Research Methodology in Global Strategy Research

DEFF Research Database (Denmark)

Cuervo-Cazurra, Alvaro; Mudambi, Ram; Pedersen, Torben

2017-01-01

We review advances in research methodology used in global strategy research and provide suggestions on how researchers can improve their analyses and arguments. Methodological advances in the extraction of information, such as computer-aided text analysis, and in the analysis of datasets......, such as differences-in-differences and propensity score matching, have helped deal with challenges (e.g., endogeneity and causality) that bedeviled earlier studies and resulted in conflicting findings. These methodological advances need to be considered as tools that complement theoretical arguments and well......-explained logics and mechanisms so that researchers can provide better and more relevant recommendations to managers designing the global strategies of their organizations....

The Islamic State’s Global Propaganda Strategy

Directory of Open Access Journals (Sweden)

Daveed Gartenstein-Ross

2016-03-01

Full Text Available This Research Paper aims to analyse in depth the global propaganda strategy of the so-called “Islamic State” (IS by looking at the methods through which this grand strategy is carried out as well as the objectives that IS wants to achieve through it. The authors first discuss IS’ growth model, explaining why global expansion and recruitment of foreign fighters are pivotal to IS success. Having in mind this critical role, the authors then explore the narratives and themes used by the group to mobilise foreign fighters and jihadists groups. Third, the paper analyses how IS deploys its narratives in those territories where it has established a foothold. Fourth, it outlines IS’ direct engagement strategy and how it is used to facilitate allegiance of other jihadist groups. The final section of the paper offers a menu of policy options that stakeholders can implement to counter IS’ global propaganda efforts.

Novel therapeutic strategies against AIDS progression based on the ...

African Journals Online (AJOL)

Novel therapeutic strategies against AIDS progression based on the pathogenic effects of HIV-1 and V pr Proteins. Ahmed A Azad. Abstract. No Abstract. Discovery and Innovation Vol. 17, 2005: 52-60. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics.

Therapeutic targeting strategies using endogenous cells and proteins.

Science.gov (United States)

Parayath, Neha N; Amiji, Mansoor M

2017-07-28

Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

GLOBAL TEAM MANAGEMENT: AN ESSENTIAL COMPONENT OF FIRMS’ INNOVATION STRATEGY

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AZİM ÖZTÜRK

2013-05-01

Full Text Available In the world marketplace some firms compete successfully and others fail to gain global competitive advantage. Some researchers argue that innovation strategy is the answer to successfully meeting today’s and tomorrow’s global business challenges.  An important aspect of the innovation strategy is managing global teams effectively.  Thus, firms of tomorrow will be characterized by values such as teamwork, innovation, cultural diversity, and a global mindset.  The rapid globalization of business, and increasing competition will continue to drive the need for effective teamwork and/in innovation management.  The purpose of our research is to gain insight into global team management and its role as a major component of innovation strategy.  We discuss the changing and developing functions of teamwork, examine the characteristics of global teams, and finally offer a process to achieve effective global team management.

Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury.

Science.gov (United States)

Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

2013-01-01

Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

Therapeutic strategies to improve control of hypertension.

Science.gov (United States)

Armario, Pedro; Waeber, Bernard

2013-03-01

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

International Pricing Strategies for Born-Global Firms

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Michael Neubert

2017-10-01

Full Text Available This paper aims to understand how born global firms develop their international pricing strategies, practices, and models. It aims to expand the study of international entrepreneurship and born global firms by including a broader and deeper range of pricing aspects than is normally found in the international entrepreneurship and pricing literature. The paper opted for a multiple case-study research design using different sources of evidence, including four in-depth interviews with CEOs of born global firms. The case-study firms were selected using a purposive selection method. The theoretical framework of Ingenbleek, Frambach & Verhallen is used. The results suggest that successful leaders act as ‘integrating forces’ on two levels: by applying a structured and disciplined price-setting process with regular reviews and by mediating between corporate financial goals and the local market reality. The results support the claim that policy makers should offer insights, training and financial support to give promising born global firms the possibility to select the most efficient international pricing models and strategies. The results are relevant for entrepreneurs to understand the importance of efficient price-modelling processes and the influence of the different price strategies and price models on financial results and sales revenues.

Colorectal cancer: diagnostic and therapeutic strategies

International Nuclear Information System (INIS)

Vaillant, J.C.

1996-01-01

Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)

Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

Science.gov (United States)

Cayabyab, Rowena; Ramanathan, Rangasamy

2016-01-01

retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally. © 2016 S. Karger AG, Basel.

[Type 2 diabetes: what therapeutic strategy?].

Science.gov (United States)

Grimaldi, A; Hartemann-Heurtier, A

2001-02-17

GOAL OF TREATMENT: Prevention of diabetic micro and macroangiopathy is the goal of treatment in type 2 diabetes mellitus. A well-controlled glucose level is the key to prevention of microangiopathy; there is no threshold level. Antihypertensive treatment, with the goal of blood pressure below 130/80 mmHg is also beneficial in preventing aggravation of microangiopathy. For macroangiopathy, prevention is based in priority on treatment of other risk factors for cardiovascular disease; the threshold level for drug treatment and the therapeutic objective are those defined for secondary prevention in non-diabetic patients, i.e. blood pressure below 140/80 mmHg and LDL cholesterol under 1.30 g/l. The beneficial effect of lower glucose levels on preventing macrovascular risk was not formally demonstrated by the UKPDS, probably because the difference between the control and the treatment group HbA1c levels was minimal, 0.9 points. REVISITING STRATEGY: It is thus time to revisit the preventive strategy for type 2 diabetes mellitus, i.e. step-by-step increments, as currently proposed for worsening glucose levels. Metformine should be prescribed if the HbA1c is above normal in order to achieve the demonstrated benefit in prevention of microangiopathy and in the hope, motivated by pathophysiology data, of preventing insulin failure. Slow-release insulin at bedtime should be added to the oral hypoglycemiants if fasting glucose exceeds 1.60 or 1.80 g/l, even if the HbA1c remains below 8%. NEW HYPOGLYCEMIANTS: The role of these new agents in this more "aggressive" strategy remains to be defined. Glinides will have to demonstrate their superiority over sulfamides (fewer episodes of hypoglycemia with comparable efficacy) to justify their high cost. Glitazones will have to demonstrate a beneficial effect in second intention combination with metformine on cardiovascular morbidity mortality in type 2 diabetes patients with a metabolic insulin-resistance syndrome and visceral obesity

Global power: Markets and strategies

International Nuclear Information System (INIS)

Poirer, J.L.

1998-01-01

The author will first present an updated view of the global power market activity, including opportunities in power generation, transmission and distribution. This will include a review of the trends in closings and transaction flowed by type of activity and geographic area. Estimates will be based on Hagler Bailly's comprehensive database on global power transactions and project announcements. The firm has also worked with dozens of global power companies since 1990. Second, the author will review trends in terms of regulatory changes, project cost trends, developers' project experiences, and financing issues. This systematic review will be the foundation for projection of future market activity (e.g., number of closing by type of project through 2000). A forecast of future greenfield and privatization activity will be provided and the key markets will be highlighted. Third, the author will present an updated view of the competition in the global power market (including the various types of competitors and changes in their respective market posture). Finally, the author will discuss the various types of strategies and business models that are followed by key global power players

What are the Essential Success Strategies for Global CIOs?

Institute of Scientific and Technical Information of China (English)

Jay Crotts

2010-01-01

@@ As a CIO in the global environment,my biggest challenge is to understand the dynamics of how my company operates in each country.Acquiring an understanding of how market maturity affects business strategy helps me develop an IT strategy that supports local markets while enhancing them with the global resources,processes and efficiencies at our disposal.

Malaysian diaspora strategies in a globalized Muslim market

DEFF Research Database (Denmark)

Fischer, Johan

2015-01-01

This paper explores Malaysia’s efforts to develop and dominate a global market in halal (literally, ‘lawful or ‘permitted’) commodities as a diaspora strategy and how Malaysian state institutions, entrepreneurs, restaurants and middle-class groups in London respond to and are affected...... and practise Malaysian diaspora strategies in the globalized market for halal products and services. This paper is based on ethnographic material from fieldwork among state institutions, entrepreneurs, restaurants and middle-class groups in Kuala Lumpur and London, namely participant observation...

Toward an Integrative Model of Global Business Strategy

DEFF Research Database (Denmark)

Li, Xin

fragmentation-integration-fragmentation-integration upward spiral. In response to the call for integrative approach to strategic management research, we propose an integrative model of global business strategy that aims at integrating not only strategy and IB but also the different paradigms within the strategy...... field. We also discuss the merit and limitation of our model....

two strategies to be integrated into globalization

OpenAIRE

Alvarado, Fernando

2011-01-01

The present thesis work intends to investigate internal and external factors determining the type of strategy of foreign policy used by Argentina and Chile in order to be part of globalization. In both cases, it is a strategy where the emphasis on the management of foreign policy, more economic than political, prevails. However, under the same external context and similar formal institutional frameworks, the main difference of both strategies may be found in the conceptual approach, which is ...

Global low-carbon transition and China's response strategies

Directory of Open Access Journals (Sweden)

Jian-Kun He

2016-12-01

Full Text Available The Paris Agreement establishes a new mechanism for post-2020 global climate governance, and sets long-term goals for global response to climate change, which will accelerate worldwide low-carbon transformation of economic development pattern, promote the revolutionary reform of energy system, boost a fundamental change in the mode of social production and consumption, and further the civilization of human society from industrial civilization to eco-civilization. The urgency of global low-carbon transition will reshape the competition situation of world's economy, trade and technology. Taking the construction of eco-civilization as a guide, China explores green and low-carbon development paths, establishes ambitious intended nationally determined contribution (INDC targets and action plans, advances energy production and consumption revolution, and speeds up the transformation of economic development pattern. These strategies and actions not only confirm to the trend of the world low-carbon transition, but also meet the intrinsic requirements for easing the domestic resources and environment constraints and realizing sustainable development. They are multi-win-win strategies for promotion of economic development and environmental protection and mitigation of carbon emissions. China should take the global long-term emission reduction targets as a guide, and formulate medium and long-term low-carbon development strategy, build the core competitiveness of low-carbon advanced technology and development pattern, and take an in-depth part in global governance so as to reflect the responsibility of China as a great power in constructing a community of common destiny for all mankind and addressing global ecological crisis.

ASSESSMENT OF THE BUSINESS ENVIRONMENT FOR DEVELOPMENT OF GLOBAL MARKETING STRATEGY

Directory of Open Access Journals (Sweden)

V. Savelyev

2014-03-01

Full Text Available The article concerns with essence of assessment of the business environment and specific directions of analysis during the working out of global marketing strategy. The classification of the global marketing environment researches and tasks sequence in the context of the decisions made on each stage of global marketing strategy is proposed.

Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

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Abdelouahid El-Khattouti

2013-01-01

Full Text Available Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

Undergraduate nursing students writing therapeutic letters to families: an educational strategy.

Science.gov (United States)

Erlingsson, Christen

2009-02-01

Writing therapeutic letters to families is discussed in this article as an educational strategy encouraging students to think reflectively about family nursing. At the University of Kalmar, Sweden, undergraduate nursing students in a primary care module interviewed families using the Calgary Family Assessment Model and wrote therapeutic letters to these families. This article describes (a) the examination process, which was the context for writing therapeutic letters, (b) results of analyses of the letters, and (c) student's post-examination evaluation comments. Results indicate that most students needed encouragement to focus on the family's strengths and resources instead of focusing on own feelings or problems they perceived the family as having. Students also needed support in relinquishing their hierarchical role of "expert nurse." Students' evaluation comments showed that writing therapeutic letters provided students with opportunities to reflect about the connections between family nursing theory and the family itself.

Forest Service Global Change Research Strategy, 2009-2019 Implementation Plan

Science.gov (United States)

Allen Solomon; Richard A. Birdsey; Linda A. Joyce

2010-01-01

In keeping with the research goals of the U.S. Global Change Research Program, the climate change strategy of the U.S. Department of Agriculture (USDA), and the climate change framework of the Forest Service, this Forest Service Global Change Research Strategy, 2009-2019 Implementation Plan (hereafter called the Research Plan), was written by Forest Service Research...

A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.

Science.gov (United States)

Orr, Miranda E; Sullivan, A Campbell; Frost, Bess

2017-07-01

There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Managing differences: the central challenge of global strategy.

Science.gov (United States)

Ghemawat, Pankaj

2007-03-01

The main goal of any international strategy should be to manage the large differences that arise at the borders of markets. Yet executives often fail to exploit market and production discrepancies, focusing instead on the tensions between standardization and localization. In this article, Pankaj Ghemawat presents a new framework that encompasses all three effective responses to the challenges of globalization. He calls it the AAA Triangle. The A's stand for the three distinct types of international strategy. Through adaptation, companies seek to boost revenues and market share by maximizing their local relevance. Through aggregation, they attempt to deliver economies of scale by creating regional, or sometimes global, operations. And through arbitrage, they exploit disparities between national or regional markets, often by locating different parts of the supply chain in different places--for instance, call centers in India, factories in China, and retail shops in Western Europe. Ghemawat draws on several examples that illustrate how organizations use and balance these strategies and describes the trade-offs they make as they do so. Because most enterprises should draw from all three A's to some extent, the framework can be used to develop a summary scorecard indicating how well the company is globalizing. However, given the tensions among the strategies, it's not enough simply to tick off the corresponding boxes. Strategic choice requires some degree of prioritization--and the framework can help with that as well. While it is possible to make progress on all three strategies, companies usually must focus on one or two when trying to build competitive advantage.

The German government's global health strategy--a strategy also to support research and development for neglected diseases?

Science.gov (United States)

Fehr, Angela; Razum, Oliver

2014-01-01

Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D) deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

The regions and global warming: Impacts and response strategies

International Nuclear Information System (INIS)

1991-01-01

To date, much of the attention given to global warming in scientific research as well as in policy development has focused on the global picture. International negotiations and agreements to stabilize, and eventually reduce, greenhouse gas emissions are very important. By themselves, however, they are not sufficient to address global warming. Regional strategies are also needed. They can help reduce greenhouse gas emissions, and they will be the most effective way to mitigate the consequences of global warming. Adaptive strategies must respond to local and regional conditions. In many countries, subnational jurisdictions such as states and provinces or community organizations can already take effective actions without direction from their national government or waiting for international agreements. An important factor in defining regional approaches is the disparate consequences of climate change for developed and developing areas. Different strategies will also be needed for industrial and agricultural regions. Wealthy industrial regions may be better able to develop capital-intensive, adaptive infrastructure than regions with fewer discretionary resources where people are more vulnerable to the vagaries of weather patterns. On the other hand, regions that rely on indigenous knowledge and local resources may be better equipped to make incremental adaptations and more willing to modify life-styles. Ultimately, all climate change effects are experienced in specific places and effective response depends upon local action. We recognize that individual localities cannot solve a problem of global proportions by acting alone. However, a regional strategy can supplement international and national action and be the focal point for addressing risks in the unique social and economic context of a particular area. These meetings discussions dealt with the impacts and implications of climate change on such things as agriculture, forestry, and policy

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

Science.gov (United States)

Pachori, Alok S; Melo, Luis G; Hart, Melanie L; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D; Stahl, Gregory L; Pratt, Richard E; Dzau, Victor J

2004-08-17

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

Science.gov (United States)

Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

2004-08-01

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

Global Strategy: The World is your Oyster (if you can shuck it!)

NARCIS (Netherlands)

T.H. Reus (Taco)

2014-01-01

textabstractIn this inaugural lecture, Taco briefly describes the disciplinary background, central research questions, and themes of Global Strategy, and he presents what may be the dominant framework of understanding how global strategy works and what determines its success. In a nutshell, the

Hydrogen energy strategies and global stability and unrest

International Nuclear Information System (INIS)

Midilli, A.; Dincer, I.; Rosen, M.A.

2004-01-01

This paper focuses on hydrogen energy strategies and global stability and unrest. In order to investigate the strategic relationship between these concepts, two empirical relations that describe the effects of fossil fuels on global stability and global unrest are developed. These relations incorporate predicted utilization ratios for hydrogen energy from non-fossil fuels, and are used to investigate whether hydrogen utilization can reduce the negative global effects related to fossil fuel use, eliminate or reduce the possibilities of global energy conflicts, and contribute to achieving world stability. It is determined that, if utilization of hydrogen from non-fossil fuels increases, for a fixed usage of petroleum, coal and natural gas, the level of global unrest decreases. However, if the utilization ratio of hydrogen energy from non-fossil fuels is lower than 100%, the level of global stability decreases as the symptoms of global unrest increase. It is suggested that, to reduce the causes of global unrest and increase the likelihood of global stability in the future, hydrogen energy should be widely and efficiently used, as one component of plans for sustainable development. (author)

Economic optimization of a global strategy to address the pandemic threat.

Science.gov (United States)

Pike, Jamison; Bogich, Tiffany; Elwood, Sarah; Finnoff, David C; Daszak, Peter

2014-12-30

Emerging pandemics threaten global health and economies and are increasing in frequency. Globally coordinated strategies to combat pandemics, similar to current strategies that address climate change, are largely adaptive, in that they attempt to reduce the impact of a pathogen after it has emerged. However, like climate change, mitigation strategies have been developed that include programs to reduce the underlying drivers of pandemics, particularly animal-to-human disease transmission. Here, we use real options economic modeling of current globally coordinated adaptation strategies for pandemic prevention. We show that they would be optimally implemented within 27 y to reduce the annual rise of emerging infectious disease events by 50% at an estimated one-time cost of approximately $343.7 billion. We then analyze World Bank data on multilateral "One Health" pandemic mitigation programs. We find that, because most pandemics have animal origins, mitigation is a more cost-effective policy than business-as-usual adaptation programs, saving between $344.0.7 billion and $360.3 billion over the next 100 y if implemented today. We conclude that globally coordinated pandemic prevention policies need to be enacted urgently to be optimally effective and that strategies to mitigate pandemics by reducing the impact of their underlying drivers are likely to be more effective than business as usual.

Therapeutic Symptomatic Strategies in the Parasomnias.

Science.gov (United States)

Manni, Raffaele; Toscano, Gianpaolo; Terzaghi, Michele

2018-06-05

The purpose of this review was to discuss the currently available pharmacologic and non-pharmacologic treatment options for parasomnias. Recent pathophysiological findings about sleep structure in parasomnias helped understanding several drug mechanisms of action. Serotoninergic theory accounts for the effect of serotoninergic drugs. Study about spectral analysis of sleep showed the effect of clonazepam on spectral bands. Cannabinoids proved to be effective in some of parasomnias, as in many other neurological disorders. A series of therapeutic strategies were analyzed and compared. Benzodiazepines, antidepressant drugs, and L-5-hydroxytryptophan may be beneficial in DOA. SSRI and topiramate are effective in SRED. RBD responds to clonazepam, melatonin, and to a lesser extent to dopaminergic and anticholinergic agents. Prazosin and cannabinoids are effective in nightmare disorder. Sleep paralysis may respond to antidepressant agents. Tricyclic antidepressant may be effective in sleep-related hallucinations and exploding head syndrome. Sleep enuresis may be successfully treated with desmopressin, anticholinergic drugs, and imipramine.

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

Directory of Open Access Journals (Sweden)

Sumit Sarkar

2016-06-01

Full Text Available Parkinsonism is a progressive motor disease that affects 1.5 million Americans and is the second most common neurodegenerative disease after Alzheimer’s. Typical neuropathological features of Parkinson’s disease (PD include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway and depositions of cytoplasmic fibrillary inclusions (Lewy bodies which contain ubiquitin and α-synuclein. The cardinal motor signs of PD are tremors, rigidity, slow movement (bradykinesia, poor balance, and difficulty in walking (Parkinsonian gait. In addition to motor symptoms, non-motor symptoms that include autonomic and psychiatric as well as cognitive impairments are pressing issues that need to be addressed. Several different mechanisms play an important role in generation of Lewy bodies; endoplasmic reticulum (ER stress induced unfolded proteins, neuroinflammation and eventual loss of dopaminergic neurons in the substantia nigra of mid brain in PD. Moreover, these diverse processes that result in PD make modeling of the disease and evaluation of therapeutics against this devastating disease difficult. Here, we will discuss diverse mechanisms that are involved in PD, neuroprotective and therapeutic strategies currently in clinical trial or in preclinical stages, and impart views about strategies that are promising to mitigate PD pathology.

European strategy/global strategy

Energy Technology Data Exchange (ETDEWEB)

Testore, R. [FIAT Auto S.p.A., Turin (Italy)

1998-08-01

In order to be `global`, a carmaker has to satisfy three main criteria: a global customer service, a global market presence, a global respect for the environment. Just in a word, the automotive industry needs to develop - and has indeed already launched - a process of global re-engineering of its: product, processes, and market. The product is not simply a `car`, but a global mobility service. This is what an increasingly diversified clientele is demanding in order to meet its particular mobility needs in terms of comfort and safety, in a way that does not damage the environment and at welldefined, competitive costs. The process is not just a matter of the way we design, manufacture and distribute our product. We have to re-design our entire corporate profile, redefine the parameters of our specific strategic mission, identifying the levels of control and our core business in a way that is consistent with our particular history, market positioning and growth targets. The market is no longer hard set, but is globally diversified, ready to expand into important niches and to meet the personalized needs of specific users: from VIPs to the elderly or the disables, and so on. (orig.)

Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

Science.gov (United States)

Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

2017-08-10

One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

A readily applicable strategy to convert peptides to peptoid-based therapeutics.

Directory of Open Access Journals (Sweden)

Minyoung Park

Full Text Available Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics.

WHO global and regional strategies for health and environment

International Nuclear Information System (INIS)

Hisashi Ogawa

1996-01-01

This paper describes the WHO global and regional strategies for health and environment and discusses research needs on environmental health to support the implementation of the strategies. Particular emphasis on applied researches which generate information, for decision making, on health effects of development and environmental changes in specific locations

WHO global and regional strategies for health and environment

Energy Technology Data Exchange (ETDEWEB)

Ogawa, Hisashi [World Health Organization, Manila (Philippines). Regional Office for the Western Pacific

1997-12-31

This paper describes the WHO global and regional strategies for health and environment and discusses research needs on environmental health to support the implementation of the strategies. Particular emphasis on applied researches which generate information, for decision making, on health effects of development and environmental changes in specific locations.

Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs.

Science.gov (United States)

Shu, Yisong; Liu, Zhenli; Zhao, Siyu; Song, Zhiqian; He, Dan; Wang, Menglei; Zeng, Honglian; Lu, Cheng; Lu, Aiping; Liu, Yuanyan

2017-08-01

Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic fashion with the synergistic function of multiple characteristic constituents. The holism philosophy of TCM is coincident with global and systematic theories of metabolomics. The proposed pseudotargeted metabolomics methodologies were employed for the establishment of reliable quality control markers for use in the screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages of both targeted and untargeted methods. In the present study, targeted metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for in vivo quantitative plasma pharmacochemistry study of characteristic prototypic constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS with better specificity and selectivity was employed for identification of untargeted metabolites in the complex plasma matrix. In all, 32 prototypic metabolites were quantitatively determined, and 66 biotransformed metabolites were convincingly identified after being orally administered with standard extracts of four labeled Citrus TCMs. The global absorption and metabolism process of complex TCMs was depicted in a systematic manner.

Global Cities and Multinational Enterprise Location Strategy

DEFF Research Database (Denmark)

Goerzen, Anthony; Geisler Asmussen, Christian; Nielsen, Bo Bernhard

2013-01-01

We combine the concept of location derived by economic geographers with theories of the multinational enterprise (MNE) and the liability of foreignness developed by international business scholars, to examine the factors that propel MNEs toward, or away from, “global cities”. We argue that three...... distinctive characteristics of global cities – global interconnectedness, cosmopolitanism, and abundance of advanced producer services – help MNEs overcome the costs of doing business abroad, and we identify the contingencies under which these characteristics combine with firm attributes to exert......- and subsidiary-level factors, including investment motives, proprietary capabilities, and business strategy. Our study provides important insights for international business scholars by shedding new light on MNE location choices and also contributes to our understanding of economic geography by examining...

[Global and national strategies against antibiotic resistance].

Science.gov (United States)

Abu Sin, Muna; Nahrgang, Saskia; Ziegelmann, Antina; Clarici, Alexandra; Matz, Sibylle; Tenhagen, Bernd-Alois; Eckmanns, Tim

2018-05-01

Antimicrobial resistance (AMR) is increasingly perceived as a global health problem. To tackle AMR effectively, a multisectoral one health approach is needed. We present some of the initiatives and activities at the national and global level that target the AMR challenge. The Global Action Plan on AMR, which has been developed by the World Health Organization (WHO), in close collaboration with the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) is considered a blueprint to combat AMR. Member states endorsed the action plan during the World Health Assembly 2015 and committed themselves to develop national action plans on AMR. The German Antibiotic Resistance Strategy (DART 2020) is based on the main objectives of the global action plan and was revised and published in 2015. Several examples of the implementation of DART 2020 are outlined here.

Priority setting of strategies and mechanisms for limiting global warming

International Nuclear Information System (INIS)

Lewis, S.J.L.

1994-01-01

Scientific communities have reached a consensus that increases of greenhouse gas emission will result in climatic warming and sea level rises despite existing uncertainties. Major uncertainties include the sensitivities of climate changes in terms of timing, magnitude, and scales of regional changes. Socioeconomic uncertainties encompass population and economic growth, changes in technology, future reliance on fossil fuel, and policies compiled to stabilize the global warming. Moreover, increase in world population coupled with limited resources will increase the vulnerability of ecosystems and social systems. Global warming has become an international concern since the destinies of all nations are closely interwoven by this issue and how nations deal with it. Appropriate strategies and mechanisms are need to slow down the buildup of CO 2 and other greenhouse gases. Questionnaires were sent to 150 experts in 30 countries to evaluate such strategies and mechanisms for dealing with global warming, from both the domestic and international perspectives. This paper will focus primarily on strategy selection

The place of physical activity in the WHO Global Strategy on Diet and Physical Activity.

Science.gov (United States)

Bauman, Adrian; Craig, Cora L

2005-08-24

In an effort to reduce the global burden of non-communicable disease, the World Health Organization released a Global Strategy for Diet and Physical Activity in May 2004. This commentary reports on the development of the strategy and its importance specifically for physical activity-related work of NGOs and researchers interested in increasing global physical activity participation. Sparked by its work on global efforts to target non-communicable disease prevention in 2000, the World Health Organization commissioned a global strategy on diet and physical activity. The physical activity interest followed efforts that had led to the initial global "Move for Health Day" in 2002. WHO assembled a reference group for the global strategy, and a regional consultation process with countries was undertaken. Underpinning the responses was the need for more physical activity advocacy; partnerships outside of health including urban planning; development of national activity guidelines; and monitoring of the implementation of the strategy. The consultation process was an important mechanism to confirm the importance and elevate the profile of physical activity within the global strategy. It is suggested that separate implementation strategies for diet and physical activity may be needed to work with partner agencies in disparate sectors (e.g. urban planning for physical activity, agriculture for diet). International professional societies are well situated to make an important contribution to global public health by advocating for the importance of physical activity among risk factors; developing international measures of physical activity and global impacts of inactivity; and developing a global research and intervention agenda.

The place of physical activity in the WHO Global Strategy on Diet and Physical Activity

Directory of Open Access Journals (Sweden)

Craig Cora L

2005-08-01

Full Text Available Abstract In an effort to reduce the global burden of non-communicable disease, the World Health Organization released a Global Strategy for Diet and Physical Activity in May 2004. This commentary reports on the development of the strategy and its importance specifically for physical activity-related work of NGOs and researchers interested in increasing global physical activity participation. Sparked by its work on global efforts to target non-communicable disease prevention in 2000, the World Health Organization commissioned a global strategy on diet and physical activity. The physical activity interest followed efforts that had led to the initial global "Move for Health Day" in 2002. WHO assembled a reference group for the global strategy, and a regional consultation process with countries was undertaken. Underpinning the responses was the need for more physical activity advocacy; partnerships outside of health including urban planning; development of national activity guidelines; and monitoring of the implementation of the strategy. The consultation process was an important mechanism to confirm the importance and elevate the profile of physical activity within the global strategy. It is suggested that separate implementation strategies for diet and physical activity may be needed to work with partner agencies in disparate sectors (e.g. urban planning for physical activity, agriculture for diet. International professional societies are well situated to make an important contribution to global public health by advocating for the importance of physical activity among risk factors; developing international measures of physical activity and global impacts of inactivity; and developing a global research and intervention agenda.

Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

Science.gov (United States)

Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

2017-08-01

Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

Economic optimization of a global strategy to address the pandemic threat

Science.gov (United States)

Pike, Jamison; Bogich, Tiffany; Elwood, Sarah; Finnoff, David C.; Daszak, Peter

2014-01-01

Emerging pandemics threaten global health and economies and are increasing in frequency. Globally coordinated strategies to combat pandemics, similar to current strategies that address climate change, are largely adaptive, in that they attempt to reduce the impact of a pathogen after it has emerged. However, like climate change, mitigation strategies have been developed that include programs to reduce the underlying drivers of pandemics, particularly animal-to-human disease transmission. Here, we use real options economic modeling of current globally coordinated adaptation strategies for pandemic prevention. We show that they would be optimally implemented within 27 y to reduce the annual rise of emerging infectious disease events by 50% at an estimated one-time cost of approximately $343.7 billion. We then analyze World Bank data on multilateral “One Health” pandemic mitigation programs. We find that, because most pandemics have animal origins, mitigation is a more cost-effective policy than business-as-usual adaptation programs, saving between $344.0.7 billion and $360.3 billion over the next 100 y if implemented today. We conclude that globally coordinated pandemic prevention policies need to be enacted urgently to be optimally effective and that strategies to mitigate pandemics by reducing the impact of their underlying drivers are likely to be more effective than business as usual. PMID:25512538

Hydrogels for central nervous system therapeutic strategies.

Science.gov (United States)

Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

2015-12-01

The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described. © IMechE 2015.

Corporate Strategies and Global Competition: Odense Steel Shipyard, 1918-2012

DEFF Research Database (Denmark)

Poulsen, Rene Taudal; Jensen, Kristoffer; Christensen, Rene Schroder

2017-01-01

This article analyzes the competitive strategies of Odense Steel Shipyard between 1918 and 2012 and challenges existing scholarship on competition in global industries. Until the 1980s, the yard adopted typical strategies in shipbuilding, starting with cost leadership and subsequently adopting...

Digital Innovations: Startup Marketing Strategy for Global Growth

OpenAIRE

Gröhn, Hanna

2017-01-01

This thesis discusses the relatively new phenomena of innovative digital products created by startup companies, who often must scale globally fast, before the volatile trends or the fierce competition of the digital marketspace take over. International entry itself is no longer the issue, but rather standing out in the crowd while balancing resources and flexibility. The focus is on how startups can induce global growth and tackle structural obstacles by means of marketing strategy. The t...

The arsenal of pathogens and antivirulence therapeutic strategies for disarming them

Directory of Open Access Journals (Sweden)

Brannon JR

2016-05-01

Full Text Available John R Brannon,1 Maria Hadjifrangiskou1,21Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, 2Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN, USAAbstract: Pathogens deploy an arsenal of virulence factors (VFs to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their development into therapeutics has made a monumental impact on human and microbial populations. Although humans have used antimicrobials for medicinal and agricultural purposes, microorganism populations have developed and shared resistance mechanisms to persevere in the face of classical antimicrobials. However, a positive substitute is antivirulence therapy; antivirulence therapeutics prevent or interrupt an infection by counteracting a pathogen’s VFs. Their application can reduce the use of broad-spectrum antimicrobials and dampen the frequency with which resistant strains emerge. Here, we summarize the contribution of VFs to various acute and chronic infections. In correspondence with this, we provide an overview of the research and development of antivirulence strategies.Keywords: virulence factors, antivirulence therapeutics, biofilms, regulation, Escherichia coli, quorum sensing, persister cells

The German government's global health strategy – a strategy also to support research and development for neglected diseases?

Directory of Open Access Journals (Sweden)

Angela Fehr

2014-07-01

Full Text Available Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

Ford Motor Company's Global Electrification Strategy

OpenAIRE

Ellen Hughes-Cromwick

2011-01-01

Ford Motor Company has developed global platforms for its vehicles, including hybrid electric vehicles and forthcoming battery-electric and plug-in hybrids. Providing electrification technologies is a key element of Ford's broader strategy of producing vehicles that have improved fuel economy and reduced greenhouse emissions. The breadth of this effort—across a range of vehicle types—is unique in the automotive industry. Of particular importance is using the same vehicle platforms for electri...

Developing Strategies for Islamic Banks to Face the Future Challenges of Financial Globalization

OpenAIRE

Al Ajlouni, Ahmed

2004-01-01

Developing Strategies for Islamic Banks to Face the Future Challenges of Financial Globalization Ahmed Al-Ajlouni Abstract This study aims at forming strategic response to assess the ability of Islamic banks in benefiting from the opportunities that may be provided by financial globalization and limits its threats, through assessing the capability of Islamic banks to meet the requirements and challenges of financial globalization, then suggests the suitable strategies that may be ...

Secular trends in mortality associated with new therapeutic strategies in surgical critical illness.

Science.gov (United States)

Hartl, Wolfgang H; Wolf, Hilde; Schneider, Christian P; Küchenhoff, Helmut; Jauch, Karl-Walter

2007-10-01

Since 1999 randomized controlled trials have shown that new therapeutic strategies, such as strict glycemic control, increased use of noninvasive ventilation and of lung-protective ventilation, and early goal-oriented shock therapy, may reduce mortality in selected groups of critically ill patients. Whether these benefits can be translated to a surgical clinical setting is unclear. We wanted to evaluate longitudinally the successive routine implementation of new therapeutic measures and its effect on postsurgical patients admitted to the intensive care unit. We performed a retrospective analysis on data collected prospectively from March 1, 1993 through February 28, 2005. A cohort of 1,802 consecutive cases requiring intensive care therapy for more than 4 days was analyzed. A significant decrease in mortality was observed in the last years of the study. With adjustment for relevant covariates, treatment after the implementation of new therapeutic strategies was identified as an independent factor linked with a reduced risk of death (odds ratio [OR] .518; 95% confidence interval [CI] .337-.796), whereas older age (OR 1.030; 95% CI 1.015-1.045), a high severity score on admission (OR 1.155; 95% CI 1.113-1.198) or during intensive care unit stay (OR 1.187; 95% CI 1.145-1.231), a high number of failing organs (OR 1.918; 95% CI 1.635-2.250), and peritonitis (OR 3.277; 95% CI 2.046-5.246) were independently associated with death. Implementing of a variety of new therapeutic measures into routine care of critically ill surgical patients was associated with improved survival after 2001.

Emerging Therapeutic Strategies for Targeting Chronic Myeloid Leukemia Stem Cells

Directory of Open Access Journals (Sweden)

Ahmad Hamad

2013-01-01

Full Text Available Chronic myeloid leukemia (CML is a clonal myeloproliferative disorder. Current targeted therapies designed to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein have made a significant breakthrough in the treatment of CML patients. However, CML remains a chronic disease that a patient must manage for life. Although tyrosine kinase inhibitors (TKI therapy has completely transformed the prognosis of CML, it has made the therapeutic management more complex. The interruption of TKI treatment results in early disease progression because it does not eliminate quiescent CML stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML to achieve a permanent cure, and to allow TKI interruption. This review summarizes recent research done on alternative targeted therapies with a particular focus on some important signaling pathways (such as Alox5, Hedgehog, Wnt/b-catenin, autophagy, and PML that have the potential to target CML stem cells and potentially provide cure for CML.

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

Science.gov (United States)

Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

2016-06-02

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

Pain and endometriosis: Etiology, impact, and therapeutics

Directory of Open Access Journals (Sweden)

Robert N. Taylor

2012-12-01

Full Text Available The association of pain and endometriosis was recognized with the first definitive published reports of this disorder. Unfortunately, the precise etiologies and pathways leading to nociception and pain symptoms in endometriosis remain poorly understood, and as a result, effective therapeutic interventions are lacking with consequent profound effects on affected women’s quality of life. In this opinion paper we summarize selected proceedings presented at the 28th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE in Istanbul, Turkey, and review the clinical and translational evidence of chronic pain, neurogenesis, and the pernicious impact of dyspareunia on women with symptomatic endometriosis. The effectiveness of medical treatments is critically assessed and the findings indicate that good therapeutic options are available with extant medications effective in some sub-groups of women with endometriosis, many of which are affordable globally. Nevertheless, new management strategies and drugs need to be developed to increase the options of all afflicted women to minimize and ideally eradicate painful symptoms of endometriosis. However, only by elucidating distinctions among sub-groups with specific symptoms, suggesting different mechanisms, are we likely to derive truly successful therapeutic strategies.

Optimal Therapeutic Strategy for Non-small Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor

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Zhong SHI

2015-02-01

Full Text Available Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in non-small cell lung cancer (NSCLC patients, it is still controversial about how to combine EGFR-TKI with chemotherapy and other targeted drugs. We have made a summary on the current therapeutic models of EGFR-TKI combined with chemotherapy/bevacizumab in this review and aimed to find the optimal therapeutic strategy for NSCLC patients with EGFR mutation.

Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

Science.gov (United States)

Vinay, Dass S; Ryan, Elizabeth P; Pawelec, Graham; Talib, Wamidh H; Stagg, John; Elkord, Eyad; Lichtor, Terry; Decker, William K; Whelan, Richard L; Kumara, H M C Shantha; Signori, Emanuela; Honoki, Kanya; Georgakilas, Alexandros G; Amin, Amr; Helferich, William G; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Keith, W Nicol; Bilsland, Alan; Bhakta, Dipita; Halicka, Dorota; Fujii, Hiromasa; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan; Choi, Beom K; Kwon, Byoung S

2015-12-01

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic strategies based on glucagon-like peptide 1

DEFF Research Database (Denmark)

Deacon, Carolyn F

2004-01-01

of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation...... excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency...... of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short...

Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

Science.gov (United States)

Simmons, Danielle A.

2017-01-01

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

Therapeutic immunization strategies against cervical cancer : induction of cell-mediated immunity in murine models

NARCIS (Netherlands)

Bungener, Laura Barbara

2004-01-01

The aim of the study described in this thesis is the development of a therapeutic immunization strategy against cervical cancer and pre-malignant precursor lesions of cervical cancer (CIN lesions). Cervical cancer is caused by high risk human papillomavirus (HPV). Two of the early proteins of high

Burnout Syndrome: Global Medicine Volunteering as a Possible Treatment Strategy.

Science.gov (United States)

Iserson, Kenneth V

2018-04-01

In the last few decades, "burnout syndrome" has become more common among clinicians, or at least more frequently recognized. Methods to prevent and treat burnout have had inconsistent results. Simultaneously, clinicians' interest in global medicine has increased dramatically, offering a possible intervention strategy for burnout while providing help to underserved areas. Caused by a variety of stressors, burnout syndrome ultimately results in physicians feeling that their work no longer embodies why they entered the medical field. This attitude harms clinicians, their patients and colleagues, and society. Few consistently successful interventions exist. At the same time, clinicians' interest in global medicine has risen exponentially. This paper reviews the basics of both phenomena and posits that global medicine experiences, although greatly assisting target populations, also may offer a strategy for combating burnout by reconnecting physicians with their love of the profession. Because studies have shown that regular volunteering improves mental health, short-term global medicine experiences may reinvigorate and reengage clinicians on the verge of, or suffering from, persistent burnout syndrome. Fortuitously, this intervention often will greatly benefit medically underserved populations. Copyright © 2018 Elsevier Inc. All rights reserved.

Music as a Therapeutic Assistant: Strategy to Reduce Work Stress

Directory of Open Access Journals (Sweden)

Dereck Sena de Lima

2017-02-01

Full Text Available Objective: to understand the influence of music as a therapeutic assistant in reducing work stress of nursing professionals in a basic health unit. Method: it is an exploratory and descriptive research with a quantitative approach, developed with 9 nursing professionals from UBS Integrated Nova Esperança in João Pessoa, Paraíba. Data collection began after approval of the Research Ethics Committee of the Health Sciences Center of the Federal University of Paraíba, nº. 0508/16, CAAE: 58741916.6.0000.5188. Results: we identified that 33.3% of nursing professionals presented signs of stress, of the 33.3% who presented stress, 100% demonstrated to be in the resistance phase, 100% of the nursing professionals evaluated the musical strategy in a positive way. Conclusion: the musical strategy received extremely positive evaluations by the participants of the research, about 100% of professionals said that listening to music can reduce work stress.

Therapeutic strategies in Sickle Cell Anemia: The past present and future.

Science.gov (United States)

Fernandes, Queenie

2017-06-01

Sickle Cell Anemia (SCA) was one of the first hemoglobinopathies to be discovered. It is distinguished by the mutation-induced expression of a sickle cell variant of hemoglobin (HbS) that triggers erythrocytes to take a characteristic sickled conformation. The complex physiopathology of the disease and its associated clinical complications has initiated multi-disciplinary research within its field. This review attempts to lay emphasis on the evolution, current standpoint and future scope of therapeutic strategies in SCA. Copyright © 2017 Elsevier Inc. All rights reserved.

WHAT FIRMS ARE REWARDED AFTER GLOBAL FINANCIAL CRISIS? THE ROLE OF INNOVATION AND GLOBALIZATION STRATEGIES IN RECOVERY

Directory of Open Access Journals (Sweden)

Victoria Golikova

2016-03-01

Full Text Available The aim of the research is to conduct an empirical investigation and reveal what types of globalization and innovation strategies in turbulent and unfavorable regional institutional environment are most likely to be associated with different trajectories of Russian manufacturing firms’ performance in 2007- 2012. We employ the results of empirical survey of 1000 medium and large enterprises in manufacturing (2009 linked to financial data from Amadeus database and the data on the regional institutional environment. We test that (1 introduction of innovations before the crisis ceteris paribus helped the firms to successfully pass the crisis and recover. We expect that (2 companies that became globalized before the crisis (via importing of intermediate and capital goods; exporting; FDI; establishment of partner linkages with foreign firms ceteris paribus are more likely to successfully pass the crisis and grow. And (3 propose the positive effect of synergy of innovation efforts and globalization strategy of the firm. We expect that the abovementioned factors are complimentary and reinforce the ability of the firm to recover after crisis shock. We found strong support for the hypothesis that firms financing introduction of new products before the crisis and simultaneously managed to promote and sell them on the global market were rewarded by quick return to the growing path after global crisis. Other strategies, i.e. solely innovations without exporting play insignificant role while exporting without attempts to introduce new products contribute even negatively to post-crisis recover. Institutional environment also matters: in the regions with less level of corruption firms were more likely to grow after the crisis.

Investigation of therapeutic strategy for acute empyema

International Nuclear Information System (INIS)

Mochinaga, Koji; Akamine, Shinji; Muraoka, Masashi; Morino, Shigeyuki

2011-01-01

Recently, it has been reported that video-assisted thoracoscopic chest drainage is a useful treatment for acute empyema, but its indication has not been clarified. We retrospectively reviewed acute empyema patients by dividing them into 3 groups: operation group (7 patients), drainage group (6 patients), and antibiotic treatment group (9 patients), and then we evaluated the therapeutic strategy by examining the radiological findings, drainage period, and hospital stay. In the antibiotic treatment group, the ratio of pleural effusion on chest radiograph was under 1/4 in all patients. There were 5 patients who showed multilocular findings on chest CT, and all patients underwent an operation. Regarding the drainage period, the operation group showed a significantly shorter period than the drainage group. Concerning the hospital stay, the drainage group showed a significantly longer stay than the other 2 groups. The ratio of pleural effusion on chest radiograph was under 1/4, giving an indication for antibiotic treatment. With multilocular findings on CT, an indication for surgery is needed. Patients requiring drainage, which necessitates a long hospital stay, should be advised to consider surgery. (author)

Cell-based therapeutic strategies for multiple sclerosis.

Science.gov (United States)

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Possible global strategies for stopping polio vaccination and how they could be harmonized.

Science.gov (United States)

Cochi, S L; Sutter, R W; Aylward, R B

2001-01-01

One of the challenges of the polio eradication initiative over the next few years will be the formulation of an optimal strategy for stopping poliovirus vaccination after global certification of polio eradication has been accomplished. This strategy must maximize the benefits and minimize the risks. A number of strategies are currently under consideration, including: (i) synchronized global discontinuation of use of oral poliovirus vaccine (OPV); (ii) regional or subregional coordinated OPV discontinuation; and (iii) moving from trivalent to bivalent or monovalent OPV. Other options include moving from OPV to global use of IPV for an interim period before cessation of IPV use (to eliminate circulation of vaccine-derived poliovirus, if necessary) or development of new OPV strains that are not transmissible. Each of these strategies is associated with specific advantages (financial benefits for OPV discontinuation) and disadvantages (cost of switch to IPV) and inherent uncertainties (risk of continued poliovirus circulation in certain populations or prolonged virus replication in immunodeficient persons). An ambitious research agenda addresses the remaining questions and issues. Nevertheless, several generalities are already clear. Unprecedented collaboration between countries, regions, and indeed the entire world will be required to implement a global OPV discontinuation strategy Regulatory approval will be needed for an interim bivalent OPV or for monovalent OPV in many countries. Manufacturers will need sufficient lead time to produce sufficient quantities of IPV Finally, the financial implications for any of these strategies need to be considered. Whatever strategy is followed it will be necessary to stockpile supplies of a poliovirus-containing vaccine (most probably all three types of monovalent OPV), and to develop contingency plans to respond should an outbreak of polio occur after stopping vaccination.

Therapeutic antibodies as a treatment option for dengue fever.

Science.gov (United States)

Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

2013-11-01

Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

The Assessment of the Colo-rectal Polyps in Order to the New Diagnostic and Therapeutic Strategies

Directory of Open Access Journals (Sweden)

Raluca Diac Andreea

2015-09-01

Full Text Available Objective. Assessment of the histological and endoscopic features of the colo-rectal polyps is requered for the application of the new diagnostic and therapeutical strategies in the managment of the diminutive polyps.

Terrestrial ecosystem responses to global change: A research strategy

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-09-01

Uncertainty about the magnitude of global change effects on terrestrial ecosystems and consequent feedbacks to the atmosphere impedes sound policy planning at regional, national, and global scales. A strategy to reduce these uncertainties must include a substantial increase in funding for large-scale ecosystem experiments and a careful prioritization of research efforts. Prioritization criteria should be based on the magnitude of potential changes in environmental properties of concern to society, including productivity; biodiversity; the storage and cycling of carbon, water, and nutrients; and sensitivity of specific ecosystems to environmental change. A research strategy is proposed that builds on existing knowledge of ecosystem responses to global change by (1) expanding the spatial and temporal scale of experimental ecosystem manipulations to include processes known to occur at large scales and over long time periods; (2) quantifying poorly understood linkages among processes through the use of experiments that manipulate multiple interacting environmental factors over a broader range of relevant conditions than did past experiments; and (3) prioritizing ecosystems for major experimental manipulations on the basis of potential positive and negative impacts on ecosystem properties and processes of intrinsic and/or utilitarian value to humans and on feedbacks of terrestrial ecosystems to the atmosphere.

Simulation analysis of globally integrated logistics and recycling strategies

Energy Technology Data Exchange (ETDEWEB)

Song, S.J.; Hiroshi, K. [Hiroshima Inst. of Tech., Graduate School of Mechanical Systems Engineering, Dept. of In formation and Intelligent Systems Engineering, Hiroshima (Japan)

2004-07-01

This paper focuses on the optimal analysis of world-wide recycling activities associated with managing the logistics and production activities in global manufacturing whose activities stretch across national boundaries. Globally integrated logistics and recycling strategies consist of the home country and two free trading economic blocs, NAFTA and ASEAN, where significant differences are found in production and disassembly cost, tax rates, local content rules and regulations. Moreover an optimal analysis of globally integrated value-chain was developed by applying simulation optimization technique as a decision-making tool. The simulation model was developed and analyzed by using ProModel packages, and the results help to identify some of the appropriate conditions required to make well-performed logistics and recycling plans in world-wide collaborated manufacturing environment. (orig.)

Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

Science.gov (United States)

Brzóska, Malgorzata M; Borowska, Sylwia; Tomczyk, Michal

2016-01-01

Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

Global History. A Curriculum Guide. Second Semester. Theme V: The Industrial Revolution Had Global Impact. Teacher Strategies. Experimental Edition.

Science.gov (United States)

New York City Board of Education, Brooklyn, NY. Div. of Curriculum and Instruction.

Designed to assist teachers and supervisors in the implementation of the global history course, this bulletin presents learning activities which include the rationale, performance objectives, and teaching strategies related to Theme V entitled, "The Industrial Revolution Had Global Impact." This theme has seven subthemes: (1)…

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

Science.gov (United States)

Gross, Christina; Berry-Kravis, Elizabeth M; Bassell, Gary J

2012-01-01

Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. PMID:21796106

The Strategy - Ending Globalization Disorders

Directory of Open Access Journals (Sweden)

Yunus Lubega Butanaziba

2010-12-01

Full Text Available Scientifically, globalization is a pure-form or model that refers to a condition whereby a dominant state unilaterally or multilaterally maintains a balance of power to fail member states in the international system it dominates. Globalization can be implemented exclusively or inclusively under blocs (regional or International Governmental Organizations (IGOs as means of the balance of power for the failure of states. This is the theme that this article pursues to objectively examine the current globalization regime as the function of two arms of the balance of power applied to fail states in the international system. One arm of the current globalization regime applies interest-lending of the Bretton Woods institutions namely, International Bank for Reconstruction (IBRD/World Bank and International Monetary Fund (IMF. The other arm uses the strategy of resource wars. The problem is that interest charges of the World Bank and IMF have failed to cause real domestic growth in 185 states since the initial Ten/Five-year Development Plans, 1946/51-56. This is seen in the domestic and foreign debt burdens arising out of loan interests of the IBRD/World Bank and IMF. There have been more than 136 resource wars that have caused over250 million deaths (market value loss of over USD 500 trillion in the period 1946 to date. The unit of analysis of the paper is that the previous and current strategies of globalization have been illegitimate, severely violated fundamental human right, contravened business ethics and caused the failure states. Thus, the Bretton Woods system has not, and will not as it stands, benefit USA and her allied member states and the Third World inclusive.Legally and morally, Latin American states who signed the Bretton Woods Agreements in 1944 were not in-due-form: African, Asian and Eastern European states were not represented; and given the most compelling fact that others from Europe (e.g. Germany and Japan agreed in the unique

Global warming: Towards a strategy for Ontario

International Nuclear Information System (INIS)

1990-01-01

A discussion paper is provided as background to a proposed public review of a strategy for Ontario's response to global warming. Global warming arises from the generation of greenhouse gases, which come from the use of fossil fuels, the use of chlorofluorocarbons, and deforestation. Energy policy is the backbone of achieving climate stability since the burning of fossil fuels releases most of the greenhouse gases, mainly carbon dioxide. Canada is, by international standards, a very energy-intensive country and is among the world's largest emitters of carbon dioxide on a per capita basis. Ontario is the largest energy-using province in Canada, and fossil fuels represent over 80% of provincial energy use. A proposed goal for Ontario is to provide leadership in stabilizing atmospheric concentrations of the greenhouse gases, while minimizing the social, economic, and environmental costs in Ontario of adapting to global warming. A proposed first step to address global warming is to achieve reductions in expected emissions of the greenhouse gases, especially carbon dioxide, so that levels by the year 2000 are lower than in 1989. Current policies and regulations helping to reduce the greenhouse effect include some of the current controls on automotive emissions and the adoption by the provincial electric utility of targets to reduce electricity demand. New initiatives include establishment of minimum energy efficiency standards and reduction of peak-day electricity use. Action steps for future consideration are detailed in the categories of greenhouse gas emissions reductions, carbon dioxide absorption, and research and analysis into global warming

Strategies for ensuring global consistency/comparability of water-quality data

Science.gov (United States)

Klein, J.M.

1999-01-01

In the past 20 years the water quality of the United States has improved remarkably-the waters are safer for drinking, swimming, and fishing. However, despite many accomplishments, it is still difficult to answer such basic questions as: 'How clean is the water?' and 'How is it changing over time?' These same questions exist on a global scale as well. In order to focus water-data issues in the United States, a national Intergovernmental Task Force on Monitoring Water Quality (ITFM) was initiated for public and private organizations, whereby key elements involved in data collection, analysis, storage, and management could be made consistent and comparable. The ITFM recommended and its members are implementing a nationwide strategy to improve water-quality monitoring, assessment, and reporting activities. The intent of this paper is to suggest that a voluntary effort be initiated to ensure the comparability and utility of hydrological data on a global basis. Consistent, long-term data sets that are comparable are necessary in order to formulate ideas regarding regional and global trends in water quantity and quality. The author recommends that a voluntary effort similar to the ITFM effort be utilized. The strategy proposed would involve voluntary representation from countries and international organizations (e.g. World Health Organization) involved in drinking-water assessments and/or ambient water-quality monitoring. Voluntary partnerships such as this will improve curability to reduce health risks and achieve a better return on public and private investments in monitoring, environmental protection, and natural resource management, and result in a collaborative process that will save millions of dollars.In this work it is suggested that a voluntary effort be initiated to ensure the comparability and utility of hydrological data on a global basis. The strategy proposed would involve voluntary representation from countries and international organizations involved in

Factors associated with therapeutic strategies in patients with splanchnic vein thrombosis: Results of an international registry

NARCIS (Netherlands)

Riva, N.; Ageno, W.; Schulman, S.; Bang, S.M.; Sartori, M.T.; Grandone, E.; Beyer, J.; Barillari, G.; Di Minno, D.; Duce, R.; Malato, A.; Santoro, R.; Poli, D.; Verhamme, P.; Martinelli, I.; Kamphuisen, P.; Alatri, A.; Becattini, C.; Bucherini, E.; Piana, A.; De Stefano, V.; Dentali, F.

2012-01-01

Background Treatment of splanchnic vein thrombosis (SVT) is challenging due to the heterogeneous clinical presentation and the increased bleeding risk. We aimed to describe current treatment strategies and factors associated with therapeutic decisions. Materials and Methods Between May 2008 and

The EU's New Global Strategy : Its Implementation in a Troubled International Environment

NARCIS (Netherlands)

Buitelaar, T.; Larik, J.E.; Matta, A.; Vos, de B.

2016-01-01

Executive Summary In June 2016, High Representative Mogherini presented the EU’s new Global Strategy on Foreign and Security Policy (EUGS) to the European Council. With the Strategy now finalized, attention needs to turn to its implementation in an environment mired by crises both within Europe and

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Science.gov (United States)

2015-01-01

Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574

Base-of-the-pyramid global strategy

Directory of Open Access Journals (Sweden)

Boşcor, D.

2010-12-01

Full Text Available Global strategies for MNCs should focus on customers in emerging and developing markets instead of customers in developed economies. The “base-of-the-pyramid segment” comprises 4 billion people in the world. In order to be successful, companies will be required to form unconventional partnerships- with entities ranging from local governments to non-profit organizations - to gain the community’s trust and understand the environmental, infrastructure and political issues that may affect business. Being able to provide affordable, high-quality products and services in this market segment often means new approaches to marketing- new packaging and pricing structures, and using unfamiliar distribution structures.

19th Annual conference ampersand exposition: Global strategies for environmental issues

International Nuclear Information System (INIS)

Anon.

1994-01-01

The 19th Annual conference and exposition on Global Strategies for Environmental Issues was held June 12-15, 1994 in New Orleans, Louisiana. This volume contains abstracts of the oral presentations. They are organized into the following sections: Environmental Management; Biodiversity/sustainable Development; Gulf Regional Issues; Environmental Ethics/Equity; NEPA Symposium; International Environmental Issues; Global Environmental Effects; and, Risk Assessment. Abstracts of poster sessions are also included

Encapsulation Strategies of Bacteriophage (Felix O1) for Oral Therapeutic Application.

Science.gov (United States)

Islam, Golam S; Wang, Qi; Sabour, Parviz M

2018-01-01

Due to emerging antibiotic-resistant strains among the pathogens, a variety of strategies, including therapeutic application of bacteriophages, have been suggested as a possible alternative to antibiotics in food animal production. As pathogen-specific biocontrol agents, bacteriophages are being studied intensively. Primarily their applications in the food industry and animal production have been recognized in the USA and Europe, for pathogens including Salmonella, Campylobacter, Escherichia coli, and Listeria. However, the viability of orally administered phage may rapidly reduce under the harsh acidic conditions of the stomach, presence of enzymes and bile. It is evident that bacteriophages, intended for phage therapy by oral administration, require efficient protection from the acidic environment of the stomach and should remain active in the animal's gastrointestinal tract where pathogen colonizes. Encapsulation of phages by spray drying or extrusion methods can protect phages from the simulated hostile gut conditions and help controlled release of phages to the digestive system when appropriate formulation strategy is implemented.

Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

International Nuclear Information System (INIS)

Obermiller, Patrice S; Tait, David L; Holt, Jeffrey T

2000-01-01

Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

TU-EF-210-00: Therapeutic Strategies and Image Guidance

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

TU-EF-210-00: Therapeutic Strategies and Image Guidance

International Nuclear Information System (INIS)

2015-01-01

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare

Global Search Strategies for Solving Multilinear Least-Squares Problems

Directory of Open Access Journals (Sweden)

Mats Andersson

2012-04-01

Full Text Available The multilinear least-squares (MLLS problem is an extension of the linear least-squares problem. The difference is that a multilinear operator is used in place of a matrix-vector product. The MLLS is typically a large-scale problem characterized by a large number of local minimizers. It originates, for instance, from the design of filter networks. We present a global search strategy that allows for moving from one local minimizer to a better one. The efficiency of this strategy is illustrated by the results of numerical experiments performed for some problems related to the design of filter networks.

USGS global change science strategy: A framework for understanding and responding to climate and land-use change

Science.gov (United States)

Burkett, Virginia R.; Taylor, Ione L.; Belnap, Jayne; Cronin, Thomas M.; Dettinger, Michael D.; Frazier, Eldrich L.; Haines, John W.; Kirtland, David A.; Loveland, Thomas R.; Milly, Paul C.D.; O'Malley, Robin; Thompson, Robert S.

2011-01-01

This U.S. Geological Survey (USGS) Global Change Science Strategy expands on the Climate Variability and Change science component of the USGS 2007 Science Strategy, “Facing Tomorrow’s Challenges: USGS Science in the Coming Decade” (U.S. Geological Survey, 2007). Here we embrace the broad definition of global change provided in the U.S. Global Change Research Act of 1990 (Public Law 101–606,104 Stat. 3096–3104)—“Changes in the global environment (including alterations in climate, land productivity, oceans or other water resources, atmospheric chemistry, and ecological systems) that may alter the capacity of the Earth to sustain life”—with a focus on climate and land-use change.There are three major characteristics of this science strategy. First, it addresses the science required to broadly inform global change policy, while emphasizing the needs of natural-resource managers and reflecting the role of the USGS as the science provider for the Department of the Interior and other resource-management agencies. Second, the strategy identifies core competencies, noting 10 critical capabilities and strengths the USGS uses to overcome key problem areas. We highlight those areas in which the USGS is a science leader, recognizing the strong partnerships and effective collaboration that are essential to address complex global environmental challenges. Third, it uses a query-based approach listing key research questions that need to be addressed to create an agenda for hypothesis-driven global change science organized under six strategic goals. Overall, the strategy starts from where we are, provides a vision for where we want to go, and then describes high-priority strategic actions, including outcomes, products, and partnerships that can get us there. Global change science is a well-defined research field with strong linkages to the ecosystems, water, energy and minerals, natural hazards, and environmental health components of the USGS Science Strategy

Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.

Science.gov (United States)

de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

2015-05-01

HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.

Reaktualisasi Strategi Pendidikan Islam: Ikhtiar Mengimbangi Pendidikan Global

Directory of Open Access Journals (Sweden)

M. Sobry

2014-06-01

Full Text Available Abstract: Globalization is inevitable phenomenon that may cause anxiety amongst countries, such as Indonesia, that still preserve their culture, ethics and religious values because it always introduces new things that are not easily adjusted to regional or local contexts. Globalization as it is reflected in rapid change and transformation in technology has affected most of human’s life, including education. Globalized education is the one that is characterized by global and transnational elements in its basic structure, for example, the use of information technologies and digital media that have both positive and negative impacts. However, for Indonesia, whose majority population is Islam, globalization is not a threat, which should be evaded. What needs to do is to integrate Islamic concepts and values in it. Globalization and its type of education that looks contrary to religious norms will no longer become a menace if it is strengthened with religious values.    Abstrak: Globalisasi merupakan fenomena kekinian yang terkadang dipandang sebagai momok dalam konteks bangsa, seperti Indonesia, yang berhasrat kuat melestarikan nilai adat, budaya, moral, dan nilai agama. Tulisan ini mencermati globalisasi yang memengaruhi dunia pendidikan sebagaimana terlihat pada semakin luasnya penggunaan media digital dengan semua manfaat dan mudarat yang menyertainya. Penulis berpendapat bahwa fenomena itu semestinya dipandang wajar dan dihadapi dengan lapang dada. Namun ia harus diimbangi dengan konsep-konsep islami dan diperkuat dengan strategi islami pula. Islam memiliki konsep moralitas dan etika yang komprehensif untuk diaktualisasikan dalam konteks arus globalisasi. Oleh karena itu, tidak ada jalan lain untuk mengimbangi pendidikan global saat ini kecuali dengan kembali kepangkuan konsep-konsep pendidikan Islam. 

Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

Science.gov (United States)

Van Goethem, Alan; Yigit, Nurten; Moreno-Smith, Myrthala; Vasudevan, Sanjeev A; Barbieri, Eveline; Speleman, Frank; Shohet, Jason; Vandesompele, Jo; Van Maerken, Tom

2017-08-22

Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis

DEFF Research Database (Denmark)

Köhler, Ralf; Wulff, Heike; Eichler, Ines

2003-01-01

hyperplasia was accompanied by decreased neointimal cell content, with no change in the rate of apoptosis or collagen content. CONCLUSIONS: The switch toward IKCa1 expression may promote excessive neointimal VSMC proliferation. Blockade of IKCa1 could therefore represent a new therapeutic strategy to prevent...

Asset-Based Community Development as a Strategy for Developing Local Global Health Curricula.

Science.gov (United States)

Webber, Sarah; Butteris, Sabrina M; Houser, Laura; Coller, Karen; Coller, Ryan J

2018-02-07

A significant and growing proportion of US children have immigrant parents, an issue of increasing importance to pediatricians. Training globally minded pediatric residents to address health inequities related to globalization is an important reason to expand educational strategies around local global health (LGH). We developed a curriculum in the pediatric global health residency track at the University of Wisconsin in an effort to address gaps in LGH education and to increase resident knowledge about local health disparities for global community members. This curriculum was founded in asset-based community development (ABCD), a strategy used in advocacy training but not reported in global health education. The initial curriculum outputs have provided the foundation for a longitudinal LGH curriculum and a community-academic partnership. Supported by a community partnership grant, this partnership is focused on establishing a community-based postpartum support group for local Latinos, with an emphasis on building capacity in the Latino community. Aspects of this curriculum can serve other programs looking to develop LGH curricula rooted in building local partnerships and capacity using an ABCD model. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Relationship Between Competitive Strategies and the Success Perception of Polish Born Globals

Directory of Open Access Journals (Sweden)

Baranowska-Prokop Ewa

2014-09-01

Full Text Available The key objective of this paper is to describe and evaluate the competitive strategies applied by Polish born global enterprises. To reveal these strategies, two competitive models developed by M.E. Porter are applied to an original data set obtained from 256 small and medium Polish enterprises through a survey employing the CATI technique. The outcomes of these strategies, as perceived by the companies applying them, are also evaluated against two hypotheses. We conclude that Polish firms apply both basic strategies of competition, i.e. cost leadership strategies and differentiation strategies and that a substantial majority of companies perceive themselves to have succeeded on the market.

Therapeutic strategies for spinal muscular atrophy: SMN and beyond

Directory of Open Access Journals (Sweden)

Melissa Bowerman

2017-08-01

Full Text Available Spinal muscular atrophy (SMA is a devastating neuromuscular disorder characterized by loss of motor neurons and muscle atrophy, generally presenting in childhood. SMA is caused by low levels of the survival motor neuron protein (SMN due to inactivating mutations in the encoding gene SMN1. A second duplicated gene, SMN2, produces very little but sufficient functional protein for survival. Therapeutic strategies to increase SMN are in clinical trials, and the first SMN2-directed antisense oligonucleotide (ASO therapy has recently been licensed. However, several factors suggest that complementary strategies may be needed for the long-term maintenance of neuromuscular and other functions in SMA patients. Pre-clinical SMA models demonstrate that the requirement for SMN protein is highest when the structural connections of the neuromuscular system are being established, from late fetal life throughout infancy. Augmenting SMN may not address the slow neurodegenerative process underlying progressive functional decline beyond childhood in less severe types of SMA. Furthermore, individuals receiving SMN-based treatments may be vulnerable to delayed symptoms if rescue of the neuromuscular system is incomplete. Finally, a large number of older patients living with SMA do not fulfill the present criteria for inclusion in gene therapy and ASO clinical trials, and may not benefit from SMN-inducing treatments. Therefore, a comprehensive whole-lifespan approach to SMA therapy is required that includes both SMN-dependent and SMN-independent strategies that treat the CNS and periphery. Here, we review the range of non-SMN pathways implicated in SMA pathophysiology and discuss how various model systems can serve as valuable tools for SMA drug discovery.

CHANGE MANAGEMENT STRATEGIES RELATED TO THE GLOBAL ENVIRONMENT COMPLEXITY

Directory of Open Access Journals (Sweden)

Elena DOVAL

2016-12-01

Full Text Available The changes in organizations appear as a reaction to the organizational environment changes. In order to manage these changes successfully, the managers need to anticipate and design alternative strategies by preparing different options.  Nevertheless, the complexity of the global environment forces the managers to adopt strategies for their organizations that are facilitating the creation of new strategic competences and competitive advantages to face the environmental rapid changes. In this context, this paper is aiming to illustrate the main directions the change management may consider to change the organization strategies in order to harmonize them to the external environment, such as: integration versus externalization, flexible specialization and flexible organization, standardization versus adaptation, market segmentation, relationship building and maintaining and communication integration.  However, the new strategies are based on a changed attitude of the managers towards the competitive advantage that is dynamic and focused on creation rather then to operations.

Goethe's anxieties, depressive episodes and (self-)therapeutic strategies: a contribution to method integration in psychotherapy.

Science.gov (United States)

Holm-Hadulla, Rainer M

2013-01-01

In psychiatry and psychotherapy, abstract scientific principles need to be exemplified by narrative case reports to gain practical precision. Goethe was one of the most creative writers, productive scientists, and effective statesmen that ever lived. His descriptions of feelings, emotions, and mental states related to anxieties, depressive episodes, dysthymia, and creativity are unique in their phenomenological precision and richness. His life and work can thus serve as an excellent example enhancing our understanding of the relationship between anxiety, depression and creativity. Furthermore, he described (self-)therapeutic strategies that reinforce and refine modern views. Goethe's self-assessments in his works and letters, and the descriptions by others are analyzed under the perspective of current psychiatric classification. His therapeutic techniques and recommendations are compared with cognitive-behavioral, psychodynamic, and existential psychotherapy to amplify modern concepts of psychotherapy. From a scientific perspective, several distinctive depressive episodes can be diagnosed in Goethe's life. They were characterized by extended depressive moods, lack of drive, and loss of interest and self-esteem combined with social retreat. Goethe displayed diffuse and phobic anxieties as well as dysthymia. His (self-)therapeutic strategies were: (a) the systematic use of helping alliances, (b) behavioral techniques, (c) cognitive reflection on meanings and beliefs, (d) psychodynamic and psychoanalytic remembering, repeating, and working through, and (e) existential striving for self-actualization, social commitment, meaning, and creativity. In Goethe's life, creative incubation, illumination, and elaboration appear to have been associated with psychic instability and dysthymia, sometimes with depressive episodes in a clinical sense. On the one hand, his creative work was triggered by anxieties, dysthymia, and depressive moods. On the other hand, his creativity

A review of Thailand's strategies for global climate change

International Nuclear Information System (INIS)

Boonchalermkit, S.

1994-01-01

Thailand is greatly concerned about global climate change, which is caused primarily by the burning of fossil fuels, deforestation and the release of chlorofluorocarbons. The country itself is not currently a major contributor to global climate change. However, as Thailand's economy expands and its burning of fossil fuels increases, the country's contribution to global climate change could increase. Thailand's use of primary energy supplies grew at an average rate of 13.4 percent per year in the period 1985 to 1990. The rapid, sustained growth was due to the overall pace of growth in the economy and the expansion of industrial, construction, and transportation activities. The primary energy demand was approximately 31,600 kilotons of oil equivalent (KTOE) in 1990. The transportation sector accounted for the largest proportion of energy demand at 30 percent. Within the next 15 years, the power sector is expected to overtake the transportation sector as the largest consumer of energy. Petroleum is currently the predominant source of energy in Thailand, accounting for 56 percent of the primary energy demand. Thailand recognizes that it has an important part to play in finding solutions to minimizing emissions of greenhouse gases and identifying viable response strategies. Thus, in this paper the authors will present several policy strategies relevant to climate change in Thailand and discuss how they have been implemented and enforced. Policies concerning forestry, energy, and environment are reviewed in detail in this paper

DaimlerChrysler - powertrain-strategy. Global requirements - global solutions; DaimlerChrysler - Powertrain-Strategie. Globale Anforderungen - Globale Loesungen

Energy Technology Data Exchange (ETDEWEB)

Mikulic, L. [Mercedes Car Group, DaimlerChrysler AG, Mercedes-Benz Technology Center, Stuttgart (Germany); Lee, R. [DaimlerChrysler Corporation, Auburn Hills, MI (United States)

2007-07-01

'Globalization' - few concepts have shaped the last fifteen years like this has. For some it is a synonym for unexpected economic and social revolution, a threatening change in familiar arrangements, whilst others see the coalescence of global structures as, more than anything, a challenge - which, if mastered, offers endless possibilities for success. The challenges facing an automotive manufacturer in a globalized world are of quite a different nature. Not least, the constantly increasing competitive pressure has reduced the number of independent automotive manufacturers, in what is known as the Triad (Europe, Japan and North America), from 42 at the beginning of the 1960's to just 15 today. Also in Europe, consolidation has led, on the one hand, to a reduction in individual brands and on the other, to a number of collaborative projects between companies. Even in the dynamically growing East Asia markets, where the number of independent carmakers is still large, such collaborations have already occurred. In the near future much dynamics can be expected within the two fastest growing markets, China and India. Within these competitive markets, a globally operating company like DaimlerChrysler is faced with new challenges. (orig.)

Global powertrains - the GM case; Globale Antriebssysteme - Die Strategie von GM

Energy Technology Data Exchange (ETDEWEB)

Johansson, R.J. [General Motors Powertrain Europe, Turin (Italy)

2006-07-01

In today's environment the development of vehicles is confronted with very high customer expectations and legislative restrictions, which can only be fulfilled with a high technological effort and profound know how. These challenges are further increased due to the diversity of markets with regional preferences and increased cost and demand for energy. At the same time it is a principle for General Motors to offer our customers a sustainable and economical individual mobility. The worldwide development strategy of GM powertrain is following exactly this philosophy: efficient and and cost-effective technologies are being developed for gasoline and diesel engines in order to fulfill all of todays and all prognosed future requirements. Based on this GM has defined it's longterm strategy, the march to zero, which includes alternative propulsion systems with the ultimate goal of the neutral emission vehicle with ensured energy supply. With a unique worldwide development network GM is in an optimal position to take on this challenge. Already today GM is successfully using the synergies of competence centers all over the world for the global development strategy. Modern powertrains are based on a common structure but allow regional adaptation to all markets by using a modular system. This development philosophy is one of the cornerstones for General Motors position as the world's largest carmaker. (orig.)

Effectiveness of multiple therapeutic strategies in neovascular glaucoma patients: A PRISMA-compliant network meta-analysis.

Science.gov (United States)

Dong, Zixian; Gong, Jianyang; Liao, Rongfeng; Xu, Shaojun

2018-04-01

Neovascular glaucoma (NVG) is a severe secondary glaucoma with uncontrolled intraocular pressure that leads to serious eye pain and vision loss. Presently, the therapeutic strategies for NVG are diverse, but the therapeutic effects are still not ideal. We performed a network analysis to assess the effect of multiple therapeutic strategies on the treatment of NVG patients. We searched public electronic databases through April 2017 using the following keywords "neovascular glaucoma," "iris neovascularization," "hemorrhagic glaucoma," and "random" without language restrictions. The outcome considered in the present analysis was treatment success rate. A network meta-analysis and multilevel mixed-effects logistic regression were used to compare regimens. We included 27 articles assessing a total of 1884 NVG patients in our analysis. According to the network analysis, interferon and mitomycin plus trabeculectomy (94.9%), glaucoma valve implantation (86.9%), and iris photocoagulation plus trabeculectomy (81.9%) were the most likely to improve treatment success rate in NVG patients. The multilevel logistic regression analysis showed that glaucoma valve, bevacizumab, interferon, cyclophotocoagulation, trabeculectomy, iris photocoagulation, ranibizumab, and mitomycin had advantages in terms of improving treatment success rate in NVG patients. However, the application of retinal photocoagulation and vitrectomy reduced patient treatment success rate. The regimen including mitomycin, interferon, and trabeculectomy was the most likely to improve the treatment success rate in NVG patients. The application of glaucoma valve and bevacizumab were more beneficial for improving patient treatment success rate as a surgery and as an agent, respectively.

Formation of the US global energy strategy in 1991-2015

Directory of Open Access Journals (Sweden)

Nikolay Vladimirovich Ponomarev

2016-12-01

Full Text Available The article explores the formation of US global energy strategy in the timeframe of 1991-2015 and shifting emphasis in strategic documents indicating new regional priorities. Provisions concerning international energy interests of the United States can be traced back to the very first national security strategy and appear to be inherent core element of the American foreign policy. Due to domestic energy consumption patterns and cold war era strategic perception of fuel reserves US policy has been extensively centered on hydrocarbon resources. It proceeded from initial focus on the Persian Gulf to a global level commitment to ensure all-out output growth and transfer routs diversification for oil and gas exports in a number of key regions including the Caspian, and the Gulf of Guinea. By mid 2000s the US had become increasingly concerned with countering international influence and limiting regional clout of great powers that were pursuing independent policy and relying on state control of national energy companies and foreign energy assets, labeled as «resource nationalism». At the dawn of a new decade climate change in the Arctic and the rise of Indo-Asia-Pacific as a new global foremost transport and economic hub brought these rich in resources and critical in terms of resources shipping maritime domains to the forefront of US policy. Although the US prepares to assume the role of energy exporting country in the wake of shale oil and gas revolution that didn’t cause revision of this strategy but is merely supplementing it with a new international leverage. Revealed continuity rests on interpretation of unconstrained extraction and transit of hydrocarbon supplies to the world market and safety of the transit spaces as essential prerequisites for the stability of the US-centric global economy and entire postbipolar world order. Significant reliance on military instruments to maintain regional security regimes for international energy exports

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

Science.gov (United States)

Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

A therapeutic HIV vaccine using coxsackie-HIV recombinants: a possible new strategy.

Science.gov (United States)

Halim, S S; Collins, D N; Ramsingh, A I

2000-10-10

The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

Science.gov (United States)

Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

2017-01-01

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

[Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus].

Science.gov (United States)

Ciotta, L; Pagano, I; Stracquadanio, M; Di Leo, S; Andò, A; Formuso, C

2011-06-01

The premenstrual dysphoric disorder (PMDD) is one of the main problems of the premenstrual phase. It consists of symptoms that sometimes invalidate the scope of employment, social and psycho-affective of patients, requiring thus a diagnostic and therapeutic approach as detailed and accurate as possible. The therapeutic strategies available for this disease are many, but recently the emphasis has been on Vitex agnus castus (VAC), considered by many as evidence drug of choice for both PMS and for the PMDD, being with satisfactory therapeutic properties and small side effects. Our study evaluated a group of patients suffering from PMDD and the clinical efficacy of treatment with VAC (and compared the effectiveness of the results of a more homogeneous group of patients treated with fluoxetine). This study confirms the data reported in the literature regarding the effectiveness of VAC therapy with no side effects.

Therapeutic Strategy for Chronic Headache in Children

Directory of Open Access Journals (Sweden)

H.O. Lezhenko

2016-05-01

Full Text Available The therapeutic efficacy of a combined homeopathic preparation Cefavora, which consists of alcoholic extracts of Ginkgo biloba, hawthorn (Crataegus and white mistletoe (Viscum album, has been studied in the treatment of chronic tension-type headache in children. It has been shown that alongside with elimination of headache manifestations, the use of homeopathic medicine has contributed to the normalization of adaptive mechanisms of autonomic regulation in children indicating its high therapeutic efficacy.

Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

Science.gov (United States)

Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

2017-06-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated Marketing Strategies of German Companies : Start-Ups vs. Global Brands

OpenAIRE

Kostin, Irina

2016-01-01

The purpose of this bachelor's thesis is to find out and analyze different marketing strategies of German fashion companies. The main part is comparing relatively young start-up companies to established companies and analyzing to what extent the strategies differ. The methodology used in this paper were semi-structured expert interviews with German start-up companies. The results were analyzed and compared to the secondary research on the big global German companies. The findings showed that ...

RNA interference-based therapeutics: new strategies to fight infectious disease.

Science.gov (United States)

López-Fraga, M; Wright, N; Jiménez, A

2008-12-01

For many years, there has been an ongoing search for new compounds that can selectively alter gene expression as a new way to treat human disease by addressing targets that are otherwise "undruggable" with traditional pharmaceutical approaches involving small molecules or proteins. RNA interference (RNAi) strategies have raised a lot of attention and several compounds are currently being tested in clinical trials. Viruses are the obvious target for RNAi-therapy, as most are difficult to treat with conventional drugs, they become rapidly resistant to drug treatment and their genes differ substantially from human genes, minimizing side effects. Antisense strategy offers very high target specificity, i.e., any viral sequence could potentially be targeted using the complementary oligonucleotide sequence. Consequently, new antisense-based therapeutics have the potential to lead a revolution in the anti-infective drug development field. Additionally, the relatively short turnaround for efficacy testing of potential RNAi molecules and that any pathogen is theoretically amenable to rapid targeting, make them invaluable tools for treating a wide range of diseases. This review will focus on some of the current efforts to treat infectious disease with RNAi-based therapies and some of the obstacles that have appeared on the road to successful clinical intervention.

Evaluating Strategies for Achieving Global Collective Action on Transnational Health Threats and Social Inequalities

OpenAIRE

Hoffman, Steven Justin

2015-01-01

This dissertation presents three studies that evaluate different strategies for addressing transnational health threats and social inequalities that depend upon or would benefit from global collective action. Each draws upon different academic disciplines, methods and epistemological traditions. Chapter 1 assesses the role of international law in addressing global health challenges, specifically examining when, how and why global health treaties may be helpful. Evidence from 90 quantitati...

Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

Science.gov (United States)

Tan, Wan Shun Daniel; Liao, Wupeng; Zhou, Shuo; Mei, Dan; Wong, Wai-Shiu Fred

2017-12-27

The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome. This review compiles and analyses recent investigations targeting RAS for the treatment of inflammatory lung diseases. Inhibition of the upstream angiotensin (Ang) I/Ang II/angiotensin receptor type 1 (AT 1 R) pathway and activation of the downstream angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas receptor pathway are two feasible strategies demonstrating efficacies in various pulmonary disease models. More recent studies favor the development of targeting the downstream ACE2/Ang (1-7)/Mas receptor pathway, in which diminazene aceturate, an ACE2 activator, GSK2586881, a recombinant ACE2, and AV0991, a Mas receptor agonist, showed much potential for further development. As the pathogenesis of pulmonary diseases is so complex that RAS modulation may be used alone or in combination with existing drugs like corticosteroids, pirfenidone/nintedanib or endothelin receptor antagonists for different pulmonary diseases. Personalized medicine through genetic screening and phenotyping for angiotensinogen or ACE would aid treatment especially for non-responsive patients. This review serves to provide an update on the latest development in the field of RAS targeting for pulmonary diseases, and offer some insights into future direction. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Future Regulatory Science through a Global Product Development Strategy to Overcome the Device Lag].

Science.gov (United States)

Tsuchii, Isao

2016-01-01

Environment that created "medical device lag (MDL)" has changed dramatically, and currently that term is not heard often. This was mainly achieved through the leadership of three groups: government, which determined to overcome MDL and took steps to do so; medical societies, which exhibited accountability in trial participation; and MD companies, which underwent a change in mindset that allowed comprehensive tripartite cooperation to reach the current stage. In particular, the global product development strategy (GPDS) of companies in a changing social environment has taken a new-turn with international harmonization trends, like Global Harmonization Task Force and International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. As a result, this evolution has created opportunities for treatment with cutting-edge MDs in Japanese society. Simultaneously, it has had a major impact on the planning process of GPDS of companies. At the same time, the interest of global companies has shifted to emerging economies for future potential profit since Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem for manufacturers. From the regulatory science viewpoint, this new environment has not made it easy to plan a global strategy that will be adaptable to local societies. Without taking hasty action, flexible thinking from the global point of view is necessary to enable the adjustment of local strategies to fit the situation on the ground so that the innovative Japanese medical technology can be exported to a broad range of societies.

Imperial or postcolonial governance? Dissecting the genealogy of a global public health strategy.

Science.gov (United States)

Brown, Tim; Bell, Morag

2008-11-01

During the last decades of the 20th century it became increasingly apparent that the inter-relationship between globalisation and health is extremely complex. This complexity is highlighted in debates surrounding the re-emergence of infectious diseases, where it is recognised that the processes of globalisation have combined to create the conditions where once localised, microbial hazards have come to pose a threat to many western nations. By contrast, in an emerging literature relating to the epidemic of non-communicable diseases, and reflected in the WHO 'Global strategy on diet, physical activity and health', it is the so-called 'western lifestyle' that has been cast as the main threat to a population's health. This paper explores critically global responses to this development. Building on our interest in questions of governance and the ethical management of the healthy body, we examine whether the global strategy, in seeking to contain the influence of a 'western lifestyle', also promotes contemporary 'western-inspired' approaches to public health practices. The paper indicates that a partial reading of the WHO strategy suggests that certain countries, especially those outside the West, are being captured or 'enframed' by the integrative ambitions of a western 'imperial' vision of global health. However, when interpreted critically through a postcolonial lens, we argue that 'integration' is more complex, and that the subtle and dynamic relations of power that exist between countries of the West/non-West, are exposed.

Towards new therapeutic strategies in chondrosarcoma

NARCIS (Netherlands)

Schrage, Yvonne Maria

2009-01-01

This thesis presents the identification of new targets for therapeutic treatment of chondrosarcoma, tumours that are highly insensitive to conventional chemo- and radiation thearapy. A relatively new array technique to identify active kinases in chondrosarcoma cell cultures was used, which

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Isaac G Onyango

2018-01-01

Full Text Available Alzheimer's disease (AD is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

Directory of Open Access Journals (Sweden)

Fiszer Agnieszka

2012-03-01

Full Text Available Abstract Background RNA interference (RNAi and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting. Results Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge. Conclusions Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that

Inflammatory bowel disease: potential therapeutic strategies

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Bregenholt, S

1997-01-01

This review deals with potential and possibly primary therapeutics that, through insight into the inflammatory cascade, result in more rational treatment principles replacing the classical therapy of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). These ne...

From Multilatina to Global Latina: Unveiling the corporate-level international strategy choices of Grupo Nutresa

Directory of Open Access Journals (Sweden)

MARIA A DE VILLA

Full Text Available Research on Multilatinas has underexplored multinationals from Colombia and their corporate-level international strategy choices to develop into Global Latinas. Building on interviews, documents, and archival data about Grupo Nutresa -Colombia's most international firm in manufactured goods-, this study unveils and discusses this firm's corporate-level international strategy choices between 1960 and 2014. A prevailing notion is that most multinationals from Latin America continue to target international operations to focus mainly on their home region through an export, multidomestic or transnational corporate-level international strategy. In contrast, data show that Grupo Nutresa chose to evolve through a sequential approach from an export to a transnational corporate-level international strategy while its international operations were able to transcend its home region to reach North America, Asia, Europe, Africa, and Oceania. These results add to international business research on emergent market multinational companies (EMNCs from Latin America by unveiling the corporate-level international strategy choices of a Colombian origin Multilatina that transformed into a Global Latina.

The global threat of antimicrobial resistance: science for intervention

Directory of Open Access Journals (Sweden)

I. Roca

2015-07-01

Full Text Available In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

Oncogenic Human Papillomavirus: Application of CRISPR/Cas9 Therapeutic Strategies for Cervical Cancer

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Shuai Zhen

2017-12-01

Full Text Available Oncogenic human papillomaviruses (HPVs cause different types of cancer especially cervical cancer. HPV-associated carcinogenesis provides a classical model system for clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 based cancer therapies since the viral oncogenes E6 and E7 are exclusively expressed in cancerous cells. Sequence-specific gene knockdown/knockout using CRISPR/Cas9 shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, CRISPR/Cas9-based targeting therapy requires further validation of its efficacy in vitro and in vivo to eliminate the potential off-target effects, necessitates verification of the delivery vehicles and the combinatory use of conventional therapies with CRISPR/Cas9 to ensure the feasibility and safety. In this review we discuss the potential of combining CRISPR/Cas9 with other treatment options as therapies for oncogenic HPVs-associated carcinogenesis. and present our assessment of the promising path to the development of CRISPR/Cas9 therapeutic strategies for clinical settings.

Investigation of China’s national public relations strategy under globalization : the hotspots around the national media

OpenAIRE

雷, 紫雯

2014-01-01

This study investigates on China’s national public relations strategy under the globalization by analyzing the national media. In recent years, in order to improve the global public opinion environment, and to improve its national public relations capabilities that match its economic power status, China has actively strengthened its national public relations strategies, including making the national “media go out”, and building world-class media. By researching on the localization of Chinese ...

Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.

Science.gov (United States)

Kintzing, James R; Filsinger Interrante, Maria V; Cochran, Jennifer R

2016-12-01

Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity. In this review we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

IMPROVEMENT OF MANGOSTEEN FARMING AND POSTHARVEST HANDLING STRATEGIES BASED ON GLOBAL GAP STANDARD AT KIARA PEDES, PURWAKARTA DISTRICT

Directory of Open Access Journals (Sweden)

Nanda Erlangga

2012-09-01

Full Text Available The objectives of this research were (1 to determine the value chain of mangosteen at Kiara Pedes Sub district, Purwakarta District, (2 to identify the gap between actual condition at Kiara Pedes and Global GAP standard, (3 to identify internal and external factors that can affect the implementation strategy of Global GAP standards, and (4 to develop alternative strategies that can be applied to improve the system of mangosteen cultivation and post harvest handling based on Global GAP standards. The analytical tools being used in this study were value chain analysis, gap analysis, internal and external factor evaluation (IFE, EFE, IE matrix, SWOT analysis, and quantitative strategic planning matrix (QSPM. Identified primary actors in mangosteen value chain were farmers, middlemen, suppliers, exporters, and local and overseas retailers. Based on IE Matrix and SWOT analysis, the strategies to implement Global GAP standards were (a to increase mangosteen productivity and improve its quality by using developed cultivation and postharvest technology, (b to increase productivity, and improve quality and transportation network in accordance with Global GAP standard, (c to improve clean water and post-harvest infrastructure through cooperation with exporters and financial institutions, and (d to improve warehouse and supporting facilities such as packaging and sanitation according to the Global GAP standard for minimizing the environmental constraints. The most priority strategies from the QSPM analysis were improving clean water and post-harvest infrastructure through cooperation with exporters and financial institutions, followed by using the developed cultivation and postharvest technology to increase mangosteen productivity and improve its quality.Keywords: Mangosteen, Global GAP Standard, Value Chain, Improvement Strategies, Farming and Postharvest Handling Practices

Strategies of EU agro-food cooperatives to confront globalization: The case of wine cooperatives

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Juan Sebastián Castillo Valero

2013-06-01

Full Text Available Due to globalization and market integration, the agro-food cooperative sector needs to be more competitive. This generates new challenges for cooperative enterprises in the agro-food sector. In this article the analysis of the wine producing sector is undertaken in the area of greatest world-wide wine production and commercialization, Castilla-La Mancha. EU wineries and cooperatives should propose strategic lines within an economy marked by a globalization process in world markets. The paradigmatic case is analyzed in this paper of the comparison of strategies followed by cooperatives confronting capitalist winery enterprises. Therefore, the degree of suitability is aimed to be elucidated and the success of the foundations of international commercial strategies that cooperative enterprises of the sector have followed, depending on their characteristics. Moreover, an exhaustive diagnosis is offered of the current strategic situation of cooperatives and their probability of gaining access to and/or growing in the international market. The parameters that have resulted significant are used as conclusions and recommendations so that cooperatives will reformulate their strategies and the organizations linked to the agro-food sector will know what factors to foment and support in their internationalization and global competitive positioning.

Development of a biochip-based assay integrated in a global strategy for identification of fusion transcripts in acute myeloid leukemia: a work flow for acute myeloid leukemia diagnosis.

Science.gov (United States)

Giusiano, S; Formisano-Tréziny, C; Benziane, A; Maroc, N; Picard, C; Hermitte, F; Taranger-Charpin, C; Gabert, J

2010-08-01

Three major types of rearrangements are involved in acute myeloid leukemias (AML): t(8;21)(q22;q22), inv(16)(p13q22), and 11q23/MLL abnormalities. Their precise identification becomes essential for diagnosis, prognosis, and therapeutic choices. Resulting fusion transcripts (FT) are also powerful markers for monitoring the efficacy of treatment, the minimal residual disease (MRD) and could become therapeutic targets. Today, the challenge is to propose an individual follow-up for each patient even for those with a rare fusion event. In this study, we propose a biochip-based assay integrated in a global strategy for identification of rare FT in AML, after fluorescence in situ hybridization detection, as described by the World Health Organization classification. Using cell lines, we developed and validated a biochip-based assay called the AMLFusionChip that identifies every FT of AML1-ETO, CBFbeta-MYH11 as well as MLL-AF9, MLL-ENL, MLL-AF6, and MLL-AF10. The original design of our AMLFusionChip.v01 enables the identification of these FT wherever the breakpoint on the partner gene may be. In case of biochip negative result, our 3'RACE amplification strategy enables to clone and then sequence the new translocation partner. This AMLFusionChip strategy fits into the concept of personalized medicine for the largest number of patients.

Strategies for Corporate Global Expansion of Pakistani Companies in the Age of Technology

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Jawaid Ahmed Qureshi

2015-04-01

Full Text Available This study intends to meticulously probe about the applications of cutting-edge strategies of globally expanding companies operative in several industrial sectors of Pakistan. Many companies craft and execute various strategies to globalize their operations and networks in several continents, which can not only benefit them but add value in the domestic cum global economy. Many researchers expounded that along with many other factors, capacity-building and competitive edges of business provide these companies the competitive strengths to excel in their global operations. Regarding such strengths, advancement in technology inclusive of research in business R&D (Research & Development, and marketing and business research, process design, automation, and e-commerce play a decisive role in providing them the core competitive edges that they leverage to advance their growth and expansion in the global market. This paper employs hybrid research techniques including qualitative and quantitative research. Semi-structured interviews have been taken for qualitative enquiry and structured survey has been undertaken for quantitative enquiry. The samples are drawn from multiple populations pertaining top-five export sectors of Pakistan by applying convenience sampling procedures for interviews and proportionate stratified sampling articulated with systematic sampling for survey. The findings uncover that after turning as retrenched domestic entities, many of the companies in Pakistan prefer global expansion. They usually resume from export operations in various countries especially where they develop a network of business associates, and then gradually move to open subsidiaries abroad. They avail technological edges to upgrade their processes, plants, products

Exploring new communication strategies for a global brand : transmedia storytelling and gamification

OpenAIRE

Brieger, Christian

2013-01-01

Marketing is changing and companies or brands try to find new ways to engage consumers and involve them in their advertising efforts. There are two new communication strategies that might be able to lead the way into a new area of advertising and marketing: transmedia storytelling and gamification. The research questions were how to use such strategies in the communication or branding environment and how to use them when a global brand wants to communicate across cultures while adapting the a...

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations

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Christopher M. Mahoney

2018-05-01

Full Text Available Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

Science.gov (United States)

Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

2018-01-01

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

Global environmental policy strategies. ''Environment and development'' in north-south relations

International Nuclear Information System (INIS)

Bruckmeier, K.

1994-01-01

Global environmental policy has hardly made headway after the United Nations World Conference on Environment and Development (UNCED) in Rio in June 1992, despite there being no shortage of programmes, institutions, and actors. Obviously, formal structures for political action based on the system of institutions of the United Nations do not suffice. Global environmental policy strategies must reach further, overcoming system-immanent obstacles to sustainable development. This necessitates analyzing the causes of environmental destruction and making a critical evaluation of the relations between the societies of the North and South that received their imprint from development policies. Only after such a preliminary elucidation by interdisciplinary approaches in the light of political and ecological economy and human ecology does an empirical analysis of politically controlled processes in environmental and development policy make sense. The analysis points to strategies for this international political field that rely on non-governmental actors and social movements, and question the traditional European model of an environmental policy determined by government institutions. (orig./UA) [de

Schistosomiasis elimination strategies and potential role of a vaccine in achieving global health goals.

Science.gov (United States)

Mo, Annie X; Agosti, Jan M; Walson, Judd L; Hall, B Fenton; Gordon, Lance

2014-01-01

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled "Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals" to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.

A Guiding Evolutionary Algorithm with Greedy Strategy for Global Optimization Problems

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Leilei Cao

2016-01-01

Full Text Available A Guiding Evolutionary Algorithm (GEA with greedy strategy for global optimization problems is proposed. Inspired by Particle Swarm Optimization, the Genetic Algorithm, and the Bat Algorithm, the GEA was designed to retain some advantages of each method while avoiding some disadvantages. In contrast to the usual Genetic Algorithm, each individual in GEA is crossed with the current global best one instead of a randomly selected individual. The current best individual served as a guide to attract offspring to its region of genotype space. Mutation was added to offspring according to a dynamic mutation probability. To increase the capability of exploitation, a local search mechanism was applied to new individuals according to a dynamic probability of local search. Experimental results show that GEA outperformed the other three typical global optimization algorithms with which it was compared.

Supplier Partnership Strategy and Global Competitiveness: A Case of Samsung Electronics

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Jangwoo Lee

2015-11-01

Full Text Available Samsung Group has accelerated its management innovation process, following the announcement of ‘New Management’ by the CEO Lee Kun-Hee. Particular attention must be paid to the smart-phone business of Samsung Electronics, which is the core company of the Samsung Group. In 2009, as Apple entered into the Korean market, the domestic smart-phone market faced the so called ‘Apple Shock’ due to its choice of a monopolistic and closed operating system. In response, Samsung Electronics introduced the innovative Galaxy series, replacing the old model of Omnia series. This move reaped dramatic success by dominating the world smart-phone market. Samsung Electronics ranked first in the 2012 world smart-phone market, and in 2013 it sold over 300 million devices for the first time in history, thereby solidifying the number one spot with a market share of 32.3%. Samsung Electronics’ achievement in its management innovation process was successful, due to its internal innovation and its partnership with sub-suppliers. Samsung Electronics strengthened its supplier partnership strategy, which in turn, led to an internalization of subparts assembly and process technology. By conducting the final assembly process on its own, it established the global supply chain that accompanies a high level of efficiency and operational elasticity. Samsung Electronics successfully systemized several hundred suppliers into an effective partnership and created an eco system where cooperation and competition can co-exist in its supply chain network. In sum, Samsung Electronics has successfully created the Samsung Production System that brings an economy of scale and allows prompt response. On the other hand, Apple did not get involved with subparts production, besides design and product design. This research identifies the effectiveness of Samsung Electronics’ supplier partnerships in its global competitiveness by examining characteristics of supplier partnership

Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

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Claudia P. Miller

2011-01-01

Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

Changing Strategies in Global Wind Energy Shipping, Logistics, and Supply Chain Management

DEFF Research Database (Denmark)

Poulsen, Thomas

2015-01-01

Within the global wind energy market, a number of derived industries support the continued expansion of the ever larger onshore and offshore wind farms. One such derived industry is that of shipping, logistics, and supply chain management. Based on extensive case study work performed since 2009......, the paper reviews different wind energy markets globally. Subsequently, a number of supply chain set-ups serviced by the shipping, logistics, and supply chain management industry are reviewed. Finally, winning business models and strategies of current as well as emerging supply chain constituencies...

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

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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.

Structuring energy supply and demand networks in a general equilibrium model to simulate global warming control strategies

International Nuclear Information System (INIS)

Hamilton, S.; Veselka, T.D.; Cirillo, R.R.

1991-01-01

Global warming control strategies which mandate stringent caps on emissions of greenhouse forcing gases can substantially alter a country's demand, production, and imports of energy products. Although there is a large degree of uncertainty when attempting to estimate the potential impact of these strategies, insights into the problem can be acquired through computer model simulations. This paper presents one method of structuring a general equilibrium model, the ENergy and Power Evaluation Program/Global Climate Change (ENPEP/GCC), to simulate changes in a country's energy supply and demand balance in response to global warming control strategies. The equilibrium model presented in this study is based on the principle of decomposition, whereby a large complex problem is divided into a number of smaller submodules. Submodules simulate energy activities and conversion processes such as electricity production. These submodules are linked together to form an energy supply and demand network. Linkages identify energy and fuel flows among various activities. Since global warming control strategies can have wide reaching effects, a complex network was constructed. The network represents all energy production, conversion, transportation, distribution, and utilization activities. The structure of the network depicts interdependencies within and across economic sectors and was constructed such that energy prices and demand responses can be simulated. Global warming control alternatives represented in the network include: (1) conservation measures through increased efficiency; and (2) substitution of fuels that have high greenhouse gas emission rates with fuels that have lower emission rates. 6 refs., 4 figs., 4 tabs

Chinese Global and Russian Spatial Strategies: Harmonization Potential

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Pavel Aleksandrovich Minakir

2017-06-01

Full Text Available A probability of the harmonization of the Chinese sub-global strategy ‘One Belt, One Road’, proposed in 2013, and Russian integration project for the Eurasia economic cooperation are reviewed as well as the influence of this potential synchronized project on the Far Eastern segment of the Russian spatial strategy. It is noted that the problems of spatial heterogeneity gave push to the ‘One Belt, One Road’ project when China approached the point in economic development where different regional economic zones demand new infrastructural solutions for maintaining economic dynamics. The article shows that the declared co-development of countries involved is based on the rigid pragmatic financial-credit and infrastructural expansion of Central Asian model: mandatory provision of significant share in property (controlling stake, if possible, mandatory financing with construction contract and guaranteed future export of services for operating the facilities, ensuring the rights on full (or no less than 50% export of raw materials for further processing to China, employing Chinese labor in Russian-Chinese enterprises, and using Chinese machinery and equipment

Therapeutic strategy for granulomatous lobular mastitis: a clinicopathological study of 12 patients.

Science.gov (United States)

Akahane, Kazuhisa; Tsunoda, Nobuyuki; Kato, Masamichi; Noda, Sumiyo; Shimoyama, Yoshie; Ishigakis, Satoko; Satake, Hiroko; Nakamura, Shigeo; Nagino, Masato

2013-08-01

Granulomatous lobular mastitis (GLM) is a rare inflammatory pseudotumor. No therapeutic modality for this disease has been established because of its rarity. The purpose of this study is to evaluate the treatment strategies of GLM. Twelve women who met the histological criteria for GLM were retrospectively studied. The clinical data and the presentation, histopathology, and management of the disease were analyzed by reviewing the patients' medical records. The diagnosis of GLM was confirmed histologically by core needle biopsy in 9 cases, by vacuum-assisted biopsy in 2 cases, and by excisional biopsy in 1 case. Ten patients received corticosteroid treatment and another two patients were treated with local excision or incision and drainage. The median initial dosage of corticosteroid (Prednisolone) was 30 mg/day (range: 15-60 mg/day), and the dosages were tapered according to improvement. The median duration of corticosteroid treatment was 5 months (range: 1-12 months). The median follow-up period was 22 months (range: 6-104 months), and no patient treated with corticosteroid demonstrated recurrence. However, patients treated with excision or incision and drainage had recurrences. These results suggest that steroid treatment may be the first choice in treatment strategies for GLM.

Impacts of climate mitigation strategies in the energy sector on global land use and carbon balance

Science.gov (United States)

Engström, Kerstin; Lindeskog, Mats; Olin, Stefan; Hassler, John; Smith, Benjamin

2017-09-01

Reducing greenhouse gas emissions to limit damage to the global economy climate-change-induced and secure the livelihoods of future generations requires ambitious mitigation strategies. The introduction of a global carbon tax on fossil fuels is tested here as a mitigation strategy to reduce atmospheric CO2 concentrations and radiative forcing. Taxation of fossil fuels potentially leads to changed composition of energy sources, including a larger relative contribution from bioenergy. Further, the introduction of a mitigation strategy reduces climate-change-induced damage to the global economy, and thus can indirectly affect consumption patterns and investments in agricultural technologies and yield enhancement. Here we assess the implications of changes in bioenergy demand as well as the indirectly caused changes in consumption and crop yields for global and national cropland area and terrestrial biosphere carbon balance. We apply a novel integrated assessment modelling framework, combining three previously published models (a climate-economy model, a socio-economic land use model and an ecosystem model). We develop reference and mitigation scenarios based on the narratives and key elements of the shared socio-economic pathways (SSPs). Taking emissions from the land use sector into account, we find that the introduction of a global carbon tax on the fossil fuel sector is an effective mitigation strategy only for scenarios with low population development and strong sustainability criteria (SSP1 Taking the green road). For scenarios with high population growth, low technological development and bioenergy production the high demand for cropland causes the terrestrial biosphere to switch from being a carbon sink to a source by the end of the 21st century.

Impacts of climate mitigation strategies in the energy sector on global land use and carbon balance

Directory of Open Access Journals (Sweden)

K. Engström

2017-09-01

Full Text Available Reducing greenhouse gas emissions to limit damage to the global economy climate-change-induced and secure the livelihoods of future generations requires ambitious mitigation strategies. The introduction of a global carbon tax on fossil fuels is tested here as a mitigation strategy to reduce atmospheric CO2 concentrations and radiative forcing. Taxation of fossil fuels potentially leads to changed composition of energy sources, including a larger relative contribution from bioenergy. Further, the introduction of a mitigation strategy reduces climate-change-induced damage to the global economy, and thus can indirectly affect consumption patterns and investments in agricultural technologies and yield enhancement. Here we assess the implications of changes in bioenergy demand as well as the indirectly caused changes in consumption and crop yields for global and national cropland area and terrestrial biosphere carbon balance. We apply a novel integrated assessment modelling framework, combining three previously published models (a climate–economy model, a socio-economic land use model and an ecosystem model. We develop reference and mitigation scenarios based on the narratives and key elements of the shared socio-economic pathways (SSPs. Taking emissions from the land use sector into account, we find that the introduction of a global carbon tax on the fossil fuel sector is an effective mitigation strategy only for scenarios with low population development and strong sustainability criteria (SSP1 Taking the green road. For scenarios with high population growth, low technological development and bioenergy production the high demand for cropland causes the terrestrial biosphere to switch from being a carbon sink to a source by the end of the 21st century.

Strategies for implementing and sustaining therapeutic lifestyle changes as part of hypertension management in African Americans.

Science.gov (United States)

Scisney-Matlock, Margaret; Bosworth, Hayden B; Giger, Joyce Newman; Strickland, Ora L; Harrison, R Van; Coverson, Dorothy; Shah, Nirav R; Dennison, Cheryl R; Dunbar-Jacob, Jacqueline M; Jones, Loretta; Ogedegbe, Gbenga; Batts-Turner, Marian L; Jamerson, Kenneth A

2009-05-01

African Americans with high blood pressure (BP) can benefit greatly from therapeutic lifestyle changes (TLC) such as diet modification, physical activity, and weight management. However, they and their health care providers face many barriers in modifying health behaviors. A multidisciplinary panel synthesized the scientific data on TLC in African Americans for efficacy in improving BP control, barriers to behavioral change, and strategies to overcome those barriers. Therapeutic lifestyle change interventions should emphasize patient self-management, supported by providers, family, and the community. Interventions should be tailored to an individual's cultural heritage, beliefs, and behavioral norms. Simultaneously targeting multiple factors that impede BP control will maximize the likelihood of success. The panel cited limited progress with integrating the Dietary Approaches to Stop Hypertension (DASH) eating plan into the African American diet as an example of the need for more strategically developed interventions. Culturally sensitive instruments to assess impact will help guide improved provision of TLC in special populations. The challenge of improving BP control in African Americans and delivery of hypertension care requires changes at the health system and public policy levels. At the patient level, culturally sensitive interventions that apply the strategies described and optimize community involvement will advance TLC in African Americans with high BP.

Global Strategy Implementation at the Business Unit Level: Operational Capabilities and Administrative Mechanisms

OpenAIRE

Kendall Roth; David M Schweiger; Allen J Morrison

1991-01-01

The study examines the impact of internationally strategy on organizational design and the influence of the organizational design on effectiveness at the business unit level. The empirical findings are based on survey responses from eighty-two business units competing in global industries. The findings are supportive of the contingency notion which suggests that business unit effectiveness is a function of the fit between the international strategy and the organizational design.© 1991 JIBS. J...

Global Supply-Chain Strategy And Global Competitiveness

OpenAIRE

Asghar Sabbaghi; Navid Sabbaghi

2011-01-01

The purpose of this study is to provide an analysis of global supply chain in a broader context that encompasses not only the producing company, but suppliers and customers.The theme of this study is to identify global sourcing and selling options, to enhance customer service and value added, to optimize inventory performance, to reduce total delivered costs and lead times, to achieve lower break-even costs, and to improve operational flexibility, customization and partner relations. In this ...

Global strategies to reduce the price of antiretroviral medicines: evidence from transactional databases.

Science.gov (United States)

Waning, Brenda; Kaplan, Warren; King, Alexis C; Lawrence, Danielle A; Leufkens, Hubert G; Fox, Matthew P

2009-07-01

To estimate the impact of global strategies, such as pooled procurement arrangements, third-party price negotiation and differential pricing, on reducing the price of antiretrovirals (ARVs), which currently hinders universal access to HIV/AIDS treatment. We estimated the impact of global strategies to reduce ARV prices using data on 7253 procurement transactions (July 2002-October 2007) from databases hosted by WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria. For 19 of 24 ARV dosage forms, we detected no association between price and volume purchased. For the other five ARVs, high-volume purchases were 4-21% less expensive than medium- or low-volume purchases. Nine of 13 generic ARVs were priced 6-36% lower when purchased under the Clinton Foundation HIV/AIDS Initiative (CHAI). Fifteen of 18 branded ARVs were priced 23-498% higher for differentially priced purchases compared with non-CHAI generic purchases. However, two branded, differentially priced ARVs were priced 63% and 73% lower, respectively, than generic non-CHAI equivalents. Large purchase volumes did not necessarily result in lower ARV prices. Although current plans for pooled procurement will further increase purchase volumes, savings are uncertain and should be balanced against programmatic costs. Third-party negotiation by CHAI resulted in lower generic ARV prices. Generics were less expensive than differentially priced branded ARVs, except where little generic competition exists. Alternative strategies for reducing ARV prices, such as streamlining financial management systems, improving demand forecasting and removing barriers to generics, should be explored.

INTEGRATING COUNTRY-SPECIFIC CULTURE IN THE BRANDING STRATEGY FOR BUILDING GLOBAL SUCCESS

Directory of Open Access Journals (Sweden)

Alexandra IOANID

2014-11-01

Full Text Available A strong brand is the one that integrates its cultural origins and values with the cultural values of the countries where it operates, building relationships based on trust with the local consumers. The chances for a company to gain share market when starting operations in a new country grows a lot if the management allows enough regional flexibility on how the brands are marketed, according to the cultural characteristics of the potential local customers. In the actual globalized business environment, the brand marketer has the choice to adopt a global or a local approach in the marketing strategy, that most of the times determines the success or the failure of the business in a specific country. An important challenge for any marketer is the integration of the brand-culture with the country-culture and in this context, the paper analyses different cultures and offers some branding strategies valid for both products and services. This paper aims to demonstrate the importance of the country-specific culture integration in the marketing strategy of a company for growing the effectiveness of all its operations. The ideas mentioned in this paper are based on literature research and also on authors’ experience with multicultural environments.

Photochemical internalisation, a minimally invasive strategy for light-controlled endosomal escape of cancer stem cell-targeting therapeutics.

Science.gov (United States)

Selbo, Pål Kristian; Bostad, Monica; Olsen, Cathrine Elisabeth; Edwards, Victoria Tudor; Høgset, Anders; Weyergang, Anette; Berg, Kristian

2015-08-01

Despite progress in radio-, chemo- and photodynamic-therapy (PDT) of cancer, treatment resistance still remains a major problem for patients with aggressive tumours. Cancer stem cells (CSCs) or tumour-initiating cells are intrinsically and notoriously resistant to conventional cancer therapies and are proposed to be responsible for the recurrence of tumours after therapy. According to the CSC hypothesis, it is imperative to develop novel anticancer agents or therapeutic strategies that take into account the biology and role of CSCs. The present review outlines our recent study on photochemical internalisation (PCI) using the clinically relevant photosensitiser TPCS2a/Amphinex® as a rational, non-invasive strategy for the light-controlled endosomal escape of CSC-targeting drugs. PCI is an intracellular drug delivery method based on light-induced ROS-generation and a subsequent membrane-disruption of endocytic vesicles, leading to cytosolic release of the entrapped drugs of interest. In different proof-of-concept studies we have demonstrated that PCI of CSC-directed immunotoxins targeting CD133, CD44, CSPG4 and EpCAM is a highly specific and effective strategy for killing cancer cells and CSCs. CSCs overexpressing CD133 are PDT-resistant; however, this is circumvented by PCI of CD133-targeting immunotoxins. In view of the fact that TPCS2a is not a substrate of the efflux pumps ABCG2 and P-glycoprotein (ABCB1), the PCI-method is a promising anti-CSC therapeutic strategy. Due to a laser-controlled exposure, PCI of CSC-targeting drugs will be confined exclusively to the tumour tissue, suggesting that this drug delivery method has the potential to spare distant normal stem cells.

Asthma Treatments for Children and Adolescents: Strategies for a Global Approach

Directory of Open Access Journals (Sweden)

Robert L Thivierge

1995-01-01

Full Text Available Strategies for a global approach to the management of asthma in children and adolescents are described. Such an approach requires the physician to explain to the patient the pathophysiology of asthma, to evaluate and, whenever possible, change predisposing environmental factors, to establish a written plan of action and to maintain a close follow-up of the patient to ensure compliance.

Long-term global nuclear energy and fuel cycle strategies

International Nuclear Information System (INIS)

Krakowski, R.A.

1997-01-01

The Global Nuclear Vision Project is examining, using scenario building techniques, a range of long-term nuclear energy futures. The exploration and assessment of optimal nuclear fuel-cycle and material strategies is an essential element of the study. To this end, an established global E 3 (energy/economics/environmental) model has been adopted and modified with a simplified, but comprehensive and multi-regional, nuclear energy module. Consistent nuclear energy scenarios are constructed using this multi-regional E 3 model, wherein future demands for nuclear power are projected in price competition with other energy sources under a wide range of long-term demographic (population, workforce size and productivity), economic (price-, population-, and income-determined demand for energy services, price- and population-modified GNP, resource depletion, world-market fossil energy prices), policy (taxes, tariffs, sanctions), and top-level technological (energy intensity and end-use efficiency improvements) drivers. Using the framework provided by the global E 3 model, the impacts of both external and internal drivers are investigated. The ability to connect external and internal drivers through this modeling framework allows the study of impacts and tradeoffs between fossil- versus nuclear-fuel burning, that includes interactions between cost, environmental, proliferation, resource, and policy issues

Long-term global nuclear energy and fuel cycle strategies

Energy Technology Data Exchange (ETDEWEB)

Krakowski, R.A. [Los Alamos National Lab., NM (United States). Technology and Safety Assessment Div.

1997-09-24

The Global Nuclear Vision Project is examining, using scenario building techniques, a range of long-term nuclear energy futures. The exploration and assessment of optimal nuclear fuel-cycle and material strategies is an essential element of the study. To this end, an established global E{sup 3} (energy/economics/environmental) model has been adopted and modified with a simplified, but comprehensive and multi-regional, nuclear energy module. Consistent nuclear energy scenarios are constructed using this multi-regional E{sup 3} model, wherein future demands for nuclear power are projected in price competition with other energy sources under a wide range of long-term demographic (population, workforce size and productivity), economic (price-, population-, and income-determined demand for energy services, price- and population-modified GNP, resource depletion, world-market fossil energy prices), policy (taxes, tariffs, sanctions), and top-level technological (energy intensity and end-use efficiency improvements) drivers. Using the framework provided by the global E{sup 3} model, the impacts of both external and internal drivers are investigated. The ability to connect external and internal drivers through this modeling framework allows the study of impacts and tradeoffs between fossil- versus nuclear-fuel burning, that includes interactions between cost, environmental, proliferation, resource, and policy issues.

Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease, GOLD Executive Summary

DEFF Research Database (Denmark)

Vestbo, Jørgen; Hurd, Suzanne S; Agusti, Alvar G

2013-01-01

Chronic obstructive pulmonary disease (COPD) is a global health problem and since 2001 the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5...

Review of the regions and global warming: Impacts and response strategies

International Nuclear Information System (INIS)

Schmandt, J.; Clarkson, J.

1992-01-01

This book is a compilation of essays prepared by the winners and finalists of the 1991 competition for the George and Cynthia Mitchell International Prize for Sustainable Development. In that year, the prize was awarded for outstanding papers on regional implications of global climate change. In the introduction that precedes the 19 essays, the editors establish that the volume focuses on mitigative and adaptive strategies that can be carried out regionally. Because the authors of the essays are from a wide range of locations and affiliations, they present a diverse set of perspectives on the global change issue. The essays are simultaneously scholarly and of uniformly high readability, and should be understandable to a general college-level audience

Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

Science.gov (United States)

Oh, Doo-Byoung

2015-08-01

Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

Developing and implementing a data acquisition strategy for global agricultural monitoring: an inter-agency initiative

Science.gov (United States)

Justice, C. O.; Whitcraft, A. K.; Becker-Reshef, I.; Killough, B.

2013-12-01

In 2011, in response to global food crises, the G20 Agricultural Ministers launched a satellite-based global agricultural monitoring initiative to develop the Group on Earth Observations Global Agriculture Monitoring (GEOGLAM) system. The GEO is aimed at enhancing the availability and use of both satellite and in situ data for societal benefit. This initiative builds on the observation requirements developed by the GEO Agricultural Community of Practice, the understanding that no one satellite system can currently provide all the data needed for agricultural monitoring and the resulting recommendation for improved acquisition and availability of data by the World's space agencies. Implicit in this recommendation is the fact that certain regions of the Earth are imagery rich while others are imagery poor, leaving knowledge gaps about agricultural processes and food supply for certain areas of the World. In order to respond to these knowledge gaps and to strengthen national, regional, and global agricultural monitoring networks, GEOGLAM is working with the Committee on Earth Observations (CEOS), the space arm of GEO, to develop a coordinated global acquisition strategy. A key component of GEOGLAM is an effort to articulate the temporal and spatial Earth Observation (EO) requirements for monitoring; second, the identification of current and planned missions which are capable of fulfilling these EO requirements; and third, the development of a multi-agency, multi-mission image acquisition strategy for agricultural monitoring. CEOS engineers and GEOGLAM scientists have been collaborating on the EO requirements since 2012, and are now beginning the first implementation phase of the acquisition strategy. The goal is to put in place an operational system of systems using a virtual constellation of satellite-based sensors acquiring data to meet the needs for monitoring and early warning of shortfalls in agricultural production, a goal that was articulated in the 1970's

Gut microbiota role in irritable bowel syndrome: New therapeutic strategies.

Science.gov (United States)

Distrutti, Eleonora; Monaldi, Lorenzo; Ricci, Patrizia; Fiorucci, Stefano

2016-02-21

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

Accuracy and speed feedback: Global and local effects on strategy use

Science.gov (United States)

Touron, Dayna R.; Hertzog, Christopher

2013-01-01

Background Skill acquisition often involves a shift from an effortful algorithm-based strategy to more fluent memory-based performance. Older adults’ slower strategy transitions can be ascribed to both slowed learning and metacognitive factors. Experimenters often provide feedback on response accuracy; this emphasis may either inadvertently reinforce older adults’ conservatism or might highlight that retrieval is generally quite accurate. RT feedback can lead to more rapid shift to retrieval (Hertzog, Touron, & Hines, 2007). Methods This study parametrically varied trial-by-trial feedback to examine whether strategy shifts in the noun-pair task in younger (M = 19) and older adults (M = 67) were influenced by type of performance feedback: none, trial accuracy, trial RT, or both accuracy and RT. Results Older adults who received accuracy feedback retrieved more often, particularly on difficult rearranged trials, and participants who receive speed feedback performed the scanning strategy more quickly. Age differences were also obtained in local (trial-level) reactivity to task performance, but these were not affected by feedback. Conclusions Accuracy and speed feedback had distinct global (general) influences on task strategies and performance. In particular, it appears that the standard practice of providing trial-by-trial accuracy feedback might facilitate older adults’ use of retrieval strategies in skill acquisition tasks. PMID:24785594

MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

Directory of Open Access Journals (Sweden)

Marcelo E Ezquer

2012-01-01

Full Text Available Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN, a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs. The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

Mobilization strategy to overcome global crisis of water consumption

Science.gov (United States)

Suzdaleva, Antonina; Goryunova, Svetlana; Marchuk, Aleksey; Borovkov, Valery

2017-10-01

Today, the global water consumption crisis is one of the main threats that can disrupt socio-economic and environmental conditions of life of the majority of the world’s population. The water consumption mobilization strategy is based on the idea of increasing the available water resources. The main direction for the implementation of this strategy is the construction of anti-rivers - the systems for inter-basin (interregional) water resources redistribution. Antirivers are intended for controlled redistribution of water resources from regions with their catastrophic excess to regions with their critical shortage. The creation of anti-rivers, taking into account the requirements of environmental safety, will form large-scale managed natural- engineering systems and implement the principle of sustainable development adopted by the United Nations. The aim of the article is to substantiate a new methodological approach to address the problem, where the implementation of this approach can prevent large-scale humanitarian and environmental disasters expected in the coming years.

The EU's Global Strategy in the Age of Brexit and 'America First'

NARCIS (Netherlands)

Larik, J.E.

2017-01-01

In June 2016, the European Union launched its new ‘Global Strategy for Foreign and Security Policy’. In less unusual times, it would have been received as merely the latest iteration of the main tenets and ambitions of EU external action, this time with an enhanced dose of pragmatism to respond to a

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

Directory of Open Access Journals (Sweden)

Jing Lin

2017-12-01

Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

The Epigenome as a therapeutic target for Parkinson's disease

Directory of Open Access Journals (Sweden)

Shane V Hegarty

2016-01-01

Full Text Available Parkinson's disease (PD is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. This article first discusses the present evidence implicating global, and dopaminergic neuron-specific, alterations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase (HAT and histone deacetylase (HDAC enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.

Priority Selection Within National Innovation Strategy in Global Context

Directory of Open Access Journals (Sweden)

Prokopenko Olha

2017-08-01

Full Text Available The article deals with global experience in analysing the priorities based on their importance for country development and on national and international criteria using algorithm for the selection process. The main aspects of the process of development and implementation of international technology strategies were considered. The authors prove that through the analysis of innovation systems at macro level decision about the priorities in optimization with the aim to improve regulations in science, technology and innovation is provided. The main techniques and decisions were considered based on foresight-studies. Authors propose to create informative and analytical system for the foresight aims.

Internationalization of product-service systems: Global, regional or national strategy?

OpenAIRE

Parry, G.; Bustinza, O. F.; Vendrell-Herrero, F.; O'Regan, N.

2016-01-01

This paper explores the validity of national, regional or global strategies in the provision of a music industry product service system. Quantitative analysis of cross-section data from over 70,000 respondents from 15 geographically spread countries identified a homogeneous group of so-called ‘Out of Touch’ consumers characterized by a shared attitude: they are interested in and have the money to purchase music, but no longer do so. The analysis ascertains if and how re-engaging this group in...

[From tic disorders to Tourette syndrome: current data, comorbidities, and therapeutic approach in children].

Science.gov (United States)

Fourneret, P; Desombre, H; Broussolle, E

2014-06-01

Motor tics are frequently observed in children during development. Usually transient and benign, they can become chronic over time, join various morbid disorders (vocal tics, attention deficit and hyperactivity disorder, and obsessive-compulsive disorders) and move toward genuine Tourette syndrome. In this case, it will be necessary to prevent impacts - mainly in terms of quality of life and emotional and relational problems - using a global therapeutic strategy combining psychoeducational approaches with appropriate medication. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies.

Science.gov (United States)

Stan, Ana D; Lewis, David A

2012-06-01

Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain's own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

COIN Goes GLOCAL: Traditional COIN With a Global Perspective: Does the Current US Strategy Reflect COIN Theory, Doctrine and Principles

Science.gov (United States)

2007-05-17

COIN goes “ GLOCAL ”: Traditional COIN with a Global Perspective: Does the Current US Strategy Reflect COIN Theory, Doctrine and Principles? A...TITLE AND SUBTITLE COIN goes “ GLOCAL ”: Traditional COIN with a Global P ti D th C t US St t R fl t COIN 5a. CONTRACT NUMBER Perspective: Does...Monograph: COIN goes “ GLOCAL ”: Traditional COIN with a Global Perspective: Does the Current US Strategy Reflect COIN Theory, Doctrine and Principles

Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies.

Science.gov (United States)

Agnihotri, Sameer; Burrell, Kelly E; Wolf, Amparo; Jalali, Sharzhad; Hawkins, Cynthia; Rutka, James T; Zadeh, Gelareh

2013-02-01

Glioblastoma (GBM) is the most common and lethal primary brain tumor. Over the past few years tremendous genomic and proteomic characterization along with robust animal models of GBM have provided invaluable data that show that "GBM", although histologically indistinguishable from one another, are comprised of molecularly heterogenous diseases. In addition, robust pre-clinical models and a better understanding of the core pathways disrupted in GBM are providing a renewed optimism for novel strategies targeting these devastating tumors. Here, we summarize a brief history of the disease, our current molecular knowledge, lessons from animal models and emerging concepts of angiogenesis, invasion, and metabolism in GBM that may lend themselves to therapeutic targeting.

A global strategy for labor.

Science.gov (United States)

Faux, Jeff

2002-01-01

The rules of the global market were established to protect the interests of investors at the expense of workers and they shift benefits to investors, costs to workers. Globalization is measured by the interests of investors. But 20 years of investor protectionism show that growth has slowed and equality has gotten worse. The purpose of neo-liberal policies has been to discipline labor to free capital from having to bargain with workers over gains from rising productivity. But such bargaining is the essence of a democratic market. Uncontrolled globalization puts government's domestic policies on the side of capital. In an economy whose growth depends on foreign markets, rising domestic wages make it harder to compete internationally. There has been a general deterioration of labor's position relative to capital's. A global marketplace implies a global politics, and the real work happens when representatives of multi-national business privately negotiate the rules. Labor must change the framework in which the investor class pursues its interest across borders, while workers are constricted by borders. Labor unions are critical; they can deny the human resource necessary for profits. The strike is the ultimate threat to investors. One solution: a "grand bargain" linking development with broadly increased living standards connected to planning for sustainable development to create a global social contract. Workers have advantages: they are the majority and they are indispensable.

The globalisation strategies of five Asian tobacco companies: a comparative analysis and implications for global health governance.

Science.gov (United States)

Lee, Kelley; Eckhardt, Jappe

2017-03-01

The global tobacco industry, from the 1960s to mid 1990s, saw consolidation and eventual domination by a small number of transnational tobacco companies (TTC). This paper draws together comparative analysis of five case studies in the special issue on 'The Emergence of Asian Tobacco Companies: Implications for Global Health Governance.' The cases suggest that tobacco industry globalisation is undergoing a new phase, beginning in the late 1990s, with the adoption of global business strategies by five Asian companies. The strategies were prompted foremost by external factors, notably market liberalisation, competition from TTCs and declining domestic markets. State protection and promotion enabled the industries in Japan, South Korea and China to rationalise their operations ahead of foreign market expansion. The TTM and TTL will likely remain domestic or perhaps regional companies, JTI and KT&G have achieved TTC status, and the CNTC is poised to dwarf all existing companies. This global expansion of Asian tobacco companies will increase competition which, in turn, will intensify marketing, exert downward price pressures along the global value chain, and encourage product innovation. Global tobacco control requires fuller understanding of these emerging changes and the regulatory challenges posed by ongoing globalisation.

Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

Directory of Open Access Journals (Sweden)

Jeehoon Kang

2016-11-01

Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

Turkey - An 'Ormuz strait' in the US strategy for global energy control

International Nuclear Information System (INIS)

Lagha, Chegrouche

2003-01-01

Following the events of September 11, 2001, rivalry in the Caspian region has taken the form of open conflicts in which the various powers confront one another via zones and 'proxy' ethnic and/or cultural communities. Alliances are circumstantial and can be changed as the geostrategic interests of the protagonists dictate. This is a rivalry that is re-shaping the geopolitical and strategic order in this region. New facts come along to expose a new American strategy for the global control of energy resources. Turkey appears as a Eurasian barrier in this new strategy and warfare as a means to open up the Caspian region. (authors)

Global demand for rare earth resources and strategies for green mining

Energy Technology Data Exchange (ETDEWEB)

Dutta, Tanushree [Department of Civil & Environmental Engineering, Hanyang University, 222 Wangsimni-Ro, Seoul 04763 (Korea, Republic of); Kim, Ki-Hyun, E-mail: kkim61@hanyang.ac.kr [Department of Civil & Environmental Engineering, Hanyang University, 222 Wangsimni-Ro, Seoul 04763 (Korea, Republic of); Uchimiya, Minori [USDA-ARS Southern Regional Research Center, 1100 Robert E. Lee Boulevard, New Orleans, LA 70124 (United States); Kwon, Eilhann E. [Department of Environment and Energy, Sejong University, Seoul 05006 (Korea, Republic of); Jeon, Byong-Hun [Department of Natural Resources & Environmental Engineering, Hanyang University, 222 Wangsimni-Ro, Seoul 04763 (Korea, Republic of); Deep, Akash [Central Scientific Instruments Organisation (CSIR-CSIO), Sector 30C, Chandigarh 160030 (India); Yun, Seong-Taek [Department of Earth and Environmental Sciences and KU-KIST Green School, Korea University, Seoul 02841 (Korea, Republic of)

2016-10-15

Rare earth elements (REEs) are essential raw materials for emerging renewable energy resources and ‘smart’ electronic devices. Global REE demand is slated to grow at an annual rate of 5% by 2020. This high growth rate will require a steady supply base of REEs in the long run. At present, China is responsible for 85% of global rare earth oxide (REO) production. To overcome this monopolistic supply situation, new strategies and investments are necessary to satisfy domestic supply demands. Concurrently, environmental, economic, and social problems arising from REE mining must be addressed. There is an urgent need to develop efficient REE recycling techniques from end-of-life products, technologies to minimize the amount of REEs required per unit device, and methods to recover them from fly ash or fossil fuel-burning wastes.

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

Science.gov (United States)

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

The Geo-strategies and Global Peace of Technology on Customer Relationship Management Performance: A Pilot Study among SME’s Logistic Operators

Directory of Open Access Journals (Sweden)

Muhamad Fairos Mohamad Shah

2017-12-01

Full Text Available Small and medium enterprises (SMEs are playing an increasingly important role in sustaining geo strategies and global peace economic growth and logistic system in Malaysia. SMEs also play a very crucial role in customer relationship as they may serve the roles of customer, distributor producer and supplier. However, adaption of customer relationship in Malaysian SMEs has not been fully explored. CRMP model for logistic service presents the combination of technology strategy in term of geo strategies and global peace. The goal of this study is to investigate customer relationship management performance and technology strategy. The dimensions for technology factors are Support information system, information sharing, Usefulness, care/help, ease of use, service portfolio, security and Update System. The populations of study were customers from a logistic company located in Pulau Pinang. Simple random sampling was selected from the target populations. Data collection resulted in 100 respondents to answers questionnaire from the customers of logistic company. Based on the finding, the result showed that, technology strategies are anchor factors in determining geo strategies and global peace on customer relationship management performance. Further study has important managerial implications as the findings will enable management of SMEs to understand progressive and highly varied CRMP practices and contextual factors that contribute to the CRMP as well as geo strategies and global peace and innovative implementation.

Myasthenia gravis: subgroup classification and therapeutic strategies.

Science.gov (United States)

Gilhus, Nils Erik; Verschuuren, Jan J

2015-10-01

Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Medicinal Chemistry of Therapeutic Oligonucleotides.

Science.gov (United States)

Wan, W Brad; Seth, Punit P

2016-11-10

Oligonucleotide-based therapeutics have made rapid progress in the clinic for treatment of a variety of disease indications. Unmodified oligonucleotides are polyanionic macromolecules with poor drug-like properties. Over the past two decades, medicinal chemists have identified a number of chemical modification and conjugation strategies which can improve the nuclease stability, RNA-binding affinity, and pharmacokinetic properties of oligonucleotides for therapeutic applications. In this perspective, we present a summary of the most commonly used nucleobase, sugar and backbone modification, and conjugation strategies used in oligonucleotide medicinal chemistry.

Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

Science.gov (United States)

Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

2015-10-01

Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

Science.gov (United States)

Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

2017-01-01

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

Science.gov (United States)

Liu, Chang; Zhang, Li; Liu, Hao; Cheng, Kun

2017-11-28

The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

A global method for calculating plant CSR ecological strategies applied across biomes world-wide

NARCIS (Netherlands)

Pierce, S.; Negreiros, D.; Cerabolini, B.E.L.; Kattge, J.; Díaz, S.; Kleyer, M.; Shipley, B.; Wright, S.J.; Soudzilovskaia, N.A.; Onipchenko, V.G.; van Bodegom, P.M.; Frenette-Dussault, C.; Weiher, E.; Pinho, B.X.; Cornelissen, J.H.C.; Grime, J.P.; Thompson, K.; Hunt, R.; Wilson, P.J.; Buffa, G.; Nyakunga, O.C.; Reich, P.B.; Caccianiga, M.; Mangili, F.; Ceriani, R.M.; Luzzaro, A.; Brusa, G.; Siefert, A.; Barbosa, N.P.U.; Chapin III, F.S.; Cornwell, W.K.; Fang, Jingyun; Wilson Fernandez, G.; Garnier, E.; Le Stradic, S.; Peñuelas, J.; Melo, F.P.L.; Slaviero, A.; Tabarrelli, M.; Tampucci, D.

2017-01-01

Competitor, stress-tolerator, ruderal (CSR) theory is a prominent plant functional strategy scheme previously applied to local floras. Globally, the wide geographic and phylogenetic coverage of available values of leaf area (LA), leaf dry matter content (LDMC) and specific leaf area (SLA)

Linking Globalization, Economic Growth and Poverty: Impacts of Agribusiness Strategies on Sub-Saharan Africa

OpenAIRE

Dave Weatherspoon; Joyce Cacho; Ralph Christy

2001-01-01

This paper analyzes the increased role of the domestic and multinational private sectors in economic development within SSA. The globalization process demands that private sector strategies must now be assessed by their contributions to emerging economies, as well as by company goals.

The globalisation strategies of five Asian tobacco companies: a comparative analysis and implications for global health governance

Science.gov (United States)

Lee, Kelley; Eckhardt, Jappe

2017-01-01

ABSTRACT The global tobacco industry, from the 1960s to mid 1990s, saw consolidation and eventual domination by a small number of transnational tobacco companies (TTC). This paper draws together comparative analysis of five case studies in the special issue on ‘The Emergence of Asian Tobacco Companies: Implications for Global Health Governance.’ The cases suggest that tobacco industry globalisation is undergoing a new phase, beginning in the late 1990s, with the adoption of global business strategies by five Asian companies. The strategies were prompted foremost by external factors, notably market liberalisation, competition from TTCs and declining domestic markets. State protection and promotion enabled the industries in Japan, South Korea and China to rationalise their operations ahead of foreign market expansion. The TTM and TTL will likely remain domestic or perhaps regional companies, JTI and KT&G have achieved TTC status, and the CNTC is poised to dwarf all existing companies. This global expansion of Asian tobacco companies will increase competition which, in turn, will intensify marketing, exert downward price pressures along the global value chain, and encourage product innovation. Global tobacco control requires fuller understanding of these emerging changes and the regulatory challenges posed by ongoing globalisation. PMID:28139967

Shifts in nitrogen acquisition strategies enable enhanced terrestrial carbon storage under elevated CO2 in a global model

Science.gov (United States)

Sulman, B. N.; Brzostek, E. R.; Menge, D.; Malyshev, S.; Shevliakova, E.

2017-12-01

Earth System Model (ESM) projections of terrestrial carbon (C) uptake are critical to understanding the future of the global C cycle. Current ESMs include intricate representations of photosynthetic C fixation in plants, allowing them to simulate the stimulatory effect of increasing atmospheric CO2 levels on photosynthesis. However, they lack sophisticated representations of plant nutrient acquisition, calling into question their ability to project the future land C sink. We conducted simulations using a new model of terrestrial C and nitrogen (N) cycling within the Geophysical Fluid Dynamics Laboratory (GFDL) global land model LM4 that uses a return on investment framework to simulate global patterns of N acquisition via fixation of N2 from the atmosphere, scavenging of inorganic N from soil solution, and mining of organic N from soil organic matter (SOM). We show that these strategies drive divergent C cycle responses to elevated CO2 at the ecosystem scale, with the scavenging strategy leading to N limitation of plant growth and the mining strategy facilitating stimulation of plant biomass accumulation over decadal time scales. In global simulations, shifts in N acquisition from inorganic N scavenging to organic N mining along with increases in N fixation supported long-term acceleration of C uptake under elevated CO2. Our results indicate that the ability of the land C sink to mitigate atmospheric CO2 levels is tightly coupled to the functional diversity of ecosystems and their capacity to change their N acquisition strategies over time. Incorporation of these mechanisms into ESMs is necessary to improve confidence in model projections of the global C cycle.

Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

OpenAIRE

Thomas L. Chenevert; Charles R. Meyer; Bradford A. Moffat; Alnawaz Rehemtulla; Suresh K. Mukherji; Stephen S. Gebarski; Douglas J. Quint; Patricia L. Robertson; Theodore S. Lawrence; Larry Junck; Jeremy M. G. Taylor; Timothy D. Johnson; Qian Dong; Karin M. Muraszko; James A. Brunberg

2002-01-01

The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular ...

Impact of the scintigraphy of somatostatin receptors upon the therapeutic strategy in patients bearing digestive endocrine tumors

International Nuclear Information System (INIS)

Lebtahi, R.; Cadiot, G.; Genin, R.; Delahaye, N.; Faraggi, M.; Daou, D.; Peker, C.; Migon, M.; Le Guludec, D.

1997-01-01

The scintigraphy of somatostatin receptors (SSR) is a sensible method for detecting the gastroenteric-pancreatic endocrine tumors and their metastases. The aim of this study is to evaluate the clinical impact of the results of SSR in taking patients in therapeutic charge. A hundred and sixty patients bearing biologically and/or histologically proved digestive endocrine tumors were prospectively studied. The patients were classified in 3 groups: group I - 90 patients with no known metastases; group II - 59 patients with liver metastases and group III - 11 patients with known extra-hepatic metastases. The results of the scintigraphy were compared with those of conventional imaging. The following results were obtained: in group 1 (90 patients) the conventional imaging has allowed detecting 53 primitive tumors in 44 patients. The SSR visualized 68% of these sites and has detected 26 supplementary primitive sites in 20 patients and 29 metastatic sites in 25 patients. In group II the scintigraphy has detected 95% of hepatic metastases and revealed 23 new metastasis sites and 18/59 patients. In group III the scintigraphy has detected 11 new sites in 7 patients. The results of scintigraphy modified the patient's classification in 38 cases (24%). The therapeutic strategy was modified for 40 patients (25%). In conclusion, the scintigraphy of somatostatin receptors is able to detect a significant number of digestive endocrine tumors what has important implications for therapeutical planning of the treatment of patients. It must be carried out during pre-therapeutic extension examination of these tumors

Therapeutic cloning: The ethical limits

International Nuclear Information System (INIS)

Whittaker, Peter A.

2005-01-01

A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

Therapeutic strategies in an animal model of neurodegeneration

NARCIS (Netherlands)

Borre, Y.E.

2013-01-01

Neurodegenerative diseases have complex and multifactorial etiologies, creating an enormous burden on society without an effective treatment. This thesis utilized olfactory bulbectomized rats to investigate therapeutic approaches to neurodegenerative disorders. Removal of the olfactory bulbs, leads

Rebuilding the Arab Economies: New Regional and Global Strategies

Directory of Open Access Journals (Sweden)

Laura - Ramona BENCHEA

2015-12-01

Full Text Available The Arab countries are facing one of their most difficult periods of the modern history. The popular uprisings which broke out at the beginning of 2011 in Tunisia and then spread to Egypt, Libya, Morocco, Jordan, Bahrain and Syria, reflect profound economic and social hardships, but also major uncertainties regarding the political perspectives of these countries. The political transition carried out by several Arab countries could represent an incentive for profound economic reorganization and structural change all over the region. The aim of this paper is to assess the structural economic challenges the Arab countries had been confronted with over many decades and to identify possible regional and global strategies for economic development.

Expression of PFKFB3 and Ki67 in lung adenocarcinomas and targeting PFKFB3 as a therapeutic strategy.

Science.gov (United States)

Li, Xiaoli; Liu, Jian; Qian, Li; Ke, Honggang; Yao, Chan; Tian, Wei; Liu, Yifei; Zhang, Jianguo

2018-01-11

Phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) catalyzes the synthesis of F2,6BP, which is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1): the rate-limiting enzyme of glycolysis. During tumorigenesis, PFKFB3 increases glycolysis, angiogenesis, and tumor progression. In this study, our aim was to investigate the significance of PFKFB3 and Ki67 in human lung adenocarcinomas and to target PFKFB3 as a therapeutic strategy. In this study, we determined the expression levels of PFKFB3 mRNA and proteins in cancerous and normal lung adenocarcinomas by quantitative reverse transcription PCR (qRT-PCR), Western blot analysis, and tissue microarray immunohistochemistry analysis, respectively. In human adenocarcinoma tissues, PFKFB3 and Ki67 protein levels were related to the clinical characteristics and overall survival. Both PFKFB3 mRNA and protein were significantly higher in lung adenocarcinoma cells (all P targeting PFKFB3, it inhibited cell viability and glycolytic activity. It also caused apoptosis and induced cell cycle arrest. Furthermore, the migration and invasion of A549 cells was inhibited. We conclude that PFKFB3 bears an oncogene-like regulatory element in lung adenocarcinoma progression. In the treatment of lung adenocarcinoma, targeting PFKFB3 would be a promising therapeutic strategy.

Therapeutic Strategies for Hereditary Kidney Cancer.

Science.gov (United States)

Sidana, Abhinav; Srinivasan, Ramaprasad

2016-08-01

The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

Global environmental policy strategies. ''Environment and development'' in north-south relations. Strategien globaler Umweltpolitik. ''Umwelt und Entwicklung'' in den Nord-Sued-Beziehungen

Energy Technology Data Exchange (ETDEWEB)

Bruckmeier, K

1994-01-01

Global environmental policy has hardly made headway after the United Nations World Conference on Environment and Development (UNCED) in Rio in June 1992, despite there being no shortage of programmes, institutions, and actors. Obviously, formal structures for political action based on the system of institutions of the United Nations do not suffice. Global environmental policy strategies must reach further, overcoming system-immanent obstacles to sustainable development. This necessitates analyzing the causes of environmental destruction and making a critical evaluation of the relations between the societies of the North and South that received their imprint from development policies. Only after such a preliminary elucidation by interdisciplinary approaches in the light of political and ecological economy and human ecology does an empirical analysis of politically controlled processes in environmental and development policy make sense. The analysis points to strategies for this international political field that rely on non-governmental actors and social movements, and question the traditional European model of an environmental policy determined by government institutions. (orig./UA)

Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data

International Nuclear Information System (INIS)

Coussens, Nathan P.; Schuck, Peter; Zhao, Huaying

2012-01-01

Highlights: ► We demonstrate the usefulness of global analysis of ITC data for proton-linked binding study. ► Various experimental strategies are evaluated for their information content. ► Data at multiple temperatures might improve the precision of binding parameters. ► Methods for detailed error analysis of parameter uncertainties are discussed. ► By global modeling, an uncertainty in molecular concentrations can be accounted for. - Abstract: Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally

Global burden of Shigella infections : implications for vaccine development and implementation of control strategies

NARCIS (Netherlands)

Kotloff, KL; Winickoff, JP; Ivanoff, B; Clemens, JD; Swerdlow, DL; Sansonetti, PJ; Adak, GK; Levine, MM

1999-01-01

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection.

Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Alireza eFaridar

2011-12-01

Full Text Available Therapeutic hypothermia (TH is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS and traumatic brain injury (TBI, however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention.Among the various methods for hypothermia induction, intravascular cooling (IVC may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.

Landslide risk reduction strategies: an inventory for the Global South

Science.gov (United States)

Maes, Jan; Kervyn, Matthieu; Vranken, Liesbet; Dewitte, Olivier; Vanmaercke, Matthias; Mertens, Kewan; Jacobs, Liesbet; Poesen, Jean

2015-04-01

Landslides constitute a serious problem globally. Moreover, landslide impact remains underestimated especially in the Global South. It is precisely there where the largest impact is experienced. An overview of measures taken to reduce risk of landslides in the Global South is however still lacking. Because in many countries of the Global South disaster risk reduction (DRR) is at an emerging stage, it is crucial to monitor the ongoing efforts (e.g. discussions on the Post-2015 Framework for DRR). The first objective of this study is to make an inventory of techniques and strategies that are applied to reduce risk from landslides in tropical countries. The second objective is to investigate what are the main bottlenecks for implementation of DRR strategies. In order to achieve these objectives, a review of both scientific and grey literature was conducted, supplemented with expert knowledge. The compilation of recommended and implemented DRR measures from landslide-prone tropical countries is based on an adapted classification proposed by the SafeLand project. According to Vaciago (2013), landslide risk can be reduced by either reducing the hazard, the vulnerability, the number or value of elements at risk or by sharing the residual risk. In addition, these measures can be combined with education and/or awareness raising and are influenced by governance structures and cultural beliefs. Global landslide datasets have been used to identify landslide-prone countries, augmented with region-specific datasets. Countries located in the tropics were selected in order to include landslide-prone countries with a different Human Development Index (HDI) but with a similar climate. Preliminary results support the statement made by Anderson (2013) that although the importance of shifting from post-disaster emergency actions to pre-disaster mitigation is acknowledged, in practice this paradigm shift seems rather limited. It is expected that this is especially the case in countries

Targeting mitochondrial respiration as a therapeutic strategy for cervical cancer.

Science.gov (United States)

Tian, Shenglan; Chen, Heng; Tan, Wei

2018-05-23

Targeting mitochondrial respiration has been documented as an effective therapeutic strategy in cancer. However, the impact of mitochondrial respiration inhibition on cervical cancer cells are not well elucidated. Using a panel of cervical cancer cell lines, we show that an existing drug atovaquone is active against the cervical cancer cells with high profiling of mitochondrial biogenesis. Atovaquone inhibited proliferation and induced apoptosis with varying efficacy among cervical cancer cell lines regardless of HPV infection, cellular origin and their sensitivity to paclitaxel. We further demonstrated that atovaquone acts on cervical cancer cells via inhibiting mitochondrial respiration. In particular, atovaquone specifically inhibited mitochondrial complex III but not I, II or IV activity, leading to respiration inhibition and energy crisis. Importantly, we found that the different sensitivity of cervical cancer cell lines to atovaquone were due to their differential level of mitochondrial biogenesis and dependency to mitochondrial respiration. In addition, we demonstrated that the in vitro observations were translatable to in vivo cervical cancer xenograft mouse model. Our findings suggest that the mitochondrial biogenesis varies among patients with cervical cancer. Our work also suggests that atovaquone is a useful addition to cervical cancer treatment, particularly to those with high dependency on mitochondrial respiration. Copyright © 2018 Elsevier Inc. All rights reserved.

[MPOWER--strategy for fighting the global tobacco epidemic].

Science.gov (United States)

Kaleta, Dorota; Kozieł, Anna; Miśkiewicz, Paulina

2009-01-01

It is estimated that tobacco use may cause death of 5 million people in 2008, which is higher than the number of deaths attributed to tuberculosis (TB), HIV/AIDS and malaria taken together. By 2030, the number of deaths related to the tobacco epidemic could exceed annually even 8 million. Despite many difficulties, a growing number of countries undertake intensive actions aimed at tobacco control. The objective of this paper was to discuss the major objectives of the MPOWER Report issued by the World Health Organization (WHO). The MPOWER package consists a set of six key and most effective strategies for fighting the global tobacco epidemic: 1) Monitoring tobacco consumption and the effectiveness of preventive measures; 2) Protect people from tobacco smoke; 3) Offer help to quit tobacco use; 4) Warn about the dangers of tobacco; 5) Enforce bans on tobacco advertising, promotion and sponsorship; and 6) Raise taxes on tobacco. It is proven that these strategies implemented in the compatible way, effectively decreases tobacco use. In addition, MPOWER comprises epidemiological data, information on implemented tobacco control measures and their efficiency. MPOWER is the only one document of a somewhat strategic nature that is a source of information on the spread of tobacco epidemic, as well as of suggestions concerning specific actions for supporting the fight against this epidemic.

The introduction of new vaccines into developing countries. IV: Global Access Strategies.

Science.gov (United States)

Mahoney, Richard T; Krattiger, Anatole; Clemens, John D; Curtiss, Roy

2007-05-16

This paper offers a framework for managing a comprehensive Global Access Strategy for new vaccines in developing countries. It is aimed at strengthening the ability of public-sector entities to reach their goals. The Bill and Melinda Gates Foundation and The Rockefeller Foundation have been leaders in stimulating the creation of new organizations - public/private product development partnerships (PDPs) - that seek to accelerate vaccine development and distribution to meet the health needs of the world's poor. Case studies of two of these PDPs - the Salmonella Anti-pneumococcal Vaccine Program and the Pediatric Dengue Vaccine Initiative - examine development of such strategies. Relying on the application of innovation theory, the strategy leads to the identification of six Components of Innovation which cover all aspects of the vaccine innovation process. Appropriately modified, the proposed framework can be applied to the development and introduction of other products in developing countries including drugs, and nutritional and agricultural products.

'Preparing ourselves to become an international organization': Thailand Tobacco Monopoly's regional and global strategies.

Science.gov (United States)

MacKenzie, Ross; Ross, Hana; Lee, Kelley

2017-03-01

The Thailand Tobacco Monopoly (TTM) controlled the country's tobacco industry from its formation in the 1940s, until the government dropped restrictions on imported cigarettes in the late 1980s in response to pressure from the United States. The TTM has since competed with transnational tobacco companies (TTCs) in a semi-monopoly market in which TTCs have steadily increased their market share. Coupled with a decline in national smoking prevalence, the result of Thailand's stringent tobacco control agenda, the TTM now accounts for a diminishing share of a contracting market. In response, the monopoly has looked to regional trade liberalisation, and proximity to markets with some of the world's highest smoking rates to expand its operations. Expansion strategies have gone largely unrealised however, and the TTM effectively remains a domestic operation. Using TTM publications, market and trade reports, industry publications, tobacco industry documents and other resources, this paper analyses TTM expansion strategies, and the limited extent to which they have been achieved. This inability to expand its operations has left the monopoly potentially vulnerable to global strategies of its transnational competitors. This article is part of the special issue 'The Emergence of Asian Tobacco Companies: Implications for Global Health Governance'.

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Alana M. Horowitz

2017-08-01

Full Text Available Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

Down-Side Risk Metrics as Portfolio Diversification Strategies across the Global Financial Crisis

Directory of Open Access Journals (Sweden)

David E. Allen

2016-06-01

Full Text Available This paper features an analysis of the effectiveness of a range of portfolio diversification strategies, with a focus on down-side risk metrics, as a portfolio diversification strategy in a European market context. We apply these measures to a set of daily arithmetically-compounded returns, in U.S. dollar terms, on a set of ten market indices representing the major European markets for a nine-year period from the beginning of 2005 to the end of 2013. The sample period, which incorporates the periods of both the Global Financial Crisis (GFC and the subsequent European Debt Crisis (EDC, is a challenging one for the application of portfolio investment strategies. The analysis is undertaken via the examination of multiple investment strategies and a variety of hold-out periods and backtests. We commence by using four two-year estimation periods and a subsequent one-year investment hold out period, to analyse a naive 1/N diversification strategy and to contrast its effectiveness with Markowitz mean variance analysis with positive weights. Markowitz optimisation is then compared to various down-side investment optimisation strategies. We begin by comparing Markowitz with CVaR, and then proceed to evaluate the relative effectiveness of Markowitz with various draw-down strategies, utilising a series of backtests. Our results suggest that none of the more sophisticated optimisation strategies appear to dominate naive diversification.

A Case Study Approach On Indian Companies And Global Companies Entry In Foreign Markets An Analysis Of Glocalization Strategies

OpenAIRE

Fernandes, Semila

2013-01-01

The present paper involved a study on Glocal communication strategy adopted by select global companies while foraying into India and Indian companies foray into the foreign markets. Glocalization concept in specific terms implies Think Global and Act Local which has been developed through Japanese business practices. The requirement of this global localization idea arrived in the late 1980s to bridge the gap between local, regional, national, global management of the businesses 20.PROBLEM STA...

A call to strengthen the global strategy for schistosomiasis and soil-transmitted helminthiasis: the time is now

Science.gov (United States)

Lo, Nathan C.; Addiss, David G.; Hotez, Peter J.; King, Charles H.; Stothard, J. Russell; Evans, Darin S.; Colley, Daniel G.; Lin, William; Coulibaly, Jean T.; Bustinduy, Amaya L.; Raso, Giovanna; Bendavid, Eran; Bogoch, Isaac I.; Fenwick, Alan; Savioli, Lorenzo; Molyneux, David; Utzinger, Jürg; Andrews, Jason R.

2016-01-01

Summary In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale up of mass administration of anthelminthic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis (STH), which affect over 1.5 billion of the world's poorest people. Since then, over a decade of research and experience has yielded critical new knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated World Health Organization (WHO) guidelines on preventive chemotherapy. Here, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and STH. This includes the development of guidance that is specific to goals of “morbidity control” and “elimination of transmission.” We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining status quo. Without change, we estimate that the population of sub-Saharan Africa will likely lose 2.3 million disability-adjusted life years and US$3.5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and STH. PMID:27914852

A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now.

Science.gov (United States)

Lo, Nathan C; Addiss, David G; Hotez, Peter J; King, Charles H; Stothard, J Russell; Evans, Darin S; Colley, Daniel G; Lin, William; Coulibaly, Jean T; Bustinduy, Amaya L; Raso, Giovanna; Bendavid, Eran; Bogoch, Isaac I; Fenwick, Alan; Savioli, Lorenzo; Molyneux, David; Utzinger, Jürg; Andrews, Jason R

2017-02-01

In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Balancing Inside and Outside Lobbying: The Political Strategies of Lobbyists at Global Diplomatic Conferences

NARCIS (Netherlands)

Hanegraaff, M.; Beyers, J.; De Bruycker, I.

2016-01-01

This article seeks to explain the use of inside and outside lobbying by organised interests at global diplomatic conferences. At first sight, the lobbying at these venues is puzzling as it does not seem to be a very fruitful way to acquire influence. The use of outside strategies especially is

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications

Directory of Open Access Journals (Sweden)

Jordi Bover

2016-11-01

Full Text Available Cardiovascular (CV calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD–MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc., we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.

The Impact of Complexity on Shaping Logistics Strategies in Global Supply Chains

Directory of Open Access Journals (Sweden)

Agnieszka Szmelter

2017-04-01

Full Text Available Aim/purpose - The paper aims to summarize approaches to complexity management by implementing particular logistics concepts within logistics strategies in global supply chains and to highlight a research gap in this regard. Additionally, complexity management concepts are presented. Design/methodology/approach - To achieve the research objective, a systematic literature review was used. 11 research paper were analyzed with use of review protocol. Findings - Approaches to mentioned research problem are heterogeneous in current literature and there is a research gap in complexity studies in logistics, precluding further research, for example, on complexity measurement systems. Research implications/limitations - Identified research gap will require further studies. Studied area requires more empirical research, especially in the field of complexity measurement and management techniques in particular global supply chains. Originality/value/contribution - The paper summarizes current knowledge about logistics concepts helping to manage complexity in global supply chains and defines research gaps. There are no available literature summary of that kind. The article contains a full review of logistics complexity management concepts presented in scientific literature until the end of 2016.

Perspective on Global Measles Epidemiology and Control and the Role of Novel Vaccination Strategies

Directory of Open Access Journals (Sweden)

Melissa M. Coughlin

2017-01-01

Full Text Available Measles is a highly contagious, vaccine preventable disease. Measles results in a systemic illness which causes profound immunosuppression often leading to severe complications. In 2010, the World Health Assembly declared that measles can and should be eradicated. Measles has been eliminated in the Region of the Americas, and the remaining five regions of the World Health Organization (WHO have adopted measles elimination goals. Significant progress has been made through increased global coverage of first and second doses of measles-containing vaccine, leading to a decrease in global incidence of measles, and through improved case based surveillance supported by the WHO Global Measles and Rubella Laboratory Network. Improved vaccine delivery methods will likely play an important role in achieving measles elimination goals as these delivery methods circumvent many of the logistic issues associated with subcutaneous injection. This review highlights the status of global measles epidemiology, novel measles vaccination strategies, and describes the pathway toward measles elimination.

Therapeutic cloning in individual parkinsonian mice

Science.gov (United States)

Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

Biliary parasites: diagnostic and therapeutic strategies.

Science.gov (United States)

Khandelwal, Niraj; Shaw, Joanna; Jain, Mamta K

2008-04-01

Parasitic infections of the biliary tract are a common cause of biliary obstruction in endemic areas. This article focuses on primary biliary parasites: Ascaris lumbricoides, Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, Dicrocoelium dendriticum, Fasciola hepatica, and Fasciola gigantica. Tropical and subtropical countries have the highest incidence and prevalence of these infections. Diagnosis is made primarily through direct microscopic examination of eggs in the stool, duodenal, or bile contents. Radiologic imaging may show intrahepatic ductal dilatation, whereas endoscopic retrograde cholangiopancreatography can be used diagnostically and therapeutically. However, oral treatment is inexpensive and effective for most of these parasites and can prevent untoward consequences. Primary and alternative treatments are available and are reviewed in this article.

Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

Directory of Open Access Journals (Sweden)

Anja Geiselhart

2012-01-01

Full Text Available Fanconi anemia (FA is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC. This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients.

Success in Global New Product Development: Impact of Strategy and the Behavioral Environment of the Firm

DEFF Research Database (Denmark)

de Brentani, U.; Kleinschmidt, E.J.; Salomo, Søren

2010-01-01

Product innovation and the trend toward globalization are two important dimensions driving business today, and a firm's global new product development (NPD) strategy is a primary determinant of performance. Succeeding in this competitive and complex market arena calls for corporate resources...... America and Europe, business-to-business, services and goods), a structural model testing for the hypothesized mediation effects was substantially supported. Specifically, having an organizational posture that, at once, values innovation plus globalization, as well as a senior management that is active...... as primary determinants of competitive advantage and, thus, of superior performance through the strategic initiatives that these enable. In the study, global NPD programs are assessed in terms of three dimensions: (1) the organizational resources or behavioral environment of the firm relevant...

Global-local feature attention network with reranking strategy for image caption generation

Science.gov (United States)

Wu, Jie; Xie, Si-ya; Shi, Xin-bao; Chen, Yao-wen

2017-11-01

In this paper, a novel framework, named as global-local feature attention network with reranking strategy (GLAN-RS), is presented for image captioning task. Rather than only adopting unitary visual information in the classical models, GLAN-RS explores the attention mechanism to capture local convolutional salient image maps. Furthermore, we adopt reranking strategy to adjust the priority of the candidate captions and select the best one. The proposed model is verified using the Microsoft Common Objects in Context (MSCOCO) benchmark dataset across seven standard evaluation metrics. Experimental results show that GLAN-RS significantly outperforms the state-of-the-art approaches, such as multimodal recurrent neural network (MRNN) and Google NIC, which gets an improvement of 20% in terms of BLEU4 score and 13 points in terms of CIDER score.

Clinical multi-omics strategies for the effective cancer management.

Science.gov (United States)

Yoo, Byong Chul; Kim, Kyung-Hee; Woo, Sang Myung; Myung, Jae Kyung

2017-08-15

Cancer is a global health issue as a multi-factorial complex disease, and early detection and novel therapeutic strategies are required for more effective cancer management. With the development of systemic analytical -omics strategies, the therapeutic approach and study of the molecular mechanisms of carcinogenesis and cancer progression have moved from hypothesis-driven targeted investigations to data-driven untargeted investigations focusing on the integrated diagnosis, treatment, and prevention of cancer in individual patients. Predictive, preventive, and personalized medicine (PPPM) is a promising new approach to reduce the burden of cancer and facilitate more accurate prognosis, diagnosis, as well as effective treatment. Here we review the fundamentals of, and new developments in, -omics technologies, together with the key role of a variety of practical -omics strategies in PPPM for cancer treatment and diagnosis. In this review, a comprehensive and critical overview of the systematic strategy for predictive, preventive, and personalized medicine (PPPM) for cancer disease was described in a view of cancer prognostic prediction, diagnostics, and prevention as well as cancer therapy and drug responses. We have discussed multi-dimensional data obtained from various resources and integration of multisciplinary -omics strategies with computational method which could contribute the more effective PPPM for cancer. This review has provided the novel insights of the current applications of each and combined -omics technologies, which showed their powerful potential for the establishment of PPPM for cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Volcano monitoring using the Global Positioning System: Filtering strategies

Science.gov (United States)

Larson, K.M.; Cervelli, Peter; Lisowski, M.; Miklius, Asta; Segall, P.; Owen, S.

2001-01-01

Permanent Global Positioning System (GPS) networks are routinely used for producing improved orbits and monitoring secular tectonic deformation. For these applications, data are transferred to an analysis center each day and routinely processed in 24-hour segments. To use GPS for monitoring volcanic events, which may last only a few hours, real-time or near real-time data processing and subdaily position estimates are valuable. Strategies have been researched for obtaining station coordinates every 15 min using a Kalman filter; these strategies have been tested on data collected by a GPS network on Kilauea Volcano. Data from this network are tracked continuously, recorded every 30 s, and telemetered hourly to the Hawaiian Volcano Observatory. A white noise model is heavily impacted by data outages and poor satellite geometry, but a properly constrained random walk model fits the data well. Using a borehole tiltmeter at Kilauea's summit as ground-truth, solutions using different random walk constraints were compared. This study indicates that signals on the order of 5 mm/h are resolvable using a random walk standard deviation of 0.45 cm/???h. Values lower than this suppress small signals, and values greater than this have significantly higher noise at periods of 1-6 hours. Copyright 2001 by the American Geophysical Union.

Mesenchymal stem cell-based gene therapy: A promising therapeutic strategy.

Science.gov (United States)

Mohammadian, Mozhdeh; Abasi, Elham; Akbarzadeh, Abolfazl

2016-08-01

Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in bone marrow, fat, and so many other tissues, and can differentiate into a variety of cell types including osteoblasts, chondrocytes, and adipocytes, as well as myocytes and neurons. Moreover, they have great capacity for self-renewal while maintaining their multipotency. Their capacity for proliferation and differentiation, in addition to their immunomodulatory activity, makes them very promising candidates for cell-based regenerative medicine. Moreover, MSCs have the ability of mobilization to the site of damage; therefore, they can automatically migrate to the site of injury via their chemokine receptors following intravenous transplantation. In this respect, they can be applied for MSC-based gene therapy. In this new therapeutic method, genes of interest are introduced into MSCs via viral and non-viral-based methods that lead to transgene expression in them. Although stem cell-based gene therapy is a relatively new strategy, it lights a new hope for the treatment of a variety of genetic disorders. In the near future, MSCs can be of use in a vast number of clinical applications, because of their uncomplicated isolation, culture, and genetic manipulation. However, full consideration is still crucial before they are utilized for clinical trials, because the number of studies that signify the advantageous effects of MSC-based gene therapy are still limited.

Patient-Reported Outcomes and Therapeutic Affordances of Social Media: Findings From a Global Online Survey of People With Chronic Pain

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Gray, Kathleen; Martin-Sanchez, Fernando; Lopez-Campos, Guillermo

2015-01-01

Background Patient-reported outcomes (PROs) from social media use in chronic disease management continue to emerge. While many published articles suggest the potential for social media is positive, there is a lack of robust examination into mediating mechanisms that might help explain social media’s therapeutic value. This study presents findings from a global online survey of people with chronic pain (PWCP) to better understand how they use social media as part of self-management. Objective Our aim is to improve understanding of the various health outcomes reported by PWCP by paying close attention to therapeutic affordances of social media. We wish to examine if demographics of participants underpin health outcomes and whether the concept of therapeutic affordances explains links between social media use and PROs. The goal is for this to help tailor future recommendations for use of social media to meet individuals’ health needs and improve clinical practice of social media use. Methods A total of 231 PWCP took part in a global online survey investigating PROs from social media use. Recruited through various chronic disease entities and social networks, participants provided information on demographics, health/pain status, social media use, therapeutic affordances, and PROs from use. Quantitative analysis was performed on the data using descriptive statistics, cross-tabulation, and cluster analysis. Results The total dataset represented 218 completed surveys. The majority of participants were university educated (67.0%, 146/218) and female (83.9%, 183/218). More than half (58.7%, 128/218) were married/partnered and not working for pay (75.9%, 88/116 of these due to ill health). Fibromyalgia (46.6%, 55/118) and arthritis (27.1%, 32/118) were the most commonly reported conditions causing pain. Participants showed a clear affinity for social network site use (90.0%, 189/210), followed by discussion forums and blogs. PROs were consistent, suggesting that social

Patient-reported outcomes and therapeutic affordances of social media: findings from a global online survey of people with chronic pain.

Science.gov (United States)

Merolli, Mark; Gray, Kathleen; Martin-Sanchez, Fernando; Lopez-Campos, Guillermo

2015-01-22

Patient-reported outcomes (PROs) from social media use in chronic disease management continue to emerge. While many published articles suggest the potential for social media is positive, there is a lack of robust examination into mediating mechanisms that might help explain social media's therapeutic value. This study presents findings from a global online survey of people with chronic pain (PWCP) to better understand how they use social media as part of self-management. Our aim is to improve understanding of the various health outcomes reported by PWCP by paying close attention to therapeutic affordances of social media. We wish to examine if demographics of participants underpin health outcomes and whether the concept of therapeutic affordances explains links between social media use and PROs. The goal is for this to help tailor future recommendations for use of social media to meet individuals' health needs and improve clinical practice of social media use. A total of 231 PWCP took part in a global online survey investigating PROs from social media use. Recruited through various chronic disease entities and social networks, participants provided information on demographics, health/pain status, social media use, therapeutic affordances, and PROs from use. Quantitative analysis was performed on the data using descriptive statistics, cross-tabulation, and cluster analysis. The total dataset represented 218 completed surveys. The majority of participants were university educated (67.0%, 146/218) and female (83.9%, 183/218). More than half (58.7%, 128/218) were married/partnered and not working for pay (75.9%, 88/116 of these due to ill health). Fibromyalgia (46.6%, 55/118) and arthritis (27.1%, 32/118) were the most commonly reported conditions causing pain. Participants showed a clear affinity for social network site use (90.0%, 189/210), followed by discussion forums and blogs. PROs were consistent, suggesting that social media positively impact psychological

Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

Directory of Open Access Journals (Sweden)

Thomas L. Chenevert

2002-10-01

Full Text Available The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator of treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a non-volumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.

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Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

2015-01-14

Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report on the structure of cellulose and cellulases, as well as known cellulose degradation mechanisms with an eye to target the Acanthamoeba cyst wall. The disruption of the cyst wall will make amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very least inhibition of the excystment process will impede infection recurrence, as we bring these promising drug targets into focus so that they can be explored to their fullest.

Pathophysiology and Therapeutic Strategies for Symptomatic Uncomplicated Diverticular Disease of the Colon.

Science.gov (United States)

Scaioli, Eleonora; Colecchia, Antonio; Marasco, Giovanni; Schiumerini, Ramona; Festi, Davide

2016-03-01

Colonic diverticulosis imposes a significant burden on industrialized societies. The current accepted causes of diverticula formation include low fiber content in the western diet with decreased intestinal content and size of the lumen, leading to the transmission of muscular contraction pressure to the wall of the colon, inducing the formation of diverticula usually at the weakest point of the wall where penetration of the blood vessels occurs. Approximately 20 % of the patients with colonic diverticulosis develop abdominal symptoms (i.e., abdominal pain and discomfort, bloating, constipation, and diarrhea), a condition which is defined as symptomatic uncomplicated diverticular disease (SUDD). The pathogenesis of SUDD symptoms remains uncertain and even less is known about how to adequately manage bowel symptoms. Recently, low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors leading to symptom development, thus changing and improving the therapeutic approach. In this review, a comprehensive search of the literature regarding on SUDD pathogenetic hypotheses and pharmacological strategies was carried out. The pathogenesis of SUDD, although not completely clarified, seems to be related to an interaction between colonic microbiota alterations, and immune, enteric nerve, and muscular system dysfunction (Cuomo et al. in United Eur Gastroenterol J 2:413-442, 2014). Greater understanding of the inflammatory pathways and gut microbiota composition in subjects affected by SUDD has increased therapeutic options, including the use of gut-directed antibiotics, mesalazine, and probiotics (Bianchi et al. in Aliment Pharmacol Ther 33:902-910, 2011; Comparato et al. in Dig Dis Sci 52:2934-2941, 2007; Tursi et al. in Aliment Pharmacol Ther 38:741-751, 2013); however, more research is necessary to validate the safety, effectiveness, and cost-effectiveness of these interventions.

Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.

Science.gov (United States)

Hegazy, Ahmed M; Yamada, Daisuke; Kobayashi, Masahiko; Kohno, Susumu; Ueno, Masaya; Ali, Mohamed A E; Ohta, Kumiko; Tadokoro, Yuko; Ino, Yasushi; Todo, Tomoki; Soga, Tomoyoshi; Takahashi, Chiaki; Hirao, Atsushi

2016-10-07

Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production. Inhibition of mitochondrial ATP synthetase was more effective in repressing sphere formation by Tsc1-deficient glioma cells than that by Tsc1-competent glioma cells, indicating a crucial function for mitochondrial bioenergetic capacity in GIC expansion. To translate this observation into the development of novel therapeutics targeting malignant gliomas, we screened drug libraries for small molecule compounds showing greater efficacy in inhibiting the proliferation/survival of Tsc1-deficient cells compared with controls. We identified several compounds able to preferentially inhibit mitochondrial activity, dramatically reducing ATP levels and blocking glioma sphere formation. In human patient-derived glioma cells, nigericin, which reportedly suppresses cancer stem cell properties, induced AMPK phosphorylation that was associated with mTORC1 inactivation and induction of autophagy and led to a marked decrease in sphere formation with loss of GIC marker expression. Furthermore, malignant characteristics of human glioma cells were markedly suppressed by nigericin treatment in vivo Thus, targeting mTORC1-driven processes, particularly those involved in maintaining a cancer cell's energy balance, may be an effective therapeutic strategy for glioma patients. © 2016 by The American

Recent advances in therapeutic recruitment of mammalian RNAi and bacterial CRISPR-Cas DNA interference pathways as emerging antiviral strategies.

Science.gov (United States)

Chin, Wei-Xin; Ang, Swee Kim; Chu, Justin Jang Hann

2017-01-01

In invertebrate eukaryotes and prokaryotes, respectively, the RNAi and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) pathways are highly specific and efficient RNA and DNA interference systems, and are well characterised as potent antiviral systems. It has become possible to recruit or reconstitute these pathways in mammalian cells, where they can be directed against desired host or viral targets. The RNAi and CRISPR-Cas systems can therefore yield ideal antiviral therapeutics, capable of specific and efficient viral inhibition with minimal off-target effects, but development of such therapeutics can be slow. This review covers recent advances made towards developing RNAi or CRISPR-Cas strategies for clinical use. These studies address the delivery, toxicity or target design issues that typically plague the in vivo or clinical use of these technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Global warming

International Nuclear Information System (INIS)

Anon.

1992-01-01

Canada's Green Plan strategy for dealing with global warming is being implemented as a multidepartmental partnership involving all Canadians and the international community. Many of the elements of this strategy are built on an existing base of activities predating the Green Plan. Elements of the strategy include programs to limit emissions of greenhouse gases, such as initiatives to encourage more energy-efficient practices and development of alternate fuel sources; studies and policy developments to help Canadians prepare and adapt to climate change; research on the global warming phenomenon; and stimulation of international action on global warming, including obligations arising out of the Framework Convention on Climate Change. All the program elements have been approved, funded, and announced. Major achievements to date are summarized, including improvements in the Energy Efficiency Act, studies on the socioeconomic impacts of global warming, and participation in monitoring networks. Milestones associated with the remaining global warming initiatives are listed

Regional strategies for the accelerating global problem of groundwater depletion

Science.gov (United States)

Aeschbach-Hertig, Werner; Gleeson, Tom

2012-12-01

Groundwater--the world's largest freshwater resource--is critically important for irrigated agriculture and hence for global food security. Yet depletion is widespread in large groundwater systems in both semi-arid and humid regions of the world. Excessive extraction for irrigation where groundwater is slowly renewed is the main cause of the depletion, and climate change has the potential to exacerbate the problem in some regions. Globally aggregated groundwater depletion contributes to sea-level rise, and has accelerated markedly since the mid-twentieth century. But its impacts on water resources are more obvious at the regional scale, for example in agriculturally important parts of India, China and the United States. Food production in such regions can only be made sustainable in the long term if groundwater levels are stabilized. To this end, a transformation is required in how we value, manage and characterize groundwater systems. Technical approaches--such as water diversion, artificial groundwater recharge and efficient irrigation--have failed to balance regional groundwater budgets. They need to be complemented by more comprehensive strategies that are adapted to the specific social, economic, political and environmental settings of each region.

Current Opinion on the Role of Neurogenesis in the Therapeutic Strategies for Alzheimer Disease, Parkinson Disease, and Ischemic Stroke; Considering Neuronal Voiding Function

Directory of Open Access Journals (Sweden)

Myung-Hoon Han

2016-12-01

Full Text Available Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports.

Global Mindset in Context

DEFF Research Database (Denmark)

Nielsen, Rikke Kristine

2017-01-01

This paper addresses the call for identification of organizational contingencies related to global mindset, exploration of different forms of global mindset and their relationship with global strategies (Osland, Bird, Mendenhall & Osland, 2006). To this end, this paper explores global mindset...... development in the context of a 3-year single case study of middle manager microfoundations of global mindset in a Danish multinational corporation working with deliberate global mindset capability development as a vehicle for strategy execution and facilitation of global performance. A force field analysis...

Radical surgery after chemotherapy: a new therapeutic strategy to envision in grade II glioma.

Science.gov (United States)

Duffau, Hugues; Taillandier, Luc; Capelle, Laurent

2006-11-01

While surgery is proned in low-grade glioma (LGG), the invasion of functional areas frequently prevents a complete resection. We report the first case of a patient operated on for a left frontal LGG, diagnosed because of seizures, with partial resection due to an invasion of the controlateral hemisphere. Chemotherapy enabled a regression of this controlateral extension. Postchemotherapy surgery performed with intraoperative functional mapping then allowed a complete resection, without sequelae. The patient has a normal socio-professional life, with no seizure. No other treatment was given. There was no recurrence, with a follow-up of 2 years since the second surgery (3.5 years since the first symptom). We propose a new therapeutic strategy in unresectable LGG, with preoperative chemotherapy, to make a radical surgery possible in a second step, while preserving the quality of life.

Strategies for mitigation of global warming

DEFF Research Database (Denmark)

Meyer, Niels I

2009-01-01

The paper analyses the international negotions on climate change leading up to COP15 in Copenhagen. Supplementary policies for mitigation of global warming are proposed.......The paper analyses the international negotions on climate change leading up to COP15 in Copenhagen. Supplementary policies for mitigation of global warming are proposed....

Targeting methionine cycle as a potential therapeutic strategy for immune disorders.

Science.gov (United States)

Li, Heng; Lu, Huimin; Tang, Wei; Zuo, Jianping

2017-08-23

Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders. Expert opinion: New targets and biomarkers grown out of methionine cycle have developed rapidly in the past decades. However, impacts of epigenetic regulations on immune disorders are unclear and whether the substances in methionine cycle can be clarified as biomarkers remains controversial. Therefore, further elucidation on the role of epigenetic regulations and substances in methionine cycle may contribute to exploring the cycle-derived biomarkers and drugs in immune disorders.

Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges.

Science.gov (United States)

Köhler, Stephan; Guhn, Anne; Betzler, Felix; Stiglmayr, Christian; Brakemeier, Eva-Lotta; Sterzer, Philipp

2017-01-01

In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT) by so-called "third-wave" strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to "classical CBT," some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a) acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT), (b) the concept of "limited reparenting" as used in Schema Therapy (ST), and (c) disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges

Directory of Open Access Journals (Sweden)

Stephan Köhler

2017-11-01

Full Text Available In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT by so-called “third-wave” strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to “classical CBT,” some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT, (b the concept of “limited reparenting” as used in Schema Therapy (ST, and (c disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP. On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.

Science.gov (United States)

Ma, Hongwei; Yang, Fan; Butler, Michael R; Belcher, Joshua; Redmond, T Michael; Placzek, Andrew T; Scanlan, Thomas S; Ding, Xi-Qin

2017-08-01

Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB , encode TRs; THRB 2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65 -/- mouse model of Leber congenital amaurosis and reduced the number of TUNEL + cells. Cone survival was significantly improved in Rpe65 -/- and Cpfl1 (a model of achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density in Cpfl1/Thrb2 -/- and Rpe65 -/- / Thrb2 -/- mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

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Apoorva Shankar

2017-09-01

Full Text Available One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV, a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics, and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.

WFH: closing the global gap--achieving optimal care.

Science.gov (United States)

Skinner, Mark W

2012-07-01

For 50 years, the World Federation of Hemophilia (WFH) has been working globally to close the gap in care and to achieve Treatment for All patients, men and women, with haemophilia and other inherited bleeding disorders, regardless of where they might live. The WFH estimates that more than one in 1000 men and women has a bleeding disorder equating to 6,900,000 worldwide. To close the gap in care between developed and developing nations a continued focus on the successful strategies deployed heretofore will be required. However, in response to the rapid advances in treatment and emerging therapeutic advances on the horizon it will also require fresh approaches and renewed strategic thinking. It is difficult to predict what each therapeutic advance on the horizon will mean for the future, but there is no doubt that we are in a golden age of research and development, which has the prospect of revolutionizing treatment once again. An improved understanding of "optimal" treatment is fundamental to the continued evolution of global care. The challenges of answering government and payer demands for evidence-based medicine, and cost justification for the introduction and enhancement of treatment, are ever-present and growing. To sustain and improve care it is critical to build the body of outcome data for individual patients, within haemophilia treatment centers (HTCs), nationally, regionally and globally. Emerging therapeutic advances (longer half-life therapies and gene transfer) should not be justified or brought to market based only on the notion that they will be economically more affordable, although that may be the case, but rather more importantly that they will be therapeutically more advantageous. Improvements in treatment adherence, reductions in bleeding frequency (including microhemorrhages), better management of trough levels, and improved health outcomes (including quality of life) should be the foremost considerations. As part of a new WFH strategic plan

Psychological treatment and therapeutic change in incarcerated rapists

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Ana Martínez-Catena

2017-01-01

Full Text Available Abstract Most Spanish prisons provide specialised treatment for incarcerated sex offenders, both rapists and child molesters. This treatment is a cognitive-behavioural intervention that has shown relative effectiveness in previous research. With regard to offenders’ rehabilitation, recidivism assessments are necessary as a final measure of treatment effectiveness. However, the evaluation of recidivism by itself does not provide sufficient information on the treatment process and the specific effects that treated subjects could undergo. This paper aims to analyse the therapeutic effectiveness of psychological treatment provided to rapists (in general, males sentenced for committing a sexual offence against women. To this aim, a group of treated rapists (N=153 serving a sentence in prison was analysed. Using a specially designed scale (PASSO, the global therapeutic change and ten specific variables (including assertiveness, readiness to change, cognitive distortions, impulsivity, etc. were assessed. The within-subjects comparison showed that treated sex offenders improved, in therapeutic terms, globally as well as in most of the specific variables assessed (improvements not experimented by the control group. Also, different therapeutic subscales showed relevant associations between them. The findings regarding treatment effectiveness are discussed.

A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

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Katsuya Endo

2016-01-01

Full Text Available Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC. Although some studies have compared the efficacy of infliximab (IFX and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac. This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX (n=48 or Tac (n=47 in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p<0.001; log-rank test. The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

Breast Cancer Stem Cell Therapeutics, Multiple Strategies Versus Using Engineered Mesenchymal Stem Cells With Notch Inhibitory Properties: Possibilities and Perspectives.

Science.gov (United States)

Bose, Bipasha; Sen, Utsav; Shenoy P, Sudheer

2018-01-01

Relapse cases of cancers are more vigorous and difficult to control due to the preponderance of cancer stem cells (CSCs). Such CSCs that had been otherwise dormant during the first incidence of cancer gradually appear as radiochemoresistant cancer cells. Hence, cancer therapeutics aimed at CSCs would be an effective strategy for mitigating the cancers during relapse. Alternatively, CSC therapy can also be proposed as an adjuvant therapy, along-with the conventional therapies. As regenerative stem cells (RSCs) are known for their trophic effects, anti-tumorogenicity, and better migration toward an injury site, this review aims to address the use of adult stem cells such as dental pulp derived; cord blood derived pure populations of regenerative stem cells for targeting CSCs. Indeed, pro-tumorogenicity of RSCs is of concern and hence has also been dealt with in relation to breast CSC therapeutics. Furthermore, as notch signaling pathways are upregulated in breast cancers, and anti-notch antibody based and sh-RNA based therapies are already in the market, this review focuses the possibilities of engineering RSCs to express notch inhibitory proteins for breast CSC therapeutics. Also, we have drawn a comparison among various possibilities of breast CSC therapeutics, about, notch1 inhibition. J. Cell. Biochem. 119: 141-149, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Gastric cancer stem cells: A novel therapeutic target

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Singh, Shree Ram

2013-01-01

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

Status of prophylactic and therapeutic genital herpes vaccines.

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Awasthi, Sita; Friedman, Harvey M

2014-06-01

A half billion people have genital herpes infections worldwide. Approximately one-fifth of American women between ages 14 and 49 are HSV-2 seropositive. The development of an effective genital herpes vaccine is a global health necessity based on the mental anguish genital herpes causes for some individuals, the fact that pregnant women with genital herpes risk transmitting infection to their newborn children, and the observation that HSV-2 infection is associated with a 3-fold to 4-fold increased probability of HIV acquisition. We review the strengths and limitations of preclinical animal models used to assess genital herpes vaccine candidates and the goals of prophylactic and therapeutic vaccines. We also discuss the current pipeline of vaccine candidates and lessons learned from past clinical trials that serve as a stimulus for new strategies, study designs and endpoint determinations. Copyright © 2014 Elsevier B.V. All rights reserved.

WHEN THE PRESENT GETS US ... GLOBALIZATION: NEW TECHNOLOGIES, STRATEGY AND POLITICAL COMMUNICATION

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Gustavo Martín Fragachán

2011-11-01

Full Text Available The current phase of the capitalist world development receives the name of globalization and has brought a series of consequences: a few positive and great very denials, some of which will try to be analyzed by me in the lines that continue later, insisting, very specially, in those who say to the development of new technologies of communication, to the called “social networks” and to the consequences that the same ones have had both for the communication and for the development of new modalities of political strategy.

Exosomes Enter Vaccine Development: Strategies Meeting Global Challenges of Emerging Infections.

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Jungbauer, Alois

2018-04-01

New approaches for vaccination must be developed in order to meet the grand challenges for emerging infectious diseases. Exosomes now enter vaccine development and these are strategies are meeting these global challenges, as demonstrated by Anticoli et al., in this issue of Biotechnology Journal. Using exosome vaccines has been now been demonstrated in vivo for several viruses such as Ebola Virus VP24, VP40, and NP, Influenza Virus NP, Crimean-Congo Hemorrhagic Fever NP, West Nile Virus NS3, and Hepatitis C Virus NS3. Now this technology must be tested in clinics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

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Belayev Ludmila

2016-01-01

Full Text Available Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3 complexed to human albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.

Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets

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Safi, Sher Zaman; Kumar, Selva; Ismail, Ikram Shah Bin

2014-01-01

The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

Understanding how and why health is integrated into foreign policy - a case study of health is global, a UK Government Strategy 2008–2013

Science.gov (United States)

2013-01-01

Background Over the past decade, global health issues have become more prominent in foreign policies at the national level. The process to develop state level global health strategies is arguably a form of global health diplomacy (GHD). Despite an increase in the volume of secondary research and analysis in this area, little primary research, particularly that which draws directly on the perspectives of those involved in these processes, has been conducted. This study seeks to fill this knowledge gap through an empirical case study of Health is Global: A UK Government Strategy 2008–2013. It aims to build understanding about how and why health is integrated into foreign policy and derive lessons of potential relevance to other nations interested in developing whole-of-government global health strategies. Methods The major element of the study consisted of an in-depth investigation and analysis of the UK global health strategy. Document analysis and twenty interviews were conducted. Data was organized and described using an adapted version of Walt and Gilson’s policy analysis triangle. A general inductive approach was used to identify themes in the data, which were then analysed and interpreted using Fidler’s health and foreign policy conceptualizations and Kingdon’s multiples streams model of the policymaking process. Results The primary reason that the UK decided to focus more on global health is self-interest - to protect national and international security and economic interests. Investing in global health was also seen as a way to enhance the UK’s international reputation. A focus on global health to primarily benefit other nations and improve global health per se was a prevalent through weaker theme. A well organized, credible policy community played a critical role in the process and a policy entrepreneur with expertise in both international relations and health helped catalyze attention and action on global health when the time was right. Support

An Analysis of Think Globally-Act Locally Strategy Implementation in Developing Relationship of Headquarters and Subsidiaries: Case Study of John Clements Consultants Inc., Philippines & Indonesia

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Dilla Noverita

2007-01-01

Moreover, this research analyses how JCCI applies “think globally – act locally” strategy in its global operations and developing relationship with subsidiaries. It brings the issues of all challenges and obstacles the company has in dealing with subsidiaries. Finally, this research recommends alternative strategies to leverage the relationship between headquarters and subsidiaries more efficiently and to minimize the obstacles in cross-cultural management so that the company will be able to strengthen its position in global service market.

MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

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Passadouro M

2014-07-01

Full Text Available Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/– (4/1 nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. Keywords: pancreatic cancer gene therapy, anti-microRNAs oligonucleotides, delivery nanosystems, albumin-associated lipoplexes

Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

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Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

2012-08-01

As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

Imaging enabled platforms for development of therapeutics

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Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

Life in unexpected places: Employing visual thinking strategies in global health training.

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Allison, Jill; Mulay, Shree; Kidd, Monica

2017-01-01

The desire to make meaning out of images, metaphor, and other representations indicates higher-order cognitive skills that can be difficult to teach, especially in the complex and unfamiliar environments like those encountered in many global health experiences. Because reflecting on art can help develop medical students' imaginative and interpretive skills, we used visual thinking strategies (VTS) during an immersive 4-week global health elective for medical students to help them construct new understanding of the social determinants of health in a low-resource setting. We were aware of no previous formal efforts to use art in global health training. We assembled a group of eight medical students in front of a street mural in Kathmandu and used VTS methods to interpret the scene with respect to the social determinants of health. We recorded and transcribed the conversation and conducted a thematic analysis of student responses. Students shared observations about the mural in a supportive, nonjudgmental fashion. Two main themes emerged from their observations: those of human-environment interactions (specifically community dynamics, subsistence land use, resources, and health) and entrapment/control, particularly relating to expectations of, and demands on, women in traditional farming communities. They used the images as well as their experience in Nepali communities to consolidate complex community health concepts. VTS helped students articulate their deepening understanding of the social determinants of health in Nepal, suggesting that reflection on visual art can help learners apply, analyze, and evaluate complex concepts in global health. We demonstrate the relevance of drawing upon many aspects of cultural learning, regarding art as a kind of text that holds valuable information. These findings may help provide innovative opportunities for teaching and evaluating global health training in the future.

The influence of globalization on the national identity formation and the new strategies of the Ukrainian youth behaviour

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Karmaliuk Sergii Pavlovich

2016-12-01

Full Text Available The article deals with the problem of the national identity and the new strategy of the Ukrainian youth behaviour in the context of the processes of globalization. The author analysed the problem whether young people, including Ukrainian, are ready for the global changes influence; whether they are able to preserve the youth’s national identity and national culture. The article also discovers the effect of mass media on the important problems of public life. It is proved that mass media contribute the consolidation (the merge of the national cultures into the regional and the gradual formation of the global culture.

Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction

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Osamu Natsume

2018-01-01

Full Text Available Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.

Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

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Joanna Huszno

2016-03-01

Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

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Yadav, Saveg; Pandey, Shrish Kumar; Singh, Vinay Kumar; Goel, Yugal; Kumar, Ajay; Singh, Sukh Mahendra

2017-01-01

Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP), with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA) and propionic acid (PA), with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

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Saveg Yadav

Full Text Available Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP, with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA and propionic acid (PA, with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

Military Strategy of Global Jihad

National Research Council Canada - National Science Library

Zabel, Sarah E

2007-01-01

.... Global jihadis have spent more than 40 years refining their philosophy, gaining experience, building their organization, and developing plans to re-establish what they see as the only true Islamic state on earth...

Do mitigation strategies reduce global warming potential in the northern U.S. corn belt?

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Johnson, Jane M-F; Archer, David W; Weyers, Sharon L; Barbour, Nancy W

2011-01-01

Agricultural management practices that enhance C sequestration, reduce greenhouse gas emission (nitrous oxide [N₂O], methane [CH₄], and carbon dioxide [CO₂]), and promote productivity are needed to mitigate global warming without sacrificing food production. The objectives of the study were to compare productivity, greenhouse gas emission, and change in soil C over time and to assess whether global warming potential and global warming potential per unit biomass produced were reduced through combined mitigation strategies when implemented in the northern U.S. Corn Belt. The systems compared were (i) business as usual (BAU); (ii) maximum C sequestration (MAXC); and (iii) optimum greenhouse gas benefit (OGGB). Biomass production, greenhouse gas flux change in total and organic soil C, and global warming potential were compared among the three systems. Soil organic C accumulated only in the surface 0 to 5 cm. Three-year average emission of N₂O and CH was similar among all management systems. When integrated from planting to planting, N₂O emission was similar for MAXC and OGGB systems, although only MAXC was fertilized. Overall, the three systems had similar global warming potential based on 4-yr changes in soil organic C, but average rotation biomass was less in the OGGB systems. Global warming potential per dry crop yield was the least for the MAXC system and the most for OGGB system. This suggests management practices designed to reduce global warming potential can be achieved without a loss of productivity. For example, MAXC systems over time may provide sufficient soil C sequestration to offset associated greenhouse gas emission. by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Targeting miRNAs by polyphenols: Novel therapeutic strategy for cancer.

Science.gov (United States)

Pandima Devi, Kasi; Rajavel, Tamilselvam; Daglia, Maria; Nabavi, Seyed Fazel; Bishayee, Anupam; Nabavi, Seyed Mohammad

2017-10-01

In the recent years, polyphenols have gained significant attention in scientific community owing to their potential anticancer effects against a wide range of human malignancies. Epidemiological, clinical and preclinical studies have supported that daily intake of polyphenol-rich dietary fruits have a strong co-relationship in the prevention of different types of cancer. In addition to direct antioxidant mechanisms, they also regulate several therapeutically important oncogenic signaling and transcription factors. However, after the discovery of microRNA (miRNA), numerous studies have identified that polyphenols, including epigallocatechin-3-gallate, genistein, resveratrol and curcumin exert their anticancer effects by regulating different miRNAs which are implicated in all the stages of cancer. MiRNAs are short, non-coding endogenous RNA, which silence the gene functions by targeting messenger RNA (mRNA) through degradation or translation repression. However, cancer associated miRNAs has emerged only in recent years to support its applications in cancer therapy. Preclinical experiments have suggested that deregulation of single miRNA is sufficient for neoplastic transformation of cells. Indeed, the widespread deregulation of several miRNA profiles of tumor and healthy tissue samples revealed the involvement of many types of miRNA in the development of numerous cancers. Hence, targeting the miRNAs using polyphenols will be a novel and promising strategy in anticancer chemotherapy. Herein, we have critically reviewed the potential applications of polyphenols on various human miRNAs, especially which are involved in oncogenic and tumor suppressor pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Therapeutic touch and agitation in individuals with Alzheimer's disease.

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Hawranik, Pamela; Johnston, Pat; Deatrich, Judith

2008-06-01

Limited effective strategies exist to alleviate or treat disruptive behaviors in people with Alzheimer's disease. Fifty-one residents of a long-term care facility with Alzheimer's disease were randomly assigned to one of three intervention groups. A multiple time series, blinded, experimental design was used to compare the effectiveness of therapeutic touch, simulated therapeutic touch, and usual care on disruptive behavior. Three forms of disruptive behavior comprised the dependent variables: physical aggression, physical nonaggression, and verbal agitation. Physical nonaggressive behaviors decreased significantly in those residents who received therapeutic touch compared with those who received the simulated version and the usual care. No significant differences in physically aggressive and verbally agitated behaviors were observed across the three study groups. The study provided preliminary evidence for the potential for therapeutic touch in dealing with agitated behaviors by people with dementia. Researchers and practitioners must consider a broad array of strategies to deal with these behaviors.

Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer

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Anthony J. Berdis

2017-11-01

Full Text Available Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on describing the molecular mechanisms of these inhibitory effects against chromosomal and mitochondrial DNA polymerases. Discussions are also provided on the mechanisms associated with resistance to these therapeutic agents. A primary focus is toward understanding the roles of specialized DNA polymerases that by-pass DNA lesions produced by DNA damaging agents. Finally, a section is provided that describes emerging areas in developing new therapeutic strategies targeting specialized DNA polymerases.

[Therapeutic strategies against myasthenia gravis].

Science.gov (United States)

Utsugisawa, Kimiaki; Nagane, Yuriko

2013-05-01

Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients taking CSR and is a target of treatment. In order to achieve early MM or better status with prednisolne strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors.

The role of global public health strategy in non-profit organisational change at country level: lessons from the joining of Save the Children and Merlin in Myanmar.

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Campbell, Fiona M; Balabanova, Dina; Howard, Natasha

2018-01-01

The paper presents a case study that critically assesses the role of global strategy 'Public Health on the Frontline 2014-2015' ('the Strategy') in supporting Merlin and Save the Children's organisational change and future programme of the combined organisation in Myanmar. Research was undertaken in 2014 in Myanmar. Twenty-six individual and three group interviews were conducted with stakeholders, and 10 meetings relevant to the country organisational transition process were observed. A conceptual framework was developed to assess the role of the global strategy in supporting the country change process. Several positive aspects of the global strategy were found, as well as critical shortcomings in its support to the organisational change process at country level. The strategy was useful in signalling Save the Children's intention to scale up humanitarian health provision. However, it had only limited influence on the early change process and outcomes in Myanmar. Results highlight several aspects that would enhance the role of a global strategy at country level. Lessons can be applied by organisations undertaking a similar process. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Implementation Strategy for a Global Solar and Wind Atlas

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-01-15

In July 2009, Major Economies Forum leaders met to prepare for the COP 15 Copenhagen Conference that took place later that year. At this occasion the Major Economies Forum Global Partnership f or low carbon and climate-friendly technology was founded and Technology Action Plans (TAPs) for ten key low-carbon technologies were drafted. At that juncture Denmark, Germany and Spain took on the responsibility for drafting TAPs for Solar and Wind Energy Technologies. The TAPs were then consolidated and presented at COP 15 that would later take place in December in Copenhagen. Since then, countries that led the development of the Action Plans have started their implementation. During a first Clean Energy Ministerial (CEM) in July 2010 in Washington on the invitation of Steven Chu, US Secretary of Energy, several initiatives were launched. Denmark, Germany and Spain took the lead in the implementation of the TAPs for Solar and Wind Technologies and initiated the Multilateral Working Group on Solar and Wind Energy Technologies (MWGSW). Several countries joined the working group in Washington and afterwards. In two international workshops in Bonn (June 2010) and Madrid (November 2010) and in meetings during the first CEM in Washington (July 2010) and the second CEM in Abu Dhabi (April 2011) the Multilateral Working Group made substantial progress in the two initial fields of action: (1) the Development of a Global Solar and Wind Atlas; and (2) the Development of a Long-term Strategy on Joint Capacity Building. Discussion papers on the respective topics were elaborated involving the Working Group's member countries as well as various international institutions. This led to concrete proposals for several pilot activities in both fields of action. After further specifying key elements of the suggested projects in two expert workshops in spring 2011, the Multilateral Working Group convened for a third international workshop in Copenhagen, Denmark, to discuss the project

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

Science.gov (United States)

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Engaging therapeutic citizenship and clientship: Untangling the reasons for therapeutic pacifism among people living with HIV in urban Zambia.

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Patterson, Amy S

2016-10-01

This article explores the reasons for therapeutic pacifism among people living with HIV (PLHIVs) in urban Zambia. It contributes to a growing ethnography on global health, biosociality, and patient-provider dynamics. Therapeutic citizenship is a biopolitical citizenship that includes claims and ethical projects that emerge from techniques to control and manage bodies. In some contexts, therapeutic citizenship has included activism and claims-making against local, national, and international power brokers. This article investigates therapeutic citizenship in the specific context of impoverished urban Zambian compounds, sites of food insecurity, unemployment, and political exclusion, as well as targets for donor, NGO, and faith-based organisation projects and PLHIV support group proliferation. The article utilises data from participant observations at two Lusaka AIDS clinics, interviews, and focused discussions with support groups of PLHIVs. It argues that PLHIVs continuously negotiate subjectivities related to kinship, clientship, religious belief, and political citizenship in processes that complicate therapeutic citizenship. Rather than fostering participation in PLHIV support groups or challenging 'politics as usual' through activist claims-making to institutions of biopower, these processes lead to therapeutic pacifism.

Inner Peace and Global Harmony: Individual Wellbeing and Global Solutions in the Art of Living

Directory of Open Access Journals (Sweden)

Stephen Jacobs

2014-10-01

Full Text Available his paper explores the discourse in the Art of Living (AOL, a Hindu derived transnational meditation movement, which suggests that solutions to global problems are best addressed at the individual level. Ethnographic fieldwork, qualita-tive interviews and an analysis of published material suggest that the primary concern of the AOL is the reduction of stress and anxiety for the individual practitioner. This reduction of stress not only means that the individual practitioner develops ‘inner peace', but also contributes to global harmony. AOL is an exemplar of ‘therapeutic solutions', which are characterized by disillusionment with estab-lished institutions and a quest for inner meaning. AOL articulates this therapeutic solution, not only in terms of narcissistic needs, but links this quest for inner meaning to wider social and global concerns.

Marketing therapeutic recreation services.

Science.gov (United States)

Thorn, B E

1984-01-01

The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

潍柴全球化战略迎来收获期%Weichai global strategy ushered in the harvest period

Institute of Scientific and Technical Information of China (English)

高凤艳

2016-01-01

Take the road of globalization, is Weichai unswerving strategic choice. By implementing capital mergers and acquisitions, overseas investment to build factories, the strategies of technical output and export trade, Weichai accelerate internationalization, expand international cooperation capacity, pushing forward the construction of the “the Belt and Road”, gradually formed and perfected the diversiifcation strategy layout.

[Cost-effectiveness analysis and diet quality index applied to the WHO Global Strategy].

Science.gov (United States)

Machado, Flávia Mori Sarti; Simões, Arlete Naresse

2008-02-01

To test the use of cost-effectiveness analysis as a decision making tool in the production of meals for the inclusion of the recommendations published in the World Health Organization's Global Strategy. Five alternative options for breakfast menu were assessed previously to their adoption in a food service at a university in the state of Sao Paulo, Southeastern Brazil, in 2006. Costs of the different options were based on market prices of food items (direct cost). Health benefits were estimated based on adaptation of the Diet Quality Index (DQI). Cost-effectiveness ratios were estimated by dividing benefits by costs and incremental cost-effectiveness ratios were estimated as cost differential per unit of additional benefit. The meal choice was based on health benefit units associated to direct production cost as well as incremental effectiveness per unit of differential cost. The analysis showed the most simple option with the addition of a fruit (DQI = 64 / cost = R$ 1.58) as the best alternative. Higher effectiveness was seen in the options with a fruit portion (DQI1=64 / DQI3=58 / DQI5=72) compared to the others (DQI2=48 / DQI4=58). The estimate of cost-effectiveness ratio allowed to identifying the best breakfast option based on cost-effectiveness analysis and Diet Quality Index. These instruments allow easy application easiness and objective evaluation which are key to the process of inclusion of public or private institutions under the Global Strategy directives.

Ebola virus (EBOV) infection: Therapeutic strategies.

Science.gov (United States)

De Clercq, Erik

2015-01-01

Within less than a year after its epidemic started (in December 2013) in Guinea, Ebola virus (EBOV), a member of the filoviridae, has spread over a number of West-African countries (Guinea, Sierra Leone and Liberia) and gained allures that have been unprecedented except by human immunodeficiency virus (HIV). Although EBOV is highly contagious and transmitted by direct contact with body fluids, it could be counteracted by the adequate chemoprophylactic and -therapeutic interventions: vaccines, antibodies, siRNAs (small interfering RNAs), interferons and chemical substances, i.e. neplanocin A derivatives (i.e. 3-deazaneplanocin A), BCX4430, favipiravir (T-705), endoplasmic reticulum (ER) α-glucosidase inhibitors and a variety of compounds that have been found to inhibit EBOV infection blocking viral entry or by a mode of action that still has to be resolved. Much has to be learned from the mechanism of action of the compounds active against VSV (vesicular stomatitis virus), a virus belonging to the rhabdoviridae, that in its mode of replication could be exemplary for the replication of filoviridae. Copyright © 2014 Elsevier Inc. All rights reserved.

A Brief Analysis on Cross-cultural Communication Strategy of Chinese Films under the Context of Globalization

Directory of Open Access Journals (Sweden)

Cao Zhiyong

2016-03-01

Full Text Available With the development of globalization waves, the cross-cultural communication becomes more and more common nowadays. Chinese films, as a kind of mass media and the carrier of ideology, must meet the challenge in the world with active attitudes and take part in cross-cultural communication worldwide extensively. The context of globalization is not only a challenge but also an opportunity for Chinese films and if Chinese films want to be successful in the process of cross-cultural communication, it must find out a conjoint point between globalization and location to implement dual-coding of them. With the objective of consensus but different for the cultural demands of cross-cultural communication, the communicational strategies in culture，subject，art and operation must extensively use for reference and boldly create to renew the situation of Chinese films．

Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

Science.gov (United States)

Tewari, Devesh; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Sureda, Antoni; Farooqi, Ammad Ahmad; Atanasov, Atanas G; Vacca, Rosa Anna; Sethi, Gautam; Bishayee, Anupam

2018-02-01

Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Korea’s Trade Strategies for Mega Free Trade Agreements in Regional and Global Economic Integration

Directory of Open Access Journals (Sweden)

Sang-Chul Park

2016-12-01

Full Text Available Korea has developed rapidly since the 1960s. It is one of the four Asian tiger economies and a good model for developing countries. Korea shows the world how a developing country can develop its economy rapidly and become industrialized. Its development strategy has mainly been an export-oriented trade policy. As a result, its trade volume grew from $1 billion in 1966 to $1 trillion in 2011, which is a 1,000-fold increase within five decades. Since 2011, Korea has become one of seven countries with a trade volume over $1 trillion. However, the Korean economy has experienced turbulence as well as positive growth. It underwent severe economic crises such as the Asian financial crisis in 1997 and the global financial crisis in 2008. Its economy has been extremely vulnerable to the external economic environment, although it has improved and strengthened, particularly since the global financial crisis. During those two crises, the government carried out an appropriate trade policy with a strategic approach to upgrade its industrial structure and competitiveness in global markets. This article comprehensively discusses Korean trade policy and strategy over the last five decades, and how its national economy has developed rapidly. It also explores how the government sets its strategic targets in Asia and the Asia Pacific region. It considers two mega free trade agreements (FTAs — the Regional Comprehensive Economic Partnership and the Trans-Pacific Partnership — as new opportunities for further development. Therefore, it is wise to analyze these regional mega FTAs in order to maximize the national interest.

Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.

Science.gov (United States)

Ciechanover, Aaron; Kwon, Yong Tae

2015-03-13

Mammalian cells remove misfolded proteins using various proteolytic systems, including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated autophagy (CMA) and macroautophagy. The majority of misfolded proteins are degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated, unfolded and cleaved into small peptides when passing through the narrow chamber of the proteasome. The substrates that expose a specific degradation signal, the KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA. Aggregation-prone substrates resistant to both the UPS and the CMA can be degraded by macroautophagy, in which cargoes are segregated into autophagosomes before degradation by lysosomal hydrolases. Although most misfolded and aggregated proteins in the human proteome can be degraded by cellular protein quality control, some native and mutant proteins prone to aggregation into β-sheet-enriched oligomers are resistant to all known proteolytic pathways and can thus grow into inclusion bodies or extracellular plaques. The accumulation of protease-resistant misfolded and aggregated proteins is a common mechanism underlying protein misfolding disorders, including neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), prion diseases and Amyotrophic Lateral Sclerosis (ALS). In this review, we provide an overview of the proteolytic pathways in neurons, with an emphasis on the UPS, CMA and macroautophagy, and discuss the role of protein quality control in the degradation of pathogenic proteins in neurodegenerative diseases. Additionally, we examine existing putative therapeutic strategies to efficiently remove cytotoxic proteins from degenerating neurons.

[Premenstrual dysphoric disorder: diagnosis and therapeutic strategy].

Science.gov (United States)

Bianchi-Demicheli, F

2006-02-08

Prementrual dysphoric disorder (PMDD) is considered to be a very severe form of the premenstrual syndrome (PMS) that occurs regularly in the last week of the luteal phase of the cycle and begin to remit after the onset of follicular phase and is absent in the week postmenses. What sets PMDD apart from PMS is its severity and its dominant psychiatric symptoms. PMDD includes depression, anxiety, tension, irritability and moodiness. Moreover, women with PMDD find that it has a very disruptive effect on their everyday lives. Although, many treatments have been used for PMDD over the years, PMDD remains difficult to be cured. Until recently, only few of these treatments were evaluated in carefully designed research studies and even fewer were shown to be effective. Here, we discuss the different therapeutic options for PMDD.

MicroRNA-targeted therapeutics for lung cancer treatment.

Science.gov (United States)

Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

2017-02-01

Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

Limited-Sampling Strategies for Therapeutic Drug Monitoring of Moxifloxacin in Patients With Tuberculosis

NARCIS (Netherlands)

Pranger, Arianna D.; Kosterink, Jos G. W.; van Altena, Richard; Aarnoutse, Rob E.; van der Werf, Tjip S.; Uges, Donald R. A.; Alffenaar, Jan-Willem C.

Background: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

Limited-sampling strategies for therapeutic drug monitoring of moxifloxacin in patients with tuberculosis

NARCIS (Netherlands)

Pranger, A.D.; Kosterink, J.G.W.; Altena, R. van; Aarnoutse, R.E.; Werf, T.S. van der; Uges, D.R.A.; Alffenaar, J.W.C.

2011-01-01

BACKGROUND: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

Science.gov (United States)

Geszke-Moritz, Małgorzata; Moritz, Michał

2016-11-01

This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

OLD AND NEW ECONOMIC GLOBALIZATION

Directory of Open Access Journals (Sweden)

Elena MĂRGULESCU

2015-07-01

Full Text Available The retrospective of the theoretical approaches of the phenomenon of economic globalization in the last three decades emphasizes the movement of attention from the globalization of markets, from the'80s, to the globalization of production and services in the current decade. This trend is essentially the result of implementing new strategies by multinational and transnational companies. We try in this context to draw a line between the "globalization of markets" and the "globalization of production and services”. A feature of the globalization of production and services is the implementation of the arbitrage strategy in respect of one or more production factors. But the "globalization of production and services’ gains a new content due to the new possibilities offered by the “modularization” of production. Following, the arbitrage strategies began to address new factors, as for example the "functions" of production resulting from the restructuring of the product value chain.

Forum on Global Climate Strategies. Beyond 2012. The Route Ahead. Looking for a consensus framework

International Nuclear Information System (INIS)

Perez-Arriaga, E.; Linares, P.; Batlle, C.; Barquin, J.

2007-06-01

The scientific knowledge on climate change has firmed up considerably. This has been made broadly known by the publication of the initial documents of the Fourth Assessment Report on global warming by the International Panel on Climate Change (IPCC). The ample body of available scientific evidence now clearly indicates that climate change is serious and urgent. There is a generalized consensus from major academic, professional and political institutions about the importance of the climate change threat. This is more than enough to urge policy makers to put together a response that measures up to the challenge. A diversity of schemes and strategies to address climate change have been already identified and debated in public forums, so the challenges of a plausible long-term strategy, as well as the viewpoints of all countries, are now mostly explicit and known. Climate change can only be effectively tackled through broad participation in the global reduction effort by all present and future major emitters. Resolved political will is needed to make real progress in reducing greenhouse gas emissions. There is a growing sense of urgency for stronger actions to curb the primary causes and to prepare for the consequences of global warming. The principal challenge for the future climate regime is to identify the nature and level of commitment that will provide sufficient incentives for all Parties, especially the largest emitters, to join a global agreement and achieve sufficient reductions in greenhouse gas (GHG) emissions to comply with art. 2 of the UN Framework Convention on Climate Change. Dialogue among the key international partners to explore global climate strategies is already being conducted in various international forums: formally under the UNFCC, but also within the G8 and other multilateral and bilateral meetings. Identification, analysis and proposals of alternatives are also being put forth in high-quality workshops run by universities and NGOs, with

A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.

Science.gov (United States)

Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew

2010-01-22

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.

Global recommendations on physical activity for health

Science.gov (United States)

... кий Español Global Strategy on Diet, Physical Activity and Health Menu Diet, Physical Activity & Health Global strategy development ... obesity Documents & publications Related links Global recommendations on physical activity for health WHO developed the "Global Recommendations on Physical Activity ...

Elder Abuse: Global Situation, Risk Factors, and Prevention Strategies.

Science.gov (United States)

Pillemer, Karl; Burnes, David; Riffin, Catherine; Lachs, Mark S

2016-04-01

Elder mistreatment is now recognized internationally as a pervasive and growing problem, urgently requiring the attention of health care systems, social welfare agencies, policymakers, and the general public. In this article, we provide an overview of global issues in the field of elder abuse, with a focus on prevention. This article provides a scoping review of key issues in the field from an international perspective. By drawing primarily on population-based studies, this scoping review provided a more valid and reliable synthesis of current knowledge about prevalence and risk factors than has been available. Despite the lack of scientifically rigorous intervention research on elder abuse, the review also identified 5 promising strategies for prevention. The findings highlight a growing consensus across studies regarding the extent and causes of elder mistreatment, as well as the urgent need for efforts to make elder mistreatment prevention programs more effective and evidence based. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Singapore's Global Schoolhouse Strategy: Retreat or Recalibration?

Science.gov (United States)

Waring, Peter

2014-01-01

In 2002 a high-level economic review committee recommended that Singapore position itself as a "global schoolhouse". An ambitious target was set to attract 150,000 international students to Singapore by 2015 and to lift the education sector's contribution to GDP from 1.9% to 5% in the same timeframe. The global schoolhouse was viewed as…

[Secondary benefits of cognitive rehabilitation for a chronic ethylic patient: effects on disorder consciousness, motivation, and global therapeutic cooperation].

Science.gov (United States)

Siccardi, L; Vautel-Pons, D; dos Santos, M Teixera; Camus, N; Louchart de la Chapelle, S

2014-06-01

Alcoholism causes psychological, behavioral and cognitive symptoms that need to be addressed together. The neuropsychological alterations among alcohol-dependent people are considered to make the therapeutic work complex and longer. A cognitive rehabilitation program is sometimes difficult to achieve with these patients. Functional results are often difficult to anticipate. However, the consequences of this therapeutic approach are multiple and there are many interactions between psycho-affective, behavioral and cognitive components. A neuropsychological approach can be used like a tool to improve metacognition. A bad contribution to treatment programs is often secondary to the illusion of a satisfying intellectual functioning. Patients' motivation for the therapeutic work is very changeable. A complete consciousness of impairments can help them to stay involved. The following case shows the cognitive effects and secondary benefits associated with a neuropsychological work, which was carried out by a chronic ethylic patient with severe physical and cognitive symptoms. The patient aged 50, with a good qualification level (scientific section in the final year of secondary school, with no diploma, then attended a training program to become a croupier) was suffering from chronic alcoholism since his adolescence. He arrived in the closed unit after many hospitalizations in psychiatric and hepato-gastroenterology units. He had been showing mental confusion. He presented a frontal and subcortical profile of alcohol-related dementia according to Oslin's criteria. MRI revealed global cerebral atrophy, more pronounced on the fronto-parietal cortex with cerebellar leukoencephalopathy, but no pontine central myelinolysis. The neurocognitive program had two main lines: reducing attentional, executive and graphical deficits with training exercises (individual and group sessions) and compensating memory, and executive disorders with an external aid. The cognitive program had been

Terrestrial Ecosystem Responses to Global Change: A Research Strategy

Energy Technology Data Exchange (ETDEWEB)

Ecosystems Working Group,

1998-09-23

Uncertainty about the magnitude of global change effects on terrestrial ecosystems and consequent feedbacks to the atmosphere impedes sound policy planning at regional, national, and global scales. A strategy to reduce these uncertainties must include a substantial increase in funding for large-scale ecosystem experiments and a careful prioritization of research efforts. Prioritization criteria should be based on the magnitude of potential changes in environmental properties of concern to society, including productivity; biodiversity; the storage and cycling of carbon, water, and nutrients; and sensitivity of specific ecosystems to environmental change. A research strategy is proposed that builds on existing knowledge of ecosystem responses to global change by (1) expanding the spatial and temporal scale of experimental ecosystem manipulations to include processes known to occur at large scales and over long time periods; (2) quantifying poorly understood linkages among processes through the use of experiments that manipulate multiple interacting environmental factors over a broader range of relevant conditions than did past experiments; and (3) prioritizing ecosystems for major experimental manipulations on the basis of potential positive and negative impacts on ecosystem properties and processes of intrinsic and/or utilitarian value to humans and on feedbacks of terrestrial ecosystems to the atmosphere. Models and experiments are equally important for developing process-level understanding into a predictive capability. To support both the development and testing of mechanistic ecosystem models, a two-tiered design of ecosystem experiments should be used. This design should include both (1) large-scale manipulative experiments for comprehensive testing of integrated ecosystem models and (2) multifactor, multilevel experiments for parameterization of process models across the critical range of interacting environmental factors (CO{sub 2}, temperature, water

The lure of global branding.

Science.gov (United States)

Aaker, D A; Joachimsthaler, E

1999-01-01

As more and more companies begin to see the world as their market, brand builders look with envy upon those businesses that appear to have created global brands--brands whose positioning, advertising strategy, personality, look, and feel are in most respects the same from one country to another. Attracted by such high-profile examples of success, these companies want to globalize their own brands. But that's a risky path to follow, according to David Aaker and Erich Joachimsthaler. Why? Because creating strong global brands takes global brand leadership. It can't be done simply by edict from on high. Specifically, companies must use organizational structures, processes, and cultures to allocate brand-building resources globally, to create global synergies, and to develop a global brand strategy that coordinates and leverages country brand strategies. Aaker and Joachimsthaler offer four prescriptions for companies seeking to achieve global brand leadership. First, companies must stimulate the sharing of insights and best practices across countries--a system in which "it won't work here" attitudes can be overcome. Second, companies should support a common global brand-planning process, one that is consistent across markets and products. Third, they should assign global managerial responsibility for brands in order to create cross-country synergies and to fight local bias. And fourth, they need to execute brilliant brand-building strategies. Before stampeding blindly toward global branding, companies need to think through the systems they have in place. Otherwise, any success they achieve is likely to be random--and that's a fail-safe recipe for mediocrity.

Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

Science.gov (United States)

Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

2018-05-01

Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Comparison between project-based learning and discovery learning toward students' metacognitive strategies on global warming concept

Science.gov (United States)

Tumewu, Widya Anjelia; Wulan, Ana Ratna; Sanjaya, Yayan

2017-05-01

The purpose of this study was to know comparing the effectiveness of learning using Project-based learning (PjBL) and Discovery Learning (DL) toward students metacognitive strategies on global warming concept. A quasi-experimental research design with a The Matching-Only Pretest-Posttest Control Group Design was used in this study. The subjects were students of two classes 7th grade of one of junior high school in Bandung City, West Java of 2015/2016 academic year. The study was conducted on two experimental class, that were project-based learning treatment on the experimental class I and discovery learning treatment was done on the experimental class II. The data was collected through questionnaire to know students metacognitive strategies. The statistical analysis showed that there were statistically significant differences in students metacognitive strategies between project-based learning and discovery learning.

Novel Therapeutic Strategy for the Prevention of Bone Fractures

Science.gov (United States)

2015-02-01

therapeutic potential for improving muscle function in older adults , perhaps leading to the prevention of falls and fractures. Body Aim 1 (months 1-12...directly to postural instability, which in turn increases the risk for falls , and falls are the main etiolog ical factor inmore than 90% of bone...vitamin D supplementation (Girgis et al., 2013) may improve muscle strength and/or neuromuscular control and proprioception, perhaps reducing fall risk

Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

Directory of Open Access Journals (Sweden)

Zoey Harris

2016-10-01

Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

Directory of Open Access Journals (Sweden)

Angel L. Pey

2013-01-01

Full Text Available Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.

An open ecosystem engagement strategy through the lens of global food safety

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Stacey, Paul; Fons, Garin; Bernardo, Theresa M

2015-01-01

The Global Food Safety Partnership (GFSP) is a public/private partnership established through the World Bank to improve food safety systems through a globally coordinated and locally-driven approach. This concept paper aims to establish a framework to help GFSP fully leverage the potential of open models. In preparing this paper the authors spoke to many different GFSP stakeholders who asked questions about open models such as: what is it?what’s in it for me?why use an open rather than a proprietary model?how will open models generate equivalent or greater sustainable revenue streams compared to the current “traditional” approaches?  This last question came up many times with assertions that traditional service providers need to see opportunity for equivalent or greater revenue dollars before they will buy-in. This paper identifies open value propositions for GFSP stakeholders and proposes a framework for creating and structuring that value. Open Educational Resources (OER) were the primary open practice GFSP partners spoke to us about, as they provide a logical entry point for collaboration. Going forward, funders should consider requiring that educational resources and concomitant data resulting from their sponsorship should be open, as a public good. There are, however, many other forms of open practice that bring value to the GFSP. Nine different open strategies and tactics (Appendix A) are described, including: open content (including OER and open courseware), open data, open access (research), open government, open source software, open standards, open policy, open licensing and open hardware. It is recommended that all stakeholders proactively pursue "openness" as an operating principle. This paper presents an overall GFSP Open Ecosystem Engagement Strategy within which specific local case examples can be situated. Two different case examples, China and Colombia, are presented to show both project-based and crowd-sourced, direct-to-public paths

IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

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Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

2015-05-14

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

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Barage, Sagar H; Sonawane, Kailas D

2015-08-01

Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

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Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

Directory of Open Access Journals (Sweden)

Michela Pasello

2011-01-01

Full Text Available Recent studies have indicated that targeting glutathione-S-transferase (GST isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthiohexanol (NBDHEX has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST. NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

Ebola virus outbreak, updates on current therapeutic strategies.

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Elshabrawy, Hatem A; Erickson, Timothy B; Prabhakar, Bellur S

2015-07-01

Filoviruses are enveloped negative-sense single-stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25,000 suspected cases, with 15,000 confirmed by laboratory testing, and over 10,000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration-approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non-human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak. Copyright © 2015 John Wiley & Sons, Ltd.

Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

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GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

2016-01-01

MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

Antisense targeting of 3' end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: a new gene-silencing approach.

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Marsollier, Anne-Charlotte; Ciszewski, Lukasz; Mariot, Virginie; Popplewell, Linda; Voit, Thomas; Dickson, George; Dumonceaux, Julie

2016-04-15

Defects in mRNA 3'end formation have been described to alter transcription termination, transport of the mRNA from the nucleus to the cytoplasm, stability of the mRNA and translation efficiency. Therefore, inhibition of polyadenylation may lead to gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting key 3' end elements involved in mRNA processing using antisense oligonucleotide drugs can be used as a strategy for gene silencing within a potentially therapeutic context. FSHD is a gain-of-function disease characterized by the aberrant expression of the Double homeobox 4 (DUX4) transcription factor leading to altered pathogenic deregulation of multiple genes in muscles. Here, we demonstrate that targeting either the mRNA polyadenylation signal and/or cleavage site is an efficient strategy to down-regulate DUX4 expression and to decrease the abnormally high-pathological expression of genes downstream of DUX4. We conclude that targeting key functional 3' end elements involved in pre-mRNA to mRNA maturation with antisense drugs can lead to efficient gene silencing and is thus a potentially effective therapeutic strategy for at least FSHD. Moreover, polyadenylation is a crucial step in the maturation of almost all eukaryotic mRNAs, and thus all mRNAs are virtually eligible for this antisense-mediated knockdown strategy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Therapeutic strategies in the treatment of periodontitis

Directory of Open Access Journals (Sweden)

Liljana Bogdanovska

2012-04-01

Full Text Available Periodontitis is a chronic inflammatory process which affects the tooth - supporting structures of the teeth. The disease is initiated by subgingival periopathogenic bacteria in susceptible periodontal sites. The host immune response towards periodontal pathogens helps to sustain periodontal disease and eventual alveolar bone loss. Although scaling and root planing is the standard treatment modality for periodontitis, it suffers from several drawbacks such as the inability to reach the base of deep pockets and doesn’t arrest migration of periodontal pathogens from other sites in the oral cavity. In order to overcome the limitations of scaling and root planning, adjunctive chemotherapeutics and host modulatory agents to the treatment are used. These therapeutic agents show substantial beneficial effects when compared to scaling and root planning alone. This review will cover an update on chemotherapeutic and past and future host immune modulatory agents used adjunctively to treat and manage periodontal diseases.

Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches.

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Hira, Vashendriya V V; Van Noorden, Cornelis J F; Carraway, Hetty E; Maciejewski, Jaroslaw P; Molenaar, Remco J

2017-08-01

Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes. Thus far, three types of HSC niches are recognized: endosteal, reticular and perivascular niches. However, we argue here that there is only one type of HSC niche, which consists of a periarteriolar compartment and a perisinusoidal compartment. In the periarteriolar compartment, hypoxia and low levels of reactive oxygen species preserve the HSC pool. In the perisinusoidal compartment, hypoxia in combination with higher levels of reactive oxygen species enables proliferation of progenitor cells and their mobilization into the circulation. Because HSC niches offer protection to LSCs against chemotherapy, we review novel therapeutic strategies to inhibit homing of LSCs in niches for the prevention of dedifferentiation of leukemic cells into LSCs and to stimulate migration of leukemic cells out of niches. These strategies enhance differentiation and proliferation and thus sensitize leukemic cells to chemotherapy. Finally, we list clinical trials of therapies that tackle LSCs in HSC niches to circumvent their protection against chemotherapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Global Regulatory Differences for Gene- and Cell-Based Therapies

DEFF Research Database (Denmark)

Coppens, Delphi G M; De Bruin, Marie L; Leufkens, Hubert G M

2017-01-01

Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between...... jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation....

Therapeutic strategies in pulmonary hypertension

Directory of Open Access Journals (Sweden)

Leonello eFuso

2011-04-01

Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.

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Basson, Abigail R; Lam, Minh; Cominelli, Fabio

2017-12-01

The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural and functional outcomes of a therapeutic strategy targeting low disease activity in patients with elderly-onset rheumatoid arthritis: a prospective cohort study (CRANE).

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Sugihara, Takahiko; Ishizaki, Tatsuro; Hosoya, Tadashi; Iga, Shoko; Yokoyama, Waka; Hirano, Fumio; Miyasaka, Nobuyuki; Harigai, Masayoshi

2015-05-01

The aim of this study was to evaluate structural damage and physical disability in patients with elderly-onset RA (EORA) who were treated in clinical practice with a therapeutic strategy targeting low disease activity (LDA). Data from 151 MTX-naive patients (mean age 74.9 years) with EORA from a prospective, monocentric registry were analysed. Treatment was adjusted every 3 months targeting LDA [28-joint DAS using ESR (DAS28-ESR) target strategy was observed in 83.4% of the 151 patients at week 24 and in 75.5% at week 52. At week 52, 67.6% of the patients were receiving a nbDMARD alone, 31.0% a TNFi with or without MTX and 1.4% tocilizumab. At week 52, structural remission (ΔmTSS/yr ≤0.5) was achieved in 49.7% of the patients, functional remission (HAQ-DI ≤0.5) in 63.4% and LDA in 51.0%. Clinical responses at weeks 12 and 24 were significant independent predictors of CRRP. Cumulative disease activity during the first 12 weeks predicted CRRP with a C-statistic of 0.888. Achieving structural remission, functional remission and LDA in clinical practice in EORA patients are realistic goals. Our results indicate significant benefits for a therapeutic strategy targeting LDA for EORA patients in clinical practice. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Therapeutic effects of saffron (Crocus sativus L. in digestive disorders: a review

Directory of Open Access Journals (Sweden)

Alireza Rezaee Khorasany

2016-05-01

Full Text Available Saffron, the dried red-orange stigmas of Crocus sativus L, has been known as a flavoring agent, food coloring and traditional herbal medicine. Pharmacological effects of saffron are mainly attributed to crocin, crocetin, picrocrocin and safranal. These components especially crocin, have significant effects including antidepressant and anticonvulsant, analgesic, anti-cancer and other therapeutic effects on different parts of our body namely cardiovascular, immune, respiratory, genital-urinary and central nervous system. According to the reports and findings, saffron plays a key role to cure different digestive system disorders via chemopreventive, inhibition of cell proliferation, induction of apoptosis, antioxidant effects and radical scavenging, genoprotective property, prevention of lipid peroxidation and anti-inflammatory processes. The outcome of the above mentioned mechanisms shows potential therapeutic properties of saffron against liver cancer, hepatotoxicity, fatty liver, hyperlipidemia, stomach cancer, peptic ulcer, colon cancer, ulcerative colitis, diabetes and pancreas cancer and ileum contractions. According to global statistics, the susceptibility to intestinal diseases is considered as a significant matter and can be important in health planning in any community. Several strategies for treatment and prevention of the digestive system diseases have provided that the use of herbal remedies seems effective and useful. Considering the available findings, the present study aims to introduce saffron as a prophylactic and therapeutic agent against gastrointestinal tract disorders. However, further clinical studies seem necessary in various aspects of saffron effects in different parts of body to verify these findings.

Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies.

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Giordano, Carmen; Albani, Diego; Gloria, Antonio; Tunesi, Marta; Batelli, Sara; Russo, Teresa; Forloni, Gianluigi; Ambrosio, Luigi; Cigada, Alberto

2009-12-01

This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimer's and Parkinson's diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of severe neurodegenerative disorders.

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

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Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

2017-12-01

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

Science.gov (United States)

Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

Public policy and risk financing strategies for global catastrophe risk management - the role of global risk initiatives

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McSharry, Patrick; Mitchell, Andrew; Anderson, Rebecca

2010-05-01

Decision-makers in both public and private organisations depend on accurate data and scientific understanding to adequately address climate change and the impact of extreme events. The financial impacts of catastrophes on populations and infrastructure can be offset through effective risk transfer mechanisms, structured to reflect the specific perils and levels of exposure to be covered. Optimal strategies depend on the likely socio-econonomic impact, the institutional framework, the overall objectives of the covers placed and the level of both the frequency and severity of loss potential expected. The diversity of approaches across different countries has been documented by the Spanish "Consorcio de Compensación de Seguros". We discuss why international public/private partnerships are necessary for addressing the risk of natural catastrophes. International initiatives such as the Global Earthquake Model (GEM) and the World Forum of Catastrophe Programmes (WFCP) can provide effective guidelines for constructing natural catastrophe schemes. The World Bank has been instrumental in the creation of many of the existing schemes such as the Turkish Catastrophe Insurance Pool, the Caribbean Catastrophe Risk Insurance Facility and the Mongolian Index-Based Livestock Insurance Program. We review existing schemes and report on best practice in relation to providing protection against natural catastrophe perils. The suitability of catastrophe modelling approaches to support schemes across the world are discussed and we identify opportunities to improve risk assessment for such schemes through transparent frameworks for quantifying, pricing, sharing and financing catastrophe risk on a local and global basis.

Strategy for selecting nanotechnology carriers to overcome immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics.

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Dobrovolskaia, Marina A; McNeil, Scott E

2015-07-01

Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation. This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents. NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.

The Military Strategy of Global Jihad

National Research Council Canada - National Science Library

Zabel, Sara E

2007-01-01

.... Global jihadis have spent more than 40 years refining their philosophy, gaining experience, building their organization, and developing plans to reestablish what they see as the only true Islamic state on earth...

Non-communicable diseases and global health governance: enhancing global processes to improve health development.

Science.gov (United States)

Magnusson, Roger S

2007-05-22

This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy.

Non-communicable diseases and global health governance: enhancing global processes to improve health development

Directory of Open Access Journals (Sweden)

Magnusson Roger S

2007-05-01

Full Text Available Abstract This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO, World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control, but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health. The paper assesses the merits of the Millennium Development Goals (MDGs and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy.

Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

Science.gov (United States)

Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

2016-12-01

Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Global strategy for the diagnosis and management of asthma in children 5 years and younger

DEFF Research Database (Denmark)

Hurd, Suzanne S; Lemanske, Robert F; Becker, Allan

2011-01-01

in this age group. For this reason, to aid in the diagnosis of asthma in young children, a symptoms-only descriptive approach that includes the definition of various wheezing phenotypes has been recommended. In 1993, the Global Initiative for Asthma (GINA) was implemented to develop a network of individuals...... and our ability to manage and control it effectively. However, in children 5 years and younger, the clinical symptoms of asthma are variable and non-specific. Furthermore, neither airflow limitation nor airway inflammation, the main pathologic hallmarks of the condition, can be assessed routinely......, organizations, and public health officials to disseminate information about the care of patients with asthma while at the same time assuring a mechanism to incorporate the results of scientific investigations into asthma care. Since then, GINA has developed and regularly revised a Global Strategy for Asthma...

EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers

Directory of Open Access Journals (Sweden)

Joanna B. Wilson

2018-04-01

Full Text Available The presence of the Epstein-Barr virus (EBV-encoded nuclear antigen-1 (EBNA1 protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another

Protein based therapeutic delivery agents: Contemporary developments and challenges.

Science.gov (United States)

Yin, Liming; Yuvienco, Carlo; Montclare, Jin Kim

2017-07-01

As unique biopolymers, proteins can be employed for therapeutic delivery. They bear important features such as bioavailability, biocompatibility, and biodegradability with low toxicity serving as a platform for delivery of various small molecule therapeutics, gene therapies, protein biologics and cells. Depending on size and characteristic of the therapeutic, a variety of natural and engineered proteins or peptides have been developed. This, coupled to recent advances in synthetic and chemical biology, has led to the creation of tailor-made protein materials for delivery. This review highlights strategies employing proteins to facilitate the delivery of therapeutic matter, addressing the challenges for small molecule, gene, protein and cell transport. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overview of the status and global strategy for neonicotinoids.

Science.gov (United States)

Jeschke, Peter; Nauen, Ralf; Schindler, Michael; Elbert, Alfred

2011-04-13

In recent years, neonicotinoid insecticides have been the fastest growing class of insecticides in modern crop protection, with widespread use against a broad spectrum of sucking and certain chewing pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors (nAChRs), their molecular target site. The discovery of neonicotinoids can be considered as a milestone in insecticide research and greatly facilitates the understanding of functional properties of the insect nAChRs. In this context, the crystal structure of the acetylcholine-binding proteins provides the theoretical foundation for designing homology models of the corresponding receptor ligand binding domains within the nAChRs, a useful basis for virtual screening of chemical libraries and rational design of novel insecticides acting on these practically relevant channels. Because of the relatively low risk for nontarget organisms and the environment, the high target specificity of neonicotinoid insecticides, and their versatility in application methods, this important class has to be maintained globally for integrated pest management strategies and insect resistance management programs. Innovative concepts for life-cycle management, jointly with the introduction of generic products, have made neonicotinoids the most important chemical class for the insecticide market.

Local industry in global networks : changing competitiveness, corporate strategies and pathways of development in Singapore and Malaysia's garment industry

NARCIS (Netherlands)

Smakman, Floortje

2004-01-01

The garment industry in Singapore and Malaysia has been incorporated into global production networks and commodity chains - driven by large US and European garment companies - since the 1960s and 1970s respectively. The industry was an intricate part of the export led industrialisation strategies

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Directory of Open Access Journals (Sweden)

Mario Gimona

2017-06-01

Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

Connecting strategy and execution in global R&D

DEFF Research Database (Denmark)

Sbernini, Federico; Granini, Nicola; Herbert-Hansen, Zaza Nadja Lee

2017-01-01

The paper investigates the relationship between global product development strategic decisions, which include outsourcing, offshoring practices as well as strategic alliances, and their impact on the day-to-day business in a global and open innovation context. By adopting an exploratory inductive...

3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration.

Science.gov (United States)

Hsieh, Fu-Yu; Hsu, Shan-hui

2015-01-01

Acute traumatic injuries and chronic degenerative diseases represent the world's largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37 °C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration.

Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

Science.gov (United States)

Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

2016-01-01

The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

Avian Influenza: a global threat needing a global solution

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Koh GCH

2008-11-01

Full Text Available Abstract There have been three influenza pandemics since the 1900s, of which the 1919–1919 flu pandemic had the highest mortality rates. The influenza virus infects both humans and birds, and mutates using two mechanisms: antigenic drift and antigenic shift. Currently, the H5N1 avian flu virus is limited to outbreaks among poultry and persons in direct contact to infected poultry, but the mortality rate among infected humans is high. Avian influenza (AI is endemic in Asia as a result of unregulated poultry rearing in rural areas. Such birds often live in close proximity to humans and this increases the chance of genetic re-assortment between avian and human influenza viruses which may produce a mutant strain that is easily transmitted between humans. Once this happens, a global pandemic is likely. Unlike SARS, a person with influenza infection is contagious before the onset of case-defining symptoms which limits the effectiveness of case isolation as a control strategy. Researchers have shown that carefully orchestrated of public health measures could potentially limit the spread of an AI pandemic if implemented soon after the first cases appear. To successfully contain and control an AI pandemic, both national and global strategies are needed. National strategies include source surveillance and control, adequate stockpiles of anti-viral agents, timely production of flu vaccines and healthcare system readiness. Global strategies such as early integrated response, curbing the disease outbreak at source, utilization of global resources, continuing research and open communication are also critical.

Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

Science.gov (United States)

Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

2017-08-22

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Strategic Complexity and Global Expansion

DEFF Research Database (Denmark)

Oladottir, Asta Dis; Hobdari, Bersant; Papanastassiou, Marina

2012-01-01

The purpose of this paper is to analyse the determinants of global expansion strategies of newcomer Multinational Corporations (MNCs) by focusing on Iceland, Israel and Ireland. We argue that newcomer MNCs from small open economies pursue complex global expansion strategies (CGES). We distinguish....... The empirical evidence suggests that newcomer MNCs move away from simplistic dualities in the formulation of their strategic choices towards more complex options as a means of maintaining and enhancing their global competitiveness....

Current Immunotherapeutic Strategies to Enhance Oncolytic Virotherapy

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Daniel E. Meyers

2017-06-01

Full Text Available Oncolytic viruses (OV represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host’s adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC. It is generally accepted that OV as monotherapy have only modest clinical efficacy. However, due to their ability to elicit specific antitumor immune responses, they are prime candidates to be paired with other immune-modulating strategies in order to optimize therapeutic efficacy. Synergistic strategies to enhance the efficacy of OV include augmenting the host antitumor response through the insertion of therapeutic transgenes such as GM-CSF, utilization of the prime-boost strategy, and combining OV with immune-modulatory drugs such as cyclophosphamide, sunitinib, and immune checkpoint inhibitors. This review provides an overview of these immune-based strategies to improve the clinical efficacy of oncolytic virotherapy.

The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson’s Disease

Science.gov (United States)

D’Ostilio, Kevin; Garraux, Gaëtan

2016-01-01

The high prevalence of major depressive disorder in people with Parkinson’s disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions. PMID:27148016

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

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Van Lint Carine

2009-12-01

Full Text Available Abstract The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.

Strategies for Sustainable Energy Development

DEFF Research Database (Denmark)

Meyer, Niels I

2009-01-01

The paper analyses international strategies for establishing a sustainable energy development. Proposals are given for mitigation of global warming.......The paper analyses international strategies for establishing a sustainable energy development. Proposals are given for mitigation of global warming....

The deregulated global economy: women workers and strategies of resistance.

Science.gov (United States)

Hale, A

1996-10-01

This article discusses the lack of input from women in international debates about the global economy. Women in the South are the most vulnerable to exploitation and most ignored in international discussions of how to protect fair labor standards. Restructuring has led to loss of secure jobs in the public sector and the expansion of female employment in low-paid, insecure, unskilled jobs. Businesses desire a cheap and flexible workforce. Declines in social services, the elimination of subsidies on basic goods, and the introduction of user fees puts pressure on women to supplement family income. A parallel outcome is reduced employment rights, neglect of health and safety standards, and increased disregard among women for their domestic responsibilities. There is a need for alternative models of development. The Self-Employed Women's Organization in India serves as a model for resisting exploitation among self-employed and home-based employees. Female industrial strikers are demanding attention to excessive hours of work, enforced overtime, bullying, and lack of sanitary and medical facilities. There is always fear that organized resistance will lead to industrial relocation or loss of jobs. The International Labor Organization has had a code for 20 years, but the threat of exposure to the press is sometimes more effective. There must be regulation throughout subcontracting chains of transnational companies. International alliances should revolve around issues/strategies identified by workers. International alliances are needed for influencing multinational companies and national governments and lobbying global economic and financial institutions. Standards that are included in social clause discussions are minimum requirements that do not address gender-specific issues. Women Working Worldwide is developing a position statement of social clauses that incorporates a women's perspective.

CSR Strategies in Greater China: Global, East Asian, American, European Style?

Directory of Open Access Journals (Sweden)

Heiduk Guenter

2014-10-01

Full Text Available The concept of Corporate Social Responsibility emerged in the United States and spread to Europe and Asia while being adapted to national/local characteristics. Since borders between markets and societies are blurring and globalization is promoting MNCs which find themselves acting in hybrid societies, international institutions put efforts into the development and moral acceptance of global CSR standards. The scientific interest in CSR focused on the conflicts between company returns and benefits for society. The resulting concepts of performance-oriented, awareness-oriented and welfare-oriented CSR should facilitate the evaluation of CSR strategies implemented by MNCs. In research on the cultural dimensions of economies, it might be possible to allocate geographically the three concepts. Regarding the newly emerging Chinese MNCs, the paper aims to shed light on which concept they follow. On the one hand, CSR concepts of American and/or European MNCs that are present in China might serve as a role model; on the other hand, by learning from Taiwanese/ Hong Kong MNCs, a “greater China CSR approach” might emerge. Empirical studies and own field research suggest that compared to American and European companies, CSR is less deeply rooted in Chinese companies. Furthermore, significant differences between Mainland China, Hong Kong and Taiwanese companies indicate that a Greater Chinese CSR approach does not yet exist. Therefore, it cannot be assumed that American and European CSR concepts will experience a Chinese influence in the near future.

Strategies for the coupling of global and local crystal growth models

Science.gov (United States)

Derby, Jeffrey J.; Lun, Lisa; Yeckel, Andrew

2007-05-01

The modular coupling of existing numerical codes to model crystal growth processes will provide for maximum effectiveness, capability, and flexibility. However, significant challenges are posed to make these coupled models mathematically self-consistent and algorithmically robust. This paper presents sample results from a coupling of the CrysVUn code, used here to compute furnace-scale heat transfer, and Cats2D, used to calculate melt fluid dynamics and phase-change phenomena, to form a global model for a Bridgman crystal growth system. However, the strategy used to implement the CrysVUn-Cats2D coupling is unreliable and inefficient. The implementation of under-relaxation within a block Gauss-Seidel iteration is shown to be ineffective for improving the coupling performance in a model one-dimensional problem representative of a melt crystal growth model. Ideas to overcome current convergence limitations using approximations to a full Newton iteration method are discussed.

Therapeutic risk management of the suicidal patient: safety planning.

Science.gov (United States)

Matarazzo, Bridget B; Homaifar, Beeta Y; Wortzel, Hal S

2014-05-01

This column is the fourth in a series describing a model for therapeutic risk management of the suicidal patient. Previous columns presented an overview of the therapeutic risk management model, provided recommendations for how to augment risk assessment using structured assessments, and discussed the importance of risk stratification in terms of both severity and temporality. This final column in the series discusses the safety planning intervention as a critical component of therapeutic risk management of suicide risk. We first present concerns related to the relatively common practice of using no-suicide contracts to manage risk. We then present the safety planning intervention as an alternative approach and provide recommendations for how to use this innovative strategy to therapeutically mitigate risk in the suicidal patient.

Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.

Science.gov (United States)

Del Nogal-Avila, Maria; Donoro-Blazquez, Hector; Saha, Manish K; Marshall, Caroline B; Clement, Lionel C; Macé, Camille E A; Chugh, Sumant S

2016-07-01

Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease. Copyright © 2016 the American Physiological Society.

Using therapeutic cloning to fight human disease: a conundrum or reality?

Science.gov (United States)

Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

2006-07-01

The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

Global gas strategies: a major player's perspective

International Nuclear Information System (INIS)

Brown, R.L.

1996-01-01

Changes in the world demand for energy and discovery of further reserves of natural gas world-wide mean that the natural gas industry is poised to expand its influence on the global fuel markets. This paper explores the industry's potential for expansion, the need for a dynamic approach to change and a respect for the complexity of market forces. Guidelines for success in expansion are drawn up. The virtues of natural gas in relation to environmental factors and diversity of supply, through pipelines or LNG, are extolled and the industry urged to grasp the challenge of the competitive global market fuels. (UK)

Therapeutic options to treat sulfur mustard poisoning--the road ahead.

Science.gov (United States)

Smith, William J

2009-09-01

For the past 15 years the international research community has conducted a basic and applied research program aimed at identifying a medical countermeasure against chemical threat vesicant, or blistering, agents. The primary emphasis of this program has been the development of therapeutic protection against sulfur mustard and its cutaneous pathology-blister formation. In addition to the work on a medical countermeasures, significant research has been conducted on the development of topical skin protectants and medical strategies for wound healing. This review will focus on the pharmacological strategies investigated, novel therapeutic targets currently under investigation and therapeutic approaches being considered for transition to advanced development. Additionally, we will review the expansion of our understanding of the pathophysiological mechanisms of mustard injury that has come from this research. While great strides have been made through these investigations, the complexity of the mustard insult demands that further studies extend the inroads made and point the way toward better understanding of cellular and tissue disruptions caused by sulfur mustard.

When Going Global Isn't Enough.

Science.gov (United States)

Randolph, Benton

1990-01-01

The traditional multinational approach to business strategy and human resource management, as well as the global approach, are not effective in a world no longer insular. A transnational approach requires global strategy and perspective, local responsiveness and flexibility, teamwork, shared responsibility, and empowered and innovative workers.…

Full of energy. A vision: The global factor-of-four strategy for mitigating greenhouse gas emissions and opting out of nuclear power

International Nuclear Information System (INIS)

Lovins, A.; Hennicke, P.

1999-01-01

Here it is at last: A sustainable global energy system. Based on a ''factor-of- four'' approach, the authors, who are experts in all matters of energy systems, explain the evolution of their energy strategy which is fit for global implementation and realization. It is technically feasible, ecologically justifiable, and economically attractive, as it relies on enhanced energy efficiency and enhanced use of renewable energy sources. (orig./CB) [de

Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial.

Science.gov (United States)

Johnston, Celeste; Campbell-Yeo, Marsha; Rich, Bonnie; Whitley, Julie; Filion, Francoise; Cogan, Jennifer; Walker, Claire-Dominique

2013-09-01

Preterm neonates below 30 weeks' gestational age undergo numerous painful procedures. Many management approaches are not appropriate for this population. Therapeutic Touch, an alternative approach based on the theory of energy medicine, has been shown to promote physiological stability in preterm neonates and reduce pain in some adult studies. The objective was to determine whether Therapeutic Touch is efficacious in decreasing pain in preterm neonates. Infants Touch (n = 27) with infant behind curtains, leaving the curtained area for the heel lance, performed by another. In the sham condition (n = 28), the therapist stood by the incubator with hands by her side. The Premature Infant Pain Profile was used for pain response and time for heart rate to return to baseline for recovery. Heart rate variability and stress response were secondary outcomes. There were no group differences in any of the outcomes. Mean Premature Infant Pain Profile scores across 2 minutes of heel lance procedure in 30-second blocks ranged from 7.92 to 8.98 in the Therapeutic Touch group and 7.64 to 8.46 in the sham group. Therapeutic Touch given immediately before and after heel lance has no comforting effect in preterm neonates. Other effective strategies involving actual touch should be considered.

A Strategy To Infuse a Global Perspective into Consumer Education.

Science.gov (United States)

McGregor, Sue L. T.; Bourbonniere, Katherine

2002-01-01

A four-phase plan for delivering consumer education from a global perspective involves teachers in gaining familiarity with (1) the conventional approach to consumer education; (2) the cultures of globalization, capitalism, and consumerism; (3) the global perspective; and (4) integration of the three to create a global curriculum. (Contains 50…

Melatonin-Based Therapeutics for Neuroprotection in Stroke

Directory of Open Access Journals (Sweden)

Cesar V. Borlongan

2013-04-01

Full Text Available The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.

"Clicking" Gene Therapeutics: A Successful Union of Chemistry and Biomedicine for New Solutions

DEFF Research Database (Denmark)

Astakhova, Kira; Ray, Roslyn; Taskova, Maria

2018-01-01

The use of nucleic acid, DNA and RNA, based strategies to disrupt gene expression as a therapeutic is quickly emerging. Indeed, synthetic oligonucleotides represent a major component of modern gene therapeutics. However, the efficiency and specificity of intracellular uptake for nonmodified oligo...

Events i den globale bykonkurrence

DEFF Research Database (Denmark)

Østergaard, Katrine

2005-01-01

Paper til ph.d. workshop, d. 9. december 2005. Dette paper beskriver, hvorfor og hvordan events kan bruges som strategi for byplanlægning og byudvikling i den globale bykonkurrence.......Paper til ph.d. workshop, d. 9. december 2005. Dette paper beskriver, hvorfor og hvordan events kan bruges som strategi for byplanlægning og byudvikling i den globale bykonkurrence....

The CEOS Global Observation Strategy for Disaster Risk Management: An Enterprise Architect's View

Science.gov (United States)

Moe, K.; Evans, J. D.; Frye, S.

2013-12-01

The Committee on Earth Observation Satellites (CEOS) Working Group on Information Systems and Services (WGISS), on behalf of the Global Earth Observation System of Systems (GEOSS), is defining an enterprise architecture (known as GA.4.D) for the use of satellite observations in international disaster management. This architecture defines the scope and structure of the disaster management enterprise (based on disaster types and phases); its processes (expressed via use cases / system functions); and its core values (in particular, free and open data sharing via standard interfaces). The architecture also details how a disaster management enterprise describes, obtains, and handles earth observations and data products for decision-support; and how it draws on distributed computational services for streamlined operational capability. We have begun to apply this architecture to a new CEOS initiative, the Global Observation Strategy for Disaster Risk Management (DRM). CEOS is defining this Strategy based on the outcomes of three pilot projects focused on seismic hazards, volcanoes, and floods. These pilots offer a unique opportunity to characterize and assess the impacts (benefits / costs) of the GA.4.D architecture in practice. In particular, the DRM Floods Pilot is applying satellite-based optical and radar data to flood mitigation, warning, and response, including monitoring and modeling at regional to global scales. It is focused on serving user needs and building local institutional / technical capacity in the Caribbean, Southern Africa, and Southeast Asia. In the context of these CEOS DRM Pilots, we are characterizing where and how the GA.4D architecture helps participants to: - Understand the scope and nature of hazard events quickly and accurately - Assure timely delivery of observations into analysis, modeling, and decision-making - Streamline user access to products - Lower barriers to entry for users or suppliers - Streamline or focus field operations in

Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

Science.gov (United States)

Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

2016-07-01

Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.

Science.gov (United States)

Wang, Chao-Qun; Li, Yang; Huang, Bi-Fei; Zhao, Yong-Ming; Yuan, Hui; Guo, Dongfang; Su, Chen-Ming; Hu, Gui-Nv; Wang, Qian; Long, Tengyun; Wang, Yan; Tang, Chih-Hsin; Li, Xiaoni

2017-11-15

Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.

Therapeutic navigations: National and transnational quests for fertility among Mozambican women and men

NARCIS (Netherlands)

Domingues Figueira de Faria, I.

2016-01-01

This thesis explores Mozambican women and couple’s processes of coping with infertility and their national and transnational therapeutic itineraries in the quest for a child. Based on the idea of therapeutic navigation, this work accounts for the manifold social and individual aspects and strategies

The Therapeutic Relationship in Cognitive-Behavioral Therapy and Pharmacotherapy for Anxious Youth

Science.gov (United States)

Cummings, Colleen M.; Caporino, Nicole E.; Settipani, Cara A.; Read, Kendra L.; Compton, Scott N.; March, John; Sherrill, Joel; Piacentini, John; McCracken, James; Walkup, John; Ginsburg, Golda; Albano, Anne Marie; Rynn, Moira; Birmaher, Boris; Sakolsky, Dara; Gosch, Elizabeth; Keeton, Courtney; Kendall, Philip C.

2014-01-01

Objective Examine the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (CAMS; Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes. Method Participants were 488 youth (ages 7-17; 50% male) randomized to cognitive-behavioral therapy (CBT; Coping cat), pharmacotherapy (SRT; sertraline), their combination, or pill placebo. Participants met DSM-IV criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. The therapeutic relationship was assessed by youth-report at weeks 6 and 12 of treatment using the Child's Perception of Therapeutic Relationship scale. Outcome measures (Pediatric Anxiety Rating Scale; Clinical Global Impressions Scales) were completed by Independent Evaluators blind to condition. Results For youth who received CBT only, a stronger therapeutic relationship predicted positive treatment outcome. In contrast, the therapeutic relationship did not predict outcome for youth receiving sertraline, combined treatment, or placebo. Conclusions A therapeutic relationship may be important for anxious youth who receive CBT alone. PMID:23750468

Humor: A Therapeutic Intervention for Child Counseling

Science.gov (United States)

Berg, Rachelle G.; Parr, Gerald; Bradley, Loretta J.; Berry, Jeremy J.

2009-01-01

Counselors utilize many strategies, techniques, and tools when building a therapeutic alliance or addressing children's issues. Due to the serious nature of discussing problems or perhaps because of the fear of seeming insensitive, counselors often overlook humor as a means to enhance therapy. Whether deliberate or spontaneous, humor can add…

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.

Science.gov (United States)

Xue, Shuai; Yin, Jianli; Shao, Jiawei; Yu, Yuanhuan; Yang, Linfeng; Wang, Yidan; Xie, Mingqi; Fussenegger, Martin; Ye, Haifeng

2017-02-01

Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Therapeutic physical exercise in neural injury: friend or foe?

Science.gov (United States)

Park, Kanghui; Lee, Seunghoon; Hong, Yunkyung; Park, Sookyoung; Choi, Jeonghyun; Chang, Kyu-Tae; Kim, Joo-Heon; Hong, Yonggeun

2015-12-01

[Purpose] The intensity of therapeutic physical exercise is complex and sometimes controversial in patients with neural injuries. This review assessed whether therapeutic physical exercise is beneficial according to the intensity of the physical exercise. [Methods] The authors identified clinically or scientifically relevant articles from PubMed that met the inclusion criteria. [Results] Exercise training can improve body strength and lead to the physiological adaptation of skeletal muscles and the nervous system after neural injuries. Furthermore, neurophysiological and neuropathological studies show differences in the beneficial effects of forced therapeutic exercise in patients with severe or mild neural injuries. Forced exercise alters the distribution of muscle fiber types in patients with neural injuries. Based on several animal studies, forced exercise may promote functional recovery following cerebral ischemia via signaling molecules in ischemic brain regions. [Conclusions] This review describes several types of therapeutic forced exercise and the controversy regarding the therapeutic effects in experimental animals versus humans with neural injuries. This review also provides a therapeutic strategy for physical therapists that grades the intensity of forced exercise according to the level of neural injury.

Global integration in times of crisis

DEFF Research Database (Denmark)

Jensen, Camilla

shock) from other subsidiaries downstream in the value chain. While in a comparative perspective multinational subsidiaries are found to perform relatively better than local firms that are integrated differently (arms' length) in global production networks (e.g. offshoring outsourcing). This paper tries...... to reconcile these findings by testing a number of hypothesis about global integration strategies in the context of the global financial crisis and how it affected exporting among multinational subsidiaries operating out of Turkey. Controlling for the impact that depreciations and exchange rate volatility has...... integration strategies throughout the course of the global financial crisis....

Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

Directory of Open Access Journals (Sweden)

Hanson Jesse E

2010-08-01

Full Text Available Abstract Background Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1 Strength of long-term potentiation (LTP, 2 Strength of long-term depression (LTD, 3 Relative inhibition levels (Inhibition, and 4 Excitatory connectivity levels (Connectivity. Results To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties. Conclusions Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.

Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

Science.gov (United States)

Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.;

Big moving day for biodiversity? A macroecological assessment of the scope for assisted colonization as a conservation strategy under global warming

DEFF Research Database (Denmark)

Svenning, J.-C.; Fløjgaard, Camilla; Morueta-Holme, Naia

2009-01-01

to corresponding losses locally. Our results suggest that there is substantial room for additional plant species across most areas of Europe, indicating that there is considerable scope for implementing assisted colonization as a proactive conservation strategy under global warming without necessarily implicating...

Driving forces: Motor vehicle trends and their implications for global warming, energy strategies, and transportation planning

International Nuclear Information System (INIS)

MacKenzie, J.J.; Walsh, M.P.

1990-01-01

Cars, trucks, and other vehicles have long been linked to smog and other urban pollution, but the part they play in the larger complex of atmospheric and energy ills that we now face is often overlooked. In Driving Forces: Motor Vehicle Trends and Their Implications for Global Warming, Energy Strategies, and Transportation Planning, James J. MacKenzie, senior associate in World Resources Institute's Program in Climate, Energy, and Pollution, and Michael P. Walsh, an international consultant on transportation and environmental issues, fill in this knowledge gap with new data and analyses. They spell out four policy shifts that can help hold the line on global warming: improve new-vehicle efficiency; make transportation more efficient; cut other greenhouse gas emissions; create the green car of the future. The report focuses especially on the US, which pioneered the automotive revolution and leads the world in oil imports and emissions

Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

Science.gov (United States)

Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

2018-01-01

Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

Vocational Education and Training and the Therapeutic Turn

Science.gov (United States)

Hyland, Terry

2006-01-01

The concept of "therapeutic education" is being increasingly used in contemporary education policy studies to identify learning initiatives which are dominated by objectives linked to personal and social skills, emotional intelligence and building self-esteem. Contemporary educational goals connected with such strategies have been…

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

Science.gov (United States)

Kim, Ye-Ram; Yang, Chul-Su

2017-09-28

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

Leveraging public finance to achieve endgame for tobacco - possible national and global strategies

Directory of Open Access Journals (Sweden)

Pranay Lal

2018-03-01

Full Text Available Background Calls for institutional investors to divest (sell off tobacco stocks threaten the industry´s share values, publicise its bad behaviour, and label it as a politically unacceptable ally. The rise of the socially responsible investment movement, increasing litigation against major tobacco companies, and an increasing emphasis on tobacco industry delegitimisation as a tobacco control strategy created a climate within which tobacco divestment was open for serious discussion. Methods This survey enquired from 19 environment (including groups working against GHGs, asbestos and Big Oil, social and development sectors (groups working on IFC exclusion criteria on the role of public finance, and the arguments to support divestment from "sin" or exclusion sectors. Results In general the respondents to this survey presented the the following arguments which support divestment: • Global obligations to the WHO´s Framework Convention on Tobacco Control, and the other global treaties like the SDG. •\tEthical argument: Governments and their agencies that hold public funds can no longer support tobacco control and tobacco industry. •\tFiscal argument: high costs of national and global litigations make companies, public funded organisations and governments prone to heavy litigation costs and potential costs for damages •\tPublic health argument: Because tobacco industry continue to hold important policy positions, they block and interfere tobacco control efforts. Conclusions To begin a campaign for divestment would require preliminary work by civil society institutions which includes: • Tracking and monitoring institutions and investments • Collaborating with organisations which advocate for ethical or socially responsible investments. • Developing a policy research and advocacy roadmap with stakeholders towards and end date for divestment

Handbook of Global and Multicultural Negotiation

CERN Document Server

Moore, Christopher W

2010-01-01

Handbook of Global and Multicultural Negotiation provides advice and strategies for effective cross-cultural negotiations. Written from a multicultural perspective, this guidebook explores cross-cultural communication for problem solving and negotiations. This resource includes real-life stories and examples compiled from over thirty years of domestic and global experience from both authors, including Chris Moore, a well-known international negotiator and best selling author. This step-by-step guide to negotiation provides practical recommendations, advice, and globally proven strategies to pr

Therapeutic strategy for the treatment of isolated spontaneous dissection of superior mesenteric arteries

International Nuclear Information System (INIS)

Xu Yongle; Xiong Jiang; Guo Wei; Liu Xiaoping; Liu Meng

2010-01-01

Objective: To summarize the treatment strategies of isolated superior mesenteric artery (SMA) dissection and to discuss the selection of therapeutic methods. Methods: The clinical data of ten patients, who were encountered during the period from Jan. 2007 to Feb. 2010 in General Hospital of Chinese PLA and diagnosed as isolated SMA dissection,were retrospectively analyzed. According to the presence or absence of intestinal ischemic necrosis and SMA rupture, the patients were divided into simple group (n = 9) and complicated group(n = 1). The treatments for different type of SMA dissection were discussed and the results and prognosis were analyzed. Results: Nine patients were divided into simple group and received conservative treatment, of which anticoagulation was not employed in 5. One patient was divided into complicated group and had to receive an iliomesenteric bypass surgery after the patient had failed to respond to conservative treatment. After the treatment the abdominal pain was relieved in all ten patients. Conclusion: With the wide use of computer tomography angiography and digital subtraction angiography, more and more isolated SMA dissections have been confirmed. For most patients with SMA dissection, especially for simple ones (i.e. without bowel ischemia or SMA rupture), excellent short-term results can be achieved by pure conservative treatment, even no anticoagulation needed. However, for the complicated isolated SMA dissections, vascular reconstruction procedure with various techniques, including open surgery, is necessary in order to obtain satisfactory short-term results. (authors)

Developing a glocalisation strategy

DEFF Research Database (Denmark)

Hollensen, Svend; Schimmelpfennig, Christian

2015-01-01

while exploiting the benefits of global integration. The challenge is to balance the local knowledge with global reach. In the case of Persil Abaya Shampoo (for the Middle East market) and Persil Black Gel (for the European market), Henkel chose a strategy that successfully benefitted from...... markets and used Persil Abayas’ particular significance in the Arab world to its advantage. The results document that it has been possible for Henkel’s Persil to gain competitive advantages in terms of higher market shares, with the ‘glocalisation strategy’ in the (Middle East) liquid detergent market.......The glocalisation strategy strives to achieve the slogan, ‘think globally but act locally’, through dynamic interdependence between headquarters and subsidiaries and/or local intermediaries around the world. Companies following such a strategy coordinate their efforts, ensuring local flexibility...

Therapeutic Vaccination for HPV Induced Cervical Cancers

Directory of Open Access Journals (Sweden)

Joeli A. Brinkman

2007-01-01

Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

[Mantle cell lymphoma: Towards a personalized therapeutic strategy?].

Science.gov (United States)

Navarro Matilla, Belén; García-Marco, José A

2015-06-22

Mantle cell lymphoma (MCL) is a clinically heterogeneous non-Hodgkin lymphoma with an aggressive clinical behaviour and short survival in some cases and an indolent course in others. Advances in the biology and pathogenesis of MCL have unveiled several genes involved in deregulation of cell cycle checkpoints and the finding of subclonal populations with specific recurrent mutations (p53, ATM, NOTCH2) with an impact on disease progression and refractoriness to treatment. Prognostic stratification helps to distinguish between indolent and aggressive forms of MCL. Currently, younger fit patients benefit from more intensive front line chemotherapy regimens and consolidation with autologous transplantation, while older or frail patients are treated with less intensive regimens and rituximab maintenance. For relapsing disease, the introduction of bortezomib and lenalidomide containing regimens and B-cell receptor pathway inhibitors such as ibrutinib and idelalisib in combination with immunochemotherapy have emerged as therapeutic agents with promising clinical outcomes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Innovation Strategies for a Global Economy: Development ...

International Development Research Centre (IDRC) Digital Library (Canada)

2010-10-01

Oct 1, 2010 ... This path-breaking book integrates theory, case studies, data and policy ... their development, implementation, measurement and management. Following the global economic crisis, people are asking: what went wrong? Here ...

Discovery and design of carbohydrate-based therapeutics.

Science.gov (United States)

Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

2010-08-01

Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90α

International Nuclear Information System (INIS)

Mehta, Adi; Shervington, Leroy; Munje, Chinmay; Shervington, Amal

2011-01-01

Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy

Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications

NARCIS (Netherlands)

Rizzo, L.Y.; Theek, B.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

2013-01-01

In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-)

Using Therapeutic Toys to Facilitate Venipuncture Procedure in Preschool Children.

Science.gov (United States)

da Silva, José Ronaldo Soares; Pizzoli, Lourdes Margareth Leite; Amorim, Amanda Regina do Prado; Pinheiros, Fernanda Tais; Romanini, Giovanna Chippari; da Silva, Jack Gomes; Joanete, Shirley; Alves, Silvana S M

2016-01-01

Intravenous access procedures in children are considered to be one of the most stressful because it is invasive, and the use of needles generates anxiety, insecurity, and fear. Playful strategies using dolls and even the materials used for venipuncture can assist children in understanding, accepting, and coping with the procedure. Field research was developed on the applicability of the therapeutic toy in the preparation of preschool children for venipuncture procedure based on the protocol developed by Martins, Ribeiro, Borba, and Silva (2001) and Kiche and Almeida (2009). The study was done in a private hospital in Greater São Paulo, Brazil, with 10 children ages 3 to 6 years. Data were gathered through observation and questionnaires completed by the children's adult guardians. Before the activity, the children showed fearful facial expressions, used monosyllabic responses, and avoided looking at the health care professional. After the strategy of using therapeutic toy dolls and puppets, 40% of the children calmly accepted the venipuncture procedure, and 100% showed a change to their initial negative reaction, became more communicative and cooperative, and participated and interacted with researchers, even after the end of the activity and procedure. The strategy of therapeutic toys helps make an unfamiliar environment, strangers, and a procedure characterized as painful and difficult less stressful. Pediatric nurses are in a good position to use this resource to offer more humanized care to children.

Emerging nanotechnology based strategies for diagnosis and therapeutics of urinary tract infections: A review.

Science.gov (United States)

Kumar, M S; Das, A P

2017-11-01

At present, various diagnostic and therapeutic approaches are available for urinary tract infections. But, still the quest for development of more rapid, accurate and reliable approach is an unending process. The pathogens, especially uropathogens are adapting to new environments and antibiotics day by day rapidly. Therefore, urinary tract infections are evolving as hectic and difficult to eradicate, increasing the economic burden to the society. The technological advances should be able to compete the adaptability characteristics of microorganisms to combat their growth in new environments and thereby preventing their infections. Nanotechnology is at present an extensively developing area of immense scientific interest since it has diverse potential applications in biomedical field. Nanotechnology may be combined with cellular therapy approaches to overcome the limitations caused by conventional therapeutics. Nanoantibiotics and drug delivery using nanotechnology are currently growing areas of research in biomedical field. Recently, various categories of antibacterial nanoparticles and nanocarriers for drug delivery have shown their potential in the treatment of infectious diseases. Nanoparticles, compared to conventional antibiotics, are more beneficial in terms of decreasing toxicity, prevailing over resistance and lessening costs. Nanoparticles present long term therapeutic effects since they are retained in body for relatively longer periods. This review focuses on recent advances in the field of nanotechnology, principally emphasizing diagnostics and therapeutics of urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Globalization, nation-state and catching up

Directory of Open Access Journals (Sweden)

Luiz Carlos Bresser-Pereira

2008-12-01

Full Text Available Globalization and nation-states are not in contradiction, since globalization is the present stage of capitalist development, and the nation-state is the territorial political unit that organizes the space and population in the capitalist system. Since the 1980s, Global Capitalism constitutes the economic system characterized by the opening of all national markets and a fierce competition between nation-states. Developing countries tend to catch up, while rich countries try to neutralize such competitive effort, using globalism as an ideology, and conventional orthodoxy as a strategy. Middle-income countries that are catching up in the realm of globalization are the ones that count with a national development strategy. This is broadly the case of the dynamic Asian countries. In contrast, Latin American countries have no longer their own strategy, and grow less. To add data to the argument, the author conducts an econometric test comparing these two groups of countries, and three variables: the rate of investment, the current account deficit or surplus that would indicate or not a competitive exchange rate, and public deficit.

IO strategies and data services for petascale data sets from a global cloud resolving model

International Nuclear Information System (INIS)

Schuchardt, K L; Palmer, B J; Daily, J A; Elsethagen, T O; Koontz, A S

2007-01-01

Global cloud resolving models at resolutions of 4km or less create significant challenges for simulation output, data storage, data management, and post-simulation analysis and visualization. To support efficient model output as well as data analysis, new methods for IO and data organization must be evaluated. The model we are supporting, the Global Cloud Resolving Model being developed at Colorado State University, uses a geodesic grid. The non-monotonic nature of the grid's coordinate variables requires enhancements to existing data processing tools and community standards for describing and manipulating grids. The resolution, size and extent of the data suggest the need for parallel analysis tools and allow for the possibility of new techniques in data mining, filtering and comparison to observations. We describe the challenges posed by various aspects of data generation, management, and analysis, our work exploring IO strategies for the model, and a preliminary architecture, web portal, and tool enhancements which, when complete, will enable broad community access to the data sets in familiar ways to the community

David Bowie and the Art of Slow Innovation: A Fast-Second Winner Strategy for Biotechnology and Precision Medicine Global Development.

Science.gov (United States)

Özdemir, Vural; Patrinos, George P

2017-11-01

Original ideas and innovation cannot always be ordered like a courier service and delivered fresh to our desk at 9 am. Yet, most creativity-based organizations, careers, and professions, science and biotechnology innovation included, emphasize the speed as the prevailing ideology. But a narrow focus on speed has several and overlooked shortcomings. For example, it does not offer the opportunity to draw from, and stitch together disparate concepts and practices for truly disruptive innovation. Preventing false starts, learning from others' or our own mistakes, and customizing innovations for local community needs are difficult in a speed-hungry innovation ecosystem. We introduce a new strategy, the Fast-Second Winner, specifically in relation to global development of biotechnologies and precision medicine. This à la carte global development strategy envisions a midstream entry into the innovation ecosystem. Moreover, we draw from the works of the late David Bowie who defied rigid classifications as an artist and prolific innovator, and introduce the concept and practice of slow innovation that bodes well with the Fast-Second Winner strategy. A type of slow innovation, the Fast-Second Winner is actually fast and sustainable in the long term, and efficient by reducing false starts in new precision medicine application contexts and geographies, learning from other innovators' failures, and shaping innovations for the local community needs. The establishment of Centers for Fast-Second Innovation (CFSIs), and their funding, for example, by crowdfunding and other innovative mechanisms, could be timely for omics and precision medicine global development. If precision medicine is about tailoring drug treatments and various health interventions to individuals, we suggest to start from tailoring new ideas, and focus not only on how much we innovate but also what and how we innovate. In principle, the Fast-Second Winner can be applied to omics and other biotechnology

Key Trends Shaping the Global Logistics Environment

DEFF Research Database (Denmark)

Handfield, Robert; Straube, Frank; Pfohl, Hans-Christian

A summary from the full study “Trends and Strategies in Logistics and Supply Chain Management. Embracing Global Logistics Complexity to Drive Market Advantage” (2013).......A summary from the full study “Trends and Strategies in Logistics and Supply Chain Management. Embracing Global Logistics Complexity to Drive Market Advantage” (2013)....

Recognition as welfare in globalization

Directory of Open Access Journals (Sweden)

Pantović Branislav

2011-01-01

Full Text Available The subject matter of this study is an interdisciplinary envisaging of cultural problem in the process of globalization. The development and theoretical organization of the project that deals with cultural identity and strategy to represent Serbia on a global level could be a part of an overall strategy of the Serbian Government for development and advancement of the country. Globalization, as a gradual, progressive cycle of the world integrations is resulting in cultural exchange increase and represents a parameter for description of changes in the society. Culture constitutes a significant segment of international integration, where cultural authenticity and its promotion are of particular significance.

Global Health Engagement: At Home and Abroad.

Science.gov (United States)

Phillips, Janet M; Riner, Mary E

2018-03-01

Nurses and nurse educators need to be prepared to accelerate progress toward the United Nations' Sustainable Development Goals to improve local and global health in the face of continued poverty, hunger, and disease. This four-part Teaching Tips series will focus on developing nurse educators to prepare nurses for global engagement on the following topics: introduction to global health, systems thinking for global health, strategies for integrating global awareness and engagement into clinical practice, and leading and participating in service trips. The authors offer tips for increasing global awareness and using frameworks, strategies, and resources for both students and nurses to use in their own settings and practice. J Contin Educ Nurs. 2018;49(3):109-110. Copyright 2018, SLACK Incorporated.

Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

Science.gov (United States)

Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

2018-06-01

The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

Next Generation Antibody Therapeutics Using Bispecific Antibody Technology.

Science.gov (United States)

Igawa, Tomoyuki

2017-01-01

Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.

Global, Local, or Regional?

DEFF Research Database (Denmark)

Verbeke, Alain; Geisler Asmussen, Christian

2016-01-01

of analysis, in addition to the country-level and the global level. Regional strategy analysis requires a fundamental rethink of mainstream theories in the international strategy sphere. This rethink involves, inter alia, internalization theory, with its resource-based view and transaction cost economics...

Design strategies to minimize the radiative efficiency of global warming molecules

Science.gov (United States)

Bera, Partha P.; Francisco, Joseph S.; Lee, Timothy J.

2010-01-01

A strategy is devised to screen molecules based on their radiative efficiency. The methodology should be useful as one additional constraint when determining the best molecule to use for an industrial application. The strategy is based on the results of a recent study where we examined molecular properties of global warming molecules using ab initio electronic structure methods to determine which fundamental molecular properties are important in assessing the radiative efficiency of a molecule. Six classes of perfluorinated compounds are investigated. For similar numbers of fluorine atoms, their absorption of radiation in the IR window decreases according to perfluoroethers > perfluorothioethers ≈ sulfur/carbon compounds > perfluorocarbons > perfluoroolefins > carbon/nitrogen compounds. Perfluoroethers and hydrofluorethers are shown to possess a large absorption in the IR window due to (i) the C─O bonds are very polar, (ii) the C-O stretches fall within the IR window and have large IR intensity due to their polarity, and (iii) the IR intensity for C-F stretches in which the fluorine atom is bonded to the carbon that is bonded to the oxygen atom is enhanced due to a larger C─F bond polarity. Lengthening the carbon chain leads to a larger overall absorption in the IR window, though the IR intensity per bond is smaller. Finally, for a class of partially fluorinated compounds with a set number of electronegative atoms, the overall absorption in the IR window can vary significantly, as much as a factor of 2, depending on how the fluorine atoms are distributed within the molecule. PMID:20439762

Stimuli-responsive nanomaterials for therapeutic protein delivery.

Science.gov (United States)

Lu, Yue; Sun, Wujin; Gu, Zhen

2014-11-28

Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Therapeutic approaches for celiac disease

Science.gov (United States)

Plugis, Nicholas M.; Khosla, Chaitan

2015-01-01

Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

Environmental strategy

DEFF Research Database (Denmark)

Zabkar, Vesna; Cater, Tomaz; Bajde, Domen

2013-01-01

perspective, appropriate environmental strategies in compliance with environmental requirements aim at building competitive advantages through sustainable development. There is no universal “green” strategy that would be appropriate for each company, regardless of its market requirements and competitive......Environmental issues and the inclusion of environmental strategies in strategic thinking is an interesting subject of investigation. In general, managerial practices organized along ecologically sound principles contribute to a more environmentally sustainable global economy. From the managerial...

OLD AND NEW ECONOMIC GLOBALIZATION

OpenAIRE

Elena MĂRGULESCU

2015-01-01

The retrospective of the theoretical approaches of the phenomenon of economic globalization in the last three decades emphasizes the movement of attention from the globalization of markets, from the'80s, to the globalization of production and services in the current decade. This trend is essentially the result of implementing new strategies by multinational and transnational companies. We try in this context to draw a line between the "globalization of markets" and the "globalization of produ...

Diagnostic and therapeutic impact of MR enterography in Crohn's disease

Energy Technology Data Exchange (ETDEWEB)

Hafeez, R. [Department of Surgery, University College London Hospitals, NW1 2BU (United Kingdom); Punwani, S. [Centre for Medical Imaging, University College London (United Kingdom); Department of Specialist X-Ray, University College London Hospitals, NW1 2BU (United Kingdom); Boulos, P. [Department of Surgery, University College London Hospitals, NW1 2BU (United Kingdom); Bloom, S.; McCartney, S. [Department of Gastroenterology, University College London Hospitals, NW1 2BU (United Kingdom); Halligan, S. [Centre for Medical Imaging, University College London (United Kingdom); Department of Specialist X-Ray, University College London Hospitals, NW1 2BU (United Kingdom); Taylor, S.A., E-mail: csytaylor@yahoo.co.uk [Centre for Medical Imaging, University College London (United Kingdom); Department of Specialist X-Ray, University College London Hospitals, NW1 2BU (United Kingdom)

2011-12-15

Aim: To assess the impact of magnetic resonance enterography (MRE) on clinician diagnostic confidence and therapeutic strategy in patients under investigation for small bowel Crohn's disease. Material and methods: Gastroenterologists completed a proforma before and following MRE in 51 patients (mean age 35 years, 26 female) under investigation for small bowel Crohn's disease, indicating percentage confidence for presence/absence of small bowel involvement. In suspected disease, diagnostic confidence (using a scoring system from 1 = no to 6 = yes) was scored for subcategories: extent >30 cm (DE), terminal ileum (lTI), jejunal (JD), colonic disease (CoD), strictures (ST), activity (AD), extraluminal complications (EL), and surgical need (NS). Therapeutic strategy was recorded. Patients were divided into three groups: 1 = suspected disease, MRE normal (n = 15); 2 = suspected disease, MRE abnormal (n = 30); 3 = no suspected disease, MRE normal (n = 6). Binomial exact and paired t-tests were use to compare confidence pre and post-MRE. Results: Mean percentage confidence for the presence/absence of small bowel disease increased from 62 to 84% (p = 0.003), 87 to 98% (p = 0.0001), and 83 to 98% (p = 0.005) after MRE for groups 1, 2, and 3, respectively. In suspected disease, confidence changed significantly for all of the subcategories (p < 0.001) except EL in group 1. The percentage of patients with a confidence change ranged from 40% (CoD) to 87% (lTI; group 1) and from 7% (EL) to 93% (DE; group 2). Therapeutic strategy changed in 31/51 (61%, 95% CI 47-74%), 14 with a reduction in planned therapy and 17 with an increase. Conclusion: MRE had a positive diagnostic impact in patients under investigation for small bowel Crohn's disease and this influenced therapeutic strategy in 61% of the patients.

Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

Science.gov (United States)

Sambola, A; Ferreira-González, I; Angel, J; Alfonso, F; Maristany, J; Rodríguez, O; Bueno, H; López-Minguez, J R; Zueco, J; Fernández-Avilés, F; San Román, A; Prendergast, B; Mainar, V; García-Dorado, D; Tornos, P

2009-09-01

To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. A prospective multicentre registry. In hospital, after discharge and follow-up by telephone call. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

Nuclear power development: global challenges and strategies

International Nuclear Information System (INIS)

Mourogov, Victor M.; )

1997-01-01

This article highlights key factors that will determine today and tomorrow's optimal energy strategies. It addresses methods to utilize the high potential energy content of uranium. Plutonium used as fuel in a nuclear reactors is discussed as is the future potential of a thorium fuel cycle. Various strategies to increase the economic viability of nuclear power are brought out. Technological means to further minimize environmental impacts and to enhance safety are covered as they are a major factor in public acceptance. Also covered are advances anticipated by mid-century in nuclear reactor and fuel cycle technologies

Nanoparticles for the delivery of therapeutic antibodies: Dogma or promising strategy?

Science.gov (United States)

Sousa, Flávia; Castro, Pedro; Fonte, Pedro; Kennedy, Patrick J; Neves-Petersen, Maria Teresa; Sarmento, Bruno

2017-10-01

Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy. Another disadvantage inherent to antibody-based therapy is the limited stability of antibodies and the low level of tissue penetration. The use of nanoparticles as delivery systems for antibodies allows for a reduction in antibody dosing and may represent a suitable alternative to increase antibody stability Areas covered: We discuss different nanocarriers intended for the delivery of antibodies as well as the corresponding encapsulation methods. Recent developments in antibody nanoencapsulation, particularly the possible toxicity issues that may arise from entrapment of antibodies into nanocarriers, are also assessed. In addition, this review will discuss the alterations in antibody structure and bioactivity that occur with nanoencapsulation. Expert opinion: Nanocarriers can protect antibodies from degradation, ensuring superior bioavailability. Encapsulation of therapeutic antibodies may offer some advantages, including potential targeting, reduced immunogenicity and controlled release. Furthermore, antibody nanoencapsulation may aid in the incorporation of the antibodies into the cells, if intracellular components (e.g. intracellular enzymes, oncogenic proteins, transcription factors) are to be targeted.

Management strategies for coral reefs and people under global environmental change: 25 years of scientific research.

Science.gov (United States)

Comte, Adrien; Pendleton, Linwood H

2018-03-01

Coral reef ecosystems and the people who depend on them are increasingly exposed to the adverse effects of global environmental change (GEC), including increases in sea-surface temperature and ocean acidification. Managers and decision-makers need a better understanding of the options available for action in the face of these changes. We refine a typology of actions developed by Gattuso et al. (2015) that could serve in prioritizing strategies to deal with the impacts of GEC on reefs and people. Using the typology we refined, we investigate the scientific effort devoted to four types of management strategies: mitigate, protect, repair, adapt that we tie to the components of the chain of impact they affect: ecological vulnerability or social vulnerability. A systematic literature review is used to investigate quantitatively how scientific effort over the past 25 years is responding to the challenge posed by GEC on coral reefs and to identify gaps in research. A growing literature has focused on these impacts and on management strategies to sustain coral reef social-ecological systems. We identify 767 peer reviewed articles published between 1990 and 2016 that address coral reef management in the context of GEC. The rate of publication of such studies has increased over the years, following the general trend in climate research. The literature focuses on protect strategies the most, followed by mitigate and adapt strategies, and finally repair strategies. Developed countries, particularly Australia and the United States, are over-represented as authors and locations of case studies across all types of management strategies. Authors affiliated in developed countries play a major role in investigating case studies across the globe. The majority of articles focus on only one of the four categories of actions. A gap analysis reveals three directions for future research: (1) more research is needed in South-East Asia and other developing countries where the impacts of

Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

International Nuclear Information System (INIS)

Motoo, Yoshiharu; Shimasaki, Takeo; Ishigaki, Yasuhito; Nakajima, Hideo; Kawakami, Kazuyuki; Minamoto, Toshinari

2011-01-01

Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation

Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

Energy Technology Data Exchange (ETDEWEB)

Motoo, Yoshiharu, E-mail: motoo@kanazawa-med.ac.jp [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Shimasaki, Takeo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan); Ishigaki, Yasuhito [Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Nakajima, Hideo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Kawakami, Kazuyuki; Minamoto, Toshinari [Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan)

2011-01-24

Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

Directory of Open Access Journals (Sweden)

Toshinari Minamoto

2011-01-01

Full Text Available Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer. We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

Managing CSR Globally and Locally

DEFF Research Database (Denmark)

L. Brown, Dana; Knudsen, Jette Steen

Corporate Responsibility (CR) is today an essential component of corporate global strategy. CR can bolster the institutional context for market expansion (Porter and Kramer 2006); fill institutional voids (Tarun, et.al. 2005); or facilitate market entry as a component of non-market strategy (Baron...... 2006). Yet, in fulfilling these functions, CR may need to be highly sensitive to local contexts. How can transnational firms organize CR so as to maximize efficiencies from globalization and to minimize the fragmentation of corporate organizational cultures? Bartlett and Ghoshal (1989) provide...... a framework for analyzing the way that corporations coordinate global and local functions. We build on this framework in a case study of Novo Nordisk and its approach to determining global and local CR policies and procedures with regard to its China and United States subsidiaries. Our findings suggest...

Provincial Globalization The Local Struggle of Place-Making

Directory of Open Access Journals (Sweden)

Magnus Andersson

2010-06-01

Full Text Available This paper focuses on the global presence in the local processes of place-making in a rural area in Sweden. As a result of increased competition – fueled by a reor-ganization of global capitalism – between places, symbolic strategies (i.e. place marketing and place branding have become a central dimension of both urban and rural governance. As a consequent, places – while still being sites for the residents’ day-to-day life – are being turned into commodities in the market of potential investors and tourists to a great extent. Subsequently, this paper deals with how this global agenda affects a rural municipality in the Swedish countryside suffering from depopulation. The paper confirms earlier statements (Woods 2007 that globalization processes should not be considered as external forces reshaping and homogenizing rural villages; rather, globalization processes are locally nego-tiated. This, however, does not mean globalization has no impact on rural places. In these negotiation processes global and local virtues are intertwined but not evenly. In some municipal strategies, the impact of global discourses is more ex-plicit, for example, policy-makers accept and incorporate strategies of place branding and policy networks while they neglect other aspects of a relatively standardized “place marketing tool kit”. Furthermore, the study shows that rural residents, also, consider the village and its global future carefully but differently from the policy-makers. The residents dislike expressions of urbanity and advocate a general small-scaleness as a strategy for the future.

Pathways to Global Markets

DEFF Research Database (Denmark)

Smith, David E.; Mitry, Darryl J.

2011-01-01

. An important case study is McDonald‘s corporation, the world‘s largest fast food restaurant chain. This company has employed divergent marketing and economic strategies in both domestic and the international markets to become a leader in the global marketplace. An overview of the company‘s background......, organizational structures, mission and vision illustrate McDonald‘s strategic focus on its proactive evolution from a small drive-through operation to a global fast-food giant. The strategy is based on its ability to adapt to the cultural differences of the markets that McDonald‘s serves while preserving its...

Therapeutic intervention in violence against women in Colombia

Directory of Open Access Journals (Sweden)

Lina María Martínez González

2018-01-01

Full Text Available The article presents some reflections regarding the unspecified place of therapeutic intervention in the Colombian State’s strategies to address violence against women in the context of couple relationships. It focuses on professional intervention, concretely, therapeutic intervention, and states that despite its significant role in the potential transformation of the imaginaries and subjectivities that support that violence, this type of intervention occupies an unspecified place in the measures stipulated by the law, as well as in Colombian public policies aimed at countering that violence. The article also highlights some of the perspectives that therapists consider useful in the construction of non-violent functional conditions for couples.

A strategy for global environmental education at the university

International Nuclear Information System (INIS)

Hussain, S.T.; Hayes, R.L.

1993-01-01

The Earth's environment is a dynamic system that is affected both by natural phenomena and by human activity. The changes occurring in the global environment are bound to have serious consequences for all its inhabitants. Therefore, the world is rapidly becoming interdependent. Multidisciplinary scientific efforts must be directed toward understanding these global environmental changes. These efforts will require sufficient funds to attract scientists into global environmental research and to disseminate new knowledge to future scholars and to the general public alike. The federal government has a definite role to play in this effort and should allocate sufficient funds to initiate and sustain these programs. Unfortunately, such funds are not currently budgeted. The academic department, as the basic structural and functional unit of the American university system, is most appropriate to ensure environmental educational goals. The authors propose the establishment of a novel Department of Global Environment at every university. That department must be multidisciplinary in nature and must accumulate a critical mass of scholars from all relevant traditional disciplines in the arts and sciences to generate knowledge, to educate students, and to provide advisory services to policy makers. The study product of this department should receive a broad-based education and should emerge as an informed individual who possesses sufficient skills to achieve sustainable communities. That student should also be equipped to assume leadership and to formulate policy about global environmental issues. The investment in education may well be the only way to secure a future for humanity and for the natural world as we now know it

[Advances in Neurological Therapeutics for Friedreich Ataxia and Machado-Joseph Disease].

Science.gov (United States)

Yabe, Ichiro; Sasaki, Hidenao

2017-08-01

We reviewed advances in therapeutics for both Friedreich ataxia and Machado-Joseph disease. Various clinical trials have been carried out, mainly for Friedreich ataxia; however, the therapeutic reports from these trials have not provided much evidence for success. Some interesting clinical trials have been reported, and further developments are expected. Regenerative therapy using umbilical cord mesenchymal stem cells and a therapeutic study investigating a new pathomechanism in animal and/or cell culture studies were reported. We expect that these results will translate to therapeutic strategies for patients with these disorders. In addition, biomarkers play an important role when novel treatments are discovered and clinical trials are performed: hence at present, a number of biomarkers such as gait analysis by triaxial accelerometers and prism adaptation of hand-reaching movements, are being examined.

Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

Directory of Open Access Journals (Sweden)

Kunio Miyake

2012-04-01

Full Text Available The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.

GAR Global Risk Assessment

Science.gov (United States)

Maskrey, Andrew; Safaie, Sahar

2015-04-01

Disaster risk management strategies, policies and actions need to be based on evidence of current disaster loss and risk patterns, past trends and future projections, and underlying risk factors. Faced with competing demands for resources, at any level it is only possible to priorities a range of disaster risk management strategies and investments with adequate understanding of realised losses, current and future risk levels and impacts on economic growth and social wellbeing as well as cost and impact of the strategy. The mapping and understanding of the global risk landscape has been greatly enhanced by the latest iteration of the GAR Global Risk Assessment and the objective of this submission is to present the GAR global risk assessment which contributed to Global Assessment Report (GAR) 2015. This initiative which has been led by UNISDR, was conducted by a consortium of technical institutions from around the world and has covered earthquake, cyclone, riverine flood, and tsunami probabilistic risk for all countries of the world. In addition, the risks associated with volcanic ash in the Asia-Pacific region, drought in various countries in sub-Saharan Africa and climate change in a number of countries have been calculated. The presentation will share thee results as well as the experience including the challenges faced in technical elements as well as the process and recommendations for the future of such endeavour.

Global Obesity Study on Drivers for Weight Reduction Strategies

Directory of Open Access Journals (Sweden)

Carola Grebitus

2015-01-01

Full Text Available Objective: To assess factors determining the reaction of individuals to the threats of overweight and obesity and to examine the interdependencies between weight-reducing strategies. Methods: Cross-country survey covering 19 countries and 13,155 interviews. Data were analysed using a bivariate probit model that allows simultaneously analysing two weight-reducing strategies. Results: Results show that weight-reducing strategies chosen are not independent from each other. Findings also reveal that different strategies are chosen by different population segments. Women are more likely to change their dietary patterns and less likely to become physically active after surpassing a weight threshold. In addition, the probability of a dietary change in case of overweight differs considerably between countries. The study also reveals that attitudes are an important factor for the strategy choice. Conclusions: It is vital for public health policies to understand determinants of citizens' engagement in weight reduction strategies once a certain threshold is reached. Thus, results can support the design of public health campaigns and programmes that aim to change community or national health behaviour trends taking into account, e.g., national differences.

Therapeutic drug monitoring of amlodipine and the Z-FHL/HHL ratio ...

African Journals Online (AJOL)

Globally, high blood pressure (BP) is the leading single risk factor for ... concentrations and clinical effect or toxicity and those with a narrow therapeutic ..... The pharmacokinetics of amlodipine in healthy volunteers after. 120 ... revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS).

The role of media in scheduling strategies in Sergipe in the mobilization of the global-local dialectics from a concrete situation: Olympics/2012

Directory of Open Access Journals (Sweden)

Cristiano Mezzaroba

2015-05-01

Full Text Available With all the mega sporting events that are happening in Brazil (The 2007 Pan-American Games, The 2013 Confederations Cup, The 2014 World Cup and the 2016 Olympic/Paralympic Games it is possible to visualize a profitable and instigator moment for researches around this topic, concentrating our attention at the 2012 London Olympic Games. The exaltation of the sport phenomenon brought, in this research, the multiple sides through which the media can present itself and join itself with (regarding economy, culture, politics, education etc.. Our objective was to analyze how the media in the state of Sergipe anticipated and gave visibility to the 2012 Olympic Games, building a “sports-media scheduling” strategy, from the mobilization of the global-local dialectic. Characterized as a qualitative study, which has a descriptive-exploratory approach, this research was developed in three areas: print media, digital media and broadcast media – which have highlighted the low effectiveness of the scheduling strategy and the global-local dialectic strategy, whether because of amateurism in journalistic entities, or because of lack of interest, since there were no athletes from Sergipe in the competition.

A brief multi-disciplinary review on antimicrobial resistance in medicine and its linkage to the global environmental microbiota

Directory of Open Access Journals (Sweden)

Leon eCantas

2013-05-01

Full Text Available The discovery and introduction of antimicrobial agents to clinical medicine was one of the greatest medical triumphs of the 20th century that revolutionized the treatment of bacterial infections. However, the gradual emergence of populations of antimicrobial-resistant pathogenic bacteria resulting from use, misuse and abuse of antimicrobials has today become a major global health concern. Antimicrobial resistance genes have been suggested to originate from environmental bacteria, as clinically relevant resistance genes have been detected on the chromosome of environmental bacteria. As only a few new antimicrobials have been developed in the last decade, the further evolution of resistance poses a serious threat to public health. Urgent measures are required not only to minimize the use of antimicrobials for prophylactic and therapeutic purposes but also to look for alternative strategies for the control of bacterial infections. This review examines the global picture of antibacterial resistance, factors that favor its spread, strategies and limitations for its control and the need for continuous training of all stake-holders i.e. medical, veterinary, public health and other relevant professionals as well as human consumers of antibiotic drugs, in the appropriate use of antimicrobials.

A brief multi-disciplinary review on antimicrobial resistance in medicine and its linkage to the global environmental microbiota

Science.gov (United States)

Cantas, L.; Shah, Syed Q. A.; Cavaco, L. M.; Manaia, C. M.; Walsh, F.; Popowska, M.; Garelick, H.; Bürgmann, H.; Sørum, H.

2013-01-01

The discovery and introduction of antimicrobial agents to clinical medicine was one of the greatest medical triumphs of the 20th century that revolutionized the treatment of bacterial infections. However, the gradual emergence of populations of antimicrobial-resistant pathogenic bacteria resulting from use, misuse, and abuse of antimicrobials has today become a major global health concern. Antimicrobial resistance (AMR) genes have been suggested to originate from environmental bacteria, as clinically relevant resistance genes have been detected on the chromosome of environmental bacteria. As only a few new antimicrobials have been developed in the last decade, the further evolution of resistance poses a serious threat to public health. Urgent measures are required not only to minimize the use of antimicrobials for prophylactic and therapeutic purposes but also to look for alternative strategies for the control of bacterial infections. This review examines the global picture of antimicrobial resistance, factors that favor its spread, strategies, and limitations for its control and the need for continuous training of all stake-holders i.e., medical, veterinary, public health, and other relevant professionals as well as human consumers, in the appropriate use of antimicrobial drugs. PMID:23675371

Climate change - global warming

International Nuclear Information System (INIS)

Ciconkov, Risto

2001-01-01

An explanation about climate, weather, climate changes. What is a greenhouse effect, i.e. global warming and reasons which contribute to this effect. Greenhouse gases (GHG) and GWP (Global Warming Potential) as a factor for estimating their influence on the greenhouse effect. Indicators of the climate changes in the previous period by known international institutions, higher concentrations of global average temperature. Projecting of likely scenarios for the future climate changes and consequences of them on the environment and human activities: industry, energy, agriculture, water resources. The main points of the Kyoto Protocol and problems in its realization. The need of preparing a country strategy concerning the acts of the Kyoto Protocol, suggestions which could contribute in the preparation of the strategy. A special attention is pointed to the energy, its resources, the structure of energy consumption and the energy efficiency. (Author)

PSA-selective activation of cytotoxic human serine proteases within the tumor microenvironment as a therapeutic strategy to target prostate cancer.

Science.gov (United States)

Rogers, Oliver C; Anthony, Lizamma; Rosen, D Marc; Brennen, W Nathaniel; Denmeade, Samuel R

2018-04-27

Prostate cancer is the most diagnosed malignancy and the second leading cause of cancer-related death in American men. While localized therapy is highly curative, treatments for metastatic prostate cancer are largely palliative. Thus, new innovative therapies are needed to target metastatic tumors. Prostate-Specific Antigen (PSA) is a chymotrypsin-like protease with a unique substrate specificity that is secreted by both normal and malignant prostate epithelial cells. Previous studies demonstrated the presence of high levels (μM-mM) of enzymatically active PSA is present in the extracellular fluid of the prostate cancer microenvironment. Because of this, PSA is an attractive target for a protease activated pro-toxin therapeutic strategy. Because prostate cancers typically grow very slowly, a strategy employing a proliferation-independent cytotoxic payload is preferred. Recently, it was shown that the human protease Granzyme B (GZMB), at low micromolar concentrations in the extracellular space, can cleave an array of extracellular matrix (ECM) proteins thus perturbing cell growth, signaling, motility, and integrity. It is also well established that other human proteases such as trypsin can induce similar effects. Because both enzymes require N-terminal proteolytic activation, we propose to convert these proteins into PSA-activated cytotoxins. In this study, we examine the enzymatic and cell targeting parameters of these PSA-activated cytotoxic serine proteases. These pro-enzymes were activated robustly by PSA and induced ECM damage that led to the death of prostate cancer cells in vitro thus supporting the potential use of this strategy as means to target metastatic prostate cancers.

[Therapeutic strategies. Evolution and current status of the European Guidelines on Cardiovascular disease prevention].

Science.gov (United States)

Guijarro, Carlos; García-Díaz, Juan de Dios

2013-01-01

The European Guidelines on Dyslipidaemias (2011) and Cardiovascular Prevention (2012) have incorporated important changes. Firstly, it highlights the identification of a group of "very high risk" patients: patients with atherosclerotic disease in any vascular area, diabetes with associated risk factors, advanced chronic renal failure, or a SCORE estimate >10%. Patients with diabetes and no other risk factors, moderate renal failure, severe hypertension, genetic dyslipidaemias, or a SCORE estimate 5-10%, are considered as "high risk". The HDL cholesterol and triglycerides levels are considered as modulators of risks, but not therapeutic objectives per se. The therapeutic objectives are set at LDL cholesterol levels < 70 mg/dl (or at least a reduction of at least 50%) for patients at very high risk, and an LDL < 100 mg/dl for high risk patients. As well as the changes in lifestyle, pharmacological treatment with statins is the focal point of lipid lowering treatments. Other pharmacological options may be considered if the treatment with the maximum tolerable doses of statins do not achieve the therapeutic objectives. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

[The relationship of therapeutic alliance with a symptom reduction and treatment satisfaction in the therapeutic treatment of children and adolescents with ADHD and/or conduct disorder].

Science.gov (United States)

Kinnen, Claudia; Döpfner, Manfred

2013-03-01

The relationship of therapeutic alliance and outcome is investigated in outpatient behavior therapies of children and adolescents with externalizing problem behavior. Therapist-patient and therapist-parent relationships were evaluated twice during the therapies of N = 53 patients using German relationship questionnaires adapted for use in child and adolescent psychotherapy (BeKi). Pre-post symptom reduction in parent and patient rating, treatment satisfaction as rated by therapist, parent and patient as well as child's global functioning by therapist rating are examined as outcome parameters. The correlations between therapeutic alliance and symptom reduction vary depending on the rater between absence of correlation and high correlation (maximum: r = .53). Most correlations are low to moderate. These results are comparable to those reported in recently published meta-analyses and studies of adult psychotherapy. There are moderate correlations between therapist-patient and therapist-parent alliance and treatment satisfaction and low to moderate correlations with improvements in the children's global functioning. Only few studies have focused on treatment satisfaction and improvements in children's global functioning as outcome variables. Besides symptom reduction, these two variables also correlate significantly with the therapist-patient and therapist-parent alliance. Because correlations highly depend on the rater, future studies should consider the various perspectives.

Positioning in the Global Value Chain as a Sustainable Strategy: A Case Study in a Mature Industry

Directory of Open Access Journals (Sweden)

Jose Albors-Garrigos

2014-06-01

Full Text Available As a result of the development of new industrialized countries, such as Brazil, China and other Southern Asian economies, as well as a globalized economy, traditional competitive paradigms based on advantages associated with costs and quality efficiencies or even innovation are no longer sufficient. These previous classical paradigms related competitiveness either to costs or technology innovation and the resources of industry incumbents. However, the combination of adequate knowledge and relationship management with marketing efforts brings forth a reconsideration of the present competitive models that go beyond those analyses from the point of view of global value chains. The objective of this investigation will analyze the governance structure of the territorial value chain in the Spanish and Italian ceramic tile industry, through the understanding of the previous and current roles of several industries involved in the value creation system. By way of both a case study and quantitative methodology approach, we will explore the paradigm change where traditional chain actors are losing their grip on their contribution to the territorial value creation system as new actors appear with a more stable status. The article concludes that proper positioning in the global value chain is a key strategy for the sustainability of the involved firms, especially Small and Medium Enterprises (SME.

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

Science.gov (United States)

Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

2015-07-01

Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

Determinants of immunogenic response to protein therapeutics.

Science.gov (United States)

Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

2012-09-01

Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

[The development of therapeutic vaccine for hepatitis C virus].

Science.gov (United States)

Kimura, Kiminori; Kohara, Michinori

2012-10-01

Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.

Local industry in global networks : changing competitiveness, corporate strategies and pathways of development in Singapore and Malaysia's garment industry

OpenAIRE

Smakman, Floortje

2004-01-01

The garment industry in Singapore and Malaysia has been incorporated into global production networks and commodity chains - driven by large US and European garment companies - since the 1960s and 1970s respectively. The industry was an intricate part of the export led industrialisation strategies adopted by both countries. However, since incorporation, changing competitiveness due to both international, regional end local pressures, has meant local garment firms have had to implement a range ...

Fowl adenovirus-induced diseases and strategies for their control - a review on the current global situation.

Science.gov (United States)

Schachner, Anna; Matos, Miguel; Grafl, Beatrice; Hess, Michael

2018-04-01

The stand-alone pathogenicity of fowl adenoviruses (FAdVs) had long been disputed, given the ubiquity of the viruses versus sporadic outbreaks, and variation between experimental studies. However, a globally emerging trend of FAdV-associated diseases has marked the past two decades, with hepatitis-hydropericardium syndrome mainly in Asia besides Arabian and Latin American countries, and geographically more disseminated outbreaks of inclusion body hepatitis. Finally, the appearance of FAdV-induced gizzard erosion (AGE) in Asia and Europe completed the range of diseases. Epidemiological studies confirmed serotype FAdV-4 as agent of hepatitis-hydropericardium syndrome, whereas inclusion body hepatitis is related to FAdV-2, -8a, -8b and -11. Members of the biologically more distant serotype FAdV-1 induce AGE. Urged by increasing problems in the field, numerous pathogenicity studies with FAdVs from outbreaks substantiated the primary aetiologic role of particular strains for distinct clinical conditions. Developments in the poultry industry towards highly specialized genetic breeds and rigorous biosecurity additionally contribute to the growing incidence of FAdV-related diseases. Confirming field observations, recent studies connected a higher susceptibility of broilers with their distinct physiology, implying the choice of bird type as a factor to be considered in infection studies. Furthermore, elevated biosecurity standards have generated immunologically naïve breeding stocks, putting broilers at risk in face of vertical FAdV transmission. Therefore, future prevention strategies should include adequate antibodies in breeders prior to production and - if necessary - vaccination, in order to protect progenies. This review aims to deliver a detailed overview on the current global situation about FAdV-induced diseases, their reproduction in vivo and vaccination strategies.

Conclusion: imaging in strategy of endocrine diagnosis and therapeutics

International Nuclear Information System (INIS)

Mornex, R.

1995-01-01

Images in medicine have to help the doctor in a diagnostic or therapeutic aim. The choice must be made in function of pathology or organ as known (it is not necessary to ask for a computed tomography where we know that only an echography can give the answer to the question we ask ), the criteria must stay the best performance for the cheapest price, but the quality of interpretation is a more important thing. It is important to avoid a lot of examinations which do not give better informations but are heavy to endure for the patients. In conclusion, the aim of this kind of proceedings is to assure to the patients who come confidently to us, the best service at the less constraints price without forgetting that a conclusion depends on a given methodological situation and reminding of beside machines we have not to forget the men

Medicalization of global health 2: The medicalization of global mental health.

Science.gov (United States)

Clark, Jocalyn

2014-01-01

Once an orphan field, 'global mental health' now has wide acknowledgement and prominence on the global health agenda. Increased recognition draws needed attention to individual suffering and the population impacts, but medicalizing global mental health produces a narrow view of the problems and solutions. Early framing by advocates of the global mental health problem emphasised biological disease, linked psychiatry with neurology, and reinforced categories of mental health disorders. Universality of biomedical concepts across culture is assumed in the globalisation of mental health but is strongly disputed by transcultural psychiatrists and anthropologists. Global mental health movement priorities take an individualised view, emphasising treatment and scale-up and neglecting social and structural determinants of health. To meet international targets and address the problem's broad social and cultural dimensions, the global mental health movement and advocates must develop more comprehensive strategies and include more diverse perspectives.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.

Science.gov (United States)

Vogelmeier, Claus F; Criner, Gerard J; Martinez, Fernando J; Anzueto, Antonio; Barnes, Peter J; Bourbeau, Jean; Celli, Bartolome R; Chen, Rongchang; Decramer, Marc; Fabbri, Leonardo M; Frith, Peter; Halpin, David M G; López Varela, M Victorina; Nishimura, Masaharu; Roche, Nicolas; Rodriguez-Roisin, Roberto; Sin, Don D; Singh, Dave; Stockley, Robert; Vestbo, Jørgen; Wedzicha, Jadwiga A; Agusti, Alvar

2017-03-01

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: 1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; 2) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; 3) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; 4) nonpharmacologic therapies are comprehensively presented and; 5) the importance of comorbid conditions in managing COPD is reviewed. Copyright ©2017 the American Thoracic Society. Published with permission from the American Thoracic Society. Design and branding are copyright ©ERS 2017.

China's Maritime Strategy Peaceful Rise

National Research Council Canada - National Science Library

Horrell, Steven L

2008-01-01

.... As a result the global maritime environment will be key to this continental power's continued growth As a subset of maritime strategy China's naval strategy and accompanying People's Liberation Army...

Global Sourcing Flexibility

DEFF Research Database (Denmark)

Ørberg Jensen, Peter D.; Petersen, Bent

2013-01-01

the higher costs (but decreased risk for value chain disruption) embedded in a more flexible global sourcing model that allows the firm to replicate and/or relocate activities across multiple locations. We develop a model and propositions on facilitating and constraining conditions of global sourcing...... sourcing flexibility. Here we draw on prior research in the fields of organizational flexibility, international business and global sourcing as well as case examples and secondary studies. In the second part of the paper, we discuss the implications of global sourcing flexibility for firm strategy...... and operations against the backdrop of the theory-based definition of the construct. We discuss in particular the importance of global sourcing flexibility for operational performance stability, and the trade-off between specialization benefits, emerging from location and service provider specialization, versus...

Albedo control as an effective strategy to tackle Global Warming: A case study

International Nuclear Information System (INIS)

Cotana, Franco; Rossi, Federico; Filipponi, Mirko; Coccia, Valentina; Pisello, Anna Laura; Bonamente, Emanuele; Petrozzi, Alessandro; Cavalaglio, Gianluca

2014-01-01

Highlights: • We modeled the energy exchanges for the system Earth–Atmosphere–Outer space. • We proposed a method quantifying the CO 2eq offset potential of high-albedo surfaces. • We presented the application of the method to a case study in Tunis. • The CO 2eq offsetting potential depends on the geometry-orientation of the surfaces. • An economic value was attributed to the Albedo control compensation mechanism. - Abstract: Recent research developments focused on Climate Change issue aimed at achieving Kyoto targets. In this context, an innovative methodology (officially recognized by WEC in 2009) is proposed to mitigate Global Warming by artificially enhancing earth’s Albedo. Such a methodology allows to quantify the maximum environmental benefit achievable through the installation of Albedo control technologies, as a function of the geographical features of the installation site, local meteorological conditions, radiative properties, tilt angle, and orientation of the surfaces. This benefit is directly quantified in terms of CO 2eq offset. Albedo control can be an effective mitigation strategy by means of three synergistic effects: a direct contribution towards Global Warming mitigation produced by an enhanced reflection to the space of the shortwave incident radiation; the indirect contribution from energy saving in buildings with high Albedo envelopes; the indirect contribution from the mitigation of Urban Heat Island phenomenon. Since the effectiveness of Albedo control is mostly relevant in Mediterranean area, for both climate conditions and historical-architectural heritage, this work presents procedures and findings of the ABCD project (Albedo, Building green, Control of Global Warming and Desertification) concluded in 2012, funded by the Italian Ministry for the Environment. A description of the analytic model is also presented. The paper focuses on the application of the methodology to a Tunisian factory site, showing that approximately

A global strategy for the European PV industry

International Nuclear Information System (INIS)

Viaud, M.; Despotou, E.; Latour, M.; Hoffmann, W.; Macias, E.; Cameron, M.; Laborde, E.

2004-01-01

The objective was to develop a comprehensive strategy that answers to the need of today European PV industry. Namely: - Develop PV markets in Europe - Develop export markets. - Position the European PV industry within the European political environment and support the effort of national actors in their local objectives. This method lends itself to brainstorming to create actions and synergies, on order to achieve strategy objectives. The whole work is based on working groups clearly defined on the purpose, where all EPIA members are invited to participate. The overall first results are presented during the 19. EU PV Conference in Paris and EPIA will do recommendations on actions to be undertaken in the future. This strategy is co-financed by EPIA members and the 6. Framework Programme for research of the European Commission through the PV Catapult project. (authors)

Strategies for global monitoring of tropical forests

Science.gov (United States)

Raymond L. Czaplewski

1994-01-01

The Food and Agricultural Organization (FAO) of the United Nations is conducting a global assessment of tropical forest resources, which will be accomplished by mid-1992. This assessment requires, in part, estimates of the total area of tropical forest cover in 1990 and the rate of change in forest cover between 1980 and 1990. The following are described here: (1) the...

Novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy

Directory of Open Access Journals (Sweden)

Sampath P

2015-06-01

Full Text Available Padma Sampath, Steve H Thorne Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA Abstract: Results from randomized clinical trials over the last several years have finally begun to demonstrate the potential of oncolytic viral therapies to treat a variety of cancers. One reason for these successes has been the realization that this platform is most effective when considered primarily as an immunotherapy. Cancer immunotherapy has also made dramatic strides recently with antibodies capable of blocking immune checkpoint inhibitors and adoptive T-cell therapies, notably CAR T-cells, leading a panel of novel and highly clinically effective therapies. It is clear therefore that an understanding of how and when these complementary approaches can most effectively be combined offers the real hope of moving beyond simply treating the disease and toward starting to talk about curative therapies. In this review we discuss approaches to combining these therapeutic platforms, both through engineering the viral vectors to more beneficially interact with the host immune response during therapy, as well as through the direct combinations of different therapeutics. This primarily, but not exclusively focuses on strains of oncolytic vaccinia virus. Some of the results reported to date, primarily in pre-clinical models but also in early clinical trials, are dramatic and hold great promise for the future development of similar therapies and their translation into cancer therapies. Keywords: oncolytic virus, CAR T-cell, adoptive cell therapy, immune checkpoint inhibitor 

The Global ECT-MRI Research Collaboration (GEMRIC)

DEFF Research Database (Denmark)

Oltedal, Leif; Bartsch, Hauke; Sørhaug, Ole Johan Evjenth

2017-01-01

biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we...

[Osteoarthritis and patient therapeutic education, learning to move more].

Science.gov (United States)

Coudeyre, Emmanuel; Gay, Chloé; Bareyre, Loïc; Coste, Nicolas; Chérillat, Marie-Sophie

2016-01-01

As part of the prevention strategies offered to people with osteoarthritis, therapeutic education plays a key role. It seeks to help the patient become a player in their own care and focuses in particular on the factors influencing regular participation in suitable physical activity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Global Sales Training's Balancing Act

Science.gov (United States)

Boehle, Sarah

2010-01-01

A one-size-fits-all global sales strategy that fails to take into account the cultural, regulatory, geographic, and economic differences that exist across borders is a blueprint for failure. For training organizations tasked with educating globally dispersed sales forces, the challenge is adapting to these differences while simultaneously…

Managing Corporate Responsibility Globally and Locally

DEFF Research Database (Denmark)

Brown, Dana; Knudsen, Jette Steen

2012-01-01

Corporate Responsibility (CR) is today an essential component of corporate global strategy. CR can bolster the institutional context for market expansion fill institutional voids or facilitate market entry as a component of non-market strategy. Yet, in fulfilling these functions, CR may need...... to be highly sensitive to local contexts. How can transnational firms organize CR so as to maximize efficiencies from globalization and to minimize the fragmentation of corporate organizational cultures? provide a framework for analyzing the way that corporations coordinate global and local functions. We build...... on this framework in a case study of Novo Nordisk and its approach to determining global and local CR policies and procedures with regard to its China and US subsidiaries. Our findings suggest that it is important for companies to define a common set of organizational norms. In addition, CR need to be sensitive...

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination

Directory of Open Access Journals (Sweden)

Markus Haug

2018-04-01

Full Text Available Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

Molecular Targets in Alzheimer’s Disease: From Pathogenesis to Therapeutics

Directory of Open Access Journals (Sweden)

Xuan Cheng

2015-01-01

Full Text Available Alzheimer’s disease (AD is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.

Goals and strategies in the global control design of the OAJ Robotic Observatory

Science.gov (United States)

Yanes-Díaz, A.; Rueda-Teruel, S.; Antón, J. L.; Rueda-Teruel, F.; Moles, M.; Cenarro, A. J.; Marín-Franch, A.; Ederoclite, A.; Gruel, N.; Varela, J.; Cristóbal-Hornillos, D.; Chueca, S.; Díaz-Martín, M. C.; Guillén, L.; Luis-Simoes, R.; Maícas, N.; Lamadrid, J. L.; López-Sainz, A.; Hernández-Fuertes, J.; Valdivielso, L.; Mendes de Oliveira, C.; Penteado, P.; Schoenell, W.; Kanaan, A.

2012-09-01

There are many ways to solve the challenging problem of making a high performance robotic observatory from scratch. The Observatorio Astrofísico de Javalambre (OAJ) is a new astronomical facility located in the Sierra de Javalambre (Teruel, Spain) whose primary role will be to conduct all-sky astronomical surveys. The OAJ control system has been designed from a global point of view including astronomical subsystems as well as infrastructures and other facilities. Three main factors have been considered in the design of a global control system for the robotic OAJ: quality, reliability and efficiency. We propose CIA (Control Integrated Architecture) design and OEE (Overall Equipment Effectiveness) as a key performance indicator in order to improve operation processes, minimizing resources and obtaining high cost reduction whilst maintaining quality requirements. The OAJ subsystems considered for the control integrated architecture are the following: two wide-field telescopes and their instrumentation, active optics subsystems, facilities for sky quality monitoring (seeing, extinction, sky background, sky brightness, cloud distribution, meteorological station), domes and several infrastructure facilities such as water supply, glycol water, water treatment plant, air conditioning, compressed air, LN2 plant, illumination, surveillance, access control, fire suppression, electrical generators, electrical distribution, electrical consumption, communication network, Uninterruptible Power Supply and two main control rooms, one at the OAJ and the other remotely located in Teruel, 40km from the observatory, connected through a microwave radio-link. This paper presents the OAJ strategy in control design to achieve maximum quality efficiency for the observatory processes and operations, giving practical examples of our approach.

Intercultural Communication: A Key Element in Global Strategies.

Science.gov (United States)

Spinks, Nelda; Wells, Barron

1997-01-01

Cultural factors in global communication include differences in customs, space, dress, religion, class, work ethic, privacy, and other areas. Language differences in oral, written, and nonverbal communication as well as semantics also complicate intercultural communication. (SK)

[Pathogenetic and therapeutic aspects of secondary anorexia].

Science.gov (United States)

Laviano, A; Cascino, A; Muscaritoli, M; Rossi Fanelli, F

2000-01-01

Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.

Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide.

Science.gov (United States)

Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana

2013-11-01

Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

Pheromone Static Routing Strategy for Complex Networks

Science.gov (United States)

Hu, Mao-Bin; Henry, Y. K. Lau; Ling, Xiang; Jiang, Rui

2012-12-01

We adopt the concept of using pheromones to generate a set of static paths that can reach the performance of global dynamic routing strategy [Phys. Rev. E 81 (2010) 016113]. The path generation method consists of two stages. In the first stage, a pheromone is dropped to the nodes by packets forwarded according to the global dynamic routing strategy. In the second stage, pheromone static paths are generated according to the pheromone density. The output paths can greatly improve traffic systems' overall capacity on different network structures, including scale-free networks, small-world networks and random graphs. Because the paths are static, the system needs much less computational resources than the global dynamic routing strategy.

A dynamic routing strategy with limited buffer on scale-free network