    Science.gov (United States)

    Reichman, Melvin; Simpson, Peter B

    2016-05-01

    Open innovation in pharmaceutical R&D evolved from a triple helix of convergent paradigm shifts in academic, industrial and government research sectors. The birth of the biotechnology sector catalyzed shifts in location dynamics that led to the first wave of open innovation in pharmaceutical R&D between big pharma and startup companies. The National Institutes of Health (NIH) Roadmap was a crucial inflection point that set the stage for a new wave of open innovation models between pharmaceutical companies and universities that have the potential to transform the pharmaceutical R&D landscape. We highlight the attributes of leading protected open innovation models that foster the sharing of proprietary small molecule collections by lowering the risk of premature escape of intellectual property, particularly structure-activity data. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Advanced and sustainable fuel cycles for innovative reactor systems

    International Nuclear Information System (INIS)

    Glatz, J. P.; Malmbeck, R.; Purroy, D. S.; Soucek, P.; Inoue, T.; Uozumi, K.

    2007-01-01

    The key objective of nuclear energy systems of the future as defined by the Generation IV road map is to provide a sustainable energy generation for the future. It includes the requirement to minimize the nuclear waste produced and thereby notably reduce the long term stewardship burden in the future. It is therefore evident that the corresponding fuel cycles will play a central role in trying to achieve these goals by creating clean waste streams which contain almost exclusively the fission products. A new concept based on a grouped separation of actinides is widely discussed in this context, but it is of course a real challenge to achieve this type of separation since technologies available today have been developed to separate actinides from each other. In France, the CEA has launched extensive research programs in the ATALANTE facility in Marcoule to develop the advanced fuel cycles for new generation reactor systems. In this so called global actinide management (GAM) concept, the actinides are extracted in a sequence of chemical reactions (grouped actinide extraction (GANEX)) and immediately reintroduced in the fuel fabrication process is to use all actinides in the energy production process. The new group separation processes can be derived as in this case from aqueous techniques but also from so-called pyrochemical partitioning processes. Significant progress was made in recent years for both routes in the frame of the European research projects PARTNEW, PYROREP and EUROPART, mainly devoted to the separation of minor actinides in the frame of partitioning and transmutation (P and T) studies. The fuels used in the new generation reactors will be significantly different from the commercial fuels of today. Because of the fuel type and the very high burn-ups reached, pyrometallurgical reprocessing could be the preferred method. The limited solubility of some of the fuel materials in acidic aqueous solutions, the possibility to have an integrated irradiation and

  16. Advancing Drug Safety Through Prospective Pharmacovigilance.

    Science.gov (United States)

    Pitts, Peter J; Le Louet, Hervé

    2018-01-01

    Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time. To improve the ability of patients to receive high-quality, safe, effective, and timely care, better information via pharmacovigilance must be a priority as the world's many regulatory systems build the capacity to harness electronic health information to improve health, care quality, and safety. Globally, the widely variable ability of nations to build reliable regulatory systems (from precise review to robust pharmacovigilance) is a dangerous source of health care inequality. Developing validated tools and techniques for "predictive pharmacovigilance" will assist all health systems in better understanding the risks and benefits of the medicines they regulate by understanding what should be happening once a new medicine moves from risk-benefit regulatory efficacy to real-world risk-effectiveness. This will be of particular utility for smaller regulatory agencies with fewer resources. By comparing preapproval predictive pharmacovigilance data, developing regulatory authorities will be able to better understand the potential gap between what was predicted and what was actually measured (via more traditional pharmacovigilance methodologies). Predictive pharmacovigilance recognizes the value of understanding the imperfect reporting of real-world clinical use and that the absence of reporting is, in itself, an important postmarketing signal.

  17. Polymeric drugs: Advances in the development of pharmacologically active polymers

    Science.gov (United States)

    Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

    2015-01-01

    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

  18. Porous silicon advances in drug delivery and immunotherapy.

    Science.gov (United States)

    Savage, David J; Liu, Xuewu; Curley, Steven A; Ferrari, Mauro; Serda, Rita E

    2013-10-01

    Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. [Recent Advances in Vaccines and Drugs Against the Ebola Virus].

    Science.gov (United States)

    Zhu, Xiang; Yao, Chenguang; Wei, Yanhong; Kou, Zheng; Hu, Kanghong

    2015-05-01

    The Ebola virus belongs to the Filovirus family, which causes Ebola hemorrhagic fever (mortality, 25%-90%). An outbreak of infection by the Ebola virus is sweeping across West Africa, leading to high mortality and worldwide panic. The Ebola virus has caused a serious threat to public health, so intensive scientific studies have been carried out. Several vaccines (e.g., rVSV-ZEBOV, ChAd3-ZEBOV) have been put into clinical trials and antiviral drugs (e.g., TKM-Ebola, ZMAPP) have been administered in the emergency setting to patients infected by the Ebola virus. Here, recent advances in vaccines and drugs against the Ebola virus are reviewed.

  20. Innovation

    Science.gov (United States)

    EPA frames innovation as critical to the protection of human health and the environment through initiatives such as sustainable practices, innovative research, prize competitions, innovation awards, partnerships, and community activities.

  1. Advances in fragment-based drug discovery platforms.

    Science.gov (United States)

    Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

    2009-11-01

    Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

  2. Advance of technological innovations of electric power in 2012

    International Nuclear Information System (INIS)

    Mayumi, Akihiko; Tanaka, Masanori; Takebe, Toshiro

    2013-01-01

    Twelve companies in Japan reported on the technological innovations in 2012. The Japan Atomic Power Company mainly studied five projects; (1) control of wall thinning of the secondary system in PWR by injection of molybdic acid, (2) application of pipe test method using electromagnetic acoustic resonance to existing equipment, (3) developed high performance Co-60 crud removal resin for Tsuruga Power Station Unit 2, (4) improvement of technology for safety of core in FBR, and (5) improvement of technology for coolant of FBR by dispersing nano-particles in liquid sodium metal. Tokyo Electric Power Company developed mainly three projects; (1) the support for the mental health care activities by industry protection staff at the Fukushima Daiichi and Daini Nuclear Power Plant, (2) laboratory test method using non-radioactive cesium for performance of decontamination reagent, and (3) decontamination effects estimation code (DeConEP). Hokuriku Electric Power Company reported the operations management measures in accordance with the safety enhancement measures to Shika nuclear power station. Other nine reports are published by Hokkaido Electric Power Co., Inc. Tohoku Electric Power Co., Inc. Chubu Electric Power Co., Inc., The Kansai Electric Power Co., Inc., The Chugoku Electric Power Co., Inc., Shikoku Electric Power Co., Inc., Kyushu Electric Power Co., Inc., Okinawa Electric Power Company Inc. and J-Power. (S.Y.)

  3. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe

    2015-12-01

    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  4. Recent advances in immunosensor for narcotic drug detection

    Science.gov (United States)

    Gandhi, Sonu; Suman, Pankaj; Kumar, Ashok; Sharma, Prince; Capalash, Neena; Suri, C. Raman

    2015-01-01

    Introduction: Immunosensor for illicit drugs have gained immense interest and have found several applications for drug abuse monitoring. This technology has offered a low cost detection of narcotics; thereby, providing a confirmatory platform to compliment the existing analytical methods. Methods: In this minireview, we define the basic concept of transducer for immunosensor development that utilizes antibodies and low molecular mass hapten (opiate) molecules. Results: This article emphasizes on recent advances in immunoanalytical techniques for monitoring of opiate drugs. Our results demonstrate that high quality antibodies can be used for immunosensor development against target analyte with greater sensitivity, specificity and precision than other available analytical methods. Conclusion: In this review we highlight the fundamentals of different transducer technologies and its applications for immunosensor development currently being developed in our laboratory using rapid screening via immunochromatographic kit, label free optical detection via enzyme, fluorescence, gold nanoparticles and carbon nanotubes based immunosensing for sensitive and specific monitoring of opiates. PMID:26929925

  5. Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

    Science.gov (United States)

    Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

    2014-01-01

    The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

  6. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum

    Directory of Open Access Journals (Sweden)

    Ahlam Zaid Alkilani

    2015-10-01

    Full Text Available The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

  7. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

    Science.gov (United States)

    Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

    2015-01-01

    The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

  8. Brian Barry: innovative contributions to transdermal and topical drug delivery.

    Science.gov (United States)

    Williams, A C

    2013-01-01

    Brian Barry published over 300 research articles across topics ranging from colloid science, vasoconstriction and the importance of thermodynamics in dermal drug delivery to exploring the structure and organisation of the stratum corneum barrier lipids and numerous strategies for improving topical and transdermal drug delivery, including penetration enhancers, supersaturation, coacervation, eutectic formation and the use of varied liposomes. As research in the area blossomed in the early 1980s, Brian wrote the book that became essential reading for both new and established dermal delivery scientists, explaining the background mathematics and principles through to formulation design. Brian also worked with numerous scientists, as collaborators and students, who have themselves taken his rigorous approach to scientific investigation into their own research groups. This paper can only describe a small fraction of the many significant contributions that Brian made to the field during his 40-year academic career.

  9. Key drivers of biomedical innovation in cancer drug discovery

    OpenAIRE

    Huber, Margit A; Kraut, Norbert

    2014-01-01

    Discovery and translational research has led to the identification of a series of ?cancer drivers??genes that, when mutated or otherwise misregulated, can drive malignancy. An increasing number of drugs that directly target such drivers have demonstrated activity in clinical trials and are shaping a new landscape for molecularly targeted cancer therapies. Such therapies rely on molecular and genetic diagnostic tests to detect the presence of a biomarker that predicts response. Here, we highli...

  10. Lessons from innovation in drug-device combination products.

    Science.gov (United States)

    Couto, Daniela S; Perez-Breva, Luis; Saraiva, Pedro; Cooney, Charles L

    2012-01-01

    Drug-device combination products introduced a new dynamic on medical product development, regulatory approval, and corporate interaction that provide valuable lessons for the development of new generations of combination products. This paper examines the case studies of drug-eluting stents and transdermal patches to facilitate a detailed understanding of the challenges and opportunities introduced by combination products when compared to previous generations of traditional medical or drug delivery devices. Our analysis indicates that the largest barrier to introduce a new kind of combination products is the determination of the regulatory center that is to oversee its approval. The first product of a new class of combination products offers a learning opportunity for the regulator and the sponsor. Once that first product is approved, the leading regulatory center is determined, and the uncertainty about the entire class of combination products is drastically reduced. The sponsor pioneering a new class of combination products assumes a central role in reducing this uncertainty by advising the decision on the primary function of the combination product. Our analysis also suggests that this decision influences the nature (pharmaceutical, biotechnology, or medical devices) of the companies that will lead the introduction of these products into the market, and guide the structure of corporate interaction thereon. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. A retrospective analysis of funding and focus in US advanced fission innovation

    Science.gov (United States)

    Abdulla, A.; Ford, M. J.; Morgan, M. G.; Victor, D. G.

    2017-08-01

    Deep decarbonization of the global energy system will require large investments in energy innovation and the deployment of new technologies. While many studies have focused on the expenditure that will be needed, here we focus on how government has spent public sector resources on innovation for a key carbon-free technology: advanced nuclear. We focus on nuclear power because it has been contributing almost 20% of total US electric generation, and because the US program in this area has historically been the world’s leading effort. Using extensive data acquired through the Freedom of Information Act, we reconstruct the budget history of the Department of Energy’s program to develop advanced, non-light water nuclear reactors. Our analysis shows that—despite spending 2 billion since the late 1990s—no advanced design is ready for deployment. Even if the program had been well designed, it still would have been insufficient to demonstrate even one non-light water technology. It has violated much of the wisdom about the effective execution of innovative programs: annual funding varies fourfold, priorities are ephemeral, incumbent technologies and fuels are prized over innovation, and infrastructure spending consumes half the budget. Absent substantial changes, the possibility of US-designed advanced reactors playing a role in decarbonization by mid-century is low.

  12. Innovations in building regulation and control for advancing sustainability in buildings (I)

    NARCIS (Netherlands)

    Meacham, B.; Visscher, H.J.; Meijer, F.M.; Chan, C.; Chan, E.; Laubscher, J.; Neng Kwei Sung, J.; Dodds, B.; Serra, J.; Tenorio, J.A.; Echeverria, J.B.; Sanches-Ostiz, A.

    2014-01-01

    This session brings together policy-makers, government officials, researchers and others to present perspectives on how innovation in building regulation and control, such as performancebased approaches, are currently being used to advance sustainability concepts in buildings, and where and how we

  13. Integrating Social Neuroscience and Social Work: Innovations for Advancing Practice-Based Research

    Science.gov (United States)

    Matto, Holly C.; Strolin-Goltzman, Jessica

    2010-01-01

    Throughout the social work profession, there is ongoing interest in building a social science agenda that can address the complex practice-based questions faced by social work professionals today. Methodological innovations and unique funding opportunities have already significantly advanced research on social work practice. Still, there is…

  14. Advancing Management Innovation: Synthesizing Processes, Levels of Analysis, and Change Agents

    NARCIS (Netherlands)

    Volberda, H.W.; van den Bosch, F.; Mihalache, R.O.

    2014-01-01

    Despite the mounting evidence that innovation in management can fuel competitive advantage, we still know relatively little about how firms introduce new ways of managing. The goal of this introductory essay—and the Themed Section it introduces—is to advance this knowledge. To this end, we first

  15. Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer

    NARCIS (Netherlands)

    Rombouts, S. J. E.; Vogel, J. A.; van Santvoort, H. C.; van Lienden, K. P.; van Hillegersberg, R.; Busch, O. R. C.; Besselink, M. G. H.; Molenaar, I. Q.

    2015-01-01

    BackgroundLocally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic

  16. Advances in drug delivery to the posterior segment.

    Science.gov (United States)

    Pearce, William; Hsu, Jason; Yeh, Steven

    2015-05-01

    Emerging developments and research for drug delivery to the posterior segment offer a promising future for the treatment of vitreoretinal disease. As new technologies enter the market, clinicians should be aware of new indications and ongoing clinical trials. This review summarizes the advantages and shortcomings of the most commonly used drug delivery methods, including vitreous dynamics, physician sustainability and patient preferences. Currently available, intravitreal, corticosteroid-release devices offer surgical and in-office management of retinal vascular disease and posterior uveitis. The suprachoroidal space offers a new anatomic location for the delivery of lower dose medications directly to the target tissue. Implantable drug reservoirs would potentially allow for less frequent intravitreal injections reducing treatment burdens and associated risks. Newer innovations in encapsulated cell technology offer promising results in early clinical trials. Although pars plana intravitreal injection remains the mainstay of therapy for many vitreoretinal diseases, targeted delivery and implantable eluting devices are rapidly demonstrating safety and efficacy. These therapeutic modalities offer promising options for the vitreoretinal therapeutic landscape.

  17. Advancing Drug Discovery through Enhanced Free Energy Calculations.

    Science.gov (United States)

    Abel, Robert; Wang, Lingle; Harder, Edward D; Berne, B J; Friesner, Richard A

    2017-07-18

    A principal goal of drug discovery project is to design molecules that can tightly and selectively bind to the target protein receptor. Accurate prediction of protein-ligand binding free energies is therefore of central importance in computational chemistry and computer aided drug design. Multiple recent improvements in computing power, classical force field accuracy, enhanced sampling methods, and simulation setup have enabled accurate and reliable calculations of protein-ligands binding free energies, and position free energy calculations to play a guiding role in small molecule drug discovery. In this Account, we outline the relevant methodological advances, including the REST2 (Replica Exchange with Solute Temperting) enhanced sampling, the incorporation of REST2 sampling with convential FEP (Free Energy Perturbation) through FEP/REST, the OPLS3 force field, and the advanced simulation setup that constitute our FEP+ approach, followed by the presentation of extensive comparisons with experiment, demonstrating sufficient accuracy in potency prediction (better than 1 kcal/mol) to substantially impact lead optimization campaigns. The limitations of the current FEP+ implementation and best practices in drug discovery applications are also discussed followed by the future methodology development plans to address those limitations. We then report results from a recent drug discovery project, in which several thousand FEP+ calculations were successfully deployed to simultaneously optimize potency, selectivity, and solubility, illustrating the power of the approach to solve challenging drug design problems. The capabilities of free energy calculations to accurately predict potency and selectivity have led to the advance of ongoing drug discovery projects, in challenging situations where alternative approaches would have great difficulties. The ability to effectively carry out projects evaluating tens of thousands, or hundreds of thousands, of proposed drug candidates

  18. Locally advanced cervix carcinoma - innovation in combined modality therapy

    International Nuclear Information System (INIS)

    Swift, Patrick S.

    1996-01-01

    Locally advanced cervical carcinoma continues to be a challenge to the clinician due to local failure as well as systemic metastases. Standard intracavitary and external beam techniques result in local control rates of only 35-65%, with long term survival rates of 25-60% in patients with state IIIA-IVA disease, indicating the need to identify new treatment strategies. Optimization programs for remote-afterloading interstitial brachytherapy allow the delivery of higher local doses of radiation to volumes that more closely approximate tumor target volumes as identified on MR scans, leading to improved therapeutic ratios. Identification of subsets of patients more likely to fail standard therapy, either locally or systemically, may be possible through such techniques as in vivo measurements of hypoxia with Eppendorf oxygen electrodes, interstitial fluid pressure measurements, the Comet assay, and nitroimidazole binding methods. Traditional chemotherapies, administered in either a neoadjuvant role or concomitantly with radiation have been disappointing in prospective trials. A variety of new agents are being investigated to determine if they can increase the frequency or duration of complete response. The taxanes, with response rates of 17-23% by themselves, are being assessed as potential radiosensitizers. The camptotheicin CRT-11 (Irinotecan) has demonstrated activity in platinum resistant cervix cancer, with response rates of 24%. Bioradiotherapeutic approaches, using 13-cis-retinoic acid and interferon-2a, are undergoing phase II studies. Neoangiogenesis inhibitors and vaccines against HPV are also being examined. The aggressive pursuit of techniques that help identify those patients most likely to fail, that allow the delivery of higher radiation doses more safely to the target volume, and that incorporate the use of more effective systemic therapies is necessary to improve the outcome for this disease

  19. Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

    Science.gov (United States)

    Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

    2016-02-10

    Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Fluorescence lifetime assays: current advances and applications in drug discovery.

    Science.gov (United States)

    Pritz, Stephan; Doering, Klaus; Woelcke, Julian; Hassiepen, Ulrich

    2011-06-01

    Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.

  1. Student and Preceptor Advancement in a Dedicated Education Site: Innovation in Clinical Education for Advanced Practice Nurses.

    Science.gov (United States)

    Hall, Katherine C; Diffenderfer, Sandy K; Stidham, April; Mullins, Christine M

    2018-04-19

    In the 1990s, dedicated education units transformed undergraduate preceptorships, but graduate preceptorships remain static. The dyadic nurse practitioner preceptorship model supports an environment where faculty, students, and preceptors may overlook nuances that affect the teaching-learning process. This article describes an innovative clinical education model, Student and Preceptor Advancement in a Dedicated Education Site, designed to improve preceptorships for advanced practice nurses. The focus is on adaptations made to facilitate use in advanced practice nursing programs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  2. Innovation

    DEFF Research Database (Denmark)

    Nielsen, Janni; Yaganeh, Suzanne; Bloch Rasmussen, Leif

    2013-01-01

    This paper contributes to a theoretical discussion of creation of innovation with participants in, or outside, organisations. We address the creation of innovation with a complex theoretical understanding drawing on the Scandinavian and the Participatory Design tradition introducing two approaches...... to the processes of innovation. We ask if innovation can be initiated and enhanced looking at two collaborative approaches; participatory innovation (PIN) and cooperative innovation (COIN). We invite to dialogue and reflections on PIN’s conflict and creative frictions on one side and COIN’s complexity......, complementarity in diversity and the didactic scaffolding of the innovation process on the other side. Our contribution focuses on the methods and practices for facilitation of co-creating activities between different groups leading to cooperation, and innovation in thinking....

  3. Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine.

    Science.gov (United States)

    Shahba, Ahmad Abdul-Wahhab; Ahmed, Abid Riaz; Alanazi, Fars Kaed; Mohsin, Kazi; Abdel-Rahman, Sayed Ibrahim

    2018-04-25

    Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.

  4. Can open-source drug R&D repower pharmaceutical innovation?

    Science.gov (United States)

    Munos, B

    2010-05-01

    Open-source R&D initiatives are multiplying across biomedical research. Some of them-such as public-private partnerships-have achieved notable success in bringing new drugs to market economically, whereas others reflect the pharmaceutical industry's efforts to retool its R&D model. Is open innovation the answer to the innovation crisis? This Commentary argues that although it may likely be part of the solution, significant cultural, scientific, and regulatory barriers can prevent it from delivering on its promise.

  5. Recent Advances in Prostate Cancer Treatment and Drug Discovery

    Directory of Open Access Journals (Sweden)

    Ekaterina Nevedomskaya

    2018-05-01

    Full Text Available Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC. Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

  6. Recent advances in liposomal nanohybrid cerasomes as promising drug nanocarriers.

    Science.gov (United States)

    Yue, Xiuli; Dai, Zhifei

    2014-05-01

    Liposomes have been extensively investigated as possible carriers for diagnostic or therapeutic agents due to their unique properties. However, liposomes still have not attained their full potential as drug and gene delivery vehicles because of their insufficient morphological stability. Recently, a super-stable and freestanding hybrid liposomal cerasome (partially ceramic- or silica-coated liposome) has drawn much attention as a novel drug delivery system because its atomic layer of polyorganosiloxane surface imparts higher morphological stability than conventional liposomes and its liposomal bilayer structure reduces the overall rigidity and density greatly compared to silica nanoparticles. Cerasomes are more biocompatible than silica nanoparticles due to the incorporation of the liposomal architecture into cerasomes. Cerasomes combine the advantages of both liposomes and silica nanoparticles but overcome their disadvantages so cerasomes are ideal drug delivery systems. The present review will first highlights some of the key advances of the past decade in the technology of cerasome production and then review current biomedical applications of cerasomes, with a view to stimulating further research in this area of study. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Advances in phage display technology for drug discovery.

    Science.gov (United States)

    Omidfar, Kobra; Daneshpour, Maryam

    2015-06-01

    Over the past decade, several library-based methods have been developed to discover ligands with strong binding affinities for their targets. These methods mimic the natural evolution for screening and identifying ligand-target interactions with specific functional properties. Phage display technology is a well-established method that has been applied to many technological challenges including novel drug discovery. This review describes the recent advances in the use of phage display technology for discovering novel bioactive compounds. Furthermore, it discusses the application of this technology to produce proteins and peptides as well as minimize the use of antibodies, such as antigen-binding fragment, single-chain fragment variable or single-domain antibody fragments like VHHs. Advances in screening, manufacturing and humanization technologies demonstrate that phage display derived products can play a significant role in the diagnosis and treatment of disease. The effects of this technology are inevitable in the development pipeline for bringing therapeutics into the market, and this number is expected to rise significantly in the future as new advances continue to take place in display methods. Furthermore, a widespread application of this methodology is predicted in different medical technological areas, including biosensing, monitoring, molecular imaging, gene therapy, vaccine development and nanotechnology.

  8. The advancement of electric vehicles - case: Tesla Motors. Disruptive technology requiring systemic innovating

    OpenAIRE

    Lehtinen, Petri

    2015-01-01

    Electric vehicles have existed for over 100 years as a disruptive innovation. Even though they have always been easier to use, quieter and cleaner, gasoline cars have beaten it in price, range and faster fueling. As gasoline cars have been the technological standard for the past 150 years there has been no motivation by car manufacturers to advance electric vehicles. By producing electric vehicles Tesla Motors has appropriately become the first successful startup car manufacturer in over 100 ...

  9. Lessons learned from the tokamak Advanced Reactor Innovation and Evaluation Study (ARIES)

    International Nuclear Information System (INIS)

    Krakowski, R.A.; Bathke, C.G.; Miller, R.L.; Werley, K.A.

    1994-01-01

    Lessons from the four-year ARIES (Advanced Reactor Innovation and Evaluation Study) investigation of a number of commercial magnetic-fusion-energy (MFE) power-plant embodiments of the tokamak are summarized. These lessons apply to physics, engineering and technology, and environmental, safety, and health (ES ampersand H) characteristics of projected tokamak power plants. Summarized herein are the composite conclusions and lessons developed in the course of four conceptual tokamak power-plant designs. A general conclusion from this extensive investigation of the commercial potential of tokamak power plants is the need for combined, symbiotic advances in both physics, engineering, and materials before economic competitiveness with developing advanced energy sources can be realized. Advances in materials are also needed for the exploitation of environmental advantages otherwise inherent in fusion power

  10. Lessons learned from the Tokamak Advanced Reactor Innovation and Evaluation Study (ARIES)

    International Nuclear Information System (INIS)

    Krakowski, R.A.; Bathke, C.G.; Miller, R.L.; Werley, K.A.

    1994-01-01

    Lessons from the four-year ARIES (Advanced Reactor Innovation and Evaluation Study) investigation of a number of commercial magnetic-fusion-energy (MFE) power-plant embodiments of the tokamak are summarized. These lessons apply to physics, engineering and technology, and environmental, safety and health (ES ampersand H) characteristics of projected tokamak power plants. A general conclusion from this extensive investigation of the commercial potential of tokamak power plants is the need for combined, symbiotic advances relative to present understanding in physics, engineering, and materials before economic competitiveness with developing advanced energy sources can be realized. Advanced tokamak plasmas configured in the second-stability regime that achieve both high β and bootstrap fractions near unity through strong profile control offer high promise in this regard

  11. Innovative grinding wheel design for cost-effective machining of advanced ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Licht, R.H.; Kuo, P.; Liu, S.; Murphy, D.; Picone, J.W.; Ramanath, S.

    2000-05-01

    This Final Report covers the Phase II Innovative Grinding Wheel (IGW) program in which Norton Company successfully developed a novel grinding wheel for cost-effective cylindrical grinding of advanced ceramics. In 1995, Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics using small prototype wheels. The Phase II program was initiated to scale-up the new superabrasive wheel specification to larger diameters, 305-mm to 406-mm, required for most production grinding of cylindrical ceramic parts, and to perform in-house and independent validation grinding tests.

  12. Innovative alcohol- and drug-user treatment of inmates in New Zealand prisons.

    Science.gov (United States)

    Huriwai, Terry

    2002-01-01

    The Kowhai Alcohol and Drug Treatment Unit at Rolleston Prison offers an innovative treatment approach for New Zealand inmates. The development of the program has involved local staff from Public Prisons, Psychological Services, and the Community Probation Service (CPS). This presentation outlines the author's impression of this bold innovation. The primary aim of the program is to reduce recidivism. This is achieved by assisting inmates to recognize the thoughts, emotions, and behaviours that are present in the period preceding and/or during the commission of criminal activity--particularly those that are precipitated and/or maintained by alcohol and drug use. This insight, coupled with the learning of specific coping skills and intensive lifestyle and reintegration planning, leads naturally to the follow-up phase that is conducted in the community. The functional relationship between offending and substance use is far more explicitly addressed in this new program compared with past programs that focused more on substance use.

  13. Innovator Organizations in New Drug Development: Assessing the Sustainability of the Biopharmaceutical Industry.

    Science.gov (United States)

    Kinch, Michael S; Moore, Ryan

    2016-06-23

    The way new medicines are discovered and brought to market has fundamentally changed over the last 30 years. Our previous analysis showed that biotechnology companies had contributed significantly to the US Food and Drug Administration approval of new molecular entities up to the mid-1980s, when the trends started to decline. Although intriguing, the focus on biotechnology necessarily precluded the wider question of how the biopharmaceutical industry has been delivering on its goals to develop new drugs. Here, we present a comprehensive analysis of all biopharmaceutical innovators and uncover unexpected findings. The present biopharmaceutical industry grew steadily from 1800 to 1950 and then stagnated for two decades, before a burst of growth attributable to the biotechnology revolution took place; but consolidation has reduced the number of active and independent innovators to a level not experienced since 1945. The trajectories and trends we observe raise fundamental questions about biopharmaceutical innovators and the sustainability of the drug-development enterprise. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Innovators.

    Science.gov (United States)

    NEA Today, 2001

    2001-01-01

    Describes various innovations that have been developed to enhance education. These innovations include: helping educators help at-risk students succeed; promoting high school journalism; ensuring quality online learning experiences; developing a student performing group that uses theater to address social issues; and having students design their…

  15. Drugs in development for toxoplasmosis: advances, challenges, and current status.

    Science.gov (United States)

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

    Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

  16. State-of-the-art Report on Innovative Fuels for Advanced Nuclear Systems

    International Nuclear Information System (INIS)

    Chauvin, N.; Minato, K.; Ogata, T.; Lee, C.B.; Pouchon, M.A.; Pasamehmetoglu, K.O.; Choi, Y.J.; Kennedy, J.R.; Massara, S.; Cornet, S.; ); Sommers, J.; ); McClellan, K.

    2014-01-01

    Development of innovative fuels such as homogeneous and heterogeneous fuels, ADS fuels, and oxide, metal, nitride and carbide fuels is an important stage in the implementation process of advanced nuclear systems. Several national and international R and D programmes are investigating minor actinide-bearing fuels due to their ability to help reduce the radiotoxicity of spent fuel and therefore decrease the burden on geological repositories. Minor actinides can be converted into a suitable fuel form for irradiation in reactor systems where they are transmuted into fission products with a significantly shorter half-life. This report compares recent studies of fuels containing minor actinides for use in advanced nuclear systems. The studies review different fuels for several types of advanced reactors by examining various technical issues associated with fabrication, characterisation, irradiation performance, design and safety criteria, as well as technical maturity. (authors)

  17. Drug delivery system innovation and Health Technology Assessment: Upgrading from Clinical to Technological Assessment.

    Science.gov (United States)

    Panzitta, Michele; Bruno, Giorgio; Giovagnoli, Stefano; Mendicino, Francesca R; Ricci, Maurizio

    2015-11-30

    Health Technology Assessment (HTA) is a multidisciplinary health political instrument that evaluates the consequences, mainly clinical and economical, of a health care technology; the HTA aim is to produce and spread information on scientific and technological innovation for health political decision making process. Drug delivery systems (DDS), such as nanocarriers, are technologically complex but they have pivotal relevance in therapeutic innovation. The HTA process, as commonly applied to conventional drug evaluation, should upgrade to a full pharmaceutical assessment, considering the DDS complexity. This is useful to study more in depth the clinical outcome and to broaden its critical assessment toward pharmaceutical issues affecting the patient and not measured by the current clinical evidence approach. We draw out the expertise necessary to perform the pharmaceutical assessment and we propose a format to evaluate the DDS technological topics such as formulation and mechanism of action, physicochemical characteristics, manufacturing process. We integrated the above-mentioned three points in the Evidence Based Medicine approach, which is data source for any HTA process. In this regard, the introduction of a Pharmaceutics Expert figure in the HTA could be fundamental to grant a more detailed evaluation of medicine product characteristics and performances and to help optimizing DDS features to overcome R&D drawbacks. Some aspects of product development, such as manufacturing processes, should be part of the HTA as innovative manufacturing processes allow new products to reach more effectively patient bedside. HTA so upgraded may encourage resource allocating payers to invest in innovative technologies and providers to focus on innovative material properties and manufacturing processes, thus contributing to bring more medicines in therapy in a sustainable manner. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. The Advanced Exploration Systems Water Recovery Project: Innovation on 2 Fronts

    Science.gov (United States)

    Sarguisingh, Miriam M.; Neumeyer, Derek; Shull, Sarah

    2012-01-01

    As NASA looks forward to sending humans farther away from Earth, we will have to develop a transportation architecture that is highly reliable and that can sustain life for long durations without the benefit of Earth s proximity for continuous resupply or even operational guidance. NASA has consistently been challenged with performing great feats of innovation, but particularly in this time of economic stress, we are challenged to go farther with less. The Advanced Exploration Systems (AES) projects were implemented to address both of these needs by not only developing innovative technologies, but by incorporating innovative management styles and processes that foster the needed technical innovation given a small amount of resources. This presentation explains how the AES Water Recovery Project is exhibiting innovation on both fronts; technical and process. The AES Water Recovery Project (WRP) is actively engineering innovative technologies in order to maximize the efficiency of water recovery. The development of reliable, energy-efficient, and low-mass spacecraft systems to provide environmental control and life support (ECLS) is critical to enable long-duration human missions outside of low-Earth orbit. Recycling of life support consumables is necessary to reduce resupply mass and provide for vehicle autonomy. To address this, the WRP is working on a rotary distiller that has shown enhanced performance over the state-of-the-art (SOA). Additionally, the WRP is looking at innovative ways to address issues present in the state-of-the-art (SOA) systems pertaining to toxicity and calcium scale buildup. As an AES project, the WRP has a more streamlined Skunk Works like approach to technology development intended to reduce overhead but achieve a more refined end product. The project has incorporated key partnerships between NASA centers as well as between NASA and industry. A minimal project management style has been implemented such that risks are managed and

  19. What is a new drug worth? An innovative model for performance-based pricing.

    Science.gov (United States)

    Dranitsaris, G; Dorward, K; Owens, R C; Schipper, H

    2015-05-01

    This article focuses on a novel method to derive prices for new pharmaceuticals by making price a function of drug performance. We briefly review current models for determining price for a new product and discuss alternatives that have historically been favoured by various funding bodies. The progressive approach to drug pricing, proposed herein, may better address the views and concerns of multiple stakeholders in a developed healthcare system by acknowledging and incorporating input from disparate parties via comprehensive and successive negotiation stages. In proposing a valid construct for performance-based pricing, the following model seeks to achieve several crucial objectives: earlier and wider access to new treatments; improved transparency in drug pricing; multi-stakeholder involvement through phased pricing negotiations; recognition of innovative product performance and latent changes in value; an earlier and more predictable return for developers without sacrificing total return on investment (ROI); more involved and informed risk sharing by the end-user. © 2014 John Wiley & Sons Ltd.

  20. Innovation

    African Journals Online (AJOL)

    In recent years ULA has emphasized advocacy, and contributed to progress towards new legislation (freedom of information, copyright, the ... East African Community e-government strategy) of importance to the library and ... Innovation Vol.

  1. Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

    Directory of Open Access Journals (Sweden)

    Wang Q

    2016-12-01

    Full Text Available Qun Wang,1,2,* Jian-Ying Huang,2,* Hua-Qiong Li,3,4 Allan Zi-Jian Zhao,4 Yi Wang,4 Ke-Qin Zhang,2,5 Hong-Tao Sun,1 Yue-Kun Lai,2,5 1College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 2National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 3Institute of Biomaterials and Engineering, Wenzhou Medical University, 4Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, 5Research Center of Cooperative Innovation for Functional Organic/Polymer Material Micro/Nanofabrication, Suzhou, People’s Republic of China *These authors contributed equally to this work Abstract: To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. Keywords: TiO2 nanotubes, electrochemical anodization, modification, stimulated drug delivery, drug-releasing implant

  2. Marijuana-based Drugs: Innovative Therapeutics or Designer Drugs of Abuse?

    OpenAIRE

    Seely, Kathryn A.; Prather, Paul L.; James, Laura P.; Moran, Jeffery H.

    2011-01-01

    Marijuana has been used recreationally and medicinally for centuries. The principle psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), activates CB1 cannabinoid receptors (CB1Rs). CB1R agonists and antagonists could potentially treat a wide variety of diseases; unfortunately, therapeutic doses produce unacceptable psychiatric effects. “K2” or “Spice” (K2/Spice), an emerging drug of abuse, exhibits psychotropic actions via CB1R activation. Because of structural dissimilarity to Δ9-THC, ...

  3. Innovative Practice in Advancement of Academic Nurse Educator Careers: Developing Scholarship From Program Grants.

    Science.gov (United States)

    Eddy, Linda L; Hoeksel, Renee; Fitzgerald, Cindy; Doutrich, Dawn

    We describe an innovative practice in advancing careers of academic nurse educators: demonstrating scholarly productivity from program grants. Scholarly productivity is often narrowly defined, especially in research-intensive institutions. The expectation may be a career trajectory based on the traditional scholarship of discovery. However, nurse educators, especially at the associate and full professor ranks, are often involved in leadership activities that include writing and managing program grants. We encourage the academy to value and support the development of program grants that include significant scholarly components, and we offer exemplars of associate and full professor scholarship derived from these projects.

  4. Innovation in Citizen Science – Perspectives on Science-Policy Advances

    Directory of Open Access Journals (Sweden)

    Susanne Hecker

    2018-04-01

    Full Text Available Citizen science is growing as a field of research with contributions from diverse disciplines, promoting innovation in science, society, and policy. Inter- and transdisciplinary discussions and critical analyses are needed to use the current momentum to evaluate, demonstrate, and build on the advances that have been made in the past few years. This paper synthesizes results of discussions at the first international citizen science conference of the European Citizen Science Association (ECSA in 2016 in Berlin, Germany, and distills major points of the discourse into key recommendations. To enhance innovation in science, citizen science needs to clearly demonstrate its scientific benefit, branch out across disciplines, and foster active networking and new formats of collaboration, including true co-design with participants. For fostering policy advances, it is important to embrace opportunities for policy-relevant monitoring and policy development and to work with science funders to find adequate avenues and evaluation tools to support citizen science. From a society angle it is crucial to engage with societal actors in various formats that suit participants and to evaluate two-way learning outcomes as well as to develop the transformative role of science communication. We hope that these key perspectives will promote citizen science progress at the science-society-policy interface.

  5. Reactor physics innovations of the advanced CANDU reactor core: adaptable and efficient

    International Nuclear Information System (INIS)

    Chan, P.S.W.; Hopwood, J.M.; Bonechi, M.

    2003-01-01

    The Advanced CANDU Reactor (ACR) is designed to have a benign, operator-friendly core physics characteristic, including a slightly negative coolant-void reactivity and a moderately negative power coefficient. The discharge fuel burnup is about three times that of natural uranium fuel in current CANDU reactors. Key features of the reactor physics innovations in the ACR core include the use of H 2 O coolant, slightly enriched uranium (SEU) fuel, and D 2 O moderator in a reduced lattice pitch. These innovations result in substantial improvements in economics, as well as significant enhancements in reactor performance and waste reduction over the current reactor design. The ACR can be readily adapted to different power outputs by increasing or decreasing the number of fuel channels, while maintaining identical fuel and fuel-channel characteristics. The flexibility provided by on-power refuelling and simple fuel bundle design enables the ACR to easily adapt to the use of plutonium and thorium fuel cycles. No major modifications to the basic ACR design are required because the benign neutronic characteristics of the SEU fuel cycle are also inherent in these advanced fuel cycles. (author)

  6. Innovation and the future of advanced dosimetry: 2D to 5D

    Science.gov (United States)

    Oldham, Mark

    2017-05-01

    Recent years have witnessed a remarkable evolution in the techniques, capabilities and applications of 3D dosimetry. Initially the goal was simple: to innovate new techniques capable of comprehensively measuring and verifying exquisitely intricate dose distributions from a paradigm changing emerging new therapy, IMRT. Basic questions emerged: how well were treatment planning systems modelling the complex delivery, and how could treatments be verified for safe use on patients? Since that time, equally significant leaps of innovation have continued in the technology of treatment delivery. In addition, clinical practice has been transformed by the addition of on-board imaging capabilities, which tend to hypo-fractionation strategies and margin reduction. The net result is a high stakes treatment setting where the clinical morbidity of any unintended treatment deviation is exacerbated by the combination of highly conformal dose distributions given with reduced margins with fractionation regimens unfriendly to healthy tissue. Not surprisingly this scenario is replete with challenges and opportunities for new and improved dosimetry systems. In particular tremendous interest exists in comprehensive 3D dosimetry systems, and systems that can resolve the dose in moving structures (4D) and even in deforming structures (5D). Despite significant progress in the capability of multi-dimensional dosimetry systems, it is striking that true 3D dosimetry systems are today largely found in academic institutions or specialist clinics. The reasons will be explored. We will highlight innovations occurring both in treatment delivery and in advanced dosimetry methods designed to verify them, and explore current and future opportunities for advanced dosimetry tools in clinical practice and translational research.

  7. Innovation

    African Journals Online (AJOL)

    The purpose of Innovation journal of appropriate librarianship and information work in Southern Africa is to publish material on libraries, information supply and other related matters in South and Southern Africa. Vol 45 (2012). DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access ...

  8. Innovation

    DEFF Research Database (Denmark)

    Torfing, Jacob; Ricard, Lykke Margot

    2017-01-01

    Innovation i krydsfeltet mellem forskellige styringsparadigmer i offentlige organisationer. New Public Governance gør det muligt at skabe offentlig værdi på nye måder. Men NPG er ingen trylledrik, der fra den ene dag til den anden skaber balance mellem borgernes store forventninger og en trængt ø...

  9. Elastic liposomes as novel carriers: recent advances in drug delivery

    Science.gov (United States)

    Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

    2017-01-01

    Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

  10. Challenges to value-enhancing innovation in health care delivery: commonalities and contrasts with innovation in drugs and devices

    National Research Council Canada - National Science Library

    Garber, Steven

    2011-01-01

    .... More specifically, they argue that policymakers should carefully distinguish between innovative activities that are worth their social costs and activities that are not worth their social costs...

  11. Open innovation for phenotypic drug discovery: The PD2 assay panel.

    Science.gov (United States)

    Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

    2011-07-01

    Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

  12. Advances in drug metabolism and pharmacogenetics research in Australia.

    Science.gov (United States)

    Mackenzie, Peter I; Somogyi, Andrew A; Miners, John O

    2017-02-01

    Metabolism facilitates the elimination, detoxification and excretion in urine or bile (as biotransformation products) of a myriad of structurally diverse drugs and other chemicals. The metabolism of drugs, non-drug xenobiotics and many endogenous compounds is catalyzed by families of drug metabolizing enzymes (DMEs). These include the hemoprotein-containing cytochromes P450, which function predominantly as monooxygenases, and conjugation enzymes that transfer a sugar, sulfate, acetate or glutathione moiety to substrates containing a suitable acceptor functional group. Drug and chemical metabolism, especially the enzymes that catalyse these reactions, has been the research focus of several groups in Australia for over four decades. In this review, we highlight the role of recent and current drug metabolism research in Australia, including elucidation of the structure and function of enzymes from the various DME families, factors that modulate enzyme activity in humans (e.g. drug-drug interactions, gene expression and genetic polymorphism) and the application of in vitro approaches for the prediction of drug metabolism parameters in humans, along with the broader pharmacological/clinical pharmacological and toxicological significance of drug metabolism and DMEs and their relevance to drug discovery and development, and to clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Innovation

    OpenAIRE

    2012-01-01

    Présenté par FutuRIS, plate-forme prospective sur la recherche, l’innovation et la société animée par l’Association Nationale de la Recherche et de la Technologie, ce volume livre un panorama du système français de recherche et d’innovation dans son environnement européen. Sont abordés dans une première partie les champs décisionnels concernés, les politiques nationales menées en matière de R&D, les relations entre enseignement supérieur et recherche et l’Espace européen de la recherche à l’h...

  14. INNOVATION

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2012-01-01

    Kravet om innovation og kreativitet er på flere måder en stor og en ny udfordring for voksenuddannelserne. Det udfordrer det didaktiske dilemma, det at vi skal gøres til kompetente og frie mennesker gennem pædagogiske handlinger, som netop pålægger os en ufrihed. – Men hvor denne ufrihed tidligere...... kunne begrundes med, at skolen eller uddannelsen vidste bedre, så er det ikke længere tilfældet. Skolen skal sørge for, at vi lærer noget – og ikke noget andet. Men det kan ikke længere med bestemthed afgøres, hvad det er vi skal lære i skolen, fordi det nye, det kreative og ikke mindst innovative...

  15. The Water-Energy-Food Nexus: Advancing Innovative, Policy-Relevant Methods

    Science.gov (United States)

    Crootof, A.; Albrecht, T.; Scott, C. A.

    2017-12-01

    The water-energy-food (WEF) nexus is rapidly expanding in scholarly literature and policy settings as a novel way to address complex Anthropocene challenges. The nexus approach aims to identify tradeoffs and synergies of water, energy, and food systems, internalize social and environmental impacts, and guide development of cross-sectoral policies. However, a primary limitation of the nexus approach is the absence - or gaps and inconsistent use - of adequate methods to advance an innovative and policy-relevant nexus approach. This paper presents an analytical framework to identify robust nexus methods that align with nexus thinking and highlights innovative nexus methods at the frontier. The current state of nexus methods was assessed with a systematic review of 245 journal articles and book chapters. This review revealed (a) use of specific and reproducible methods for nexus assessment is uncommon - less than one-third of the reviewed studies present explicit methods; (b) nexus methods frequently fall short of capturing interactions among water, energy, and food - the very concept they purport to address; (c) assessments strongly favor quantitative approaches - 70% use primarily quantitative tools; (d) use of social science methods is limited (26%); and (e) many nexus methods are confined to disciplinary silos - only about one-quarter combine methods from diverse disciplines and less than one-fifth utilize both quantitative and qualitative approaches. Despite some pitfalls of current nexus methods, there are a host of studies that offer innovative approaches to help quantify nexus linkages and interactions among sectors, conceptualize dynamic feedbacks, and support mixed method approaches to better understand WEF systems. Applying our analytical framework to all 245 studies, we identify, and analyze herein, seventeen studies that implement innovative multi-method and cross-scalar tools to demonstrate promising advances toward improved nexus assessment. This paper

  16. Elastic liposomes as novel carriers: recent advances in drug delivery

    Directory of Open Access Journals (Sweden)

    Hussain A

    2017-07-01

    Full Text Available Afzal Hussain,1,2 Sima Singh,1 Dinesh Sharma,3 Thomas J Webster,4 Kausar Shafaat,2 Abdul Faruk5 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 2Faculty of Pharmacy, Sachchidananda Sinha College, Aurangabad, Bihar, India; 3Zifam Pyrex Myanmar Co. Ltd., Yangon, Myanmar; 4Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 5Department of Pharmaceutical Sciences, Hemwati Nandan Bahuguna Garhwal University, Srinagar, Uttarakhand, India Abstract: Elastic liposomes (EL are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. Keywords: elastic liposomes, drug delivery, topical, transdermal, enhanced delivery 

  17. From Imitation to Innovation: A Study of China’s Drug R&D and Relevant National Policies

    Directory of Open Access Journals (Sweden)

    Jinxi Ding

    2011-06-01

    Full Text Available Research & Development (R&D plays an increasingly important role in China’s pharmaceutical industry. To gain a competitive edge in the global pharmaceutical market, the current national strategy of China forcefully pushes for independent drug innovations. This article investigates the historical, legal, and institutional contexts in which China’s drug R&D has evolved. Based on an analysis of the drug R&D evolution and national policies in China, it predicts the future trend of China’s policies relevant to drug innovations. This paper helps to understand the impact of national policies on drug R&D in China, which can be used to inform decision-making on investments in China’s pharmaceutical market or conducting technology trade and international cooperation with Chinese partners.

  18. Innovations and advances in computing, informatics, systems sciences, networking and engineering

    CERN Document Server

    Elleithy, Khaled

    2015-01-01

    Innovations and Advances in Computing, Informatics, Systems Sciences, Networking and Engineering  This book includes a set of rigorously reviewed world-class manuscripts addressing and detailing state-of-the-art research projects in the areas of Computer Science, Informatics, and Systems Sciences, and Engineering. It includes selected papers from the conference proceedings of the Eighth and some selected papers of the Ninth International Joint Conferences on Computer, Information, and Systems Sciences, and Engineering (CISSE 2012 & CISSE 2013). Coverage includes topics in: Industrial Electronics, Technology & Automation, Telecommunications and Networking, Systems, Computing Sciences and Software Engineering, Engineering Education, Instructional Technology, Assessment, and E-learning.  ·       Provides the latest in a series of books growing out of the International Joint Conferences on Computer, Information, and Systems Sciences, and Engineering; ·       Includes chapters in the most a...

  19. State of an innovation system: theoretical and empirical advance towards an innovation efficiency index. Or: Walking between ridicule and praise: measuring innovation systems effieciency with a single indicator

    NARCIS (Netherlands)

    Montalvo Corral, C.; Mohammadian Moghayer, S.

    2011-01-01

    Innovation is currently seen as a cornerstone not only for economic development but also as an intrinsic human activity that could help to face the great challenges of human kind. Given the importance of innovation in the new European 2020 Strategy, measuring progress but also monitoring what drives

  20. RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

    OpenAIRE

    YEŞİLADA, Akgül; ÖZKANLI, Fügen

    2004-01-01

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

  1. Exploring open innovation with a patient focus in drug discovery: an evolving paradigm of patient engagement.

    Science.gov (United States)

    Allarakhia, Minna

    2015-06-01

    It is suggested in this article that patient engagement should occur further upstream during the drug discovery stage. 'Lead patients', namely those patients who are proactive with respect to their health, possess knowledge of their disease and resulting symptoms. They are also well informed about the conventional as well as non-conventional treatments for disease management; and so can provide a nuanced perspective to drug design. Understanding how patients view the management of their diseases and how they view the use of conventional versus non-conventional interventions is of imperative importance to researchers. Indeed, this can provide insight into how conventional treatments might be designed from the outset to encourage compliance and positive health outcomes. Consequently, a continuum of lead patient engagement is employed that focuses on drug discovery processes ranging from participative, informative to collaborative engagement. This article looks at a variety of open innovation models that are currently employed across this engagement spectrum. It is no longer sufficient for industry stakeholders to consider conventional therapies as the only mechanisms being sought after by patients. Without patient engagement, the industry risks being re-prioritized in terms of its role in the patient journey towards not only recovery of health, but also sustained health and wellness before disease onset.

  2. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  3. The OGC Innovation Program Testbeds - Advancing Architectures for Earth and Systems

    Science.gov (United States)

    Bermudez, L. E.; Percivall, G.; Simonis, I.; Serich, S.

    2017-12-01

    The OGC Innovation Program provides a collaborative agile process for solving challenging science problems and advancing new technologies. Since 1999, 100 initiatives have taken place, from multi-million dollar testbeds to small interoperability experiments. During these initiatives, sponsors and technology implementers (including academia and private sector) come together to solve problems, produce prototypes, develop demonstrations, provide best practices, and advance the future of standards. This presentation will provide the latest system architectures that can be used for Earth and space systems as a result of the OGC Testbed 13, including the following components: Elastic cloud autoscaler for Earth Observations (EO) using a WPS in an ESGF hybrid climate data research platform. Accessibility of climate data for the scientist and non-scientist users via on demand models wrapped in WPS. Standards descriptions for containerize applications to discover processes on the cloud, including using linked data, a WPS extension for hybrid clouds and linking to hybrid big data stores. OpenID and OAuth to secure OGC Services with built-in Attribute Based Access Control (ABAC) infrastructures leveraging GeoDRM patterns. Publishing and access of vector tiles, including use of compression and attribute options reusing patterns from WMS, WMTS and WFS. Servers providing 3D Tiles and streaming of data, including Indexed 3d Scene Layer (I3S), CityGML and Common DataBase (CDB). Asynchronous Services with advanced pushed notifications strategies, with a filter language instead of simple topic subscriptions, that can be use across OGC services. Testbed 14 will continue advancing topics like Big Data, security, and streaming, as well as making easier to use OGC services (e.g. RESTful APIs). The Call for Participation will be issued in December and responses are due on mid January 2018.

  4. Nanotechnology inspired advanced engineering fundamentals for optimizing drug delivery.

    Science.gov (United States)

    Kassem, Ahmed Alaa

    2018-02-06

    Drug toxicity and inefficacy are commonly experienced problems with drug therapy failure. To face these problems, extensive research work took place aiming to design new dosage forms for drug delivery especially nanoparticulate systems. These systems are designed to increase the quantity of the therapeutic molecule delivered to the desired site concurrently with reduced side effects. In order to achieve this objective, nanocarriers must principally display suitable drug vehiculization abilities and a controlled biological destiny of drug molecules. Only the intelligent design of the nanomedicine will accomplish these fundamentals. The present review article is dedicated to the discussion of the important fundamentals to be considered in the fabrication of nanomedicines. These include the therapeutic agent, the nanocarrier and the functionalization moieties. Special consideration is devoted to the explanation and compilation of highly potential fabrication approaches assisting how to control the in vivo destiny of the nanomedicine. Finally, some nanotechnology-based drug delivery systems, for the development of nanomedicine, are also discussed. The nanotechnology-based drug delivery systems showed remarkable outcomes based on passive and active targeting as well as improvement of the drug pharmacodynamic and pharmacokinetic profiles. Multifunctional nanocarrier concept affords a revolutionary drug delivery approach for maximizing the efficacy, safety and monitoring the biological fate of the therapeutic molecule. Nanomedicines may enhance the efficacy of therapeutic molecules and reduce their toxic effects. Meanwhile, further research works are required to rightly optimize (and define) the effectiveness, nanotoxicity, in vivo destiny and feasibility of these nanomedicines which, from a preclinical standpoint, are actually promising. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Research and development in drug innovation: reflections from the 2013 bioeconomy conference in China, lessons learned and future perspectives.

    Science.gov (United States)

    Liu, Changxiao; Constantinides, Panayiotis P; Li, Yazhuo

    2014-04-01

    The enormous progress biotechnology, bioinformatics and nanotechnology made in recent years provides opportunities and scientific framework for development of biomedicine and constitutes a paradigm shift in pharmaceutical R&D and drug innovation. By analyzing the data and related information at R&D level over the past decades, developmental tendency and R&D patterns were summarized. We found that a growing number of biologics in the pipeline of pharma companies with successful products already in the market though, small molecular entities have primarily dominated drug innovation. Additionally, small/medium size companies will continue to play a key role in the development of small molecule drugs and biologics in a multi-channel integrated process. More importantly, modern and effective R&D strategies in biomedicine development to predict and evaluate efficacy and/or safety of 21st century therapeutics are urgently needed. To face new challenges, developmental strategies were proposed, in terms of molecular targeted medicine, generic drugs, new drug delivery system and protein-based drugs. Under the current circumstances, interdisciplinary cooperation mode and policy related to drug innovation in China were deeply discussed as well.

  6. Convergence of decision rules for value-based pricing of new innovative drugs.

    Science.gov (United States)

    Gandjour, Afschin

    2015-04-01

    Given the high costs of innovative new drugs, most European countries have introduced policies for price control, in particular value-based pricing (VBP) and international reference pricing. The purpose of this study is to describe how profit-maximizing manufacturers would optimally adjust their launch sequence to these policies and how VBP countries may best respond. To decide about the launching sequence, a manufacturer must consider a tradeoff between price and sales volume in any given country as well as the effect of price in a VBP country on the price in international reference pricing countries. Based on the manufacturer's rationale, it is best for VBP countries in Europe to implicitly collude in the long term and set cost-effectiveness thresholds at the level of the lowest acceptable VBP country. This way, international reference pricing countries would also converge towards the lowest acceptable threshold in Europe.

  7. Biomarkers: refining diagnosis and expediting drug development - reality, aspiration and the role of open innovation.

    Science.gov (United States)

    Salter, H; Holland, R

    2014-09-01

    In the last decade, there have been intensive efforts to invent, qualify and use novel biomarkers as a means to improve success rates in drug discovery and development. The biomarkers field is maturing and this article considers whether these research efforts have brought about the expected benefits. The characteristics of a clinically useful biomarker are described and the impact this area of research has had is evaluated by reviewing a few, key examples of emerging biomarkers. There is evidence that the impact has been genuine and is increasing in both the drug and the diagnostic discovery and development processes. Beneficial impact on patient health outcomes seems relatively limited thus far, with the greatest impact in oncology (again, both in terms of novel drugs and in terms of more refined diagnoses and therefore more individualized treatment). However, the momentum of research would indicate that patient benefits are likely to increase substantially and to broaden across multiple therapeutic areas. Even though this research was originally driven by a desire to improve the drug discovery and development process, and was therefore funded with this aim in mind, it seems likely that the largest impact may actually come from more refined diagnosis. Refined diagnosis will facilitate both better allocation of healthcare resources and the use of treatment regimens which are optimized for the individual patient. This article also briefly reviews emerging technological approaches and how they relate to the challenges inherent in biomarker discovery and validation, and discusses the role of public/private partnerships in innovative biomarker research. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  8. A Nanodroplet Processor for Advanced Microencapsulated Drug Formulations, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this proposal is to provide a demonstration of a nanodroplet synthesis of multifunctional liposomes for drug delivery based on immiscible...

  9. Allogeneic mesenchymal precursor cells (MPCs): an innovative approach to treating advanced heart failure.

    Science.gov (United States)

    Westerdahl, Daniel E; Chang, David H; Hamilton, Michele A; Nakamura, Mamoo; Henry, Timothy D

    2016-09-01

    Over 37 million people worldwide are living with Heart Failure (HF). Advancements in medical therapy have improved mortality primarily by slowing the progression of left ventricular dysfunction and debilitating symptoms. Ultimately, heart transplantation, durable mechanical circulatory support (MCS), or palliative care are the only options for patients with end-stage HF. Regenerative therapies offer an innovative approach, focused on reversing myocardial dysfunction and restoring healthy myocardial tissue. Initial clinical trials using autologous (self-donated) bone marrow mononuclear cells (BMMCs) demonstrated excellent safety, but only modest efficacy. Challenges with autologous stem cells include reduced quality and efficacy with increased patient age. The use of allogeneic mesenchymal precursor cells (MPCs) offers an "off the shelf" therapy, with consistent potency and less variability than autologous cells. Preclinical and initial clinical trials with allogeneic MPCs have been encouraging, providing the support for a large ongoing Phase III trial-DREAM-HF. We provide a comprehensive review of preclinical and clinical data supporting MPCs as a therapeutic option for HF patients. The current data suggest allogeneic MPCs are a promising therapy for HF patients. The results of DREAM-HF will determine whether allogeneic MPCs can decrease major adverse clinical events (MACE) in advanced HF patients.

  10. Advancing innovations in social/personality psychology and health: opportunities and challenges.

    Science.gov (United States)

    Rothman, Alexander J; Klein, William M P; Cameron, Linda D

    2013-05-01

    Social, personality, and health psychologists have a long tradition of active and productive collaborations that have advanced the development of intervention strategies that promote health and well-being and the specification of the theoretical principles that underlie those strategies. This special issue is designed to continue this tradition of collaboration and to highlight areas of research and investigative strategies that offer opportunities for innovation. This concluding paper examines how investigators construe the interface between theory and practice and, with that lens, considers several themes that have emerged across the papers that comprise this special issue. As evidenced by the papers in this special issue, investigators are well-positioned to leverage advances in understanding of human health and well-being. However, to capitalize on this opportunity, investigators need to commit to cultivating a culture of scientific activity that prioritizes the engagement of theory and practice-the pursuit of both understanding and use. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  11. Advanced Recyclable Media System reg-sign. Innovative technology summary report

    International Nuclear Information System (INIS)

    1998-12-01

    The objective of the Large-Scale Demonstration Project (LSDP) is to select and demonstrate potentially beneficial technologies at the Argonne National Laboratory East's (ANL) Chicago Pile-5 (CP-5) Research Reactor. The purpose of the LSDP is to demonstrate that using innovative and improved deactivation and decommissioning (D and D) technologies from various sources can result in significant benefits, such as decreased cost and increased health and safety, as compared with baseline D and D technologies. This report describes a demonstration of the Advanced Recyclable Media System reg-sign technology which was employed by Surface Technology Systems, Inc. to remove coatings from a concrete floor. This demonstration is part of the CP-5 LSDP sponsored by the US Department of Energy (DOE) Office of Science and Technology Deactivation and Decommissioning Focus Area (DDFA). The Advanced Recyclable Media System reg-sign (ARMS) technology is an open blast technology which uses a soft recyclable media. The patented ARMS Engineered Blast Media consists of a fiber-reinforced polymer matrix which can be manufactured in various grades of abrasiveness. The fiber media can be remade and/or reused up to 20 times and can clean almost any surface (e.g., metal, wood, concrete, lead) and geometry including corners and the inside of air ducts

  12. Penile prosthesis implant: scientific advances and technological innovations over the last four decades.

    Science.gov (United States)

    Chung, Eric

    2017-02-01

    Despite introduction of oral phosphodiesterase type 5 inhibitors and intracavernosal vasoactive agents, penile prosthesis implant remains a relevant and desired option with sales of penile prostheses continue to stay high, as many men became refractory to medical therapy and/or seeking a more effective and permanent therapy. There are two types of penile prosthesis implants: inflatable and non-inflatable types, and the inflatable penile implants can be subdivided into single-, two- and three-piece devices. Non-inflatable penile prosthesis (non-IPP) may be referred to as semi-rigid rod or malleable prosthesis. IPP is considered a superior option to malleable prosthesis as it produces penile rigidity and flaccidity that closely replicates a normal penile erectile function. Since the introduction of IPP by Scott in 1973, surgical landscape for penile prosthesis implantation has changed dramatically. Advances in prosthesis design, device technologies and surgical techniques have made penile prosthesis implant a more natural, durable and reliable device. The following article reviews the scientific advances and technological innovation in modern penile prosthesis implants over the last four decades.

  13. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  14. Recent advances in inkjet dispensing technologies: applications in drug discovery.

    Science.gov (United States)

    Zhu, Xiangcheng; Zheng, Qiang; Yang, Hu; Cai, Jin; Huang, Lei; Duan, Yanwen; Xu, Zhinan; Cen, Peilin

    2012-09-01

    Inkjet dispensing technology is a promising fabrication methodology widely applied in drug discovery. The automated programmable characteristics and high-throughput efficiency makes this approach potentially very useful in miniaturizing the design patterns for assays and drug screening. Various custom-made inkjet dispensing systems as well as specialized bio-ink and substrates have been developed and applied to fulfill the increasing demands of basic drug discovery studies. The incorporation of other modern technologies has further exploited the potential of inkjet dispensing technology in drug discovery and development. This paper reviews and discusses the recent developments and practical applications of inkjet dispensing technology in several areas of drug discovery and development including fundamental assays of cells and proteins, microarrays, biosensors, tissue engineering, basic biological and pharmaceutical studies. Progression in a number of areas of research including biomaterials, inkjet mechanical systems and modern analytical techniques as well as the exploration and accumulation of profound biological knowledge has enabled different inkjet dispensing technologies to be developed and adapted for high-throughput pattern fabrication and miniaturization. This in turn presents a great opportunity to propel inkjet dispensing technology into drug discovery.

  15. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    Science.gov (United States)

    The purpose of this poster is to present the application and assessment of advanced technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs (azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, and methylenedioxy...

  16. Innovations in the Endovascular Management of Critical Limb Ischemia: Retrograde Tibiopedal Access and Advanced Percutaneous Techniques.

    Science.gov (United States)

    Mustapha, Jihad A; Diaz-Sandoval, Larry J; Saab, Fadi

    2017-08-01

    Retrograde tibiopedal access and interventions have contributed to advance of endovascular techniques to treat critical limb ischemia (CLI) patients. This review encompasses the spectrum from advanced diagnostic imaging and technical therapeutic approaches for infrapopliteal occlusions, to a discussion of current standards and future directions. Contemporary studies of infrapopliteal angioplasty show suboptimal short-term and 1-year clinical outcomes. Comparative data is needed to shift the focus from PTA to disruptive treatment modalities that can further improve outcomes. Retrograde pedal access has emerged as an important tool to facilitate successfully percutaneous revascularization and limb salvage in patients with CLI. To efficiently approach the complexity of CLI, new thought processes are needed to change the reigning paradigms. Retrograde tibial-pedal access has shown improvement in the rate of successful revascularizations and is an important tool in the amputation-prevention armamentarium. Additional technologies may further improve success rates. Drug-eluting stents have shown better outcomes than PTA in patients with focal infrapopliteal lesions. Registry data have demonstrated the advantage of several atherectomy devices in the tibial arteries. More recently, bioresorbable vascular scaffolds have been used successfully, and further studies with drug-coated balloons are underway. Interventional operators are now even working in the inframalleolar space to reconstitute the plantar arch. Well-conducted studies are needed to generate high-quality evidence in the field of critical limb ischemia management.

  17. Technological advances in precision medicine and drug development.

    Science.gov (United States)

    Maggi, Elaine; Patterson, Nicole E; Montagna, Cristina

    New technologies are rapidly becoming available to expand the arsenal of tools accessible for precision medicine and to support the development of new therapeutics. Advances in liquid biopsies, which analyze cells, DNA, RNA, proteins, or vesicles isolated from the blood, have gained particular interest for their uses in acquiring information reflecting the biology of tumors and metastatic tissues. Through advancements in DNA sequencing that have merged unprecedented accuracy with affordable cost, personalized treatments based on genetic variations are becoming a real possibility. Extraordinary progress has been achieved in the development of biological therapies aimed to even further advance personalized treatments. We provide a summary of current and future applications of blood based liquid biopsies and how new technologies are utilized for the development of biological therapeutic treatments. We discuss current and future sequencing methods with an emphasis on how technological advances will support the progress in the field of precision medicine.

  18. [Most innovative drugs labelled during the last years in paediatrics: does the paediatrician have the tools for their identification?].

    Science.gov (United States)

    Autret-Leca, E

    2010-08-01

    When a new drug is labelled, before deciding its integration in the therapeutic strategy, the doctor has to know the degree of innovation of the drug, i.e. its actual benefit and the improvement of actual benefit, also called added value over other available drugs. For each new medicine in France, after drug approval by the French Drug Agency, the French National Authority for Health thought its "Commission de transparence" (Transparency Commission) issues an opinion about the degree of innovation of the drug, which is independent of the marketing authorization. The added value over other available drugs is quantified by five levels of improvement: level I, major progress to level V, no progress. The complete opinion of the Transparency Commission and its synthesis (one page) is online http://www.has-sante.fr/. Between 2006 and 2008, no paediatric drug has obtained a level I of improvement (major progress), ten have obtained a level II (significant progress), 11 a level III (moderate progress), 12 a level IV (minor progress) and for 38 drugs, no progress has been retained. The need to know and to follow therapeutic recommendations is the evidence based medicine. The opinions of the Transparency Commission are one of those recommendations. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  19. Patterns of Innovation in Alzheimer's Disease Drug Development: A Strategic Assessment Based on Technological Maturity.

    Science.gov (United States)

    Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Ledley, Fred D

    2015-08-01

    This article examines the current status of translational science for Alzheimer's disease (AD) drug discovery by using an analytical model of technology maturation. Previous studies using this model have demonstrated that nascent scientific insights and inventions generate few successful leads or new products until achieving a requisite level of maturity. This article assessed whether recent failures and successes in AD research follow patterns of innovation observed in other sectors. The bibliometric-based Technology Innovation Maturation Evaluation model was used to quantify the characteristic S-curve of growth for AD-related technologies, including acetylcholinesterase, N-methyl-d-aspartate (NMDA) receptors, B-amyloid, amyloid precursor protein, presenilin, amyloid precursor protein secretases, apolipoprotein E4, and transactive response DNA binding protein 43 kDa (TDP-43). This model quantifies the accumulation of knowledge as a metric for technological maturity, and it identifies the point of initiation of an exponential growth stage and the point at which growth slows as the technology is established. In contrast to the long-established acetylcholinesterase and NMDA receptor technologies, we found that amyloid-related technologies reached the established point only after 2000, and that the more recent technologies (eg, TDP-43) have not yet approached this point. The first approvals for new molecular entities targeting acetylcholinesterase and the NMDA receptor occurred an average of 22 years after the respective technologies were established, with only memantine (which was phenotypically discovered) entering clinical trials before this point. In contrast, the 6 lead compounds targeting the formation of amyloid plaques that failed in Phase III trials between 2009 and 2014 all entered clinical trials before the respective target technologies were established. This analysis suggests that AD drug discovery has followed a predictable pattern of innovation in which

  20. Grand Challenges of Advanced Computing for Energy Innovation Report from the Workshop Held July 31-August 2, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Larzelere, Alex R.; Ashby, Steven F.; Christensen, Dana C.; Crawford, Dona L.; Khaleel, Mohammad A.; John, Grosh; Stults, B. Ray; Lee, Steven L.; Hammond, Steven W.; Grover, Benjamin T.; Neely, Rob; Dudney, Lee Ann; Goldstein, Noah C.; Wells, Jack; Peltz, Jim

    2013-03-06

    On July 31-August 2 of 2012, the U.S. Department of Energy (DOE) held a workshop entitled Grand Challenges of Advanced Computing for Energy Innovation. This workshop built on three earlier workshops that clearly identified the potential for the Department and its national laboratories to enable energy innovation. The specific goal of the workshop was to identify the key challenges that the nation must overcome to apply the full benefit of taxpayer-funded advanced computing technologies to U.S. energy innovation in the ways that the country produces, moves, stores, and uses energy. Perhaps more importantly, the workshop also developed a set of recommendations to help the Department overcome those challenges. These recommendations provide an action plan for what the Department can do in the coming years to improve the nation’s energy future.

  1. Findings: Sector-Leading and Innovative Practice in Advancing Equality and Diversity. Report to HEFCE by the Equality Challenge Unit

    Science.gov (United States)

    Higher Education Funding Council for England, 2017

    2017-01-01

    Following our "Call for evidence of sector-leading and innovative practice in advancing equality and diversity" (HEFCE Circular letter 16/2016), HEFCE commissioned the Equality Challenge Unit (ECU) to report back on the range of equality and diversity practice undertaken across the higher education sector. Of 120 submissions received,…

  2. Recent Advances and Perspectives in Liposomes for Cutaneous Drug Delivery.

    Science.gov (United States)

    Carita, Amanda C; Eloy, Josimar O; Chorilli, Marlus; Lee, Robert J; Leonardi, Gislaine Ricci

    2018-02-13

    The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. [Evaluation of the safety of innovative drugs against viruses and infectious agents].

    Science.gov (United States)

    Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana

    2013-01-01

    Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.

  4. Advances in polyelectrolyte multilayer nanofilms as tunable drug delivery systems

    Science.gov (United States)

    Jiang, Bingbing; Barnett, John B; Li, Bingyun

    2009-01-01

    There has been considerable interest in polyelectrolyte multilayer nanofilms, which have a variety of applications ranging from optical and electrochemical materials to biomedical devices. Polyelectrolyte multilayer nanofilms are constructed from aqueous solutions using electrostatic layer-by-layer self-assembly of oppositely-charged polyelectrolytes on a solid substrate. Multifunctional polyelectrolyte multilayer nanofilms have been studied using charged dyes, metal and inorganic nanoparticles, DNA, proteins, and viruses. In the past few years, there has been increasing attention to developing polyelectrolyte multilayer nanofilms as drug delivery vehicles. In this mini-review, we present recent developments in polyelectrolyte multilayer nanofilms with tunable drug delivery properties, with particular emphasis on the strategies in tuning the loading and release of drugs in polyelectrolyte multilayer nanofilms as well as their applications. PMID:24198464

  5. Recent advances in co-amorphous drug formulations

    DEFF Research Database (Denmark)

    Dengale, Swapnil Jayant; Grohganz, Holger; Rades, Thomas

    2016-01-01

    with other amorphous stabilization techniques. Because of this, several research groups started to investigate the co-amorphous formulation approach, resulting in an increasing amount of scientific publications over the last few years. This study provides an overview of the co-amorphous field and its recent......Co-amorphous drug delivery systems have recently gained considerable interest in the pharmaceutical field because of their potential to improve oral bioavailability of poorly water-soluble drugs through drug dissolution enhancement as a result of the amorphous nature of the material. A co...... findings. In particular, we investigate co-amorphous formulations from the viewpoint of solid dispersions, describe their formation and mechanism of stabilization, study their impact on dissolution and in vivo performance and briefly outline the future potentials....

  6. In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery.

    Science.gov (United States)

    Darvesh, Altaf S; Carroll, Richard T; Geldenhuys, Werner J; Gudelsky, Gary A; Klein, Jochen; Meshul, Charles K; Van der Schyf, Cornelis J

    2011-02-01

    INTRODUCTION: Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates. AREAS COVERED: In this review we present a brief overview of the principles and procedures related to in vivo microdialysis and detail the use of this technique in the pre-clinical measurement of drugs designed to be used in the treatment of chemical addiction, neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and as well as psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. This review offers insight into the tremendous utility and versatility of this technique in pursuing neuropharmacological investigations as well its significant potential in rational drug discovery. EXPERT OPINION: In vivo microdialysis is an extremely versatile technique, routinely used in the neuropharmacological investigation of drugs used for the treatment of neurological disorders. This technique has been a boon in the elucidation of the neurochemical profile and mechanism of action of several classes of drugs especially their effects on neurotransmitter systems. The exploitation and development of this technique for drug discovery in the near future will enable investigational new drug candidates to be rapidly moved into the clinical trial stages and to market thus providing new successful therapies for neurological diseases

  7. Recent Advances in Drug Discovery from South African Marine Invertebrates

    Directory of Open Access Journals (Sweden)

    Michael T. Davies-Coleman

    2015-10-01

    Full Text Available Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA, is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared.

  8. 77 FR 12059 - Using Innovative Technologies and Other Conditions of Safe Use To Expand Which Drug Products Can...

    Science.gov (United States)

    2012-02-28

    ...] Using Innovative Technologies and Other Conditions of Safe Use To Expand Which Drug Products Can Be... over-the- counter or OTC products) can be purchased by consumers in pharmacies, supermarkets, and other retail establishments without the need for a prescription. Currently, consumers can purchase...

  9. Insoluble drug delivery strategies: review of recent advances and business prospects

    Science.gov (United States)

    Kalepu, Sandeep; Nekkanti, Vijaykumar

    2015-01-01

    The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects. PMID:26579474

  10. Insoluble drug delivery strategies: review of recent advances and business prospects

    Directory of Open Access Journals (Sweden)

    Sandeep Kalepu

    2015-09-01

    Full Text Available The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.

  11. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    Science.gov (United States)

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-11-01

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  12. Innovations in management of cardiac disease: drugs, treatment strategies and technology.

    Science.gov (United States)

    Foëx, P

    2017-12-01

    Within the last generation, the management of patients with heart disease has been transformed by advances in drug treatments, interventions and diagnostic technologies. The management of arterial hypertension saw beta-blockers demoted from first- to third-line treatment. Recent studies suggest that the goal of treatment may have to change to lower systolic blood pressures to prevent long-term organ damage. Today less than 15% of coronary revascularizations are surgical and more than 85% are done by interventional cardiologists inserting coronary stents. Thus, managing patients on dual antiplatelet therapy has become an important issue. With new generations of coronary stents, recommendations are changing fast. In the past, decisions concerning non-cardiac surgery after acute myocardial infarction were based on the delay between infarction and non-cardiac surgery. Today, the main concern is the patient's status in respect of dual antiplatelet therapy after primary percutaneous intervention. There have been advances in the management of heart failure but new drugs (ivabradine, sacubitril/valsartan) and cardiac resynchronization are recommended only in patients with an ejection fraction below 35% on optimal medication. Heart failure remains a major perioperative risk factor. Prospective studies have shown that troponin elevations represent myocardial injury (not necessarily myocardial infarction), are mostly silent and are associated with increased 30-day mortality. Monitoring (troponin assays) for myocardial injury in non-cardiac surgery (MINS) seems increasingly justified. The treatment of MINS needs further research. Technological advances, such as intelligent, portable monitors benefit not only patients with cardiac disease but all patients who have undergone major surgery and are on the wards postoperatively. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please

  13. Current advances in transdermal delivery of drugs for Alzheimer's disease

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

  14. Current advances in transdermal delivery of drugs for Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

  15. NOTE: An innovative phantom for quantitative and qualitative investigation of advanced x-ray imaging technologies

    Science.gov (United States)

    Chiarot, C. B.; Siewerdsen, J. H.; Haycocks, T.; Moseley, D. J.; Jaffray, D. A.

    2005-11-01

    Development, characterization, and quality assurance of advanced x-ray imaging technologies require phantoms that are quantitative and well suited to such modalities. This note reports on the design, construction, and use of an innovative phantom developed for advanced imaging technologies (e.g., multi-detector CT and the numerous applications of flat-panel detectors in dual-energy imaging, tomosynthesis, and cone-beam CT) in diagnostic and image-guided procedures. The design addresses shortcomings of existing phantoms by incorporating criteria satisfied by no other single phantom: (1) inserts are fully 3D—spherically symmetric rather than cylindrical; (2) modules are quantitative, presenting objects of known size and contrast for quality assurance and image quality investigation; (3) features are incorporated in ideal and semi-realistic (anthropomorphic) contexts; and (4) the phantom allows devices to be inserted and manipulated in an accessible module (right lung). The phantom consists of five primary modules: (1) head, featuring contrast-detail spheres approximate to brain lesions; (2) left lung, featuring contrast-detail spheres approximate to lung modules; (3) right lung, an accessible hull in which devices may be placed and manipulated; (4) liver, featuring conrast-detail spheres approximate to metastases; and (5) abdomen/pelvis, featuring simulated kidneys, colon, rectum, bladder, and prostate. The phantom represents a two-fold evolution in design philosophy—from 2D (cylindrically symmetric) to fully 3D, and from exclusively qualitative or quantitative to a design accommodating quantitative study within an anatomical context. It has proven a valuable tool in investigations throughout our institution, including low-dose CT, dual-energy radiography, and cone-beam CT for image-guided radiation therapy and surgery.

  16. An innovative phantom for quantitative and qualitative investigation of advanced x-ray imaging technologies

    International Nuclear Information System (INIS)

    Chiarot, C B; Siewerdsen, J H; Haycocks, T; Moseley, D J; Jaffray, D A

    2005-01-01

    Development, characterization, and quality assurance of advanced x-ray imaging technologies require phantoms that are quantitative and well suited to such modalities. This note reports on the design, construction, and use of an innovative phantom developed for advanced imaging technologies (e.g., multi-detector CT and the numerous applications of flat-panel detectors in dual-energy imaging, tomosynthesis, and cone-beam CT) in diagnostic and image-guided procedures. The design addresses shortcomings of existing phantoms by incorporating criteria satisfied by no other single phantom: (1) inserts are fully 3D-spherically symmetric rather than cylindrical; (2) modules are quantitative, presenting objects of known size and contrast for quality assurance and image quality investigation; (3) features are incorporated in ideal and semi-realistic (anthropomorphic) contexts; and (4) the phantom allows devices to be inserted and manipulated in an accessible module (right lung). The phantom consists of five primary modules: (1) head, featuring contrast-detail spheres approximate to brain lesions; (2) left lung, featuring contrast-detail spheres approximate to lung modules; (3) right lung, an accessible hull in which devices may be placed and manipulated; (4) liver, featuring conrast-detail spheres approximate to metastases; and (5) abdomen/pelvis, featuring simulated kidneys, colon, rectum, bladder, and prostate. The phantom represents a two-fold evolution in design philosophy-from 2D (cylindrically symmetric) to fully 3D, and from exclusively qualitative or quantitative to a design accommodating quantitative study within an anatomical context. It has proven a valuable tool in investigations throughout our institution, including low-dose CT, dual-energy radiography, and cone-beam CT for image-guided radiation therapy and surgery. (note)

  17. Current advances in transdermal delivery of drugs for alzheimer's disease

    OpenAIRE

    Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...

  18. Recent advances in combinatorial biosynthesis for drug discovery

    Directory of Open Access Journals (Sweden)

    Sun H

    2015-02-01

    Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1 precursor-directed biosynthesis; 2 enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3 pathway-level recombination. Recent examples of combinatorial biosynthesis employing these

  19. Otolaryngology--head and neck surgery in undergraduate medical education: advances and innovations.

    Science.gov (United States)

    Fung, Kevin

    2015-02-01

    Medical students graduate with the knowledge and skills to be undifferentiated general physicians. Otolaryngology-head and neck surgery (OtoHNS) is an essential component of primary healthcare, but is disproportionately under-represented in undergraduate medical education (UME). Advances and innovations in educational technology may represent an exciting and creative solution to this important problem. Failure to meet this educational need will result in substantial downstream effects in primary healthcare delivery. The objectives of this study were to 1) demonstrate current deficits in OtoHNS teaching at the UME level; 2) develop, validate, and critically appraise educational innovations that may enrich OtoHNS teaching in medical school curricula; and 3) propose a process for standardization of learning objectives for OtoHNS in UME as it relates to development and deployment of such educational tools. A white paper, prepared as a Triological Society thesis, which consolidates a prospective 10-year investigation of the problem of and potential solutions for under-representation of OtoHNS in UME. Cited datasets include multicenter surveys, cohort studies, and prospective, randomized controlled trials. A series of published and unpublished data were synthesized that addresses the following: 1) the current state of OtoHNS teaching at the UME level with respect to content, volume, structure, and methods; and 2) educational innovations including e-learning and simulation with emphasis on validity and learning effectiveness. Educational innovations specific to postgraduate (residency) training were excluded. Data support the observation that there is uniformly disproportionate under-representation of OtoHNS within UME curricula. Medical school graduates, especially those pursuing primary care specialties, report poor overall comfort levels in managing OtoHNS problems. A series of novel teaching methods were developed and validated using e-learning and simulation

  20. Advanced practice physiotherapy in paediatric orthopaedics: innovation and collaboration to improve service delivery.

    Science.gov (United States)

    Ó Mír, M; O'Sullivan, C

    2018-02-01

    One in eight paediatric primary care presentations is for a musculoskeletal (MSK) disorder. These patients are frequently referred to paediatric orthopaedic surgeons; however, up to 50% of referrals are for normal variants. This results in excessive wait-times and impedes access for urgent surgical cases. Adult MSK medicine has successfully utilised advanced practice physiotherapists (APP) managing non-surgical candidates, with documented benefits both to patients and services. There is a gap in the literature with regard to APP in paediatric orthopaedics. In this review, we investigate demands on paediatric orthopaedic services, examine the literature regarding APP in paediatric orthopaedics and explore the value the role has to offer current outpatient services. Paediatric orthopaedic services are under-resourced with concurrent long wait times. Approximately 50% of referrals are for normal variants, which do not require specialist intervention. Poor musculoskeletal examination skills and low diagnostic confidence amongst primary care physicians have been identified as a cause of inappropriate referrals. APP clinics for normal variants have reported independent management rate and discharge rates of 95% and marked reduction in patient wait times. There is limited evidence to support the APP in paediatric orthopaedics. Further studies are needed investigating diagnostic agreement, patient/stakeholder satisfaction, patient outcomes and economic evaluation. Paediatric orthopaedics is in crisis as to how to effectively manage the overwhelming volume of referrals. Innovative multidisciplinary solutions are required so that the onus is not solely on physicians to provide all services. The APP in paediatric orthopaedics may be part of the solution.

  1. Assimilation Patterns in the Use of Advanced Manufacturing Technologies in SMEs: Exploring their Effects on Product Innovation Performance

    Directory of Open Access Journals (Sweden)

    Sylvestre Uwizeyemungu

    2015-10-01

    Full Text Available Manufacturing small and medium-sized enterprises (SMEs are more and more adopting advanced manufacturing technologies (AMT aimed at fostering product innovation process, improving product quality, streamlining the production process, and gaining productivity. In this study, we analyze the relationship between AMT proficiency levels in manufacturing SMEs and product innovation performance. Using data from 616 manufacturing SMEs, and considering a wide range of various AMT (20 different types of AMT grouped into 5 categories, we derived three AMT assimilation patterns through a cluster analysis procedure combining hierarchical and non-hierarchical clustering algorithms. The analysis of the relationship between AMT assimilation patterns and product innovation performance shows a rather unexpected picture: in spite of the existence of clearly distinct patterns of AMT assimilation, we find no significant relationship between any pattern and product innovation performance. Instead, we find the organizational and environmental context of SMEs to be more determinant for product innovation performance than any of the AMT assimilation patterns. From a practical point of view, this study indicates that manufacturing SMEs managers interested in fostering their innovation capabilities through AMT assimilation need to be aware of the contingency effects of their organizational size, age, and sector of activity.

  2. Advances in the synthesis and application of nanoparticles for drug delivery.

    Science.gov (United States)

    Park, Wooram; Na, Kun

    2015-01-01

    The continuous development of drug delivery systems (DDSs) has been extensively researched by the need to maximize therapeutic efficacy while minimizing undesirable side effects. Nanoparticle technology was recently shown to hold great promise for drug delivery applications in nanomedicine due to its beneficial properties, such as better encapsulation, bioavailability, control release, and lower toxic effect. Despite the great progress in nanomedicine, there remain many limitations for clinical application. To overcome these limitations, advanced nanoparticles for drug delivery have been developed to enable the spatially and temporally controlled release of drugs in response to specific stimuli at disease sites. Furthermore, the controlled self-assembly of organic and inorganic materials may enable their use in theranostic applications. This review presents an overview of a recent advanced nanoparticulate system that can be used as a potential drug delivery carrier and focuses on the potential applications of nanoparticles in various biomedical fields for human health care. © 2015 Wiley Periodicals, Inc.

  3. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

    Directory of Open Access Journals (Sweden)

    Vinh NQ

    2015-06-01

    Full Text Available Nguyen Quoc Vinh,1 Shigeyuki Naka,1 Horacio Cabral,2 Hiroyuki Murayama,1 Sachiko Kaida,1 Kazunori Kataoka,2 Shigehiro Morikawa,3 Tohru Tani4 1Department of Surgery, Shiga University of Medical Science, Shiga, Japan; 2Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan; 3Department of Nursing, Shiga University of Medical Science, Shiga, Japan; 4Biomedical Innovation Center, Shiga University of Medical Science, Shiga, Japan Abstract: Hepatocellular carcinoma (HCC is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexaneplatinum(II (DACHPt] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or

  4. Energy, economic, and environmental impacts of advanced industrial process innovations, 1976--1996

    International Nuclear Information System (INIS)

    Quinn, J.E.; Reed, J.E.

    1997-01-01

    The mission of the Office of Industrial Technologies (OIT), within the Office of Energy Efficiency and Renewable Energy, is to develop and deploy advanced energy efficiency, renewable energy, and pollution-prevention technologies, through partnerships with industry, government, and non-governmental organizations. OIT's objectives have evolved and broadened over nearly two decades, continually responding to a changing energy situation and shifting national priorities. Today, the key focus of the OIT programs is the Industries of the Future approach. This strategy of close collaboration with industry catalyzes and facilitates technology development and transfer efforts in seven manufacturing industries that together account for over 80% of the energy used and over 80% of the wastes produced by the manufacturing sector. In this approach senior level industry groups develop a future vision of their industry and a technology roadmap to attain the vision. DOE helps facilitate this process and partners with industry to identify and pursue an advanced technology R and D portfolio. The seven industries are aluminum, chemicals, forest products, glass, metalcasting, petroleum refining, and steel. In managing all its activities, OIT draws upon program support provided primarily by national Laboratories, universities, and private-sector research organizations throughout the country that have the diverse and specialized expertise needed to develop advanced industrial technologies. Approximately 78 industrial technologies developed with Office of Industrial Technology (OIT) support have successfully entered commercial markets. These technologies have saved a cumulative total of almost 900 trillion Btu, representing a new production cost savings of over $1.8 billion. These dollar savings represent the net total value of all energy saved by technologies developed with OIT support minus the net cost to industry of using the technologies (including capital costs, operating and

  5. Advanced Drug Delivery Systems - a Synthetic and Biological Applied Evaluation

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    function as the targeting moiety on the surface of the liposomes. Several examples of synthetic procedures known from the literature are presented. The chapter is completed with a study covering the conjugation efficiencies of a variety of chemical functionalities. Large differences are revealed between...... to guide the uptake, in addition to an enzymatically cleavable peptide sequence, whose cleavage would result in removal of the polymer layer as well as uncovering cationic charges on the liposomal surface. These systems were shown to have superior drug efficacy in vitro....

  6. [Nurturing clinician investigators is the best way to promote innovative drug development from academia].

    Science.gov (United States)

    Fukuhara, Shunichi; Sakushima, Ken; Nishimura, Masaharu

    2012-03-01

    Clinical research in Japan is still lacking in quality and quantity, and that situation is worsening. One important cause of those problems is the dearth of clinician-investigators. A recent change in the system for post-graduate clinical training affected the career paths of medical residents and reduced the number of young doctors who enter graduate school. Even those who are interested in clinical research now have incentives to avoid graduate school. In Japan, 19th-century biological absolutism is still the dominant paradigm in the medical-research community. Science for public health in the 21st century will benefit from a probabilistic paradigm, which can help to restore an appropriate balance between basic sciences and clinical research. Research done by clinician-investigators should be based on clinical questions that arise in medical practice. That research includes investigation of disease and practice, exploration of associations between causes and outcomes, evaluation of diagnostic tests, and studies of the efficacy of treatments and prevention strategies. We emphasize the importance of nurturing clinician-investigators for the development of clinical research in Japan. This may not be the fastest way to promote innovative drug development from academia, but it is certainly the best.

  7. From innovation to application: social-ecological context, diagnostics, drugs and integrated control of schistosomiasis.

    Science.gov (United States)

    Utzinger, Jürg; N'goran, Eliézer K; Caffrey, Conor R; Keiser, Jennifer

    2011-09-01

    Compared to malaria, tuberculosis and HIV/AIDS, schistosomiasis remains a truly neglected tropical disease. Schistosomiasis, perhaps more than any other disease, is entrenched in prevailing social-ecological systems, since transmission is governed by human behaviour (e.g. open defecation and patterns of unprotected surface water contacts) and ecological features (e.g. living in close proximity to suitable freshwater bodies in which intermediate host snails proliferate). Moreover, schistosomiasis is intimately linked with poverty and the disease has spread to previously non-endemic areas as a result of demographic, ecological and engineering transformations. Importantly though, thanks to increased advocacy there is growing awareness, financial and technical support to control and eventually eliminate schistosomiasis as a public health problem at local, regional and global scales. The purpose of this review is to highlight recent progress made in innovation, validation and application of new tools and strategies for research and integrated control of schistosomiasis. First, we explain that schistosomiasis is deeply embedded in social-ecological systems and explore linkages with poverty. We then summarize and challenge global statistics, risk maps and burden estimates of human schistosomiasis. Discovery and development research pertaining to novel diagnostics and drugs forms the centrepiece of our review. We discuss unresolved issues and emerging opportunities for integrated and sustainable control of schistosomiasis and conclude with a series of research needs. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Innovative sampling and extraction methods for the determination of nonsteroidal anti-inflammatory drugs in water.

    Science.gov (United States)

    Tanwar, Shivani; Di Carro, Marina; Magi, Emanuele

    2015-03-15

    Two different innovative approaches were used for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in water: stir bar sorptive extraction (SBSE) and passive sampling, followed by electrospray ionization liquid chromatography-tandem mass spectrometry. SBSE was developed by comparing EG-Silicone and PDMS stir bars and optimizing main parameters to attain high preconcentration. Quantitative analysis was carried out by mass spectrometry in negative ionization mode and multiple reaction monitoring. The SBSE-LC-MS/MS method provided satisfactory figures of merit with LOD (7.5-71 ng L(-1)) and LOQ (22.5-213 ng L(-1)). The developed method was successfully applied to real samples collected from river water and wastewater effluents. The obtained results showed the presence of all analytes at trace levels, in a wide range of concentrations. The passive sampling approach was carried out by using Polar Organic Chemical Integrative Sampler (POCIS); samplers were deployed for 15 days in river and tap water, allowing to detect analytes at ultra-trace levels. Time-Weighted Average concentration of NSAIDs in river water was estimated in the range 0.33-0.46 ng L(-1), using the sampling rates previously obtained by means of a simple calibration system. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Aerosol processing: a wind of innovation in the field of advanced heterogeneous catalysts.

    Science.gov (United States)

    Debecker, Damien P; Le Bras, Solène; Boissière, Cédric; Chaumonnot, Alexandra; Sanchez, Clément

    2018-04-16

    Aerosol processing is long known and implemented industrially to obtain various types of divided materials and nanomaterials. The atomisation of a liquid solution or suspension produces a mist of aerosol droplets which can then be transformed via a diversity of processes including spray-drying, spray pyrolysis, flame spray pyrolysis, thermal decomposition, micronisation, gas atomisation, etc. The attractive technical features of these aerosol processes make them highly interesting for the continuous, large scale, and tailored production of heterogeneous catalysts. Indeed, during aerosol processing, each liquid droplet undergoes well-controlled physical and chemical transformations, allowing for example to dry and aggregate pre-existing solid particles or to synthesise new micro- or nanoparticles from mixtures of molecular or colloidal precursors. In the last two decades, more advanced reactive aerosol processes have emerged as innovative means to synthesise tailored-made nanomaterials with tunable surface properties, textures, compositions, etc. In particular, the "aerosol-assisted sol-gel" process (AASG) has demonstrated tremendous potential for the preparation of high-performance heterogeneous catalysts. The method is mainly based on the low-cost, scalable, and environmentally benign sol-gel chemistry process, often coupled with the evaporation-induced self-assembly (EISA) concept. It allows producing micronic or submicronic, inorganic or hybrid organic-inorganic particles bearing tuneable and calibrated porous structures at different scales. In addition, pre-formed nanoparticles can be easily incorporated or formed in a "one-pot" bottom-up approach within the porous inorganic or hybrid spheres produced by such spray drying method. Thus, multifunctional catalysts with tailored catalytic activities can be prepared in a relatively simple way. This account is an overview of aerosol processed heterogeneous catalysts which demonstrated interesting performance in

  10. Evaluation of Students' Perceptions Towards An Innovative Teaching-Learning Method During Pharmacology Revision Classes: Autobiography of Drugs.

    Science.gov (United States)

    Joshi, Anuradha; Ganjiwale, Jaishree

    2015-07-01

    Various studies in medical education have shown that active learning strategies should be incorporated into the teaching-learning process to make learning more effective, efficient and meaningful. The aim of this study was to evaluate student's perceptions on an innovative revision method conducted in Pharmacology i.e. in form of Autobiography of Drugs. The main objective of study was to help students revise the core topics in Pharmacology in an interesting way. Questionnaire based survey on a newer method of pharmacology revision in two batches of second year MBBS students of a tertiary care teaching medical college. Various sessions on Autobiography of Drugs were conducted amongst two batches of second year MBBS students, during their Pharmacology revision classes. Student's perceptions were documented with the help of a five point likert scale through a questionnaire regarding quality, content and usefulness of this method. Descriptive analysis. Students of both the batches appreciated the innovative method taken up for revision. The median scores in most of the domains in both batches were four out of five, indicative of good response. Feedback from open-ended questions also revealed that the innovative module on "Autobiography of Drugs" was taken as a positive learning experience by students. Autobiography of drugs has been used to help students recall topics that they have learnt through other teachings methods. Autobiography sessions in Pharmacology during revision slots, can be one of the interesting ways in helping students revise and recall topics which have already been taught in theory classes.

  11. The impact of cardiovascular drug innovation on the longevity of elderly residents of Switzerland, 2003-2012

    Directory of Open Access Journals (Sweden)

    Frank R Lichtenberg

    2015-03-01

    Full Text Available Previous investigators have argued that one of the two most important contributors to improved human survival is the treatment of cardiovascular disease. Among Swiss inhabitants age 65 and over, 90% of the 1994-2010 decline in the overall death rate was due to the decline in the rate of deaths from diseases of the circulatory system. Little if any of the decline in cardiovascular mortality is likely to have been due to changes in behavioral risk factors, especially tobacco use and obesity. This study examines the impact of cardiovascular drug innovation on the longevity of elderly residents of Switzerland using cross-sectional patient-level data on about 22 thousand patients insured by a major health insurer (CSS during the period 2003-2011. We investigate the effect of the vintage (world launch year of the cardiovascular drugs used by an individual in 2003 on his or her longevity (time till death, controlling for several demographic characteristics and indicators of health status. We are able to track a patient’s vital status until 12/31/2011: 8 years after the end of the period in which cardiovascular drug use (and other variables are measured. Our estimates indicate that people who used newer cardiovascular drugs in 2003 had longer time till death than people who used older cardiovascular drugs, controlling for the number of 2003 prescriptions and their distribution by main anatomical group, the number of 2003 doctor visits and their distribution by specialty, whether the person was hospitalized in 2003, sex, and age. Our most conservative estimates imply that cardiovascular drug innovation accounted for almost a quarter of the increase in longevity among elderly residents of Switzerland during 2003-2012, and that it increased their longevity by almost 3 months. Other estimates are about twice as large. All of the estimates are consistent with the hypothesis that newer classes of drugs tend to be therapeutically superior to older classes of

  12. Innovative Approaches to Development and Ground Testing of Advanced Bimodal Space Power and Propulsion Systems

    International Nuclear Information System (INIS)

    Hill, T.; Noble, C.; Martinell, J.; Borowski, S.

    2000-01-01

    The last major development effort for nuclear power and propulsion systems ended in 1993. Currently, there is not an initiative at either the National Aeronautical and Space Administration (NASA) or the U.S. Department of Energy (DOE) that requires the development of new nuclear power and propulsion systems. Studies continue to show nuclear technology as a strong technical candidate to lead the way toward human exploration of adjacent planets or provide power for deep space missions, particularly a 15,000 lbf bimodal nuclear system with 115 kW power capability. The development of nuclear technology for space applications would require technology development in some areas and a major flight qualification program. The last major ground test facility considered for nuclear propulsion qualification was the U.S. Air Force/DOE Space Nuclear Thermal Propulsion Project. Seven years have passed since that effort, and the questions remain the same, how to qualify nuclear power and propulsion systems for future space flight. It can be reasonably assumed that much of the nuclear testing required to qualify a nuclear system for space application will be performed at DOE facilities as demonstrated by the Nuclear Rocket Engine Reactor Experiment (NERVA) and Space Nuclear Thermal Propulsion (SNTP) programs. The nuclear infrastructure to support testing in this country is aging and getting smaller, though facilities still exist to support many of the technology development needs. By renewing efforts, an innovative approach to qualifying these systems through the use of existing facilities either in the U.S. (DOE's Advance Test Reactor, High Flux Irradiation Facility and the Contained Test Facility) or overseas should be possible

  13. Innovation Approaches to Development and Ground Testing of Advanced Bimodal Space Power and Propulsion Systems

    Energy Technology Data Exchange (ETDEWEB)

    Hill, T.; Noble, C.; Martinell, J. (INEEL); Borowski, S. (NASA Glenn Research Center)

    2000-07-14

    The last major development effort for nuclear power and propulsion systems ended in 1993. Currently, there is not an initiative at either the National Aeronautical and Space Administration (NASA) or the U.S. Department of Energy (DOE) that requires the development of new nuclear power and propulsion systems. Studies continue to show nuclear technology as a strong technical candidate to lead the way toward human exploration of adjacent planets or provide power for deep space missions, particularly a 15,000 lbf bimodal nuclear system with 115 kW power capability. The development of nuclear technology for space applications would require technology development in some areas and a major flight qualification program. The last major ground test facility considered for nuclear propulsion qualification was the U.S. Air Force/DOE Space Nuclear Thermal Propulsion Project. Seven years have passed since that effort, and the questions remain the same, how to qualify nuclear power and propulsion systems for future space flight. It can be reasonably assumed that much of the nuclear testing required to qualify a nuclear system for space application will be performed at DOE facilities as demonstrated by the Nuclear Rocket Engine Reactor Experiment (NERVA) and Space Nuclear Thermal Propulsion (SNTP) programs. The nuclear infrastructure to support testing in this country is aging and getting smaller, though facilities still exist to support many of the technology development needs. By renewing efforts, an innovative approach to qualifying these systems through the use of existing facilities either in the U.S. (DOE's Advance Test Reactor, High Flux Irradiation Facility and the Contained Test Facility) or overseas should be possible.

  14. Innovative Approaches to Development and Ground Testing of Advanced Bimodal Space Power and Propulsion Systems

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Thomas Johnathan; Noble, Cheryl Ann; Noble, C.; Martinell, John Stephen; Borowski, S.

    2000-07-01

    The last major development effort for nuclear power and propulsion systems ended in 1993. Currently, there is not an initiative at either the National Aeronautical and Space Administration (NASA) or the U.S. Department of Energy (DOE) that requires the development of new nuclear power and propulsion systems. Studies continue to show nuclear technology as a strong technical candidate to lead the way toward human exploration of adjacent planets or provide power for deep space missions, particularly a 15,000 lbf bimodal nuclear system with 115 kW power capability. The development of nuclear technology for space applications would require technology development in some areas and a major flight qualification program. The last major ground test facility considered for nuclear propulsion qualification was the U.S. Air Force/DOE Space Nuclear Thermal Propulsion Project. Seven years have passed since that effort, and the questions remain the same, how to qualify nuclear power and propulsion systems for future space flight. It can be reasonable assumed that much of the nuclear testing required to qualify a nuclear system for space application will be performed at DOE facilities as demonstrated by the Nuclear Rocket Engine Reactor Experiment (NERVA) and Space Nuclear Thermal Propulsion (SNTP) programs. The nuclear infrastructure to support testing in this country is aging and getting smaller, though facilities still exist to support many of the technology development needs. By renewing efforts, an innovative approach to qualifying these systems through the use of existing facilities either in the U.S. (DOE's Advance Test Reactor, High Flux Irradiation Facility and the Contained Test Facility) or overseas should be possible.

  15. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    Science.gov (United States)

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  16. Disruptive technology: new medical advances are troublesome for even the most successful health systems and innovator health companies.

    Science.gov (United States)

    Michaelis, Lawrence; Vaul, Joanne; Chumer, Kathleen; Faul, Maureen; Sheehan, Lisa; DeCerce, Jack

    2004-01-01

    An independent expert panel conducted a multi-year research/education/advocacy initiative on the impact of the new drug-eluting stent technology. They conclude that this technology represents a "tipping point" in a series of transformative drugs and medical devices, often used in combination, and recommend that healthcare decision makers develop careful, data-based strategies to avoid the disruptiveness of these medical advances.

  17. Next-Generation Entrepreneurs Ready to Advance Breast Cancer Research Innovations | Poster

    Science.gov (United States)

    By Michele Newton and Thomas Stackhouse, Contributing Writers, and Rosemarie Truman, Guest Writer Editor’s note: In May 2014, the Breast Cancer Start-Up Challenge was named one of six finalists in the HHS Innovates Award Competition. This award celebrates innovations developed by employees of the U.S. Department of Health and Human Services (HHS) to support the mission of HHS.

  18. Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

    Science.gov (United States)

    Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

    2017-01-01

    Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2018-02-01

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

  20. Vegetable Oil-Loaded Nanocapsules: Innovative Alternative for Incorporating Drugs for Parenteral Administration.

    Science.gov (United States)

    Venturinil, C G; Bruinsmann, A; Oliveira, C P; Contri, R V; Pohlmann, A R; Guterres, S S

    2016-02-01

    An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.

  1. Volpe Center Annual Accomplishments: Advancing Transportation Innovation for the Public Good - January 2018

    Science.gov (United States)

    2018-01-01

    The Volpe Centers Annual Accomplishments highlights our best work of 2017 and illustrates the sustained impact of the Volpe Center in supporting the U.S. DOTs top priorities and strategic goals: safety, infrastructure, innovation, and accountab...

  2. An Innovative Unmanned System for Advanced Environmental Monitoring: Design and Development

    Science.gov (United States)

    Marsella, Ennio; Giordano, Laura; Evangelista, Lorenza; Iengo, Antonio; di Filippo, Alessandro; Coppola, Aniello

    2015-04-01

    The paper summarizes the design and development of a new technology and tools for real-time coordination and control of unmanned vehicles for advanced environmental monitoring. A new Unmanned System has been developed at Institute for Coastal Marine Environmental - National Research Council (Italy), in the framework of two National Operational Programs (PON): Technological Platform for Geophysical and Environmental Marine Survey-PITAM and Integrated Systems and Technologies for Geophysical and Environmental Monitoring in coastal-marine areas-STIGEAC. In particular, the system includes one Unmanned Aerial Vehicle (UAV) and two Unmanned Marine Vehicles (UMV). Major innovations concern the implementation of a new architecture to control each drone and/or to allow the cooperation between heterogeneous vehicles, the integration of distributed sensing techniques and real-time image processing capabilities. Part of the research in these projects involves, therefore, an architecture, where the ground operator can communicate with the Unmanned Vehicles at various levels of abstraction using pointing devices and video viewing. In detail, a Ground Control Station (GCS) has been design and developed to allow the government in security of the drones within a distance up to twenty kilometers for air explorations and within ten nautical miles for marine activities. The Ground Control Station has the following features: 1. hardware / software system for the definition of the mission profiles; 3. autonomous and semi-autonomous control system by remote control (joystick or other) for the UAV and UMVs; 4. integrated control system with comprehensive visualization capabilities, monitoring and archiving of real-time data acquired from scientific payload; 5. open structure to future additions of systems, sensors and / or additional vehicles. In detail, the UAV architecture is a dual-rotor, with an endurance ranging from 55 to 200 minutes, depending on payload weight (maximum 26 kg) and

  3. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

  4. Coordination conjugates of therapeutic proteins with drug carriers: A new approach for versatile advanced drug delivery

    Czech Academy of Sciences Publication Activity Database

    Kejík, Z.; Bříza, T.; Králová, Jarmila; Poučková, P.; Kral, A.; Martásek, P.; Král, V.

    2011-01-01

    Roč. 21, č. 18 (2011), s. 5514-5520 ISSN 0960-894X R&D Projects: GA ČR GA203/09/1311 Grant - others:MPO(CZ) FR-TI3/521; AV ČR(CZ) KAN200100801 Program:FR; KA Institutional research plan: CEZ:AV0Z50520514 Keywords : combined cancer therapy * photodynamic therapy * targeted drug delivery Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.554, year: 2011

  5. Redefining responsible research and innovation for the advancement of biobanking and biomedical research.

    Science.gov (United States)

    Yu, Helen

    2016-12-01

    One of the core objectives of responsible research and innovation (RRI) is to maximize the value of publicly funded research so that it may be returned to benefit society. However, while RRI encourages innovation through societal engagement, it can give rise to complex and previously untested issues that challenge the existing legal frameworks on intellectual property (IP) and public entitlement to benefits of research. In the case of biobanking, the personal nature of human biological materials and often altruistic intention of participants to donate samples intensifies the need to adhere to RRI principles with respect to the research, development, and commercialization of innovations derived from biobanks. However, stakeholders participate and collaborate with others in the innovation process to fulfill their own agenda. Without IP to safeguard investments in R&D, stakeholders may hesitate to contribute to the translation of discoveries into innovations. To realize the public benefit objective, RRI principles must protect the interests of stakeholders involved in the translation and commercialization of knowledge. This article explores the seemingly contradictory and competing objectives of open science and commercialization and proposes a holistic innovation framework directed at improving RRI practice for positive impact on obtaining the optimal social and economic values from research.

  6. Prices, profits, and innovation: examining criticisms of new psychotropic drugs' value.

    Science.gov (United States)

    Huskamp, Haiden A

    2006-01-01

    High profits and high drug costs have brought increased scrutiny of the pharmaceutical industry over the issue of whether the drugs they produce are worth the costs. I examine several related complaints, including the proliferation of me-too drugs and product reformulations, which some argue have little value relative to their cost; the baseless promotion of newer drug classes as more effective than existing, less expensive drugs; legal strategies to extend market exclusivity that result in high brand-name drug prices for an extended period of time; and large promotional expenditures that result in higher prices.

  7. Prices, Profits and Innovation: Examining Criticisms of the Value of New Psychotropic Drugs

    Science.gov (United States)

    Huskamp, Haiden A.

    2008-01-01

    High profits and high drug costs have brought increased scrutiny of the pharmaceutical industry over the issue of whether the drugs they produce are worth the costs. I examine several related complaints, including the proliferation of me-too drugs and product reformulations, which some argue have little value relative to their cost; promotion of newer drug classes as more effective than existing, less expensive drugs in the absence of evidence of superior effectiveness; legal strategies to extend market exclusivity that result in high brand drug prices for an extended period of time; and large promotional expenditures that result in higher prices. PMID:16684726

  8. Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    H.A. Daniel Lagassé

    2017-02-01

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

  9. Innovation in Flight: Research of the NASA Langley Research Center on Revolutionary Advanced Concepts for Aeronautics

    Science.gov (United States)

    Chambers, Joseph R.

    2005-01-01

    The goal of this publication is to provide an overview of the topic of revolutionary research in aeronautics at Langley, including many examples of research efforts that offer significant potential benefits, but have not yet been applied. The discussion also includes an overview of how innovation and creativity is stimulated within the Center, and a perspective on the future of innovation. The documentation of this topic, especially the scope and experiences of the example research activities covered, is intended to provide background information for future researchers.

  10. Accelerating Innovation that Enhances Resource Recovery in the Wastewater Sector: Advancing a National Testbed Network.

    Science.gov (United States)

    Mihelcic, James R; Ren, Zhiyong Jason; Cornejo, Pablo K; Fisher, Aaron; Simon, A J; Snyder, Seth W; Zhang, Qiong; Rosso, Diego; Huggins, Tyler M; Cooper, William; Moeller, Jeff; Rose, Bob; Schottel, Brandi L; Turgeon, Jason

    2017-07-18

    This Feature examines significant challenges and opportunities to spur innovation and accelerate adoption of reliable technologies that enhance integrated resource recovery in the wastewater sector through the creation of a national testbed network. The network is a virtual entity that connects appropriate physical testing facilities, and other components needed for a testbed network, with researchers, investors, technology providers, utilities, regulators, and other stakeholders to accelerate the adoption of innovative technologies and processes that are needed for the water resource recovery facility of the future. Here we summarize and extract key issues and developments, to provide a strategy for the wastewater sector to accelerate a path forward that leads to new sustainable water infrastructures.

  11. Innovations: Alcohol & drug abuse: Narcotics on the net: the availability of Web sites selling controlled substances.

    Science.gov (United States)

    Forman, Robert F

    2006-01-01

    The Internet is not only a vital medium for communication, entertainment, and commerce, but it is also an outlet for illicit drug sales. Although the U.S. Controlled Substances Act regulates access to certain drugs by requiring prescriptions, unique characteristics of the Internet create significant challenges for the enforcement of U.S. drug policies. In the late 1990s "no prescription Web sites" (NPWs) began to emerge, which allow persons to purchase drugs, such as opiates, without a prescription. Given the likely role of NPWs in increasing prescription drug abuse, health care professionals must develop and disseminate strategies for helping patients who are affected by these Web sites.

  12. Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

    Science.gov (United States)

    Patel, Mayur M; Patel, Bhoomika M

    2017-02-01

    CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

  13. Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

    Directory of Open Access Journals (Sweden)

    Song Y

    2016-12-01

    Full Text Available Yuanhui Song, Yihong Li, Qien Xu, Zhe Liu Wenzhou Institute of Biomaterials and Engineering (WIBE, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Abstract: With the development of nanotechnology, the application of nanomaterials in the field of drug delivery has attracted much attention in the past decades. Mesoporous silica nanoparticles as promising drug nanocarriers have become a new area of interest in recent years due to their unique properties and capabilities to efficiently entrap cargo molecules. This review describes the latest advances on the application of mesoporous silica nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive controlled release systems that are able to respond to intracellular environmental changes, such as pH, ATP, GSH, enzyme, glucose, and H2O2. Moreover, drug delivery induced by exogenous stimuli including temperature, light, magnetic field, ultrasound, and electricity is also summarized. These advanced technologies demonstrate current challenges, and provide a bright future for precision diagnosis and treatment. Keywords: mesoporous silica nanoparticle, drug delivery system, controlled release, stimuli-responsive, chemotherapy

  14. Conference Scene: From innovative polymers to advanced nanomedicine: Key challenges, recent progress and future perspectives

    NARCIS (Netherlands)

    Feijen, Jan; Hennink, W.E.; Zhong, Zhiyuan

    2013-01-01

    Recent developments in polymer-based controlled delivery systems have made a significant clinical impact. The second Symposium on Innovative Polymers for Controlled Delivery (SIPCD) was held in Suzhou, China to address the key challenges and provide up-to-date progress and future perspectives in the

  15. Evaluation of Students’ Perceptions Towards An Innovative Teaching-Learning Method During Pharmacology Revision Classes: Autobiography of Drugs

    Science.gov (United States)

    Ganjiwale, Jaishree

    2015-01-01

    Introduction Various studies in medical education have shown that active learning strategies should be incorporated into the teaching–learning process to make learning more effective, efficient and meaningful. Objectives The aim of this study was to evaluate student’s perceptions on an innovative revision method conducted in Pharmacology i.e. in form of Autobiography of Drugs. The main objective of study was to help students revise the core topics in Pharmacology in an interesting way. Settings and Design Questionnaire based survey on a newer method of pharmacology revision in two batches of second year MBBS students of a tertiary care teaching medical college. Materials and Methods Various sessions on Autobiography of Drugs were conducted amongst two batches of second year MBBS students, during their Pharmacology revision classes. Student’s perceptions were documented with the help of a five point likert scale through a questionnaire regarding quality, content and usefulness of this method. Statistical analysis used Descriptive analysis. Results Students of both the batches appreciated the innovative method taken up for revision. The median scores in most of the domains in both batches were four out of five, indicative of good response. Feedback from open-ended questions also revealed that the innovative module on “Autobiography of Drugs” was taken as a positive learning experience by students. Conclusions Autobiography of drugs has been used to help students recall topics that they have learnt through other teachings methods. Autobiography sessions in Pharmacology during revision slots, can be one of the interesting ways in helping students revise and recall topics which have already been taught in theory classes. PMID:26393138

  16. HOW ADVERSE DRUG-REACTIONS CAN PLAY A ROLE IN INNOVATIVE DRUG RESEARCH - SIMILARITIES IN ADVERSE DRUG REACTION PROFILES OF CAPTOPRIL AND PENICILLAMINE

    NARCIS (Netherlands)

    RIKKEN, F; VOS, R

    1995-01-01

    We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We

  17. Tourists' acceptance of advanced technology-based innovations for promoting arts and culture

    NARCIS (Netherlands)

    Pantano, E.; Corvello, V.

    2014-01-01

    Advanced technologies are able to influence tourists' decisions. They can be exploited for attracting touristic flows towards cultural destinations. In particular, virtual tours are new tools based on advanced 3D graphics that can be useful for promoting arts and culture. In this paper, we test

  18. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery

    Science.gov (United States)

    Kesharwani, Prashant; Iyer, Arun K.

    2015-01-01

    Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748

  19. Recent advances in polymeric microspheres for parenteral drug delivery--part 1.

    Science.gov (United States)

    Mao, Shirui; Guo, Chunqiang; Shi, Yi; Li, Luk Chiu

    2012-09-01

    Polymeric microspheres have been established as a valuable parenteral drug delivery system for sustained release of therapeutic agents via subcutaneous or intramuscular injection. Biodegradable polymers which are either synthetic or from natural sources are reviewed with respect to recent advances in exploring their applications for microsphere fabrications. New information on the impact of formulation variables on the properties of microspheres formed by an emulsion method was also presented. The characterization of microspheres using advanced physical analytical techniques was also reviewed and the utilization of the information in assessing in vivo performance of the product was also highlighted. The broad clinical use of microspheres for delivery of therapeutic agents in particular biologics such as proteins has not been realized commercially. The limited availability of biodegradable polymers with a long history of regulatory approval and the challenges in gaining regulatory approval of a new polymer have hindered the development of microspheres for parenteral drug delivery.

  20. Advanced surface chemical analysis of continuously manufactured drug loaded composite pellets.

    Science.gov (United States)

    Hossain, Akter; Nandi, Uttom; Fule, Ritesh; Nokhodchi, Ali; Maniruzzaman, Mohammed

    2017-04-15

    The aim of the present study was to develop and characterise polymeric composite pellets by means of continuous melt extrusion techniques. Powder blends of a steroid hormone (SH) as a model drug and either ethyl cellulose (EC N10 and EC P7 grades) or hydroxypropyl methylcellulose (HPMC AS grade) as polymeric carrier were extruded using a Pharma 11mm twin screw extruder in a continuous mode of operation to manufacture extruded composite pellets of 1mm length. Molecular modelling study using commercial Gaussian 09 software outlined a possible drug-polymer interaction in the molecular level to develop solid dispersions of the drug in the pellets. Solid-state analysis conducted via a differential scanning calorimetry (DSC), hot stage microscopy (HSM) and X-ray powder diffraction (XRPD) analyses revealed the amorphous state of the drug in the polymer matrices. Surface analysis using SEM/energy dispersive X-ray (EDX) of the produced pellets arguably showed a homogenous distribution of the C and O atoms in the pellet matrices. Moreover, advanced chemical surface analysis conducted via atomic force microscopy (AFM) showed a homogenous phase system having the drug molecule dispersed onto the amorphous matrices while Raman mapping confirmed the homogenous single-phase drug distribution in the manufactured composite pellets. Such composite pellets are expected to deliver multidisciplinary applications in drug delivery and medical sciences by e.g. modifying drug solubility/dissolutions or stabilizing the unstable drug (e.g. hormone, protein) in the composite network. Copyright © 2016. Published by Elsevier Inc.

  1. Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

    Directory of Open Access Journals (Sweden)

    Lígia N. M. Ribeiro

    2017-01-01

    Full Text Available The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

  2. A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network.

    Science.gov (United States)

    Roman, Paul M; Abraham, Amanda J; Rothrauff, Tanja C; Knudsen, Hannah K

    2010-06-01

    The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future.

  3. Highlights from the 2015 WIN Symposium: novel targets, innovative agents, and advanced technologies-a WINning strategy?

    Science.gov (United States)

    Schilsky, Richard L

    2015-01-01

    The worldwide innovative networking (WIN) consortium comprises a global alliance of 28 academic and clinical cancer centres, 11 pharmaceutical and technology companies and five charitable or health payer organisations. Since its inception the consortium has striven to provide a forum for all of its members to network, share information and experience, and perform clinical trials with the overarching goal of advancing the care of patients with cancer through the use of precision medicine. The annual 2-day WIN Symposium is the most visible output of the consortium and provides an opportunity for around 400 experts and other delegates to meet and discuss the latest research and initiatives in personalised cancer medicine. The seventh WIN Symposium, held in Paris, France, 29-30 June 2015, consisted of nine plenary and eight poster sessions that covered the overarching theme of novel targets, innovative agents, and advanced technologies being a winning strategy. Highlights included discussions of immune mechanisms and ways to target the cancer immunome and systems biology approaches to supporting personalised cancer. The latest data from the BATTLE-2 and WINther trials were discussed, and round table discussions were held that focused on how best to design the next generation of clinical trials, which included SPRING, SUMMER, and BOOSTER being initiated by the WIN Consortium.

  4. Recent Advances in the Application of Vitamin E TPGS for Drug Delivery

    Science.gov (United States)

    Yang, Conglian; Wu, Tingting; Qi, Yan; Zhang, Zhiping

    2018-01-01

    D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future. PMID:29290821

  5. The industrial research project: “Blu-Archeosys – Innovative Technologies and Advanced Systems as Support in Underwater Archaeology”

    Directory of Open Access Journals (Sweden)

    Salvatore Lorusso

    2003-02-01

    Full Text Available The reasons of the research about new technologies as support in naval and underwater archaeology or, more generally, in waters archaeology are various and described in this work, where the characteristics of the research project “BLU-ARCHEOSYS – Innovative Technologies and Advanced SYStems as Support in Underwater ARCHaeology” are illustrated. This industrial research project faces problems regarding innovative technologies and instruments in waters archaeology and it comprehends synergic steps and joined works among skilled professionals that have the competences to interpret qualitative and/or quantitative data within an artistic – historical and technical – historical study, also with the involvement of various public and private institutions. The BLUARCHEOSYS project has, in fact, the objective to create technologies that have a reply in underwater archaeology and contemporaneously in other sectors. In particular, starting from the methodological way that spans from the discovery in underwater or subaerial environment to the collocation of the objects in museums, the intent is to support the different methodological stages with specific tools and innovative technologies. The education project, presented to the Ministry with the research one, is articulated in the different branches of artistic-historical character, of the management, normative and operative character, and of the technical-diagnostic-material-preservative character. The professionals will have not only theoretical knowledge about standard and consolidated technologies, but they will be also experts about methodologies, in particular the diagnostic ones, that put in field the innovative tools evaluated in the project, with consequent competitive advantage in the working field, more and more demanding specific sector competences.

  6. Innovation strategies for functional foods and supplements. Challenges of the positioning between foods and drugs

    NARCIS (Netherlands)

    Bröring, S.

    2010-01-01

    Functional benefits delivering more than a nutritional value to consumers present an opportunity for above average returns and, thus, have triggered numerous innovations from food as well as pharmaceutical companies. This development of functional foods and supplements has led to a new

  7. Recent Advances in the Synthesis of Graphene-Based Nanomaterials for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Zhuqing Wang

    2017-11-01

    Full Text Available Graphene-based nanomaterials have exhibited wide applications in nanotechnology, materials science, analytical science, and biomedical engineering due to their unique physical and chemical properties. In particular, graphene has been an excellent nanocarrier for drug delivery application because of its two-dimensional structure, large surface area, high stability, good biocompatibility, and easy surface modification. In this review, we present the recent advances in the synthesis and drug delivery application of graphene-based nanomaterials. The modification of graphene and the conjugation of graphene with other materials, such as small molecules, nanoparticles, polymers, and biomacromolecules as functional nanohybrids are introduced. In addition, the controlled drug delivery with the fabricated graphene-based nanomaterials are demonstrated in detail. It is expected that this review will guide the chemical modification of graphene for designing novel functional nanohybrids. It will also promote the potential applications of graphene-based nanomaterials in other biomedical fields, like biosensing and tissue engineering.

  8. Advanced drug delivery nanosystems (aDDnSs): a mini-review.

    Science.gov (United States)

    Demetzos, Costas; Pippa, Natassa

    2014-06-01

    Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and to improve its pharmacokinetics. Biocompatible nanomaterials have been used as biological markers, contrast agents for imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. The classification of drug delivery nanosystems (DDnSs) is a crucial issue and fundamental efforts on this subject are missing from the literature. This article deals with the classification of DDnSs with a modulatory controlled release profile (MCR) denoted as modulatory controlled release nanosystems (MCRnSs). Conventional (c) and advanced (a) DDnSs are denoted by the acronyms cDDnSs and aDDnSs, and can be composed of a single or more than one biomaterials, respectively. The classification was based on their characteristics such as: surface functionality (f), the nature of biomaterials used and the kind of interactions between biomaterials. The aDDnSs can be classified as hybridic (Hy-) or chimeric (Chi-) based on the nature - same or different respectively - of biomaterials and inorganic materials used. The nature of the elements used for producing advanced biomaterials is of great importance and medicinal chemistry contributes effectively to the production of aDDnSs.

  9. Diffusion of innovations in social interaction systems. An agent-based model for the introduction of new drugs in markets.

    Science.gov (United States)

    Pombo-Romero, Julio; Varela, Luis M; Ricoy, Carlos J

    2013-06-01

    The existence of imitative behavior among consumers is a well-known phenomenon in the field of Economics. This behavior is especially common in markets determined by a high degree of innovation, asymmetric information and/or price-inelastic demand, features that exist in the pharmaceutical market. This paper presents evidence of the existence of imitative behavior among primary care physicians in Galicia (Spain) when choosing treatments for their patients. From this and other evidence, we propose a dynamic model for determining the entry of new drugs into the market. To do this, we introduce the structure of the organization of primary health care centers and the presence of groups of doctors who are specially interrelated, as well as the existence of commercial pressure on doctors. For modeling purposes, physicians are treated as spins connected in an exponentially distributed complex network of the Watts-Strogatz type. The proposed model provides an explanation for the differences observed in the patterns of the introduction of technological innovations in different regions. The main cause of these differences is the different structure of relationships among consumers, where the existence of small groups that show a higher degree of coordination over the average is particularly influential. The evidence presented, together with the proposed model, might be useful for the design of optimal strategies for the introduction of new drugs, as well as for planning policies to manage pharmaceutical expenditure.

  10. How excluding some benefits from value assessment of new drugs impacts innovation.

    Science.gov (United States)

    Cook, Joseph P; Golec, Joseph

    2017-12-01

    Payers often assess the benefits of new drugs relative to costs for reimbursement purposes, but they frequently exclude some drugs' option-related benefits, reducing their reimbursement chances, and making them less attractive R&D investments. We develop and test a real options model of R&D investment that shows that excluding option-related benefits heightens drug developers' incentives to avoid high-risk (volatile) R&D investments and instead encourages them to focus on "safer" (positively skewed) investments. Our model and empirical results could partly explain the decline in the number of risky new molecular entities. Copyright © 2017 John Wiley & Sons, Ltd.

  11. The Sylvia Fedoruk Canadian Centre for Nuclear Innovation: advancing knowledge through partnerships

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, N.; Root, J.H., E-mail: neil.alexander@usask.ca, E-mail: john.root@usask.ca [Sylvia Fedoruk Canadian Centre for Nuclear Innovation, Saskatoon, SK (Canada); Chad, K., E-mail: karen.chad@usask.ca [Univ. of Saskatchewan, Saskatoon, SK (Canada); Bereznai, G., E-mail: george.bereznai@uoit.ca [Univ. of Ontario Inst. of Tech., Faculty of Energy Systems and Nuclear Science, Oshawa, ON (Canada); Dalzell, M.T.J., E-mail: matthew.dalzell@usask.ca [Sylvia Fedoruk Canadian Centre for Nuclear Innovation, Saskatoon, SK (Canada)

    2014-07-01

    The vision of the Sylvia Fedoruk Canadian Centre for Nuclear Innovation is to place the Canadian province of Saskatchewan among global leaders in nuclear research, development and training through partnerships with industry and academia for economic and social benefit. Saskatchewan is one of the world's largest producers of uranium and home to pioneering research in nuclear medicine, most notably the development of cobalt-60 teletherapy. The Fedoruk Centre is striving to build on this legacy through the attainment of four strategic goals: (1) building nuclear expertise and capacity through the support to academic programs and research projects in partnership with industry, academic institutions and research organizations in nuclear medicine, materials research, energy and the environment; (2) enhancing innovation in partnership with the research community and industry; (3) engaging communities and increasing understanding of risks, benefits and potential impacts of nuclear technologies; and (4) ensuring the sustainability and accountability of the Centre and its resources. The Fedoruk Centre's mandate includes the stewardship of select nuclear facilities, the first being a 24 MeV cyclotron and nuclear substances laboratory as a resource for the development of novel imaging agents, training and production of radioisotopes for clinical diagnoses. By attracting new research leadership in the nuclear domain, developing networks of expertise, training highly-qualified personnel in nuclear disciplines, stimulating industrial partnerships, and creating conditions for fact-based conversation regarding nuclear issues, the Fedoruk Centre is working to establish a research and innovation capacity to support a vibrant nuclear sector in Saskatchewan. (author)

  12. The Sylvia Fedoruk Canadian Centre for Nuclear Innovation: advancing knowledge through partnerships

    International Nuclear Information System (INIS)

    Alexander, N.; Root, J.H.; Chad, K.; Bereznai, G.; Dalzell, M.T.J.

    2014-01-01

    The vision of the Sylvia Fedoruk Canadian Centre for Nuclear Innovation is to place the Canadian province of Saskatchewan among global leaders in nuclear research, development and training through partnerships with industry and academia for economic and social benefit. Saskatchewan is one of the world's largest producers of uranium and home to pioneering research in nuclear medicine, most notably the development of cobalt-60 teletherapy. The Fedoruk Centre is striving to build on this legacy through the attainment of four strategic goals: (1) building nuclear expertise and capacity through the support to academic programs and research projects in partnership with industry, academic institutions and research organizations in nuclear medicine, materials research, energy and the environment; (2) enhancing innovation in partnership with the research community and industry; (3) engaging communities and increasing understanding of risks, benefits and potential impacts of nuclear technologies; and (4) ensuring the sustainability and accountability of the Centre and its resources. The Fedoruk Centre's mandate includes the stewardship of select nuclear facilities, the first being a 24 MeV cyclotron and nuclear substances laboratory as a resource for the development of novel imaging agents, training and production of radioisotopes for clinical diagnoses. By attracting new research leadership in the nuclear domain, developing networks of expertise, training highly-qualified personnel in nuclear disciplines, stimulating industrial partnerships, and creating conditions for fact-based conversation regarding nuclear issues, the Fedoruk Centre is working to establish a research and innovation capacity to support a vibrant nuclear sector in Saskatchewan. (author)

  13. Advancing Innovation Through Collaboration: Implementation of the NASA Space Life Sciences Strategy

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth E.

    2010-01-01

    On October 18, 2010, the NASA Human Health and Performance center (NHHPC) was opened to enable collaboration among government, academic and industry members. Membership rapidly grew to 90 members (http://nhhpc.nasa.gov ) and members began identifying collaborative projects as detailed in this article. In addition, a first workshop in open collaboration and innovation was conducted on January 19, 2011 by the NHHPC resulting in additional challenges and projects for further development. This first workshop was a result of the SLSD successes in running open innovation challenges over the past two years. In 2008, the NASA Johnson Space Center, Space Life Sciences Directorate (SLSD) began pilot projects in open innovation (crowd sourcing) to determine if these new internet-based platforms could indeed find solutions to difficult technical problems. From 2008 to 2010, the SLSD issued 34 challenges, 14 externally and 20 internally. The 14 external challenges were conducted through three different vendors: InnoCentive, Yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive platform, customized to NASA use, and promoted as NASA@Work. The results from the 34 challenges involved not only technical solutions that were reported previously at the 61st IAC, but also the formation of new collaborative relationships. For example, the TopCoder pilot was expanded by the NASA Space Operations Mission Directorate to the NASA Tournament Lab in collaboration with Harvard Business School and TopCoder. Building on these initial successes, the NHHPC workshop in January of 2011, and ongoing NHHPC member discussions, several important collaborations have been developed: (1) Space Act Agreement between NASA and GE for collaborative projects (2) NASA and academia for a Visual Impairment / Intracranial Hypertension summit (February 2011) (3) NASA and the DoD through the Defense Venture Catalyst Initiative (DeVenCI) for a technical needs workshop (June 2011) (4

  14. Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

    Science.gov (United States)

    Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

    2013-12-10

    Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Innovative experimental particle physics through technological advances: Past, present and future

    International Nuclear Information System (INIS)

    Cheung, Harry W.K.; Fermilab

    2005-01-01

    This mini-course gives an introduction to the techniques used in experimental particle physics with an emphasis on the impact of technological advances. The basic detector types and particle accelerator facilities will be briefly covered with examples of their use and with comparisons. The mini-course ends with what can be expected in the near future from current technology advances. The mini-course is intended for graduate students and post-docs and as an introduction to experimental techniques for theorists

  16. Overview of experimental work to ensure innovation of nuclear fuel for future advanced PWRs

    International Nuclear Information System (INIS)

    Zymak, J.; Valach, M.; Hejna, J.

    2002-11-01

    It is envisaged that advanced nuclear fuel will be operated in high burnup conditions, at a high linear power and at considerable mechanical fuel-cladding interactions. The report gives an overview of experimental work investigating phenomena that will affect APWR fuel, such as the manufacturing technology, thermal properties and safety requirements

  17. Launching the dialogue: Safety and innovation as partners for success in advanced manufacturing.

    Science.gov (United States)

    Geraci, C L; Tinkle, S S; Brenner, S A; Hodson, L L; Pomeroy-Carter, C A; Neu-Baker, N

    2018-06-01

    Emerging and novel technologies, materials, and information integrated into increasingly automated and networked manufacturing processes or into traditional manufacturing settings are enhancing the efficiency and productivity of manufacturing. Globally, there is a move toward a new era in manufacturing that is characterized by: (1) the ability to create and deliver more complex designs of products; (2) the creation and use of materials with new properties that meet a design need; (3) the employment of new technologies, such as additive and digital techniques that improve on conventional manufacturing processes; and (4) a compression of the time from initial design concept to the creation of a final product. Globally, this movement has many names, but "advanced manufacturing" has become the shorthand for this complex integration of material and technology elements that enable new ways to manufacture existing products, as well as new products emerging from new technologies and new design methods. As the breadth of activities associated with advanced manufacturing suggests, there is no single advanced manufacturing industry. Instead, aspects of advanced manufacturing can be identified across a diverse set of business sectors that use manufacturing technologies, ranging from the semiconductors and electronics to the automotive and pharmaceutical industries. The breadth and diversity of advanced manufacturing may change the occupational and environmental risk profile, challenge the basic elements of comprehensive health and safety (material, process, worker, environment, product, and general public health and safety), and provide an opportunity for development and dissemination of occupational and environmental health and safety (OEHS) guidance and best practices. It is unknown how much the risk profile of different elements of OEHS will change, thus requiring an evolution of health and safety practices. These changes may be accomplished most effectively through multi

  18. Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications.

    Science.gov (United States)

    DiMasi, Joseph A

    2013-06-01

    Much of the literature on trends and factors affecting biopharmaceutical innovation has focused overwhelmingly on the development and approval of never-before approved drugs and biologics. Little attention has been paid to new uses for already-approved compounds, which can be an important form of innovation. This paper aimed to determine and analyze recent trends in the number and type of new or modified US indication approvals for drugs and biologics. We also examine regulatory approval-phase times for new-use efficacy supplements and compare them to approval-phase times for original-use approvals over the same period. We developed a data set of efficacy supplements approved by the US Food and Drug Administration (FDA) from 1998 to 2011 that includes information on the type, approval-phase time (time from submission to the FDA of an application for marketing approval to approval of the application), and FDA therapeutic-significance rating for the approved application, which we obtained from an FDA Web site. This data set was merged with a Tufts Center for the Study of Drug Development (CSDD) data set of US new drug and biologics approvals. We developed descriptive statistics on trends in the number and type of new-use efficacy supplements, on US regulatory approval-phase times for the supplements, and on original new drug and biologics approvals over the study period and for the time from original- to new-use approval. The total number of new-use efficacy-supplement approvals did not exhibit a marked trend, but the number of new pediatric-indication approvals increased substantially. Approval-phase times for new-use supplements varied by therapeutic class and FDA therapeutic-significance rating. Mean approval-phase times were highest for central nervous system compounds (13.8 months) and lowest for antineoplastics (8.9 months). The mean time from original to supplement approval was substantially longer for new pediatric indications than for other new uses. Mean

  19. Music Therapy Advances in Neuro-disability - Innovations in Research and Practice

    DEFF Research Database (Denmark)

    O'Kelly, Julian; Magee, Wendy L.; Street, Alex

    2014-01-01

    therapy, music neuroscience and music psychology addressing the needs of those with acquired and degenerative neurological conditions. The diverse and evolving work in this field is reflected in the topics covered, including disorders of consciousness, dementia, stroke, and the use of modern neuro......-imaging methods to measure the effects of music therapy at a cortical level. A discussion of the implications of these converging foci highlights the benefits of the cross-disciplinary dialogue that characterised the conference.......This article provides a summary of the oral papers presented during a two day international conference, which took place on 7th & 8th June 2013, at the Royal Hospital for Neuro-disability (RHN) in London. The summary texts detail innovative research projects and clinical developments across music...

  20. Advanced impedance matching system for ICRF heating using innovative twin stub tuner and frequency variation

    International Nuclear Information System (INIS)

    Kumazawa, R.; Saito, K.; Kasahara, H.; Seki, T.; Mutoh, T.; Shimpo, F.; Nomura, G.; Kato, A.; Okada, H.; Zhao, Y.; Kwak, J.G.; Yoon, J.S.

    2008-01-01

    Ion cyclotron range of frequency (ICRF) heating has been a reliable tool for steady-state plasma heating with high RF power of several tens of megawatts. However, a sudden increase in the reflected RF power during ICRF heating experiments with ELMy H-mode plasmas is an issue which must be solved for future fusion experimental devices or fusion reactors. This paper describes an innovative ICRF heating system using a frequency feedback control to reduce the reflected power in response to the rapid change in the plasma impedance in the ELMy H-mode plasma. A twin stub tuner has been newly invented for this purpose. The feasibility of keeping the reflected RF power fraction at a low level, e.g. 1%, is demonstrated even with a large change in plasma resistance, e.g. 2 ∼ 8Ω. Calculated and experimental results are presented for the conventional double stub tuner impedance matching system equipped with the twin stub tuner.

  1. Coevolution of patients and hospitals: how changing epidemiology and technological advances create challenges and drive organizational innovation.

    Science.gov (United States)

    Lega, Federico; Calciolari, Stefano

    2012-01-01

    Over the last 20 years, hospitals have revised their organizational structures in response to new environmental pressures. Today, demographic and epidemiologic trends and recent technological advances call for new strategies to cope with ultra-elderly frail patients characterized by chronic conditions, high-severity health problems, and complex social situations. The main areas of change surround new ways of managing emerging clusters of patients whose needs are not efficiently or effectively met within traditional hospital organizations. Following the practitioner and academic literature, we first identify the most relevant clusters of new kinds of patients who represent an increasingly larger share of the hospital population in developed countries. Second, we propose a framework that synthesizes the major organizational innovations adopted by successful organizations around the world. We conclude by substantiating the trends of and the reasoning behind the prospective pattern of hospital organizational development.

  2. Metabolism-Activated Multitargeting (MAMUT): An Innovative Multitargeting Approach to Drug Design and Development.

    Science.gov (United States)

    Mátyus, Péter; Chai, Christina L L

    2016-06-20

    Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Mother-infant consultation during drug treatment: Research and innovative clinical practice

    Directory of Open Access Journals (Sweden)

    Lester Barry M

    2008-02-01

    Full Text Available Abstract Background This paper details a model for consulting with mothers and infants, and drug treatment staff used in a residential drug treatment program and relevant to other treatment settings. The role of parent-infant consultation based on the Neonatal Network Neurobehavioral Scale (NNNS was evaluated. Methods A sequential cohort model was used to assign participants to 1. NNNS consultation versus 2. standard care. The effects of NNNS consultation were evaluated using the Parenting Stress Index and NNNS summary scores. Results Participants in the NNNS consultation condition had significantly less stress overall, and less stress related to infant behavior than participants in standard care. There were no differences in infant behavior on the NNNS Summary scores. Conclusion The implications for NNNS consultation in drug treatment programs is outlined. The importance of prevention/intervention to establish satisfactory mother-infant interaction in recovery programs which include a central parenting component is indicated.

  4. Synergy between scientific advancement and technological innovation, illustrated by a mechanism-based model characterizing sodium-glucose cotransporter-2 inhibition.

    Science.gov (United States)

    Zhang, Liping; Ng, Chee M; List, James F; Pfister, Marc

    2010-09-01

    Advances in experimental medicine and technological innovation during the past century have brought tremendous progress in modern medicine and generated an ever-increasing amount of data from bench and bedside. The desire to extend scientific knowledge motivates effective data integration. Technological innovation makes this possible, which in turn accelerates the advancement in science. This mutually beneficial interaction is illustrated by the development of an expanded mechanism-based model for understanding a novel mechanism, sodium-glucose cotransporter-2 SGLT2 inhibition for potential treatment of type 2 diabetes mellitus.

  5. Advanced technology care innovation for older people in Italy: necessity and opportunity to promote health and wellbeing.

    Science.gov (United States)

    Lattanzio, Fabrizia; Abbatecola, Angela M; Bevilacqua, Roberta; Chiatti, Carlos; Corsonello, Andrea; Rossi, Lorena; Bustacchini, Silvia; Bernabei, Roberto

    2014-07-01

    Even though there is a constant and accelerating growth of the aging population worldwide, such a rapid rise is negatively impacting available home and community services not able to encompass the necessities associated with the increased number of older people. In particular, there are increasing demands on e-health care services and smart technologies needed for frail elders with chronic diseases and also for those experiencing active aging. Advanced Technology Care Innovation for older persons encompasses all sectors (assistive technology, robotics, home automation, and home care- and institution-based healthcare monitoring, telemedicine) dedicated to promoting health and wellbeing in all types of living environments. Considering that there is a large concern and demand by older persons to remain in familiar social living surroundings, study projects joined with industries have been currently initiated, especially across Europe to improve health and wellbeing. This article will highlight the latest updates in Europe and, in particular in Italy, regarding scientific projects dedicated to unraveling how diverse needs can be translated into an up-to-date technology innovation for the growing elder population. We will provide information regarding advanced technology designed for those with specific geriatric-correlated conditions in familiar living settings and for individuals aging actively. This is an important action because numerous emerging developments are based on user needs identified by geriatricians, thus, underlining the indispensable role of geriatric medicine toward future guidelines on specific technology. Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  6. Porous silicon for drug delivery applications and theranostics: recent advances, critical review and perspectives.

    Science.gov (United States)

    Kumeria, Tushar; McInnes, Steven J P; Maher, Shaheer; Santos, Abel

    2017-12-01

    Porous silicon (pSi) engineered by electrochemical etching has been used as a drug delivery vehicle to address the intrinsic limitations of traditional therapeutics. Biodegradability, biocompatibility, and optoelectronic properties make pSi a unique candidate for developing biomaterials for theranostics and photodynamic therapies. This review presents an updated overview about the recent therapeutic systems based on pSi, with a critical analysis on the problems and opportunities that this technology faces as well as highlighting pSi's growing potential. Areas covered: Recent progress in pSi-based research includes drug delivery systems, including biocompatibility studies, drug delivery, theranostics, and clinical trials with the most relevant examples of pSi-based systems presented here. A critical analysis about the technical advantages and disadvantages of these systems is provided along with an assessment on the challenges that this technology faces, including clinical trials and investors' support. Expert opinion: pSi is an outstanding material that could improve existing drug delivery and photodynamic therapies in different areas, paving the way for developing advanced theranostic nanomedicines and incorporating payloads of therapeutics with imaging capabilities. However, more extensive in-vivo studies are needed to assess the feasibility and reliability of this technology for clinical practice. The technical and commercial challenges that this technology face are still uncertain.

  7. Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

    Science.gov (United States)

    Teixeira, M C; Carbone, C; Souto, E B

    2017-10-01

    Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Millimeter-wave imaging of magnetic fusion plasmas: technology innovations advancing physics understanding

    Science.gov (United States)

    Wang, Y.; Tobias, B.; Chang, Y.-T.; Yu, J.-H.; Li, M.; Hu, F.; Chen, M.; Mamidanna, M.; Phan, T.; Pham, A.-V.; Gu, J.; Liu, X.; Zhu, Y.; Domier, C. W.; Shi, L.; Valeo, E.; Kramer, G. J.; Kuwahara, D.; Nagayama, Y.; Mase, A.; Luhmann, N. C., Jr.

    2017-07-01

    Electron cyclotron emission (ECE) imaging is a passive radiometric technique that measures electron temperature fluctuations; and microwave imaging reflectometry (MIR) is an active radar imaging technique that measures electron density fluctuations. Microwave imaging diagnostic instruments employing these techniques have made important contributions to fusion science and have been adopted at major fusion facilities worldwide including DIII-D, EAST, ASDEX Upgrade, HL-2A, KSTAR, LHD, and J-TEXT. In this paper, we describe the development status of three major technological advancements: custom mm-wave integrated circuits (ICs), digital beamforming (DBF), and synthetic diagnostic modeling (SDM). These have the potential to greatly advance microwave fusion plasma imaging, enabling compact and low-noise transceiver systems with real-time, fast tracking ability to address critical fusion physics issues, including ELM suppression and disruptions in the ITER baseline scenario, naturally ELM-free states such as QH-mode, and energetic particle confinement (i.e. Alfvén eigenmode stability) in high-performance regimes that include steady-state and advanced tokamak scenarios. Furthermore, these systems are fully compatible with today’s most challenging non-inductive heating and current drive systems and capable of operating in harsh environments, making them the ideal approach for diagnosing long-pulse and steady-state tokamaks.

  9. Innovation in the planning of V-Y rotation advancement flaps: A template for flap design

    Directory of Open Access Journals (Sweden)

    Utku Can Dölen

    2018-01-01

    Full Text Available Local flaps exhibit excellent color matching that no other type of flap can compete with. Moreover, surgery using a local flap is easier and faster than surgery using a distant or free flap. However, local flaps can be much more difficult to design. We designed 2 templates to plan a V-Y rotation advancement flap. The template for a unilateral V-Y rotation advancement flap was used on the face (n=5, anterior tibia (n=1, posterior axilla (n=1, ischium (n=1, and trochanter (n=2. The template for a bilateral flap was used on the sacrum (n=8, arm (n=1, and anterior tibia (n=1. The causes of the defects were meningocele (n=3, a decubitus ulcer (n=5, pilonidal sinus (n=3, and skin tumor excision (n=10. The meningocele patients were younger than 8 days. The mean age of the adult patients was 50.4 years (range, 19–80 years. All the donor areas of the flaps were closed primarily. None of the patients experienced wound dehiscence or partial/total flap necrosis. The templates guided surgeons regarding the length and the placement of the incision for a V-Y rotation advancement flap according to the size of the wound. In addition, they could be used for the training of residents.

  10. The emergence of forensic nursing and advanced nursing practice in Switzerland: an innovative case study consultation.

    Science.gov (United States)

    Romain-Glassey, Nathalie; Ninane, Françoise; de Puy, Jacqueline; Abt, Maryline; Mangin, Patrice; Morin, Diane

    2014-01-01

    The objectives of this article were to systematically describe and examine the novel roles and responsibilities assumed by nurses in a forensic consultation for victims of violence at a University Hospital in French-speaking Switzerland. Utilizing a case study methodology, information was collected from two main sources: (a) discussion groups with nurses and forensic pathologists and (b) a review of procedures and protocols. Following a critical content analysis, the roles and responsibilities of the forensic nurses were described and compared with the seven core competencies of advanced nursing practice as outlined by Hamric, Spross, and Hanson (2009). Advanced nursing practice competencies noted in the analysis included "direct clinical practice," "coaching and guidance," and "collaboration." The role of the nurse in terms of "consultation," "leadership," "ethics," and "research" was less evident in the analysis. New forms of nursing are indeed practiced in the forensic clinical setting, and our findings suggest that nursing practice in this domain is following the footprints of an advanced nursing practice model. Further reflections are required to determine whether the role of the forensic nurse in Switzerland should be developed as a clinical nurse specialist or that of a nurse practitioner.

  11. The potential of protein-nanomaterial interaction for advanced drug delivery

    DEFF Research Database (Denmark)

    Peng, Qiang; Mu, Huiling

    2016-01-01

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself...... of such interaction for advanced drug delivery are presented........ Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized...

  12. Introduction to the College on Problems of Drug Dependence special issue: contemporary advances in opioid neuropharmacology.

    Science.gov (United States)

    Walsh, Sharon L; Unterwald, Ellen M; Izenwasser, Sari

    2010-05-01

    Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G, and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.

  13. Does innovation in obesity drugs affect stock markets? An event study analysis.

    Science.gov (United States)

    Pérez-Rodríguez, Jorge V; González López-Valcárcel, Beatriz

    2012-01-01

    This study empirically analyzes the effects of public information about the pharmaceutical R&D process on the market valuation of the sponsoring firm. We examined the market's response to scientific news and regulatory decisions about an antiobesity drug, rimonabant, and the effects on the sponsoring company (Sanofi-Aventis) and its incumbent competitors (Abbott and Roche). Event study methodology was used to test the null hypothesis of no market response. We covered the full life cycle of rimonabant (1994-2008), using a data set of daily closing price and volume. The results suggest that scientific news in the initial stages of the drug R&D process (i.e., drug discovery, preclinical and clinical trials) had no significant effects. However, news related to regulatory decisions, such as recall or safety warning, had significant negative effects on the company's market value. No spillover/contagion effects on competitor firms were detected. Market reactions occur at the time when the regulator takes decisions about drugs. Scientific news, even those of high-impact, may pass unnoticed. Copyright © 2011 SESPAS. Published by Elsevier España, S.L. All rights reserved.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  15. IMPLICATIONS OF GLOBAL PRICING POLICIES ON ACCESS TO INNOVATIVE DRUGS: THE CASE OF TRASTUZUMAB IN SEVEN LATIN AMERICAN COUNTRIES.

    Science.gov (United States)

    Pichon-Riviere, Andres; Garay, Osvaldo Ulises; Augustovski, Federico; Vallejos, Carlos; Huayanay, Leandro; Bueno, Maria del Pilar Navia; Rodriguez, Alarico; de Andrade, Carlos José Coelho; Buendía, Jefferson Antonio; Drummond, Michael

    2015-01-01

    Differential pricing, based on countries' purchasing power, is recommended by the World Health Organization to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage, and accessibility for patients with breast cancer in Latin America (LA). A Markov model was designed to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country. Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent and 26.6 percent, respectively). Trastuzumab price would need to decrease between 69.6 percent to 94.9 percent to became CE in LA. Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries.

  16. Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations.

    Science.gov (United States)

    Cournia, Zoe; Allen, Bryce; Sherman, Woody

    2017-12-26

    Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives

  17. Advanced core physics and thermal hydraulics analysis of boiling water reactors using innovative fuel concepts

    International Nuclear Information System (INIS)

    Winter, Dominik

    2014-01-01

    The economical operation of a boiling water reactor (BWR) is mainly achieved by the axially uniform utilization of the nuclear fuel in the assemblies which is challenging because the neutron spectrum in the active reactor core varies with the axial position. More precisely, the neutron spectrum becomes harder the higher the position is resulting in a decrease of the fuel utilization because the microscopic fission cross section is smaller by several orders of magnitude. In this work, the use of two fuel concepts based on a mixed oxide (MOX) fuel and an innovative thorium-plutonium (ThPu) fuel is investigated by a developed simulation model encompassing thermal hydraulics, neutronics, and fuel burnup. The main feature of these fuel concepts is the axially varying enrichment in plutonium which is, in this work, recycled from spent nuclear fuel and shows a high fission fraction of the absorption cross section for fast incident neutron energies. The potential of balancing the overall fuel utilization by an increase of the fission rate in the upper part of the active height with a combination of the harder spectrum and the higher fission fraction of the absorption cross section in the BWR core is studied. The three particular calculational models for thermal hydraulics, neutronics, and fuel burnup provide results at fuel assembly and/or at core level. In the former case, the main focus lies on the thermal hydraulics analysis, fuel burnup, and activity evolution after unloading from the core and, in the latter case, special attention is paid to reactivity safety coefficients (feedback effects) and the optimization of the operational behavior. At both levels (assembly and core), the isotopic buildup and depletion rates as a function of the active height are analyzed. In addition, a comparison between the use of conventional fuel types with homogeneous enrichments and the use of the innovative fuel types is made. In the framework of the simulations, the ThPu and the MOX

  18. Innovative Graduate Research Education for Advancement of Implementation Science in Adolescent Behavioral Health.

    Science.gov (United States)

    Burton, Donna L; Levin, Bruce Lubotsky; Massey, Tom; Baldwin, Julie; Williamson, Heather

    2016-04-01

    An innovative approach to research education that integrates the theory and principles of implementation science, participatory research, and service learning in the area of adolescent behavioral health is presented. Qualitative interviews and surveys of program participants have been conducted to assess the program's curricula, service-learning partnerships, student (scholar) satisfaction, and views of community partnerships and academic mentors. The Institute has experienced the successful completion of its first and second cohorts and enrollment of a third cohort of scholars. Community partners are utilizing results of service-learning projects to influence agency operations. Institute scholars have identified research and service learning experiences as key factors in the decision to apply to the Institute graduate certificate program. The availability of tuition support is identified as valuable but not ranked as the most important reason for scholar interest in the program. Academic mentors report positive relationships with community agencies. Future iterations of the program will expand options for distance learning and alternatives to traditional graduate education for community-based scholars. Community partner agency capacity for participation is expected to change over time. Methods are being identified to both sustain existing partnerships and develop new community partnership relationships.

  19. Towards an advanced e-Infrastructure for Civil Protection applications: Research Strategies and Innovation Guidelines

    Science.gov (United States)

    Mazzetti, P.; Nativi, S.; Verlato, M.; Angelini, V.

    2009-04-01

    In the context of the EU co-funded project CYCLOPS (http://www.cyclops-project.eu) the problem of designing an advanced e-Infrastructure for Civil Protection (CP) applications has been addressed. As a preliminary step, some studies about European CP systems and operational applications were performed in order to define their specific system requirements. At a higher level it was verified that CP applications are usually conceived to map CP Business Processes involving different levels of processing including data access, data processing, and output visualization. At their core they usually run one or more Earth Science models for information extraction. The traditional approach based on the development of monolithic applications presents some limitations related to flexibility (e.g. the possibility of running the same models with different input data sources, or different models with the same data sources) and scalability (e.g. launching several runs for different scenarios, or implementing more accurate and computing-demanding models). Flexibility can be addressed adopting a modular design based on a SOA and standard services and models, such as OWS and ISO for geospatial services. Distributed computing and storage solutions could improve scalability. Basing on such considerations an architectural framework has been defined. It is made of a Web Service layer providing advanced services for CP applications (e.g. standard geospatial data sharing and processing services) working on the underlying Grid platform. This framework has been tested through the development of prototypes as proof-of-concept. These theoretical studies and proof-of-concept demonstrated that although Grid and geospatial technologies would be able to provide significant benefits to CP applications in terms of scalability and flexibility, current platforms are designed taking into account requirements different from CP. In particular CP applications have strict requirements in terms of: a) Real

  20. Digital Therapeutics: An Integral Component of Digital Innovation in Drug Development.

    Science.gov (United States)

    Sverdlov, Oleksandr; van Dam, Joris; Hannesdottir, Kristin; Thornton-Wells, Tricia

    2018-07-01

    Digital therapeutics represent a new treatment modality in which digital systems such as smartphone apps are used as regulatory-approved, prescribed therapeutic interventions to treat medical conditions. In this article we provide a critical overview of the rationale for investing in such novel modalities, including the unmet medical needs addressed by digital therapeutics and the potential for reducing current costs of medical care. We also discuss emerging pathways to regulatory approval and how innovative business models are enabling further growth in the development of digital therapeutics. We conclude by providing some recent examples of digital therapeutics that have gained regulatory approval and highlight opportunities for the near future. © 2018 American Society for Clinical Pharmacology and Therapeutics.

  1. WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

    Energy Technology Data Exchange (ETDEWEB)

    Xing, L [Stanford University, Stanford, CA (United States); Wong, J [Johns Hopkins University, Baltimore, MD (United States); Li, R [Stanford University, Palo Alto, CA (United States)

    2014-06-15

    Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gated VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.

  2. WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

    International Nuclear Information System (INIS)

    Xing, L; Wong, J; Li, R

    2014-01-01

    Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gated VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications

  3. Energy systems. Tome 3: advanced cycles, low environmental impact innovative systems

    International Nuclear Information System (INIS)

    Gicquel, R.

    2009-01-01

    This third tome about energy systems completes the two previous ones by showing up advanced thermodynamical cycles, in particular having a low environmental impact, and by dealing with two other questions linked with the study of systems with a changing regime operation: - the time management of energy, with the use of thermal and pneumatic storage systems and time simulation (schedule for instance) of systems (solar energy type in particular); - the technological dimensioning and non-nominal regime operation studies. Because this last topic is particularly complex, new functionalities have been implemented mainly by using the external classes mechanism, which allows the user to freely personalize his models. This tome is illustrated with about 50 examples of cycles modelled with Thermoptim software. Content: foreword; 1 - generic external classes; 2 - advanced gas turbine cycles; 3 - evaporation-concentration, mechanical steam compression, desalination, hot gas drying; 4 - cryogenic cycles; 5 - electrochemical converters; 6 - global warming, CO 2 capture and sequestration; 7 - future nuclear reactors (coupled to Hirn and Brayton cycles); 8 - thermodynamic solar cycles; 10 - pneumatic and thermal storage; 11 - calculation of thermodynamic solar facilities; 12 - problem of technological dimensioning and non-nominal regime; 13 - exchangers modeling and parameterizing for the dimensioning and the non-nominal regime; 14 - modeling and parameterizing of volumetric compressors; 15 - modeling and parameterizing of turbo-compressors and turbines; 16 - identification methodology of component parameters; 17 - case studies. (J.S.)

  4. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Directory of Open Access Journals (Sweden)

    Dubravka Svob Strac

    2016-11-01

    Full Text Available A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions and comorbid psychiatric disorders commonly seen in people with epilepsy. However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine and melatonin in epilepsy. Recent experimental, clinical and genetic evidence, will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of one-molecule-one-target, have turned out to be effective only in a percentage of people with epilepsy. Although no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins present on both neurons and glia cells may represent a new approach in the management of seizures and their generation as well as comorbid neuropsychiatric disorders.

  5. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Science.gov (United States)

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

  6. Sudden death related to advanced coronary atherosclerosis in mini-pigs. Influence of some drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jacobsson, L.; Lundholm, L.; Wingren, G. (Department of Pharmacology, Linkoeping University, Linkoeping, Sweden)

    1984-01-01

    Advanced coronary atherosclerosis was produced in 30 mini-pigs by a combination of a hypercholesterolaemic diet and X-irradiation to the precordial region. Within 11-25 weeks after the irradiation, 13 of the 30 animals died a sudden death probably caused by coronary atherosclerosis. The contents of free and ester-bound cholesterol in the right coronary artery were significantly higher in the animals which died spontaneously than in surviving animals. In an untreated group of 12 animals 7 died whereas in a group treated with ..beta..-pyridylcarbinol only 1 out of 5 died. In the coronary arteries, the contents of both free and ester-bound cholesterol were significantly lower in the ..beta..-pyridylcarbinol-treated animals. In a sulfinpyrazontreated group 3 out of 8, and in a metoprolol-treated group 2 out of 5 animals died. None of these drugs reduced the accumulation of cholesterol in the coronary arteries. The rate of sudden death was 26 +- 6% (P<0.05) lower in the combined group of treated animals than in the untreated ones. By regular ECG recordings, signs which could predict the fatal outcome of the experiment were looked for. Although depressed ST segments were present before death in a few animals, this was not a regular phenomenon. It is concluded that advanced coronary atherosclerosis in mini-pigs often leads to sudden death and that this animal model seems suitable for testing the potential therapeutic effects of drugs.

  7. Innovative partnerships to advance public health training in community-based academic residency programs

    Directory of Open Access Journals (Sweden)

    Lo JC

    2017-10-01

    Full Text Available Joan C Lo,1–3 Thomas E Baudendistel,2,3 Abhay Dandekar,3,4 Phuoc V Le,5 Stanton Siu,2,3 Bruce Blumberg6 1Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA; 2Department of Medicine, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA; 3Graduate Medical Education, Kaiser Permanente East Bay, Oakland, CA, USA; 4Department of Pediatrics, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA; 5School of Public Health, University of California Berkeley, Berkeley, CA, USA; 6Graduate Medical Education, Kaiser Permanente Northern California, Oakland, CA, USA Abstract: Collaborative partnerships between community-based academic residency ­training programs and schools of public health, represent an innovative approach to training future physician leaders in population management and public health. In Kaiser Permanente Northern California, development of residency-Masters in Public Health (MPH tracks in the Internal Medicine Residency and the Pediatrics Residency programs, with MPH graduate studies completed at the University of California Berkeley School of Public Health, enables physicians to integrate clinical training with formal education in epidemiology, biostatistics, health policy, and disease prevention. These residency-MPH programs draw on more than 50 years of clinical education, public health training, and health services research – creating an environment that sparks inquiry and added value by developing skills in patient-centered care through the lens of population-based outcomes. Keywords: graduate medical education, public health, master’s degree, internal medicine, pediatrics, residency training

  8. Advanced Practice Nursing Committee on Process Improvement in Trauma: An Innovative Application of the Strong Model.

    Science.gov (United States)

    West, Sarah Katherine

    2016-01-01

    This article aims to summarize the successes and future implications for a nurse practitioner-driven committee on process improvement in trauma. The trauma nurse practitioner is uniquely positioned to recognize the need for clinical process improvement and enact change within the clinical setting. Application of the Strong Model of Advanced Practice proves to actively engage the trauma nurse practitioner in process improvement initiatives. Through enhancing nurse practitioner professional engagement, the committee aims to improve health care delivery to the traumatically injured patient. A retrospective review of the committee's first year reveals trauma nurse practitioner success in the domains of direct comprehensive care, support of systems, education, and leadership. The need for increased trauma nurse practitioner involvement has been identified for the domains of research and publication.

  9. Technologic advances in aural rehabilitation: applications and innovative methods of service delivery.

    Science.gov (United States)

    Sweetow, Robert W; Sabes, Jennifer Henderson

    2007-06-01

    The level of interest in aural rehabilitation has increased recently, both in clinical use and in research presentations and publications. Advances in aural rehabilitation have seen previous techniques such as speech tracking and analytic auditory training reappear in computerized forms. These new delivery methods allow for a consistent, cost-effective, and convenient training program. Several computerized aural rehabilitation programs for hearing aid wearers and cochlear implant recipients have recently been developed and were reported on at the 2006 State of the Science Conference of the Rehabilitation Engineering Research Center on Hearing Enhancement at Gallaudet University. This article reviews these programs and outlines the similarities and differences in their design. Another promising area of aural rehabilitation research is the use of pharmaceuticals in the rehabilitation process. The results from a study of the effect of d-amphetamine in conjunction with intensive aural rehabilitation with cochlear implant patients are also described.

  10. Innovative grinding wheel design for cost-effective machining of advanced ceramics. Phase I, final report

    Energy Technology Data Exchange (ETDEWEB)

    Licht, R.H.; Ramanath, S.; Simpson, M.; Lilley, E.

    1996-02-01

    Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics. This program was a cooperative effort involving three Norton groups representing a superabrasive grinding wheel manufacturer, a diamond film manufacturing division and a ceramic research center. The program was divided into two technical tasks, Task 1, Analysis of Required Grinding Wheel Characteristics, and Task 2, Design and Prototype Development. In Task 1 we performed a parallel path approach with Superabrasive metal-bond development and the higher technical risk, CVD diamond wheel development. For the Superabrasive approach, Task 1 included bond wear and strength tests to engineer bond-wear characteristics. This task culminated in a small-wheel screening test plunge grinding sialon disks. In Task 2, an improved Superabrasive metal-bond specification for low-cost machining of ceramics in external cylindrical grinding mode was identified. The experimental wheel successfully ground three types of advanced ceramics without the need for wheel dressing. The spindle power consumed by this wheel during test grinding of NC-520 sialon is as much as to 30% lower compared to a standard resin bonded wheel with 100 diamond concentration. The wheel wear with this improved metal bond was an order of magnitude lower than the resin-bonded wheel, which would significantly reduce ceramic grinding costs through fewer wheel changes for retruing and replacements. Evaluation of ceramic specimens from both Tasks 1 and 2 tests for all three ceramic materials did not show evidence of unusual grinding damage. The novel CVD-diamond-wheel approach was incorporated in this program as part of Task 1. The important factors affecting the grinding performance of diamond wheels made by CVD coating preforms were determined.

  11. Advanced Artificial Science. The development of an artificial science and engineering research infrastructure to facilitate innovative computational modeling, analysis, and application to interdisciplinary areas of scientific investigation.

    Energy Technology Data Exchange (ETDEWEB)

    Saffer, Shelley (Sam) I.

    2014-12-01

    This is a final report of the DOE award DE-SC0001132, Advanced Artificial Science. The development of an artificial science and engineering research infrastructure to facilitate innovative computational modeling, analysis, and application to interdisciplinary areas of scientific investigation. This document describes the achievements of the goals, and resulting research made possible by this award.

  12. Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

    Directory of Open Access Journals (Sweden)

    Jalani G

    2014-05-01

    Full Text Available Ghulam Jalani,* Chan Woo Jung,* Jae Sang Lee, Dong Woo Lim Department of Bionano Engineering, College of Engineering Sciences, Hanyang University, Education Research Industry Cluster at Ansan Campus, Ansan, South Korea*These authors contributed equally to this workAbstract: Stimuli-responsive, polymer-based nanostructures with anisotropic compartments are of great interest as advanced materials because they are capable of switching their shape via environmentally-triggered conformational changes, while maintaining discrete compartments. In this study, a new class of stimuli-responsive, anisotropic nanofiber scaffolds with physically and chemically distinct compartments was prepared via electrohydrodynamic cojetting with side-by-side needle geometry. These nanofibers have a thermally responsive, physically-crosslinked compartment, and a chemically-crosslinked compartment at the nanoscale. The thermally responsive compartment is composed of physically crosslinkable poly(N-isopropylacrylamide poly(NIPAM copolymers, and poly(NIPAM-co-stearyl acrylate poly(NIPAM-co-SA, while the thermally-unresponsive compartment is composed of polyethylene glycol dimethacrylates. The two distinct compartments were physically crosslinked by the hydrophobic interaction of the stearyl chains of poly(NIPAM-co-SA or chemically stabilized via ultraviolet irradiation, and were swollen in physiologically relevant buffers due to their hydrophilic polymer networks. Bicompartmental nanofibers with the physically-crosslinked network of the poly(NIPAM-co-SA compartment showed a thermally-triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA. Furthermore, when bovine serum albumin and dexamethasone phosphate were separately loaded into each compartment, the bicompartmental nanofibers with anisotropic actuation exhibited decoupled, controlled release profiles of both drugs in response to a temperature. A new class of multicompartmental nanofibers could be

  13. Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

    Science.gov (United States)

    Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

    2017-01-01

    There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. A disease looking for innovative drugs: The case of pulmonary arterial hypertension.

    Science.gov (United States)

    Joppi, Roberta; Gerardi, Chiara; Bertele', Vittorio; Garattini, Silvio

    2018-05-25

    Pulmonary arterial hypertension (PAH) is a life-threatening rare disease. Between 2001 and 2016 the European Medicines Agency (EMA) approved nine drugs to treat PAH. Considering the poor prognosis of patients with PAH it would be useful to understand whether the approved therapies can change the natural history of the disease. We assessed the therapeutic value and the quality of the evidence on medicines that have been authorized by the EMA in the 2000s. Information about drug approval was obtained from the EMA website and the European Public Assessment Reports. MedLine, Embase, and Cochrane databases were systematically searched for published randomized clinical trials and meta-analyses of the selected drugs and their combinations. At the time of approval no medicine had been proved to reduce mortality or slow the progression of the disease or to improve patients' quality of life. Recent meta-analyses concluded that, compared to placebo, active treatments reduced mortality but there was no conclusion on any preferred therapeutic option. Approvals of monotherapies in the absence of best evidence of their efficacy, have prompted the search for better efficacy of their combinations. Three meta-analyses found no advantage in survival from combinations as opposed to monotherapies. This model case confirms previous analyses that marketing authorizations granted in spite of low evidence of therapeutic efficacy not only expose patients to treatments with unknown benefit-risk profiles but also hamper post-marketing research aimed at filling the information gap. Copyright © 2018. Published by Elsevier B.V.

  15. Incentivising innovation in antibiotic drug discovery and development: progress, challenges and next steps.

    Science.gov (United States)

    Simpkin, Victoria L; Renwick, Matthew J; Kelly, Ruth; Mossialos, Elias

    2017-12-01

    Political momentum and funding for combatting antimicrobial resistance (AMR) continues to build. Numerous major international and national initiatives aimed at financially incentivising the research and development (R&D) of antibiotics have been implemented. However, it remains unclear how to effectively strengthen the current set of incentive programmes to further accelerate antibiotic innovation. Based on a literature review and expert input, this study first identifies and assesses the major international, European Union, US and UK antibiotic R&D funding programmes. These programmes are then evaluated across market and public health criteria necessary for comprehensively improving the antibiotic market. The current set of incentive programmes are an important initial step to improving the economic feasibility of antibiotic development. However, there appears to be a lack of global coordination across all initiatives, which risks duplicating efforts, leaving funding gaps in the value chain and overlooking important AMR goals. This study finds that incentive programmes are overly committed to early-stage push funding of basic science and preclinical research, while there is limited late-stage push funding of clinical development. Moreover, there are almost no pull incentives to facilitate transition of antibiotic products from early clinical phases to commercialisation, focus developer concentration on the highest priority antibiotics and attract large pharmaceutical companies to invest in the market. Finally, it seems that antibiotic sustainability and patient access requirements are poorly integrated into the array of incentive mechanisms.

  16. The strategic relevance of manufacturing technology: An overall quality concept to promote innovation preventing drug shortage.

    Science.gov (United States)

    Panzitta, Michele; Ponti, Mauro; Bruno, Giorgio; Cois, Giancarlo; D'Arpino, Alessandro; Minghetti, Paola; Mendicino, Francesca Romana; Perioli, Luana; Ricci, Maurizio

    2017-01-10

    Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Innovating Chinese Herbal Medicine: From Traditional Health Practice to Scientific Drug Discovery

    Directory of Open Access Journals (Sweden)

    Shuo Gu

    2017-06-01

    Full Text Available As one of the major contemporary alternative medicines, traditional Chinese medicine (TCM continues its influence in Chinese communities and has begun to attract the academic attention in the world of western medicine. This paper aims to examine Chinese herbal medicine (CHM, the essential branch of TCM, from both narrative and scientific perspectives. CHM is a traditional health practice originated from Chinese philosophy and religion, holding the belief of holism and balance in the body. With the development of orthodox medicine and science during the last centuries, CHM also seized the opportunity to change from traditional health practice to scientific drug discovery illustrated in the famous story of the herb-derived drug artemisinin. However, hindered by its culture and founding principles, CHM faces the questions of the research paradigm posed by the convention of science. To address these questions, we discussed two essential questions concerning the relationship of CHM and science, and then upheld the paradigm of methodological reductionism in scientific research. Finally, the contemporary narrative of CHM in the 21st century was discussed in the hope to preserve this medical tradition in tandem with scientific research.

  18. Innovating Chinese Herbal Medicine: From Traditional Health Practice to Scientific Drug Discovery.

    Science.gov (United States)

    Gu, Shuo; Pei, Jianfeng

    2017-01-01

    As one of the major contemporary alternative medicines, traditional Chinese medicine (TCM) continues its influence in Chinese communities and has begun to attract the academic attention in the world of western medicine. This paper aims to examine Chinese herbal medicine (CHM), the essential branch of TCM, from both narrative and scientific perspectives. CHM is a traditional health practice originated from Chinese philosophy and religion, holding the belief of holism and balance in the body. With the development of orthodox medicine and science during the last centuries, CHM also seized the opportunity to change from traditional health practice to scientific drug discovery illustrated in the famous story of the herb-derived drug artemisinin. However, hindered by its culture and founding principles, CHM faces the questions of the research paradigm posed by the convention of science. To address these questions, we discussed two essential questions concerning the relationship of CHM and science, and then upheld the paradigm of methodological reductionism in scientific research. Finally, the contemporary narrative of CHM in the 21st century was discussed in the hope to preserve this medical tradition in tandem with scientific research.

  19. An Innovative Cell Microincubator for Drug Discovery Based on 3D Silicon Structures

    Directory of Open Access Journals (Sweden)

    Francesca Aredia

    2016-01-01

    Full Text Available We recently employed three-dimensional (3D silicon microstructures (SMSs consisting in arrays of 3 μm-thick silicon walls separated by 50 μm-deep, 5 μm-wide gaps, as microincubators for monitoring the biomechanical properties of tumor cells. They were here applied to investigate the in vitro behavior of HT1080 human fibrosarcoma cells driven to apoptosis by the chemotherapeutic drug Bleomycin. Our results, obtained by fluorescence microscopy, demonstrated that HT1080 cells exhibited a great ability to colonize the narrow gaps. Remarkably, HT1080 cells grown on 3D-SMS, when treated with the DNA damaging agent Bleomycin under conditions leading to apoptosis, tended to shrink, reducing their volume and mimicking the normal behavior of apoptotic cells, and were prone to leave the gaps. Finally, we performed label-free detection of cells adherent to the vertical silicon wall, inside the gap of 3D-SMS, by exploiting optical low coherence reflectometry using infrared, low power radiation. This kind of approach may become a new tool for increasing automation in the drug discovery area. Our results open new perspectives in view of future applications of the 3D-SMS as the core element of a lab-on-a-chip suitable for screening the effect of new molecules potentially able to kill tumor cells.

  20. Innovative practice: exploring acculturation theory to advance rehabilitation from pediatric to adult "cultures" of care.

    Science.gov (United States)

    Nguyen, Tram; Baptiste, Sue

    2015-01-01

    This perspective paper explores the application of acculturation and the inherent concepts and ideas associated with this theory in rehabilitation to provide a framework for interpreting patient circumstances, responses and behaviours as they move from one culture to the next. Traditionally acculturation theory has been use to examine changes in culture in an ethnic or country sense, however, this paper is among the first to apply acculturation theory to the rehabilitation service cultures from pediatric to adult care for youth with chronic health conditions. The objectives of this paper are threefold: (1) to critically appraise key literature in the development of acculturation theory, (2) to discuss how acculturation theory can be applied in rehabilitation practice through a clinical vignette, and finally (3) to discuss how acculturation theory can advance rehabilitation by enhancing client-centered practice. Acculturation theory can provide insight into how patients are experiencing a change in health care "cultures", in the context of their overarching life circumstances. This, coming from a broader societal perspective can in turn inform an optimal approach to client-centered practice, and the application of rehabilitation-specific team inputs. This theoretical framework can heighten practitioners' awareness of patients' unique worldviews related to their expectations for care and treatment thus reducing fear of diversity to establish positive partnerships between patients and clinicians. An understanding of patients' acculturation processes will add new insight into how we can best deliver services and supports to optimise health, opportunities and experiences for youth with chronic conditions.

  1. The DNP/MPH Dual Degree: An Innovative Graduate Education Program for Advanced Public Health Nursing.

    Science.gov (United States)

    Shaw, Kathy; Harpin, Scott; Steinke, Geraldine; Stember, Marilyn; Krajicek, Marilyn

    2017-03-01

    Strong professional priorities, evolving Affordable Care Act requirements, and a significantly limited public health nursing workforce prompted the University of Colorado College of Nursing to collaborate with the School of Public Health to implement one of the first Doctor of Nursing Practice/Master of Public Health dual degree programs in the nation. Federal grant funding supported the development, implementation, and evaluation of this unique post-baccalaureate dual degree program, for which there were no roadmaps, models, or best practices to follow. Several key issues emerged that serve as lessons learned in creating a new, novel higher education pathway for Advanced Public Health Nursing. This paper highlights two of those: (1) marketing, admission, and matriculation across two programs, and (2) enhancing curricula through distance coursework and interprofessional education. When collaboration with a school of public health is possible, the Doctor of Nursing Practice/Master of Public Health dual degree is an efficient way to prepare public health nurses' with the highest level of public health knowledge, practice, and leadership expertise. © 2016 Wiley Periodicals, Inc.

  2. Advancing the Frontiers in Nanocatalysis, Biointerfaces, and Renewable Energy Conversion by Innovations of Surface Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Somorjai, G.A.; Frei, H.; Park, J.Y.

    2009-07-23

    The challenge of chemistry in the 21st century is to achieve 100% selectivity of the desired product molecule in multipath reactions ('green chemistry') and develop renewable energy based processes. Surface chemistry and catalysis play key roles in this enterprise. Development of in situ surface techniques such as high-pressure scanning tunneling microscopy, sum frequency generation (SFG) vibrational spectroscopy, time-resolved Fourier transform infrared methods, and ambient pressure X-ray photoelectron spectroscopy enabled the rapid advancement of three fields: nanocatalysts, biointerfaces, and renewable energy conversion chemistry. In materials nanoscience, synthetic methods have been developed to produce monodisperse metal and oxide nanoparticles (NPs) in the 0.8-10 nm range with controlled shape, oxidation states, and composition; these NPs can be used as selective catalysts since chemical selectivity appears to be dependent on all of these experimental parameters. New spectroscopic and microscopic techniques have been developed that operate under reaction conditions and reveal the dynamic change of molecular structure of catalysts and adsorbed molecules as the reactions proceed with changes in reaction intermediates, catalyst composition, and oxidation states. SFG vibrational spectroscopy detects amino acids, peptides, and proteins adsorbed at hydrophobic and hydrophilic interfaces and monitors the change of surface structure and interactions with coadsorbed water. Exothermic reactions and photons generate hot electrons in metal NPs that may be utilized in chemical energy conversion. The photosplitting of water and carbon dioxide, an important research direction in renewable energy conversion, is discussed.

  3. Crossdisciplinary fundamental research--the seed for scientific advance and technological innovation.

    Science.gov (United States)

    Kroto, Harold

    2011-12-28

    As it was earlier in the 1980's, so it is now, fundamental science research is under threat as decisions are made on science funding by people who do not do fundamental research, seem congenitally incapable of understanding what it is and furthermore in the face of countless examples seem blind to how important it has been to the technologies that govern our modern life and will be to the future technologies that we desperately need to develop to survive. In this article some general observations are made on how the fascination for what happens in space and stars was the key trigger that gave birth to Science itself and a particular case is outlined which indicates that this same fascination is still the catalyst of some fundamental breakthroughs today. This article also outlines an archetypal example of the way major breakthroughs are often made by the synergy that comes from cross-disciplinary research in a way which is totally surprising. In this case it started from a curiosity about the quantum mechanical description of molecular dynamics and involved pioneering advances in synthetic organic chemistry which led to the suprising discovery that some exotic carbon molecules were abundant in space and stars. These results initiated an experiment using a new technology that represented a major breakthrough in cluster science. The upshot was totally unpredictable, the birth of a whole new field of Chemistry as well as a paradigm shift in major areas of Nanoscience and Nanotechnology.

  4. Next generation human skin constructs as advanced tools for drug development.

    Science.gov (United States)

    Abaci, H E; Guo, Zongyou; Doucet, Yanne; Jacków, Joanna; Christiano, Angela

    2017-11-01

    Many diseases, as well as side effects of drugs, manifest themselves through skin symptoms. Skin is a complex tissue that hosts various specialized cell types and performs many roles including physical barrier, immune and sensory functions. Therefore, modeling skin in vitro presents technical challenges for tissue engineering. Since the first attempts at engineering human epidermis in 1970s, there has been a growing interest in generating full-thickness skin constructs mimicking physiological functions by incorporating various skin components, such as vasculature and melanocytes for pigmentation. Development of biomimetic in vitro human skin models with these physiological functions provides a new tool for drug discovery, disease modeling, regenerative medicine and basic research for skin biology. This goal, however, has long been delayed by the limited availability of different cell types, the challenges in establishing co-culture conditions, and the ability to recapitulate the 3D anatomy of the skin. Recent breakthroughs in induced pluripotent stem cell (iPSC) technology and microfabrication techniques such as 3D-printing have allowed for building more reliable and complex in vitro skin models for pharmaceutical screening. In this review, we focus on the current developments and prevailing challenges in generating skin constructs with vasculature, skin appendages such as hair follicles, pigmentation, immune response, innervation, and hypodermis. Furthermore, we discuss the promising advances that iPSC technology offers in order to generate in vitro models of genetic skin diseases, such as epidermolysis bullosa and psoriasis. We also discuss how future integration of the next generation human skin constructs onto microfluidic platforms along with other tissues could revolutionize the early stages of drug development by creating reliable evaluation of patient-specific effects of pharmaceutical agents. Impact statement Skin is a complex tissue that hosts various

  5. U.S. Food and Drug Administration drug approval: slow advances in obstetric care in the United States.

    Science.gov (United States)

    Wing, Deborah A; Powers, Barbara; Hickok, Durlin

    2010-04-01

    The process for drug approval in the United States is complex and time-consuming. There are comparatively few drugs with U.S. Food and Drug Administration (FDA)-approved indications for obstetric use in this country at this time; however, several are under development. We review the process for drug approval and recount the approval histories of obstetric drugs reviewed in the recent past. We also outline the current status of two progestational agents that are under development. For a variety of reasons, including a small market compared with others such as cardiology or oncology, and the potential of being drawn into medical-legal litigation, sponsors are disinclined to pursue drug development for obstetric purposes in this country. We compare the procedures for review and approval of drugs in the United States with those in Europe, and note that recent changes within the FDA may result in not only more drugs being approved but also changes in labeling of already approved drugs. Special programs to facilitate drug development and reforms to modernize the process and improve safety are discussed. These may result in changes in labeling of already approved drugs. Obstacles such as funding and liability are also discussed.

  6. Strategies to Advance Drug Discovery in Rare Monogenic Intellectual Disability Syndromes

    Science.gov (United States)

    Hettige, Nuwan C; Manzano-Vargas, Karla; Jefri, Malvin; Ernst, Carl

    2018-01-01

    Abstract Some intellectual disability syndromes are caused by a mutation in a single gene and have been the focus of therapeutic intervention attempts, such as Fragile X and Rett Syndrome, albeit with limited success. The rate at which new drugs are discovered and tested in humans for intellectual disability is progressing at a relatively slow pace. This is particularly true for rare diseases where so few patients make high-quality clinical trials challenging. We discuss how new advances in human stem cell reprogramming and gene editing can facilitate preclinical study design and we propose new workflows for how the preclinical to clinical trajectory might proceed given the small number of subjects available in rare monogenic intellectual disability syndromes. PMID:29040584

  7. Real-time potentiometric sensor; an innovative tool for monitoring hydrolysis of chemo/bio-degradable drugs in pharmaceutical sciences.

    Science.gov (United States)

    Ma'mun, Ahmed; Abd El-Rahman, Mohamed K; Abd El-Kawy, Mohamed

    2018-05-30

    In recent years, the whole field of ion-selective electrodes(ISEs) in pharmaceutical sciences has expanded far beyond its original roots. The diverse range of opportunities offered by ISEs was broadly used in a number of pharmaceutical applications, with topics presented ranging from bioanalysis of drugs and metabolites, to protein binding studies, green analytical chemistry, impurity profiling, and drug dissolution in biorelevant media. Inspired from these advances and with the aim of extending the functional capabilities of ISEs, the primary focus of the present paper is the utilization of ISE as a tool in personalized medicine. Given the opportunity to explore biological events in real-time (such as drug metabolism) could be central to personalized medicine. (ATR) is a chemo-degradable and bio-degradable pharmaceutically active drug. Laudanosine (LDS) is the major degradation product and metabolite of ATR and is potentially toxic and reported to possess epileptogenic activity which increases the risk of convulsive effects. In this work, ATR have been subjected to both chemical and biological hydrolysis, and the course of the reactions is monitored by means of a ISE. In this study, we have designed an efficient real-time tracking strategy which substantially resolve the challenges of the ATR chemical and biological degradation kinetics. By utilizing a potentiometric sensor, tracking of ATR chemical and biological degradation kinetics can be performed in a very short time with excellent accuracy. The LOD was calculated to be 0.23 μmol L -1 , the potential drift was investigated over a period of 60 min and the value was 0.25 mV h -1 . Real serum samples for measurement the rate of in vitro metabolism of ATR was performed. Furthermore, a full description of the fabricated screen-printed sensor was presented. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Drive Cost Reduction, Increase Innovation and Mitigate Risk with Advanced Knowledge Discovery Tools Designed to Unlock and Leverage Prior Knowledge

    International Nuclear Information System (INIS)

    Mitchell, I.

    2016-01-01

    Full text: The nuclear industry is knowledge-intensive and includes a diverse number of stakeholders. Much of this knowledge is at risk as engineers, technicians and project professionals retire, leaving a widening skills and information gap. This knowledge is critical in an increasingly complex environment with information from past projects often buried in decades-old, non-integrated systems enterprise. Engineers can spend 40% or more of their time searching for answers across the enterprise instead of solving problems. The inability to access trusted industry knowledge results in increased risk and expense. Advanced knowledge discovery technologies slash research times by as much as 75% and accelerate innovation and problem solving by giving technical professionals access to the information they need, in the context of the problems they are trying to solve. Unlike traditional knowledge management approaches, knowledge discovery tools powered by semantic search technologies are adept at uncovering answers in unstructured data and require no tagging, organization or moving of data, meaning a smaller IT footprint and faster time-to-knowledge. This session will highlight best-in-class knowledge discovery technologies, content, and strategies to give nuclear industry organizations the ability to leverage the corpus of enterprise knowledge into the future. (author

  9. Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

    Science.gov (United States)

    Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

    2016-01-01

    Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

  10. An update on dry eye disease molecular treatment: advances in drug pipelines.

    Science.gov (United States)

    Colligris, Basilio; Crooke, Almudena; Huete-Toral, Fernando; Pintor, Jesus

    2014-07-01

    Dry eye disease is a common disorder provoking changes in tear film and ocular surface. Untreated dry eye could cause ocular infections, corneal ulcer and blindness. Only a few drugs are authorized so far for the treatment of dry eye disease and the possibilities of evolution in this sector are immense. Consequently, a significant number of new potential solutions are under development or placed in the pharmaceutical pipeline, promising better results and lesser side effects. In this article, the corresponding literature and recent Phase III clinical trial data and the corresponding literature, for dry eye disease treatment are reviewed, revealing the new strategic movements in drug pipelines. From the clinical trial results, the advancement in tear substitutes and secretagogues in addressing specific deficiencies of tear components even though not resolving the underlying conditions of the disease is evident. The vast majority of new compounds under development are anti-inflammatories, steroids, non-steroids and antibiotics; however, there are also some novel lubricating drops and mucin-tear secretagogues. A future aggressive therapy for dry eye, depending on the severity of the symptoms, would include combinations of soft steroids, anti-inflammatories, such as cyclosporine A, with the addition of the new polyvalent mucin and tear secretagogues.

  11. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    Science.gov (United States)

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  12. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.

    Science.gov (United States)

    Sicherer, Scott H; Leung, Donald Y M

    2006-07-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported primarily in the Journal in 2005. Although studies documented deficiencies in community management of anaphylaxis, guidelines and National Institutes of Health summary reports provide direction toward improved research and education. At least 9% of young children "outgrow" a tree nut allergy. Advances in food allergy diagnosis include reports of probability of reactions to peanut at various peanut-specific IgE concentrations and skin test response size and the utility of evaluating IgE binding to specific epitopes. Future food allergy treatments might include selection of "less allergenic" fruit cultivars, genetic silencing of major allergens, and treatment of allergic patients with Chinese herbal remedies. Osteopontin might be a useful biomarker for success of venom immunotherapy. Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.

  13. MRI after magnetic drug targeting in patients with advanced solid malignant tumors

    International Nuclear Information System (INIS)

    Lemke, A.-J.; Senfft von Pilsach, M.-I.; Felix, R.; Luebbe, A.; Bergemann, C.; Riess, H.

    2004-01-01

    The purpose of this study was to evaluate the ability of MRI to detect magnetic particle uptake into advanced solid malignant tumors and to document the extension of these tumors, carried out in the context of magnetic drug targeting. In a prospective phase I trial, 11 patients were examined with MRI before and after magnetic drug targeting. The sequence protocol included T1-WI and T2-WI in several planes, followed by quantitative and qualitative evaluation of the signal intensities and tumor extensions. In nine patients, a signal decrease was observed in the early follow-up (2-7 days after therapy) on the T2-weighted images; two patients did not show a signal change. The signal changes in T1-WI were less distinct. In late follow-up (4-6 weeks after therapy), signal within nine tumors reached their initially normal level on both T1-WI and T2-WI; two tumors showed a slight signal decrease on T2-WI and a slight signal increase on T1-WI. Within the surveillance period, tumor remission in 3 out of 11 patients was observed, and in 5 patients tumor growth had stopped. The remaining three patients showed significant tumor growth. There was no statistically significant correlation between signal change and response. MRI is a suitable method to detect magnetite particles, deposited at the tumor site via magnetic drug targeting. MRI is therefore eligible to control the success of MDT and to assess the tumor size after the end of therapy. (orig.)

  14. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

    Science.gov (United States)

    Sicherer, Scott H; Leung, Donald Y M

    2010-01-01

    This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Advance of study on the influence of different drugs on the efficacy of 131I treatment for Graves' disease

    International Nuclear Information System (INIS)

    Wang Peng; Tan Jian

    2011-01-01

    Graves' disease is the most common cause of hyperthyroidism. 131 I treatment is one main treatment method for Graves' disease, and being used on an increasing scale in China recently. During the peritherapeutic period, however, the application of other drugs may affect the efficacy of 131 I treatment. In this review, the advances of study were summarized on the influence of different drugs on the efficacy of 131 I treatment in recent years. (authors)

  16. Impact of the Pharma Economic Act on Diffusion of Innovation and Reduction of Costs in the Hungarian Prescription Drug Market (2007-2010).

    Science.gov (United States)

    Hren, Rok

    In this study, we examined the impact of the Pharma Economic Act, which was introduced in Hungary in 2007. We used detailed data on the Hungarian prescription drug market, which had been made publicly available by the authorities. We evaluated the effect of the Pharma Economic Act on both dynamic and static efficiencies and also on equity, which has been historically a controversial issue in Hungary. We analyzed the overall prescription drug market and statin and atorvastatin markets; as a proxy for determining dynamic efficiency, we examined the oncology drug market for some specific products (e.g., bortezomib) and the long-acting atypical antipsychotic drugs market. There is no denying that the authorities managed to control the overall prescription drug costs; however, they were still paying excessive rents for off-patent drugs. Examples of oncology and long-acting atypical antipsychotic drugs showed that the diffusion of innovation was on per-capita basis at least comparable to G-5 countries. While the share of out-of-pocket co-payments markedly increased and the reimbursement was lowered, the concurrent price decreases often meant that the co-payment per milligram of a given dispensed drug was actually lower than that before the Act, thereby benefiting the patient. It appears that strong mechanisms to control volume rather than price on the supply side (marketing authorization holders) contained the drug expenditure, while offering enough room to strive for innovation. Making data on prescription drug expenditures and associated co-payments publicly available is an item that should be definitely followed by the surrounding jurisdictions. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

  17. DESI-MS2: a rapid and innovative method for trace analysis of six cytostatic drugs in health care setting.

    Science.gov (United States)

    Fabrizi, Giovanni; Fioretti, Marzia; Rocca, Lucia Mainero; Curini, Roberta

    2012-05-01

    With the aim of establishing exposure levels for hospital personnel preparing and administering cytostatic drugs (CDs), here, we present an innovative screening method based on the use of the desorption electrospray ionization (DESI) interface coupled with a hybrid quadrupole linear ion trap mass spectrometer. A rapid, simple, and sensitive procedure was developed for the simultaneous surface monitoring of cyclophosphamide, dacarbazine, methotrexate, vincristine, gemcitabine, and cytarabine. Since analytes were in the solid state, a novel approach based on the use of passive samplers was combined with the direct analysis of wipes. A PTFE-printed glass slide was used as a passive sampler, while hydrophobic centers of Swiffer® cloths were judged extremely efficient as wipe samplers. After the sampling period, the CD collectors were directly processed with the DESI-MS system without any further treatment. MS/MS confirmatory analysis was conducted using selected reaction monitoring in the positive ion mode and detection limits were evaluated. Values were at the picograms per square millimeter levels on the passive collector and at the picograms per square centimeter levels for the wipe ones. Direct determination on solid-state samples combined with mass spectrometry selectivity provided a powerful tool so far unapplied to occupational hygiene.

  18. Antibiotic effectiveness: balancing conservation against innovation.

    Science.gov (United States)

    Laxminarayan, Ramanan

    2014-09-12

    Antibiotic effectiveness is a natural societal resource that is diminished by antibiotic use. As with other such assets, keeping it available requires both conservation and innovation. Conservation encompasses making the best use of current antibiotic effectiveness by reducing demand through vaccination, infection control, diagnostics, public education, incentives for clinicians to prescribe fewer antibiotics, and restrictions on access to newer, last-resort antibiotics. Innovation includes improving the efficacy of current drugs and replenishing effectiveness by developing new drugs. In this paper, I assess the relative benefits and costs of these two approaches to maintaining our ability to treat infections. Copyright © 2014, American Association for the Advancement of Science.

  19. The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer.

    Science.gov (United States)

    Soekmadji, Carolina; Nelson, Colleen C

    2015-01-01

    Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

  20. Innovation: Advanced Search

    African Journals Online (AJOL)

    Search tips: Search terms are case-insensitive; Common words are ignored; By default only articles containing all terms in the query are returned (i.e., AND is implied); Combine multiple words with OR to find articles containing either term; e.g., education OR research; Use parentheses to create more complex queries; e.g., ...

  1. Effects of the Advanced Innovative Internet-Based Communication Education Program on Promoting Communication Between Nurses and Patients With Dementia.

    Science.gov (United States)

    Chao, Hui-Chen; Kaas, Merrie; Su, Ying-Hwa; Lin, Mei-Feng; Huang, Mei-Chih; Wang, Jing-Jy

    2016-06-01

    Effective communication between nurses and patients with dementia promotes the quality of patient care by improving the identification of patient needs and by reducing the miscommunication-related frustration of patients and nurses. This study evaluates the effects of an advanced innovative Internet-based communication education (AIICE) program on nurses' communication knowledge, attitudes, frequency of assessing patient communication capacity, and communication performance in the context of care for patients with dementia. In addition, this study attempts to evaluate the indirect effects of this program on outcomes for patients with dementia, including memory and behavior-related problems and depressive symptoms. A quasi-experimental research design with a one-group repeated measure was conducted. Convenience sampling was used to recruit nurses from long-term care facilities in southern Taiwan. Data were analyzed using general estimating equations to compare changes over time across three points: baseline, fourth-week posttest, and 16th-week posttest. One hundred five nurses completed the AIICE program and the posttest surveys. The findings indicate that nurses' communication knowledge, frequency in assessing patients' communication capacity, and communication performance had improved significantly over the baseline by either the 4th- or 16th-week posttest (p < .01). However, communication attitude showed no significant improvement in the posttest survey (p = .40). Furthermore, the findings indicate that the memory and behavior-related problems and the depressive symptoms of patients had decreased significantly by the 16th-week posttest (p = .05). This study showed that the AIICE program improves nurses' communication knowledge, frequency to assess patients' communication capacity, and communication performance and alleviates the memory and behavior-related problems and depressive symptoms of patients. The continuous communication training of nurses using the

  2. Advancing Clouds Lifecycle Representation in Numerical Models Using Innovative Analysis Methods that Bridge ARM Observations and Models Over a Breadth of Scales

    Energy Technology Data Exchange (ETDEWEB)

    Kollias, Pavlos [McGill Univ., Montreal, QC (Canada

    2016-09-06

    This the final report for the DE-SC0007096 - Advancing Clouds Lifecycle Representation in Numerical Models Using Innovative Analysis Methods that Bridge ARM Observations and Models Over a Breadth of Scales - PI: Pavlos Kollias. The final report outline the main findings of the research conducted using the aforementioned award in the area of cloud research from the cloud scale (10-100 m) to the mesoscale (20-50 km).

  3. Approach to the open advanced facilities initiative for innovation (strategic use by industry) at the University of Tsukuba, Tandem Accelerator Complex

    International Nuclear Information System (INIS)

    Sasa, K.; Tagishi, Y.; Naramoto, H.; Kudo, H.; Kita, E.

    2010-01-01

    The University of Tsukuba, Tandem Accelerator Complex (UTTAC) possesses the 12UD Pelletron tandem accelerator and the 1 MV Tandetron accelerator for University's inter-department education research. We have actively advanced collaborative researches with other research institutes and industrial users. Since the Open Advanced Facilities Initiative for Innovation by the Ministry of Education, Culture, Sports, Science and Technology started in 2007, 12 industrial experiments have been carried out at the UTTAC. This report describes efforts by University's accelerator facility to get industrial users. (author)

  4. Design of multifunctional nanoparticles for combined in-vivo imaging and advanced drug delivery

    Science.gov (United States)

    Leary, James F.

    2018-02-01

    Design of multifunctional nanoparticles for multimodal in-vivo imaging and advanced targeting to diseased single cells for massive parallel processing nanomedicine approaches requires careful overall design and a multilayered approach. Initial core materials can include non-toxic metals which not only serve as an x-ray contrast agent for CAT scan imaging, but can contain T1 or T2 contrast agents for MRI imaging. One choice is superparamagnetic iron oxide NPs which also allow for convenient magnetic manipulation during manufacturing but also for re-positioning inside the body and for single cell hyperthermia therapies. To permit real-time fluorescence-guided surgery, fluorescence molecules can be included. Advanced targeting can be achieved by attaching antibodies, peptides, aptamers, or other targeting molecules to the nanoparticle in a multilayered approach producing "programmable nanoparticles" whereby the "programming" means controlling a sequence of multi-step targeting methods. Addition of membrane permeating peptides can facilitate uptake by the cell. Addition of "stealth" molecules (e.g. PEG or chitosan) to the outer surfaces of the nanoparticles can permit greatly enhanced circulation times in-vivo which in turn lead to lower amounts of drug exposure to the patient which can reduce undesirable side effects. Nanoparticles with incomplete layers can be removed by affinity purification methods to minimize mistargeting events in-vivo. Nanoscale imaging of these manufactured, multifunctional nanoparticles can be achieved either directly through superresolution microscopy or indirectly through single nanoparticle zeta-sizing or x-ray correlation microscopy. Since these multifunctional nanoparticles are best analyzed by technologies permitting analysis in aqueous environments, superresolution microscopy is, in most cases, the preferred method.

  5. Gene therapy for spinomuscular atrophy: a biomedical advance, a missed opportunity for more equitable drug pricing.

    Science.gov (United States)

    Friedmann, T

    2017-09-01

    An experimental approach for gene therapy of spinomuscular atrophy has been reported to prevent development of the neuromuscular features of this lethal and previously untreatable disorder. The approach involves treatment of patients suffering from SMN1-associated infantile form of the disease with a splice-switching antisense oligonucleotide (ASO) that corrects aberrant splicing of the nearly identical SMN2 gene to allow the generation of functional SMN protein, thereby mitigating the development of the disease. This technique represents the first apparently effective therapy for spinal muscular atrophy (SMA) and an important documentation for ASO technology for therapy of neurodegenerative disease. These results with one form of SMA are likely to be relevant for similar applications to other SMA types and are likely to inspire application to a number of other intractable neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis and possibly even the extremely common Parkinson's and Alzheimer's diseases and others. Nevertheless, the scientific and medical importance of this advance is marred by a pricing policy by the corporate sponsors that may complicate accessibility of the drug for some desperate patients.

  6. An Advanced Multifunctional Hydrogel-Based Dressing for Wound Monitoring and Drug Delivery.

    Science.gov (United States)

    Mirani, Bahram; Pagan, Erik; Currie, Barbara; Siddiqui, Mohammad Ali; Hosseinzadeh, Reihaneh; Mostafalu, Pooria; Zhang, Yu Shrike; Ghahary, Aziz; Akbari, Mohsen

    2017-10-01

    Wound management is a major global challenge and poses a significant financial burden to the healthcare system due to the rapid growth of chronic diseases such as diabetes, obesity, and aging population. The ability to detect pathogenic infections and release drug at the wound site is of the utmost importance to expedient patient care. Herein, this study presents an advanced multifunctional dressing (GelDerm) capable of colorimetric measurement of pH, an indicator of bacterial infection, and release of antibiotic agents at the wound site. This study demonstrates the ability of GelDerm to detect bacterial infections using in vitro and ex vivo tests with accuracies comparable to the commercially available systems. Wireless interfaces to digital image capture hardware such as smartphones serve as a means for quantitation and enable the patient to record the wound condition at home and relay the information to the healthcare personnel for following treatment strategies. Additionally, the dressing is integrated within commercially available patches and can be placed on the wound without chemical or physical irritation. This study demonstrates the ability of GelDerm to eradicate bacteria by the sustained release of antibiotics. The proposed technology holds great promise in managing chronic and acute injuries caused by trauma, surgery, or diabetes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer.

    Science.gov (United States)

    Clermont, Pier-Luc; Crea, Francesco; Chiang, Yan Ting; Lin, Dong; Zhang, Amy; Wang, James Z L; Parolia, Abhijit; Wu, Rebecca; Xue, Hui; Wang, Yuwei; Ding, Jiarui; Thu, Kelsie L; Lam, Wan L; Shah, Sohrab P; Collins, Colin C; Wang, Yuzhuo; Helgason, Cheryl D

    2016-01-01

    While localized prostate cancer (PCa) can be effectively cured, metastatic disease inevitably progresses to a lethal state called castration-resistant prostate cancer (CRPC). Emerging evidence suggests that aberrant epigenetic repression by the polycomb group (PcG) complexes fuels PCa progression, providing novel therapeutic opportunities. In the search for potential epigenetic drivers of CRPC, we analyzed the molecular profile of PcG members in patient-derived xenografts and clinical samples. Overall, our results identify the PcG protein and methyl-lysine reader CBX2 as a potential therapeutic target in advanced PCa. We report that CBX2 was recurrently up-regulated in metastatic CRPC and that elevated CBX2 expression was correlated with poor clinical outcome in PCa cohorts. Furthermore, CBX2 depletion abrogated cell viability and induced caspase 3-mediated apoptosis in metastatic PCa cell lines. Mechanistically explaining this phenotype, microarray analysis in CBX2-depleted cells revealed that CBX2 controls the expression of many key regulators of cell proliferation and metastasis. Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug target in lethal CRPC.

  8. The potential of protein-nanomaterial interaction for advanced drug delivery.

    Science.gov (United States)

    Peng, Qiang; Mu, Huiling

    2016-03-10

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself, would be the real substance the organs and cells firstly encounter. Consequently, the behavior of nanomaterials in vivo is uncontrollable and some undesired effects may occur, like rapid clearance from blood stream; risk of capillary blockage; loss of targeting capacity; and potential toxicity. Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized by selected protein corona using endogenous proteins would have greater promise for clinical use. In this review, we aim to provide a comprehensive understanding of protein-nanomaterial interaction. Importantly, a discussion about how to use such interaction is launched and some possible applications of such interaction for advanced drug delivery are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Regional Innovation Clusters

    Data.gov (United States)

    Small Business Administration — The Regional Innovation Clusters serve a diverse group of sectors and geographies. Three of the initial pilot clusters, termed Advanced Defense Technology clusters,...

  10. Technological Innovations from NASA

    Science.gov (United States)

    Pellis, Neal R.

    2006-01-01

    The challenge of human space exploration places demands on technology that push concepts and development to the leading edge. In biotechnology and biomedical equipment development, NASA science has been the seed for numerous innovations, many of which are in the commercial arena. The biotechnology effort has led to rational drug design, analytical equipment, and cell culture and tissue engineering strategies. Biomedical research and development has resulted in medical devices that enable diagnosis and treatment advances. NASA Biomedical developments are exemplified in the new laser light scattering analysis for cataracts, the axial flow left ventricular-assist device, non contact electrocardiography, and the guidance system for LASIK surgery. Many more developments are in progress. NASA will continue to advance technologies, incorporating new approaches from basic and applied research, nanotechnology, computational modeling, and database analyses.

  11. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Anupama Shrivastav

    2013-01-01

    Full Text Available Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system.

  12. Issues In-Depth: Advancing Understanding of Drug Addiction and Treatment

    Science.gov (United States)

    Miller, Roxanne Greitz

    2009-01-01

    While most school districts utilize a drug abuse resistance curriculum, as science teachers, it is our responsibility to understand the science behind drug addiction in order to most effectively educate our students against drug abuse. In the last two decades, increases in scientific technology have permitted significant discoveries surrounding…

  13. The Innovative Medicines Initiative's New Drugs for Bad Bugs programme: European public-private partnerships for the development of new strategies to tackle antibiotic resistance.

    Science.gov (United States)

    Kostyanev, T; Bonten, M J M; O'Brien, S; Steel, H; Ross, S; François, B; Tacconelli, E; Winterhalter, M; Stavenger, R A; Karlén, A; Harbarth, S; Hackett, J; Jafri, H S; Vuong, C; MacGowan, A; Witschi, A; Angyalosi, G; Elborn, J S; deWinter, R; Goossens, H

    2016-02-01

    Antibiotic resistance (ABR) is a global public health threat. Despite the emergence of highly resistant organisms and the huge medical need for new drugs, the development of antibacterials has slowed to an unacceptable level worldwide. Numerous government and non-government agencies have called for public-private partnerships and innovative funding mechanisms to address this problem. To respond to this public health crisis, the Innovative Medicines Initiative Joint Undertaking programme has invested more than €660 million, with a goal of matched contributions from the European Commission and the European Federation of Pharmaceutical Industries and Associations, in the development of new antibacterial strategies. The New Drugs for Bad Bugs (ND4BB) programme, an Innovative Medicines Initiative, has the ultimate goal to boost the fight against ABR at every level from basic science and drug discovery, through clinical development to new business models and responsible use of antibiotics. Seven projects have been launched within the ND4BB programme to achieve this goal. Four of them will include clinical trials of new anti-infective compounds, as well as epidemiological studies on an unprecedented scale, which will increase our knowledge of ABR and specific pathogens, and improve the designs of the clinical trials with new investigational drugs. The need for rapid concerted action has driven the funding of seven topics, each of which should add significantly to progress in the fight against ABR. ND4BB unites expertise and provides a platform where the commitment and resources required by all parties are streamlined into a joint public-private partnership initiative of unprecedented scale. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. 77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

    Science.gov (United States)

    2012-11-23

    ...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...

  15. [Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

    Science.gov (United States)

    Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

    2016-05-01

    The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

  16. Energy systems. Tome 3: advanced cycles, low environmental impact innovative systems; Systeme energetiques, TOME 3: cycles avances, systemes innovants a faible impact environnemental

    Energy Technology Data Exchange (ETDEWEB)

    Gicquel, R

    2009-07-01

    This third tome about energy systems completes the two previous ones by showing up advanced thermodynamical cycles, in particular having a low environmental impact, and by dealing with two other questions linked with the study of systems with a changing regime operation: - the time management of energy, with the use of thermal and pneumatic storage systems and time simulation (schedule for instance) of systems (solar energy type in particular); - the technological dimensioning and non-nominal regime operation studies. Because this last topic is particularly complex, new functionalities have been implemented mainly by using the external classes mechanism, which allows the user to freely personalize his models. This tome is illustrated with about 50 examples of cycles modelled with Thermoptim software. Content: foreword; 1 - generic external classes; 2 - advanced gas turbine cycles; 3 - evaporation-concentration, mechanical steam compression, desalination, hot gas drying; 4 - cryogenic cycles; 5 - electrochemical converters; 6 - global warming, CO{sub 2} capture and sequestration; 7 - future nuclear reactors (coupled to Hirn and Brayton cycles); 8 - thermodynamic solar cycles; 10 - pneumatic and thermal storage; 11 - calculation of thermodynamic solar facilities; 12 - problem of technological dimensioning and non-nominal regime; 13 - exchangers modeling and parameterizing for the dimensioning and the non-nominal regime; 14 - modeling and parameterizing of volumetric compressors; 15 - modeling and parameterizing of turbo-compressors and turbines; 16 - identification methodology of component parameters; 17 - case studies. (J.S.)

  17. Advances in research of targeting delivery and controlled release of drug-loaded nanoparticles

    International Nuclear Information System (INIS)

    Tan Zhonghua

    2003-01-01

    Biochemistry drug, at present, is still the main tool that human struggle to defeat the diseases. So, developing safe and efficacious technique of drug targeting delivery and controlled release is key to enhance curative effect, decrease drug dosage, and lessen its side effect. Drug-loaded nanoparticles, which is formed by conjugate between nanotechnology and modern pharmaceutics, is a new fashioned pharmic delivery carrier. Because of advantages in pharmic targeting transport and controlled or slow release and improving bioavailability, it has been one of developing trend of modern pharmaceutical dosage forms

  18. Novel approach for a PTX/VEGF dual drug delivery system in cardiovascular applications-an innovative bulk and surface drug immobilization.

    Science.gov (United States)

    Wulf, Katharina; Teske, Michael; Matschegewski, Claudia; Arbeiter, Daniela; Bajer, Dalibor; Eickner, Thomas; Schmitz, Klaus-Peter; Grabow, Niels

    2018-06-01

    The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated. The advantage of this DDDS is that the bulk incorporation of fluorescein diacetate (FDAc) (model drug for paclitaxel (PTX)) via spray coating enhanced the subsequent cleavable surface coupling of vascular endothelial growth factor (VEGF) via the crosslinker bissulfosuccinimidyl suberate (BS 3 ). In the presence of the embedded FDAc, the VEGF loading and release are about twice times higher than in absence. Furthermore, the DDDS combines the diffusion drug delivery (FDAc or PTX) and the chemical controlled drug release, VEGF via hydrolysable ester bonds, without loss in quantity and quality of the drug release curves. Additionally, the performed in vitro biocompatibility study showed the bimodal influences of PTX and VEGF on human endothelial EA.hy926 cells. In conclusion, it was possible to show the feasibility to develop a novel DDDS which has a high potential for the medical application due to the possible easy and short modification of a polymer-based PTX delivery system.

  19. Social Capital and Entrepreneurial Behaviour Advancing Innovativeness in Interaction between Small Rural Entrepreneurs and Researchers: A Phenomenographic Study

    Science.gov (United States)

    Iivonen, Sari; Kyro, Paula; Mynttinen, Sinikka; Sarkka-Tirkkonen, Marjo; Kahiluoto, Helena

    2011-01-01

    Innovation processes between entrepreneurs and researchers are activated by interaction. Social capital increases the efficiency of action, for example, information dissemination by minimising redundancy. To learn more about how to build and develop social capital assumes that we understand how entrepreneurs behave and what their expectations of…

  20. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  1. Innovating innovation Policy. Rethinking green innovation policy in evolutionary perspective

    NARCIS (Netherlands)

    Arentsen, Maarten J.; Dinica, V.; Marquart, N.E.

    1999-01-01

    Advanced environmental standards such as sustainability require substantial improvements in the environmental performances of present technologies. Governments are faced with the challenge to design green innovation policies able to support producers and users of technologies to comply with such

  2. How to create innovation by building the translation bridge from basic research into medicinal drugs: an industrial perspective.

    Science.gov (United States)

    Germann, Paul G; Schuhmacher, Alexander; Harrison, Juan; Law, Ronald; Haug, Kevin; Wong, Gordon

    2013-03-05

    The global healthcare industry is undergoing substantial changes and adaptations to the constant decline of approved new medical entities. This decrease in internal research productivity is resulting in a major decline of patent-protected sales (patent cliff) of most of the pharmaceutical companies. Three major global adaptive trends as driving forces to cope with these challenges are evident: cut backs of internal research and development jobs in the western hemisphere (Europe and USA), following the market growth potential of Asia by building up internal or external research and development capabilities there and finally, 'early innovation hunting' with an increased focus on identifying and investing in very early innovation sources within academia and small start-up companies. Early innovation hunting can be done by different approaches: increased corporate funding, establishment of translational institutions to bridge innovation, increasing sponsored collaborations and formation of technology hunting groups for capturing very early scientific ideas and concepts. This emerging trend towards early innovation hunting demands special adaptations from both the pharmaceutical industry and basic researchers in academia to bridge the translation into new medicines which deliver innovative medicines that matters to the patient. This opinion article describes the different modalities of cross-fertilisation between basic university or publicly funded institutional research and the applied research and development activities within the pharmaceutical industry. Two key factors in this important translational bridge can be identified: preparation of both partnering organisations to open up for new and sometime disruptive ideas and creation of truly trust-based relationships between the different groups allowing long-term scientific collaborations while acknowledging that value-creating differences are an essential factor for successful collaboration building.

  3. Innovation at DARPA

    Science.gov (United States)

    2016-07-01

    Distribution Statement A: Approved for Public Release, Distribution Unlimited Innovation at DARPA July 2016 1 Distribution...Statement A: Approved for Public Release, Distribution Unlimited Innovation at DARPA A Long History of Innovation DARPA, the Defense Advanced Research...guided work that has “changed the world"—a phrase frequently heard at DARPA to ensure a focus on transformative innovation as opposed to incremental

  4. Application of the Price-Volume Approach in Cases of Innovative Drugs Where Value-Based Pricing is Inadequate: Description of Real Experiences in Italy.

    Science.gov (United States)

    Messori, Andrea

    2016-08-01

    Several cases of expensive drugs designed for large patient populations (e.g. sofosbuvir) have raised a complex question in terms of drug pricing. Even assuming value-based pricing, the treatment with these drugs of all eligible patients would have an immense budgetary impact, which is unsustainable also for the richest countries. This raises the need to reduce the prices of these agents in comparison with those suggested by the value-based approach and to devise new pricing methods that can achieve this goal. The present study discusses in detail the following two methods: (i) The approach based on setting nation-wide budget thresholds for individual innovative agents in which a fixed proportion of the historical pharmaceutical expenditure represents the maximum budget attributable to an innovative treatment; (ii) The approach based on nation-wide price-volume agreements in which drug prices are progressively reduced as more patients receive the treatment. The first approach has been developed in the USA by the Institute for Clinical and Economic Review and has been applied to PCSK9 inhibitors (alirocumab and evolocumab). The second approach has been designed for the Italian market and has found a systematic application to manage the price of ranibizumab, sofosbuvir, and PCSK9 inhibitors. While, in the past, price-volume agreements have been applied only on an empirical basis (i.e. in the absence of any quantitative theoretical rule), more recently some explicit mathematical models have been described. The performance of these models is now being evaluated on the basis of the real-world experiences conducted in some European countries, especially Italy.

  5. Webinar as the innovative marketing tool: its place and a role in system of advancement of educational services

    Directory of Open Access Journals (Sweden)

    Matuhina Tatiana Vasilevna

    2011-04-01

    Full Text Available Marketing of webinar represents research which is carried out by seminar carrying out in a network the Internet, by means of virtual conference. Webinar as the innovative marketing tool allows the buyer to investigate a product or service, and to the supplier to investigate requirements and interests of the consumers by means of decrease in expenses for marketing since the technology of webinar-marketing is much more economic traditional than means of marketing, advertising, polls, seminars and conferences.

  6. Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers

    NARCIS (Netherlands)

    Chen, Wei; Meng, Fenghua; Cheng, R.; Deng, C.; Feijen, Jan; Zhong, Zhiyuan

    2014-01-01

    Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention

  7. Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Piyush Mehta

    2016-01-01

    Full Text Available Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases.

  8. Assessment of an Innovative Voluntary Substance Abuse Treatment Program Designed to Replace Compulsory Drug Detention Centers in Malaysia.

    Science.gov (United States)

    Khan, Farrah; Krishnan, Archana; Ghani, Mansur A; Wickersham, Jeffrey A; Fu, Jeannia J; Lim, Sin How; Dhaliwal, Sangeeth Kaur; Kamarulzaman, Adeeba; Altice, Frederick L

    2018-01-28

    As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services.   We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan. In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C. Drug use was compared for the 30-day-period before C&C entry and the 30-day-period before the interview. Self-reported drug use levels decreased significantly among both inpatient and outpatient clients after enrolling in C&C treatment. Higher levels of past drug use, lower levels of social support, and more severe mental health issues were reported by participants who were previously imprisoned. Self-reported satisfaction with C&C treatment services was high. Conclusions/Importance: Preliminary evidence of reduced drug use and high levels of client satisfaction among C&C clients provide support for Malaysia's ongoing transition from compulsory drug detention centers (CDDCs) to these voluntary drug treatment centers. If C&C centers are successful, Malaysia plans to gradually transition away from CDDCs entirely.

  9. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

    Science.gov (United States)

    Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

    2013-11-18

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  10. Recent advances in nanoformulations for co-delivery of curcumin and chemotherapeutic drugs

    Directory of Open Access Journals (Sweden)

    Maryam Hashemi

    2017-01-01

    Full Text Available The application of chemotherapy in cancer treatment has been limited due to cause side effects such as toxicity against normal cells and drug resistance. In recent years, numerous studies have been focused on using natural products with chemotherapeutic drugs to enhance therapeutic efficiency and reduce cytotoxicity. On the other hand, encapsulation of drugs into nanoparticles (NPs can improve solubility of hydrophobic drug; circulation time in blood and the residence at the pathological site by enhance permeation and retention (EPR effect. It has been shown that curcumin (CUR has  wide range of pharmacological activities against many diseases such as cancer. CUR has been demonstrated to be a potent chemosensitizer that can induce additive or synergistic effects with chemotherapeutic drugs against different cancer cell lines.  Recently, various types of nanocarriers have been investigated for CUR.  In this review, different co-formulations containing Cur and chemotherapeutic drugs used in cancer therapy are discussed with emphasis on their pharmaceutical properties.

  11. A hybrid approach to advancing quantitative prediction of tissue distribution of basic drugs in human

    International Nuclear Information System (INIS)

    Poulin, Patrick; Ekins, Sean; Theil, Frank-Peter

    2011-01-01

    A general toxicity of basic drugs is related to phospholipidosis in tissues. Therefore, it is essential to predict the tissue distribution of basic drugs to facilitate an initial estimate of that toxicity. The objective of the present study was to further assess the original prediction method that consisted of using the binding to red blood cells measured in vitro for the unbound drug (RBCu) as a surrogate for tissue distribution, by correlating it to unbound tissue:plasma partition coefficients (Kpu) of several tissues, and finally to predict volume of distribution at steady-state (V ss ) in humans under in vivo conditions. This correlation method demonstrated inaccurate predictions of V ss for particular basic drugs that did not follow the original correlation principle. Therefore, the novelty of this study is to provide clarity on the actual hypotheses to identify i) the impact of pharmacological mode of action on the generic correlation of RBCu-Kpu, ii) additional mechanisms of tissue distribution for the outlier drugs, iii) molecular features and properties that differentiate compounds as outliers in the original correlation analysis in order to facilitate its applicability domain alongside the properties already used so far, and finally iv) to present a novel and refined correlation method that is superior to what has been previously published for the prediction of human V ss of basic drugs. Applying a refined correlation method after identifying outliers would facilitate the prediction of more accurate distribution parameters as key inputs used in physiologically based pharmacokinetic (PBPK) and phospholipidosis models.

  12. Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity.

    Science.gov (United States)

    Murphy, Cormac D; Sandford, Graham

    2015-04-01

    Fluorine's unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed. The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.

  13. [How to adapt to the requirements of "clinical value-oriented drug innovation" for pharmaceutical research in application process of new traditional Chinese medicine].

    Science.gov (United States)

    Jin, Fang

    2017-05-01

    On August 9, 2015, the State Council promulgated the "Opinions of the State Council on the reform of drug and medical device review and approval system" (Guofa 2015 No. 44), and established the "clinical value-oriented drug innovation" model to encourage the research and development of new drugs. Following that, China Food and Drug Administration (CFDA) promulgated the "Notice on several policies for drug registration review and approval" (2015 No. 230 ) on November 11, 2015, clearly specifying that CFDA would "implement one-time approval for clinical trials application of the new drugs, and no longer take a phased declaration, review and approval system; for the new drugs that apply for clinical trials, mainly review the scientific natureof the clinical protocols and the risk control of the new drugs to guarantee the safety of subjects". Accordingly, the evaluation ideas and forms of new drug registration have also been adjusted greatly. For example, issues like the rationality of the drug manufacturing process, whether the scale can reflect the stability of the process, whether the preparation process is sufficient, and whether the choice of dosage form is reasonable are no longer the focus of evaluation before clinical trials. Issues regarding whether the preparation process design is reasonable, whether the effective components can be transferred to the preparation to a maximum extent, whether the process parameters determined in small and middle pilot trials can adapt to the requirements of mass production, no longer act as the reasons for refusing the clinical trials. The corresponding risks shall be borne by the applicant as the subject of liability. The focus in registration evaluation is mainly transferred to how to ensure the consistence of quality between clinical trial samples and the samples already available on market by guaranteeing stable sources of drug raw materials and stable quality of medicines as well as control of the whole preparation

  14. Latest developments in innovative manufacturing to combine nanotechnology with healthcare

    OpenAIRE

    Parhizkar, M.; Mahalingam, S.; Homer-Vanniasinkam, S.; Edirisinghe, M.

    2017-01-01

    Nanotechnology has become increasingly important in advancing the frontiers of many key areas of healthcare, for example, drug delivery and tissue engineering. To fully harness the many benefits of nanotechnology in healthcare, innovative manufacturing is necessary to mass produce nanoparticles and nanofibers, the two major types of nanofeatures currently sought after and of immense utilitarian value in healthcare. For example, nanoparticles are a key drug delivery enabler, the structural and...

  15. Technological advances and proteomic applications in drug discovery and target deconvolution: identification of the pleiotropic effects of statins.

    Science.gov (United States)

    Banfi, Cristina; Baetta, Roberta; Gianazza, Erica; Tremoli, Elena

    2017-06-01

    Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'. The case of statins highlights the unique contribution of proteomics to the target profiling of a drug molecule. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Advances in immobilized artificial membrane (IAM) chromatography for novel drug discovery.

    Science.gov (United States)

    Tsopelas, Fotios; Vallianatou, Theodosia; Tsantili-Kakoulidou, Anna

    2016-01-01

    The development of immobilized artificial membrane (IAM) chromatography has unfolded new perspectives for the use of chromatographic techniques in drug discovery, combining simulation of the environment of cell membranes with rapid measurements. The present review describes the characteristics of phosphatidylcholine-based stationary phases and analyses the molecular factors governing IAM retention in comparison to n-octanol-water and liposomes partitioning systems as well as to reversed phase chromatography. Other biomimetic stationary phases are also briefly discussed. The potential of IAM chromatography to model permeability through the main physiological barriers and drug membrane interactions is outlined. Further applications to calculate complex pharmacokinetic properties, related to tissue binding, and to screen drug candidates for phospholipidosis, as well as to estimate cell accumulation/retention are surveyed. The ambivalent nature of IAM chromatography, as a border case between passive diffusion and binding, defines its multiple potential applications. However, despite its successful performance in many permeability and drug-membrane interactions studies, IAM chromatography is still used as a supportive and not a stand-alone technique. Further studies looking at IAM chromatography in different biological processes are still required if this technique is to have a more focused and consistent application in drug discovery.

  17. Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria.

    Science.gov (United States)

    Kumar, Sahil; Singh, Rajesh K; Patial, Babita; Goyal, Sachin; Bhardwaj, T R

    2016-01-01

    Malaria is a major public health problem all over the world, particularly in tropical and subtropical countries due to the development of resistance and most deadly infection is caused by Plasmodium falciparum. There is a direct need for the discovery of new drugs with unique structures and mechanism of action to treat sensitive and drug-resistant strains of various plasmodia for radical cure of this disease. Traditional compounds such as quinine and related derivatives represent a major source for the development of new drugs. This review presents recent modifications of 4-aminoquinoline and 8-aminoquinolone rings as leads to novel active molecules which are under clinical trials. The review also encompasses the other heterocyclic compounds emerged as potential antimalarial agents with promising results such as acridinediones and acridinone analogues, pyridines and quinolones as antimalarials. Miscellaneous heterocyclics such as tetroxane derivatives, indole derivatives, imidazolopiperazine derivatives, biscationic choline-based compounds and polymer-linked combined antimalarial drugs are also discussed. At last brief introduction to heterocyclics in natural products is also reviewed. Most of them have been under clinical trials and found to be promising in the treatment of drug-resistant strains of Plasmodium and others can be explored for the same purpose.

  18. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    NARCIS (Netherlands)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger; Schellens, Jan H M; Mach, Nicholas; Tan, Eugene; Anand, Suraj; Scott, Jeffrey W; Lassen, Ulrik N

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS:

  19. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    DEFF Research Database (Denmark)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger

    2018-01-01

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS: ...

  20. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems.

    Science.gov (United States)

    Goyanes, Alvaro; Det-Amornrat, Usanee; Wang, Jie; Basit, Abdul W; Gaisford, Simon

    2016-07-28

    Acne is a multifactorial inflammatory skin disease with high prevalence. In this work, the potential of 3D printing to produce flexible personalised-shape anti-acne drug (salicylic acid) loaded devices was demonstrated by two different 3D printing (3DP) technologies: Fused Deposition Modelling (FDM) and stereolithography (SLA). 3D scanning technology was used to obtain a 3D model of a nose adapted to the morphology of an individual. In FDM 3DP, commercially produced Flex EcoPLA™ (FPLA) and polycaprolactone (PCL) filaments were loaded with salicylic acid by hot melt extrusion (HME) (theoretical drug loading - 2% w/w) and used as feedstock material for 3D printing. Drug loading in the FPLA-salicylic acid and PCL-salicylic acid 3D printed patches was 0.4% w/w and 1.2% w/w respectively, indicating significant thermal degradation of drug during HME and 3D printing. Diffusion testing in Franz cells using a synthetic membrane revealed that the drug loaded printed samples released printed as a nose-shape mask by FDM 3DP, but the PCL-salicylic acid filament was not. In the SLA printing process, the drug was dissolved in different mixtures of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) (PEG) that were solidified by the action of a laser beam. SLA printing led to 3D printed devices (nose-shape) with higher resolution and higher drug loading (1.9% w/w) than FDM, with no drug degradation. The results of drug diffusion tests revealed that drug diffusion was faster than with the FDM devices, 229 and 291μg/cm(2) within 3h for the two formulations evaluated. In this study, SLA printing was the more appropriate 3D printing technology to manufacture anti-acne devices with salicylic acid. The combination of 3D scanning and 3D printing has the potential to offer solutions to produce personalised drug loaded devices, adapted in shape and size to individual patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Challenges and advances in the assessment of the disposition of antibody‐drug conjugates

    Science.gov (United States)

    Iyer, Suhasini

    2015-01-01

    Abstract Antibody‐drug conjugates (ADCs) are a rapidly growing therapeutic platform for the treatment of cancer. ADCs consist of a cytotoxic small molecule drug linked to an antibody to provide targeted delivery of the cytotoxic agent to the tumor. Understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of ADCs is crucial in their design to optimize dose and regimen, to maximize efficacy and to minimize toxicity in patients. Significant progress has been made in recent years in this area, however, many fundamental questions still remain. This review discusses factors to consider while assessing the disposition of ADCs, and the unique challenges associated with these therapeutics. Current tools that are available and strategies to enable appropriate assessment are also discussed. © 2015 Genentech Inc. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd. PMID:25904406

  2. 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

    Science.gov (United States)

    Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

    2018-04-12

    A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Behaviour of pharmaceuticals and psychotic drugs in conventional and advanced wastewater treatments

    International Nuclear Information System (INIS)

    Cortacans Torre, J. A.; Castillo Gonzalez, I. del; Hernandez Lehmann, A.; Hernandez Munoz, A.; Rodriguez Barrera, X.

    2009-01-01

    The occurrence of various pharmaceuticals and psychotic drugs in wastewater and their removal rates in a conventional wastewater treatment plant has been investigated. The psychoactive drugs are poorly removed in the biological step. However, most pharmaceuticals except of carbamazepine, are significantly biodegraded depending the removal degree on the type of compound and on the sludge retention time of the biological treatment. Also, the removal efficiency of conventional tertiary treatments and ultrafiltration and nano filtration membranes using two pilot plants was examined. the effects of retaining pharmaceuticals with ultrafiltration and nano filtration membranes do not greatly differ despite the difference in their pore size. (Author) 25 refs.

  4. The weak-ties in advanced business services as a major force of innovation and diffusion; Las Eak-Ties en los servicios avanzados a empresas como factor relevante de la innovacion y su difusion

    Energy Technology Data Exchange (ETDEWEB)

    Almenar i Llongo, V.; Hernandez Sancho, F.; Solar i Marco, V.

    2012-07-01

    This paper tries to expose the role of weak-ties of advanced business services in both mechanisms which generate innovation as well as allow technological diffusion and transfer of innovations (spillovers). Assuming that the latest information generally flows to agents through weak ties, the Weak-Ties Hypothesis (WTH) is an approach that helps to explain the importance of the relations with the environment in the process of innovation and generation of new knowledge and its implementation and dissemination, evaluating the synergy's resulting from cooperation between agents. (Author) 21 refs.

  5. Teaching Groups as Foci for Evaluating Performance in Cost-Effectiveness of GCE Advanced Level Provision: Some Practical Methodological Innovations.

    Science.gov (United States)

    Fielding, Antony

    2002-01-01

    Analyzes subject teaching-group effectiveness in English and Welsh General Certification of Education (GCE) Advanced Level prior to a linking to resources; suggests cross-classified multilevel models with weighted random effects for disentangling student, group, and teacher effects; finds that teacher effects are considerable, but cannot find…

  6. Palliative therapy of advanced breast cancer with targeted polymer-bound drug

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka; Strohalm, Jiří; Kubáčková, K.; Jelínková, Markéta; Rozprimová, L.; Šírová, Milada; Plocová, Daniela; Etrych, Tomáš; Mrkvan, Tomáš; Kovář, Marek; Ulbrich, Karel

    2003-01-01

    Roč. 12, č. 1 (2003), s. 375 ISSN 1107-3756. [World Congress on Advances in Oncology /8./. Crete, 16.10.2003-18.10.2003] Institutional research plan: CEZ:AV0Z4050913; CEZ:AV0Z5020903 Keywords : hpma * epr * lak Subject RIV: EE - Microbiology, Virology Impact factor: 1.940, year: 2003

  7. The eTOX Data-Sharing Project to Advance in Silico Drug-Induced Toxicity Prediction

    Directory of Open Access Journals (Sweden)

    Montserrat Cases

    2014-11-01

    Full Text Available The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data. In 2010, under the auspices of the Innovative Medicines Initiative, the eTOX project started with the objective of extracting and sharing preclinical study data from paper or pdf archives of toxicology departments of the 13 participating pharmaceutical companies and using such data for establishing a detailed, well-curated database, which could then serve as source for read-across approaches (early assessment of the potential toxicity of a drug candidate by comparison of similar structure and/or effects and training of predictive models. The paper describes the efforts undertaken to allow effective data sharing intellectual property (IP protection and set up of adequate controlled vocabularies and to establish the database (currently with over 4000 studies contributed by the pharma companies corresponding to more than 1400 compounds. In addition, the status of predictive models building and some specific features of the eTOX predictive system (eTOXsys are presented as decision support knowledge-based tools for drug development process at an early stage.

  8. Bridging Innovation and Outreach to Overcome Global Gaps in Radiation Oncology Through Information and Communication Tools, Trainee Advancement, Engaging Industry, Attention to Ethical Challenges, and Political Advocacy.

    Science.gov (United States)

    Dad, Luqman; Royce, Trevor J; Morris, Zachary; Moran, Meena; Pawlicki, Todd; Khuntia, Deepak; Hardenbergh, Patricia; Cummings, Bernard; Mayr, Nina; Hu, Kenneth

    2017-04-01

    An evolving paradigm in global outreach in radiation oncology has been the implementation of a more region-specific, needs-based approach to help close the gap in radiation services to low- and middle-income countries through the use of innovative tools in information and communication technology. This report highlights 4 information and communication technology tools in action today: (1) the NCCN Framework for Resource Stratification of NCCN guidelines, (2) ASTRO e-Contouring, (3) i.treatsafely.org, and (4) ChartRounds.com. We also render special consideration to matters related to global outreach that we believe require distinct attention to help us meet the goals established by the 2011 United Nations׳ Declaration on noncommunicable diseases: (1) trainee advancement toward careers in global health, (2) ethical challenges of international outreach, (3) critical importance of political advocacy, and (4) collaboration with Industry. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The categorization of the impacts of the results of scientific and technological innovation in the Agency of Nuclear energy and advanced technologies (AENTA)

    International Nuclear Information System (INIS)

    Rodriguez Cardona, R.; Cobas Aranda, M.

    2010-01-01

    Science and technology are essential to the development of contemporary societies, however, there are different concepts and methodologies internationally to assess the economic and social impact of science and technology. In our country he has worked intensely with this aim and has established a national nomenclature of impact of science, technology and innovation. The Agency of Nuclear energy and advanced technologies (AEN-TA) is intended to improve the management of the programmes and projects management system framed within the system of science and technological innovation of the Republic of Cuba (SCIT) and one of the aspects of your special attention is the proper selection and follow-up (ex - before and during) projects to ensure that they contribute to improving the level of economic and social of our country one of his fundamental premises. This work has aims to show how the bases of the categorization of the impacts of the projects were established in the AEN-Mt management programs, as a management tool for the selection and monitoring of them, and which are characterized by a flexibility that keeping their identity do not differ from the established in the country. (author)

  10. Recent and future advances in anticancer drug delivery: an interview with Khaled Greish.

    Science.gov (United States)

    Greish, Khaled

    2018-05-01

    Khaled Greish speaks to Hannah Makin, Commissioning Editor: Khaled Greish is Associate Professor of Molecular Medicine, and head of the Nano-research unit, at Princes Al-Jawhara Center, Arabian Gulf University, Kingdom of Bahrain. His previous appointments included Senior lecturer of Pharmacology at the University of Otago, New Zealand, and Assistant Professor of Pharmaceutical Chemistry at University of Utah (UT, USA). He has published >70 peer reviewed papers, and ten book chapters in the field of targeted anticancer drug delivery. Controlled Release Society (CRS) awarded him the CRS Postdoctoral Achievement Award in 2008 and in 2010; he was elected as member of the CRS College of Fellows. In recognition of his research, University of Otago awarded him "Early Career Awards for Distinction in Research" in 2014. His research focuses on nanomedicine, tumor vascular biology and anticancer drug discovery/development.

  11. Recent advances in protein and Peptide drug delivery: a special emphasis on polymeric nanoparticles.

    Science.gov (United States)

    Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K

    2014-01-01

    Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly em- ployed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transder mal, and ocular administrations.

  12. Parent Engagement in Youth Drug Prevention in Chinese Families: Advancement in Program Development and Evaluation

    Directory of Open Access Journals (Sweden)

    Sandra K. M. Tsang

    2011-01-01

    Full Text Available The escalating youth drug abuse problem in Hong Kong has attracted intense attention from the government, schools, and youth service professionals. Most preventive efforts have focused directly on positive youth development, very often through school programs delivered to secondary school students. There have been limited efforts to engage parents even though it is obvious that the family is actually the primary context of children and youth development. This paper will assert the importance of parental engagement in youth drug-prevention work, discuss some barriers in such parental involvement, present some promising local attempts and their strengths and limitations, and propose that sustained efforts are needed to build up theory-driven and evidence-based resources for Chinese communities on the subject.

  13. Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity

    OpenAIRE

    Murphy, Cormac D.; Sandford, Graham

    2015-01-01

    Introduction: Fluorine’s unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. Areas covered: This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the p...

  14. Iterative photoinduced chain functionalization as a generic platform for advanced polymeric drug delivery systems

    Czech Academy of Sciences Publication Activity Database

    Al Samad, A.; Bethry, A.; Janoušková, Olga; Ciccione, J.; Wenk, C.; Coll, J.-L.; Subra, G.; Etrych, Tomáš; El Omar, F.; Bakkour, Y.; Coudane, J.; Nottelet, B.

    2018-01-01

    Roč. 39, č. 3 (2018), s. 1-5, č. článku 1700502. ISSN 1022-1336 R&D Projects: GA MŠk(CZ) LO1507; GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : drug delivery systems * functionalization of polymers * photochemistry Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.265, year: 2016

  15. Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.

    Science.gov (United States)

    Denora, Nunzio; Trapani, Adriana; Laquintana, Valentino; Lopedota, Angela; Trapani, Giuseppe

    2009-01-01

    This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

  16. Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

    Directory of Open Access Journals (Sweden)

    Chendi Ding

    2016-12-01

    Full Text Available Benefiting from the development of nanotechnology, drug delivery systems (DDSs with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs, quantum dots (QDs and carbon nanotubes (CNTs. The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules and extrinsic (temperature, light irradiation, magnetic field and ultrasound ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

  17. Intestinal Stem Cells to Advance Drug Development, Precision, and Regenerative Medicine: A Paradigm Shift in Translational Research.

    Science.gov (United States)

    Mochel, Jonathan P; Jergens, Albert E; Kingsbury, Dawn; Kim, Hyun Jung; Martín, Martín G; Allenspach, Karin

    2017-12-12

    Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at lower costs compared with live animal studies. Importantly, because they are derived from individuals with different genotypes, environmental risk factors and drug sensitivity profiles, organoids are a highly relevant screening system for personalized therapy in both human and veterinary medicine. Lastly, and in the context of patient-specific congenital diseases, orthotopic transplantation of engineered organoids could repair and/or replace damaged epithelial tissues reported in various GI diseases, such as inflammatory bowel disease, cystic fibrosis, and tuft enteropathy. Ongoing translational research on organoids derived from dogs with naturally occurring digestive disorders has the potential to improve the predictability of preclinical models used for optimizing the therapeutic management of severe chronic enteropathies in human patients.

  18. Innovative methods to study human intestinal drug metabolism in vitro : Precision-cut slices compared with Ussing chamber preparations

    NARCIS (Netherlands)

    van de Kerkhof, Esther G.; Ungell, Anna-Lena B.; Sjoberg, Asa K.; de Jager, Marina H.; Hilgendorf, Constanze; de Graaf, Inge A. M.; Groothuis, Geny M. M.

    2006-01-01

    Predictive in vitro methods to investigate drug metabolism in the human intestine using intact tissue are of high importance. Therefore, we studied the metabolic activity of human small intestinal and colon slices and compared it with the metabolic activity of the same human intestinal segments

  19. Organizational Innovation and Redesign in the Information Age: The Drug War, Netwar, and Other Lower-End Conflict.

    Science.gov (United States)

    1998-03-01

    the nation’s attitude of lawlessness and rebellion was fueled by illegal drugs. In a campaign speech given at Disneyland , Nixon stated, "As I look...organizations. However, ignoring the changing environment will lead to problems that can threaten the security of the United States. Granted these

  20. Innovative approach to produce submicron drug particles by vibrational atomization spray drying: influence of the type of solvent and surfactant.

    Science.gov (United States)

    Durli, T L; Dimer, F A; Fontana, M C; Pohlmann, A R; Beck, R C R; Guterres, S S

    2014-08-01

    Spray drying is a technique used to produce solid particles from liquid solutions, emulsions or suspensions. Buchi Labortechnik developed the latest generation of spray dryers, Nano Spray Dryer B-90. This study aims to obtain, directly, submicron drug particles from an organic solution, employing this equipment and using dexamethasone as a model drug. In addition, we evaluated the influence of both the type of solvent and surfactant on the properties of the powders using a 3(2) full factorial analysis. The particles were obtained with high yields (above 60%), low water content (below 2%) and high drug content (above 80%). The surface tension and the viscosity were strongly influenced by the type of solvent. The highest powder yields were obtained for the highest surface tension and the lowest viscosity of the drug solutions. The use of ionic surfactants led to higher process yields. The laser diffraction technique revealed that the particles deagglomerate into small ones with submicrometric size, (around 1 µm) that was also observed by scanning electron microscopy. Interaction between the raw materials in the spray-dried powders was verified by calorimetric analysis. Thus, it was possible to obtain dexamethasone submicrometric particles by vibrational atomization from organic solution.

  1. The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

    NARCIS (Netherlands)

    Heslop, Emma; Csimma, Cristina; Straub, Volker; McCall, John; Nagaraju, Kanneboyina; Wagner, Kathryn R.; Caizergues, Didier; Korinthenberg, Rudolf; Flanigan, Kevin M.; Kaufmann, Petra; McNeil, Elizabeth; Mendell, Jerry; Hesterlee, Sharon; Wells, Dominic J.; Bushby, Kate; McNeil, Dawn Elizabeth; Allen, Hugh; Bourke, John; Burghes, Arthur; Buyse, Gunnar; Catlin, Nick; Clemens, Paula; Cnaan, Avital; Comi, Giacomo; Connor, Edward; de Luca, Annamaria; de Montleau, Béatrice; de Visser, Marianne; Day, Simon; Dittrich, Sven; Dubrosky, Alberto; Eagle, Michelle; Finkel, Richard; Fishbeck, Kenneth; Furlong, Patricia; Grounds, Miranda; Hauschke, Dieter; Hoffman, Eric; Irwin, Joseph; Jarecki, Jill; Kelly, Michael; Laforêt, Pascal; Lovering, Richard; Larkindale, Jane; Mayer, Henry; McDonald, Robert; McNally, Elizabeth; Miller, Debra; North, Kathryn; Ouillade, Marie-Christine

    2015-01-01

    Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a

  2. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Andersen, Jacob; Kristensen, Anders Skov; Bang-Andersen, Benny

    2009-01-01

    The biogenic monoamine transporters are integral membrane proteins that perform active transport of extracellular dopamine, serotonin and norepinephrine into cells. These transporters are targets for therapeutic agents such as antidepressants, as well as addictive substances such as cocaine...... and amphetamine. Seminal advances in the understanding of the structure and function of this transporter family have recently been accomplished by structural studies of a bacterial transporter, as well as medicinal chemistry and pharmacological studies of mammalian transporters. This feature article focuses...

  3. Marketing Authorization Procedures for Advanced Cancer Drugs: Exploring the Views of Patients, Oncologists, Healthcare Decision Makers, and Citizens in France.

    Science.gov (United States)

    Protiére, Christel; Baker, Rachel; Genre, Dominique; Goncalves, Anthony; Viens, Patrice

    2017-07-01

    The past decades have seen advances in cancer treatments in terms of toxicity and side effects but progress in the treatment of advanced cancer has been modest. New drugs have emerged improving progression free survival but with little impact on overall survival, raising questions about the criteria on which to base decisions to grant marketing authorizations and about the authorization procedure itself. For decisions to be fair, transparent and accountable, it is necessary to consider the views of those with relevant expertise and experience. We conducted a Q-study to explore the views of a range of stakeholders in France, involving: 54 patients (18 months after diagnosis); 50 members of the general population; 27 oncologists; 19 healthcare decision makers; and 2 individuals from the pharmaceutical industry. Three viewpoints emerged, focussing on different dimensions entitled: 1) 'Quality of life (QoL), opportunity cost and participative democracy'; 2)'QoL and patient-centeredness'; and 3) 'Length of life'. Respondents from all groups were associated with each viewpoint, except for healthcare decision makers, who were only associated with the first one. Our results highlight plurality in the views of stakeholders, emphasize the need for transparency in decision making processes, and illustrate the importance of a re-evaluation of treatments for all 3 viewpoints. In the context of advanced cancer, our results suggest that QoL should be more prominent amongst authorization criteria, as it is a concern for 2 of the 3 viewpoints.

  4. Novel opportunities for computational biology and sociology in drug discovery☆

    Science.gov (United States)

    Yao, Lixia; Evans, James A.; Rzhetsky, Andrey

    2013-01-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development, explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy–industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies. PMID:20349528

  5. Novel opportunities for computational biology and sociology in drug discovery

    Science.gov (United States)

    Yao, Lixia

    2009-01-01

    Drug discovery today is impossible without sophisticated modeling and computation. In this review we touch on previous advances in computational biology and by tracing the steps involved in pharmaceutical development, we explore a range of novel, high value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry ties for scientific and human benefit. Attention to these opportunities could promise punctuated advance, and will complement the well-established computational work on which drug discovery currently relies. PMID:19674801

  6. Advancing the vesosome, a multifunctional drug delivery platform, toward applied in vivo testing

    Science.gov (United States)

    Wong, Benjamin J.

    An optimal drug delivery vehicle should circulate long enough to reach the site of illness or disease, possess a large drug loading capacity, retain its contents over the course of treatment, and be able deliver its contents at a rate appropriate for maximum therapeutic benefit at the site of interest. The vesosome, a large lipid bilayer enclosing multiple, smaller liposomes, is our solution to addressing these needs. The external lipid bilayer offers a second barrier of protection for interior components and can also serve as the anchor for active targeting components. Furthermore, internal compartmentalization permits customization of separate environments for multiple therapeutics and release triggers. Previous work established the ability of the vesosome to retain its contents in vitro an order of magnitude longer than liposomes. To be viable in vivo, the vesosome must be functionalized for biocompatibility and tracking, and its synthetic procedure must be repeatable, reliable and result in a purified product. The vesosome was functionalized by introducing biocompatible polymers, such as poly(ethylene glycol) (PEG), and fluorescent dyes in their lipid-bound forms into the external membrane of the vesosome. The external vesosomal membrane is formed from large, flat lipid sheets in the interdigitated (L betaI) phase which, when heated, are used to encapsulate smaller drug-containing vesicles. Through X-Ray diffraction (XRD) and freeze-fracture transmission electron microscopy (FF-TEM), we established that the molar amounts of functionalized lipid required to label the vesosome for tracking and biocompatibility (˜5--7mol% total) did not prevent the formation of the interdigitated phase. Thus, functionalization of the external vesosome membrane can be achieved through functionalization of interdigitated sheets. For in vivo testing, functionalized vesosomes must be separated from unencapsulated vesicles and purification was performed using size exclusion

  7. Key Challenges in the Search for Innovative Drug Treatments for Special Populations. Converging Needs in Neonatology, Pediatrics, and Medical Genetics.

    Science.gov (United States)

    MacLeod, Stuart

    2017-08-04

    The explosion of knowledge concerning the interplay of genetic and environmental factors determining pathophysiology and guiding therapeutic choice has altered the landscape in pediatric clinical pharmacology and pharmacy. The need for innovative research methods and design expertise for small clinical trials to be undertaken in sparse populations has been accentuated. At the same time, shortfalls in critical human resources represent a key challenge, especially in low- and middle-income countries where the need for new research and education directions is greatest. Unless a specific action plan is urgently developed, there will be a continuing gap in availability of the essential expertise needed to address treatment challenges in special patient populations such as neonates, patients suffering from rare or neglected diseases, and children of all ages.

  8. Innovative Training Experience for Advancing Entry Level, Mid-Skilled and Professional Level URM Participation in the Geosciences Workforce

    Science.gov (United States)

    Okoro, M. H.; Johnson, A.

    2015-12-01

    The representation of URMs in the U.S. Geosciences workforce remains proportionally low compared to their representation in the general population (Bureau of Labor Sta.s.cs, 2014). Employment in this and related industries is projected to grow 32% by 2030 for minority workers (Gillula and Fullenbaum, 2014), corresponding to an additional 48,000 jobs expected to be filled by minorities (National Research Council, 2014). However, there is a shortage of employees with proper training in the hard sciences (Holeywell, 2014; Ganzglass, 2011), as well as craft skills (Hoover and Duncan, 2013), both important for middle skill employment. Industry recognizes the need for developing and retaining a diverse workforce, therefore we hightlight a program to serve as a potential vanguard initative for developing an innovative training experience for URM and underserved middle skilled workers with essential knowledge, experience and skills necessary to meet the demands of the Geosciences industry's growing need for a safe, productive and diverse workforce. Objectives are for participants to achieve the following: understanding of geosciences workforce trends and associated available opportunities; mastery of key environmental, health and safety topics; improvements in decision making skills and preparedness for responding to potential environmental, health and safety related situations; and engagement in one-on-one coaching sessions focused on resume writing, job interviewing and key "soft skills" (including conflict resolution, problem solving and critical observation, representing 3 major skills that entry- level workers typically lack.

  9. Evaluation of innovative stationary phase ligand chemistries and analytical conditions for the analysis of basic drugs by supercritical fluid chromatography.

    Science.gov (United States)

    Desfontaine, Vincent; Veuthey, Jean-Luc; Guillarme, Davy

    2016-03-18

    Similar to reversed phase liquid chromatography, basic compounds can be highly challenging to analyze by supercritical fluid chromatography (SFC), as they tend to exhibit poor peak shape, especially those with high pKa values. In this study, three new stationary phase ligand chemistries available in sub -2 μm particle sizes, namely 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA) and diethylamine (DEA), were tested in SFC conditions for the analysis of basic drugs. Due to the basic properties of these ligands, it is expected that the repulsive forces may improve peak shape of basic substances, similarly to the widely used 2-ethypyridine (2-EP) phase. However, among the 38 tested basic drugs, less of 10% displayed Gaussian peaks (asymmetry between 0.8 and 1.4) using pure CO2/methanol on these phases. The addition of 10mM ammonium formate as mobile phase additive, drastically improved peak shapes and increased this proportion to 67% on 2-PIC. Introducing the additive in the injection solvent rather than in the organic modifier, gave acceptable results for 2-PIC only, with 31% of Gaussian peaks with an average asymmetry of 1.89 for the 38 selected basic drugs. These columns were also compared to hybrid silica (BEH), DIOL and 2-EP stationary phases, commonly employed in SFC. These phases commonly exhibit alternative retention and selectivity. In the end, the two most interesting ligands used as complementary columns were 2-PIC and BEH, as they provided suitable peak shapes for the basic drugs and almost orthogonal selectivities. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Pharmacists' advancing roles in drug and disease management: a review of states' legislation.

    Science.gov (United States)

    McKnight, Alicia G; Thomason, Angela R

    2009-01-01

    To determine which states in the United States have provisions in place for pharmacist participation in drug and disease management programs and/or collaborative practice agreements and to provide comparison and discussion regarding such provisions. A secondary endpoint was the requirements of certification, credentialing, and registration with the specific state's rules and regulations. Information was gathered from states' statutes, rules, and regulations. Acquisition of each state's laws was achieved through various forms of electronic media. Data were accessed from January to March 2008. 19 states (38%) had specific provisions for disease management, 33 (66%) had provisions for drug therapy management, and 37 (74%) had provisions for collaborative practice. A total of 11 states (22%) specified that pharmacists receive specialized training to participate in such endeavors. Board approval or notification for collaborative practice agreements was required in 16 states (32%). With varying degrees of autonomy and restriction, pharmacists in certain states have the ability to develop disease management and/or collaborative practice programs. For pharmacists to take advantage of these new direct patient care opportunities, knowing the rules and requirements of their state's legislation is essential.

  11. Advanced real-time multi-display educational system (ARMES): An innovative real-time audiovisual mentoring tool for complex robotic surgery.

    Science.gov (United States)

    Lee, Joong Ho; Tanaka, Eiji; Woo, Yanghee; Ali, Güner; Son, Taeil; Kim, Hyoung-Il; Hyung, Woo Jin

    2017-12-01

    The recent scientific and technologic advances have profoundly affected the training of surgeons worldwide. We describe a novel intraoperative real-time training module, the Advanced Robotic Multi-display Educational System (ARMES). We created a real-time training module, which can provide a standardized step by step guidance to robotic distal subtotal gastrectomy with D2 lymphadenectomy procedures, ARMES. The short video clips of 20 key steps in the standardized procedure for robotic gastrectomy were created and integrated with TilePro™ software to delivery on da Vinci Surgical Systems (Intuitive Surgical, Sunnyvale, CA). We successfully performed the robotic distal subtotal gastrectomy with D2 lymphadenectomy for patient with gastric cancer employing this new teaching method without any transfer errors or system failures. Using this technique, the total operative time was 197 min and blood loss was 50 mL and there were no intra- or post-operative complications. Our innovative real-time mentoring module, ARMES, enables standardized, systematic guidance during surgical procedures. © 2017 Wiley Periodicals, Inc.

  12. Passive Safety Systems in Advanced Water Cooled Reactors (AWCRS). Case Studies. A Report of the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO)

    International Nuclear Information System (INIS)

    2013-09-01

    This report presents the results from the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) collaborative project (CP) on Advanced Water Cooled Reactor Case Studies in Support of Passive Safety Systems (AWCR), undertaken under the INPRO Programme Area C. INPRO was launched in 2000 - on the basis of a resolution of the IAEA General Conference (GC(44)/RES/21) - to ensure that nuclear energy is available in the 21st century in a sustainable manner, and it seeks to bring together all interested Member States to consider actions to achieve innovation. An important objective of nuclear energy system assessments is to identify 'gaps' in the various technologies and corresponding research and development (R and D) needs. This programme area fosters collaboration among INPRO Member States on selected innovative nuclear technologies to bridge technology gaps. Public concern about nuclear reactor safety has increased after the Fukushima Daiichi nuclear power plant accident caused by the loss of power to pump water for removing residual heat in the core. As a consequence, there has been an increasing interest in designing safety systems for new and advanced reactors that are passive in nature. Compared to active systems, passive safety features do not require operator intervention, active controls, or an external energy source. Passive systems rely only on physical phenomena such as natural circulation, thermal convection, gravity and self-pressurization. Passive safety features, therefore, are increasingly recognized as an essential component of the next-generation advanced reactors. A high level of safety and improved competitiveness are common goals for designing advanced nuclear power plants. Many of these systems incorporate several passive design concepts aimed at improving safety and reliability. The advantages of passive safety systems include simplicity, and avoidance of human intervention, external power or signals. For these reasons, most

  13. Innovation and employment

    OpenAIRE

    Vivarelli, Marco

    2015-01-01

    Studies find that technological change has contributed 
to the decline in manufacturing and to persistent unemployment in many advanced economies. While 
process innovation can be job-destroying, product innovation can imply the emergence of new firms, new sectors, and thus new jobs. But even for process innovation, the final impact on labor demand is shaped by market mechanisms that can compensate for the direct job-destroying impact if market and institutional rigidities do not impede them....

  14. The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development.

    Science.gov (United States)

    Heslop, Emma; Csimma, Cristina; Straub, Volker; McCall, John; Nagaraju, Kanneboyina; Wagner, Kathryn R; Caizergues, Didier; Korinthenberg, Rudolf; Flanigan, Kevin M; Kaufmann, Petra; McNeil, Elizabeth; Mendell, Jerry; Hesterlee, Sharon; Wells, Dominic J; Bushby, Kate

    2015-04-23

    Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD.We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme.To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation

  15. Novel Hydrogel-Advanced Modified Clay Nanocomposites as Possible Vehicles for Drug Delivery and Controlled Release

    Directory of Open Access Journals (Sweden)

    Raluca Ianchis

    2017-12-01

    Full Text Available Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid (PMAA with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N,N’-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel. In vitro MTS ([3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, inner salt] colorimetric assay showed that direct exposure with PMMA-clay-based constructs did not affect cell viability and proliferation in time (24 and 48 h on either normal or adenocarcinoma cell lines.

  16. Novel Hydrogel-Advanced Modified Clay Nanocomposites as Possible Vehicles for Drug Delivery and Controlled Release.

    Science.gov (United States)

    Ianchis, Raluca; Ninciuleanu, Claudia M; Gifu, Ioana C; Alexandrescu, Elvira; Somoghi, Raluca; Gabor, Augusta R; Preda, Silviu; Nistor, Cristina L; Nitu, Sabina; Petcu, Cristian; Icriverzi, Madalina; Florian, Paula E; Roseanu, Anca M

    2017-12-13

    Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid) (PMAA) with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N , N '-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel. In vitro MTS ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium, inner salt]) colorimetric assay showed that direct exposure with PMMA-clay-based constructs did not affect cell viability and proliferation in time (24 and 48 h) on either normal or adenocarcinoma cell lines.

  17. Irinotecan drug eluting beads used as a treatment of advanced intra hepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Jean Amede Roch

    2008-10-01

    Full Text Available

    This report describes a 74-year-old male with unresectable intrahepatic cholangiocarcinoma (ICC. However surgical procedure is the only curative treatment, it often seems to be ineffective because of the aggressive behaviour of the disease. The role of systemic chemotherapy in the ICC is undefined with a median survival between 6.43 to 12.17 months obtained by using the combination chemotherapy of gemcitabine with cisplatin. In the present case, we performed a targeted treatment using drug eluting beads (DEB with irinotecan (IRI administered as transarterial-chemoembolization (TACE. After one session, the tumour vascularity decreased significantly at the one month evaluation on computed tomography (CT scan of the liver.  This case report suggested that minimally invasive transcatheter DEB embolization could be a promising, safe and effective treatment for selective patients with unresectable ICC.

  18. Proceedings of the 2013 CINP summit: innovative partnerships to accelerate CNS drug discovery for improved patient care.

    Science.gov (United States)

    Phillips, Anthony George; Hongaard-Andersen, Peter; Moscicki, Richard A; Sahakian, Barbara; Quirion, Rémi; Krishnan, K Ranga Rama; Race, Tim

    2014-12-25

    Central nervous system (CNS) diseases and, in particular, mental health disorders, are becoming recognized as the health challenge of the 21(st) century. Currently, at least 10% of the global population is affected by a mental health disorder, a figure that is set to increase year on year. Meanwhile, the rate of development of new CNS drugs has not increased for many years, despite unprecedented levels of investment. In response to this state of affairs, the Collegium Internationale Neuro-Psychopharmacologicum (CINP) convened a summit to discuss ways to reverse this disturbing trend through new partnerships to accelerate CNS drug discovery. The objectives of the Summit were to explore the issues affecting the value chain (i.e. the chain of activities or stakeholders that a company engages in/with to deliver a product to market) in brain research, thereby gaining insights from key stakeholders and developing actions to address unmet needs; to identify achievable objectives to address the issues; to develop action plans to bring about measurable improvements across the value chain and accelerate CNS drug discovery; and finally, to communicate recommendations to governments, the research and development community, and other relevant stakeholders. Summit outputs include the following action plans, aligned to the pressure points within the brain research-drug development value chain: Code of conduct dealing with conflict of interest issues, Prevention, early diagnosis, and treatment, Linking science and regulation, Patient involvement in trial design, definition of endpoints, etc., Novel trial design, Reproduction and confirmation of data, Update of intellectual property (IP) laws to facilitate repurposing and combination therapy (low priority), Large-scale, global patient registries, Editorials on nomenclature, biomarkers, and diagnostic tools, and Public awareness, with brain disease advocates to attend G8 meetings and World Economic Forum (WEF) Annual meetings in

  19. Innovative learning for innovation

    NARCIS (Netherlands)

    Dr.Ir. Hay Geraedts

    2010-01-01

    Introduction Innovation is crucial for companies who have to react to constantly changing markets. Several national and European research institutes stress the importance of developing innovation for small and medium size enterprises (SMEs). This was a trigger to design a minor on strategic

  20. Bio-inspired crosslinking and matrix-drug interactions for advanced wound dressings with long-term antimicrobial activity.

    Science.gov (United States)

    Dhand, Chetna; Venkatesh, Mayandi; Barathi, Veluchami Amutha; Harini, Sriram; Bairagi, Samiran; Goh Tze Leng, Eunice; Muruganandham, Nandhakumar; Low, Kenny Zhi Wei; Fazil, Mobashar Hussain Urf Turabe; Loh, Xian Jun; Srinivasan, Dinesh Kumar; Liu, Shou Ping; Beuerman, Roger W; Verma, Navin Kumar; Ramakrishna, Seeram; Lakshminarayanan, Rajamani

    2017-09-01

    There is a growing demand for durable advanced wound dressings for the management of persistent infections after deep burn injuries. Herein, we demonstrated the preparation of durable antimicrobial nanofiber mats, by taking advantage of strong interfacial interactions between polyhydroxy antibiotics (with varying number of OH groups) and gelatin and their in-situ crosslinking with polydopamine (pDA) using ammonium carbonate diffusion method. Polydopamine crosslinking did not interfere with the antimicrobial efficacy of the loaded antibiotics. Interestingly, incorporation of antibiotics containing more number of alcoholic OH groups (N OH  ≥ 5) delayed the release kinetics with complete retention of antimicrobial activity for an extended period of time (20 days). The antimicrobials-loaded mats displayed superior mechanical and thermal properties than gelatin or pDA-crosslinked gelatin mats. Mats containing polyhydroxy antifungals showed enhanced aqueous stability and retained nanofibrous morphology under aqueous environment for more than 4 weeks. This approach can be expanded to produce mats with broad spectrum antimicrobial properties by incorporating the combination of antibacterial and antifungal drugs. Direct electrospinning of vancomycin-loaded electrospun nanofibers onto a bandage gauze and subsequent crosslinking produced non-adherent durable advanced wound dressings that could be easily applied to the injured sites and readily detached after treatment. In a partial thickness burn injury model in piglets, the drug-loaded mats displayed comparable wound closure to commercially available silver-based dressings. This prototype wound dressing designed for easy handling and with long-lasting antimicrobial properties represents an effective option for treating life-threatening microbial infections due to thermal injuries. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Advancing Drug Discovery and Development from Active Constituents of Yinchenhao Tang, a Famous Traditional Chinese Medicine Formula

    Directory of Open Access Journals (Sweden)

    Aihua Zhang

    2013-01-01

    Full Text Available Traditional Chinese medicine (TCM formula has been playing a very important role in health protection and disease control for thousands of years. Guided by TCM syndrome theories, formula are designed to contain a combination of various kinds of crude drugs that, when combined, will achieve synergistic efficacy. However, the precise mechanism of synergistic action remains poorly understood. One example is a famous TCM formula Yinchenhao Tang (YCHT, whose efficacy in treating hepatic injury (HI and Jaundice syndrome, has recently been well established as a case study. We also conducted a systematic analysis of synergistic effects of the principal compound using biochemistry, pharmacokinetics and systems biology, to explore the key molecular mechanisms. We had found that the three component (6,7-dimethylesculetin (D, geniposide (G, and rhein (R combination exerts a more robust synergistic effect than any one or two of the three individual compounds by hitting multiple targets. They can regulate molecular networks through activating both intrinsic and extrinsic pathways to synergistically cause intensified therapeutic effects. This paper provides an overview of the recent and potential developments of chemical fingerprinting coupled with systems biology advancing drug discovery towards more agile development of targeted combination therapies for the YCHT.

  2. Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

    Science.gov (United States)

    Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

    2017-03-01

    Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

  3. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-01-01

    Full Text Available Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD with immediate release and improved bioavailability was prepared using Soluplus (Sol as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72 and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72 and Cmax higher than those with the commercial capsule (Noxafil. Molecular dynamic (MD simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  4. Evaluation of a novel photosensitizing drug having antitumor effect for advanced prostate cancer

    Science.gov (United States)

    Saito, Sachiko; Inai, Mizuho; Honda, Norihiro; Hazama, Hisanao; Kaneda, Yasufumi; Awazu, Kunio

    2017-07-01

    Prostate cancer is the second most frequently diagnosed cancer among men worldwide and a novel treatment for the disease is required. Replication-deficient virus particles, hemagglutinating virus of Japan envelope (HVJ-E), has cytotoxicity to cancer cells. To enhance the therapeutic effect of HVJ-E by photodynamic therapy (PDT) as a trigger of HVJ-E's anti-tumor effect, talaporfin sodium (Laserphyrin) used for PDT was encapsulated into HVJ-E to produce a novel photosensitizing drug, named Laserphyrin ®-HVJ-E, and its therapeutic effect for prostate cancer cells (PC-3) was evaluated. As the results, direct cytotoxicities of HVJ-E and Laserphyrin ®-HVJ-E for PC-3 after an administration time of 48 h were almost the same. Cell survival rates of PC-3, which were irradiated 2 h after administration of Laserphyrin ®-HVJ-E, were about 7.8%. Although further study is needed to find an optimal PDT condition, these results suggest that Laserphyrin ®-HVJ-E is useful for treatment of prostate cancer due to the combination of cytotoxicities of HVJ-E and PDT.

  5. Advanced topical drug delivery system for the management of vaginal candidiasis.

    Science.gov (United States)

    Johal, Himmat Singh; Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

    2016-01-01

    Vaginal candidiasis or vulvovaginal candidiasis (VC) is a common mucosal infection of vagina, mainly caused by Candida species. The major symptoms of VC are dyspareunia, pruritis, itching, soreness, vagina as well as vulvar erythema and edema. Most common risk factors that lead to the imbalance in the vaginal micro biota are the use of antibiotics, pregnancy, diabetes mellitus, immuno suppression as in AIDS or HIV patients, frequent sexual intercourse, spermicide and intra-uterine devices and vaginal douching. Various anti-fungal drugs are available for effective treatment of VC. Different conventional vaginal formulations (creams, gels, suppositories, powder, ointment, etc.) for VC are available today but have limited efficacy because of lesser residence time on vaginal epithelium due to self-cleansing action of vagina. So to overcome this problem, an extended and intimate contact with vaginal mucosa is desired; which can be accomplished by utilizing mucoadhesive polymers. Mucoadhesive polymers have an excellent binding capacity to mucosal tissues for considerable period of time. This unique property of these polymers significantly enhances retention time of different formulations on mucosal tissues. Currently, various novel formulations such as liposomes, nano- and microparticles, micro-emulsions, bio-adhesive gel and tablets are used to control and treat VC. In this review, we focused on current status of vaginal candidiasis, conventional and nanotechnology inspired formulation approaches.

  6. Introduction for the special issue on recent advances in drug delivery across tissue barriers.

    Science.gov (United States)

    Mrsny, Randall J; Brayden, David J

    2016-01-01

    This special issue of Tissue Barriers contains a series of reviews with the common theme of how biological barriers established at epithelial tissues limit the uptake of macromolecular therapeutics. By improving our functional understanding of these barriers, the majority of the authors have highlighted potential strategies that might be applied to the non-invasive delivery of biopharmaceuticals that would otherwise require an injection format for administration. Half of the articles focus on the potential of particular technologies to assist oral delivery of peptides, proteins and other macromolecules. These include use of prodrug chemistry to improve molecule stability and permeability, and the related potential for oral delivery of poorly permeable agents by cell-penetrating peptides and dendrimers. Safety aspects of intestinal permeation enhancers are discussed, along with the more recent foray into drug-device combinations as represented by intestinal microneedles and externally-applied ultrasound. Other articles highlight the crossover between food research and oral delivery based on nanoparticle technology, while the final one provides a fascinating interpretation of the physiological problems associated with subcutaneous insulin delivery and how inefficient it is at targeting the liver.

  7. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

    Science.gov (United States)

    Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-12-01

    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  8. Genetic variations in radiation and chemotherapy drug action pathways and survival in locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

    Directory of Open Access Journals (Sweden)

    Huai Liu

    Full Text Available BACKGROUND AND PURPOSE: Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC. The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. MATERIAL AND METHODS: Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR analysis was performed to detect potential gene-gene interaction. RESULTS: After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001. The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010, MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021, MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001 and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026 genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms. CONCLUSIONS: Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.

  9. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    Directory of Open Access Journals (Sweden)

    Scanlon SA

    2011-12-01

    Full Text Available Samantha A Scanlon1, Joseph A Murray1,21Department of Internal Medicine, 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAAbstract: Celiac disease (CD is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions.Keywords: immune-mediated enteropathy, gliadin, gluten, epidemiology, CD diagnosis, therapy

  10. Opening the door to innovation.

    Science.gov (United States)

    Schuurman, Janine; Graus, Yvo F; Labrijn, Aran F; Ruuls, Sigrid; Parren, Paul W H I

    2014-01-01

    Open innovation is the new buzz, with initiatives popping up left and right. Here, we give a personal perspective on a very successful, knowledge-driven innovation initiated in an academia- industry alliance, which culminated in technology platforms that enable the generation of therapeutic antibodies with novel properties. To start, we provide a general background on open innovation in the drug development field.

  11. 19th International School on Condensed Matter Physics (ISCMP): Advances in Nanostructured Condensed Matter: Research and Innovations

    International Nuclear Information System (INIS)

    2017-01-01

    We are pleased to introduce the Proceedings of the 19 th International School on Condensed Matter Physics “Advances in Nanostructured Condensed Matter: Research and Innovations” (19 th ISCMP). The school was held from August 28 th till September 2 nd , 2016 in Varna, Bulgaria. It was organized by the Institute of Solid State Physics of the Bulgarian Academy of Sciences (ISSP-BAS), and took place at one of the fine resorts on the Bulgarian Black Sea “Saints Constantine and Helena”. The aim of this international school is to bring together top experimentalists and theoreticians, with interests in interdisciplinary areas, with the younger generation of scientists, in order to discuss current research and to communicate new forefront ideas. This year special focus was given to discussions on membrane biophysics and quantum information, also not forgotten were some traditionally covered areas, such as characterization of nanostructured materials. Participants from 12 countries presented 28 invited lectures, 12 short oral talks and 44 posters. The hope of the organizing committee is that the 19 th ISCMP provided enough opportunities for direct scientific contacts, interesting discussions and interactive exchange of ideas between the participants. The nice weather certainly helped a lot in this respect. The editors would like to thank all authors for their high-quality contributions and the members of the international program committee for their commitment. The papers submitted for publication in the Proceedings were refereed according to the publishing standards of the Journal of Physics: Conference Series. The Editorial Committee members are very grateful to the Journal’s staff for the continuous fruitful relations and for giving us the opportunity to present the work from the 19 th ISCMP. Prof. DSc Hassan Chamati, Assist. Prof. Dr. Alexander A. Donkov, Assoc. Prof. Dr. Julia Genova, and Assoc. Prof. Dr. Emilia Pecheva (paper)

  12. Medical innovation laws: an unnecessary innovation.

    Science.gov (United States)

    Richards, Bernadette

    2016-06-01

    Objective This paper aims to demonstrate that any suggestion that there is a need for specific innovation laws is flawed. Innovation is central to good medical practice and is adequately supported by current law. Methods The paper reviews the nature of medical innovation and outlines recent attempts in the UK to introduce specific laws aimed at 'encouraging' and 'supporting' innovation. The current legal framework is outlined and the role of the law in relation to medical innovation explored. Results The analysis demonstrates the cyclic relationship between medical advancement and the law and concludes that there is no requirement for specific innovation laws. Conclusions The law not only supports innovation and development in medical treatment but encourages it as central to a functioning medical system. There is no need to introduce specific laws aimed at medical innovation; to do so represents an unnecessary legal innovation and serves to complicate matters. What is known about the topic? Over recent months, there has been a great deal of discussion surrounding the law in the context of medical innovation. This was driven by the attempts in the UK to introduce specific laws in the Medical Innovation Bill. The general subject matter - negligence and the expected standard of care in the provision of treatment - is very well understood, but not in cases where the treatment can be described as innovative. The general rhetoric in both the UK and Australia around the Medical Innovation Bill demonstrates a lack of understanding of the position of the law with regards to innovative treatment. What does this paper add? This paper adds clarity to the debate. It presents the law and explains the manner in which the law can operate around innovative treatment. The paper asserts that medical innovation is both supported and encouraged by existing legal principles. What are the implications for practitioners? The paper presents an argument that can guide the policy position

  13. Insulin-like plant proteins as potential innovative drugs to treat diabetes-The Moringa oleifera case study.

    Science.gov (United States)

    Paula, P C; Oliveira, J T A; Sousa, D O B; Alves, B G T; Carvalho, A F U; Franco, O L; Vasconcelos, I M

    2017-10-25

    Various plant species have long been used in traditional medicine worldwide to treat diabetes. Among the plant-based compounds with hypoglycemic properties, studies on insulin-like proteins isolated from leaves, fruits and seeds are rarely reported in the relevant literature. Our research group has been investigating the presence of insulin-like proteins in Moringa oleifera, a plant species native to India, and we have obtained a leaf protein isolate and semi-purified derived fractions, as well as a seed coat protein fraction (Mo-SC), with hypoglycemic activity in chemically induced diabetic mice that have increased tolerance to orally administered glucose. Equally importantly, Mo-SC possesses insulin-like antigenic epitopes. In this context, the present review aims to highlight that prospection of insulin-like proteins in plants is of the utmost importance both for finding new drugs for the treatment of diabetes and for shedding light on the mechanisms involved in diabetes. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Projects to accelerate the practical use of innovative medical devices to collaborate with TWIns, Center for Advanced Biomedical Sciences, Waseda University and School of Engineering, The University of Tokyo].

    Science.gov (United States)

    Niimi, Shingo; Umezu, Mitsuo; Iseki, Hiroshi; Harada, Hiroshi Kasanuki Noboru; Mitsuishi, Mamoru; Kitamori, Takehiko; Tei, Yuichi; Nakaoka, Ryusuke; Haishima, Yuji

    2014-01-01

    Division of Medical Devices has been conducting the projects to accelerate the practical use of innovative medical devices to collaborate with TWIns, Center for Advanced Biomedical Sciences, Waseda University and School of Engineering, The University of Tokyo. The TWIns has been studying to aim at establishment of preclinical evaluation methods by "Engineering Based Medicine", and established Regulatory Science Institute for Medical Devices. School of Engineering, The University of Tokyo has been studying to aim at establishment of assessment methodology for innovative minimally invasive therapeutic devices, materials, and nanobio diagnostic devices. This report reviews the exchanges of personnel, the implement systems and the research progress of these projects.

  15. Measuring Manufacturing Innovativeness

    DEFF Research Database (Denmark)

    Blichfeldt, Henrik; Knudsen, Mette Præst

    2017-01-01

    Globalization and customization increases the pressure on manufacturing companies, and the ability to provide innovativeness is a potential source of competitive advantage. This paper positions the manufacturing entity in the innovation process, and investigates the relation between innovation vers...... technology and organizational concepts. Based on Danish survey data from the European Manufacturing Survey (EMS-2015) this paper finds that there is a relation between innovative companies, and their level of technology and use of organizational concepts. Technology and organizational concepts act...... as manufacturing levers to support the manufacturing and production system to provide innovativeness. The managerial implication lies in building manufacturing capabilities to support the innovative process, by standardization, optimization and creating stability in combination with automation and advanced...

  16. Describing the implementation of an innovative intervention and evaluating its effectiveness in increasing research capacity of advanced clinical nurses: using the consolidated framework for implementation research.

    Science.gov (United States)

    McKee, Gabrielle; Codd, Margaret; Dempsey, Orla; Gallagher, Paul; Comiskey, Catherine

    2017-01-01

    Despite advanced nursing roles having a research competency, participation in research is low. There are many barriers to participation in research and few interventions have been developed to address these. This paper aims to describe the implementation of an intervention to increase research participation in advanced clinical nursing roles and evaluate its effectiveness. The implementation of the intervention was carried out within one hospital site. The evaluation utilised a mixed methods design and a implementation science framework. All staff in advanced nursing roles were invited to take part, all those who were interested and had a project in mind could volunteer to participate in the intervention. The intervention consisted of the development of small research groups working on projects developed by the nurse participant/s and supported by an academic and a research fellow. The main evaluation was through focus groups. Output was analysed using thematic analysis. In addition, a survey questionnaire was circulated to all participants to ascertain their self-reported research skills before and after the intervention. The results of the survey were analysed using descriptive statistics. Finally an inventory of research outputs was collated. In the first year, twelve new clinical nurse-led research projects were conducted and reported in six peer reviewed papers, two non-peer reviewed papers and 20 conference presentations. The main strengths of the intervention were its promptness to complete research, to publish and to showcase clinical innovations. Main barriers identified were time, appropriate support from academics and from peers. The majority of participants had increased experience at scientific writing and data analysis. This study shows that an intervention, with minor financial resources; a top down approach; support of a hands on research fellow; peer collaboration with academics; strong clinical ownership by the clinical nurse researcher

  17. Alternating treatment with didanosine and zidovudine versus either drug alone for the treatment of advanced HIV infection. The Alter Study. Nordic HIV Therapy Group

    DEFF Research Database (Denmark)

    Gerstoft, J; Melander, H; Bruun, J N

    1997-01-01

    The efficacy and safety of an alternating regime with zidovudine and didanosine versus treatment with either drug alone were investigated in a randomized, open, controlled trial, 552 patients with advanced HIV infection, 47% of whom had received prior treatment with zidovudine, were enrolled...... distributed between the 3 treatment groups. In the subgroup of patients with a CD4 count

  18. Innovation Production Models

    Directory of Open Access Journals (Sweden)

    Tamam N. Guseinova

    2016-01-01

    Full Text Available The article is dedicated to the study of the models of production of innovations at enterprise and state levels. The shift towards a new technology wave induces a change in systems of division of labour as well as establishment of new forms of cooperation that are reflected both in theory and practice of innovation policy and management. Within the scope of the research question we have studied different generation of innovation process, starting with simple linear models - "technology push" and "market pull" - and ending with a complex integrated model of open innovations. There are two organizational models of innovation production at the enterprise level: start-ups in the early stages of their development and ambidextrous organizations. The former are prone to linear models of innovation process, while the latter create innovation within more sophisticated inclusive processes. Companies that effectuate reciprocal ambidexterity stand out from all the rest, since together with start-ups, research and development centres, elements of innovation infrastructure and other economic agents operating in the same value chain they constitute the core of most advanced forms of national innovation systems, namely Triple Helix and Quadruple Helix systems. National innovation systems - models of innovation production at the state level - evolve into systems with a more profound division of labour that enable "line production" of innovations. These tendencies are closely related to the advent and development of the concept of serial entrepreneurship that transforms entrepreneurship into a new type of profession. International experience proves this concept to be efficient in various parts of the world. Nevertheless, the use of above mentioned models and concepts in national innovation system should be justified by socioeconomic conditions of economic regions, since they determine the efficiency of implementation of certain innovation processes and

  19. The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

    Science.gov (United States)

    Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

    2014-11-01

    Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

  20. Innovation af innovation

    DEFF Research Database (Denmark)

    Harste, Gorm

    2009-01-01

    , at innovation af innovationen forsøges gennemført på en måde, hvor tiden kræves at forholde sig til sin egen tidslighed i form af fremtid, nutid, fortid og ikke mindst i form af samtidighed. I tiden skal vi iagttage, hvordan vi iagttager tiden. Vi dobbelt-koder tiden på samme måde, som forskning forsker i...... organisationssystemerne. De to typer systemer kan noget helt bestemt med fænomenet tid. De kan synkronisere. Analyseres organisationssystemer ser vi, imidlertid at innovation kræver ro. Stærkt innovative systemer er militærsystemet og kunstsystemet, der også inddrages, og hvor vi ser paradokset mellem innovation og...... involution. Tid er med et medium og ikke et lufttomt rum. Tid er end ikke en gasart, men udgør et solidt fluidum, som samfundet bader i og flyder i, konstant i bevægelse. Reformer forudsætter former, og innovation forudsætter involution. Kun sådan muliggøres evolution....

  1. Orchestrating innovation

    NARCIS (Netherlands)

    Berkers, F.T.H.M.; Klein Woolthuis, R.J.A.; Boer, J. de

    2015-01-01

    Orchestrating Innovation increases the probability of success, minimizing the probability of failure of technological innovations by creating sustained societal and economic value. Orchestrating innovation propagates to take into account and actively involve all relevant stakeholders of the (future)

  2. Recent advances in porous nanoparticles for drug delivery in antitumoral applications: inorganic nanoparticles and nanoscale metal-organic frameworks.

    Science.gov (United States)

    Baeza, Alejandro; Ruiz-Molina, Daniel; Vallet-Regí, María

    2017-06-01

    Nanotechnology has provided new tools for addressing unmet clinical situations, especially in the oncology field. The development of smart nanocarriers able to deliver chemotherapeutic agents specifically to the diseased cells and to release them in a controlled way has offered a paramount advantage over conventional therapy. Areas covered: Among the different types of nanoparticle that can be employed for this purpose, inorganic porous materials have received significant attention in the last decade due to their unique properties such as high loading capacity, chemical and physical robustness, low toxicity and easy and cheap production in the laboratory. This review discuss the recent advances performed in the application of porous inorganic and metal-organic materials for antitumoral therapy, paying special attention to the application of mesoporous silica, porous silicon and metal-organic nanoparticles. Expert opinion: The use of porous inorganic nanoparticles as drug carriers for cancer therapy has the potential to improve the life expectancy of the patients affected by this disease. However, much work is needed to overcome their drawbacks, which are aggravated by their hard nature, exploiting the advantages offered by highly the ordered pore network of these materials.

  3. Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

    Science.gov (United States)

    Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-06-01

    From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

  4. Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

    Science.gov (United States)

    Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-11-21

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  5. Discovery and Innovation: Advanced Search

    African Journals Online (AJOL)

    Search tips: Search terms are case-insensitive; Common words are ignored; By default only articles containing all terms in the query are returned (i.e., AND is implied); Combine multiple words with OR to find articles containing either term; e.g., education OR research; Use parentheses to create more complex queries; e.g., ...

  6. Discovery and Innovation: Advanced Search

    African Journals Online (AJOL)

    ... containing either term; e.g., education OR research; Use parentheses to create more complex queries; e.g., archive ((journal OR conference) NOT theses); Search for an exact phrase by putting it in quotes; e.g., "open access publishing"; Exclude a word by prefixing it with - or NOT; e.g. online -politics or online NOT politics ...

  7. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Innovation In Music

    OpenAIRE

    2014-01-01

    The music industry is a fast moving field with new technology and methodological advances combining to catalyse innovations all the time. 'Innovation in Music 2013' was an international conference exploring this topic, held in December 2013 in York, Uk. The event covered specific and cross-disciplinary aspects of the music industry including music creation, technology, production and business, sound engineering, mastering, post production and sound design, games music and cross-disciplinary t...

  9. Orchestrating innovation

    OpenAIRE

    Berkers, F.T.H.M.; Klein Woolthuis, R.J.A.; Boer, J. de

    2015-01-01

    Orchestrating Innovation increases the probability of success, minimizing the probability of failure of technological innovations by creating sustained societal and economic value. Orchestrating innovation propagates to take into account and actively involve all relevant stakeholders of the (future) ecosystem in which the innovation will, can or has to be adopted.

  10. Mindful innovation

    DEFF Research Database (Denmark)

    Olsen, Poul Bitsch

    2008-01-01

    Mindful innovation is an approach to innovation that pays attention to people's experience in an organization rather than to formal organization or social role.......Mindful innovation is an approach to innovation that pays attention to people's experience in an organization rather than to formal organization or social role....

  11. Innovative didaktik

    DEFF Research Database (Denmark)

    Lund, Birthe

    Innovative didaktik. This deals with innovative didaktik from at methodological point of view in three ways - how to define the concept, how to develop it and how analyse it. Issues analysed: How to create innovative students? How to create innovative learning envoriments? These are core question...... in "Projekt Innovativ didaktik". The hidden curriculum is to inspire students to develop entreprenuership and creativty....

  12. The Innovating Self

    DEFF Research Database (Denmark)

    Hellström, Tomas; Hellström, Christina; Berglund, Henrik

    2002-01-01

    This paper explores the relevance of the concept of self in the process of independent technological innovation. In‐depth interviews were conducted with technological innovators from start‐up firms in IT, biotech and advanced services concerning the subjective and social forms of engagement...... in the innovation process. Emerging factors in the interview data revealed aspects pertaining to the innovator’s reflexive self‐conception, innovator ego‐involvement in the venture, forms of commitment and control, personal and social stakes, and various self‐oriented cognitive strategies. It is argued...... that the self‐concept allows the innovator to come into view as a social and subjective being who is involved in reflexive activities such as dynamic role‐taking, “is” vs “ought” reflections and social negotiations....

  13. Managing Innovation to Maximize Value Along the Discovery-Translation-Application Continuum.

    Science.gov (United States)

    Waldman, S A; Terzic, A

    2017-01-01

    Success in pharmaceutical development led to a record 51 drugs approved in the past year, surpassing every previous year since 1950. Technology innovation enabled identification and exploitation of increasingly precise disease targets ensuring next generation diagnostic and therapeutic products for patient management. The expanding biopharmaceutical portfolio stands, however, in contradistinction to the unsustainable costs that reflect remarkable challenges of clinical development programs. This annual Therapeutic Innovations issue juxtaposes advances in translating molecular breakthroughs into transformative therapies with essential considerations for lowering attrition and improving the cost-effectiveness of the drug-development paradigm. Realizing the discovery-translation-application continuum mandates a congruent approval, adoption, and access triad. © 2016 ASCPT.

  14. An RNA polymerase II-driven Ebola virus minigenome system as an advanced tool for antiviral drug screening.

    Science.gov (United States)

    Nelson, Emily V; Pacheco, Jennifer R; Hume, Adam J; Cressey, Tessa N; Deflubé, Laure R; Ruedas, John B; Connor, John H; Ebihara, Hideki; Mühlberger, Elke

    2017-10-01

    Ebola virus (EBOV) causes a severe disease in humans with the potential for significant international public health consequences. Currently, treatments are limited to experimental vaccines and therapeutics. Therefore, research into prophylaxis and antiviral strategies to combat EBOV infections is of utmost importance. The requirement for high containment laboratories to study EBOV infection is a limiting factor for conducting EBOV research. To overcome this issue, minigenome systems have been used as valuable tools to study EBOV replication and transcription mechanisms and to screen for antiviral compounds at biosafety level 2. The most commonly used EBOV minigenome system relies on the ectopic expression of the T7 RNA polymerase (T7), which can be limiting for certain cell types. We have established an improved EBOV minigenome system that utilizes endogenous RNA polymerase II (pol II) as a driver for the synthesis of minigenome RNA. We show here that this system is as efficient as the T7-based minigenome system, but works in a wider range of cell types, including biologically relevant cell types such as bat cells. Importantly, we were also able to adapt this system to a reliable and cost-effective 96-well format antiviral screening assay with a Z-factor of 0.74, indicative of a robust assay. Using this format, we identified JG40, an inhibitor of Hsp70, as an inhibitor of EBOV replication, highlighting the potential for this system as a tool for antiviral drug screening. In summary, this updated EBOV minigenome system provides a convenient and effective means of advancing the field of EBOV research. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Innovative spectrophotometric methods for simultaneous estimation of the novel two-drug combination: Sacubitril/Valsartan through two manipulation approaches and a comparative statistical study

    Science.gov (United States)

    Eissa, Maya S.; Abou Al Alamein, Amal M.

    2018-03-01

    Different innovative spectrophotometric methods were introduced for the first time for simultaneous quantification of sacubitril/valsartan in their binary mixture and in their combined dosage form without prior separation through two manipulation approaches. These approaches were developed and based either on two wavelength selection in zero-order absorption spectra namely; dual wavelength method (DWL) at 226 nm and 275 nm for valsartan, induced dual wavelength method (IDW) at 226 nm and 254 nm for sacubitril and advanced absorbance subtraction (AAS) based on their iso-absorptive point at 246 nm (λiso) and 261 nm (sacubitril shows equal absorbance values at the two selected wavelengths) or on ratio spectra using their normalized spectra namely; ratio difference spectrophotometric method (RD) at 225 nm and 264 nm for both of them in their ratio spectra, first derivative of ratio spectra (DR1) at 232 nm for valsartan and 239 nm for sacubitril and mean centering of ratio spectra (MCR) at 260 nm for both of them. Both sacubitril and valsartan showed linearity upon application of these methods in the range of 2.5-25.0 μg/mL. The developed spectrophotmetric methods were successfully applied to the analysis of their combined tablet dosage form ENTRESTO™. The adopted spectrophotometric methods were also validated according to ICH guidelines. The results obtained from the proposed methods were statistically compared to a reported HPLC method using Student t-test, F-test and a comparative study was also developed with one-way ANOVA, showing no statistical difference in accordance to precision and accuracy.

  16. Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region.

    Science.gov (United States)

    Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Hamano, Nobuhito; Li, Shyh-Dar; Chougule, Mahavir; Shoyele, Sunday A; Gupta, Umesh; Ajazuddin; Alexander, Amit

    2018-06-01

    Brain is supposed to be the most complicated part of the body which is very far from the reach of drug moieties. The drug entry in to the brain region depends upon various factors, and among those, the blood-brain-barrier remains the most prominent one. This barrier restricts the entry of almost all the drug and most of the essential biological components like proteins, peptides, etc. and hinders treatment of the CNS disorders. Alzheimer Disease (AD) is one such brain disorder, more specifically a neurodegenerative disorder which primarily affects the older adults. Areas covered: From solubility enhancement to targeted delivery, the nanoparticulate system became the answer for almost all the criticality related to drug delivery. Hence, nanoparticulate drug carrier system has been widely utilizing to remove the hurdles of brain drug delivery. Keeping this in mind, we have underlined the proficiencies of the nanocarrier systems which claim to improve the drug efficacy for the treatment of the AD. Expert opinion: The nanotechnological approaches are highly exploited by the researchers to enhance the drug permeation across the BBB to improve its bioavailability and efficacy by protecting the drug from peripheral degradation. However, still in this area of drug targeting provides vast scope for discoveries towards the enhancement of drug efficacy through surface modifications, site specification, reduced toxicity of the nanocarrier system and so on.

  17. Drug promotion practices: A review.

    Science.gov (United States)

    Jacob, Nilan T

    2018-01-18

    Over the years, the pharmaceutical industry has been at the forefront of research and innovation in drug discovery and development. The process of drug discovery extending from preclinical studies to multicentric clinical trials and postmarketing phase is a costly affair running into billions of dollars. On the flip side, not all investigational molecules clear the trial phases and get approved, which puts pressure on the manufacturers to maximize the profit from approved drugs. It is in this key area that the practice of drug promotion plays its role. The World Health Organization defines drug promotion as "all informational and persuasive activities by manufacturers and distributors, the effect of which is to influence the prescription, supply, purchase or use of medicinal drugs". With its humble intent of creating awareness among healthcare professionals and updating their knowledge on recent advances in treatment options, drug promotion has been an important tool, but gradually it has evolved to embrace aggressive marketing strategies and sometimes unethical business and scientific practices where the need for profit-making eclipses commitment to patient care and scientific exploration. In this review, we discuss the evolution of drug promotion practices, the various types, its merits and demerits, the influence of drug promotion on physician prescribing behaviour, the role of regulatory bodies, unethical promotional practices and finally summarize with future directions. © 2018 The British Pharmacological Society.

  18. Innovation in nuclear technology

    International Nuclear Information System (INIS)

    Bertel, E.

    2007-01-01

    Innovation has been a driving force for the success of nuclear energy and remains essential for its future. For the continued safe and economically effective operation and maintenance of existing nuclear systems, and to meet the goals set out by projects aiming at designing and implementing advanced systems for the future, efficient innovation systems are needed. Consequently, analysing innovation systems is essential to understand their characteristics and enhance their performance in the nuclear sector. Lessons learnt from innovation programmes that have already been completed can help enhance the effectiveness of future programmes. The analysis of past experience provides a means for identifying causes of failure as well as best practices. Although national and local conditions are important factors, the main drivers for the success of innovative endeavors are common to all countries. Cooperation and coordination among the various actors are major elements promoting success. All interested stakeholders, including research organisations, industrial actors, regulators and civil society, have a role to play in supporting the success of innovation, but governments are an essential trigger, especially for projects with long durations and very ambitious objectives. Governments have a major role to play in promoting innovation because they are responsible for the overall national energy policy which sets the stage for the eventual deployment of innovative products and processes. Moreover, only governments can create the stable legal and regulatory framework favourable to the undertaking and successful completion of innovation programmes. International organisations such as the NEA may help enhance the effectiveness of national policies and innovation programmes by providing a forum for exchanging information, facilitating multilateral collaboration and joint endeavors, and offering technical support for the management of innovative programmes

  19. In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

    Science.gov (United States)

    Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

    2014-08-01

    The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI conditioning regimens for allo-SCT in advanced-phase CML.

  20. The pharmacotherapy of the HeartMate II, a continuous flow left ventricular assist device, in patients with advanced heart failure: integration of disease, device, and drug.

    Science.gov (United States)

    Jennings, Douglas L; Chambers, Rachel M; Schillig, Jessica M

    2010-10-01

    Advanced heart failure continues to be a significant cause of morbidity and mortality in the US. Patients with advanced heart failure have a poor prognosis without cardiac transplantation. The use of left ventricular assist devices (LVADs) as destination therapy for these patients is therefore expected to increase in the coming years as technology advances. The HeartMate II, a continuous flow implantable device, is currently the only LVAD that has been approved by the Food and Drug Administration for destination therapy in patients with advanced heart failure. The pharmacotherapy associated with this device is very complex and, therefore, the need for expertly trained clinical pharmacists to care for this expanding patient population will also likely increase. Unfortunately, most pharmacists are unfamiliar with the effect of LVADs on the physiology and pharmacotherapy of a patient's heart failure. The purpose of this article is to give clinical pharmacists an introduction to the most common pharmacotherapeutic issues for patients with LVADs and present practical solutions for managing common drug therapy problems.

  1. Microchips and controlled-release drug reservoirs.

    Science.gov (United States)

    Staples, Mark

    2010-01-01

    This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.

  2. Science Innovation

    Science.gov (United States)

    EPA provides innovative research activities that help transform the protection of human health and the environment with high-risk, high-reward Pathfinder Innovation Projects, the P3 student competition, and low-cost air monitoring.

  3. Technology Innovation

    Science.gov (United States)

    EPA produces innovative technologies and facilitates their creation in line with the Agency mission to create products such as the stormwater calculator, remote sensing, innovation clusters, and low-cost air sensors.

  4. Political innovations

    DEFF Research Database (Denmark)

    Sørensen, Eva

    2017-01-01

    are mainly interested in assessing and promoting innovations in public service delivery, but have paid little or no attention to the need for innovations in polity, politics and policy. This article develops a research agenda for studying innovations in political institutions, in the political process...... and in policy outputs. It proposes a number of research themes related to political innovations that call for scholarly attention, and identifies push and pull factors influencing the likelihood that these themes will be addressed in future research....

  5. Innovation hubs

    DEFF Research Database (Denmark)

    O´Hara, J.; Hansen, Poul H. Kyvsgård; Turner, N.

    2008-01-01

    "Whilst ‘incremental innovation' is an imperative for the short-to-medium term success of a company, there is also a need for companies to engage in innovation activity that goes beyond the incremental in order to guarantee long-term success. However, such ‘radical innovation' (RI) poses new chal...

  6. Brugerdreven innovation

    DEFF Research Database (Denmark)

    Helms, Niels Henrik; Larsen, Lasse Juel

    2007-01-01

    På et generelt plan er vores afsæt et opgør med traditionelle modeller for kreativitet og innovation. Artiklen mener, at brugerdreven innovation ikke bare en god idé, men en beskrivelse af, hvordan innovation finder sted. Vores afsæt er interaktionsdesign, hvor vi bygger på den antagelse...

  7. A Strategy for Innovative Teaching.

    Science.gov (United States)

    Hagan, G. W.

    Within the context of a discussion of the challenges facing Canadian higher education, this paper reviews some of the innovative approaches to student retention, curriculum development, and modularization in use at Mohawk College in Ontario. After stressing the need for innovation in advanced technological education in Canada, the paper offers an…

  8. HIMSS Venture+ Forum and HX360 Provide Industry View of Health Technology Innovation, Startup and Investment Activity; Advancing the New Model of Care.

    Science.gov (United States)

    Burde, Howard A; Scarfo, Richard

    2015-01-01

    Presented by HIMSS, the Venture+ Forum program and pitch competition provides a 360-degree view on health technology investing and today's top innovative companies. It features exciting 3-minute pitch presentations from emerging and growth-stage companies, investor panels and a networking reception. Recent Venture+ Forum winners include TowerView Health, Prima-Temp, ActuaiMeds and M3 Clinician. As an industry catalyst for health IT innovation and business-building resource for growing companies and emerging technology solutions, HIMSS has co-developed with A VIA, a new initiative that addresses how emerging technologies, health system business model changes and investment will transform the delivery of care. HX360 engages senior healthcare leaders, innovation teams, investors and entrepreneurs around the vision of transforming healthcare delivery by leveraging technology, process and structure.

  9. Indigenous innovation in China

    DEFF Research Database (Denmark)

    Jin, Jun; Slepniov, Dmitrij

    2012-01-01

    champions. However, recently growing number of Chinese companies are seeking to create a foundation for growth and development based on innovation. As a result of this, many of them spread their operations to the countries of the traditional industrial ‘triad’ of North America, Europe and Japan to capture...... a foothold in these markets and to tap into the advanced technologies and concepts originating from this developed context. Another category of Chinese companies includes those who seek to move from routine transactional tasks to more innovation-intensive concepts while remaining in China and relying...... on their own in-house resources. The development and implementation of indigenous innovation solutions for these companies is an imperative which has not been adequately addressed in the literature. Therefore, by employing an explorative case of a Chinese company behind an innovative logistics concept...

  10. Service innovation in China

    DEFF Research Database (Denmark)

    Slepniov, Dmitrij; Jin, Jun

    2014-01-01

    Purpose – The aim of this paper is to advance our understanding of service innovation in China and to identify the major drivers and impediments for manufacturing companies pushing into services in China. Design/methodology/approach – By employing an in-depth longitudinal case of a Chinese company...... Chinese cities. Both internal and external factors played a significant role in influencing the development and implementation of service innovation in the case. The paper details and discusses the factors that affect service innovation in China. Research Limitations – The study is exposed...... in informing our expectations about the push of many Chinese manufacturing companies into services. The paper provides insights into the development and diffusion of service innovation in many fast transforming industrial companies in China. Lessons for other developing countries can also be drawn from...

  11. Successful introduction of innovation

    International Nuclear Information System (INIS)

    Schoots, K.; Jeeninga, H.

    2008-01-01

    The introduction of new technology sometimes proceeds sluggishly due to discontinuity in incentive schemes. Estimating in advance which means are required, what a realistic time span is for the incentive scheme and continuing this scheme until the technology is marketable can significantly increase the success of innovation trajectories. [mk] [nl

  12. DUAL-MODE PROPULSION SYSTEM ENABLING CUBESAT EXPLORATION OF THE SOLAR SYSTEM NASA Innovative Advanced Concepts (NIAC) Phase I Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Nathan Jerred; Troy Howe; Adarsh Rajguru; Dr. Steven Howe

    2014-06-01

    -based systems. The second scenario allows for the production of electrical power, which is then available for electric-based propulsion. Additionally, once at location the production of electrical power can be dedicated to the payload’s communication system for data transfer. Ultimately, the proposed dual-mode propulsion platform capitalizes on the benefits of two types of propulsion methods – the thrust of thermal propulsion ideal for quick orbital maneuvers and the specific impulse of electric propulsion ideal for efficient inter-planetary travel. Previous versions of this RTR-based concept have been studied for various applications [NETS 1-3]. The current version of this concept is being matured through a NASA Innovative Advanced Concepts (NIAC) Phase I grant, awarded for FY 2014. In this study the RTR concept is being developed to deliver a 6U CubeSat payload to the orbit of the Saturnian moon - Enceladus. Additionally, this study will develop an entire mission architecture for Enceladus targeting a total allowable launch mass of 1,000 kg.

  13. Framing Innovation

    DEFF Research Database (Denmark)

    Haase, Louise Møller; Laursen, Linda Nhu

    2017-01-01

    Designing a remarkable product innovation is a difficult challenge, which businesses today continuously are striving to tackle. This challenge is particularly present in the early phase of innovation, where the main product concept and frames of the innovation is determined. As a main challenge...... in the early phase is the reasoning process; innovation team are faced with open- ended ill-defines problems, where they need to make decisions about an unknown future having only incomplete, ambiguous and contradicting insights available. We study the reasoning of experts, how they frame to make sense of all...... the insights and create a basis for decision making in relation to a new project. Based on case studies of five innovative products from various industries, we suggest a Product Reasoning Model for understanding reasoning and envisioning of new product innovations in the early phases of innovation....

  14. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

    Science.gov (United States)

    Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

    2017-04-01

    Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

  15. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  16. Business Process Innovation using the Process Innovation Laboratory

    DEFF Research Database (Denmark)

    Møller, Charles

    for practical applications has not been identified. The aim of this paper is to establish a conceptual framework for business process innovation in the supply chain based on advanced enterprise systems. The main approach to business process innovation in this context is to create a new methodology for exploring...... process models and patterns of applications. The paper thus presents a new concept for business process innovation called the process innovation laboratory a.k.a. the ?-Lab. The ?-Lab is a comprehensive framework for BPI using advanced enterprise systems. The ?-Lab is a collaborative workspace...... for experimenting with process models and an explorative approach to study integrated modeling in a controlled environment. The ?-Lab facilitates innovation by using an integrated action learning approach to process modeling including contemporary technological, organizational and business perspectives....

  17. From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery.

    Science.gov (United States)

    Ferreira, Leonardo G; Andricopulo, Adriano D

    2017-01-01

    Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery

    Directory of Open Access Journals (Sweden)

    Cervantes Serena

    2009-06-01

    Full Text Available Abstract Background Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes. Results After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells. Conclusion This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.

  19. Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples.

    Science.gov (United States)

    Lin, Shan-Yang; Wang, Shun-Li

    2012-04-01

    The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Enzalutamide and blocking androgen receptor in advanced prostate cancer: lessons learnt from the history of drug development of antiandrogens.

    Science.gov (United States)

    Ito, Yusuke; Sadar, Marianne D

    2018-01-01

    Enzalutamide is a nonsteroidal antiandrogen for the treatment of metastatic castration-resistant prostate cancer (mCRPC) both before and after chemotherapy. Enzalutamide is more effective than its predecessor bicalutamide, which was analyzed in head-to-head studies of patients with CRPC. This family of nonsteroidal antiandrogens is now comprised of four drugs approved by the US Food and Drug Administration with two investigational drugs in clinical trials. Antiandrogens have been employed clinically for more than five decades to provide a rich resource of information. Steady-state concentration minimums (C min or trough) in the range of ~1-13 μg/mL are measured in patients at therapeutic doses. Interestingly, enzalutamide which is considered to have strong affinity for the androgen receptor (AR) requires C min levels >10 μg/mL. The sequence of antiandrogens and the clinical order of application in regard to other drugs that target the androgen axis remain of high interest. One novel first-in-class drug, called ralaniten, which binds to a unique region in the N-terminus domain of both the full-length and the truncated constitutively active splice variants of the AR, is currently in clinical trials for patients who previously received abiraterone, enzalutamide, or both. This highlights the trend to develop drugs with novel mechanisms of action and potentially differing mechanisms of resistance compared with antiandrogens. Better and more complete inhibition of the transcriptional activity of the AR appears to continue to provide improvements in the clinical management of mCRPC.

  1. Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project.

    Science.gov (United States)

    Moreno, Lucas; Caron, Hubert; Geoerger, Birgit; Eggert, Angelika; Schleiermacher, Gudrun; Brock, Penelope; Valteau-Couanet, Dominique; Chesler, Louis; Schulte, Johannes H; De Preter, Katleen; Molenaar, Jan; Schramm, Alexander; Eilers, Martin; Van Maerken, Tom; Johnsen, John Inge; Garrett, Michelle; George, Sally L; Tweddle, Deborah A; Kogner, Per; Berthold, Frank; Koster, Jan; Barone, Giuseppe; Tucker, Elizabeth R; Marshall, Lynley; Herold, Ralf; Sterba, Jaroslav; Norga, Koen; Vassal, Gilles; Pearson, Andrew Dj

    2017-08-01

    Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.

  2. Framing Innovation

    DEFF Research Database (Denmark)

    Haase, Louise Møller; Laursen, Linda Nhu

    2017-01-01

    Designing a remarkable product innovation is a difficult challenge, which businesses today continuously are striving to tackle. This challenge is particularly present in the early phase of innovation, where the main product concept and frames of the innovation is determined. As a main challenge...... in the early phase is the reasoning process; innovation team are faced with open-ended ill-defines problems, where they need to make decisions about an unknown future having only incomplete, ambiguous and contradicting insights available. We study the reasoning of experts, how they frame to make sense of all...... the insights and create a basis for decision making in relation to a new project. Based on case studies of five innovative products from various industries, we suggest a Product Reasoning Model for understanding reasoning and envisioning of new product innovations in the early phases...

  3. Online Innovation

    DEFF Research Database (Denmark)

    Vujovic, Sladjana; Ulhøi, John Parm

    2008-01-01

      Purpose - The aim of this paper is to investigate the role of online networking during the innovation process, including its role(s) in communication, cooperation and coordination. The paper neither implicitly assumes that online computer-based networking is a prerequisite for the innovation...... process nor denies the possibility that innovation can emerge and successfully survive without it. It merely presupposes that, in cases of innovation where information and communication technologies play a substantial role, non-proprietarity may offer an interesting alternative to innovations based...... on proprietary knowledge. Design/methodology/approach - The paper borrows from the theory of communities-of-practice, which takes into account social relations, contacts, and the transfer and incorporation of knowledge. Open source innovation is not the exclusive preserve of computer nerds, but also has...

  4. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  5. Drug Elucidation: Invertebrate Genetics Sheds New Light on the Molecular Targets of CNS Drugs

    Directory of Open Access Journals (Sweden)

    Donard S. Dwyer

    2014-07-01

    Full Text Available Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts.

  6. Financing Innovation

    OpenAIRE

    William R. Kerr; Ramana Nanda

    2014-01-01

    We review the recent literature on the financing of innovation, inclusive of large companies and new startups. This research strand has been very active over the past five years, generating important new findings, questioning some long-held beliefs, and creating its own puzzles. Our review outlines the growing body of work that documents a role for debt financing related to innovation. We highlight the new literature on learning and experimentation across multi-stage innovation projects and h...

  7. Innovative Strategy for Treatment of Lung Cancer: Inhalatory Codelivery of Anticancer Drugs and siRNA for Suppression of Cellular Resistance

    Science.gov (United States)

    2011-07-01

    attributed to a self-quenching effect of the drug ( Gaber 1995; Kwon 1997). Consequently, the registered fluorescence of the drug inside the cells was...Endocytosis and cationic cell-penetrating peptides--a merger of concepts and methods. Curr Pharm Des 11:3613-28. Gaber MH, Hong K, Huang SK

  8. Supplier Innovation

    DEFF Research Database (Denmark)

    Søberg, Peder Veng; Notman, Dorian Mark; Wæhrens, Brian Vejrum

    2017-01-01

    The prevailing research in supplier innovation has been conceptual or based on small data sets. The analysis of a large data set gives a clearer perspective on the actual type and degree of involvement of suppliers in the customer’s innovation process. The supplier perspective of the research...... counterbalances the customer bias that exists in the prevailing literature in this area. Similarly, the issue of the benefit of supplier involvement in the innovation/NPD process can be better understood. Manufacturing suppliers benefit financially from their involvement in the innovation/NPD process of their key...

  9. Responsive Innovation

    DEFF Research Database (Denmark)

    Pedersen, Carsten

    Although the importance of stakeholder networks has been recognized in recent years, a non-teleological model that incorporates their collective sensing into innovation processes has so far not been developed. Hence, this paper argues that traditional linear and sequential innovation models...... are insufficient in hypercompetitive environments. Instead, it is proposed that companies should ground their innovation processes in the collective sensing of frontline-employees and customers that operate around the organizational periphery. This frames the concept of responsive innovation, where key...... stakeholders engaged in the organization’s ongoing business activities collectively identify issues that central managers subsequently can resolve....

  10. Innovation @ NASA

    Science.gov (United States)

    Roman, Juan A.

    2014-01-01

    This presentation provides an overview of the activities National Aeronautics and Space Administration (NASA) is doing to encourage innovation across the agency. All information provided is available publicly.

  11. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

    Directory of Open Access Journals (Sweden)

    Smita Raghuvanshi

    2014-01-01

    Full Text Available Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

  12. How state and federal policies as well as advances in genome science contribute to the high cost of cancer drugs.

    Science.gov (United States)

    Ramsey, Scott D

    2015-04-01

    During a time when cancer drug prices are increasing at an unprecedented rate, a debate has emerged as to whether these drugs continue to provide good value. In this article I argue that this debate is irrelevant because under today's highly distorted market, prices will not be set with value considerations in mind. As an alternative, I suggest considering the "value" of three policy changes—Medicare's "average sales price plus 6 percent" payment program, laws that require insurance coverage of all new cancer drugs, and the Affordable Care Act—that are fueling manufacturers' willingness to set higher prices. More important than these issues, however, is the revolution that is occurring in molecular biology and its impact on scientists' ability to detect changes in the cancer genome. The lowered cost of discovery is driving more competitors into the market, which under distorted pricing paradoxically encourages drug makers to charge ever higher prices for their products. Project HOPE—The People-to-People Health Foundation, Inc.

  13. Direct coupling of electromembrane extraction to mass spectrometry - Advancing the probe functionality toward measurements of zwitterionic drug metabolites.

    Science.gov (United States)

    Rye, Torstein Kige; Fuchs, David; Pedersen-Bjergaard, Stig; Petersen, Nickolaj Jacob

    2017-08-29

    A triple-flow electromembrane extraction (EME) probe was developed and coupled directly to electrospray-ionization mass spectrometry (ESI-MS). Metabolic reaction mixtures (pH 7.4) containing drug substances and related metabolites were continuously drawn (20 μL/min) into the EME probe in one flow channel, and mixed inside the probe with 7.5 μL min -1 of 1 M formic acid as make-up flow from a second flow channel. Following this acidification, the drug substances and their related metabolites were continuously extracted by EME at 400 V, across a supported liquid membrane (SLM) comprising 2-nitrophenyl octyl ether (and for some experiments containing 30% triphenyl phosphate (TPP)), and into 20 μL min -1 of formic acid as acceptor phase, which was introduced through a third flow channel. The acceptor phase was pumped directly to the MS system, and the ion intensity of extracted analytes was followed continuously as function of time. The triple-flow EME probe was used for co-extraction of positively charged parent drugs and their zwitterionic drug metabolites (hydroxyzine and its carboxylic acid metabolite cetirizine; and vortioxetine and its carboxylic acid metabolite Lu AA34443). While the zwitterionic metabolites could not be extracted at pH 7.4, it was shown that by acidifying the sample solution the zwitterionic metabolites could be extracted effectively. Various extraction parameters like make-up flow, extraction voltage and SLM composition were optimized for simultaneous extraction of parent drugs and metabolites. It was found that TPP added to the SLM improved extraction efficiencies of certain drug metabolites. Finally the optimized and characterized triple-flow EME probe was used for online studying the in-vitro metabolism of hydroxyzine and vortioxetine by rat liver microsomes. Due to the automated pre-extraction acidification of the rat liver microsomal solutions, it was possible to continuously monitor formation of the zwitterionic drug

  14. Commercialization in Innovation Management

    DEFF Research Database (Denmark)

    Sløk-Madsen, Stefan Kirkegaard; Ritter, Thomas; Sornn-Friese, Henrik

    For any firm, the ultimate purpose of new product development is the commercialization of the new offerings. Despite its regular use in the product innovation and general management science literature, commercialization is only loosely defined and applied. This lack of conceptual clarity about...... the processes at the interface between product development and customer application is noteworthy as it hinders the theoretical development of the field. In this paper, we explore how research has advanced our understanding of commercialization in product innovation over a 30 year period by mapping different...

  15. Tokamak concept innovations

    International Nuclear Information System (INIS)

    1986-04-01

    This document contains the results of the IAEA Specialists' Meeting on Tokamak Concept Innovations held 13-17 January 1986 in Vienna. Although it is the most advanced fusion reactor concept the tokamak is not without its problems. Most of these problems should be solved within the ongoing R and D studies for the next generation of tokamaks. Emphasis for this meeting was placed on innovations that would lead to substantial improvements in a tokamak reactor, even if they involved a radical departure from present thinking

  16. 4D-QSAR: Perspectives in Drug Design

    Directory of Open Access Journals (Sweden)

    Carolina H. Andrade

    2010-05-01

    Full Text Available Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

  17. Drug repositioning: playing dirty to kill pain.

    Science.gov (United States)

    Bastos, Leandro Francisco Silva; Coelho, Márcio Matos

    2014-01-01

    The number of approved new molecular entity drugs has been decreasing as the pharmaceutical company investment in research and development is increasing. As we face this painful crisis, called an innovation gap, there is increasing awareness that development of new uses of existing drugs may be a powerful tool to help overcome this obstacle because it takes too long, costs too much and can be risky to release drugs developed de novo. Consequently, drug repositioning is emerging in different therapeutic areas, including the pain research area. Worldwide, pain is the main reason for seeking healthcare, and pain relief represents an unmet global clinical need. Therefore, development of analgesics with better efficacy, safety and cost effectiveness is of paramount importance. Despite the remarkable advancement in research on cellular and molecular mechanisms underlying pain pathophysiology over the past three decades, target-based therapeutic opportunities have not been pursued to the same extent. Phenotypic screening remains a more powerful tool for drug development than target-based screening so far. It sounds somewhat heretical, but some multi-action drugs, rather than very selective ones, have been developed intentionally. In the present review, we first critically discuss the utility of drug repositioning for analgesic drug development and then show examples of 'old' drugs that have been successfully repositioned or that are under investigation for their analgesic actions. We conclude that drug repositioning should be more strongly encouraged to help build a bridge between basic research and pain relief worldwide.

  18. Liability versus innovation: the legal case for regenerative medicine.

    Science.gov (United States)

    Keren-Paz, Tsachi; El Haj, Alicia J

    2014-10-01

    Medical innovation occupies a position somewhere between standard practice and clinical research, but innovation is primarily intended to benefit an individual patient where standard treatment fails. Medical innovations in the area of regenerative medicine have the potential to completely transform medical practice, but rely upon some major revision to the nature of treatments beyond drug-based therapies. There is considerable investment in scientific and clinical research, but further attention could be paid to legal barriers to medical innovation imposed by the threat of medical malpractice. We survey in this article the legal framework for making determinations of medical malpractice in general, and highlight the issues specific to innovative treatments. In essence, liability could be imposed for failing to adequately inform the patient about the innovative nature of the suggested therapy or based on the fact that the risks outweighed the benefits. As for the latter, we examine whether liability is likely to be based merely on deviating from existing practice or on an examination on the merits of the treatments' risks and benefits. The facts that some risks are unforeseeable and some benefits are external to the patient complicate negligence determinations. The first fact relates to the problem of judging adverse events in hindsight; the second, to the obligation to make decisions based on the patient's best interest and avoid conflict of interests. In addition, we evaluate the relationship between the obligations to secure the patient's informed consent and to avoid clinical negligence. We identify the need for further research to examine the significance of the putative anti-innovation bias that current liability regimen has, and to examine whether a move to strict liability might avoid such bias, while being fair to patients who contribute for the advancement of medical knowledge by participating in innovative therapies.

  19. The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

    Science.gov (United States)

    Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

    2011-04-01

    The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

  20. Innovation process

    DEFF Research Database (Denmark)

    Kolodovski, A.

    2006-01-01

    Purpose of this report: This report was prepared for RISO team involved in design of the innovation system Report provides innovation methodology to establish common understanding of the process concepts and related terminology The report does not includeRISO- or Denmark-specific cultural, econom...

  1. Informal Innovation

    DEFF Research Database (Denmark)

    Hartmann, Mia Rosa Koss; Hartmann, Rasmus Koss

    Informal innovation, defined as the development and putting-into-use of novel solutions by non-R&D employees without prior formal approval from or subsequent revealing to superiors, has been recurrently observed in organizational research. But even as it is increasingly recognized that R&D is not......Informal innovation, defined as the development and putting-into-use of novel solutions by non-R&D employees without prior formal approval from or subsequent revealing to superiors, has been recurrently observed in organizational research. But even as it is increasingly recognized that R......&D is not the only plausible source of innovation inside organizations, informal innovation has yet to be systematically explored or theorized. We propose a theory of informal innovation based on analyses of prior literature and mixed-method, multi-site studies of innovation at the working level of two extreme......-case organizations. We propose that informal innovation occurs as 1) employees personally experience problems that they believe are not recognized or prioritized by superiors; 2) some employees are able to develop solutions, essentially at no cost; 3) innovators face no benefits from revealing to superiors, but can...

  2. Open innovation

    DEFF Research Database (Denmark)

    Bogers, Marcel; Chesbrough, Henry; Moedas, Carlos

    2018-01-01

    Open innovation is now a widely used concept in academia, business, and policy making. This article describes the state of open innovation at the intersection of research, practice, and policy. It discusses some key trends (e.g., digital transformation), challenges (e.g., uncertainty...

  3. Managing Innovation.

    Science.gov (United States)

    White, Ronald V.

    The management of innovation in instruction in English as a second language can benefit from the experience and techniques of management in the world of commerce as well as from theories and procedures in education. A systematic approach to the management of innovation emphasizes the importance of clearly defined objectives, evaluation that…

  4. Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    Patricia Miranda Romero

    2015-02-01

    Full Text Available Trastuzumab emtansina (T-DM1 is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC, who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS and the overall survival (OS. It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients

  5. Smart materials on the way to theranostic nanorobots: Molecular machines and nanomotors, advanced biosensors, and intelligent vehicles for drug delivery.

    Science.gov (United States)

    Sokolov, Ilya L; Cherkasov, Vladimir R; Tregubov, Andrey A; Buiucli, Sveatoslav R; Nikitin, Maxim P

    2017-06-01

    Theranostics, a fusion of two key parts of modern medicine - diagnostics and therapy of the organism's disorders, promises to bring the efficacy of medical treatment to a fundamentally new level and to become the basis of personalized medicine. Extrapolating today's progress in the field of smart materials to the long-run prospect, we can imagine future intelligent agents capable of performing complex analysis of different physiological factors inside the living organism and implementing a built-in program thereby triggering a series of therapeutic actions. These agents, by analogy with their macroscopic counterparts, can be called nanorobots. It is quite obscure what these devices are going to look like but they will be more or less based on today's achievements in nanobiotechnology. The present Review is an attempt to systematize highly diverse nanomaterials, which may potentially serve as modules for theranostic nanorobotics, e.g., nanomotors, sensing units, and payload carriers. Biocomputing-based sensing, externally actuated or chemically "fueled" autonomous movement, swarm inter-agent communication behavior are just a few inspiring examples that nanobiotechnology can offer today for construction of truly intelligent drug delivery systems. The progress of smart nanomaterials toward fully autonomous drug delivery nanorobots is an exciting prospect for disease treatment. Synergistic combination of the available approaches and their further development may produce intelligent drugs of unmatched functionality. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. MAPPING INNOVATION

    DEFF Research Database (Denmark)

    Thuesen, Christian Langhoff; Koch, Christian

    2011-01-01

    By adopting a theoretical framework from strategic niche management research (SNM) this paper presents an analysis of the innovation system of the Danish Construction industry. Theories within SNM look upon innovation in a sector as a socio-technical phenomenon and identifies three levels of socio......-technical interaction within which sectorial innovation can be explained. The analysis shows a multifaceted landscape of innovation around an existing regime, built in the existing ways of working and developing over generations. The regime is challenged from various niches and the sociotechnical landscape through...... trends as globalization. Three niches (Lean Construction, BIM and System Deliveries) are subject to a detailed analysis showing partly incompatible rationales and various degrees of innovation potential. The paper further discusses how existing policymaking operates in a number of tensions one being...

  7. Accidental Innovation

    DEFF Research Database (Denmark)

    Austin, Robert D.; Devin, Lee; Sullivan, Erin E.

    2012-01-01

    Historical accounts of human achievement suggest that accidents can play an important role in innovation. In this paper, we seek to contribute to an understanding of how digital systems might support valuable unpredictability in innovation processes by examining how innovators who obtain value from...... they incorporate accidents into their deliberate processes and arranged surroundings. By comparing makers working in varied conditions, we identify specific factors (e.g., technologies, characteristics of technologies) that appear to support accidental innovation. We show that makers in certain specified...... conditions not only remain open to accident but also intentionally design their processes and surroundings to invite and exploit valuable accidents. Based on these findings, we offer advice for the design of digital systems to support innovation processes that can access valuable unpredictability....

  8. Collaborative innovation

    DEFF Research Database (Denmark)

    Torfing, Jacob; Sørensen, Eva; Hartley, Jean

    2013-01-01

    , which emphasizes market competition; the neo-Weberian state, which emphasizes organizational entrepreneurship; and collaborative governance, which emphasizes multiactor engagement across organizations in the private, public, and nonprofit sectors. The authors conclude that the choice of strategies......-driven private sector is more innovative than the public sector by showing that both sectors have a number of drivers of as well as barriers to innovation, some of which are similar, while others are sector specific. The article then systematically analyzes three strategies for innovation: New Public Management......There are growing pressures for the public sector to be more innovative but considerable disagreement about how to achieve it. This article uses institutional and organizational analysis to compare three major public innovation strategies. The article confronts the myth that the market...

  9. Responsible innovation

    CERN Document Server

    De Woot, Philippe

    2015-01-01

    Economic development is rooted in disruption, not in equilibrium. And a powerful engine of economic development is innovation; but is this innovation always for the common good? The dark side of the extraordinary dynamism of innovation lies precisely in its destructive power. If simply left to market forces, it could lead to social chaos and great human suffering. To face the challenges of our time, we must create the proper climate and culture to develop strong entrepreneurial drive. But, more than ever, we must give this entrepreneurial drive its ethical and societal dimensions. Responsible innovation means a more voluntary orientation towards the great problems of the 21st century, e.g. depletion of the planet's resources, rising inequality, and new scientific developments potentially threatening freedom, democracy and human integrity. We need to transform our ceaseless creativity into real progress for humankind. In this respect, the rapid development of social innovation opens the door for new methods an...

  10. A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

    Directory of Open Access Journals (Sweden)

    Li T

    2013-10-01

    Full Text Available Tianshu Li, Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Shinjuku-ku, Tokyo, JapanAbstract: Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol% of maleimide-polyethylene glycol (PEG to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG/cholesterol/poly(ethylene glycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03. Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of

  11. Nuclear innovation in Saskatchewan: innovation

    International Nuclear Information System (INIS)

    Alexander, N.

    2015-01-01

    This paper describes nuclear innovation in Saskatchewan. The first stage is the Canadian Institute for Science and Innovation Policy (CSIP) and how you have a successful discussion about a technically complex issue, understand what information people need in order to have an informed discussion, understand how to convey that information to those people in a constructive way.

  12. Participatory Innovation

    DEFF Research Database (Denmark)

    Buur, Jacob; Matthews, Ben

    2008-01-01

    An increasing number of corporations engage with users in co-innovation of products and services. But there are a number of competing perspectives on how best to integrate these understandings into existing corporate innovation development processes. This paper maps out three of the dominant appr...... the challenges such an approach sets to innovation management, and discuss research directions we see as fundamental to the development of the field of user-driven innovation. Udgivelsesdato: September......An increasing number of corporations engage with users in co-innovation of products and services. But there are a number of competing perspectives on how best to integrate these understandings into existing corporate innovation development processes. This paper maps out three of the dominant...... approaches, compares them in terms of goals, methods and basic philosophy, and shows how they may beneficially enrich one another. We will present an industrial innovation case that has been instrumental to the development of what we have termed ‘Participatory Innovation’. Based on this we will list...

  13. Recent Advances in Nanoparticle-Based Förster Resonance Energy Transfer for Biosensing, Molecular Imaging and Drug Release Profiling

    Directory of Open Access Journals (Sweden)

    Nai-Tzu Chen

    2012-12-01

    Full Text Available Förster resonance energy transfer (FRET may be regarded as a “smart” technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of “visible” and “activatable” FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery.

  14. Market Access Advancements and Challenges in “Drug-Companion Diagnostic Test” Co-Development in Europe

    Directory of Open Access Journals (Sweden)

    Ildar Akhmetov

    2015-06-01

    Full Text Available The pharma ecosphere is witnessing a measured transformation from the one-size-fits-all or blockbuster model of drugs to more informed and tailored personalized treatments that facilitate higher safety and efficacy for a relevant sub-population. However, with several breakthroughs still in a nascent stage, market access becomes a crucial factor for commercial success, especially when it comes to co-creating value for pertinent stakeholders. This article highlights diverse issues from stakeholder perspectives in Europe, specifically the ones which require immediate resolution. Furthermore, the article also discusses case studies articulating potential solutions for the issues discussed.

  15. Controlled drug delivery systems towards new frontiers in patient care

    CERN Document Server

    Rossi, Filippo; Masi, Maurizio

    2016-01-01

    This book offers a state-of-the-art overview of controlled drug delivery systems, covering the most important innovative applications. The principles of controlled drug release and the mechanisms involved in controlled release are clearly explained. The various existing polymeric drug delivery systems are reviewed, and new frontiers in material design are examined in detail, covering a wide range of polymer modification techniques. The concluding chapter is a case study focusing on use of a drug-eluting stent. The book is designed to provide the reader with a complete understanding of the mechanisms and design of controlled drug delivery systems, and to this end includes numerous step-by-step tutorials. It illustrates how chemical engineers can advance medical care by designing polymeric delivery systems that achieve either temporal or spatial control of drug delivery and thus ensure more effective therapy that eliminates the potential for both under-and overdosing.

  16. Participatory Innovation

    DEFF Research Database (Denmark)

    Buur, Jacob; Matthews, Ben

    In this paper we discuss the potential for Participatory Design (PD) to make a fundamental contribution to the business-oriented field of user-driven innovation, taking note of where we find PD can best benefit from interaction with this other field. We examine some of the challenges that must...... be addressed if PD is to contribute to innovation processes in companies. We conclude by presenting a research agenda comprising of six promising topics to shape a new discipline of Participatory Innovation....

  17. Design & Innovation

    DEFF Research Database (Denmark)

    Boelskifte, Per; Jørgensen, Ulrik

    2005-01-01

    The new design and innovation programme at DTU is challenging some of the standard concepts dominating most engineering educations. The programme, its background, context and basic educational ideas are presented and discussed in this paper. To build competences that match the need for innovative...... and design oriented engineers in industry and society has turned out to challenge a number of the standard – and often taken for granted – concepts in engineering education still dominated world wide by rather strict norms and concepts of learning that do not challenge the students creativity and innovative...

  18. Medtech: Potential for innovation.

    Science.gov (United States)

    Bestetti, Gilberto

    2009-10-17

    Switzerland, with its ETHZ and EPFL, universities, advanced technical colleges, the CSEM, the Empa and the Paul Scherrer Institute, possesses a complete chain of knowledge and interdisciplinary competence which ranks it among the worldwide leaders in medical technology. To ensure that a wider range of excellent research results are translated into marketable products and methods, the CTI Agency for the Promotion of Innovation launched the Medtech initiative, a success story.

  19. An exploratory qualitative assessment of self-reported treatment outcomes and satisfaction among patients accessing an innovative voluntary drug treatment centre in Malaysia.

    Science.gov (United States)

    Ghani, Mansur A; Brown, Shan-Estelle; Khan, Farrah; Wickersham, Jeffrey A; Lim, Sin How; Dhaliwal, Sangeeth K; Kamarulzaman, Adeeba; Altice, Frederick L

    2015-02-01

    In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as "Cure and Care" (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation. An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis was used to identify the salient themes. Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection. C&Cs represents a dramatic shift in the Malaysian government's approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. An Exploratory Qualitative Assessment of Self-Reported Treatment Outcomes and Satisfaction Among Patients Accessing an Innovative Voluntary Drug Treatment Centre in Malaysia

    Science.gov (United States)

    Ghani, Mansur A.; Brown, Shan-Estelle; Khan, Farrah; Wickersham, Jeffrey A.; Lim, Sin How; Dhaliwal, Sangeeth K.; Kamarulzaman, Adeeba; Altice, Frederick L.

    2014-01-01

    Background In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as “Cure and Care” (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation. Methods An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis approach was used to identify the salient themes. Results Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection. Conclusion C&Cs represents a dramatic shift in the Malaysian government’s approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country. PMID:25577322

  1. Funding pharmaceutical innovation through direct tax credits.

    Science.gov (United States)

    Lybecker, Kristina M; Freeman, Robert A

    2007-07-01

    Rising pharmaceutical prices, increasing demand for more effective innovative drugs and growing public outrage have heightened criticism of the pharmaceutical industry. The public debate has focused on drug prices and access. As a consequence, the patent system is being reexamined as an efficient mechanism for encouraging pharmaceutical innovation and drug development. We propose an alternative to the existing patent system, instead rewarding the innovating firm with direct tax credits in exchange for marginal cost pricing. This concept is based on the fundamental assumption that innovation that benefits society at large may be financed publicly. As an industry which produces a social good characterized by high fixed costs, high information and regulatory costs, and relatively low marginal costs of production, pharmaceuticals are well-suited to such a mechanism. Under this proposal, drug prices fall, consumer surplus increases, access is enhanced, and the incentives to innovate are preserved.

  2. The NRNU MEPhI activities in the development and applications of advanced tools for innovative nuclear energy systems sustainability assessments - 5020

    International Nuclear Information System (INIS)

    Andrianov, A.; Dogov, A.; Kuptsov, I.; Fedorova, E.; Svetlichnyy, L.; Utianskaia, T.; Korovin, Y.

    2015-01-01

    This report delineates the multi-objective optimization and uncertainty treatment modules for the IAEA energy planning software MESSAGE developed at the National Research Nuclear University MEPhI and the Obninsk Institute for Nuclear Power Engineering intended for multi-objective optimization and sustainability assessments of innovative nuclear energy systems with account of uncertainty. The authors present some results of implementation of these tools for multi-objective nuclear energy system optimization studies. The developed software allows searching for compromises between the conflicting factors that determine the nuclear energy systems' effectiveness and calculating corresponding trade-off rates; carrying out comparative multi-criteria analysis of alternatives as well as choosing, ranking, and sorting corresponding options taking into account the evolution dynamics, structure and organization of a nuclear fuel cycle and the most important system constraints and restrictions. (authors)

  3. MAPPING INNOVATION

    DEFF Research Database (Denmark)

    Thuesen, Christian Langhoff; Koch, Christian

    2011-01-01

    By adopting a theoretical framework from strategic niche management research (SNM) this paper presents an analysis of the innovation system of the Danish Construction industry. The analysis shows a multifaceted landscape of innovation around an existing regime, built around existing ways of working...... and developed over generations. The regime is challenged from various niches and the socio-technical landscape through trends as globalization. Three niches (Lean Construction, BIM and System Deliveries) are subject to a detailed analysis showing partly incompatible rationales and various degrees of innovation...... potential. The paper further discusses how existing policymaking operates in a number of tensions one being between government and governance. Based on the concepts from SNM the paper introduces an innovation map in order to support the development of meta-governance policymaking. By mapping some...

  4. Innovation Awards

    Science.gov (United States)

    EPA promotes environmental stewardship by recognizing innovators in schools, communities and businesses in categories such as environmental education, green chemistry, smart growth, green power, and reducing air pollution and climate change impacts.

  5. The innovative use of a large-scale industry biomedical consortium to research the genetic basis of drug induced serious adverse events.

    Science.gov (United States)

    Holden, Arthur L

    2007-01-01

    The International Serious Adverse Event Consortium (SAEC) is a pharmaceutical industry and FDA led international (501 c3 non-profit) consortium, focused on identifying and validating DNA-variants useful in predicting the risk of drug induced, rare serious adverse events (SAEs). As such, it functions with the explicit purpose of enhancing the 'public good'. Its members are (i) organizations engaged principally in the business of discovering, developing and marketing pharmaceutical products, or (ii) a charitable, governmental, or other non-profit organization with an interest in researching the molecular basis of drug response.Drug-induced, rare SAEs present significant health issues for patients; and pose challenges for the safe use of approved drugs and the development of new drugs. Examples of drug-induced, rare SAEs include hepatotoxicity, QT prolongation, rhabdomyolosis, serious skin rashes (e.g. SJS), edema, acute renal failure, acute hypersensitivity, anemias/neutropenias, excessive weigh gain, retinopathy, vasculitis, among others. The rarity of such drug induced SAEs and the absence of effective government surveillance/research networks, makes it extremely difficult for any one company or research entity to accrue enough SAE cases and controls to conduct effective whole genome studies. Central to the notion of the SAEC is industry, government and health care providers can join forces to make use of a variety of sample and data resources in researching the genetic basis of these events.The purpose of the SAEC is threefold:•To carry out research directed toward the discovery of DNA-variants clinically useful in understanding and predicting the risk of drug induced serious adverse events and similar scientific research.•To ensure the widespread availability of the results of such research to the scientific research community and the public at large for no charge through publication and web-based methods; and•To educate the scientific research and medical

  6. Leadership Innovations

    Science.gov (United States)

    1993-04-01

    leadership " and " leadership in innovation." 3 THEORY , AS AN INSTRUMENT OF ANALYSIS FOR INNOVATION IN LEADERSHIP There are many...attributes of a leader.𔃺 Attempts to define leadership usually contrast it with "followship", management ," or sometimes - with ’beadship."’" These...plausible theory . - . . . -. - -- Nevertheless, some authors consider, and I agree, that there is no true leadership theory because existing

  7. Direct coupling of electromembrane extraction to mass spectrometry – Advancing the probe functionality toward measurements of zwitterionic drug metabolites

    DEFF Research Database (Denmark)

    Kige Rye, Torstein; Fuchs, David; Pedersen-Bjergaard, Stig

    2017-01-01

    A triple-flow electromembrane extraction (EME) probe was developed and coupled directly to electrospray-ionization mass spectrometry (ESI-MS). Metabolic reaction mixtures (pH 7.4) containing drug substances and related metabolites were continuously drawn (20 μL/min) into the EME probe in one flow......-nitrophenyl octyl ether (and for some experiments containing 30% triphenyl phosphate (TPP)), and into 20 μL min-1 of formic acid as acceptor phase, which was introduced through a third flow channel. The acceptor phase was pumped directly to the MS system, and the ion intensity of extracted analytes......, the system can potentially be used for direct analysis of various kinds of chemical reactions that have to be run at pH conditions unfavorable for direct analyte extractions....

  8. Prostanoid receptors as possible targets for anti-allergic drugs: recent advances in prostanoids on allergy and immunology.

    Science.gov (United States)

    Honda, Tetsuya; Tokura, Yoshiki; Miyachi, Yoshiki; Kabashima, Kenji

    2010-12-01

    Prostanoids, consisting of prostaglandins and thromboxane, are cyclooxygenase metabolites of arachidonic acid released in various pathophysiological conditions which exert a range of actions mediated through their respective receptors expressed on target cells. Although it has been difficult to analyze the physiological role of prostanoids, recent developments in both the disruption of the respective gene and receptor selective compounds have enabled us to investigate the physiological roles for each receptor. It has been demonstrated that each prostanoid receptor has multiple functions, and that their expression is regulated in a context-dependent manner that sometimes results in opposite, excitatory and inhibitory, outcomes. The balance of prostanoid production and receptor expression has been revealed to be important for homeostasis of the human body. Here, we review new findings on the roles of prostanoids in allergic and immune diseases, focusing on contact dermatitis, atopic dermatitis, asthma, rheumatoid arthritis, and encephalomyelitis, and also discuss the clinical potentials of receptor-selective drugs.

  9. Problem framing in new innovation spaces

    DEFF Research Database (Denmark)

    Lema, Rasmus

    2015-01-01

    This paper is concerned with the global distribution of innovation activity. It uses the case of the software industry to show that there is considerable scope for innovation as an incremental extension of routine outsourcing low-cost countries. To show this, the paper develops a new vocabulary...... for the analysis of innovation outsourcing in global value chains. It then draws on qualitative case study research focused on outsourcing from firms in OECD countries to firms in Bangalore, India. Some buyers are willing to farm out ‘advanced’ activities to firms of the new innovation spaces. But such advanced...... to developing countries fails to recognize that innovation tasks, even advanced ones, are becoming increasingly mobile. It also explains why innovative software activities including problem framing activities are likely to follow the relocation of routine ‘software production’ activities to the new innovation...

  10. Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

    Directory of Open Access Journals (Sweden)

    Mark Holodniy

    2011-03-01

    Full Text Available Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR and limited retreatment options. We assessed two novel antiretroviral (ARV treatment approaches in this setting.We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART failure requiring retreatment, to two options (a re-treatment with either standard (≤4 ARVs or intensive (≥5 ARVs ART and b either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59, or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30, or in the rate of non-HIV associated serious adverse events between re-treatment options.We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.Clinicaltrials.gov NCT00050089.

  11. Policy Innovation in Innovation Policy

    DEFF Research Database (Denmark)

    Borras, Susana

    During the past two decades Europe has experienced important changes and transformations in the way in which governments approach the issue of science, technology and innovation, and their relation to economic growth and competitiveness. This has to do with the European Union level as well...... as with national and sub-national governments in Europe, all of them introducing interesting novelties in their innovation policy. These changes refer to different aspects of policy, mainly the content of policy initiatives towards science, technology and innovation; the instruments governments are using...... at the EU level, and mentions similar trends taking place at national and sub-national levels. The questions that guide the contents here are essentially three, namely, what are the main traits of innovation policies in Europe since the 1990s and how have the EU and different national governments approached...

  12. Challenges Related to the Use of Liquid Metal and Molten Salt Coolants in Advanced Reactors. Report of the collaborative project COOL of the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO)

    International Nuclear Information System (INIS)

    2013-05-01

    The International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) was launched in 2000, based on a resolution by the IAEA General Conference (GC(44)/RES/21). INPRO aims at helping to ensure that nuclear energy is available in the twenty-first century in a sustainable manner, and seeks to bring together all interested Member States, both technology holders and technology users, to jointly consider actions to achieve desired innovations. INPRO is taking care of the specific needs of developing countries. One of the aims of INPRO is to develop options for enhanced sustainability through promotion of technical and institutional innovations in nuclear energy technology through collaborative projects among IAEA Member States. Collaboration among INPRO members is fostered on selected innovative nuclear technologies to bridge technology gaps. Collaborative projects have been selected so that they complement other national and international R and D activities. The INPRO Collaborative Project COOL on Investigation of Technological Challenges Related to the Removal of Heat by Liquid Metal and Molten Salt Coolants from Reactor Cores Operating at High Temperatures investigated the technological challenges of cooling reactor cores that operate at high temperatures in advanced fast reactors, high temperature reactors and accelerator driven systems by using liquid metals and molten salts as coolants. The project was initiated in 2008 and was led by India; experts from Brazil, China, Germany, India, Italy and the Republic of Korea participated and provided chapters of this report. The INPRO Collaborative Project COOL addressed the following fields of research regarding liquid metal and molten salt coolants: (i) survey of thermophysical properties; (ii) experimental investigations and computational fluid dynamics studies on thermohydraulics, specifically pressure drop and heat transfer under different operating conditions; (iii) monitoring and control of coolant

  13. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules.

    Science.gov (United States)

    Choonara, Bibi F; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2014-11-15

    The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Recent advances in the design of drug-loaded polymeric implants for the treatment of solid tumors.

    Science.gov (United States)

    Wadee, Ameena; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Penny, Clement; Ndesendo, Valence M K; Kumar, Pradeep; Murphy, Caragh S

    2011-10-01

    The effective treatment of solid tumors continues to be a great challenge to clinicians, despite the development of novel drugs. In order to improve the clinical efficacy of existing chemotherapeutic agents, researchers have considered the possibility of site-specific solid tumor treatment. The greatest advantage of localized delivery is the significantly fewer side effects experienced by patients. Recently, in situ forming implants have attracted considerable interest. These polymeric systems are injected as solutions into tumor sites and the injected solution forms an implant as a result of local environmental stimuli and hence removes the need for surgical implantation. This review summarizes the attempts that have been made to date in the development of polymeric implants for the treatment of solid tumors. Both in situ forming implants and preformed implants, fabricated using natural and synthetic polymers, are described. In addition, the peri- or intra-tumoral delivery of chemotherapeutic agents based on implants inserted surgically into the affected region is also discussed along with a short coverage of implants having an undesirable initial burst release effect. Although these implants have been shown to improve the treatment of various solid tumors, the ideal implant that is able to deliver high doses of chemotherapeutics to the tumor site, over prolonged periods with relatively few side effects on normal tissue, is yet to be formulated.

  15. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  16. Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction

    Directory of Open Access Journals (Sweden)

    Francoeur RB

    2011-09-01

    Full Text Available Richard B FrancoeurSchool of Social Work, Adelphi University, Garden City, NY, USA; Center for the Psychosocial Study of Health and Illness, Columbia University, New York, NY, USAAbstract: This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples; expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1 developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper- or abuse-resistant/deterrent drug formulations; and (2 expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse

  17. Market incentives and pharmaceutical innovation.

    Science.gov (United States)

    Yin, Wesley

    2008-07-01

    I study the impact of the Orphan Drug Act (ODA), which established tax incentives for rare disease drug development. I examine the flow of new clinical drug trials for a large set of rare diseases. Among more prevalent rare diseases, the ODA led to a significant and sustained increase in new trials. The impact for less prevalent rare diseases was limited to an increase in the stock of drugs. Tax credits can stimulate R & D; yet because they leave revenue margins unaffected, tax credits appear to have a more limited impact on private innovation in markets with smaller revenue potential.

  18. Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.

    Science.gov (United States)

    Esposito, Francesca; Mandrone, Manuela; Del Vecchio, Claudia; Carli, Ilaria; Distinto, Simona; Corona, Angela; Lianza, Mariacaterina; Piano, Dario; Tacchini, Massimo; Maccioni, Elias; Cottiglia, Filippo; Saccon, Elisa; Poli, Ferruccio; Parolin, Cristina; Tramontano, Enzo

    2017-08-31

    Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors. Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function. We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket. On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol. Results supported the potential of this plant as a valuable multitarget active drug source. In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Clinical outcomes from an innovative protocol using serial ultrasound imaging and a single MR image to guide brachytherapy for locally advanced cervix cancer.

    Science.gov (United States)

    van Dyk, Sylvia; Narayan, Kailash; Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Khaw, Pearly; Lin, Ming Yin; Schneider, Michal

    The aim of this study was to report clinical outcomes in a series of patients who underwent serial ultrasound and a single MRI to plan and verify intracavitary brachytherapy. Data for patients who were referred for curative intent radiotherapy for International Federation of Gynecology and Obstetrics (FIGO) Stage 1-1V cervix cancer between January 2007 and March 2012 were analyzed. All patients received external beam radiotherapy with concurrent chemotherapy and sequential high-dose rate brachytherapy. Brachytherapy was planned and verified using serial ultrasound imaging and a single MRI. Data from 191 patients were available for analyses. The median (range) followup time was 5.08 (0.25-8.25) years. Five-year local control, failure-free survival, cancer-specific survival, and overall survival were 86%, 57.3%, 70% and 63%, respectively. Mean (standard deviation) combined external beam radiotherapy and brachytherapy target doses, equivalent to doses in 2 Gy fractions were 80.4 Gy10 (3.89), median (range) 80 (49-96) Gy10. Grade 3 or greater gastrointestinal, genitourinary, or vaginal late toxicity occurred in 3%, 1.6%, and 2% of patients, respectively. Survival, patterns of failure, and late complication rates were similar to published series of MRI/CT-based brachytherapy practices. This large study demonstrates that favorable treatment outcomes can be obtained using a pragmatic and innovative combination of ultrasound and MR imaging. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  20. Enhancing collaborative innovation in the public sector

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob

    2011-01-01

    demand for public innovation, and demonstrates how it can be enhanced through multiactor collaboration. The case for collaborative innovation is supported by insights from three different social science theories. The theoretical discussion leads to the formulation of an analytical model that can be used......Encouraged by the proliferation of governance networks and the growing demands for public innovation, this article aims to advance “collaborative innovation” as a cross-disciplinary approach to studying and enhancing public innovation. The article explains the special conditions and the growing...... in future studies of collaborative innovation in the public sector....

  1. Open innovation

    DEFF Research Database (Denmark)

    West, Joel; Bogers, Marcel

    2017-01-01

    Interest in open innovation (OI) as a field of research has grown exponentially since the phrase was coined by Chesbrough in his 2003 book, with numerous articles, special issues, books, and conference sessions. Various reviews of the literature have summarized prior work, offered new frameworks......, and identified opportunities for future research. Here we summarize these opportunities, which include more research on outbound OI, the role of open innovation in services, and network forms of collaboration such as consortia, communities, ecosystems, and platforms. Research should also examine the use of OI...... by small, new, and not-for-profit organizations, as well as the linkage of individual actions and motivations to open innovation. Other opportunities include better measuring the costs, benefits, antecedents, mediators and moderators of the effects of OI on performance, and understanding why and how OI...

  2. Everyday Innovation

    DEFF Research Database (Denmark)

    Lippke, Lena; Wegener, Charlotte

    2014-01-01

    Purpose – The purpose of this paper is to explore how vocational teachers’ everyday practices can constitute innovative learning spaces that help students to experience engagement and commitment towards education and thus increase their possibilities for completing their studies despite notable...... difficulties. Design/methodology/approach – Based on two ethnographic field studies, we analyse vocational teaching situations in which teachers and students engage in daily remaking of the vocational educational training practice. It is argued that these everyday situations can be understood as innovative....... Practical implications – Based on the analysis, we argue that students’ engagement in education can be enhanced by transforming the educational settings on various parameters such as buildings, artefacts, emotions and experiences. Thus, innovation should be recognised as emerging everyday activities...

  3. Reconsidering Innovation

    DEFF Research Database (Denmark)

    Vaaben, Nana Katrine

    Innovation og reformer er på dagsordenen allevegne, ikke mindst i politiske forsøg på at reorganisere den offentlige sektor for at få velfærdssamfundet til at kunne overleve økonomisk tumult og dystre fremtidsprognoser. Dette papir undersøger, hvordan klassiske antropologiske teorier og debatter om...... forandring og myter kan hjælpe os med at genoverveje teoretiske forståelser af innovation i organisatoriske studier. I særlig grad sættes der fokus på de implikationer som vores "innovationsmyte" kan have for offentligt ansatte og værdsættelsen af deres arbejde. Analysens argument er, at innovation ikke skal...

  4. Innovation Assessment

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob

    2017-01-01

    Current regulatory approaches are ill-equipped to address the challenges of governing through periods of disruptive technological change. This article hones in on the use of assessment regimes at the level of the European Union, particularly in the work of the Commission, to argue for a missing...... I label innovation assessment, to steer polities through periods of disruptive technological change, during which innovations have taken concrete forms and are beginning to diffuse, but still exhibit much scope for rapid, unexpected change and alternative trajectories of development. By juxtaposing...

  5. Innovative clean coal technology: 500 MW demonstration of advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NOx) emissions from coal-fired boilers. Final report, Phases 1 - 3B

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-01-01

    This report presents the results of a U.S. Department of Energy (DOE) Innovative Clean Coal Technology (ICCT) project demonstrating advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NOx) emissions from coal-fired boilers. The project was conducted at Georgia Power Company`s Plant Hammond Unit 4 located near Rome, Georgia. The technologies demonstrated at this site include Foster Wheeler Energy Corporation`s advanced overfire air system and Controlled Flow/Split Flame low NOx burner. The primary objective of the demonstration at Hammond Unit 4 was to determine the long-term effects of commercially available wall-fired low NOx combustion technologies on NOx emissions and boiler performance. Short-term tests of each technology were also performed to provide engineering information about emissions and performance trends. A target of achieving fifty percent NOx reduction using combustion modifications was established for the project. Short-term and long-term baseline testing was conducted in an {open_quotes}as-found{close_quotes} condition from November 1989 through March 1990. Following retrofit of the AOFA system during a four-week outage in spring 1990, the AOFA configuration was tested from August 1990 through March 1991. The FWEC CF/SF low NOx burners were then installed during a seven-week outage starting on March 8, 1991 and continuing to May 5, 1991. Following optimization of the LNBs and ancillary combustion equipment by FWEC personnel, LNB testing commenced during July 1991 and continued until January 1992. Testing in the LNB+AOFA configuration was completed during August 1993. This report provides documentation on the design criteria used in the performance of this project as it pertains to the scope involved with the low NOx burners and advanced overfire systems.

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

    Science.gov (United States)

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

    2018-04-25

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

  7. Assessing construction innovation: theoretical and practical perspectives

    Directory of Open Access Journals (Sweden)

    Peter Davis

    2016-09-01

    Full Text Available Innovation is key for productivity improvement and advancements in different sectors of the economy, including the construction sector.  The criticism of the slow pace of innovation in construction industry may be unwarranted, considering the structure of the industry and nature of the construction business.  The loosely coupled nature of firms, mostly Small and Medium Enterprises (SME’s, delivering ‘projects’ through partial engagement, together with the distinction between the project innovation and firm innovation makes it difficult to extract innovations in a meaningful way.  The problem also lies in conceptualising, defining, articulating and assessing innovation in construction.  The literature is replete with research into construction innovation, however, there is limited research into understanding how innovation is perceived and narrated in practice.  The paper aims to explore how innovation is assessed and narrated in construction, specifically analysing theory and practice perspectives.  A theoretical model was constructed from a structured literature review illustrating existing discourse and narratives of construction innovation assessment.  A qualitative analysis of ‘Professional Excellence in Building’ submission documents to the Australian Institute of Building was performed to identify the practice perspective of innovation.  The findings suggest that internal organizational and process innovation account for the majority of improvements identified.  Importantly a taxonomy of narrative is developed that articulates how the construction industry in Australia views industry innovation.

  8. Challenges in developing drugs for primary headaches

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  9. Advancing Climate Change Education and Youth Empowerment: Preparing Our Communities with the Skills, Knowledge, and Passion to Push for and Develop Innovative Solutions

    Science.gov (United States)

    Niepold, F., III; Johnston, E.; Rooney-varga, J. N.; Qusba, L.; Staveloz, W.; Poppleton, K.; Cloyd, E. T.; Kretser, J.; Bozuwa, J.; Edkins, M. T.

    2016-12-01

    Today's youth are the first generation to come of age amid rapid climate change, and they have the most at stake in how society responds to it. Climate change will bring economic and environmental challenges as well as opportunities, and citizens who understand the issues at stake will be better prepared to respond. Climate education is a necessary foundation for them to understand and help tackle the complex issue of climate change. Many will become leaders with the skills, knowledge, and passion to push for and develop innovative solutions. As such, this topic requires interdisciplinary and transdisciplinary approaches from a professionally diverse group of experts to effectively build the solid foundation for a low carbon and sustainable economy. Educators from all disciplines need to be enlisted to contribute their talents in building students knowledge and skills to limit human-induced climate change while being prepared for the projected impacts that will continue, and it will accelerate significantly if global emissions of heat-trapping gases continue to increase. This presentation will discuss the new youth and educator engagement partnerships that developed to achieve ways of addressing the problems and opportunities resulting from climate change. We will describe how the partnerships are helping lift up and raise the profile of effective programs that enable transdisciplinary solutions to societal issues. The #Youth4Climate and #Teach4Climate social media campaigns were organized by a flotilla of federal and non-federal partners to inspire young people around the world to take actions on climate change and inspire teachers to prepare students to be part of the solutions to climate change. The largest one, the #Youth4Climate campaign for COP21 youth engagement had over 33 million impressions and opened a discussion for all to join with youth for climate actions at COP21. Each of these three social media campaigns had a simple ask, give young people a voice

  10. DISTINCT: Diversity in Solar Talent Through INnovative Curriculum and Training: An Integrated Research and Education Approach towards Creating Diversity and Advancing Utility-Scale Solar Technology

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaswami, Hariharan [Univ. of Texas, San Antonio, TX (United States)

    2018-02-05

    The DISTINCT project research objective is to develop an innovative N-port power converter for a utility-scale PV system that is modular, compact and cost-effective and that will enable the integration of a high-frequency, high-voltage solid-state transformer. The novelty of the proposed research is the electrical power conversion architecture using an N-port converter system that replaces the output 60Hz transformer with an integrated high-frequency low-weight solid-state transformer reducing power electronics and BOS costs to meet SunShot goals through modularity and direct high-voltage interconnection. A challenge in direct integration with a 13.8kV line is the high voltage handling capacity of the converters combined with high efficiency operation. The front-end converter for each port is a Neutral-Point Clamped (NPC) Multi-Level dc-dc Dual-Active Bridge (ML-DAB) which allows Maximum Power Point Tracking (MPPT). The integrated high frequency transformer provides the galvanic isolation between the PV and grid side and also steps up the low dc voltage from PV source. Following the ML-DAB stage, in each port, is an inverter with H-bridge configuration or NPC configuration. N number of NPC inverters’ outputs are cascaded to attain the per-phase line-to-neutral voltage to connect directly to the distribution grid (i.e. 13.8 kV). The cascaded inverters have the inherent advantage of using lower rated devices, smaller filters and low Total Harmonic Distortion (THD) required for PV grid interconnection. Our analysis and simulation results show improved performance on cost, efficiency, service life with zero downtime and THD. A comprehensive control scheme is presented to ensure the maximum power from each port and each phase are sent to the grid. A functional prototype of a 2-port converter with ML-DAB and cascaded H-bridges has been designed, built, and tested in a laboratory setup to verify the target technical metrics. The N-port converter system due to its

  11. Multisensory innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Kampfer, Kristina; Ivens, Bjoern

    2017-01-01

    For many companies, differentiating their offerings from competitors' value propositions is becoming increasingly challenging. In order to formulate convincing value propositions, a holistic approach is required that takes human perception and sensation into consideration. This article assesses t...... and ultimately alters behavior and thus substantiates its role in multisensory innovation and product design....

  12. Innovations (INNO)

    International Nuclear Information System (INIS)

    1978-01-01

    The annual report of the working group on innovations (INNO) deals with the projects carried out by the participating institutes and laboratories in the two fields of 1) application of non-nuclear methods and 2) non-nuclear research and development. (HK) [de

  13. Effektiv innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret; Brandi, Ulrik

    2011-01-01

    Er det vækst og udvikling eller åbenhed, videnudvikling, netværk, leg og innovation? Eller er det prisregulering, tilpasning og stærk styring, som skal gøre universiteterne til førende drivkræfter for dansk vækst?...

  14. Software Innovation

    DEFF Research Database (Denmark)

    Rose, Jeremy

      Innovation is the forgotten key to modern systems development - the element that defines the enterprising engineer, the thriving software firm and the cutting edge software application.  Traditional forms of technical education pay little attention to creativity - often encouraging overly...

  15. Balanced Innovation Management

    National Research Council Canada - National Science Library

    King, David R

    2007-01-01

    The Department of Defense has demonstrated success in managing innovation. The military's approach to innovation management extends beyond traditional distinctions between internal and external innovation modes...

  16. ALTERNATIVE ROUTES OF DRUG ADMINISTRATION: ADVANTAGES AND DISADVANTAGES (SUBJECT REVIEW OF AMERICAN ACADEMY OF PEDIATRICS

    Directory of Open Access Journals (Sweden)

    article editorial

    2006-01-01

    Full Text Available During the past 20 years advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regiment and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless. Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravinus access which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients especially factors that could lead to drug-relaxed toxicity or adverse responses are emphasized.Key words: drug formulation, pharmacoKINETICS, pharmacodynamics, drug, children.

  17. Disruption or innovation? A qualitative descriptive study on the use of electronic patient-physician communication in patients with advanced cancer.

    Science.gov (United States)

    Voruganti, Teja; Husain, Amna; Grunfeld, Eva; Webster, Fiona

    2018-03-04

    In the advanced cancer context, care coordination is often inadequate, leading to suboptimal continuity of care. We evaluated an electronic web-based tool which assembles the patient, their caregivers, and their healthcare providers in a virtual space for team-based communication. We sought to understand participant perceptions on electronic communication in general and the added value of the new tool in particular. We conducted a qualitative descriptive study with participants (patients, caregivers, cancer physicians) who participated in a 3-month pilot trial evaluating the tool. Interviews were thematically analyzed and the perspectives from patients, caregivers, and cancer physicians were triangulated. Interviews from six patients, five of their caregivers, and seven cancer physicians conducted alongside monthly outcome assessments were analyzed. We identified five themes relating participants' perspectives on electronic communication to their experience of care: (1) apparent gaps in care, (2) uncertainty in defining the circle of care, (3) relational aspects of communication, (4) incongruence between technology and social norms of patient-physician communication, and (5) appreciation but apprehension about the team-based communication tool for improving the experience of care. The potential of tools for electronic communication to bring together a team of healthcare providers with the patient and caregivers is significant but may pose new challenges to existing team structure and interpersonal dynamics. Patients and physicians were worried about the impact that electronic communication may have on the patient-physician relationship. Implementation approaches, which build on the relationship and integrate the team as a whole, could positively position electronic communication to enhance the team-based care.

  18. Advanced Manufacturing Technologies

    Science.gov (United States)

    Fikes, John

    2016-01-01

    Advanced Manufacturing Technologies (AMT) is developing and maturing innovative and advanced manufacturing technologies that will enable more capable and lower-cost spacecraft, launch vehicles and infrastructure to enable exploration missions. The technologies will utilize cutting edge materials and emerging capabilities including metallic processes, additive manufacturing, composites, and digital manufacturing. The AMT project supports the National Manufacturing Initiative involving collaboration with other government agencies.

  19. INNOVATIVE PRACTICES IN SCIENCE EDUCATION: A PANACEA ...

    African Journals Online (AJOL)

    Global Journal

    innovative practices for enhanced students' academic achievement in science subjects. KEYWORDS: Academic ... a new invention or way of doing something. Furthermore .... associated with scientific processes needed for advancement in ...

  20. Artificial Intelligence and Public Healthcare Service Innovation

    DEFF Research Database (Denmark)

    Sun, Tara Qian; Medaglia, Rony

    Public healthcare ecosystems are complex networks of diverse actors that are subject to pressures to innovate, also a result of technological advancements. Artificial Intelligence (AI), in particular, has the potential to transform the way hospitals, doctors, patients, government agencies...