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Sample records for global therapeutic strategy

  1. Global Strategy

    Li, Peter Ping

    2013-01-01

    Global strategy differs from domestic strategy in terms of content and process as well as context and structure. The content of global strategy can contain five key elements, while the process of global strategy can have six major stages. These are expounded below. Global strategy is influenced...... by rich and complementary local contexts with diverse resource pools and game rules at the national level to form a broad ecosystem at the global level. Further, global strategy dictates the interaction or balance between different entry strategies at the levels of internal and external networks....

  2. European strategy/global strategy

    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.)

  3. Therapeutic strategies in pulmonary hypertension

    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.

  4. [Therapeutic strategies against myasthenia gravis].

    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.

  5. Military Strategy of Global Jihad

    Zabel, Sarah E

    2007-01-01

    .... The 9/11 attacks set this plan in motion. In the years leading up to and following the 9/11 attacks, global jihadis have written copiously on their military strategy for creating an Islamic state...

  6. [Therapeutic strategy for different types of epicanthus].

    Gaofeng, Li; Jun, Tan; Zihan, Wu; Wei, Ding; Huawei, Ouyang; Fan, Zhang; Mingcan, Luo

    2015-11-01

    To explore the reasonable therapeutic strategy for different types of epicanthus. Patients with epicanthus were classificated according to the shape, extent and inner canthal distance and treated with different methods appropriately. Modified asymmetric Z plasty with two curve method was used in lower eyelid type epicanthus, inner canthus type epicanthus and severe upper eyelid type epicanthus. Moderate upper epicanthus underwent '-' shape method. Mild Upper epicanthus in two conditions which underwent nasal augumentation and double eyelid formation with normal inner canthal distance need no correction surgery. The other mild epicanthus underwent '-' shape method. A total of 66 cases underwent the classification and the appropriate treatment. All wounds healed well. During 3 to 12 months follow-up period, all epicanthus were corrected completely with natural contour and unconspicuous scars. All patients were satisfied with the results. Classification of epicanthus hosed on the shape, extent and inner canthal distance and correction with appropriate methods is a reasonable therapeutic strategy.

  7. Therapeutic strategies to improve control of hypertension.

    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.

  8. Therapeutic and prevention strategies against human enterovirus 71 infection

    Kok, Chee Choy

    2015-01-01

    Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved. PMID:25964873

  9. 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.

    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.

  10. Colorectal cancer: diagnostic and therapeutic strategies

    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)

  11. Hydrogels for central nervous system therapeutic strategies.

    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.

  12. Therapeutic Symptomatic Strategies in the Parasomnias.

    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.

  13. Global power: Markets and strategies

    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

  14. [Type 2 diabetes: what therapeutic strategy?].

    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

  15. Investigation of therapeutic strategy for acute empyema

    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)

  16. The Strategy - Ending Globalization Disorders

    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

  17. Strategi Pemasaran Global di Pasar Indonesia

    Freddy Simbolon

    2013-05-01

    Full Text Available Globalization is a new challenge for companies in the implementation of marketing strategy. Due to globalization, companies are required to compete with world class companies that have large capital and higher quality products. Indonesia currently becomes the market target for global companies to enjoy huge profits, while the Indonesian companies lost the competition. This study aims to obtain global marketing strategy for Indonesian companies in Indonesian market. Research method used is descriptive analisys. Merger between adaptation of marketing strategies and standard marketing strategy is appropriate strategy in Indonesian market.

  18. Towards new therapeutic strategies in chondrosarcoma

    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

  19. Therapeutic Strategy for Chronic Headache in Children

    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.

  20. Global strategies to prevent chronic diseases1

    Nicky

    leading global causes of death and disability, are ... global strategies for the prevention and control of chronic ... Preventing Chronic Diseases: A Vital Investment, will ..... Millennium Development Goals for Health In Europe and Central Asia.

  1. Inflammatory bowel disease: potential therapeutic strategies

    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...

  2. Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

    Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

    2017-01-01

    Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries

  3. Therapeutic strategies to fight HIV-1 latency: progress and challenges

    Manoto, Sello L

    2017-10-01

    Full Text Available —1112, 2017 Therapeutic strategies to fight HIV-1 latency: progress and challenges Sello Lebohang Manoto, Lebogang Thobakgale, Rudzani Malabi, Charles Maphanga, Saturnin Ombinda-Lemboumba, Patience Mthunzi-Kufa Abstract: The life...

  4. Myasthenia gravis: subgroup classification and therapeutic strategies.

    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.

  5. Therapeutic Strategies for Hereditary Kidney Cancer.

    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.

  6. Biliary parasites: diagnostic and therapeutic strategies.

    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.

  7. [Premenstrual dysphoric disorder: diagnosis and therapeutic strategy].

    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.

  8. Therapeutic strategies in the treatment of periodontitis

    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.

  9. Corporate Strategies in Global Investment Business

    Tetiana Frolova

    2012-02-01

    Full Text Available The article deals with topical issues of the development of corporate strategies for businesses. We proposed the classification and defined the ways to implement corporate strategies. We also analysed the current trends in the development of global corporate strategies mainly implemented through mergers and acquisitions.

  10. Military Strategy of Global Jihad

    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...

  11. A global strategy for labor.

    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.

  12. [The place of a new drug in the therapeutic strategy].

    Castaigne, A; Goehrs, J M; Ravoire, S

    A therapeutic strategy is a hierarchical set of appropriate measures to provide an answer to a pathological state. A drug is a part of this set (together with the diagnosis, the environment and the other medicinal interventions or not). A new drug's place in a therapeutic strategy can be evaluated according to one or several referential(s) when it (or they) exist, referentials which express the state of knowledge before launch of the new drug. The drug's profile (indication or contraindication, etc.), at the point when the marketing authorization is given, is purely theoretical. One must evaluate the real place of the drug under its real conditions of use (pragmatic trials, observable surveys). A new drugs' place in a therapeutic strategy can only be evaluated in the course of time unless a therapeutic revolution occurs.

  13. Ebola virus (EBOV) infection: Therapeutic strategies.

    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.

  14. Therapeutic Strategies and Intellectualism in On Anger by Seneca

    Rodrigo Sebastián Braicovich

    2015-08-01

    Full Text Available I try to show that a the treatise On Anger by Seneca includes not one but two therapeutic strategies designed to avoid anger and that b the second of these strategies –which has been neglected in the secondary literature– presents unsolvable problems when we contrast it with the Stoic theory of action, which is rooted in intellectualist premises.

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

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

    2013-05-01

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

  16. two strategies to be integrated into globalization

    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 ...

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

    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.

  18. Research Methodology in Global Strategy Research

    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....

  19. Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

    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.

  20. Cell-based therapeutic strategies for multiple sclerosis

    Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C

    2017-01-01

    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...

  1. [Global and national strategies against antibiotic resistance].

    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.

  2. National action strategy on global warming

    1990-11-01

    A document prepared by a committee of Canadian environmental ministries proposes a strategic framework for a national action plan concerning global warming. The strategy would be carried out jointly by governments and all other sectors of the economy, taking into account the present state of scientific knowledge on global warming. Within this framework, the governments in cooperation with interested parties would take certain measures in their respective areas of competence. The main recommendations of the document include the following. The action strategy should comprise 3 elements: limiting emissions of greenhouse gases; forecasting climatic changes which Canada could undergo due to global warming and preparing for such changes; and improving scientific knowledge and the capacity to predict climatic changes. Limitations on this strategy should take into account such matters as the interaction of greenhouse gases with other pollutants, the importance of the international context, the need to adapt to new discoveries, and the importance of regional differences. Implementation of the strategy should incorporate widespread consultation of all affected sectors, sustained work on establishing international conventions and protocols on reducing greenhouse gas emissions, objectives and schedules for such reductions, and stepwise actions to control emissions in order to enable an adequate evaluation of the consequences and effectiveness of such measures. 10 figs., 2 tabs

  3. Ford Motor Company's Global Electrification Strategy

    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...

  4. Global Cities and Multinational Enterprise Location Strategy

    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...

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

    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.

  6. Global warming: Towards a strategy for Ontario

    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

  7. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

    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.

  8. Therapeutic targeting strategies using endogenous cells and proteins.

    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.

  9. Base-of-the-pyramid global strategy

    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.

  10. Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

    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.

  11. Therapeutic strategies based on glucagon-like peptide 1

    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...

  12. Emerging Therapeutic Strategies for Targeting Chronic Myeloid Leukemia Stem Cells

    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.

  13. Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

    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

  14. Music as a Therapeutic Assistant: Strategy to Reduce Work Stress

    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.

  15. Therapeutic strategies for spinal muscular atrophy: SMN and beyond

    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.

  16. Targeting mitochondrial respiration as a therapeutic strategy for cervical cancer.

    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.

  17. Cell-based therapeutic strategies for multiple sclerosis.

    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.

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

    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.

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

    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.

  20. Postponement in logistics strategies of global supply chains

    Agnieszka Szmelter

    2015-12-01

    Full Text Available The paper aims to present postponement strategy as a crucial element of logistics strategies of today’s global supply chains. The article presents the history of postponement, characteristics of this concept, types of postponement and important information about its implementation in global supply chains. The paper also contains guidelines for future research on postponement concept.

  1. What are the Essential Success Strategies for Global CIOs?

    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.

  2. Global Supply-Chain Strategy And Global Competitiveness

    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 ...

  3. The Mutual Impact of Global Strategy and Organizational Learning

    Hotho, Jasper J.; Lyles, Marjorie A.; Easterby-Smith, Mark

    2015-01-01

    Despite the interest in issues of knowing and learning in the global strategy field, there has been limited mutual engagement and interaction between the fields of global strategy and organizational learning. The purpose of our article is to reflect on and articulate how the mutual exchange...... of ideas between these fields can be encouraged. To this end, we first conduct a review of the intersection of the fields of global strategy and organizational learning. We then present two recommendations regarding how the interaction between the two fields can be enhanced. Our first recommendation...... is for global strategy research to adopt a broader notion of organizational learning. Our second recommendation is for global strategy research to capitalize on its attention to context in order to inform and enhance organizational learning theory. We discuss the use of context in a number of common research...

  4. Singapore's Global Schoolhouse Strategy: Retreat or Recalibration?

    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…

  5. Strategies for mitigation of global warming

    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....

  6. Therapeutic strategies in an animal model of neurodegeneration

    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

  7. Toward an Integrative Model of Global Business Strategy

    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....

  8. The Military Strategy of Global Jihad

    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...

  9. Innovation Strategies for a Global Economy: Development ...

    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 ...

  10. Indications of hematopoietic stem cell transplantations and therapeutic strategies of accidental irradiations

    2003-01-01

    Produced by a group of experts, this document first discusses the issue of accidental irradiations in terms of medical management. They notably outline the peculiar characteristics of these irradiations with respect to therapeutic irradiations. They agreed on general principles regarding casualty sorting criteria and process, and their medical treatment (systematic hematopoiesis stimulation, allogeneic transplantation of hematopoietic stem cells). They discuss some practical aspects of these issues: casualty sorting within a therapeutic perspective (actions to be performed within 48 hours), therapeutic strategies (support therapy, use of cytokines, and therapy by hematopoietic stem cell transplant). They state a set of recommendations regarding the taking into care and diagnosis, therapeutic strategies, research perspectives, and teaching

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

    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.)

  12. Global gas strategies: a major player's perspective

    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)

  13. Strategies for global monitoring of tropical forests

    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...

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

    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.

  15. Nuclear power development: global challenges and strategies

    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

  16. Novel Therapeutic Strategy for the Prevention of Bone Fractures

    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

  17. [Global brain metastases management strategy: a multidisciplinary-based approach].

    Métellus, P; Tallet, A; Dhermain, F; Reyns, N; Carpentier, A; Spano, J-P; Azria, D; Noël, G; Barlési, F; Taillibert, S; Le Rhun, É

    2015-02-01

    Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources. Copyright © 2015. Published by Elsevier SAS.

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

    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

  19. WHO global and regional strategies for health and environment

    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

  20. WHO global and regional strategies for health and environment

    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.

  1. Global integration strategies in times of crisis

    Jensen, Camilla

    2017-01-01

    In recent years, we can observe the emergence of firms, born both digital and global, that have disrupted existing industries. Deploying digital technologies, they have developed innovative value chains and business models that threaten established multinational companies (MNCs). In this chapter......, we examine how MNCs can and do respond to the challenge digital technologies represent. We describe the main facets of digital technologies and discus the potential these have to undermine the value chains and business models of established MNCs. In order to illustrate this, we employ longitudinal...... data from Telenor, a leading multinational mobile telecom company. Telenor perceives digitalization as a critical threat that in turn is causing a radical rethink about the viability of its decentralized, locally responsive value chain and business model. Our data provides insights into business models...

  2. An Analysis of Yip's Global Strategy Model, Using Coca-Cola ...

    Analysis of the selected business cases suggest a weak fit between the Yip model of a truly Global strategy ... like Coca-Cola in the beverage industry for effective implementation of a global strategy. ... Keywords: Global Strategy, Leadership.

  3. Conclusion: imaging in strategy of endocrine diagnosis and therapeutics

    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

  4. Ebola virus outbreak, updates on current therapeutic strategies.

    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.

  5. A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

    Yuji Tada

    2013-01-01

    Full Text Available Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

  6. Focus on Therapeutic Strategies of Nonalcoholic Fatty Liver Disease

    Marilena Durazzo

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in the Western world (it affects 30% of the general adult population. The NAFLD encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, defined by steatosis, hepatocellular damage, and lobular inflammation in individuals without significant alcohol consumption and negative viral, congenital, and autoimmune liver disease markers. Currently, NAFLD is considered an emerging epidemic in light of the dramatic increase in obesity rates. With the progressive nature of NASH and its rising prevalence there is a significant need for a specific and targeted treatments since to date there has not been any validated therapies for NAFLD other than weight loss, which is well known to have a poor long-term success rate. In recent years, visceral adipose tissue has taken an important role in NAFLD pathogenesis, and current therapeutic approaches aim at reducing visceral obesity and free fatty acid overflow to the liver. This paper is focused on the treatments used for NAFLD and the potential new therapy.

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

    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.

  8. Priority setting of strategies and mechanisms for limiting global warming

    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

  9. The Islamic State’s Global Propaganda Strategy

    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.

  10. Hydrogen energy strategies and global stability and unrest

    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)

  11. Digital Innovations: Startup Marketing Strategy for Global Growth

    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...

  12. Malaysian diaspora strategies in a globalized Muslim market

    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...

  13. Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

    Hiroshi Katoh

    2015-01-01

    Full Text Available Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs. Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

  14. Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment

    Jaume Folch

    2016-01-01

    Full Text Available Alzheimer’s disease (AD currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC. PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5. Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease.

  15. Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies

    Yu-Wai-Man, Patrick; Griffiths, Philip G.; Chinnery, Patrick F.

    2011-01-01

    paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies. PMID:21112411

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

    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.

  17. International Pricing Strategies for Born-Global Firms

    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.

  18. The regions and global warming: Impacts and response strategies

    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

  19. Global low-carbon transition and China's response strategies

    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.

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

    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.

  1. Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer's Disease.

    Menendez-Gonzalez, Manuel; Padilla-Zambrano, Huber S; Alvarez, Gabriel; Capetillo-Zarate, Estibaliz; Tomas-Zapico, Cristina; Costa, Agustin

    2018-01-01

    Although immunotherapies against the amyloid-β (Aβ) peptide tried so date failed to prove sufficient clinical benefit, Aβ still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aβ from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aβ clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aβ-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink." We also present Aβ-immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Aβ including the "CSF-sink" therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Aβ oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a "CSF-sink" of Aβ will probably produce a steady clearance of Aβ in the ISF and therefore it may represent a new therapeutic strategy in AD.

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

    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

  3. CHANGE MANAGEMENT STRATEGIES RELATED TO THE GLOBAL ENVIRONMENT COMPLEXITY

    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.

  4. Global Search Strategies for Solving Multilinear Least-Squares Problems

    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.

  5. Simulation analysis of globally integrated logistics and recycling strategies

    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.)

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

    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.

  7. Managing differences: the central challenge of global strategy.

    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.

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

    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.

  9. Reaktualisasi Strategi Pendidikan Islam: Ikhtiar Mengimbangi Pendidikan Global

    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. 

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

    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.

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

    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.

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

    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.

  13. A review of Thailand's strategies for global climate change

    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

  14. Terrestrial ecosystem responses to global change: A research strategy

    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.

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

    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.

  16. Priority Selection Within National Innovation Strategy in Global Context

    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.

  17. Long-term global nuclear energy and fuel cycle strategies

    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

  18. Long-term global nuclear energy and fuel cycle strategies

    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.

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

    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.

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

    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.

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

    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.

  2. Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

    Seung Taek Ji

    2017-01-01

    Full Text Available The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  9. Rebuilding the Arab Economies: New Regional and Global Strategies

    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.

  10. Implementation Strategy for a Global Solar and Wind Atlas

    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

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

    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.

  12. Regional strategies for the accelerating global problem of groundwater depletion

    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.

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

    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.

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

    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.

  15. Volcano monitoring using the Global Positioning System: Filtering strategies

    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.

  16. Mobilization strategy to overcome global crisis of water consumption

    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.

  17. Chinese Global and Russian Spatial Strategies: Harmonization Potential

    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

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

    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

  19. The arsenal of pathogens and antivirulence therapeutic strategies for disarming them

    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

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

    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

  1. ASSESSMENT OF THE BUSINESS ENVIRONMENT FOR DEVELOPMENT OF GLOBAL MARKETING STRATEGY

    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.

  2. Landslide risk reduction strategies: an inventory for the Global South

    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

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

  10. A Strategy To Infuse a Global Perspective into Consumer Education.

    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…

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

    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.

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

    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.)

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

    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.

  14. Overview of the status and global strategy for neonicotinoids.

    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.

  15. Terrestrial Ecosystem Responses to Global Change: A Research Strategy

    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

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

    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.

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

    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.

  18. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

  12. An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

    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

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

    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)…

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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...

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

    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

  6. Global Networks: Emerging Constraints on Strategy (Defense Horizons, July 2004)

    Fonow, Bob

    2004-01-01

    .... This shift is problematic for U.S. national security, because the global telecommunications infrastructure is becoming an important strategic battlespace the physical battlefield of information warfare...

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

    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.

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

    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

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

    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

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

    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.

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

    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.

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

    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 ...

  13. Connecting strategy and execution in global R&D

    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...

  14. China's Coal Methane: Actors, Structures, Strategies and their Global Impacts

    Chen, Ke; Charnoz, Olivier

    2012-12-01

    The need for China to alleviate its energy shortage, reduce its dependence on foreign sources and mitigate its climate impact is driving a dire quest for alternative fuels. Coal Mine Methane (CMM), in this context, holds significant potential. While the 11. Five-Year Plan aimed to capture and use 10 billion m"3 per year of CMM by 2010, the country achieved less than a quarter of this. This paper enquires into this puzzling outcome, which bears consequences for the world at large. China is indeed responsible for more than 40% of the world's total un-captured CMM emissions - which act as a greenhouse gas 21 times more potent than CO_2, and whose role in global warming is often underestimated, especially in short- and medium-term climate strategies. While the Chinese central government may have incentive to work towards promoting CMM, the benefits of such policies at the sub-national level are far from self-evident. National CMM policies can have significant economic and social costs at the local level, and thus their implementation can be jeopardized. Implementation of such policies is inherently ambiguous, conflicting, and as such, political. Current research on the Chinese CMM industry has largely focused on its techno-economic aspects, with little if any politico-institutional analyses. As for policy research on the larger Chinese energy sector, this seems sturdily to embody a top-down view: it mostly ends up blaming the country's decentralized governance structure and lack of a stringent implementation chain. Such top-down approaches do not help uncover 'the sinews of war': the range of less formal mechanisms, negotiations and agreements among the local actors, without which implementation does not in fact occur at the sub-national level. Nor do top-down research approaches facilitate inquiry into the way local stakeholders re-frame the meaning, content and impact of CMM policies. More generally, the top-down approaches fail to consider the significance of

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

    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

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

    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.

  17. Strategies for Combating Global Economic Crisis in Nigeria through ...

    First Lady

    2012-10-27

    Oct 27, 2012 ... cash-productive; boosting the students interest I n science; and developing ... Global economic depression, according to Babalola and Tiamiyu (2009) ... help to overcome the problem of economic crisis in the country? 2.

  18. Global Insurgency Strategy and the Salafi Jihad Movement

    Shultz, Jr, Richard H

    2008-01-01

    ... on a global scale by the Salafi Jihad movement. This work lays out the case that terrorism and insurgency differ, and that the current "long war" is actually being fought by the other side as an insurgency...

  19. Intercultural Communication: A Key Element in Global Strategies.

    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)

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

    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.

  1. Targeting endoplasmic reticulum and/or mitochondrial Ca2+ fluxes as therapeutic strategy for HCV infection

    Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

    2018-03-01

    Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

  2. 3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration.

    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.

  3. Targeting Endoplasmic Reticulum and/or Mitochondrial Ca2+ Fluxes as Therapeutic Strategy for HCV Infection.

    Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

    2018-01-01

    Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca 2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

  4. New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

    Ebbe Toftgaard Poulsen

    2015-12-01

    Full Text Available The Amyloid Precursor Protein (APP has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ in Alzheimer’s disease (AD. However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y682 mutation in the 682YENPTY687 domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS on hippocampal tissue extracts of three month-old mice incubated with either the 682YENPTY687 peptide, its mutated form, 682GENPTY687 or its phosphorylated form, 682pYENPTY687. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc and its Adaptor Protein 2 (AP-2. Overall our results consolidate and refine the importance of Y682 in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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)

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

    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.

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

    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.

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

    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.

  16. A Revised Strategy for the Global War on Terrorism

    Maxwell, Jeffrey W

    2007-01-01

    .... A more complete strategy is needed to counter this ideology. New priorities of action include information operations, strategic communications and strengthening societies. These actions will help undermine the enemy's ability to transfer feelings of oppression and hopelessness into hatred and violence. With a balanced strategy, in the long run we will win both the battle of arms and ideas.

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

    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...

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

    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

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

    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.

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

    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.

  1. Global Obesity Study on Drivers for Weight Reduction Strategies

    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.

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

    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 ...

  3. Statistical strategies for global monitoring of tropical forests

    Raymond L. Czaplewski

    1991-01-01

    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. This paper describes: (1) the strategic...

  4. The Global Enery and Water Cycle Experiment Science Strategy

    Chahine, M. T.

    1997-01-01

    The distribution of water in the atmosphere and at the surface of the Earth is the most influential factor regulating our environment, not only because water is essential for life but also because through phase transitions it is the main energy source that control clouds and radiation and drives the global circulation of the atmosphere.

  5. A strategy for global environmental education at the university

    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

  6. Targeting miRNAs by polyphenols: Novel therapeutic strategy for cancer.

    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.

  7. Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination

    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.

  8. Computationally derived points of fragility of a human cascade are consistent with current therapeutic strategies.

    Deyan Luan

    2007-07-01

    Full Text Available The role that mechanistic mathematical modeling and systems biology will play in molecular medicine and clinical development remains uncertain. In this study, mathematical modeling and sensitivity analysis were used to explore the working hypothesis that mechanistic models of human cascades, despite model uncertainty, can be computationally screened for points of fragility, and that these sensitive mechanisms could serve as therapeutic targets. We tested our working hypothesis by screening a model of the well-studied coagulation cascade, developed and validated from literature. The predicted sensitive mechanisms were then compared with the treatment literature. The model, composed of 92 proteins and 148 protein-protein interactions, was validated using 21 published datasets generated from two different quiescent in vitro coagulation models. Simulated platelet activation and thrombin generation profiles in the presence and absence of natural anticoagulants were consistent with measured values, with a mean correlation of 0.87 across all trials. Overall state sensitivity coefficients, which measure the robustness or fragility of a given mechanism, were calculated using a Monte Carlo strategy. In the absence of anticoagulants, fluid and surface phase factor X/activated factor X (fX/FXa activity and thrombin-mediated platelet activation were found to be fragile, while fIX/FIXa and fVIII/FVIIIa activation and activity were robust. Both anti-fX/FXa and direct thrombin inhibitors are important classes of anticoagulants; for example, anti-fX/FXa inhibitors have FDA approval for the prevention of venous thromboembolism following surgical intervention and as an initial treatment for deep venous thrombosis and pulmonary embolism. Both in vitro and in vivo experimental evidence is reviewed supporting the prediction that fIX/FIXa activity is robust. When taken together, these results support our working hypothesis that computationally derived points of

  9. A global strategy for the European PV industry

    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)

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

    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.

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

    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.

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

    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.

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

    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.

  14. Strategies for high-precision Global Positioning System orbit determination

    Lichten, Stephen M.; Border, James S.

    1987-01-01

    Various strategies for the high-precision orbit determination of the GPS satellites are explored using data from the 1985 GPS field test. Several refinements to the orbit determination strategies were found to be crucial for achieving high levels of repeatability and accuracy. These include the fine tuning of the GPS solar radiation coefficients and the ground station zenith tropospheric delays. Multiday arcs of 3-6 days provided better orbits and baselines than the 8-hr arcs from single-day passes. Highest-quality orbits and baselines were obtained with combined carrier phase and pseudorange solutions.

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

    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

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

    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

  17. Global warming mitigation strategies and programs for power plant developers

    Holmes, N.R.

    1992-01-01

    Power plant developers are increasingly being surprised by regulatory agencies requiring them to mitigate the carbon dioxide(CO 2 ) emissions from their proposed power plants, as part of the plant's operating permit conditions. Since carbon dioxide is not a criteria pollutant with a National Ambient Air Quality Standard, power plant developers are often troubled by this additional regulatory requirement. This presentation will describe the contribution that CO 2 makes to global warming, the role of trees and forests as carbon sequesters or sinks, some non-forestry related and forestry related mitigation programs, including the advantages, disadvantages, and some cost estimates for the forestry related CO 2 mitigation programs. As public concern about global warming continues to escalate, it is almost certain that regulatory agencies will increase their focus on CO 2 mitigation

  18. Global Salafist Jihad in UK -- Strategies of Prevention

    2007-05-24

    global Jihadist movement has become decentralised and more diffuse, events in Iraq are shaping a new generation of terrorist leaders and operatives...Qaeda’s(pl~ers could conceive, plan and prepare attacks. Germany was favoured due to their security forces’ ignorance ofMiddle Eastern networks - most...social value, there is little intellectkI energy devoted to a better understanding of radicalisation and methods to blunt its ¢ffect, a paucity of

  19. Global Corporate Priorities and Demand-Led Learning Strategies

    Dealtry, Richard

    2008-01-01

    Purpose: The purpose of this article is to start the process of exploring how to optimise connections between the strategic needs of an organisation as directed by top management and its learning management structures and strategies. Design/methodology/approach: The article takes a broad brush approach to a complex and large subject area that is…

  20. Slowing global warming. Mitigation strategy for the developing world

    Pachauri, R.K.; Barathan, S.

    1995-01-01

    Globally, a range of human activities that characterize modern economic systems are leading to emissions of greenhouse gases. For some activities like the cultivation of paddy rice in flooded soils, there is reason to believe that there are no economically viable or practical alternatives to the current methods which produce these emissions. However, there are several other areas of human activity ranging from the generation of electricity to the provision of passenger and freight transport, in which there clearly exists the potential for preparing the agenda for change which would mitigate global warming. The objective of this paper is to discuss and evaluate a suitable mix of innovative measures which would make efficient use of scarce resources and maximize returns from the resources invested to limit CO 2 emissions. In particular, this paper evolves a three phase approach for mitigating CO 2 emissions that can be widely applied to reorient economic development policies in the developing world. Comprising an agenda for change, it underlines specific failures in national policies, identifies thrust areas for mitigating CO 2 emissions and suggests policy responses in major sectors of the economy. The guiding premise here is simple and straightforward - the energy sector (inclusive of the services provided by energy rather than energy per se) which has been a major cause for invoking the threat of climate change and global warming, must now become a part of the solution. (au) 11 refs

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

    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...

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

    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...

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

    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

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

    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...

  5. Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

    Kumar, S; Peng, X; Daley, J; Yang, L; Shen, J; Nguyen, N; Bae, G; Niu, H; Peng, Y; Hsieh, H-J; Wang, L; Rao, C; Stephan, C C; Sung, P; Ira, G; Peng, G

    2017-04-17

    Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in replication and HR repair. Here we demonstrate that DNA2 is overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90-95% of cases. In addition, depletion of DNA2 significantly reduces pancreatic cancer cell survival and xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition. Finally, we develop a robust high-throughput biochemistry assay to screen for inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion, including decreased DNA double strand break end resection and attenuation of HR repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2 selectively attenuates the growth of various cancer cells with oncogene-induced replication stress. Taken together, our findings open a new avenue to develop a new class of anticancer drugs by targeting druggable nuclease DNA2. We propose DNA2 inhibition as new strategy in cancer therapy by targeting

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

    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.

  7. Global optimization numerical strategies for rate-independent processes

    Benešová, Barbora

    2011-01-01

    Roč. 50, č. 2 (2011), s. 197-220 ISSN 0925-5001 R&D Projects: GA ČR GAP201/10/0357 Grant - others:GA MŠk(CZ) LC06052 Program:LC Institutional research plan: CEZ:AV0Z20760514 Keywords : rate-independent processes * numerical global optimization * energy estimates based algorithm Subject RIV: BA - General Mathematics Impact factor: 1.196, year: 2011 http://math.hnue.edu.vn/portal/rss.viewpage.php?id=0000037780&ap=L3BvcnRhbC9ncmFiYmVyLnBocD9jYXRpZD0xMDEyJnBhZ2U9Mg==

  8. Remote sensing strategies for global resource exploration and environmental management

    Henderson, Frederick B.

    Since 1972, satellite remote sensing, when integrated with other exploration techniques, has demonstrated operational exploration and engineering cost savings and reduced exploration risks through improved geological mapping. Land and ocean remote sensing satellite systems under development for the 1990's by the United States, France, Japan, Canada, ESA, Russia, China, and others, will significantly increase our ability to explore for, develop, and manage energy and mineral resources worldwide. A major difference between these systems is the "Open Skies" and "Non-Discriminatory Access to Data" policies as have been practiced by the U.S. and France and the restrictive nationalistic data policies as have been practiced by Russia and India. Global exploration will use satellite remote sensing to better map regional structural and basin-like features that control the distribution of energy and mineral resources. Improved sensors will better map lithologic and stratigraphic units and identify alteration effects in rocks, soils, and vegetation cover indicative of undiscovered subsurface resources. These same sensors will also map and monitor resource development. The use of satellite remote sensing data will grow substantially through increasing integration with other geophysical, geochemical, and geologic data using improved geographic information systems (GIS). International exploration will focus on underdeveloped countries rather than on mature exploration areas such as the United States, Europe, and Japan. Energy and mineral companies and government agencies in these countries and others will utilize available remote sensing data to acquire economic intelligence on global resources. If the "Non-Discriminatory Access to Data" principle is observed by satellite producing countries, exploration will remain competitive "on the ground". In this manner, remote sensing technology will continue to be developed to better explore for and manage the world's needed resources

  9. Are therapeutic vaccines an answer to the global problem of drug and alcohol abuse?

    Brashier, Dick B S; Sharma, Ashok Kumar; Akhoon, Neha

    2016-01-01

    Drug Abuse has become a major challenging problem for the society. It effects people of all countries economical strata's and all ages. According. Monetary loss all over the world regarding drug abuse is in million dollars, it not only has an impact on human productivity and healthcare cost but also on cost of crimes conducted by these drugs and alcohol abuse. Therapeutic vaccine has come as new approach to deal with this problem, after failures in search for a pharmaceutical agent to deal with drug of abuse and alcohol. Research in field of nicotine abuse has gone a way ahead with number of vaccines being tried clinically followed by cocaine, opioids, methamphetamine, phencyclidine and alcohol. All of them have a common mechanism of action by antibody production whereas alcohol acts by genetic intervention. None have being approved yet due to poor results in phase II trials, possibly due to not able to trigger an adequate immunological response. But still quest is on for cracking the ice by developing first successful vaccine against drug of abuse, that would follow for other drugs too. It would be great step in field of therapeutic vaccines for drug abuse after similar successful vaccines being approved for other diseases like cancer.

  10. Energy and the environment. A global view and strategies

    Pasztor, J.

    1988-01-01

    It should be recognized that the key to the future is in the rational use of energy, that is, a more efficient use of energy rather than a continuous increase in the supply of energy. Every unit of energy saved is a unit of energy which does not have to be produced, and whose environmental impacts do not have to be dealt with. Massive reductions in the growth rates, and, where possible, in the absolute use of energy will help us to gain time to better understand and develop response strategies to problems like climate change on the acidification of the environment. In this sense the rational use of energy, including intensified energy efficiency measures is the most environmentally sound energy option with which we should move into the next century. 25 refs., 4 figs

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

    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.

  12. Workshop Builds Strategies to Address Global Positioning System Vulnerabilities

    Fisher, Genene

    2011-01-01

    When we examine the impacts of space weather on society, do we really understand the risks? Can past experiences reliably predict what will happen in the future? As the complexity of technology increases, there is the potential for it to become more fragile, allowing for a single point of failure to bring down the entire system. Take the Global Positioning System (GPS) as an example. GPS positioning, navigation, and timing have become an integral part of daily life, supporting transportation and communications systems vital to the aviation, merchant marine, cargo, cellular phone, surveying, and oil exploration industries. Everyday activities such as banking, mobile phone operations, and even the control of power grids are facilitated by the accurate timing provided by GPS. Understanding the risks of space weather to GPS and the many economic sectors reliant upon it, as well as how to build resilience, was the focus of a policy workshop organized by the American Meteorological Society (AMS) and held on 13-14 October 2010 in Washington, D. C. The workshop brought together a select group of policy makers, space weather scientists, and GPS experts and users.

  13. Global approaches and local strategies for phase unwrapping

    Guerriero, L.; Refice, A.; Stramaglia, S.; Chiaradia, M. T.; Satalino, G.; Veneziani, N.; Blonda, P.; Pasquariello, G.

    2001-01-01

    Phase unwrapping, i.e. the retrieval of absolute phases from wrapped, noisy measures, is a tough problem because of the presence of rotational inconsistencies (residues), randomly generated by noise and undersampling on the principal phase gradient field. These inconsistencies prevent the recovery of the absolute phase field by direct integration of the wrapped gradients. In this paper it is examined the relative merit of known global approaches and then it is presented evidence that the approach based on stochastic annealing can recover the true phase field also in noisy areas with severe undersampling, where other methods fail. Then, some experiments with local approaches are presented. A fast neural filter has been trained to eliminate close residue couples by joining them in a way which takes into account the local phase information. Performances are about 60-70% of the residues. Finally, other experiments have been aimed at designing an automated method for the determination of weight matrices to use in conjunction with local phase unwrapping algorithms. The method, tested with the minimum cost flow algorithm, gives good performances over both simulated and real data

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

    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.

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

    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.

  16. Pricing hospital care: Global budgets and marginal pricing strategies.

    Sutherland, Jason M

    2015-08-01

    The Canadian province of British Columbia (BC) is adding financial incentives to increase the volume of surgeries provided by hospitals using a marginal pricing approach. The objective of this study is to calculate marginal costs of surgeries based on assumptions regarding hospitals' availability of labor and equipment. This study is based on observational clinical, administrative and financial data generated by hospitals. Hospital inpatient and outpatient discharge summaries from the province are linked with detailed activity-based costing information, stratified by assigned case mix categorizations. To reflect a range of operating constraints governing hospitals' ability to increase their volume of surgeries, a number of scenarios are proposed. Under these scenarios, estimated marginal costs are calculated and compared to prices being offered as incentives to hospitals. Existing data can be used to support alternative strategies for pricing hospital care. Prices for inpatient surgeries do not generate positive margins under a range of operating scenarios. Hip and knee surgeries generate surpluses for hospitals even under the most costly labor conditions and are expected to generate additional volume. In health systems that wish to fine-tune financial incentives, setting prices that create incentives for additional volume should reflect knowledge of hospitals' underlying cost structures. Possible implications of mis-pricing include no response to the incentives or uneven increases in supply. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. Adenosine can thwart antitumor immune responses elicited by radiotherapy. Therapeutic strategies alleviating protumor ADO activities

    Vaupel, Peter [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Multhoff, Gabriele [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Helmholtz Zentrum Muenchen, Institute for innovative Radiotherapy (iRT), Experimental Immune Biology, Neuherberg (Germany)

    2016-05-15

    By studying the bioenergetic status we could show that the development of tumor hypoxia is accompanied, apart from myriad other biologically relevant effects, by a substantial accumulation of adenosine (ADO). ADO has been shown to act as a strong immunosuppressive agent in tumors by modulating the innate and adaptive immune system. In contrast to ADO, standard radiotherapy (RT) can either stimulate or abrogate antitumor immune responses. Herein, we present ADO-mediated mechanisms that may thwart antitumor immune responses elicited by RT. An overview of the generation, accumulation, and ADO-related multifaceted inhibition of immune functions, contrasted with the antitumor immune effects of RT, is provided. Upon hypoxic stress, cancer cells release ATP into the extracellular space where nucleotides are converted into ADO by hypoxia-sensitive, membrane-bound ectoenzymes (CD39/CD73). ADO actions are mediated upon binding to surface receptors, mainly A2A receptors on tumor and immune cells. Receptor activation leads to a broad spectrum of strong immunosuppressive properties facilitating tumor escape from immune control. Mechanisms include (1) impaired activity of CD4 + T and CD8 + T, NK cells and dendritic cells (DC), decreased production of immuno-stimulatory lymphokines, and (2) activation of Treg cells, expansion of MDSCs, promotion of M2 macrophages, and increased activity of major immunosuppressive cytokines. In addition, ADO can directly stimulate tumor proliferation and angiogenesis. ADO mechanisms described can thwart antitumor immune responses elicited by RT. Therapeutic strategies alleviating tumor-promoting activities of ADO include respiratory hyperoxia or mild hyperthermia, inhibition of CD39/CD73 ectoenzymes or blockade of A2A receptors, and inhibition of ATP-release channels or ADO transporters. (orig.) [German] Untersuchungen des bioenergetischen Status ergaben, dass Tumorhypoxie neben vielen anderen bedeutsamen biologischen Effekten zu einem starken

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

    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.

  19. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

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

    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.

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

    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.

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

    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

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

    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.

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

    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

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

    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.

  6. 19th Annual conference ampersand exposition: Global strategies for environmental issues

    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

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

    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.

  8. [Therapeutic strategies. Evolution and current status of the European Guidelines on Cardiovascular disease prevention].

    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.

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

    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.

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

    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

  11. Integrative medical therapy: examination of meditation's therapeutic and global medicinal outcomes via nitric oxide (review).

    Stefano, George B; Esch, Tobias

    2005-10-01

    Relaxation techniques are part of the integrative medicine movement that is of growing importance for mainstream medicine. Complementary medical therapies have the potential to affect many physiological systems. Repeatedly studies show the benefits of the placebo response and relaxation techniques in the treatment of hypertension, cardiac arrhythmias, chronic pain, insomnia, anxiety and mild and moderate depression, premenstrual syndrome, and infertility. In itself, relaxation is characterized by a decreased metabolism, heart rate, blood pressure, and rate of breathing as well as an increase in skin temperature. Relaxation approaches, such as progressive muscle relaxation, autogenic training, meditation and biofeedback, are effective in lowering systolic and diastolic blood pressure in hypertensive patients by a significant margin. Given this association with changes in vascular tone, we have hypothesized that nitric oxide, a demonstrated vasodilator substance, contribute to physiological activity of relaxation approaches. We examined the scientific literature concerning the disorders noted earlier for their nitric oxide involvement in an attempt to provide a molecular rationale for the positive effects of relaxation approaches, which are physiological and cognitive process. We conclude that constitutive nitric oxide may crucially contribute to potentially beneficial outcomes and effects in diverse pathologies, exerting a global healing effect.

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

    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...

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

    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...

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

    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 ...

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

    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.

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

    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.

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

    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.

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

    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.

  19. Place of the brachytherapy in the therapeutic strategy of rhabdomyosarcomas of the nasogenian groove of children

    Breton-Callu, C.; Haie-Meder, C.; Oberlin, O.; Delapierre, M.; Gerbaulet, A.

    2000-01-01

    The brachytherapy in the treatment of rhabdomyosarcomas of the nasogenian groove has to be discussed when it exists a residual tumor after an initial chemotherapy and leads to good results, in term of local control. An advantage of the brachytherapy in comparison with external irradiation, in the treatment of children tumors, is the small size of the treated volume, that allows to decrease the aftereffects incidence. The brachytherapy comes in the frame of a therapeutic needing a multidisciplinary approach and a cooperation between surgeons, brachy-therapists and onco-pediatricians. (N.C.)

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

    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.

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

    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.

  2. Novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy

    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 

  3. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases.

    Matthew J Haney

    Full Text Available The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD. This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders.

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

    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.

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

    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.

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

    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)

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

    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

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  17. Repressing CD147 is a novel therapeutic strategy for malignant melanoma.

    Hu, Xing; Su, Juan; Zhou, Youyou; Xie, Xiaoyun; Peng, Cong; Yuan, Zhimin; Chen, Xiang

    2017-04-11

    CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM.

  18. MESENCHYMAL STEM CELLS AS A THERAPEUTIC STRATEGY FOR MULTIPLE SCLEROSIS: ISSUES AND PERSPECTIVES

    M. M. Zafranskaya

    2017-01-01

    Full Text Available The ability of mesenchymal stem cells (MSC to influence the regulatory/suppressive effect in the autoimmune process and promote remyelination allows to consider them a new method of multiple sclerosis (MS therapy, by means of modifying the disease activity. Genetic stability, proliferative potential, ability to migrate into the damaged tissue areas and agreed protocols for isolation and culture are the main advantages for successful autologous, as well as allogeneic MSC therapy. Preliminary results from clinical studies using MSC application in MS patients show efficiency and safety of this therapeutic approach. Nevertheless, successful demonstration of the cell therapy in MS is only possible after detailed analysis and understanding of MSC biology and mechanisms of appropriate intercellular interactions. The article reviews general experience in usage of immunomodulatory and neuroprotective properties of MSС in MS, and highlights the issues of validity in cell-based therapy taking into account both in vitro и in vivo studies.

  19. Novel strategies and therapeutic options for the management of primary biliary cholangitis.

    Khanna, Amardeep; Jones, David E

    2017-10-01

    Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. It has a varied course of progression ranging from being completely asymptomatic to aggressive disease leading to cirrhosis and resulting in liver transplantation. In addition, symptoms can be debilitating and can have a major impact on quality of life. For decades, there was only one anti-cholestatic agent available to target this disease and that was only effective in around half of patients, with little or no effect on symptoms. With increasing understanding of the pathogenic mechanisms of PBC and potential targets for drug treatment, pharmaceutical companies have shown a greater interest in this rare disease. A large number of novel therapeutic molecules have been developed and are currently being evaluated. In this review article all the novel molecules in use and in trials targeting cholestasis and symptoms in PBC are discussed.

  20. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy.

    Wander, Seth A

    2011-04-01

    Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

  1. Electrochemotherapy as a new therapeutic strategy in advanced Merkel cell carcinoma of head and neck region

    Scelsi, Daniele; Mevio, Niccolò; Bertino, Giulia; Occhini, Antonio; Brazzelli, Valeria; Morbini, Patrizia; Benazzo, Marco

    2013-01-01

    Merkel Cell Carcinoma (MCC) is a rare and aggressive tumour, arising from a cutaneous mechanoceptor cell located in the basal layer of epidermis, with poor prognosis. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. We report a case of 84 years old woman with a recurrent MCC of the chin treated with electrochemotherapy (ECT). During the period of 20 months, four sessions of ECT were employed, which resulted in an objective response of the tumour and good quality of residual life. Our case shows the effectiveness of ECT in the treatment of locally advanced MCC of the head and neck region in a patient not suitable for standard therapeutic options

  2. Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.

    Ling, Song; Liu, Ying; Fu, Jiaqi; Colletta, Alessandro; Gilon, Chaim; Holoshitz, Joseph

    2015-05-01

    The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA-DRB1-coded 5-amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)-mediated bone damage in collagen-induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis-associated bone damage, we sought to determine the therapeutic targetability of calreticulin. A library of backbone-cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE-activated signaling and OC differentiation was tested in vitro. The effect on disease severity and OC-mediated bone damage was studied by weekly intraperitoneal administration of the compounds to DBA/1 mice with CIA. Two members of the peptidomimetics library were found to have SE-antagonistic effects and antiosteoclast differentiation effects at picomolar concentrations in vitro. The lead mimetic compound, designated HS(4-4)c Trp, potently ameliorated arthritis and bone damage in vivo when administered in picogram doses to mice with CIA. Another mimetic analog, designated HS(3-4)c Trp, was found to lack activity, both in vitro and in vivo. The differential activity of the 2 analogs depended on minor differences in their respective ring sizes and correlated with distinctive geometry when computationally docked to the SE binding site on calreticulin. These findings identify calreticulin as a novel therapeutic target in erosive arthritis and provide sound rationale and early structure/activity relationships for future drug design. © 2015, American College of Rheumatology.

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

    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...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  9. Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: Case report

    Altmeyer Peter

    2004-09-01

    Full Text Available Abstract Background Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. Case presentation We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. Conclusions Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

  10. Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer.

    Wang, Meng; Medeiros, Bruno C; Erba, Harry P; DeAngelo, Daniel J; Giles, Francis J; Swords, Ronan T

    2011-03-01

    The NEDD8 (neural precursor cell-expressed developmentally downregulated 8) conjugation pathway regulates the post-translational modification of oncogenic proteins. This pathway has important potential for cancer therapeutics. Several proteins vital in cancer biology are regulated by protein neddylation. These observations led to the development of a small molecule inhibitor that disrupts protein neddylation and leads to cancer cell death and important activity in early phase clinical trials. This review provides an extensive coverage of cellular protein homeostasis with particular emphasis on the NEDD8 conjugation pathway. Insights into a new investigational drug that specifically disrupts the NEDD8 pathway are discussed. The clinical data for this agent are also updated. Neddylation controls key cellular pathways found to be dysregulated in many cancers. Protein neddylation is a relatively under-explored pathway for pharmacologic inhibition in cancer. Selective disruption of this pathway has demonstrated clinical activity in patients with myeloid neoplasms and is worth exploring further in combination with other anti-leukemia agents.

  11. The impact of cellular senescence in skin ageing: A notion of mosaic and therapeutic strategies.

    Toutfaire, Marie; Bauwens, Emilie; Debacq-Chainiaux, Florence

    2017-10-15

    Cellular senescence is now recognized as one of the nine hallmarks of ageing. Recent data show the involvement of senescent cells in tissue ageing and some age-related diseases. Skin represents an ideal model for the study of ageing. Indeed, skin ageing varies between individuals depending on their chronological age but also on their exposure to various exogenous factors (mainly ultraviolet rays). If senescence traits can be detected with ageing in the skin, the senescent phenotype varies among the various skin cell types. Moreover, the origin of cellular senescence in the skin is still unknown, and multiple origins are possible. This reflects the mosaic of skin ageing. Senescent cells can interfere with their microenvironment, either via the direct secretion of factors (the senescence-associated secretory phenotype) or via other methods of communication, such as extracellular vesicles. Knowledge regarding the impact of cellular senescence on skin ageing could be integrated into dermatology research, especially to limit the appearance of senescent cells after photo(chemo)therapy or in age-related skin diseases. Therapeutic approaches include the clearance of senescent cells via the use of senolytics or via the cooperation with the immune system. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Gene Editing and CRISPR Therapeutics: Strategies Taught by Cell and Gene Therapy.

    Ramirez, Juan C

    2017-01-01

    A few years ago, we assisted in the demonstration for the first time of the revolutionary idea of a type of adaptive-immune system in the bacteria kingdom. This system, named CRISPR, and variants engineered in the lab, have been demonstrated as functional with extremely high frequency and fidelity in almost all eukaryotic cells studied to date. The capabilities of this RNA-guided nuclease have added to the interest that was announced with the advent of previous technologies for genome editing tools, such as ZFN and TALEN. The capabilities exhibited by these gene editors, opens up a novel scenario that indicates the promise of a next-generation medicine based on precision and personalized objectives, mostly due to the change in the paradigm regarding gene-surgery. This has certainly attracted, like never before, the attention of the biotech business and investor community. This chapter offers a brief overview of some of the factors that have contributed to a rapid entry into the biotech and pharmaceutical company's pipeline, focusing on how cell and gene therapies (CGT), collectively known as advanced therapies, have become the driving forces toward the therapeutic uses of gene editing technology. The sum of all those efforts for more than 30years has contributed to the new paradigm of considering genes as medicines. Copyright © 2017. Published by Elsevier Inc.

  13. [Therapeutics strategies for the management of urinary tract infection in children].

    Launay, E; Bingen, E; Cohen, R

    2012-11-01

    Urinary tract infections is one of the most common bacterial infections in pediatrics The increasing involvement of multiresistant bacteria including E. coli producing extended spectrum ß-lactamase (ESBL) makes its management difficult. The purpose of this article is to evaluate the state of the art and to propose ways of thinking about the management of E. coli urinary tract infection in children. The current percentage (less than 10%) of E. coli strains resistant to third generation cephalosporins and the relative efficiency of the latter, should not led to an immediate change of our protocols. Nevertheless, we should verify as soon as possible susceptibility of E. coli responsible for urinary tract infections and consider other therapeutic options for initial therapy and adaptation after obtaining antibiogram. The use of an aminoglycosid as initial treatment seems very interesting. Aminoglycosides have a very good distribution in the renal parenchyma and are still working on the majority of ESBL-producing bacteria. A rapid oral relay after 48 to 72 hours may be proposed according to the results of the susceptibility with either cotrimoxazole, cefixime, ciprofloxacin or an association cefixime-amoxicilline/clavulanate. The treatment of cystitis due to ESBL E. coli is much less problematic given the good urinary beta-lactam antibiotics diffusion. If clinical improvement occurs, even if antibiogram shows that the strain is resistant to the antibiotic prescribed, it is usually unnecessary to change treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. The third therapeutic system: faith healing strategies in the context of a generalized AIDS epidemic.

    Manglos, Nicolette D; Trinitapoli, Jenny

    2011-03-01

    Faith healing in sub-Saharan Africa has primarily been studied qualitatively among Pentecostal-Charismatic groups, and considered as its own phenomenon with little attention to its relationship to other modes of healing. Using data from Malawi, a religiously diverse African country with high HIV prevalence, we find that faith healing is pervasive across multiple religious traditions. For individuals, attending a faith healing congregation is associated with lower levels of generalized worry about AIDS, and this association is driven by those who switched churches before AIDS became widespread in rural areas. Use of condoms and traditional medicine are, on the other hand, positively associated with worry about AIDS. We argue that faith healing can be understood as a third therapeutic system that coexists with the well-documented biomedical and traditional systems. The success of faith healing approaches lies in their unique ability to combine individual-pragmatic and communal-ritualized aspects of healing to inform interpretations of the AIDS epidemic and its consequences.

  15. Bariatric Surgery for Adolescents with Type 2 Diabetes: an Emerging Therapeutic Strategy.

    Stefater, M A; Inge, T H

    2017-08-01

    Type 2 diabetes (T2D) is a growing public health problem in youth, but conventional treatments are often insufficient to treat this disease and its comorbidities. We review evidence supporting an emerging role for bariatric surgery as a treatment for adolescent T2D. Paralleling what has been seen in adult patients, bariatric surgery dramatically improves glycemic control in patients with T2D. In fact, remission of T2D has been observed in as many as 95-100% of adolescents with diabetes after bariatric surgery, particularly vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) surgery. This striking outcome may be due to both weight-dependent- and weight-independent factors, and recent studies suggest that T2D-related comorbidities may also improve after surgery. Bariatric surgery including RYGB and VSG is a powerful therapeutic option for obese adolescents with T2D. Benefits must be weighed against risk for postoperative complications such as nutritional deficiencies, but earlier surgical intervention might lead to more complete metabolic remission in obese patients with T2D.

  16. Mini-Review: Novel Therapeutic Strategies to Blunt Actions of Pneumolysin in the Lungs

    Martin Leustik

    2013-07-01

    Full Text Available Severe pneumonia is the main single cause of death worldwide in children under five years of age. The main etiological agent of pneumonia is the G+ bacterium Streptococcus pneumoniae, which accounts for up to 45% of all cases. Intriguingly, patients can still die days after commencing antibiotic treatment due to the development of permeability edema, although the pathogen was successfully cleared from their lungs. This condition is characterized by a dramatically impaired alveolar epithelial-capillary barrier function and a dysfunction of the sodium transporters required for edema reabsorption, including the apically expressed epithelial sodium channel (ENaC and the basolaterally expressed sodium potassium pump (Na+-K+-ATPase. The main agent inducing this edema formation is the virulence factor pneumolysin, a cholesterol-binding pore-forming toxin, released in the alveolar compartment of the lungs when pneumococci are being lysed by antibiotic treatment or upon autolysis. Sub-lytic concentrations of pneumolysin can cause endothelial barrier dysfunction and can impair ENaC-mediated sodium uptake in type II alveolar epithelial cells. These events significantly contribute to the formation of permeability edema, for which currently no standard therapy is available. This review focuses on discussing some recent developments in the search for the novel therapeutic agents able to improve lung function despite the presence of pore-forming toxins. Such treatments could reduce the potentially lethal complications occurring after antibiotic treatment of patients with severe pneumonia.

  17. The Third Therapeutic System: Faith Healing Strategies in the Context of a Generalized AIDS Epidemic

    Manglos, Nicolette D.; Trinitapoli, Jenny

    2014-01-01

    Faith healing in sub-Saharan Africa has primarily been studied qualitatively among Pentecostal-Charismatic groups, and considered as its own phenomenon with little attention to its relationship to other modes of healing. Using data from Malawi, a religiously diverse African country with high HIV prevalence, we find that faith healing is pervasive across multiple religious traditions. For individuals, attending a faith healing congregation is associated with lower levels of generalized worry about AIDS, and this association is driven by those who switched churches before AIDS became widespread in rural areas. Use of condoms and traditional medicine are, on the other hand, positively associated with worry about AIDS. We argue that faith healing can be understood as a third therapeutic system that coexists with the well-documented biomedical and traditional systems. The success of faith healing approaches lies in their unique ability to combine individual-pragmatic and communal-ritualized aspects of healing to inform interpretations of the AIDS epidemic and its consequences. PMID:21362615

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

    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

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

    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.

  20. Novel therapeutic strategy in the management of COPD: a systems medicine approach.

    Lococo, Filippo; Cesario, Alfredo; Del Bufalo, Alessandra; Ciarrocchi, Alessia; Prinzi, Giulia; Mina, Marco; Bonassi, Stefano; Russo, Patrizia

    2015-01-01

    Respiratory diseases including chronic-obstructive-pulmonary-disease (COPD) are globally increasing, with COPD predicted to become the third leading cause of global mortality by 2020. COPD is a heterogeneous disease with COPD-patients displaying different phenotypes as a result of a complex interaction between various genetic, environmental and life-style factors. In recent years, several investigations have been performed to better define such interactions, but the identification of the resulting phenotypes is still somewhat difficult, and may lead to inadequate assessment and management of COPD (usually based solely on the severity of airflow limitation parameter FEV1). In this new scenario, the management of COPD has been driven towards an integrative and holistic approach. The degree of complexity requires analyses based on large datasets (also including advanced functional genomic assays) and novel computational biology approaches (essential to extract information relevant for the clinical decision process and for the development of new drugs). Therefore, according to the emerging "systems/network medicine", COPD should be re.-evaluated considering multiple network(s) perturbations such as genetic and environmental changes. Systems Medicine (SM) platforms, in which patients are extensively characterized, offer a basis for a more targeted clinical approach, which is predictive, preventive, personalized and participatory ("P4-medicine"). It clearly emerges that in the next future, new opportunities will become available for clinical research on rare COPD patterns and for the identification of new biomarkers of comorbidity, severity, and progression. Herein, we overview the literature discussing the opportunity coming from the adoption of SMapproaches in COPD management, focusing on proteomics and metabolomics, and emphasizing the identification of disease sub-clusters, to improve the development of more effective therapies.

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

    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...

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

    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.

  3. Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases

    Singh R

    2018-03-01

    Full Text Available Rajan Singh,1,2 Shehla Pervin,1,2 Se-Jin Lee,3,4 Alan Kuo,5 Victor Grijalva,6 John David,7 Laurent Vergnes,8 Srinivasa T Reddy1,6 1Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA, USA; 2Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; 3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; 4Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, CT, USA; 5Department of Biology, California State University Dominguez Hills, CA, USA; 6Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; 7Department of Comparative Medicine, Pfizer Inc, San Diego, CA, USA; 8Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA, USA Background: Follistatin (Fst promotes brown adipocyte characteristics in adipose tissues.Methods: Abdominal fat volume (CT scan, glucose clearance (GTT test, and metabolomics analysis (mass spectrometry of adipose tissues from Fst transgenic (Fst-Tg and wild type (WT control mice were analyzed. Oxygen consumption (Seahorse Analyzer and lipidomics (gas chromatography was analyzed in 3T3-L1 cells.Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice. Furthermore, overexpression of Fst in 3T3-L1 cells resulted in up regulation of key brown/beige markers and changes in lipidomics profiles. Conclusion: Fst modulates key factors involved in promoting metabolic syndrome and could be used for therapeutic intervention. Keywords: follistatin, transgenic, adipocyte, fibroblast growth factor 21, AdipoQ

  4. Cost-effectiveness of diagnostic-therapeutic strategies for paediatric visceral leishmaniasis in Morocco.

    Alonso, Sergi; Tachfouti, Nabil; Najdi, Adil; Sicuri, Elisa; Picado, Albert

    2017-01-01

    Visceral leishmaniasis (VL) is a neglected parasitic disease with a high fatality rate if left untreated. Endemic in Morocco, as well as in other countries in the Mediterranean basin, VL mainly affects children living in rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow (BM) aspirates is used to diagnose VL and meglumine antimoniate (SB) is the first line of treatment. Less invasive, more efficacious and safer alternatives exist. In this study we estimate the cost-effectiveness of alternative diagnostic-therapeutic algorithms for paediatric VL in Morocco. A decision tree was used to estimate the cost-effectiveness of using BM or rapid diagnostic tests (RDTs) as diagnostic tools and/or SB or two liposomal amphotericin B (L-AmB) regimens: 6-day and 2-day courses to treat VL. Incremental cost-effectiveness ratios, expressed as cost per death averted, were estimated by comparing costs and effectiveness of the alternative algorithms. A threshold analysis evaluated at which price L-AmB became cost-effective compared with current practices. Implementing RDT and/or L-AmB treatments would be cost-effective in Morocco according to the WHO thresholds. Introducing the 6-day course L-AmB, current second-line treatment, would be highly cost-effective if L-AmB price was below US$100/phial. The 2-day L-AmB treatment, current standard treatment of paediatric VL in France, is highly cost-effective, with L-AmB at its market price (US$165/phial). The results of this study should encourage the implementation of RDT and/or short-course L-AmB treatments for paediatric VL management in Morocco and other North African countries.

  5. Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

    Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

    2018-05-15

    To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    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.

  7. Therapeutic Strategies against Epstein-Barr Virus-Associated Cancers Using Proteasome Inhibitors.

    Hui, Kwai Fung; Tam, Kam Pui; Chiang, Alan Kwok Shing

    2017-11-21

    Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers.

  8. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

    Manna, Prasenjit

    2015-01-01

    Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue

  9. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

    Manna, Prasenjit; Jain, Sushil K

    2015-12-01

    Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in

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

    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)

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

    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.

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

    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.

  13. Therapeutic strategies for metabolic diseases: Small-molecule diacylglycerol acyltransferase (DGAT) inhibitors.

    Naik, Ravi; Obiang-Obounou, Brice W; Kim, Minkyoung; Choi, Yongseok; Lee, Hyun Sun; Lee, Kyeong

    2014-11-01

    Metabolic diseases such as atherogenic dyslipidemia, hepatic steatosis, obesity, and type II diabetes are emerging as major global health problems. Acyl-CoA:diacylglycerol acyltransferase (DGAT) is responsible for catalyzing the final reaction in the glycerol phosphate pathway of triglycerol synthesis. It has two isoforms, DGAT-1 and DGAT-2, which are widely expressed and present in white adipose tissue. DGAT-1 is most highly expressed in the small intestine, whereas DGAT-2 is primarily expressed in the liver. Therefore, the selective inhibition of DGAT-1 has become an attractive target with growing potential for the treatment of obesity and type II diabetes. Furthermore, DGAT-2 has been suggested as a new target for the treatment of DGAT-2-related liver diseases including hepatic steatosis, hepatic injury, and fibrosis. In view the discovery of drugs that target DGAT, herein we attempt to provide insight into the scope and further reasons for optimization of DGAT inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    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

  15. A Guiding Evolutionary Algorithm with Greedy Strategy for Global Optimization Problems

    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.

  16. Novel Therapeutic Strategies in the Management of Non-Variceal Upper Gastrointestinal Bleeding

    Ari Garber

    2016-09-01

    Full Text Available Non-variceal upper gastrointestinal bleeding, the most common etiology of which is peptic ulcer disease, remains a persistent challenge despite a reduction in both its incidence and mortality. Both pharmacologic and endoscopic techniques have been developed to achieve hemostasis, with varying degrees of success. Among the pharmacologic therapies, proton pump inhibitors remain the mainstay of treatment, as they reduce the risk of rebleeding and requirement for recurrent endoscopic evaluation. Tranexamic acid, a derivative of the amino acid lysine, is an antifibrinolytic agent whose role requires further investigation before application. Endoscopically delivered pharmacotherapy, including Hemospray (Cook Medical, EndoClot (EndoClot Plus Inc., and Ankaferd Blood Stopper (Ankaferd Health Products, in addition to standard epinephrine, show promise in this regard, although their mechanisms of action require further investigation. Non-pharmacologic endoscopic techniques use one of the following two methods to achieve hemostasis: ablation or mechanical tamponade, which may involve using endoscopic clips, cautery, argon plasma coagulation, over-the-scope clipping devices, radiofrequency ablation, and cryotherapy. This review aimed to highlight these novel and fundamental hemostatic strategies and the research supporting their efficacy.

  17. Interplay Between Peripheral and Central Inflammation in Autism Spectrum Disorders: Possible Nutritional and Therapeutic Strategies

    Claudia Cristiano

    2018-03-01

    Full Text Available Pre- and post-natal factors can affect brain development and function, impacting health outcomes with particular relevance to neurodevelopmental diseases, such as autism spectrum disorders (ASDs. Maternal obesity and its associated complications have been related to the increased risk of ASDs in offspring. Indeed, animals exposed to maternal obesity or high fat diets are prone to social communication impairment and repetitive behavior, the hallmarks of autism. During development, fatty acids and sugars, as well as satiety hormones, like insulin and leptin, and inflammatory factors related to obesity-induced low grade inflammation, could play a role in the impairment of neuroendocrine system and brain neuronal circuits regulating behavior in offspring. On the other side, post-natal factors, such as mode of delivery, stress, diet, or antibiotic treatment are associated to a modification of gut microbiota composition, perturbing microbiota-gut-brain axis. Indeed, the interplay between the gastrointestinal tract and the central nervous system not only occurs through neural, hormonal, and immune pathways, but also through microbe-derived metabolic products. The modification of unhealthy perinatal and postnatal environment, manipulation of gut microbiota, nutritional, and dietary interventions could represent possible strategies in preventing or limiting ASDs, through targeting inflammatory process and gut microbiota.

  18. Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells.

    Silva, Luisa H A; Cruz, Fernanda F; Morales, Marcelo M; Weiss, Daniel J; Rocco, Patricia R M

    2017-03-09

    Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice.

  19. Targeting Hsp90-Cdc37: A Promising Therapeutic Strategy by Inhibiting Hsp90 Chaperone Function.

    Wang, Lei; Li, Li; Gu, Kai; Xu, Xiao-Li; Sun, Yuan; You, Qi-Dong

    2017-01-01

    The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein- protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Review: Pichia pastoris represents an alternative for human glycoprotein production for therapeutic use. Fermentation strategies

    Henry Córdoba Ruiz

    2003-07-01

    Full Text Available Producing human proteins in lower organisms' cells using recombinant technology represents a very promising approach for treating many diseases produced by a particular protein deficiency, including close to 40 lysosomal storage diseases. Although E. coli has been the first host successfully employed in expressing human recombinant proteins, it has some limitations owing to its inability to perform some post-traductional steps such as glycosylation. The yeast Saccharomyces cerevisiae (S. cerevisiae has thusbeen initially considered and used. However, S. cerevisiae glycosylates proteins in a very different way to human cells producing highly antigenic proteins and thus some other non-conventional yeasts such as Pichia pastoris have been used recently. Human protein expression is not assodated with growth in this system; growth may occur at high cell concentrations, increasing heterologous protein productivity and yield. The system employs a very efficient, methanol-induced promoter which may be used as sole carbon and energy source. Post-traductional modifications seem more similar to human cells than those produced by other non-mammalian systems used in producing human glycoproteins; they do not secrete large amounts of endogenous proteins, simplifying expressed protein purification. This review presents some strategies for producing heterologous proteins in high density cultures using P. pastoris as an expression system.

  1. Nanomedicine targeting the tumor microenvironment: Therapeutic strategies to inhibit angiogenesis, remodel matrix, and modulate immune responses

    Elizabeth L. Siegler

    2016-11-01

    Full Text Available Increasing attention has been given to the tumor microenvironment (TME, which includes cellular and structural components such as fibroblasts, immune cells, vasculature, and extracellular matrix (ECM that surround tumor sites. These components contribute to tumor growth and metastasis and are one reason why traditional chemotherapy often is insufficient to eradicate the tumor completely. Newer treatments that target aspects of the TME, such as antiangiogenic and immunostimulatory therapies, have seen limited clinical success despite promising preclinical results. This can be attributed to a number of reasons, including a lack of drug penetration deeper into the necrotic tumor core, nonspecific delivery, rapid clearance from serum, or toxic side effects at high doses. Nanoparticles offer a potential solution to all of these obstacles, and many recent studies have shown encouraging results using nanomedicine to target TME vasculature, ECM, and immune response. While few of these platforms have made it to clinical trials to date, these strategies are relatively new and may offer a way to improve the effects of anticancer therapies.

  2. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  3. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer.

    McKeage, Mark J; Baguley, Bruce C

    2010-04-15

    The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared with chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. (c) 2010 American Cancer Society.

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

    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.

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

    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.

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

    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.

  7. Transcutaneous spinal stimulation as a therapeutic strategy for spinal cord injury: state of the art

    Grecco LH

    2015-03-01

    Full Text Available Leandro H Grecco,1,3,4,* Shasha Li,1,5,* Sarah Michel,1,6,* Laura Castillo-Saavedra,1 Andoni Mourdoukoutas,7 Marom Bikson,7 Felipe Fregni1,21Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, 2Spaulding-Harvard Spinal Cord Injury Model System, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, USA; 3Special Laboratory of Pain and Signaling, Butantan Institute, 4Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; 5Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; 6Department of Pharmacy and Biomedical Sciences, University of Namur, Belgium; 7Department of Biomedical Engineering, The City College of New York, New York, NY, USA*These authors contributed equally to this workAbstract: Treatments for spinal cord injury (SCI still have limited effects. Electrical stimulation might facilitate plastic changes in affected spinal circuitries that may be beneficial in improving motor function and spasticity or SCI-related neuropathic pain. Based on available animal and clinical evidence, we critically reviewed the physiological basis and therapeutic action of transcutaneous spinal cord stimulation in SCI. We analyzed the literature published on PubMed to date, looking for the role of three main noninvasive stimulation techniques in the recovery process of SCI and focusing mainly on transcutaneous spinal stimulation. This review discusses the main clinical applications, latest advances, and limitations of noninvasive electrical stimulation of the spinal cord. Although most recent research in this topic has focused on transcutaneous spinal direct current stimulation (tsDCS, we also reviewed the technique of transcutaneous electric nerve stimulation (TENS and neuromuscular electrical stimulation (NMES as potential methods to modulate spinal cord

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

    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

  9. A clinical feature and therapeutic strategy in pituitary adenomas associated with intracranial aneurysms

    Sasagawa, Yasuo; Tachibana, Osamu; Shiraga, Shunsuke; Takata, Hisasi; Akai, Takuya; Iizuka, Hideaki

    2012-01-01

    We studied the clinical feature and treatment strategy of pituitary adenomas associated with intracranial aneurysms. Among 102 pituitary adenoma patients (mean age: 54.8 years old) who received MR angiography and/or 3D-CT angiography,seven patients (6.9%) had intracranial aneurysms. The association of an aneurysm was more common in large size adenomas (p<0.05). According to the location of the aneurysms,five patients had these in the paraclinoid portion or cavernous portion of the internal carotid artery. Using MR images,we classified the aneurysms associated with pituitary adenomas as non-adjacent,adjacent,and intra-adenoma types. In non-adjacent types,an aneurysm is located apart from the adenoma,and has less chance of exposure during transsphenoidal surgery. In adjacent types,an aneurysm is located adjacent to the adenoma,and could be exposed during transsphenoidal surgery. In intra-adenoma types,an aneurysm is encased in the adenoma. In non-adjacent type aneurysms,a resection of the pituitary adenoma can be carried out before aneurysm treatment due to the low risk of rupture during surgery. In adjacent types,a tumor resection can precede aneurysm treatment in cases of low rupture risk aneurysms and untreatable aneurysms. In intra-adenoma types,adenoma resection should come after treatment of the aneurysms. Neurosurgeons should be careful about not only the presence of aneurysms in preoperative images during transsphenoidal surgery planning,but also their locations and proximity to adenomas. Such information may be crucial in deciding the order of treatment. (author)

  10. Deciphering the therapeutic stem cell strategies of large and midsize pharmaceutical firms.

    Vertès, Alain A

    2014-01-01

    The slow adoption of cytotherapeutics remains a vexing hurdle given clinical progress achieved to date with a variety of stem cell lineages. Big and midsize pharmaceutical companies as an asset class still delay large-scale investments in this arena until technological and market risks will have been further reduced. Nonetheless, a handful of stem cell strategic alliance and licensing transactions have already been implemented, indicating that progress is actively monitored, although most of these involve midsize firms. The greatest difficulty is, perhaps, that the regenerative medicine industry is currently only approaching the point of inflexion of the technology development S-curve, as many more clinical trials read out. A path to accelerating technology adoption is to focus on innovation outliers among healthcare actors. These can be identified by analyzing systemic factors (e.g., national science policies and industry fragmentation) and intrinsic factors (corporate culture, e.g., nimble decision-making structures; corporate finance, e.g., opportunity costs and ownership structure; and operations, e.g., portfolio management strategies, threats on existing businesses and patent expirations). Another path is to accelerate the full clinical translation and commercialization of an allogeneic cytotherapeutic product in any indication to demonstrate the disease-modifying potential of the new products for treatment and prophylaxis, ideally for a large unmet medical need such as dry age-related macular degeneration, or for an orphan disease such as biologics-refractory acute graft-versus-host disease. In times of decreased industry average research productivities, regenerative medicine products provide important prospects for creating new franchises with a market potential that could very well mirror that achieved with the technology of monoclonal antibodies.

  11. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

    Kenneth Maiese

    2016-01-01

    Full Text Available Throughout the globe, diabetes mellitus (DM is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1 and mTOR Complex 2 (mTORC2 and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K, protein kinase B (Akt, AMP activated protein kinase (AMPK, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae (SIRT1, Wnt1 inducible signaling pathway protein 1 (WISP1, and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

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

    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...

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

    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

  14. Strategies for targeting tetraspanin proteins: potential therapeutic applications in microbial infections.

    Hassuna, Noha; Monk, Peter N; Moseley, Gregory W; Partridge, Lynda J

    2009-01-01

    The identification of novel targets and strategies for therapy of microbial infections is an area of intensive research due to the failure of conventional vaccines or antibiotics to combat both newly emerging diseases (e.g. viruses such as severe acute respiratory syndrome (SARS) and new influenza strains, and antibiotic-resistant bacteria) and entrenched, pandemic diseases exemplified by HIV. One clear approach to this problem is to target processes of the host organism rather than the microbe. Recent data have indicated that members of the tetraspanin superfamily, proteins with a widespread distribution in eukaryotic organisms and 33 members in humans, may provide such an approach. Tetraspanins traverse the membrane four times, but are distinguished from other four-pass membrane proteins by the presence of conserved charged residues in the transmembrane domains and a defining 'signature' motif in the larger of the two extracellular domains (the EC2). They characteristically form promiscuous associations with one another and with other membrane proteins and lipids to generate a specialized type of microdomain: the tetraspanin-enriched microdomain (TEM). TEMs are integral to the main role of tetraspanins as 'molecular organizers' involved in functions such as membrane trafficking, cell-cell fusion, motility, and signaling. Increasing evidence demonstrates that tetraspanins are used by intracellular pathogens as a means of entering and replicating within human cells. Although previous investigations focused mainly on viruses such as hepatitis C and HIV, it is now becoming clear that other microbes associate with tetraspanins, using TEMs as a 'gateway' to infection. In this article we review the properties and functions of tetraspanins/TEMs that are relevant to infective processes and discuss the accumulating evidence that shows how different pathogens exploit these properties in infection and in the pathogenesis of disease. We then investigate the novel and exciting

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

    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.

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

    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

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

    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.

  18. Formation of the US global energy strategy in 1991-2015

    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

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

    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

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

    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.

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

    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'.

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

    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

  3. Global demand for rare earth resources and strategies for green mining

    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.

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

    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

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

    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

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

    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...

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

    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.

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

    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...

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

    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.

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

    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.

  11. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    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

  12. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    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.

  13. Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

    Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

    2012-01-01

    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. PMID:22675615

  14. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    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.

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

    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

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

    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 ...

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

    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.

  18. Management strategies for coral reefs and people under global environmental change: 25 years of scientific research.

    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

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

    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.

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

    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

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

    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.

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

    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.

  3. Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

    Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

    2018-04-07

    Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Mitochondrial protection impairs BET bromodomain inhibitor-mediated cell death and provides rationale for combination therapeutic strategies.

    Lasorsa, E; Smonksey, M; Kirk, J S; Rosario, S; Hernandez-Ilizaliturri, F J; Ellis, L

    2015-12-10

    Inhibitors of the bromodomain and extraterminal domain family (BETI) have recently entered phase I clinical trials. In patients with advanced leukemia's, potent antileukemia activity was displayed with minimum dose-limiting toxicity. In preclinical models of hematological malignancies, including aggressive B-cell lymphomas, BETI induced cell-cycle arrest and apoptosis. However, the underlying cell death mechanisms are still not well understood. Dissecting the mechanisms required by BETI to mediate cell death would provide strong direction on how to best utilize BETI to treat patients with aggressive hematological malignancies. Herein, we provide understanding of the molecular mechanisms underlying BETI-mediated cell death using I-BET762. Induction of cell death occurred in primary murine and human B-cell lymphomas through apoptosis. Genetic dissection using Eμ-myc B-cell lymphoma compound mutants demonstrated that I-BET762-induced apoptosis does not require the p53 pathway. Furthermore, deletion of Apaf1, and thus the absence of a functional apoptosome, is associated with a delayed drug response but do not provide long-term resistance. Prolonged treatment of this model in fact fails to suppress the therapeutic efficacy of the drug and is associated with biochemical features of autophagy. However, lack of mitochondrial permeability completely inhibited I-BET762-mediated tumor cell death, indicating mitochondrial damage as key events for its activity. Combination of I-BET762 with BH3-only mimetics ABT-263 or obatoclax, restored sensitivity to I-BET762 lymphoma killing; however, success was determined by expression of Bcl-2 family antiapoptotic proteins. Our study provides critical insight for clinical decisions regarding the appropriate strategy for using BETI as a single agent or in combination to treat patients with aggressive B-cell lymphomas.

  5. Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.

    Zhang, Liang; Wang, Xiaoen; Bullock, Andrea J; Callea, Marcella; Shah, Harleen; Song, Jiaxi; Moreno, Kelli; Visentin, Barbara; Deutschman, Douglas; Alsop, David C; Atkins, Michael B; Mier, James W; Signoretti, Sabina; Bhasin, Manoj; Sabbadini, Roger A; Bhatt, Rupal S

    2015-04-15

    VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC. In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK-S1P pathway is upregulated at the time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Resistant tumors expressed several hypoxia-regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC, suggesting that human RCC behavior could, in part, be due to overproduction of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment-naïve RCC and also in the setting of resistance to VEGFR TKI therapy. ©2015 American Association for Cancer Research.

  6. Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

    Hanumantha Rao Madala

    2018-02-01

    Full Text Available Isocitrate dehydrogenases 1 and 2 (IDH1,2, the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs and gain an unusual new activity of reducing the α-ketoglutarate (α-KG to D-2 hydroxyglutarate (D-2HG in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation, JmjC domain-containing KDMs (histone lysine demethylases, and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma.

  7. Therapeutic approaches of hematopoietic syndrome after serious accidental global irradiation. Ex vivo expansion interest of hematopoietic cells

    Thierry, D.

    1994-01-01

    Aplasia is one of the main syndrome, appearing after one global accidental irradiation by one ionizing radiation source. The hematopoietic syndrome is characterized by a peripheric blood cell number fall; the cell marrow is reduced too

  8. Globalization

    Tulio Rosembuj

    2006-12-01

    Full Text Available There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  9. Globalization

    Tulio Rosembuj

    2006-01-01

    There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

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

    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

  11. Strategies for the coupling of global and local crystal growth models

    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.

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

    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

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

    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

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

    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.

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

    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

  16. The global challenge of type 2 diabetes and the strategies for response in ethnic minority groups.

    Lirussi, Flavio

    2010-09-01

    Ethnic minorities living in high-income countries usually exhibit a greater risk of developing diabetes along with higher morbidity and mortality rates. We evaluated the effectiveness of interventions to improve glycaemic control in ethnic minority groups. Results of major controlled trials, systematic reviews and meta-analyses were included in the review. Only 1/47 studies addressing diet and exercise interventions reported details on the ethnicity of the studied population. Self-management education was successful if associated with increased self-efficacy; delivered over a longer period; of high intensity; culturally tailored; and when using community educators. Strategies adopted in community-gathering places, family-based, multifaceted, and those tackling the social context were likely to be more effective. A positive relationship was found between social support and self-management behaviour as well as quality of life, but there is little evidence about the impact of organizational changes within health-care services on diabetes control. More research is needed to strengthen the evidence on effective strategies for response to diabetes in ethnic minorities. Also, there is a need to take into account diabetes beliefs and communication difficulties, as well as potential protective factors. Globally, many health-care systems are inadequately equipped to improve diabetes prevention and disease outcomes in these communities. 2010 John Wiley & Sons, Ltd.

  17. Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

    O'Keefe, Denise

    2002-01-01

    Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver...

  18. Preclinical models for an innovative glioblastoma therapeutical strategy by 188Re-SSS encapsulated in nano-tools: translational view

    Cikankowitz, A.; Belloche, C.; Verger, E.; Garcion, E.; Hindre, F.; Chassain, G.; Fellah, B.; Abadie, J.; Chouin, N.; Ibisch, C.; Davodeau, F.; Couez, D.; Lepareur, N.; Lacoeuille, F.; Menei, P.

    2015-01-01

    Full text of publication follows. Aim: Glioblastoma (GBM) is the most frequent cancer of the nervous system and therapies currently used cannot treat definitively this disease. By the way of NucSan (Nuclear for health) program which supports research development about the use of radio pharmaceutics in oncology, the aim of the proposed work is to provide evidences that internal radiotherapy through lipid nanocapsules loaded with Rhenium-188 (LNC 188 Re-SSS) is an alternative therapeutic strategy for GBM that can be translated to human medicine. Previous works have shown a remarkable efficiency of this tool among syngeneic rats linked with local and peripheral recruitments of the immune system's effectors. In this context, two animal models have been chosen to validate the feasibility of this new innovative therapy design (LNC 188 Re-SSS stereotactic injection). Materials and methods: the syngeneic six weeks old C57BL/6J female mice were treated 6 or 12 days after stereotactic GL261 cells implantation, by a single injection of increasing activities of LNC 188 Re-SSS (0,925; 1,85 and 2,7 MBq/5μl). MRI was used to follow tumor progression to determine the mass volume through the selection of regions of interest. The increased median survival time (IMST) was also assessed for treated mice versus control mice (stereotactic injection of saline solution). For long time survival animals (3 times the median survival time), they were rechallenged through the same procedure in the other hemisphere. The brachy-cephalic dog bearing spontaneous tumor will lead to additional evidences to specifically highlight the potential of this innovative technology for GBM treatment. In order to validate procedures of intracerebral injections, a stereotactic head frame specially designed for dog has been conceived which allow both images acquisition (MRI-SPECT and PET) and the achievement of biopsies. Results/Perspectives: as previously observed on rat models, the preliminary data show

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

    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

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

    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.

  1. From Risks to Shared Value? Corporate Strategies in Building a Global Water Accounting and Disclosure Regime

    Marco A. Daniel

    2012-10-01

    Full Text Available The current debate on water accounting and accountability among transnational actors such as corporations and NGOs is likely to contribute to the emergence of a global water governance regime. Corporations within the food and beverage sector (F-B are especially vulnerable to water risks; therefore, in this article we analyse motivations and strategies of the major F-B corporations participating in the debate and developing different water accounting, disclosure and risk-assessment tools. Neo-institutionalism and neo-Gramscian regime theory provide the basis for our framework to analyse the discursive, material and organisational corporate water strategies. Findings based on an analysis of the chosen F-B corporations’ sustainability reports and interviews with key informants suggest that the corporations share similar goals and values with regard to the emerging regime. They seek a standardisation that is practical and supportive in improving their water efficiency and communication with stakeholders. This indicates that some harmonisation has taken place over time and new actors have been pursuing the path of the pioneering companies, but the lead corporations are also differentiating their strategies, thus engaging in hegemonic positioning. However, so far the plethora of NGO-driven accountability initiatives and tools has fragmented the field more than 'war of position' amongst the corporations. Furthermore, several companies claim to have proceeded from internal water-risk management to reducing risks throughout their value chains and watersheds. As a result they are 'creating shared value' with stakeholders, and potentially manifesting an emergent paradigm that goes beyond a private regime framework. Nevertheless, in the absence of verification schemes, questions of sustainability and legitimacy of such actions on the ground prevail and remain a topic for further research.

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

    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

  3. Globalization

    Andru?cã Maria Carmen

    2013-01-01

    The field of globalization has highlighted an interdependence implied by a more harmonious understanding determined by the daily interaction between nations through the inducement of peace and the management of streamlining and the effectiveness of the global economy. For the functioning of the globalization, the developing countries that can be helped by the developed ones must be involved. The international community can contribute to the institution of the development environment of the gl...

  4. Therapeutic affordances of social media: emergent themes from a global online survey of people with chronic pain.

    Merolli, Mark; Gray, Kathleen; Martin-Sanchez, Fernando

    2014-12-22

    Research continues to present tenuous suggestions that social media is well suited to enhance management of chronic disease and improve health outcomes. Various studies have presented qualitative reports of health outcomes from social media use and have examined discourse and communication themes occurring through different social media. However, there is an absence of published studies examining and unpacking the underlying therapeutic mechanisms driving social media's effects. This paper presents a qualitative analysis thoroughly describing what social media therapeutically affords people living with chronic pain who are self-managing their condition. From this therapeutic affordance perspective, we aim to formulate a preliminary conceptual model aimed at better understanding "how" social media can influence patient outcomes. In total, 218 people with chronic pain (PWCP) completed an online survey, investigating patient-reported outcomes (PROs) from social media use. Supplementary to quantitative data collected, participants were also given the opportunity to provide further open commentary regarding their use of social media as part of chronic pain management; 68/218 unique users (31.2%) chose to provide these free-text responses. Through thematic content analysis, 117 free-text responses regarding 10 types of social media were coded. Quotes were extracted and tabulated based on therapeutic affordances that we had previously identified. Inductive analysis was then performed to code defining language and emergent themes central to describing each affordance. Three investigators examined the responses, developed the coding scheme, and applied the coding to the data. We extracted 155 quotes from 117 free-text responses. The largest source of quotes came from social network site users (78/155, 50.3%). Analysis of component language used to describe the aforementioned affordances and emergent themes resulted in a final revision and renaming of therapeutic affordances

  5. Therapeutic Affordances of Social Media: Emergent Themes From a Global Online Survey of People With Chronic Pain

    Gray, Kathleen; Martin-Sanchez, Fernando

    2014-01-01

    Background Research continues to present tenuous suggestions that social media is well suited to enhance management of chronic disease and improve health outcomes. Various studies have presented qualitative reports of health outcomes from social media use and have examined discourse and communication themes occurring through different social media. However, there is an absence of published studies examining and unpacking the underlying therapeutic mechanisms driving social media’s effects. Objective This paper presents a qualitative analysis thoroughly describing what social media therapeutically affords people living with chronic pain who are self-managing their condition. From this therapeutic affordance perspective, we aim to formulate a preliminary conceptual model aimed at better understanding "how" social media can influence patient outcomes. Methods In total, 218 people with chronic pain (PWCP) completed an online survey, investigating patient-reported outcomes (PROs) from social media use. Supplementary to quantitative data collected, participants were also given the opportunity to provide further open commentary regarding their use of social media as part of chronic pain management; 68/218 unique users (31.2%) chose to provide these free-text responses. Through thematic content analysis, 117 free-text responses regarding 10 types of social media were coded. Quotes were extracted and tabulated based on therapeutic affordances that we had previously identified. Inductive analysis was then performed to code defining language and emergent themes central to describing each affordance. Three investigators examined the responses, developed the coding scheme, and applied the coding to the data. Results We extracted 155 quotes from 117 free-text responses. The largest source of quotes came from social network site users (78/155, 50.3%). Analysis of component language used to describe the aforementioned affordances and emergent themes resulted in a final revision

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

    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

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

    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

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

    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

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

    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

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

    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.

  11. Impact of management strategies on the global warming potential at the cropping system level

    Goglio, Pietro; Grant, Brian B.; Smith, Ward N.; Desjardins, Raymond L.; Worth, Devon E.; Zentner, Robert; Malhi, Sukhdev S.

    2014-01-01

    Estimating the greenhouse gas (GHG) emissions from agricultural systems is important in order to assess the impact of agriculture on climate change. In this study experimental data supplemented with results from a biophysical model (DNDC) were combined with life cycle assessment (LCA) to investigate the impact of management strategies on global warming potential of long-term cropping systems at two locations (Breton and Ellerslie) in Alberta, Canada. The aim was to estimate the difference in global warming potential (GWP) of cropping systems due to N fertilizer reduction and residue removal. Reducing the nitrogen fertilizer rate from 75 to 50 kg N ha −1 decreased on average the emissions of N 2 O by 39%, NO by 59% and ammonia volatilisation by 57%. No clear trend for soil CO 2 emissions was determined among cropping systems. When evaluated on a per hectare basis, cropping systems with residue removal required 6% more energy and had a little change in GWP. Conversely, when evaluated on the basis of gigajoules of harvestable biomass, residue removal resulted in 28% less energy requirement and 33% lower GWP. Reducing nitrogen fertilizer rate resulted in 18% less GWP on average for both functional units at Breton and 39% less GWP at Ellerslie. Nitrous oxide emissions contributed on average 67% to the overall GWP per ha. This study demonstrated that small changes in N fertilizer have a minimal impact on the productivity of the cropping systems but can still have a substantial environmental impact. - Highlights: • LCA was combined with DNDC model to estimate the GWP of a cropping system. • N 2 O, NO and NH 3 flux increased by 39% under the higher fertilizer rate. • A change from 75 to 50 kg N ha −1 reduced the GWP per ha and GJ basis by 18%. • N 2 O emissions contributed 67% to the overall GWP of the cropping system. • Small changes in N fertilizer can have a substantial environmental impact

  12. Goals and strategies in the global control design of the OAJ Robotic Observatory

    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.

  13. Which way to go. Observations based on discussion on global perspectives and energy strategies

    Sassin, W; Lovins, A; Meadows, D; Penczynski, P

    1977-09-01

    One of the most controversial topics of the present time seems to be the world's future energy supply and demand. To establish a balanced view, the IIASA Energy Systems Program has sought periodically to compare its own work with that of other groups researching similar areas. At the beginning of 1977, Dennis Meadows, co-author of the Club-of-Rome study ''Limits to Growth'', and Amory Lovins of ''Friends of the Earth'' joined IIASA for a limited time. Both of them favor a ''soft technology'' path for the world's future energy system. Their stay at IIASA was an opportunity to check whether or not their results provide for a deeper understanding of a complex global future. This short note summarizes some conclusions that emerged from discussions of D. Meadows, A. Lovins, and members of the Energy Systems Program. In searching for the sources of opposing conclusions with respect to nuclear, large-scale solar, coal, renewable sources in a local or regional context (like wind, wave power, biomass utilization, and small-scale solar heat) and energy conservation measures such as better insulation or the co-generation of electricity and process heat, it turned out to be helpful to address the following questions: (1) Which long-term fundamental problems other than energy questions have to be faced by mankind within the coming 50 years. (2) Is the appropriate scale for analyzing these problems global, regional, or local. (3) In which subsectors should the economy be disaggregated in order to tackle the problem of self-reliance and resilience. (4) How can one define a technological solution for the energy supply with respect to the anticipated state of affairs in terms of do's and not in terms of don'ts. (5) How can one specify an energy strategy leading from today's situation into a long-term future when the goals to be achieved vary with time and in principle are subject to revision. (MCW)

  14. Impact of management strategies on the global warming potential at the cropping system level.

    Goglio, Pietro; Grant, Brian B; Smith, Ward N; Desjardins, Raymond L; Worth, Devon E; Zentner, Robert; Malhi, Sukhdev S

    2014-08-15

    Estimating the greenhouse gas (GHG) emissions from agricultural systems is important in order to assess the impact of agriculture on climate change. In this study experimental data supplemented with results from a biophysical model (DNDC) were combined with life cycle assessment (LCA) to investigate the impact of management strategies on global warming potential of long-term cropping systems at two locations (Breton and Ellerslie) in Alberta, Canada. The aim was to estimate the difference in global warming potential (GWP) of cropping systems due to N fertilizer reduction and residue removal. Reducing the nitrogen fertilizer rate from 75 to 50 kg N ha(-1) decreased on average the emissions of N2O by 39%, NO by 59% and ammonia volatilisation by 57%. No clear trend for soil CO2 emissions was determined among cropping systems. When evaluated on a per hectare basis, cropping systems with residue removal required 6% more energy and had a little change in GWP. Conversely, when evaluated on the basis of gigajoules of harvestable biomass, residue removal resulted in 28% less energy requirement and 33% lower GWP. Reducing nitrogen fertilizer rate resulted in 18% less GWP on average for both functional units at Breton and 39% less GWP at Ellerslie. Nitrous oxide emissions contributed on average 67% to the overall GWP per ha. This study demonstrated that small changes in N fertilizer have a minimal impact on the productivity of the cropping systems but can still have a substantial environmental impact. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  15. Huntington's disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database.

    Kalathur, Ravi Kiran Reddy; Hernández-Prieto, Miguel A; Futschik, Matthias E

    2012-06-28

    Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally

  16. Huntington's Disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database

    Kalathur Ravi Kiran

    2012-06-01

    Full Text Available Abstract Background Huntington’s disease (HD is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. Methods To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. Results Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling, but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling. For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are

  17. Albedo control as an effective strategy to tackle Global Warming: A case study

    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

  18. Design strategies to minimize the radiative efficiency of global warming molecules

    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

  19. TES ammonia retrieval strategy and global observations of the spatial and seasonal variability of ammonia

    M. W. Shephard

    2011-10-01

    Full Text Available Presently only limited sets of tropospheric ammonia (NH3 measurements in the Earth's atmosphere have been reported from satellite and surface station measurements, despite the well-documented negative impact of NH3 on the environment and human health. Presented here is a detailed description of the satellite retrieval strategy and analysis for the Tropospheric Emission Spectrometer (TES using simulations and measurements. These results show that: (i the level of detectability for a representative boundary layer TES NH3 mixing ratio value is ~0.4 ppbv, which typically corresponds to a profile that contains a maximum level value of ~1 ppbv; (ii TES NH3 retrievals generally provide at most one degree of freedom for signal (DOFS, with peak sensitivity between 700 and 900 mbar; (iii TES NH3 retrievals show significant spatial and seasonal variability of NH3 globally; (iv initial comparisons of TES observations with GEOS-CHEM estimates show TES values being higher overall. Important differences and similarities between modeled and observed seasonal and spatial trends are noted, with discrepancies indicating areas where the timing and magnitude of modeled NH3 emissions from agricultural sources, and to lesser extent biomass burning sources, need further study.

  20. Strategies for antiviral stockpiling for future influenza pandemics: a global epidemic-economic perspective.

    Carrasco, Luis R; Lee, Vernon J; Chen, Mark I; Matchar, David B; Thompson, James P; Cook, Alex R

    2011-09-07

    Influenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offset their negative impacts; however, little is known about the long-term optimal size of the stockpile under uncertainty and the characteristics of different countries. Using an epidemic-economic model we studied the effect on total mortality and costs of antiviral stockpile sizes for Brazil, China, Guatemala, India, Indonesia, New Zealand, Singapore, the UK, the USA and Zimbabwe. In the model, antivirals stockpiling considerably reduced mortality. There was greater potential avoidance of expected costs in the higher resourced countries (e.g. from $55 billion to $27 billion over a 30 year time horizon for the USA) and large avoidance of fatalities in those less resourced (e.g. from 11.4 to 2.3 million in Indonesia). Under perfect allocation, higher resourced countries should aim to store antiviral stockpiles able to cover at least 15 per cent of their population, rising to 25 per cent with 30 per cent misallocation, to minimize fatalities and economic costs. Stockpiling is estimated not to be cost-effective for two-thirds of the world's population under current antivirals pricing. Lower prices and international cooperation are necessary to make the life-saving potential of antivirals cost-effective in resource-limited countries.

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

    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

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

    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.

  3. On the strategy of modernization and development of Russian economy in a global depression

    Sergey Yurievich Glazyev

    2011-06-01

    Full Text Available This paper reveals the essence of the program proposed by author on preemptive measures to develop the Russian economy in terms of a global depression. The distinctive features of the present global crisis and the prospects of overcoming it are identified. We propose three possible scenarios for the world economy after the crisis: 1 the scenario of quick withdrawal to a long wave of economic growth (optimistic; 2 the catastrophic scenario; 3 the inertial scenario. The key idea of forming a national strategy for accelerated development lies in: the timely establishment of basic industries, the new technological order and early withdrawal of the Russian economy on the associated new long wave of growth, increasing the power of multiple domestic banking and investment system; economic stabilization and creating a zone of sustainable development in the regions of the Eurasian Economic Community and the CIS. Taking into account the experience of anti-crisis policy of foreign countries, strategic mistakes in the planning of anti-crisis measures are identified. In the analysis of national anti-crisis policies and assessing the effectiveness of anti-crisis measures it is justified that the same mistakes were made in Russia. To overcome them, it is required to provide consistency of macroeconomic policies with the priorities of long-term economic and technological development. It might be achieved by concentrating resources on the development of advanced industrial and technological systems that require dedicated work of the national financial and investment system, including the mechanisms of monetary, fiscal and foreign exchange policy. Conceptual parameters of the strategic planning system that can identify promising areas of economic growth as well as guide the development of state institutions to implement them are formulated. The elements of such a system created in Russia in recent years and requiring its introduction are defined. The efficiency

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

    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.

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

    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

  6. Adoption of Technology as a Response Strategy to Globalization: A Study of Manufacturing Firms in Kenya

    Solomon Kinyanjui; Margaret A. Oloko; Hazel G. Gachunga; Beatrice G. Gathondu

    2014-01-01

    Globalization affects local and international firms in many ways. Studies have shown that factors in the internal as well as external environments of firms influence the rate to which globalization will affect them. On the local scene however, no known studies have been done on the response of manufacturing firms to counter globalization. In addition, since the concept of globalization is multidimensional and its influence is varied in nature, this study aimed at investigating how manufacturi...

  7. Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

    Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

    2017-09-01

    Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel

  8. Impact of management strategies on the global warming potential at the cropping system level

    Goglio, Pietro; Grant, Brian B.; Smith, Ward N. [Eastern Cereal and Oilseed Research Centre, Agriculture and Agri-Food Canada, K.W. Neatby Building, Ottawa, Ontario K1A 0C6 (Canada); Desjardins, Raymond L., E-mail: ray.desjardins@agr.gc.ca [Eastern Cereal and Oilseed Research Centre, Agriculture and Agri-Food Canada, K.W. Neatby Building, Ottawa, Ontario K1A 0C6 (Canada); Worth, Devon E. [Eastern Cereal and Oilseed Research Centre, Agriculture and Agri-Food Canada, K.W. Neatby Building, Ottawa, Ontario K1A 0C6 (Canada); Zentner, Robert [Swift Current Research Station, Swift Current, Saskatchewan S0E 1A0 (Canada); Malhi, Sukhdev S. [Melfort Research Farm, PO Box 1240, Melfort, Saskatchewan S0E 1A0 (Canada)

    2014-08-15

    Estimating the greenhouse gas (GHG) emissions from agricultural systems is important in order to assess the impact of agriculture on climate change. In this study experimental data supplemented with results from a biophysical model (DNDC) were combined with life cycle assessment (LCA) to investigate the impact of management strategies on global warming potential of long-term cropping systems at two locations (Breton and Ellerslie) in Alberta, Canada. The aim was to estimate the difference in global warming potential (GWP) of cropping systems due to N fertilizer reduction and residue removal. Reducing the nitrogen fertilizer rate from 75 to 50 kg N ha{sup −1} decreased on average the emissions of N{sub 2}O by 39%, NO by 59% and ammonia volatilisation by 57%. No clear trend for soil CO{sub 2} emissions was determined among cropping systems. When evaluated on a per hectare basis, cropping systems with residue removal required 6% more energy and had a little change in GWP. Conversely, when evaluated on the basis of gigajoules of harvestable biomass, residue removal resulted in 28% less energy requirement and 33% lower GWP. Reducing nitrogen fertilizer rate resulted in 18% less GWP on average for both functional units at Breton and 39% less GWP at Ellerslie. Nitrous oxide emissions contributed on average 67% to the overall GWP per ha. This study demonstrated that small changes in N fertilizer have a minimal impact on the productivity of the cropping systems but can still have a substantial environmental impact. - Highlights: • LCA was combined with DNDC model to estimate the GWP of a cropping system. • N{sub 2}O, NO and NH{sub 3} flux increased by 39% under the higher fertilizer rate. • A change from 75 to 50 kg N ha{sup −1} reduced the GWP per ha and GJ basis by 18%. • N{sub 2}O emissions contributed 67% to the overall GWP of the cropping system. • Small changes in N fertilizer can have a substantial environmental impact.

  9. Will Transition of Staple Food Strategy in China Really Mitigate Global Climate Change?

    Liu, B.; Zhao, D.

    2017-12-01

    With the increase in agricultural demand, reducing greenhouse gas (GHG) emissions is a vital challenge in mitigating climate change. Potato staple food strategy in China introduced by Ministry of Agriculture in 2015 is to gradually adjust staple food structure, which provides an opportunity to meet with the challenge. Apart from staple food structure, difference on energy, material input, geography, and crop management are essential to determine agriculture's contribution to climate change. In this study, we conduct a life cycle analysis of four staple foods in China, namely rice, wheat, maize, and potato, to develop crop-specific estimates of GHG emissions and GHG intensity by using `Production intensity' (carbon dioxide equivalent emissions per kilocalorie produced), to help us understand potential synergies and frictions between food producing and climate mitigation. Data used in this study is on city / province levels if city level is unavailable in 2015. First, we evaluate GHG reductions due to transition of staple food structure in China. Staple food GHG emissions in China are 546.90 Tg CO2e yr-1 in 2015, with 47.6%, 21.9%, 27.3% and 3.2% from rice, wheat, maize and potato. Mean production intensity of staple food is 0.45 Mg CO2e M kcal-1 in 2015. Maize leads the intensity with 0.77 Mg CO2e M kcal-1, followed by rice (0.49 Mg CO2e M kcal-1), wheat (0.28 Mg CO2e M kcal-1) and potato (0.24 Mg CO2e M kcal-1). After staple food structure adjustment, 25 Tg CO2e yr-1 (4.2%) reduction will be accomplished in 2020 without any crop management improvement. Further reduction (33.3% - 40.4%) could be achieved with crop management improvement. In addition, because of staple food structure switching, native rice production will decline, which might lead to more export from countries with higher production intensity. Estimated emission leakage from rice import is 30.10 Tg CO2e yr-1, exceeds emission reduction in native China. Therefore, potato staple food strategy could

  10. A global epidemiological survey and strategy of treatment of military ocular injury

    Mao-nian ZHANG

    2011-10-01

    Full Text Available Objective To investigate the current global status of military ocular injury for the purpose of improving the level of domestic epidemiological investigation,in order to improve treatment strategies,and to prevent and reduce the incidence of military ocular injury in Chinese PLA.Methods The epidemiological literature concerning military ocular injury occurring in our country and abroad in recent five years was retrieved by information research;the problems and experiences in the aspects of epidemiological survey,registry,data collection,systematic treatment and prevention of military ocular injury existed in PLA were also summarized and analyzed.Results There were currently no systematic epidemiological data about ocular injury in PLA.A few articles about epidemiological study on ocular injury showed that servicemen were the high risk population of ocular injury.Both in peacetime or wartime the ocular injury was the primary cause leading to monocular blindness of soldiers.As to the ocular injury,in 51.55% of the patients,it occurred in the military operations and work,and 30.31% in military training.The incidence of ocular injury was different in various services,for example,the incidence in the internal security forces of armed police could be as high as 78.85% due to training of martial arts and boxing and wrestling.The deficiency of microsurgery equipments and untimely evacuation were the main causes affecting prognosis during treatment course in primary military hospitals.Conclusions Military affairs,physical training,military maneuver and defense constructions are the main causes of ocular injury in servicemen,and young male soldiers are the main group for prevention and treatment for military ocular injury.More attention should be paid to the epidemiological survey of military ocular injury to find out the causes leading to ocular injury,to improve treatment strategies,to formulate feasible protective measures and then military ocular

  11. LC-MS/MS strategies for therapeutic antibodies and investigation into the quantitative impact of antidrug-antibodies.

    Ewles, Matthew; Mannu, Ranbir; Fox, Chris; Stanta, Johannes; Evans, Graeme; Goodwin, Lee; Duffy, James; Bell, Len; Estdale, Sian; Firth, David

    2016-12-01

    We aimed to establish novel, high-throughput LC-MS/MS strategies for quantification of monoclonal antibodies in human serum and examine the potential impact of antidrug antibodies. We present two strategies using a thermally stable immobilized trypsin. The first strategy uses whole serum digestion and the second introduces Protein G enrichment to improve the selectivity. The impact of anti-trastuzumab antibodies on the methods was tested. Whole serum digestion has been validated for trastuzumab (LLOQ 0.25 µg/ml). Protein G enrichment has been validated for trastuzumab (LLOQ 0.1 µg/ml), bevacizumab (LLOQ 0.1 µg/ml) and adalimumab (LLOQ 0.25 µg/ml). We have shown the potential for anti-drug antibodies to impact on the quantification and we have subsequently established a strategy to overcome this impact where total quantification is desired.

  12. Globalization

    Plum, Maja

    Globalization is often referred to as external to education - a state of affair facing the modern curriculum with numerous challenges. In this paper it is examined as internal to curriculum; analysed as a problematization in a Foucaultian sense. That is, as a complex of attentions, worries, ways...... of reasoning, producing curricular variables. The analysis is made through an example of early childhood curriculum in Danish Pre-school, and the way the curricular variable of the pre-school child comes into being through globalization as a problematization, carried forth by the comparative practices of PISA...

  13. Globalization

    F. Gerard Adams

    2008-01-01

    The rapid globalization of the world economy is causing fundamental changes in patterns of trade and finance. Some economists have argued that globalization has arrived and that the world is “flat†. While the geographic scope of markets has increased, the author argues that new patterns of trade and finance are a result of the discrepancies between “old†countries and “new†. As the differences are gradually wiped out, particularly if knowledge and technology spread worldwide, the t...

  14. Global alliance against chronic respiratory diseases in Italy (GARD-Italy): strategy and activities.

    Laurendi, Giovanna; Mele, Sonia; Centanni, Stefano; Donner, Claudio F; Falcone, Franco; Frateiacci, Sandra; Lazzeri, Marta; Mangiacavallo, Antonino; Indinnimeo, Luciana; Viegi, Giovanni; Pisanti, Paola; Filippetti, Giuseppe

    2012-01-01

    The steady increase in incidence of chronic respiratory disease (CRD) now constitutes a serious public health problem. CRDs are often underdiagnosed and many patients are not diagnosed until the CRD is too severe to prevent normal daily activities. The prevention of CRDs and reducing their social and individual impacts means modifying environmental and social factors and improving diagnosis and treatment. Prevention of risk factors (tobacco smoke, allergens, occupational agents, indoor/outdoor air pollution) will significantly impact on morbidity and mortality. The Italian Ministry of Health (MoH) has made respiratory disease prevention a top priority and is implementing a comprehensive strategy with policies against tobacco smoking, indoor/outdoor pollution, obesity, and communicable diseases. Presently these actions are not well coordinated. The Global Alliance against Chronic Respiratory Diseases (GARD), set up by the World Health Organization, envisages national bodies; the GARD initiative in Italy, launched 11/6/2009, represents a great opportunity for the MoH. Its main objective is to promote the development of a coordinated CRD program in Italy. Effective prevention implies setting up a health policy with the support of healthcare professionals and citizen associations at national, regional, and district levels. What is required is a true inter-institutional synergy: respiratory diseases prevention cannot and should not be the responsibility of doctors alone, but must involve politicians/policymakers, as well as the media, local institutions, and schools, etc. GARD could be a significant experience and a great opportunity for Italy to share the GARD vision of a world where all people can breathe freely. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

    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.

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

    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

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

    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.

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

    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.

  19. Research strategy of the therapeutic quality of mud and salty water from Ursu(Bear Lake, Sovata, 

    Munteanu Constantin

    2012-05-01

    Full Text Available Infertility (sterility is a health problem affecting 15% of couples of reproductive age. Today only a few are known about causes and treatment options involved in the pathology of infertility, while a number of issues remain unknown. Currently natural therapeutic factors from Sovata are used, based on experience over the years, for the following causes of infertility: tubal obstruction, laparoscopic postneosalpingostomiei recovery treatment (prevention of restenozations, sequelae after pelvic inflammatory disease, peritonitis, post-inflammatory adhesions; secretory ovarian dysfunction (estrogen, progesterone, polycystic ovarian syndrome, endometriosis, infertility induced by stress.

  20. Global navigation satellite systems performance analysis and augmentation strategies in aviation

    Sabatini, Roberto; Moore, Terry; Ramasamy, Subramanian

    2017-11-01

    In an era of significant air traffic expansion characterized by a rising congestion of the radiofrequency spectrum and a widespread introduction of Unmanned Aircraft Systems (UAS), Global Navigation Satellite Systems (GNSS) are being exposed to a variety of threats including signal interferences, adverse propagation effects and challenging platform-satellite relative dynamics. Thus, there is a need to characterize GNSS signal degradations and assess the effects of interfering sources on the performance of avionics GNSS receivers and augmentation systems used for an increasing number of mission-essential and safety-critical aviation tasks (e.g., experimental flight testing, flight inspection/certification of ground-based radio navigation aids, wide area navigation and precision approach). GNSS signal deteriorations typically occur due to antenna obscuration caused by natural and man-made obstructions present in the environment (e.g., elevated terrain and tall buildings when flying at low altitude) or by the aircraft itself during manoeuvring (e.g., aircraft wings and empennage masking the on-board GNSS antenna), ionospheric scintillation, Doppler shift, multipath, jamming and spurious satellite transmissions. Anyone of these phenomena can result in partial to total loss of tracking and possible tracking errors, depending on the severity of the effect and the receiver characteristics. After designing GNSS performance threats, the various augmentation strategies adopted in the Communication, Navigation, Surveillance/Air Traffic Management and Avionics (CNS + A) context are addressed in detail. GNSS augmentation can take many forms but all strategies share the same fundamental principle of providing supplementary information whose objective is improving the performance and/or trustworthiness of the system. Hence it is of paramount importance to consider the synergies offered by different augmentation strategies including Space Based Augmentation System (SBAS), Ground

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

    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

  2. Global health promotion: how can we strengthen governance and build effective strategies?

    Lee, Kelley

    2006-12-01

    This paper discusses what is meant by 'global health promotion' and the extent to which global governance architecture is emerging, enabling people to increase control over, and to improve, their health within an increasingly global context. A review of selected initiatives on breast-milk substitutes, healthy cities, tobacco control and diet and nutrition suggests that existing institutions are uneven in their capacity to tackle global health issues. The strategic building of a global approach to health promotion will draw on a broad range of governance instruments, give careful attention to implementation in the medium to longer term, reflect on the nature and appropriateness of partnerships and develop fuller understanding of effective policies for harnessing the positive influences of globalization and countering the negatives.

  3. Assessment of refractive astigmatism and simulated therapeutic refractive surgery strategies in coma-like-aberrations-dominant corneal optics.

    Zhou, Wen; Stojanovic, Aleksandar; Utheim, Tor Paaske

    2016-01-01

    The aim of the study is to raise the awareness of the influence of coma-like higher-order aberrations (HOAs) on power and orientation of refractive astigmatism (RA) and to explore how to account for that influence in the planning of topography-guided refractive surgery in eyes with coma-like-aberrations-dominant corneal optics. Eleven eyes with coma-like-aberrations-dominant corneal optics and with low lenticular astigmatism (LA) were selected for astigmatism analysis and for treatment simulations with topography-guided custom ablation. Vector analysis was used to evaluate the contribution of coma-like corneal HOAs to RA. Two different strategies were used for simulated treatments aiming to regularize irregular corneal optics: With both strategies correction of anterior corneal surface irregularities (corneal HOAs) were intended. Correction of total corneal astigmatism (TCA) and RA was intended as well with strategies 1 and 2, respectively. Axis of discrepant astigmatism (RA minus TCA minus LA) correlated strongly with axis of coma. Vertical coma influenced RA by canceling the effect of the with-the-rule astigmatism and increasing the effect of the against-the-rule astigmatism. After simulated correction of anterior corneal HOAs along with TCA and RA (strategies 1 and 2), only a small amount of anterior corneal astigmatism (ACA) and no TCA remained after strategy 1, while considerable amount of ACA and TCA remained after strategy 2. Coma-like corneal aberrations seem to contribute a considerable astigmatic component to RA in eyes with coma-like-aberrations dominant corneal optics. If topography-guided ablation is programmed to correct the corneal HOAs and RA, the astigmatic component caused by the coma-like corneal HOAs will be treated twice and will result in induced astigmatism. Disregarding RA and treating TCA along with the corneal HOAs is recommended instead.

  4. Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases?

    Jansen, Manon A A; Spiering, Rachel; Broere, Femke; van Laar, Jacob M; Isaacs, John D; van Eden, Willem; Hilkens, Catharien M U

    2018-01-01

    Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T-cell response while leaving other, protective, T-cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. A possible solution is to use surrogate autoantigens for loading of tolDCs. We propose that heat-shock proteins may be a relevant surrogate antigen, as they are evolutionarily conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models. In this review, we provide an overview on how immune tolerance may be restored by tolDCs, the problem of selecting relevant autoantigens for loading of tolDCs, and why heat-shock proteins could be used as surrogate autoantigens. © 2017 John Wiley & Sons Ltd.

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

    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.

  6. 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

    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.

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

    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.

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

    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.

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

    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

  10. Global Learning and Development as an Engagement Strategy for Christian Higher Education: A Macro Study

    Decker, Allyn; Hawkins, Greg

    2016-01-01

    The purpose of this research was to better understand the variety of student and faculty global learning and development programs by member institutions of the Council for Christian Colleges & Universities (CCCU), and what motivated the creation of these types of programs. Although various forms of global engagement programming were examined,…

  11. Acting locally, developing knowledge globally: a transitions perspective on designing climate change adaptation strategies

    Grin, J.; Driessen, J.; Leroy, P.; van Vierssen, W.

    2010-01-01

    Climate change, from many perspectives and for many reasons, is a complex issue: scientifically, politically, and in terms of global justice. As such, climate change might be the global societal and political challenge of the 21st century. Dealing with it, either via mitigation or via adaptation,

  12. Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy.

    Timpani, Cara A; Hayes, Alan; Rybalka, Emma

    2017-05-25

    Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

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

    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 ...

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

    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.

  15. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

    Crighton, Gemma L; Estcourt, Lise J; Wood, Erica M; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon

    2015-01-01

    expected by The Cochrane Collaboration. Main results We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm. Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding. Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine

  16. Recombinant Endolysins as Potential Therapeutics against Antibiotic-Resistant Staphylococcus aureus: Current Status of Research and Novel Delivery Strategies.

    Haddad Kashani, Hamed; Schmelcher, Mathias; Sabzalipoor, Hamed; Seyed Hosseini, Elahe; Moniri, Rezvan

    2018-01-01

    Staphylococcus aureus is one of the most common pathogens of humans and animals, where it frequently colonizes skin and mucosal membranes. It is of major clinical importance as a nosocomial pathogen and causative agent of a wide array of diseases. Multidrug-resistant strains have become increasingly prevalent and represent a leading cause of morbidity and mortality. For this reason, novel strategies to combat multidrug-resistant pathogens are urgently needed. Bacteriophage-derived enzymes, so-called endolysins, and other peptidoglycan hydrolases with the ability to disrupt cell walls represent possible alternatives to conventional antibiotics. These lytic enzymes confer a high degree of host specificity and could potentially replace or be utilized in combination with antibiotics, with the aim to specifically treat infections caused by Gram-positive drug-resistant bacterial pathogens such as methicillin-resistant S. aureus . LysK is one of the best-characterized endolysins with activity against multiple staphylococcal species. Various approaches to further enhance the antibacterial efficacy and applicability of endolysins have been demonstrated. These approaches include the construction of recombinant endolysin derivatives and the development of novel delivery strategies for various applications, such as the production of endolysins in lactic acid bacteria and their conjugation to nanoparticles. These novel strategies are a major focus of this review. Copyright © 2017 American Society for Microbiology.

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

    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)

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

    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.

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

    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.

  20. Early and rapid globalization as part of innovation and growth strategies

    Zijdemans, Erik; Azimi, Zohreh; Tanev, Stoyan

    propositions (Bailetti & Zijdemans, 2014). The GVG was tested empirically through its application to 12 cybersecurity start-ups in Ottawa, ON, Canada. Additionally, the applicability of the GVG was validated by an in depth case study of a business development agency focusing on supporting the global start......) – a framework linking the ex-ante value drivers and ex-post characteristics of BG firms. Our aim is to use the GVG to help innovative start-ups in making strategic ex-ante decisions contributing to the development of competitive global business models, complementary global resources and differentiated value...... of newly created technology firms. The preliminary results indicate that business development agencies currently do not actively or efficiently support the global start of new firms. They need however appropriate tools and mechanisms that would help them developing such capacity....

  1. Haemophilia at various stages of life: design of new therapeutic strategies through an interactive course--the Kogeniale project.

    Santagostino, Elena; Messina, Maria; Tagliaferri, Annarita; Iorio, Alfonso; Morfini, Massimo

    2013-04-01

    High-quality evidence is lacking in several areas of haemophilia treatment, in part because little time is allocated to the treatment and care of haemophilia in university education in Italy. Physicians caring for patients with haemophilia must, therefore, rely on their information on background pathophysiology and more experienced colleagues. This makes diagnostic and therapeutic choices difficult, especially when the patient has concomitant disorders or psychological issues. This article describes a course to educate young physicians who were already engaged in the management of haemophilia on the emerging and unmet issues of haemophilia care and to implement existing guidelines. Physicians (n=53) already caring for patients with haemophilia in their haematology, internal medicine, or paediatric practices in Italy attended the course. Problem-solving group activity and open discussion were the methods chosen to formulate consensus statements. During the specifically designed interactive course, three clinical cases were simulated: a young child with congenital dislocation of the hip, an adolescent refusing prophylactic treatment, and an elderly man with cardiovascular disorders. The physicians were asked questions during the course and, through a Wi-Fi console, were able to answer and discuss each case interactively. Following discussion of each case, agreement was reached regarding general statements on the management of patients with severe haemophilia A in the three different age ranges considered. This project helped to outline useful decision-making tools for handling diagnostic and treatment issues in the field of haemophilia.

  2. Global Market Entry Strategy and Point-A Perspective of Chinese Pharmaceutical Enterprise

    TonyZhang

    2003-01-01

    After joining WTO, China will not only open its door wider to foreign investment and operations in Chinese market, but also play an increasing role in global market. However, unlike many other Chinese industries that are already major suppliers or producers of consumer products at global market, majority of pharmaceutical enterprises in China remain domestic operations. Today there are still major obstacles for Chinese pharmaceutical enterprises to overcome in entering key markets such as US and Europe.

  3. An Analysis of American Animated Movies Marketing Strategies on the Angle of Globalization

    康静丹

    2016-01-01

    In a global age, the American animated film in⁃dustry that features a solid industrial foundation with the mature operational mechanism and takes a large share of global market. The thesis is going to illustrate the operational system and pat⁃terns of American animated film industry on the basis of the sta⁃tus quo of American cartoon movie market, to be a reference to the further development of Chinese cartoon movie industry.

  4. Globalization and sustainable development: a political ecology strategy to realize ecological justice

    Byrne, John; Glover, Leigh; Alrøe, Hugo Fjelsted

    2006-01-01

    Organic agriculture is, like mainstream agriculture, faced with the challenges of globalization and sustainable development. Ecological justice, the fair distribution of livelihoods and environments, has emerged as a key concept in efforts, on the one hand, to resist negative consequences of globalization and ecological modernization and, on the other to propose new agenda and institutional arrangements. This chapter investigates the role that ecological justice as a political ecology strateg...

  5. Global environmental security: Research and policy strategies for the 1990s

    Lazaro, M.A.; Wang, Hua.

    1992-01-01

    The subject of global environmental change is emerging as one of the most hotly debated international issues for the 1990s. In fact, our earth system has undergone a nature-induced gradual change in climate on both a temporal scale that spans over millions of years and a spatial scale ranging from regional to transcontinental. Pollutant emissions associated with population growth and industrial activities manifest the anthropogenic climatic forcing that has been superimposed on the background of natural climate fluctuations. Our incomplete understanding of the global impacts of environmental pollution on the earth systems (atmosphere, biosphere, hydrosphere, cryosphere, and lithosphere), however, make the prediction of the timing, magnitude, and patterns of future global change uncertain. This paper examines the science and policy background of global environmental change. The major scientific uncertainties and policy issues confronting decision makers are identified; and the scientific framework, as well as current national and international research programs aimed at resolving the scientific uncertainties, are discussed. A coherent, stable, and flexible policy is needed to provide a foundation for coordinated international-interagency programs of observation, research, analysis, and international negotiation toward a policy consensus concerning global environmental security. On the basis of what is currently known about global change, recommendations are presented on both near-term and long-term policy option decisions

  6. Global environmental security: Research and policy strategies for the 1990s

    Lazaro, M.A.; Wang, Hua

    1992-09-01

    The subject of global environmental change is emerging as one of the most hotly debated international issues for the 1990s. In fact, our earth system has undergone a nature-induced gradual change in climate on both a temporal scale that spans over millions of years and a spatial scale ranging from regional to transcontinental. Pollutant emissions associated with population growth and industrial activities manifest the anthropogenic climatic forcing that has been superimposed on the background of natural climate fluctuations. Our incomplete understanding of the global impacts of environmental pollution on the earth systems (atmosphere, biosphere, hydrosphere, cryosphere, and lithosphere), however, make the prediction of the timing, magnitude, and patterns of future global change uncertain. This paper examines the science and policy background of global environmental change. The major scientific uncertainties and policy issues confronting decision makers are identified; and the scientific framework, as well as current national and international research programs aimed at resolving the scientific uncertainties, are discussed. A coherent, stable, and flexible policy is needed to provide a foundation for coordinated international-interagency programs of observation, research, analysis, and international negotiation toward a policy consensus concerning global environmental security. On the basis of what is currently known about global change, recommendations are presented on both near-term and long-term policy option decisions.

  7. Global environmental security: Research and policy strategies for the 1990s

    Lazaro, M.A.; Wang, Hua.

    1992-01-01

    The subject of global environmental change is emerging as one of the most hotly debated international issues for the 1990s. In fact, our earth system has undergone a nature-induced gradual change in climate on both a temporal scale that spans over millions of years and a spatial scale ranging from regional to transcontinental. Pollutant emissions associated with population growth and industrial activities manifest the anthropogenic climatic forcing that has been superimposed on the background of natural climate fluctuations. Our incomplete understanding of the global impacts of environmental pollution on the earth systems (atmosphere, biosphere, hydrosphere, cryosphere, and lithosphere), however, make the prediction of the timing, magnitude, and patterns of future global change uncertain. This paper examines the science and policy background of global environmental change. The major scientific uncertainties and policy issues confronting decision makers are identified; and the scientific framework, as well as current national and international research programs aimed at resolving the scientific uncertainties, are discussed. A coherent, stable, and flexible policy is needed to provide a foundation for coordinated international-interagency programs of observation, research, analysis, and international negotiation toward a policy consensus concerning global environmental security. On the basis of what is currently known about global change, recommendations are presented on both near-term and long-term policy option decisions.

  8. Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

    Bernard Waeber

    2008-02-01

    Full Text Available Bernard Waeber1, Jean-Jacques Mourad21Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland; 2Hôpital Avicienne, Bobigny, FranceAbstract: A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118, a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108, or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103. The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 ± 70.5 (mean ± SD using the fixed-dose combination strategy, compared with –7.2 ± 81.0 using the sequential monotherapy approach and –17.5 ± 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril and a diuretic (indapamide.Keywords: antihypertensive therapy, tolerability, antihypertensive efficacy, fixed-dose combination, sequential monotherapy, stepped-care treatment

  9. Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy

    Balvers, K.; van Dieren, S.; Baksaas-Aasen, K.

    2017-01-01

    Background: The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing......) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes ‘alive and free from massive...... number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies...

  10. The Wound Healing and Antibacterial Activity of Five Ethnomedical Calophyllum inophyllum Oils: An Alternative Therapeutic Strategy to Treat Infected Wounds.

    Teddy Léguillier

    Full Text Available Calophyllum inophyllum L. (Calophyllaceae is an evergreen tree ethno-medically used along the seashores and islands of the Indian and Pacific Oceans, especially in Polynesia. Oil extracted from the seeds is traditionally used topically to treat a wide range of skin injuries from burn, scar and infected wounds to skin diseases such as dermatosis, urticaria and eczema. However, very few scientific studies reported and quantified the therapeutic properties of Calophyllum inophyllum oil (CIO. In this work, five CIO from Indonesia (CIO1, Tahiti (CIO2, 3, Fiji islands (CIO4 and New Caledonia (CIO5 were studied and their cytotoxic, wound healing, and antibacterial properties were presented in order to provide a scientific support to their traditional use and verify their safety.The safety of the five CIO was ascertained using the Alamar blue assay on human keratinocyte cells. CIO wound healing properties were determined using the scratch test assay on human keratinocyte cells. CIO-stimulated antibacterial innate immune response was evaluated using ELISA by measuring β defensin-2 release in human derivative macrophage cells. CIO antibacterial activity was tested using oilogramme against twenty aerobic Gram- bacteria species, twenty aerobic Gram+ bacteria species, including a multi-drug resistant Staphylococcus aureus strain and two anaerobic Gram+ bacteria species e.g. Propionibacterium acnes and Propionibacterium granulosum. To detect polarity profile of the components responsible of the antibacterial activity, we performed bioautography against a Staphylococcus aureus strain.Based on Alamar Blue assay, we showed that CIO can be safely used on keratinocyte cells between 2.7% and 11.2% depending on CIO origin. Concerning the healing activity, all the CIO tested accelerated in vitro wound closure, the healing factor being 1.3 to 2.1 higher compared to control when keratinocytes were incubated after scratch with CIO at 0.1%. Furthermore, our results

  11. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

    Protim Sarker

    Full Text Available BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18 in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB, a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR and release of the CAP-18 peptide/protein in stool (Western blot. PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from

  12. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

    Sarker, Protim; Ahmed, Sultan; Tiash, Snigdha; Rekha, Rokeya Sultana; Stromberg, Roger; Andersson, Jan; Bergman, Peter; Gudmundsson, Gudmundur H; Agerberth, Birgitta; Raqib, Rubhana

    2011-01-01

    Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in

  13. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease.

    Tohru Fujiwara

    Full Text Available Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of the hepcidin gene, HAMP, is increased in patients with anemia of chronic disease. Previously, the synthetic compound K7174 was identified through chemical screening as a novel inhibitor of the adhesion of monocytes to cytokine-stimulated endothelial cells. K7174 also ameliorated anemia induced by inflammatory cytokines in mice, which suggests a possible involvement of hepcidin regulation. The present study was performed to assess the impact of K7174 on hepcidin expression in a human hematoma cell line and in mice in vivo. We first demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP expression. Then, we conducted microarray analysis to determine the molecular mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly induced GDF15, known as a negative regulator of HAMP expression. Western blotting analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment. Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB. Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. Subsequently, we also examined whether K7174 inhibits hepcidin expression in mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp expression, as compared to control mice. Furthermore, serum hepcidin concentration was also significantly decreased in K7174-treated mice. In conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 may be a potential therapeutic option to treat

  14. Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

    Anusuya, Shanmugam; Natarajan, Jeyakumar

    2012-12-01

    Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.

    Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

    2013-01-01

    [Corrected] Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

  16. Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy.

    Balvers, K; van Dieren, S; Baksaas-Aasen, K; Gaarder, C; Brohi, K; Eaglestone, S; Stanworth, S; Johansson, P I; Ostrowski, S R; Stensballe, J; Maegele, M; Goslings, J C; Juffermans, N P

    2017-02-01

    The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes 'alive and free from massive transfusion' (at least 10 units of RBCs in 24 h) and early 'normalization of coagulopathy' (defined as an international normalized ratio of 1·2 or less). A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  17. Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease

    Padilla-Zambrano, Huber S.; Tomás-Zapico, Cristina; García, Benjamin Fernández

    2018-01-01

    This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson’s disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain. PMID:29570693

  18. Identification of new tumor associated antigens and their usage for new therapeutic strategies based on the combination of chemotherapy and immunotherapy for colorectal cancer patients

    Proietti, E.; Maccalli, C.; Rosenberg, S.A.; Robbins, P.F.

    2009-01-01

    The main general objective of this project was to characterize a new colorectal carcinoma (CRC) tumor-associated antigen (TAA) and validate a new therapeutic strategy combining chemotherapy and tumor vaccination for the treatment of cancer patients. To this purpose a strategic interaction between Drs. Proietti/Maccali at the ISS and the group of Drs. Rosenberg/Robbins at the NIH was established. A stage of Dr. Maccalli at the NIH allowed to carry out the first steps for the identification and the initial characterization of the CRC TAA named COA-1. A laboratory meeting with Dr. Robbins has been planned on May 24-25 2006 at the ISS, during the International Meeting on Immunotherapy of Cancer: Challenges and Needs, for discussing results and perspectives of this research project

  19. Rescue therapeutic strategy combining ultra-protective mechanical ventilation with extracorporeal CO2 removal membrane in near-fatal asthma with severe pulmonary barotraumas: A case report.

    Pavot, Arthur; Mallat, Jihad; Vangrunderbeeck, Nicolas; Thevenin, Didier; Lemyze, Malcolm

    2017-10-01

    Mechanical ventilation of severe acute asthma is still considered a challenging issue, mainly because of the gas trapping phenomenon with the potential for life-threatening barotraumatic pulmonary complications. Herein, we describe 2 consecutive cases of near-fatal asthma for whom the recommended protective mechanical ventilation approach using low tidal volume of 6 mL/kg and small levels of PEEP was rapidly compromised by giant pneumomediastinum with extensive subcutaneousemphysema. Near fatal asthma. A rescue therapeutic strategy combining extracorporeal CO2 removal membrane with ultra-protective extremely low tidal volume (3 mL/kg) ventilation was applied. Both patients survived hospital discharge. These 2 cases indicate that ECCO2R associated with ultra-protective ventilation could be an alternative to surgery in case of life-threatening barotrauma occurring under mechanical ventilation.

  20. Therapeutic strategies evaluated by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) Core Set Questionnaire in more than 1000 patients with cutaneous lupus erythematosus

    Sigges, Johanna; Biazar, Cyrus; Landmann, Aysche

    2013-01-01

    The aim of this prospective, cross-sectional, multicentre study performed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) was to investigate different therapeutic strategies and their efficacies in cutaneous lupus erythematosus (CLE) throughout Europe. Using the EUSCLE Core Set...... Questionnaire, topical and systemic treatment options were analysed in a total of 1002 patients (768 females and 234 males) with different CLE subtypes. The data were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the criteria of the American College...... of Rheumatology (ACR) for the classification of systemic lupus erythematosus. Sunscreens were applied by 84.0% of the study cohort and showed a high efficacy in preventing skin lesions in all disease subtypes, correlating with a lower CLASI activity score. Topical steroids were used in 81.5% of the patients...

  1. Effect of Global Posture Strategy on U.S. Influence in Europe

    McCormack, Daniel F

    2005-01-01

    .... interest in NATO and Europe. Will following this new strategy take the U.S. across an invisible threshold where its force presence in Europe no longer guaranties leadership and influence in NATO? How is U.S...

  2. A Review of America's Strategy: What It Will Take to Win the Global War on Terror

    Wallace, Mark R

    2006-01-01

    .... To eliminate terrorism nations of the world must first recognize the seriousness of the threat and fully comprehend our enemy's goals as well as their strategy for achieving their revolutionary objectives...

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

    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.

  4. The Global Petrochemical Industry: the market. Market Analysis - 2017-2023 Trends - Corporate Strategies

    2017-02-01

    This study presents: The medium-term and mega trends of the industry market developments and geographical segments; The competitive landscape and the main corporate rankings; The main conclusions of the report, summarised in 10 analytical slides. Content: 1. Market Fundamentals: Overview, The Industry; 2. Market Environment and Prospects: Market Environment, Demand, Supply, Trade; 3. Corporate Strategies and Competition: Competitive Environment, Structure of Competition, Business Strategies; 4. Case Studies; 5. Statistical Appendix; 6. Sources; 7. Annexes

  5. Innovative Strategies Development of the Company in Terms of Global Competition

    Radu Riana Iren; Necsulescu Ecaterina

    2011-01-01

    Blue ocean strategy challenges companies to emerge in the middle of the fierce competition that is by creating undisputed market areas which result in competition to become irrelevant. Only, instead of dividing the existing market demand, blue ocean strategy refers to a growing demand and to eliminate competition. Blue Ocean opportunities have always existed and have been explored as the universe expanded business. This expansion is the foundation of economic growth.

  6. The Global Oil and Gas Industry: the Market. Market Analysis - 2017-2020 Trends - Corporate Strategies

    2017-07-01

    This study presents: The medium-term and mega trends of the industry market developments and geographical segments; The competitive landscape and the main corporate rankings; The main conclusions of the report, summarised in 10 analytical slides. Content: 1. Market Fundamentals: Overview The Industry; 2. Market Environment and Prospects: Market Overview, Supply, Demand, Prices, Trade; 3. Corporate Strategies and Competition: Competitive Environment, Leaders' Recent Performances, Corporate Strategies; 4. Case Studies; 5. Statistical Appendix; 6. Sources; 7. Annexes

  7. The Global Renewable Energy Equipment Industry: the Market. Market Analysis - 2017-2035 Trends - Corporate Strategies

    2017-08-01

    This study presents: The medium-term and mega trends of the industry market developments and geographical segments; The competitive landscape and the main corporate rankings; The main conclusions of the report, summarised in 10 analytical slides. Content: 1. Market Fundamentals: Overview, The Industry; 2. Market Environment and Prospects: Market Overview, Demand, Supply; 3. Corporate Strategies and Competition: Competitive Forces, Structure of Competition, Corporate Strategies; 4. Case Studies; 5. Statistical Appendix; 6. Sources; 7. Annexes

  8. Quality of diabetes care worldwide and feasibility of implementation of the Alphabet Strategy: GAIA project (Global Alphabet Strategy Implementation Audit).

    Lee, James D; Saravanan, Ponnusamy; Varadhan, Lakshminarayanan; Morrissey, John R; Patel, Vinod

    2014-10-11

    The Alphabet Strategy (AS) is a diabetes care checklist ensuring "important, simple things are done right all the time." Current audits of diabetes care in developed countries reveal wide variations in quality with performance of care processes frequently sub-optimal. This study had three components:• an audit to assess diabetes care quality worldwide,• a questionnaire study seeking opinions on the merits of the AS,• a pilot study to assess the practicality of implementation of the AS in a low socioeconomic setting. Audit data was collected from 52 centres across 32 countries. Data from 4537 patients were converted to Quality and Outcome Framework (QOF) scores to enable inter-centre comparison. These were compared to each country's Gross Domestic Product (GDP), and Total Health Expenditure percentage per capita (THE%). The opinions of diabetes patients and healthcare professionals from the diabetes care team at each of these centres were sought through a structured questionnaire. A retrospective audit on 100 randomly selected case notes was conducted prior to AS implementation in a diabetes outpatient clinic in India, followed by a prospective audit after four months to assess its impact on care quality. QOF scores showed wide variation across the centres (mean 49.0, range 10.2-90.1). Although there was a positive relationship between GDP and THE% to QOF scores, there were exceptions. 91% of healthcare professionals felt the AS approach was practical. Patients found the checklist to be a useful education tool. Significant improvements in several aspects of care as well as 36% improvement in QOF score were seen following implementation. International centres observed large variations in care quality, with standards frequently sub-optimal. 71% of health care professionals would consider adopting the AS in their daily practice. Implementation in a low resource country resulted in significant improvements in some aspects of diabetes care. The AS checklist for

  9. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

    French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

    2013-08-09

    The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  10. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

    Sonia Fernandez

    2013-08-01

    Full Text Available The development of vaccines to treat and prevent human immunodeficiency virus (HIV infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK cell responses and plasmacytoid dendritic cell (pDC responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  11. Effectiveness of forest management strategies to mitigate effects of global change in Siberia

    Eric Gustafson; Anatoly Shvidenko; Robert Scheller; Brian. Sturtevant

    2011-01-01

    Siberian forest ecosystems are experiencing multiple global changes. Climate change produces direct (temperature and precipitation) and indirect (altered fire regimes and increase in cold-limited insect outbreaks) effects. Although much of Siberia has not yet been subject to timber harvest, the frontier of timber cutting is advancing steadily across the region. We...

  12. Internationalization Strategies for the Global Knowledge Society. CBIE PhD Research Series

    Szyszlo, Peter

    2016-01-01

    The purpose of this article is to improve understanding of internationalization as a strategic response to the catalysts of globalization and the knowledge society. The paper will attempt to critically identify and interpret how the aforementioned elements are being recontextualized and translated into responsive internationalization policies and…

  13. Global financial strategies for economic growth and energy in a charged world

    Wappenhans, W.A.

    1994-01-01

    The need for environment and financing for the economical and technical development of the energy sector is referred to from a global view. On the understanding of a transition to a privatised supply industry, the measure of financing the fixed energy industry investments is not seen as the greatest problem of the future. (UA) [de

  14. Do company strategies and structures converge in global markets? Evidence from the computer industry

    Duysters, G.M.; Hagedoorn, J.

    2001-01-01

    This note examines isomorphism and diversity in a global industry. We study how the ongoing internationalisation process has affected companies from various regions of the world. Empirical research is focussed on the international computer industry. We find that companies in this sector have become

  15. Positioning Global Education for the 1990s: Strategies for Higher Education.

    Scott, Robert A.

    All colleges and universities should be considering how they will incorporate global aspects of education and society into their curricula. The degree of program development will depend upon the goals and missions of each campus, but the programs should build from each campus' strength. The purpose of this paper is to discuss: (1) the principles…

  16. Climate of Concern--A Search for Effective Strategies for Teaching Children about Global Warming

    Taber, Fiona; Taylor, Neil

    2009-01-01

    Recent research suggests that the issue of global warming is one of great concern for Australian children. This point to the need for effective teaching about this issue. Children should be properly informed about actions that help reduce carbon emissions as this may give them a sense of empowerment and go some way to alleviating concerns. This…

  17. Globalization and Developing Countries: Emerging Strategies of Rural Development and Poverty Alleviation

    Bigman, D.

    2002-01-01

    The globalization process and the internal policy reforms that the developing countries have implemented during the past decade have changed the relative prices of practically all their inputs and outputs. Agricultural producers have therefore been forced to change the structure and methods of their

  18. Minding the carbon store: Weighing U.S. forestry strategies to slow global warming

    Trexler, M.C.

    1991-01-01

    If global warming is to be slowed heat-trapping gases must be controlled but, in addition, carbon sinks must be expanded. This document provides economic, political and technical analyses for each of seven biotic policy options that are feasible for the US. Individual chapters were indexed separately for the data base

  19. Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?

    Herrera-Marschitz, Mario; Perez-Lobos, Ronald; Lespay-Rebolledo, Carolyne; Tapia-Bustos, Andrea; Casanova-Ortiz, Emmanuel; Morales, Paola; Valdes, Jose-Luis; Bustamante, Diego; Cassels, Bruce K

    2018-02-01

    Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult.PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD + exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1β and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss

  20. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies.

    Graf, Michaela; Hecht, Karin; Reif, Susanne; Pelka-Fleischer, Renate; Pfister, Karin; Schmetzer, Helga

    2004-02-01

    Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR-supported therapeutic considerations. We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence-activated cell sorting (FACS) analysis using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM-CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. All investigated CKR were more frequently expressed in AML-samples than in healthy BM-samples, except CD130, which was only expressed on 5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+). Within the French-American-British (FAB) types we observed a maturation- and lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases. Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+), and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive in FAB-type M0 (n = 2). No differences in CKR-expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G-CSF-R(+) blasts in the cytogenetic good risk group than in the bad risk group (P