WorldWideScience

Sample records for guide adjuvant strategies

  1. Opioid adjuvant strategy: improving opioid effectiveness.

    Science.gov (United States)

    Bihel, Frédéric

    2016-01-01

    Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

  2. Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

    Science.gov (United States)

    Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

    2018-06-01

    Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

  3. Web 2.0: A Strategy Guide

    CERN Document Server

    Shuen, Amy

    2008-01-01

    Web 2.0 makes headlines, but how does it make money? This concise guide explains what's different about Web 2.0 and how those differences can improve the bottom line. Whether you're an executive, a small business owner, or an entrepreneur, Web 2.0: A Strategy Guide illustrates through real life examples how various businesses are creating new opportunities on today's Web. This book is about strategy rather than the technology itself.

  4. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    Directory of Open Access Journals (Sweden)

    Signe Tandrup Schmidt

    2016-03-01

    Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

  5. A DIY guide to statistical strategy

    International Nuclear Information System (INIS)

    Pregibon, D.

    1986-01-01

    This chapter is a do it yourself (DIY) guide to developing statistical strategy for a particular data analysis task. The primary audience of the chapter is research statisticians. The material should also be of interest to nonstatisticians, especially knowledge engineers, who are interested in using statistical data analysis as an application domain for Artificial Intelligence techniques. The do's and don'ts of strategy development are outlined. The ''linear regression'' task is used to illustrate many of the ideas

  6. A Novel Adjuvant-Solution Layer Strategy for Improving the Efficacy of Cryosurgery.

    Science.gov (United States)

    Ramajayam, K K; Kumar, A; Sarangi, S K; Thirugnanam, A

    During cryosurgery, studies reported earlier suggest increased destruction inside the tumour due to adjuvants or the prevention of damage to neighbouring healthy tissue through different methods. This study advocates a novel strategy that increases the freezing inside agarose gel phantoms by addition of glycine and limits the freezing to the desired location using a perfluorohexane layer during cryosurgery. Cryosurgery of glycine containing gels is carried out with and without perfluorohexane layer and the thermal history is measured using K-type thermocouples connected to a data acquisition system. The presence of glycine causes increased freezing during cryosurgery with an ice ball depth of 16 mm, while with a perfluorohexane layer at this gel interface, this depth is 13 mm, indicating the ability of this layer to limit freezing. It can be concluded that glycine addition results in substantial temperature decrease and perfluorohexane layer insulates the glycine gel effectively during cryosurgical cooling.

  7. Refrigerated Warehouse Demand Response Strategy Guide

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Doug [VaCom Technologies, San Luis Obispo, CA (United States); Castillo, Rafael [VaCom Technologies, San Luis Obispo, CA (United States); Larson, Kyle [VaCom Technologies, San Luis Obispo, CA (United States); Dobbs, Brian [VaCom Technologies, San Luis Obispo, CA (United States); Olsen, Daniel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-11-01

    This guide summarizes demand response measures that can be implemented in refrigerated warehouses. In an appendix, it also addresses related energy efficiency opportunities. Reducing overall grid demand during peak periods and energy consumption has benefits for facility operators, grid operators, utility companies, and society. State wide demand response potential for the refrigerated warehouse sector in California is estimated to be over 22.1 Megawatts. Two categories of demand response strategies are described in this guide: load shifting and load shedding. Load shifting can be accomplished via pre-cooling, capacity limiting, and battery charger load management. Load shedding can be achieved by lighting reduction, demand defrost and defrost termination, infiltration reduction, and shutting down miscellaneous equipment. Estimation of the costs and benefits of demand response participation yields simple payback periods of 2-4 years. To improve demand response performance, it’s suggested to install air curtains and another form of infiltration barrier, such as a rollup door, for the passageways. Further modifications to increase efficiency of the refrigeration unit are also analyzed. A larger condenser can maintain the minimum saturated condensing temperature (SCT) for more hours of the day. Lowering the SCT reduces the compressor lift, which results in an overall increase in refrigeration system capacity and energy efficiency. Another way of saving energy in refrigerated warehouses is eliminating the use of under-floor resistance heaters. A more energy efficient alternative to resistance heaters is to utilize the heat that is being rejected from the condenser through a heat exchanger. These energy efficiency measures improve efficiency either by reducing the required electric energy input for the refrigeration system, by helping to curtail the refrigeration load on the system, or by reducing both the load and required energy input.

  8. Dexmedetomidine as an adjuvant to 0.5% ropivacaine in ultrasound-guided axillary brachial plexus block.

    Science.gov (United States)

    Koraki, E; Stachtari, C; Kapsokalyvas, I; Stergiouda, Z; Katsanevaki, A; Trikoupi, A

    2018-06-01

    The aim of this study was to elucidate the effect of dexmedetomidine added to ropivacaine on the onset and duration of sensory and motor block and duration of analgesia of ultrasound-guided axillary brachial plexus block. Thirty-seven ASA physical status I-II patients with elective forearm and hand surgery under ultrasound-guided axillary brachial plexus block were randomly divided into 2 groups. Patients in ropivacaine-dexmedetomidine group (group RD, n = 19) received 15 mL of 0.5% ropivacaine with 100 μg (1 mL) dexmedetomidine, and patients in ropivacaine group (group R, n = 18) received 15 mL of 0.5% ropivacaine with 1 mL of normal saline. Onset time and duration of sensory and motor block and duration of analgesia were assessed. Duration of sensory block (U-value = 35, P block (P = .001) and duration of analgesia (P block in group RD was significantly faster than in group R (U-value = 65.5, P = .001). Onset time of motor block showed no significant difference between the 2 groups (U-value = 116.5, P = .096). Adverse reactions were reported only in group RD (bradycardia in 2 and hypotension in 3 patients). Our study indicated that dexmedetomidine 100 μg as adjuvant on ultrasound-guided axillary plexus block significantly prolonged the duration of sensory block and analgesia, as well as accelerated the time to onset of sensory block. These results should be weighed against the increased risks of motor block prolongation, transient bradycardia and hypotension and allow for attentive optimism, only if prolonged clinical trials provide a definitive answer. © 2017 John Wiley & Sons Ltd.

  9. Guide to National Security Policy and Strategy

    National Research Council Canada - National Science Library

    Bartholomees, Jr, J. B

    2006-01-01

    ...: Theory of War and Strategy and National Security Policy and Strategy. The result for this book is the expansion of the block on strategic theory and the introduction of a block on specific strategic issues...

  10. Drunk Driving Public Information Program Strategies and Planning Guide.

    Science.gov (United States)

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This guide, designed to accompany a videocassette of selected television spots is a compendium of specific drunk driving topics and issues for each of the major planning steps of a public information program. The guide is organized around these steps, which are (1) select program strategies, (2) select target audiences, (3) select media channels,…

  11. A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens.

    Science.gov (United States)

    Davitt, Christopher J H; McNeela, Edel A; Longet, Stephanie; Tobias, Joshua; Aversa, Vincenzo; McEntee, Craig P; Rosa, Monica; Coulter, Ivan S; Holmgren, Jan; Lavelle, Ed C

    2016-07-10

    Diarrhoeal infections are a major cause of morbidity and mortality with enterotoxigenic Escherichia coli (ETEC) and cholera imposing a significant global burden. There is currently no licensed vaccine for ETEC. Development of new nonliving oral vaccines has proven difficult due to the physicochemical and immunological challenges associated with the oral route. This demands innovative delivery solutions to protect antigens, control their release and build in immune-stimulatory activity. We describe the Single Multiple Pill® (SmPill®) vaccine formulation which combines the benefits of enteric polymer coating to protect against low gastric pH, a dispersed phase to control release and aid the solubility of non-polar components and an optimized combination of adjuvant and antigen to promote mucosal immunity. We demonstrate the effectiveness of this system with whole cell killed E. coli overexpressing colonization factor antigen I (CFA/I), JT-49. Alpha-galactosylceramide was identified as a potent adjuvant within SmPill® that enhanced the immunogenicity of JT-49. The bacteria associated with the dispersed phase were retained within the capsules at gastric pH but released at intestinal pH. Vaccination with an optimized SmPill® formulation promoted CFA/I-specific immunoglobulin A (IgA) responses in the intestinal mucosa in addition to serum IgG and a solubilized adjuvant was indispensable for efficacy. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Association of chitosan and aluminium as a new adjuvant strategy for improved vaccination.

    Science.gov (United States)

    Lebre, F; Bento, D; Ribeiro, J; Colaço, M; Borchard, G; de Lima, M C Pedroso; Borges, O

    2017-07-15

    The use of particulate adjuvants offers an interesting possibility to enhance and modulate the immune responses elicited by vaccines. Aluminium salts have been extensively used as vaccine adjuvants, but they lack the capacity to induce a strong cellular and mucosal immune response. Taking this into consideration, in this study we designed a new antigen delivery system combining aluminium salts with chitosan. Chitosan-aluminium nanoparticles (CH-Al NPs) exhibited a mean diameter of 280nm and a positive surface charge. The newly developed CH-Al NPs are more stable at physiological environment than classical CH NPs, showing no cytotoxic effects and revealing potential as a delivery system for a wide range of model antigens. In vivo studies showed that mice immunized with hepatitis B surface antigen (HBsAg)-containing CH NPs display high anti-HBsAg IgG titers in the serum, as well as the highest antigen-specific IgG on vaginal washes. Furthermore, in contrast to mice receiving antigen alone, mice immunized with the particulate adjuvant were able to elicit IgG2c antibody titers and exhibited higher antigen-specific IFN-γ levels in splenocytes. In conclusion, we established that CH-Al NPs, combining two immunostimulants to enhance both humoral and cellular immune responses, are a safe and promising system for antigen delivery. Our findings point towards their potential in future vaccination approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. TOEFL strategies a complete guide to the iBT

    CERN Document Server

    Stirling, Bruce

    2016-01-01

    TOEFL students all ask: How can I get a high TOEFL iBT score? Answer: Learn argument scoring strategies. Why? Because the TOEFL iBT recycles opinion-based and fact-based arguments for testing purposes from start to finish. In other words, the TOEFL iBT is all arguments. That's right, all arguments. If you want a high score, you need essential argument scoring strategies. That is what TOEFL STRATEGIES A COMPLETE GUIDE gives you, and more!

  14. Guides' Intercultural Strategies in an Interaction Perspective

    DEFF Research Database (Denmark)

    Meged, Jane Widtfeldt

    2010-01-01

    Guidede ture foregår ofte i et interkulturelt spændingsfelt mellem guider, turister og destinationen.  I samspil med turisterne undvikler og anvender guiderne en række interkulturelle kommunikations strategier til at skabe sammenhæng, spænding og identitet i fortællingerne. Artiklen undersøger...... hvordan en række autoriserede guider fra København i samspil med hhv. engelsk, tysk, italiensk og spansktalende turister performer interkulturelle strategier....

  15. Strategies for continuous evaluation of the benefit-risk profile of HPV-16/18-AS04-adjuvanted vaccine.

    Science.gov (United States)

    Angelo, Maria-Genalin; Taylor, Sylvia; Struyf, Frank; Tavares Da Silva, Fernanda; Arellano, Felix; David, Marie-Pierre; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

    2014-11-01

    The HPV types 16/18-AS04-adjuvanted cervical cancer vaccine, Cervarix(®) (HPV-16/18-vaccine, GlaxoSmithKline, Belgium) was first approved in 2007 and is licensed in 134 countries for the prevention of persistent infection, premalignant cervical lesions and cervical cancer caused by oncogenic HPV. Benefit-risk status requires continual re-evaluation as vaccine uptake increases, as the epidemiology of the disease evolves and as new information becomes available. This paper provides an example of benefit-risk considerations and risk-management planning. Evaluation of the benefit-risk of HPV-16/18-vaccine post-licensure includes studies with a range of designs in many countries and in collaboration with national public agencies and regulatory authorities. The strategy to assess benefit versus risk will continue to evolve and adapt to the changing HPV-16/18-vaccine market.

  16. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

    Directory of Open Access Journals (Sweden)

    Heng Liu

    Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

  17. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    Science.gov (United States)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  18. Magnesium sulphate as an adjuvant to bupivacaine in ultrasound-guided transversus abdominis plane block in patients scheduled for total abdominal hysterectomy under subarachnoid block

    Directory of Open Access Journals (Sweden)

    Shelly Rana

    2016-01-01

    Full Text Available Background and Aims: Transversus abdominis plane (TAP block has proven to be an effective component of multimodal analgesic regimens for a variety of abdominal procedures. Magnesium sulphate (MgSO4 N-methyl-D-aspartate receptor antagonist has the potential to be an ideal adjuvant in TAP block. We studied the efficacy of MgSO4as an adjuvant to bupivacaine in TAP block in patients scheduled for total abdominal hysterectomy (TAH under subarachnoid block (SAB. Methods: Sixty-five women belonging to American Society of Anesthesiologists physical status 1 or 2, aged between 35 and 70 years, scheduled for TAH under SAB were recruited. Patients in Group B (n = 32 received 18 mL 0.25% bupivacaine (45 mg with 2 mL normal saline (NS, whereas those in Group BM (n = 33 received 18 mL 0.25% bupivacaine (45 mg with 1.5 mL (150 mg MgSO4and 0.5 mL NS in the ultrasound (USG-guided TAP block performed on each side after the completion of the surgery under SAB. They were evaluated for pain at 0, 2, 4, 6, 12 and 24 h, time to first rescue analgesic and duration of postoperative analgesia were noted. Results: The post-operative visual analogue scale (VAS scores were lower in Group BM at 4, 6 and 12 h (P < 0.05. Mean duration of analgesia was significantly prolonged in Group BM with lesser requirement of rescue analgesic (P < 0.05 up to 12 h. Conclusion: MgSO4 (150 mg as an adjuvant to bupivacaine in USG-guided TAP block reduces post-operative pain scores, prolongs the duration of analgesia and decreases demands for rescue analgesics.

  19. Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model

    Directory of Open Access Journals (Sweden)

    Du Y

    2017-11-01

    Full Text Available Yang Du,1,2,* Ting Sun,3,* Xiaolong Liang,4,* Yuan Li,3 Zhengyu Jin,3 Huadan Xue,3 Yihong Wan,5 Jie Tian1,2 1CAS Key Laboratory of Molecular Imaging, 2The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, 3Department of Radiology, Peking Union Medical College Hospital, 4Department of Ultrasound, Peking University Third Hospital, Beijing, China; 5Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA *These authors contributed equally to this work Abstract: An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model. Fluorescence molecular imaging was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging was performed to monitor tumor growth and evaluate postsurgical tumor residuals, recurrences, and metastases. The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and thus improved survival rate. Our study demonstrates the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from tumor residuals. Keywords: PD-1, programmed cell

  20. Strategies for Biologic Image-Guided Dose Escalation: A Review

    International Nuclear Information System (INIS)

    Sovik, Aste; Malinen, Eirik; Olsen, Dag Rune

    2009-01-01

    There is increasing interest in how to incorporate functional and molecular information obtained by noninvasive, three-dimensional tumor imaging into radiotherapy. The key issues are to identify radioresistant regions that can be targeted for dose escalation, and to develop radiation dose prescription and delivery strategies providing optimal treatment for the individual patient. In the present work, we review the proposed strategies for biologic image-guided dose escalation with intensity-modulated radiation therapy. Biologic imaging modalities and the derived images are discussed, as are methods for target volume delineation. Different dose escalation strategies and techniques for treatment delivery and treatment plan evaluation are also addressed. Furthermore, we consider the need for response monitoring during treatment. We conclude with a summary of the current status of biologic image-based dose escalation and of areas where further work is needed for this strategy to become incorporated into clinical practice

  1. The problem resident behavior guide: strategies for remediation.

    Science.gov (United States)

    Williamson, Kelly; Quattromani, Erin; Aldeen, Amer

    2016-04-01

    In 2012, the ACGME supplemented the core competencies with outcomes-based milestones for resident performance within the six competency domains. These milestones address the knowledge, skills, abilities, attitudes, and experiences that a resident is expected to progress through during the course of training. Even prior to the initiation of the milestones, there was a paucity of EM literature addressing the remediation of problem resident behaviors and there remain few readily accessible tools to aid in the implementation of a remediation plan. The goal of the "Problem Resident Behavior Guide" is to provide specific strategies for resident remediation based on deficiencies identified within the framework of the EM milestones. The "Problem Resident Behavior Guide" is a written instructional manual that provides concrete examples of remediation strategies to address specific milestone deficiencies. The more than 200 strategies stem from the experiences of the authors who have professional experience at three different academic hospitals and emergency medicine residency programs, supplemented by recommendations from educational leaders as well as utilization of valuable education adjuncts, such as focused simulation exercises, lecture preparation, and themed ED shifts. Most recommendations require active participation by the resident with guidance by faculty to achieve the remediation expectations. The ACGME outcomes-based milestones aid in the identification of deficiencies with regards to resident performance without providing recommendations on remediation. The Problem Resident Behavior Guide can therefore have a significant impact by filling in this gap.

  2. Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

    DEFF Research Database (Denmark)

    Swanton, Charles; Szallasi, Zoltan Imre; Brenton, James D.

    2008-01-01

    The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and 5-fluorouracil, targeted agents such as trastuzumab and inhibitors of AKT and Poly(ADP-ribose) polymerase (PARP...

  3. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls

    Directory of Open Access Journals (Sweden)

    Anouk Kaulmann

    2016-01-01

    Full Text Available Inflammatory bowel diseases (IBDs are characterized by autoimmune and inflammation-related complications of the large intestine (ulcerative colitis and additional parts of the digestive tract (Crohn’s disease. Complications include pain, diarrhoea, chronic inflammation, and cancer. IBD prevalence has increased during the past decades, especially in Westernized countries, being as high as 1%. As prognosis is poor and medication often ineffective or causing side effects, additional preventive/adjuvant strategies are sought. A possible approach is via diets rich in protective constituents. Polyphenols, the most abundant phytochemicals, have been associated with anti-inflammatory, antioxidant, immunomodulatory, and apoptotic properties. Locally reducing oxidative stress, they can further act on cellular targets, altering gene expression related to inflammation, including NF-κB, Nrf-2, Jak/STAT, and MAPKs, suppressing downstream cytokine formation (e.g., IL-8, IL-1β, and TNF-α, and boosting the bodies’ own antioxidant status (HO-1, SOD, and GPx. Moreover, they may promote, as prebiotics, healthy microbiota (e.g., Bifidobacteria, Akkermansia, short-chain fatty acid formation, and reduced gut permeability/improved tight junction stability. However, potential adverse effects such as acting as prooxidants, or perturbations of efflux transporters and phase I/II metabolizing enzymes, with increased uptake of undesired xenobiotics, should also be considered. In this review, we summarize current knowledge around preventive and arbitrary actions of polyphenols targeting IBD.

  4. Defense Strategy of Aircraft Confronted with IR Guided Missile

    Directory of Open Access Journals (Sweden)

    Hesong Huang

    2017-01-01

    Full Text Available Surface-type infrared (IR decoy can simulate the IR characteristics of the target aircraft, which is one of the most effective equipment to confront IR guided missile. In the air combat, the IR guided missile poses a serious threat to the aircraft when it comes from the front of target aircraft. In this paper, firstly, the model of aircraft and surface-type IR decoy is established. To ensure their authenticity, the aircraft maneuver and radiation models based on real data of flight and exhaust system radiation in the state of different heights and different speeds are established. Secondly, the most effective avoidance maneuver is simulated when the missile comes from the front of the target aircraft. Lastly, combining maneuver with decoys, the best defense strategy is analysed when the missile comes from the front of aircraft. The result of simulation, which is authentic, is propitious to avoid the missile and improve the survivability of aircraft.

  5. Women’s Beliefs on Early Adherence to Adjuvant Endocrine Therapy for Breast Cancer: A Theory-Based Qualitative Study to Guide the Development of Community Pharmacist Interventions

    Directory of Open Access Journals (Sweden)

    Brittany Humphries

    2018-06-01

    Full Text Available Adjuvant endocrine therapy (AET taken for a minimum of five years reduces the recurrence and mortality risks among women with hormone-sensitive breast cancer. However, adherence to AET is suboptimal. To guide the development of theory-based interventions to enhance AET adherence, we conducted a study to explore beliefs regarding early adherence to AET. This qualitative study was guided by the Theory of Planned Behavior (TPB. We conducted focus groups and individual interviews among women prescribed AET in the last two years (n = 43. The topic guide explored attitudinal (perceived advantages and disadvantages, normative (perception of approval or disapproval, and control beliefs (barriers and facilitating factors towards adhering to AET. Thematic analysis was conducted. Most women had a positive attitude towards AET regardless of their medication-taking behavior. The principal perceived advantage was protection against a recurrence while the principal inconvenience was side effects. Almost everyone approved of the woman taking her medication. The women mentioned facilitating factors to encourage medication-taking behaviors and cope with side effects. For adherent women, having trouble establishing a routine was their main barrier to taking medication. For non-adherent women, it was side effects affecting their quality of life. These findings could inform the development of community pharmacy-based adherence interventions.

  6. A dose-finding randomised controlled trial of magnesium sulphate as an adjuvant in ultrasound-guided supraclavicular brachial plexus block

    Directory of Open Access Journals (Sweden)

    Versha Verma

    2017-01-01

    Full Text Available Background and Aim: Magnesium sulphate (MgSO4 has been used as an adjuvant in brachial plexus block with encouraging results; however, there is no consensus regarding its optimal dose. Thereby, we compared the efficacy of two doses of MgSO4 as an adjuvant in ultrasound (USG guided supraclavicular brachial plexus block. Methods: Ninety patients, aged 20–60 years, belonging to American Society of Anesthesiologists physical status 1 or 2, were given USG-guided supraclavicular block. Group B (n = 30 received 20 ml of 0.5%bupivacaine + 5 ml normal saline (NS, Group BM0.5(n = 30 received 20 ml of 0.5%bupivacaine + 3.75 ml NS and 125 mg MgSO4 (1.25 ml and Group BM1(n = 30 received 20 ml of 0.5%bupivacaine + 2.5 ml NS and 250 mg MgSO4 (2.5 ml. The primary outcome of study was the duration of post-operative analgesia. The normally distributed data were analysed using analysis of variance and categorical data analysed using Chi-square test. Results: Duration of post-operative analgesia was prolonged in Groups BM1 and BM0.5 (665.13 ± 97.874, 475.10 ± 53.294 min respectively as compared to Group B (272.03 ± 40.404 min: P = 0.00. The onset times of sensory and motor block were shorter in Group BM1 (5.17 ± 2.2 minas compared to Groups BM0.5 and B (8.9 ± 2.3 and 17.7 ± 5.1 min: P = 0.00 respectively. Sensory and motor block durations were prolonged in Group BM1 as compared to BM0.5 and B (P = 0.00. Conclusions: MgSO4 as adjuvant in brachial plexus block increases the duration of post-operative analgesia. MgSO4 in the dose of 250mg has greater efficacy as compared to 125 mg.

  7. New therapeutical strategies in adjuvant treatment of stage I B and II A cervical cancer after Wertheim-Mergs radical hysterectomy

    International Nuclear Information System (INIS)

    Ivanov, S.

    2003-01-01

    Patients after Wertheim-Mergs radical hysterectomy of stage I B and II A cervical cancer with positive lymph nodes and unfavourable prognostic factors are usually given adjuvant radiotherapy. The aim of our study was to research retrospectively and to analyse the survival of patients after radical hysterectomy and postoperative radiotherapy. Prognostic factors, survival rate failures of treatment and the way of recurrence were evaluated for 420 patients in I B and II A stage for the period of 1990-2003. All patients were radically operated and underwent an adjuvant radiotherapy, 25 of them received adjuvant chemotherapy. Positive lymph nodes were found in 24.52%. All patients having positive for metastases lymph nodes and those with negative lymph nodes but unfavorable prognostic factors received adjuvant radiotherapy (RT). The 5 years survival rate was 63% for the patients with positive lymph nodes and 89% for those with negative lymph nodes. The level of recurrence was 14% for patients with negative and 35% for those with positive lymph nodes. There were 39 pelvic and 41 distant recurrences, but the behavior was different between patients with negative lymph nodes (32 pelvic and 12 distant recurrences) and with positive ones (7 pelvic and 29 distant recurrences). The updated 5 years survival was 24% for patients with pelvic recurrences and 6% for the patients with distant ones. Our therapy strategy for patients with negative lymph nodes who have distant recurrences involves an adjuvant chemotherapy. All patients with negative lymph nodes but positive parametric and positive surgical margins receive postsurgical radiotherapy or an intensive follow up. (author)

  8. The Explicit Instruction of Reading Strategies: Directed Reading Thinking Activity vs. Guided Reading Strategies

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Yazdani

    2015-05-01

    Full Text Available Investigating the efficiencies and deficiencies of reading strategies is one of the noticeable issues in the related theory and research in reading comprehension instruction. This study was to examine the impact of Directed Reading Thinking Activity (DRTA and Guided Reading (GR on reading comprehension. Sixty three Iranian students of grade one in Shahed high school in the city of Bojnourd took part in the study. They were assigned in three groups, one control and two experimental groups. The instruction lasted for ten weeks. This study utilized a pretest posttest control group in quantitative quasi- experimental design. The same reading comprehension test was administered as pre-test and post-test. The results were twofold: First, the instruction of learning strategies could foster reading comprehension skill. Second, while the explicit instruction of both strategies could improve the students' reading comprehension skill, Directed Reading Thinking Activity had a more significant positive effect than Guided Reading.

  9. A systematic review of optimal treatment strategies for localized Ewing's sarcoma of bone after neo-adjuvant chemotherapy.

    Science.gov (United States)

    Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; Di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

    2016-03-01

    To perform a systematic review to investigate the optimal treatment strategy among the options of surgery alone, radiotherapy (RT) alone, and the combination of RT plus surgery in the management of localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy. MEDLINE and EMBASE (1999 to February 2015), the Cochrane Library, and relevant conferences were searched. Two systematic reviews and eight full texts met the pre-planned study selection criteria. When RT was compared with surgery, a meta-analysis combining two papers showed that surgery resulted in a higher event-free survival (EFS) than RT in any location (HR = 1.50, 95% CI 1.12-2.00; p = 0.007). However another paper did not find a statistically significant difference in patients with pelvic disease, and no papers identified a significant difference in overall survival. When surgery plus RT was compared with surgery alone, a meta-analysis did not demonstrate a statistically significant difference for EFS between the two groups (HR = 1.21, 95% CI 0.90-1.63). Both surgical morbidities and radiation toxicities were reported. The existing evidence is based on very low aggregate quality as assessed by the GRADE approach. In patients with localized Ewing's sarcoma, either surgery alone (if complete surgical excision with clear margin can be achieved) or RT alone may be a reasonable treatment option. The optimal local treatment for an individual patient should be decided through consideration of patient characteristics, the potential benefit and harm of the treatment options, and patient preference. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  10. Task Rotation: Strategies for Differentiating Activities and Assessments by Learning Style. A Strategic Teacher PLC Guide

    Science.gov (United States)

    Silver, Harvey; Moirao, Daniel; Jackson, Joyce

    2011-01-01

    One of the hardest jobs in teaching is to differentiate learning activities and assessments to your students' learning styles. But you and your colleagues can learn how to do this together when each of you has this guide to the Task Rotation strategy from our ultimate guide to teaching strategies, "The Strategic Teacher". Use the guide in your…

  11. Co-administration of cholera toxin and apple polyphenol extract as a novel and safe mucosal adjuvant strategy.

    Science.gov (United States)

    Yoshino, Naoto; Fujihashi, Kohtaro; Hagiwara, Yukari; Kanno, Hiroyuki; Takahashi, Kiyomi; Kobayashi, Ryoki; Inaba, Noriyuki; Noda, Masatoshi; Sato, Shigehiro

    2009-07-30

    Although native cholera toxin (CT) is an extremely effective adjuvant, its toxicity prevents its use in humans. We report here that apple polyphenol extract (APE), obtained from unripe apples, reduces CT-induced morphological changes and cAMP accumulation. Based upon this finding, we have attempted to design a novel, effective and safe mucosal vaccine by using CT with several dosages of APE as nasal adjuvants. Mice nasally immunized with OVA plus CT and an optimal dosage of APE showed significantly reduced levels of inflammatory responses as well as total and OVA-specific IgE antibodies when compared with mice given without APE. However, levels of both mucosal and systemic OVA-specific antibody responses were maintained. Further, APE significantly down-regulated accumulation of CT in the olfactory nerves and epithelium. In summary, an optimal dosage of APE would take full advantage of mucosal adjuvanticity of native CT without any toxicity for application in humans.

  12. Clinical trials using IFN-α as a vaccine adjuvant: new strategies for the molecular monitoring of the immune response

    International Nuclear Information System (INIS)

    Belardelli, F.; Arico, E.; Marincola, F.; Wang, E.

    2009-01-01

    The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients

  13. Gene expression profiling for guiding adjuvant chemotherapy decisions in women with early breast cancer: an evidence-based and economic analysis.

    Science.gov (United States)

    2010-01-01

    In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of published literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide evidence-based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario.Evidence-based analyses have been prepared for each of these technologies. These have been completed in conjunction with internal and external stakeholders, including a Provincial Expert Panel on Pharmacogenomics (PEPP). Within the PEPP, subgroup committees were developed for each disease area. For each technology, an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative (THETA) and is summarized within the reports.THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER: An Evidence-Based and Economic AnalysisEpidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: An Evidence-Based and Ecopnomic AnalysisK-RAS testing in Treatment Decisions for Advanced Colorectal Cancer: an Evidence-Based and Economic Analysis To review and synthesize the available evidence regarding the laboratory performance, prognostic value, and predictive value of Oncotype-DX for the target population. CONDITION AND TARGET POPULATION The target population of this review is women with newly diagnosed early stage (stage I-IIIa) invasive breast cancer that is estrogen-receptor (ER) positive and/or progesterone-receptor (PR) positive. Much of this review, however, is relevant for women with early stage (I and II) invasive breast

  14. Collaboration and Team Science Field Guide - Center for Research Strategy

    Science.gov (United States)

    Collaboration and Team Science: A Field Guide provides insight into the practices of conducting collaborative work. Since its 2010 publication, the authors have worked and learned from teams and organizations all over the world. Learn from these experiences in the second edition of the Team Science Field Guide.

  15. U.S. Army War College Guide to Strategy

    National Research Council Canada - National Science Library

    Cerami, Joseph

    2001-01-01

    For more than 3 decades, the Army War College Department of National Security and Strategy has faced the challenge of educating future strategic leaders on the subject of national security, or grand strategy...

  16. Tech Prep Marketing Guide. The Complete Book of Strategies and Practical Experiences.

    Science.gov (United States)

    Williamson, Patty

    This guide explains the concept of marketing tech prep and provides marketing principles and strategies to promote tech prep programs. The guide covers the following topics: (1) why it is necessary to market tech prep; (2) what a comprehensive tech prep marketing plan should include; (3) targeting the benefits message; (4) marketing tech prep to…

  17. Interaction between Gaming and Multistage Guiding Strategies on Students' Field Trip Mobile Learning Performance and Motivation

    Science.gov (United States)

    Chen, Chih-Hung; Liu, Guan-Zhi; Hwang, Gwo-Jen

    2016-01-01

    In this study, an integrated gaming and multistage guiding approach was proposed for conducting in-field mobile learning activities. A mobile learning system was developed based on the proposed approach. To investigate the interaction between the gaming and guiding strategies on students' learning performance and motivation, a 2 × 2 experiment was…

  18. Gaze strategies during visually-guided versus memory-guided grasping.

    Science.gov (United States)

    Prime, Steven L; Marotta, Jonathan J

    2013-03-01

    Vision plays a crucial role in guiding motor actions. But sometimes we cannot use vision and must rely on our memory to guide action-e.g. remembering where we placed our eyeglasses on the bedside table when reaching for them with the lights off. Recent studies show subjects look towards the index finger grasp position during visually-guided precision grasping. But, where do people look during memory-guided grasping? Here, we explored the gaze behaviour of subjects as they grasped a centrally placed symmetrical block under open- and closed-loop conditions. In Experiment 1, subjects performed grasps in either a visually-guided task or memory-guided task. The results show that during visually-guided grasping, gaze was first directed towards the index finger's grasp point on the block, suggesting gaze targets future grasp points during the planning of the grasp. Gaze during memory-guided grasping was aimed closer to the blocks' centre of mass from block presentation to the completion of the grasp. In Experiment 2, subjects performed an 'immediate grasping' task in which vision of the block was removed immediately at the onset of the reach. Similar to the visually-guided results from Experiment 1, gaze was primarily directed towards the index finger location. These results support the 2-stream theory of vision in that motor planning with visual feedback at the onset of the movement is driven primarily by real-time visuomotor computations of the dorsal stream, whereas grasping remembered objects without visual feedback is driven primarily by the perceptual memory representations mediated by the ventral stream.

  19. Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goody, Rebecca B. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); MacKay, Helen [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Pitcher, Bethany [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Oza, Amit; Siu, Lillian L. [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John; Wong, Rebecca K.S. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Chen, Eric [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Swallow, Carol [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Knox, Jennifer [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket, Ontario (Canada); Cummings, Bernard [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Feld, Ron; Hedley, David; Liu, Geoffrey; Krzyzanowska, Monika K. [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Dinniwell, Robert; Brade, Anthony M.; Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Pintilie, Melania [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); and others

    2016-12-01

    Purpose: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. Methods and Materials: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m{sup 2}/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m{sup 2}) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. Results: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m{sup 2} cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. Conclusion: Cisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

  20. A Sales Execution Strategy Guide for Technology Startups

    Directory of Open Access Journals (Sweden)

    Ian Gilbert

    2011-10-01

    Full Text Available The majority of startups fail to consider sales execution as part of their overall strategy. This article demonstrates how a sales execution strategy can help a company take a product or service to market more efficiently and effectively by focusing on the customers that are key to generating revenue. Combined with techniques for recruiting effectively and measuring sales outcomes, a sales execution strategy helps technology startups exceed growth aspirations and potentially reduce or even eliminate the requirement for external investment. In this article, we first describe the focus of assistance currently given to startups and the reasons why sales execution strategies are often overlooked. Next, we outline recommendations for developing, implementing, and supporting a sales execution strategy. Finally, we summarize the key points presented in the article.

  1. ITIL V3 service strategy a management guide

    CERN Document Server

    Van Bon, Jan

    2008-01-01

    The Management Guides are a concise summary of the 'Foundations of IT Service Management based on ITIL V3'. A quick, portable reference tool to the standards used within the Service Management community. Not only includes the Lifecycle Approach but in addition covers the processes in a separate section as well. What are the key service management processes? What is the 'lifecycle' approach? English version available: June 2008 Dutch, French, Spanish, German available July 2008.

  2. Effects of Guided Writing Strategies on Students' Writing Attitudes Based on Media Richness Theory

    Science.gov (United States)

    Lan, Yu-Feng; Hung, Chun-Ling; Hsu, Hung-Ju

    2011-01-01

    The purpose of this paper is to develop different guided writing strategies based on media richness theory and further evaluate the effects of these writing strategies on younger students' writing attitudes in terms of motivation, enjoyment and anxiety. A total of 66 sixth-grade elementary students with an average age of twelve were invited to…

  3. Learning strategy as a guide to career succes in organisations

    NARCIS (Netherlands)

    Hoeksema, L.H.

    1995-01-01

    Our lack of understanding regarding how managers learn is in sharp contrast to the importance attached and money spend on management development. This research explores how managers acquire their competences by establishing the relationships between organizational structure, learning strategy and

  4. Reading Strategy Guides to Assist Middle School Educators of Students with Dyslexia

    Science.gov (United States)

    Nichols-Yehling, M.; Strohl, C.

    2014-07-01

    According to the 2010 International Dyslexia Association publication, “Knowledge and Practice Standards for Teachers of Reading,” effective instruction is the key to addressing students' reading difficulties associated with dyslexia, a language-based disorder of learning to read and write. “Informed and effective classroom instruction. . . can prevent or at least effectively address and limit the severity of reading and writing problems.” The Interstellar Boundary Explorer (IBEX) mission Education and Public Outreach program recently funded the development of six strategy guides for teachers of middle school students with reading difficulties, especially dyslexia. These guides utilize space science-themed reading materials developed by the Great Exploration in Math and Science (GEMS), including the IBEX-funded GEMS Space Science Sequence (Grades 6-8). The aforementioned reading strategy guides are now available on the IBEX mission website.

  5. Multiple models guide strategies for agricultural nutrient reductions

    Science.gov (United States)

    Scavia, Donald; Kalcic, Margaret; Muenich, Rebecca Logsdon; Read, Jennifer; Aloysius, Noel; Bertani, Isabella; Boles, Chelsie; Confesor, Remegio; DePinto, Joseph; Gildow, Marie; Martin, Jay; Redder, Todd; Robertson, Dale M.; Sowa, Scott P.; Wang, Yu-Chen; Yen, Haw

    2017-01-01

    In response to degraded water quality, federal policy makers in the US and Canada called for a 40% reduction in phosphorus (P) loads to Lake Erie, and state and provincial policy makers in the Great Lakes region set a load-reduction target for the year 2025. Here, we configured five separate SWAT (US Department of Agriculture's Soil and Water Assessment Tool) models to assess load reduction strategies for the agriculturally dominated Maumee River watershed, the largest P source contributing to toxic algal blooms in Lake Erie. Although several potential pathways may achieve the target loads, our results show that any successful pathway will require large-scale implementation of multiple practices. For example, one successful pathway involved targeting 50% of row cropland that has the highest P loss in the watershed with a combination of three practices: subsurface application of P fertilizers, planting cereal rye as a winter cover crop, and installing buffer strips. Achieving these levels of implementation will require local, state/provincial, and federal agencies to collaborate with the private sector to set shared implementation goals and to demand innovation and honest assessments of water quality-related programs, policies, and partnerships.

  6. Comparison of Meaning and Graphophonemic Feedback Strategies for Guided Reading Instruction of Children with Language Delays

    Science.gov (United States)

    Kouri, Theresa A.; Selle, Carrie A.; Riley, Sarah A.

    2006-01-01

    Purpose: Guided reading is a common practice recommended for children in the early stages of literacy development. While experts agree that oral reading facilitates literacy skills, controversy exists concerning which corrective feedback strategies are most effective. The purpose of this study was to compare feedback procedures stemming from 2…

  7. A guided note taking strategy supports student learning in the large lecture classes

    Science.gov (United States)

    Tanamatayarat, J.; Sujarittham, T.; Wuttiprom, S.; Hefer, E.

    2017-09-01

    In higher education, lecturing has been found to be the most prevalent teaching format for large classes. Generally, this format tends not to result in effective learning outcomes. Therefore, to support student learning in these large lecture classes, we developed guided notes containing quotations, blank spaces, pictures, and problems. A guided note taking strategy was selected and has been used in our introductory physics course for many years. In this study, we investigated the results of implementing the guided note taking strategy to promote student learning on electrostatics. The samples were three groups of first-year students from two universities: 163 and 224 science students and 147 engineering students. All of the students were enrolled in the introductory physics course in the second semester. To assess the students’ understanding, we administered pre- and post-tests to the students by using the electrostatics test. The questions were selected from the conceptual survey of electricity and magnetism (CSEM) and some leading physics textbooks. The results of the students’ understanding were analyzed by the average normalized gains (). The value of each group was 0.61, 0.55, and 0.54, respectively. Furthermore, the students’ views on learning with the guided note taking strategy were explored by using the five-point rating scale survey. Most students perceived that the strategy helped support their active learning and engagement in the lectures.

  8. The use of story boxes as an adjuvant strategy to cope with hospitalization of children and adolescents with cancer

    Directory of Open Access Journals (Sweden)

    Nathália Rodrigues Garcia-Schinzari

    2014-12-01

    Full Text Available Introduction: Storytelling in hospital environments contributes to the reduction of tension and anxiety; it is, therefore, a possible strategy to cope with hospitalization of patients under cancer treatment. Objective: To identify and analyze the contributions of the program “Box of Stories” (storytelling program in coping with hospitalization of children and adolescents. Methodological Procedures: It is a non-experimental, cross-sectional, descriptive, applied research of quali-quantitative approach conducted in a pediatric oncology unit in the countryside of Sao Paulo state. Twenty children and adolescents ages 4 to 15 participated in the study. Data collection consisted of (1 pretest (indication on the scale of faces or verbal expression of one’s feeling at that moment; (2 record of the behaviors of children during the storytelling; and (3 posttest (indication on the scale of faces or verbal expression of one’s feeling after the storytelling. Results: The participants interacted with the people present during storytelling (interaction with undergraduate students of occupational therapy and with peers as well as with material from the boxes (manipulation of objects and participation in the activity proposed, and demonstrated cognitive abilities (attention and imagination and motivation (liveliness and curiosity about the stories. Nine participants presented significant changes in their emotional state after the storytelling (p=0.0111. Conclusions: The use of story boxes proved to be an important intervention in improving the way children and adolescents with cancer cope with hospitalization, restoring their playful universe and facilitating health recovery.

  9. Radiation Therapy–First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Woo [Department of Hematology-Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Noh, O Kyu, E-mail: okyu.noh@gmail.com [Department of Radiation Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Oh, Young-Taek [Department of Radiation Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Choi, Jin-Hyuk [Department of Hematology-Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Chun, Mison; Kim, Hwan-Ik; Heo, Jaesung [Department of Radiation Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Ahn, Mi Sun [Department of Hematology-Oncology, Ajou University School of Medicine, Suwon (Korea, Republic of); Park, Seong Yong [Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon (Korea, Republic of); Park, Rae Woong; Yoon, Dukyong [Department of Biomedical Informatics, Ajou University School of Medicine, Suwon (Korea, Republic of)

    2016-03-01

    Purpose: Postoperative radiation therapy (PORT) and postoperative chemotherapy (POCT) can be administered as adjuvant therapies in patients with non-small cell lung cancer (NSCLC). The aim of this study was to present the clinical outcomes in patients treated with PORT-first with or without subsequent POCT in stage IIIA-N2 NSCLC. Methods and Materials: From January 2002 to November 2014, the conditions of 105 patients with stage IIIA-N2 NSCLC who received PORT-first with or without subsequent POCT were analyzed. PORT was initiated within 4 to 6 weeks after surgical resection. Platinum-based POCT was administered 3 to 4 weeks after the completion of PORT. We analyzed the outcomes and the clinical factors affecting survival. Results: Of 105 patients, 43 (41.0%) received POCT with a median of 4 cycles (range, 2-6 cycles). The follow-up times ranged from 3 to 123 months (median, 30 months), and the 5-year overall survival (OS) was 40.2%. The 5-year OS of patients treated with PORT and POCT was significantly higher than that of patients with PORT (61.3% vs 29.2%, P<.001). The significant prognostic factors affecting OS were the use of POCT (hazard ratio [HR] = 0.453, P=.036) and type of surgery (pneumonectomy/lobectomy; HR = 2.845, P<.001). Conclusions: PORT-first strategy after surgery appeared not to compromise the clinical outcomes in the treatment of stage IIIA-N2 NSCLC. The benefit of POCT on OS was preserved even in the PORT-first setting. Further studies are warranted to compare the sequencing of PORT and POCT, guaranteeing the proper use of POCT.

  10. Self-Regulated Learning Strategies of Engineering College Students While Learning Electric Circuit Concepts with Enhanced Guided Notes

    Science.gov (United States)

    Lawanto, Oenardi; Santoso, Harry

    2013-01-01

    The current study evaluated engineering college students' self-regulated learning (SRL) strategies while learning electric circuit concepts using enhanced guided notes (EGN). Our goal was to describe how students exercise SRL strategies and how their grade performance changes after using EGN. Two research questions guided the study: (1) To what…

  11. A guide to understanding and implementing risk evaluation and mitigation strategies in organ transplantation.

    Science.gov (United States)

    Gabardi, Steven; Tichy, Eric M

    2013-03-01

    To review the components of the Congressional mandate for risk evaluation and mitigation strategies (REMS) managed by the Food and Drug Administration and assess their impact on health care providers practicing within the organ transplant arena. A non-date-limited search of MEDLINE and EMBASE (January 2007-June 2012) was conducted by using the following search terms: risk evaluation and mitigation strategies, REMS, and organ transplant, including a query of the individual organs. Information from the Federal Register and the Food and Drug Administration was also evaluated. REMS are strategies implemented to manage known or potential risks associated with medications and to ensure ongoing pharmacovigilance throughout the life of a pharmaceutical product. Elements of REMS programs may consist of 3 levels: a medication guide, communication plan, and elements to assure safe use. A medication guide is used to help prevent serious adverse events, aid in patients' decision making, and enhance medication adherence. Communication plans help educate health care providers and encourage adherence with REMS. The elements to assure safe use is a restrictive process implemented when it is deemed necessary to ensure safe access for patients to products with known serious risks. In transplant medicine, REMS currently exist for belatacept (medication guide and communication plan) and the mycophenolic acid derivatives (medication guide and elements to assure safe use). REMS are another step in the evolution of the development and marketing of pharmaceutical agents. Use of REMS in solid-organ transplant is becoming common. Transplant clinicians must provide required patient education and become involved with other aspects of REMS implementation to reduce the serious risks of pharmaceuticals and to improve patients' outcomes.

  12. Metagenomic Taxonomy-Guided Database-Searching Strategy for Improving Metaproteomic Analysis.

    Science.gov (United States)

    Xiao, Jinqiu; Tanca, Alessandro; Jia, Ben; Yang, Runqing; Wang, Bo; Zhang, Yu; Li, Jing

    2018-04-06

    Metaproteomics provides a direct measure of the functional information by investigating all proteins expressed by a microbiota. However, due to the complexity and heterogeneity of microbial communities, it is very hard to construct a sequence database suitable for a metaproteomic study. Using a public database, researchers might not be able to identify proteins from poorly characterized microbial species, while a sequencing-based metagenomic database may not provide adequate coverage for all potentially expressed protein sequences. To address this challenge, we propose a metagenomic taxonomy-guided database-search strategy (MT), in which a merged database is employed, consisting of both taxonomy-guided reference protein sequences from public databases and proteins from metagenome assembly. By applying our MT strategy to a mock microbial mixture, about two times as many peptides were detected as with the metagenomic database only. According to the evaluation of the reliability of taxonomic attribution, the rate of misassignments was comparable to that obtained using an a priori matched database. We also evaluated the MT strategy with a human gut microbial sample, and we found 1.7 times as many peptides as using a standard metagenomic database. In conclusion, our MT strategy allows the construction of databases able to provide high sensitivity and precision in peptide identification in metaproteomic studies, enabling the detection of proteins from poorly characterized species within the microbiota.

  13. Mobile Guide System Using Problem-Solving Strategy for Museum Learning: A Sequential Learning Behavioural Pattern Analysis

    Science.gov (United States)

    Sung, Y.-T.; Hou, H.-T.; Liu, C.-K.; Chang, K.-E.

    2010-01-01

    Mobile devices have been increasingly utilized in informal learning because of their high degree of portability; mobile guide systems (or electronic guidebooks) have also been adopted in museum learning, including those that combine learning strategies and the general audio-visual guide systems. To gain a deeper understanding of the features and…

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Mobile strategies for digital publishing a practical guide to the evolving landscape

    CERN Document Server

    McIlroy, Thad

    2015-01-01

    The explosion of mobile devices around the world is transforming the nature of digital publishing. Publishers and digital content developers must rethink every node of the publishing process in order to take advantage of the fast-approaching mobile future. Mobile Strategies for Digital Publishing: A Practical Guide to the Evolving Landscape offers an in-depth look at the latest mobile trends and how they're changing the shape of the industry. Publishing analyst Thad McIlroy, founder of the Future of Publishing blog, assembles and a reviews a wide range of recent data on e-reading prac

  16. Adjuvant chemo- and radiotherapy in gastrointestinal tumors

    International Nuclear Information System (INIS)

    Sendler, A.; Feldmann, H.J.; Fink, U.; Molls, M.; Siewert, J.R.

    1995-01-01

    In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R 0 resection) and additive therapies following incomplete tumor resections (UICC R 1 or R 2 resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R 0 resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [de

  17. An Elastic Charging Service Fee-Based Load Guiding Strategy for Fast Charging Stations

    Directory of Open Access Journals (Sweden)

    Shu Su

    2017-05-01

    Full Text Available Compared with the traditional slow charging loads, random integration of large scale fast charging loads will exert more serious impacts on the security of power network operation. Besides, to maximize social benefits, effective scheduling strategies guiding fast charging behaviors should be formulated rather than simply increasing infrastructure construction investments on the power grid. This paper first analyzes the charging users’ various responses to an elastic charging service fee, and introduces the index of charging balance degree to a target region by considering the influence of fast charging loads on the power grid. Then, a multi-objective optimization model of the fast charging service fee is constructed, whose service fee can be further optimized by employing a fuzzy programming method. Therefore, both users’ satisfaction degree and the equilibrium of charging loads can be maintained simultaneously by reasonably guiding electric vehicles (EVs to different fast charging stations. The simulation results demonstrate the effectiveness of the proposed dynamic charging service pricing and the corresponding fast charging load guidance strategy.

  18. Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

    Science.gov (United States)

    García-Blas, Sergio; Bonanad, Clara; Llàcer, Pau; Ventura, Silvia; Núñez, José María; Sánchez, Ruth; Chamorro, Carlos; Fácila, Lorenzo; de la Espriella, Rafael; Vaquer, Juana María; Cordero, Alberto; Roqué, Mercè; Ortiz, Víctor; Racugno, Paolo; Bodí, Vicent; Valero, Ernesto; Santas, Enrique; Moreno, María Del Carmen; Miñana, Gema; Carratalá, Arturo; Bondanza, Lourdes; Payá, Ana; Cardells, Ingrid; Heredia, Raquel; Pellicer, Mauricio; Valls, Guillermo; Palau, Patricia; Bosch, María José; Raso, Rafael; Sánchez, Andrés; Bertomeu-González, Vicente; Bertomeu-Martínez, Vicente; Montagud-Balaguer, Vicente; Albiach-Montañana, Cristina; Pendás-Meneau, Jezabel; Marcaida, Goitzane; Cervantes-García, Sonia; San Antonio, Rodolfo; de Mingo, Elisabet; Chorro, Francisco J; Sanchis, Juan; Núñez, Julio

    2017-12-01

    The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  19. STRATEGY FOR THE USE OF ERYTHROPOETIN ALPHA TO MAINTAIN HEMOGLOBIN LEVEL IN BREAST CANCER PATIENT TREATED WITH ANTHRACYCLINE-BASE OF ADJUVANT CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Dimyati Achmad

    2015-07-01

    Full Text Available Objective: To evaluate the value of erythropoietin alpha (epoetin administration, as an alternative treatment of anemia in the operable breast cancer patients. Methods: This is a multicenter phase III randomized clinical trial to evaluate the value of epoetin administration among anemic breast cancer patients who are undergoing anthracyclin-based adjuvant chemotherapy. Sixty four patients were incuded in this trial with initial hemoglobin (Hb level of 10–12 g/dL. The patients were randomly distributed into two groups: one group received aministration of 40,000 IU epoetin/week for six times a week after operation and the other did not. In the third week after the operation, both groups were started on a 6 cycles of adjuvant chemotherapy with three weeks intervals. Hb levels were evaluated during every chemotherapy cycle. Results: The Hb levels in the epoetin group were always above 10 g/dL up until the end of the sixth chemotherapy cycle or until the twenty first week post operation without blood transfusion. Conclusions: The administration of epoetin 3 weeks prior and 3 weeks after the first cycles of chemotherapy, maintains a sufficient/normal Hb level in breast cancer patients receiving anthracycline-based chemotherapy.

  20. Hypothesis driven development of new adjuvants: short peptides as immunomodulators.

    Science.gov (United States)

    Dong, Jessica C; Kobinger, Gary P

    2013-04-01

    To date, vaccinations have been one of the key strategies in the prevention and protection against infectious pathogens. Traditional vaccines have well-known limitations such as safety and efficacy issues, which consequently deems it inappropriate for particular populations and may not be an effective strategy against all pathogens. This evidence highlights the need to develop more efficacious vaccination regiments. Higher levels of protection can be achieved by the addition of immunostimulating adjuvants. Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects. Hypothesis driven development of adjuvants is needed to achieve a more specific and directed immune response required for optimal and safe vaccine-induced immune protection. An example of such hypothesis driven development includes the use of short immunomodulating peptides as adjuvants. These peptides have the ability to influence the immune response and can be extrapolated for adjuvant use, but requires further investigation.

  1. Phase II/III multicentre randomised controlled trial evaluating a strategy of primary surgery and adjuvant chemotherapy versus peri-operative chemotherapy for resectable gastric signet ring cell adenocarcinomas – PRODIGE 19 – FFCD1103 – ADCI002

    International Nuclear Information System (INIS)

    Piessen, Guillaume; Mariette, Christophe; Messager, Mathieu; Le Malicot, Karine; Robb, William B; Di Fiore, Frédéric; Guilbert, Marie; Moreau, Marie; Christophe, Véronique; Adenis, Antoine

    2013-01-01

    A dramatic increase in the incidence of the diffuse form of gastric adenocarcinomas and particularly signet ring cell carcinomas has been observed in Western countries. Evidence is accruing that signet ring cell carcinomas may have inherent chemo resistance leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach. PRODIGE-19-FFCD1103-ADCI002 is a prospective multicentre controlled randomised phase II/III trial comparing current standard of care of perioperative chemotherapy (2x3 cycles of Epirubicin, cisplatin, 5-fluorouracil) with a strategy of primary surgery followed by adjuvant chemotherapy (6 cycles of Epirubicin, cisplatin, 5-fluorouracil) in patients with a stage IB-III gastric signet ring cell tumour. The principal objective of the phase II study (84 patients) is to determine if the experimental arm (primary surgery followed by adjuvant chemotherapy) has sufficient interest in terms of percentage of living patients at 24 months to be evaluated in a phase III trial. If 7 or less patients in the experimental arm are alive at 24 months, phase III will not be initiated. The primary objective of phase III (230 additional patients) is to demonstrate superiority of the experimental arm in terms of overall survival. Secondary endpoints include overall survival at 36 months, disease free survival at 24 and 36 months, R0 resection rates, treatment tolerance, postoperative mortality and morbidity evaluated by Clavien-Dindo severity index, the prognostic impact of positive peritoneal cytology and the assessment of quality of life. An ancillary study will assess the emotional and cognitive impact of surgery and perioperative chemotherapy for both the patient and their partner. As inherent chemo resistance of signet ring cell tumours and delay in definitive surgery may favour tumour progression we hypothesise that a policy of primary surgery followed by adjuvant chemotherapy will improve overall survival compared to a standard

  2. Damage detection strategies for aircraft shell-like structures based on propagation guided elastic waves

    International Nuclear Information System (INIS)

    Zak, A; Ostachowicz, W; Krawczuk, M

    2011-01-01

    Damage of aircraft structural elements in any form always present high risks. Failures of these elements can be caused by various reasons including material fatigue or impact leading to damage initiation and growth. Detection of these failures at their earliest stage of development, estimation of their size and location, are one of the most crucial factors for each damage detection method. Structural health monitoring strategies based on propagation of guided elastic waves in structures and wave interaction with damage related discontinuities are very promising tools that offer not only damage detection capabilities, but are also meant to provide precise information about the state of the structures and their remaining lifetime. Because of that various techniques are employed to simulate and mimic the wave-discontinuity interactions. The use of various types of sensors, their networks together with sophisticated contactless measuring techniques are investigated both numerically and experimentally. Certain results of numerical simulations obtained by the use of the spectral finite element method are presented by the authors and related with propagation of guided elastic waves in shell-type aircraft structures. Two types of structures are considered: flat 2D panels with or without stiffeners and 3D shell structures. The applicability of two different damage detection approaches is evaluated in order to detect and localise damage in these structures. Selected results related with the use of laser scanning vibrometry are also presented and discussed by the authors.

  3. Guided Inquiry with Cognitive Conflict Strategy: Drilling Indonesian High School Students’ Creative Thinking Skills

    Science.gov (United States)

    Syadzili, A. F.; Soetjipto; Tukiran

    2018-01-01

    This research aims to produce physics learning materials in Indonesian high school using guided inquiry with cognitive conflict strategy to drill students’ creative thinking skills in a static fluid learning. This development research used 4D model with one group pre-test and post-test design implemented in the eleventh grade students in the second semester of 2016/2017 academic year. The data were collected by validation sheets, questionnaires, tests and observations, while data analysis techniques is descriptive quantitative analysis. This research obtained several findings, they are : the learning material developed had an average validity score with very valid category. The lesson plan can be implemented very well. The students’ responses toward the learning process were very possitive with the students’ interest to follow the learning. Creative thinking skills of student before the implementation of product was inadequate, then it is very creative after product was implemented. The impacts of the research suggest that guided inquiry may stimulate the students to think creatifly.

  4. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

    Directory of Open Access Journals (Sweden)

    Jan eStenvang

    2013-12-01

    Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

  5. Effects of Guided Discovery and Think-Pair-Share Strategies on Secondary School Students’ Achievement in Chemistry

    Directory of Open Access Journals (Sweden)

    Adekunle Oladipupo Bamiro

    2015-01-01

    Full Text Available This study investigated the effects of three strategies (i.e., guided discovery, think-pair-share, and lecture on senior secondary school students’ achievement in chemistry. A pretest, posttest, control group quasi-experimental design with a 3 × 3 × 2 factorial matrix was adopted for the study. Treatment was at three levels (guided discovery, think-pair-share, and lecture strategies. Intervening variables were cognitive entry behavior at three levels (high, middle, and low and gender at two levels (male and female. Two hundred forty-two Senior Secondary 1 students in intact classes from six secondary schools in Ijebu Ode and Odogbolu Local Government Areas of Ogun State were randomly assigned to the treatment and control groups. Three instruments were developed and used to collect data from students during the 8-week treatment program. The data collected were subjected to analysis of covariance and multiple classification analysis. Scheffé test was further used as post hoc measures. Where significant interactions were observed, they were represented with graphical illustrations. It was found that students taught with guided discovery and think-pair-share strategies obtained significantly higher posttest mean scores than those in the lecture strategy, F(4, 223 = 51.66, p < .05. The use of guided discovery and think-pair-share strategies had great potential for improving achievement in chemistry and science learning generally.

  6. Cost-effectiveness of MR Imaging-guided Strategies for Detection of Prostate Cancer in Biopsy-Naive Men.

    Science.gov (United States)

    Pahwa, Shivani; Schiltz, Nicholas K; Ponsky, Lee E; Lu, Ziang; Griswold, Mark A; Gulani, Vikas

    2017-10-01

    Purpose To evaluate the cost-effectiveness of multiparametric diagnostic magnetic resonance (MR) imaging examination followed by MR imaging-guided biopsy strategies in the detection of prostate cancer in biopsy-naive men presenting with clinical suspicion of cancer for the first time. Materials and Methods A decision-analysis model was created for biopsy-naive men who had been recommended for prostate biopsy on the basis of abnormal digital rectal examination results or elevated prostate-specific antigen levels (age groups: 41-50 years, 51-60 years, and 61-70 years). The following three major strategies were evaluated: (a) standard transrectal ultrasonography (US)-guided biopsy; (b) diagnostic MR imaging followed by MR imaging-targeted biopsy, with no biopsy performed if MR imaging findings were negative; and (c) diagnostic MR imaging followed by MR imaging-targeted biopsy, with a standard biopsy performed when MR imaging findings were negative. The following three MR imaging-guided biopsy strategies were further evaluated in each MR imaging category: (a) biopsy with cognitive guidance, (b) biopsy with MR imaging/US fusion guidance, and (c) in-gantry MR imaging-guided biopsy. Model parameters were derived from the literature. The primary outcome measure was net health benefit (NHB), which was measured as quality-adjusted life-years (QALYs) gained or lost by investing resources in a new strategy compared with a standard strategy at a willingness-to-pay (WTP) threshold of $50 000 per QALY gained. Probabilistic sensitivity analysis was performed by using Monte Carlo simulations. Results Noncontrast MR imaging followed by cognitively guided MR biopsy (no standard biopsy if MR imaging findings were negative) was the most cost-effective approach, yielding an additional NHB of 0.198 QALY compared with the standard biopsy approach. Noncontrast MR imaging followed by in-gantry MR imaging-guided biopsy (no standard biopsy if MR imaging findings were negative) led to the

  7. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. The Effective Teacher's Guide to Autism and Communication Difficulties: Practical Strategies, Second Edition. The Effective Teacher's Guides

    Science.gov (United States)

    Farrell, Michael

    2011-01-01

    In this welcome second edition of "The Effective Teacher's Guide to Autism and Communication Difficulties", best-selling author Michael Farrell addresses how teachers and others can develop provision for students with autism and students that have difficulties with speech, grammar, meaning, use of language and comprehension. Updated and expanded,…

  9. Radiation Therapy-First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Lee, Hyun Woo; Noh, O Kyu; Oh, Young-Taek; Choi, Jin-Hyuk; Chun, Mison; Kim, Hwan-Ik; Heo, Jaesung; Ahn, Mi Sun; Park, Seong Yong; Park, Rae Woong; Yoon, Dukyong

    2016-03-01

    Postoperative radiation therapy (PORT) and postoperative chemotherapy (POCT) can be administered as adjuvant therapies in patients with non-small cell lung cancer (NSCLC). The aim of this study was to present the clinical outcomes in patients treated with PORT-first with or without subsequent POCT in stage IIIA-N2 NSCLC. From January 2002 to November 2014, the conditions of 105 patients with stage IIIA-N2 NSCLC who received PORT-first with or without subsequent POCT were analyzed. PORT was initiated within 4 to 6 weeks after surgical resection. Platinum-based POCT was administered 3 to 4 weeks after the completion of PORT. We analyzed the outcomes and the clinical factors affecting survival. Of 105 patients, 43 (41.0%) received POCT with a median of 4 cycles (range, 2-6 cycles). The follow-up times ranged from 3 to 123 months (median, 30 months), and the 5-year overall survival (OS) was 40.2%. The 5-year OS of patients treated with PORT and POCT was significantly higher than that of patients with PORT (61.3% vs 29.2%, Ptreatment of stage IIIA-N2 NSCLC. The benefit of POCT on OS was preserved even in the PORT-first setting. Further studies are warranted to compare the sequencing of PORT and POCT, guaranteeing the proper use of POCT. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Adapting to climate change in forest based land use systems: A guide to strategy

    Energy Technology Data Exchange (ETDEWEB)

    Secrett, C M

    1997-12-31

    The prospect of climate change and sea level rise as a result of greenhouse gas emissions presents a serious challenge to decision-makers concerned with ensuring sustainable development. This report provides a guide to means of reducing the potential impact of the global warming problem on the forest sector whilst ensuring that more immediate development priorities are met. The most effective response strategy will be one that simultaneously brings both immediate development and longer-term adaptive benefits. This report outlines ways of constructing an adaptive response strategy that can help achieve these ends. The approach is referred to as sustainable adaptation. A prototype methodological framework of the sustainable adaptation approach has been provided with the summary. The first priority of sustainable adaption is to base climate change responses on actions that meet basic ecological and social needs now and in the future. Solutions should necessarily include relieving current development pressures in the tropical forest sector. The key is to couple adaptive responses to climate change with sustainable development solutions to present-day forest use problems. Implementing adaptive land-use policies and management practices which are likely to minimise the adverse impacts of anticipated climate change should meet current sustainable management goals. Implementing sustainable land-use and forestry management practices should meet adaptation goals. This report presents a discussion of the fundamental issues underlying the development of a sustainable adaptation strategy and a prototype methodological framework. The findings are based on case studies conducted in Central America (Costa Rica and Nicaragua); SADCC countries in Africa (Zimbabwe, Botswana, Tanzania); and Asia (Vietnam). 450 refs

  11. Adapting to climate change in forest based land use systems: A guide to strategy

    Energy Technology Data Exchange (ETDEWEB)

    Secrett, C.M.

    1996-12-31

    The prospect of climate change and sea level rise as a result of greenhouse gas emissions presents a serious challenge to decision-makers concerned with ensuring sustainable development. This report provides a guide to means of reducing the potential impact of the global warming problem on the forest sector whilst ensuring that more immediate development priorities are met. The most effective response strategy will be one that simultaneously brings both immediate development and longer-term adaptive benefits. This report outlines ways of constructing an adaptive response strategy that can help achieve these ends. The approach is referred to as sustainable adaptation. A prototype methodological framework of the sustainable adaptation approach has been provided with the summary. The first priority of sustainable adaption is to base climate change responses on actions that meet basic ecological and social needs now and in the future. Solutions should necessarily include relieving current development pressures in the tropical forest sector. The key is to couple adaptive responses to climate change with sustainable development solutions to present-day forest use problems. Implementing adaptive land-use policies and management practices which are likely to minimise the adverse impacts of anticipated climate change should meet current sustainable management goals. Implementing sustainable land-use and forestry management practices should meet adaptation goals. This report presents a discussion of the fundamental issues underlying the development of a sustainable adaptation strategy and a prototype methodological framework. The findings are based on case studies conducted in Central America (Costa Rica and Nicaragua); SADCC countries in Africa (Zimbabwe, Botswana, Tanzania); and Asia (Vietnam). 450 refs

  12. Intertextual learning strategy with guided inquiry on solubility equilibrium concept to improve the student’s scientific processing skills

    Science.gov (United States)

    Wardani, K. U.; Mulyani, S.; Wiji

    2018-04-01

    The aim of this study was to develop intertextual learning strategy with guided inquiry on solubility equilibrium concept to enhance student’s scientific processing skills. This study was conducted with consideration of some various studies which found that lack of student’s process skills in learning chemistry was caused by learning chemistry is just a concept. The method used in this study is a Research and Development to generate the intertextual learning strategy with guided inquiry. The instruments used in the form of sheets validation are used to determine the congruence of learning activities by step guided inquiry learning and scientific processing skills with aspects of learning activities. Validation results obtained that the learning activities conducted in line with aspects of indicators of the scientific processing skills.

  13. Adjuvant Biological Therapies in Chronic Leg Ulcers

    Directory of Open Access Journals (Sweden)

    Natalia Burgos-Alonso

    2017-11-01

    Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

  14. A practical approach to assess depression risk and to guide risk reduction strategies in later life.

    Science.gov (United States)

    Almeida, Osvaldo P; Alfonso, Helman; Pirkis, Jane; Kerse, Ngaire; Sim, Moira; Flicker, Leon; Snowdon, John; Draper, Brian; Byrne, Gerard; Goldney, Robert; Lautenschlager, Nicola T; Stocks, Nigel; Scazufca, Marcia; Huisman, Martijn; Araya, Ricardo; Pfaff, Jon

    2011-03-01

    Many factors have been associated with the onset and maintenance of depressive symptoms in later life, although this knowledge is yet to be translated into significant health gains for the population. This study gathered information about common modifiable and non-modifiable risk factors for depression with the aim of developing a practical probabilistic model of depression that can be used to guide risk reduction strategies. A cross-sectional study was undertaken of 20,677 community-dwelling Australians aged 60 years or over in contact with their general practitioner during the preceding 12 months. Prevalent depression (minor or major) according to the Patient Health Questionnaire (PHQ-9) assessment was the main outcome of interest. Other measured exposures included self-reported age, gender, education, loss of mother or father before age 15 years, physical or sexual abuse before age 15 years, marital status, financial stress, social support, smoking and alcohol use, physical activity, obesity, diabetes, hypertension, and prevalent cardiovascular diseases, chronic respiratory diseases and cancer. The mean age of participants was 71.7 ± 7.6 years and 57.9% were women. Depression was present in 1665 (8.0%) of our subjects. Multivariate logistic regression showed depression was independently associated with age older than 75 years, childhood adverse experiences, adverse lifestyle practices (smoking, risk alcohol use, physical inactivity), intermediate health hazards (obesity, diabetes and hypertension), comorbid medical conditions (clinical history of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, emphysema or cancers), and social or financial strain. We stratified the exposures to build a matrix that showed that the probability of depression increased progressively with the accumulation of risk factors, from less than 3% for those with no adverse factors to more than 80% for people reporting the maximum number of risk factors. Our

  15. Process-oriented guided inquiry learning strategy enhances students' higher level thinking skills in a pharmaceutical sciences course.

    Science.gov (United States)

    Soltis, Robert; Verlinden, Nathan; Kruger, Nicholas; Carroll, Ailey; Trumbo, Tiffany

    2015-02-17

    To determine if the process-oriented guided inquiry learning (POGIL) teaching strategy improves student performance and engages higher-level thinking skills of first-year pharmacy students in an Introduction to Pharmaceutical Sciences course. Overall examination scores and scores on questions categorized as requiring either higher-level or lower-level thinking skills were compared in the same course taught over 3 years using traditional lecture methods vs the POGIL strategy. Student perceptions of the latter teaching strategy were also evaluated. Overall mean examination scores increased significantly when POGIL was implemented. Performance on questions requiring higher-level thinking skills was significantly higher, whereas performance on questions requiring lower-level thinking skills was unchanged when the POGIL strategy was used. Student feedback on use of this teaching strategy was positive. The use of the POGIL strategy increased student overall performance on examinations, improved higher-level thinking skills, and provided an interactive class setting.

  16. Laser vaccine adjuvants

    Science.gov (United States)

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  17. A strategy to objectively evaluate the necessity of correcting detected target deviations in image guided radiotherapy

    International Nuclear Information System (INIS)

    Yue, Ning J.; Kim, Sung; Jabbour, Salma; Narra, Venkat; Haffty, Bruce G.

    2007-01-01

    Image guided radiotherapy technologies are being increasingly utilized in the treatment of various cancers. These technologies have enhanced the ability to detect temporal and spatial deviations of the target volume relative to planned radiation beams. Correcting these detected deviations may, in principle, improve the accuracy of dose delivery to the target. However, in many situations, a clinical decision has to be made as to whether it is necessary to correct some of the deviations since the relevant dosimetric impact may or may not be significant, and the corresponding corrective action may be either impractical or time consuming. Ideally this decision should be based on objective and reproducible criteria rather than subjective judgment. In this study, a strategy is proposed for the objective evaluation of the necessity of deviation correction during the treatment verification process. At the treatment stage, without any alteration from the planned beams, the treatment beams should provide the desired dose coverage to the geometric volume identical to the planning target volume (PTV). Given this fact, the planned dose distribution and PTV geometry were used to compute the dose coverage and PTV enclosure of the clinical target volume (CTV) that was detected from imaging during the treatment setup verification. The spatial differences between the detected CTV and the planning CTV are essentially the target deviations. The extent of the PTV enclosure of the detected CTV as well as its dose coverage were used as criteria to evaluate the necessity of correcting any of the target deviations. This strategy, in principle, should be applicable to any type of target deviations, including both target deformable and positional changes and should be independent of how the deviations are detected. The proposed strategy was used on two clinical prostate cancer cases. In both cases, gold markers were implanted inside the prostate for the purpose of treatment setup

  18. Cheating experience: Guiding novices to adopt the gaze strategies of experts expedites the learning of technical laparoscopic skills.

    Science.gov (United States)

    Vine, Samuel J; Masters, Rich S W; McGrath, John S; Bright, Elizabeth; Wilson, Mark R

    2012-07-01

    Previous research has demonstrated that trainees can be taught (via explicit verbal instruction) to adopt the gaze strategies of expert laparoscopic surgeons. The current study examined a software template designed to guide trainees to adopt expert gaze control strategies passively, without being provided with explicit instructions. We examined 27 novices (who had no laparoscopic training) performing 50 learning trials of a laparoscopic training task in either a discovery-learning (DL) group or a gaze-training (GT) group while wearing an eye tracker to assess gaze control. The GT group performed trials using a surgery-training template (STT); software that is designed to guide expert-like gaze strategies by highlighting the key locations on the monitor screen. The DL group had a normal, unrestricted view of the scene on the monitor screen. Both groups then took part in a nondelayed retention test (to assess learning) and a stress test (under social evaluative threat) with a normal view of the scene. The STT was successful in guiding the GT group to adopt an expert-like gaze strategy (displaying more target-locking fixations). Adopting expert gaze strategies led to an improvement in performance for the GT group, which outperformed the DL group in both retention and stress tests (faster completion time and fewer errors). The STT is a practical and cost-effective training interface that automatically promotes an optimal gaze strategy. Trainees who are trained to adopt the efficient target-locking gaze strategy of experts gain a performance advantage over trainees left to discover their own strategies for task completion. Copyright © 2012 Mosby, Inc. All rights reserved.

  19. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    Science.gov (United States)

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  20. Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

    Science.gov (United States)

    Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

    2010-12-01

    A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

  1. The reHABITAT Guide: For Energy- and Resource-Efficient Retrofit Strategies

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-07-01

    This guide seeks to advance the goal of the U.S. Department of Energy’s Existing Residential Buildings Program (ERBP): to develop approaches that will enable the housing retrofit industry to deliver energy-efficient housing improvements.

  2. Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound

    Science.gov (United States)

    Odéen, Henrik; Todd, Nick; Diakite, Mahamadou; Minalga, Emilee; Payne, Allison; Parker, Dennis L.

    2014-01-01

    Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes

  3. Guiding health promotion efforts with urban Inuit: a community-specific perspective on health information sources and dissemination strategies.

    Science.gov (United States)

    McShane, Kelly E; Smylie, Janet K; Hastings, Paul D; Martin, Carmel M

    2006-01-01

    To develop a community-specific perspective of health information sources and dissemination strategies of urban Inuit to better guide health promotion efforts. Through a collaborative partnership with the Tungasuvvingat Inuit Family Resource Centre, a series of key informant interviews and focus groups were conducted to gather information on specific sources of health information, strategies of health information dissemination, and overall themes in health information processes. Distinct patterns of health information sources and dissemination strategies emerged from the data. Major themes included: the importance of visual learning, community Elders, and cultural interpreters; community cohesion; and the Inuit and non-Inuit distinction. The core sources of health information are family members and sources from within the Inuit community. The principal dissemination strategy for health information was direct communication, either through one-on-one interactions or in groups. This community-specific perspective of health information sources and dissemination strategies shows substantial differences from current mainstream models of health promotion and knowledge translation. Health promotion efforts need to acknowledge the distinct health information processes of this community, and should strive to integrate existing health information sources and strategies of dissemination with those of the community.

  4. Process-Oriented Guided Inquiry Learning Strategy Enhances Students’ Higher Level Thinking Skills in a Pharmaceutical Sciences Course

    Science.gov (United States)

    Verlinden, Nathan; Kruger, Nicholas; Carroll, Ailey; Trumbo, Tiffany

    2015-01-01

    Objective. To determine if the process-oriented guided inquiry learning (POGIL) teaching strategy improves student performance and engages higher-level thinking skills of first-year pharmacy students in an Introduction to Pharmaceutical Sciences course. Design. Overall examination scores and scores on questions categorized as requiring either higher-level or lower-level thinking skills were compared in the same course taught over 3 years using traditional lecture methods vs the POGIL strategy. Student perceptions of the latter teaching strategy were also evaluated. Assessment. Overall mean examination scores increased significantly when POGIL was implemented. Performance on questions requiring higher-level thinking skills was significantly higher, whereas performance on questions requiring lower-level thinking skills was unchanged when the POGIL strategy was used. Student feedback on use of this teaching strategy was positive. Conclusion. The use of the POGIL strategy increased student overall performance on examinations, improved higher-level thinking skills, and provided an interactive class setting. PMID:25741027

  5. The reHABITAT Guide: For Energy- and Resource-Efficient Retrofit Strategies; February 2003--February 2004

    Energy Technology Data Exchange (ETDEWEB)

    2004-07-01

    The reHABITAT Guide for Energy- and Resource-Efficient Retrofit Strategies seeks to advance the goal of the U.S. Department of Energy's Existing Residential Buildings Program (ERBP): to develop approaches that will enable the housing retrofit industry to deliver energy-efficient housing improvements and to ensure that energy-efficient retrofit technologies incorporated into projects are viable over conventional approaches. This guide was developed for Habitat for Humanity International and is the result of lessons learned from demonstration retrofit projects undertaken by Habitat for Humanity affiliates in Newburgh, New York; Baltimore, Maryland; and Philadelphia, Pennsylvania; with building systems consulting and technical assistance provided by Steven Winter Associates, Inc. (SWA).

  6. Scoring Strategies for the TOEFL iBT A Complete Guide

    CERN Document Server

    Stirling, Bruce

    2012-01-01

    TOEFL students all ask: How can I get a high TOEFL iBT score? Answer: Learn argument scoring strategies. Why? Because the TOEFL iBT recycles opinion-based and fact-based arguments for testing purposes from start to finish. In other words, the TOEFL iBT is all arguments. That's right, all arguments. If you want a high score, you need essential argument scoring strategies. That is what Scoring Strategies for the TOEFL iBT gives you, and more!. TEST-PROVEN STRATEGIES. Learn essential TOEFL iBT scoring strategies developed in American university classrooms and proven successful on the TOEFL iBT. R

  7. A Pragmatic Approach to Guide Implementation Evaluation Research: Strategy Mapping for Complex Interventions

    Directory of Open Access Journals (Sweden)

    Alexis K. Huynh

    2018-05-01

    Full Text Available IntroductionGreater specification of implementation strategies is a challenge for implementation science, but there is little guidance for delineating the use of multiple strategies involved in complex interventions. The Cardiovascular (CV Toolkit project entails implementation of a toolkit designed to reduce CV risk by increasing women’s engagement in appropriate services. The CV Toolkit project follows an enhanced version of Replicating Effective Programs (REP, an evidence-based implementation strategy, to implement the CV Toolkit across four phases: pre-conditions, pre-implementation, implementation, and maintenance and evolution. Our current objective is to describe a method for mapping implementation strategies used in real time as part of the CV Toolkit project. This method supports description of the timing and content of bundled strategies and provides a structured process for developing a plan for implementation evaluation.MethodsWe conducted a process of strategy mapping to apply Proctor and colleagues’ rubric for specification of implementation strategies, constructing a matrix in which we identified each implementation strategy, its conceptual group, and the corresponding REP phase(s in which it occurs. For each strategy, we also specified the actors involved, actions undertaken, action targets, dose of the implementation strategy, and anticipated outcome addressed. We iteratively refined the matrix with the implementation team, including use of simulation to provide initial validation.ResultsMapping revealed patterns in the timing of implementation strategies within REP phases. Most implementation strategies involving the development of stakeholder interrelationships and training and educating stakeholders were introduced during the pre-conditions or pre-implementation phases. Strategies introduced in the maintenance and evolution phase emphasized communication, re-examination, and audit and feedback. In addition to its value

  8. School Programs To Prevent Smoking: The National Cancer Institute Guide to Strategies That Succeed.

    Science.gov (United States)

    Glynn, Thomas J.

    This guide to school-based smoking prevention programs for educators is the product of five years of work to prevent cancer. The National Cancer Institute (NCI) is currently funding 23 coordinated intervention trials directed at youth. Although not all the studies are complete, sufficient results are available to recommend the most effective…

  9. The executive's guide to enterprise social media strategy how social networks are radically transforming your business

    CERN Document Server

    Barlow, Mike

    2010-01-01

    An actionable framework for developing and executing successful social media strategies supporting collaboration, teamwork and communication in modern corporationsUsing straightforward language, this book offers real-world stories and revealing anecdotes to demonstrate how executives and business leaders develop successful corporate social media strategies.High level guidance to developing the practical business frameworks and policies necessary for implementing and managing successful corporate social media strategiesDescribes the actual processes, organizational structures, and technology pl

  10. Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.

    Science.gov (United States)

    Gungor, Bilgi; Yagci, Fuat Cem; Gursel, Ihsan; Gursel, Mayda

    Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon α (IFNα) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity.

  11. Optimal Power Flow Using Gbest-Guided Cuckoo Search Algorithm with Feedback Control Strategy and Constraint Domination Rule

    Directory of Open Access Journals (Sweden)

    Gonggui Chen

    2017-01-01

    Full Text Available The optimal power flow (OPF is well-known as a significant optimization tool for the security and economic operation of power system, and OPF problem is a complex nonlinear, nondifferentiable programming problem. Thus this paper proposes a Gbest-guided cuckoo search algorithm with the feedback control strategy and constraint domination rule which is named as FCGCS algorithm for solving OPF problem and getting optimal solution. This FCGCS algorithm is guided by the global best solution for strengthening exploitation ability. Feedback control strategy is devised to dynamically regulate the control parameters according to actual and specific feedback value in the simulation process. And the constraint domination rule can efficiently handle inequality constraints on state variables, which is superior to traditional penalty function method. The performance of FCGCS algorithm is tested and validated on the IEEE 30-bus and IEEE 57-bus example systems, and simulation results are compared with different methods obtained from other literatures recently. The comparison results indicate that FCGCS algorithm can provide high-quality feasible solutions for different OPF problems.

  12. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    Skov, J.; Chettri, J. K.; Jaafar, R. M.

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

  13. National Security Strategy: A Flawed Guide to the Future, Political Science

    National Research Council Canada - National Science Library

    Leahy, Michael

    2003-01-01

    The Goldwater-Nichols Defense Department Reorganization Act of 1986 requires the executive branch to periodically provide written documentation of the United States National Security Strategy (NSS). The George W...

  14. Physical activity guides for Canadians: messaging strategies, realistic expectations for change, and evaluation.

    Science.gov (United States)

    Brawley, Lawrence R; Latimer, Amy E

    2007-01-01

    Physical activity guidelines offer evidence-based behavioural benchmarks that relate to reduced risk of morbidity and mortality if people adhere to them. Essentially, the guidelines tell people what to do, but not why and how they should do it. Thus, to motivate adherence, messages that translate guidelines should convey not only how much physical activity one should attempt and why it is recommended, but also how to achieve such a recommendation. Canada's physical activity guides exemplify how guidelines can be translated. This paper (i) provides a brief overview of the challenges encountered in creating the existing guides and (ii) highlights important practical issues and empirical evidence that should be considered in the future when translating guidelines into messages and disseminating these messages. We draw on the successes of past efforts to translate the goals of physical activity guidelines and on recent literature on messages and media campaigns to make recommendations. Information to motivate people to move toward the goals in physical activity guidelines should be translated into a set of messages that are informative, thought provoking, and persuasive. These messages should be disseminated to the public via a multi-phase social-marketing campaign that is carefully planned and thoroughly evaluated.

  15. A comparison of prostate tumor targeting strategies using magnetic resonance imaging-targeted, transrectal ultrasound-guided fusion biopsy.

    Science.gov (United States)

    Martin, Peter R; Cool, Derek W; Fenster, Aaron; Ward, Aaron D

    2018-03-01

    Magnetic resonance imaging (MRI)-targeted, three-dimensional (3D) transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21-47% false-negative rate of clinical two-dimensional (2D) TRUS-guided systematic biopsy, but continues to yield false-negative results. This may be improved via needle target optimization, accounting for guidance system errors and image registration errors. As an initial step toward the goal of optimized prostate biopsy targeting, we investigated how needle delivery error impacts tumor sampling probability for two targeting strategies. We obtained MRI and 3D TRUS images from 49 patients. A radiologist and radiology resident assessed these MR images and contoured 81 suspicious regions, yielding tumor surfaces that were registered to 3D TRUS. The biopsy system's root-mean-squared needle delivery error (RMSE) and systematic error were modeled using an isotropic 3D Gaussian distribution. We investigated two different prostate tumor-targeting strategies using (a) the tumor's centroid and (b) a ring in the lateral-elevational plane. For each simulation, targets were spaced at equal arc lengths on a ring with radius equal to the systematic error magnitude. A total of 1000 biopsy simulations were conducted for each tumor, with RMSE and systematic error magnitudes ranging from 1 to 6 mm. The difference in median tumor sampling probability and probability of obtaining a 50% core involvement was determined for ring vs centroid targeting. Our simulation results indicate that ring targeting outperformed centroid targeting in situations where systematic error exceeds RMSE. In these instances, we observed statistically significant differences showing 1-32% improvement in sampling probability due to ring targeting. Likewise, we observed statistically significant differences showing 1-39% improvement in 50% core involvement probability due to ring targeting. Our results suggest that the optimal targeting scheme for prostate biopsy depends on

  16. Alternative Teaching Strategies; Helping Behaviorally Troubled Children Achieve. A Guide for Teachers and Psychologists.

    Science.gov (United States)

    Swift, Marshall S.; Spivack, George

    This book provides (1) specific information about overt classroom behaviors that affect or reflect academic success or failure, and (2) information and suggestions about alternative teaching strategies that may be used to increase behavioral effectiveness and subsequent academic achievement. The focus of the book is on specific behaviors, behavior…

  17. Ab Initio Guided Low Temperature Synthesis Strategy for Smooth Face–Centred Cubic FeMn Thin Films

    Directory of Open Access Journals (Sweden)

    Friederike Herrig

    2018-05-01

    Full Text Available The sputter deposition of FeMn thin films with thicknesses in the range of hundred nanometres and beyond requires relatively high growth temperatures for the formation of the face-centred cubic (fcc phase, which results in high thin film roughness. A low temperature synthesis strategy, based on local epitaxial growth of a 100 nm thick fcc FeMn film as well as a Cu nucleation layer on an α-Al2O3 substrate at 160 °C, enables roughness values (Ra as low as ~0.6 nm, which is in the same order of magnitude as the pristine substrate (~0.1 nm. The synthesis strategy is guided by ab initio calculations, indicating very strong interfacial bonding of the Cu nucleation layer to an α-Al2O3 substrate (work of separation 5.48 J/m²—which can be understood based on the high Cu coordination at the interface—and between fcc FeMn and Cu (3.45 J/m². Accompanied by small lattice misfits between these structures, the strong interfacial bonding is proposed to enable the local epitaxial growth of a smooth fcc FeMn thin film. Based on the here introduced synthesis strategy, the implementation of fcc FeMn based thin film model systems for materials with interface dominated properties such as FeMn steels containing κ-carbide precipitates or secondary phases appears meaningful.

  18. A guide to the translation of the Global Initiative for Asthma (GINA) strategy into improved care

    DEFF Research Database (Denmark)

    Boulet, Louis-Philippe; FitzGerald, J Mark; Levy, Mark L

    2012-01-01

    In 1995, the Global Initiative for Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure that recommendations remain current. Although the report has been widely disseminated and influenced clinical...... practice and research, its major objective, of forming the basis for local and national initiatives to improve services for asthma patients, remains to be achieved. Over recent years, the science of guideline implementation has progressed, and encouraging examples of successful asthma programmes have been...... published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socioeconomic...

  19. Guided university debate: Effect of a new teaching-learning strategy for undergraduate nursing students.

    Science.gov (United States)

    Arrue, Marta; Unanue, Saloa; Merida, David

    2017-12-01

    A number of studies have shown that the traditional lecture suffers from limitations in the development of many important competencies such as reasoning ability for nursing professionals. In view of this issue, the authors present a promising alternative to the traditional lecture: the Guided University Debate (GUD). With regard to this aim a teaching-learning sequence of schizophrenia is described based on the GUD. Next, the improvement in the argumentative and declarative knowledge of the students who have participated in the said methodology is demonstrated. Quasi-experimental study with pre-test and post-test design to measure differences in the improvement of declarative and argumentative knowledge. To determine if there is a statistically significant difference in the score obtained in the pre-test and in the post-test score a parametric t-tests was carried. 64 students participated in the study. Implementation of the study took place during the 2015-2016 academic year in the third year of the Nursing undergraduate degree course in the University of the Basque Country (UPV/EHU) as part of the Mental Health class. The results showed a statistically-significant improvement in the students' scores for all learning outcomes analysed: Identifies symptoms of schizophrenia (p≤0.001), identifies the nursing interventions (p≤0.001), provides a rationale for nursing interventions (p≤0.001) and provides evidence of nursing interventions (p≤0.001). That is, the declarative and argumentative capacity of the group improved significantly with the Guided University Debate methodology. Although the teaching design feasibility and outcomes may vary in different contexts, based on this studies' positive outcome, the authors call today's educators to be able to use GUD as a teaching method. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Strategies for reducing ocean plastic debris should be diverse and guided by science

    Science.gov (United States)

    Rochman, Chelsea M.

    2016-04-01

    Studies suggest that trillions of microplastic particles are floating on the surface of the global oceans and that the total amount of plastic waste entering the ocean will increase by an order of magnitude by 2025. As such, this ever-increasing problem demands immediate mitigation and reduction. Diverse solutions have been proposed, ranging from source reduction to ocean-based cleanup. These solutions are most effective when guided by scientific evidence. A study published in Environmental Research Letters (Sherman and van Sebille 2016 Environ. Res. Lett. 11 014006) took a closer look at the potential effectiveness of ocean-based cleanup. They conclude that it will be most cost-effective and ecologically beneficial if clean-up efforts focus on the flux of microplastics from the coasts rather than in the center of the oceans where plastic accumulates in so called ‘garbage patches’. If followed, this example may become one of a series of examples where science has informed a solution to the complex problem of plastic pollution.

  1. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2013-01-01

    Full Text Available Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR, root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  2. Adjuvant chemotherapy for osteosarcoma.

    Science.gov (United States)

    Eilber, F R; Rosen, G

    1989-08-01

    present to minimally include high-dose methotrexate, Adriamycin, and cisplatin. It would also appear from several of these reports that not only is the adjuvant use of these chemotherapeutic agents indicated, but that the preoperative use of these agents has had significant advantages. The neoadjuvant chemotherapy begins the essential systemic chemotherapy at a very early stage, allows histologic assessment of treatment effect, permits altering drug regimens postoperative, and in many reported trials has allowed less than amputative surgery (limb salvage) to be performed. Finally, close follow-up of patients with osteosarcoma has therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)

  3. Adjuvant chemotherapy and cancer cure

    International Nuclear Information System (INIS)

    Bertino, J.R.

    1983-01-01

    The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

  4. Impact of a magnetic resonance imaging-guided treat-to-target strategy on disease activity and progression in patients with rheumatoid arthritis (the IMAGINE-RA trial)

    DEFF Research Database (Denmark)

    Møller-Bisgaard, Signe; Hørslev-Petersen, Kim; Ejbjerg, Bo Jannik

    2015-01-01

    /absence of BME may therefore be clinically beneficial. We present the design of a randomized controlled trial (RCT) aiming to evaluate whether an MRI-guided treatment strategy compared to a conventional treatment strategy in anti-CCP-positive erosive RA is better to prevent progression of erosive joint damage...... swollen joints and treatment with synthetic disease-modifying antirheumatic drugs (DMARDs) will be included. Patients will be randomized to either a treatment strategy based on conventional laboratory and clinical examinations (control group) or a treatment strategy based on conventional laboratory...

  5. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  6. Management of Cervical Cancer: Strategies for Limited-Resource Centres - A Guide for Radiation Oncologists

    International Nuclear Information System (INIS)

    2013-01-01

    Cervical cancer remains a significant cause of morbidity and mortality among women globally, even though it is the cancer with the greatest demonstrated potential for secondary prevention. In some regions of the world the incidence is alarmingly high, such as in sub-Saharan Africa, some countries in Latin America, India and South-East Asia. This disease is highly preventable and curable at a relatively low risk and low cost when screening of asymptomatic women is available, together with appropriate diagnosis, treatment and follow-up. In developing clinical guidelines, the International Atomic Energy Agency (IAEA) has selected forms of cancer or clinical situations that are very common in low and middle income Member States and for which radiation oncologists consistently express a need for guidance. Clinical guidelines for the management of cervical cancer do exist in the published literature. However, these guidelines have usually been developed in and for affluent environments where all modern diagnosis and treatment modalities are available for the practitioner. In limited resource environments, the radiation oncologist is faced with the question, what would be the minimally acceptable line of action with the limited resources available? Clinical guidelines focusing on low and middle income countries provide a practical tool to these practitioners. This publication is aimed at the radiation oncologist working in centres with limited resources and treating a large number of patients with cervical cancer on a daily basis. The approach and techniques are intended to be simple, feasible and resource sparing to the extent that this is possible when dealing with a complex treatment modality. The Division of Human Health is placing special emphasis on the subject of cervical cancer, which is addressed not only in this guide but also in regional training courses and coordinated research projects on the subject

  7. Repository Integration Program: RIP performance assessment and strategy evaluation model theory manual and user's guide

    International Nuclear Information System (INIS)

    1995-11-01

    This report describes the theory and capabilities of RIP (Repository Integration Program). RIP is a powerful and flexible computational tool for carrying out probabilistic integrated total system performance assessments for geologic repositories. The primary purpose of RIP is to provide a management tool for guiding system design and site characterization. In addition, the performance assessment model (and the process of eliciting model input) can act as a mechanism for integrating the large amount of available information into a meaningful whole (in a sense, allowing one to keep the ''big picture'' and the ultimate aims of the project clearly in focus). Such an integration is useful both for project managers and project scientists. RIP is based on a '' top down'' approach to performance assessment that concentrates on the integration of the entire system, and utilizes relatively high-level descriptive models and parameters. The key point in the application of such a ''top down'' approach is that the simplified models and associated high-level parameters must incorporate an accurate representation of their uncertainty. RIP is designed in a very flexible manner such that details can be readily added to various components of the model without modifying the computer code. Uncertainty is also handled in a very flexible manner, and both parameter and model (process) uncertainty can be explicitly considered. Uncertainty is propagated through the integrated PA model using an enhanced Monte Carlo method. RIP must rely heavily on subjective assessment (expert opinion) for much of its input. The process of eliciting the high-level input parameters required for RIP is critical to its successful application. As a result, in order for any project to successfully apply a tool such as RIP, an enormous amount of communication and cooperation must exist between the data collectors, the process modelers, and the performance. assessment modelers

  8. [Leadership strategies--the Bible as a guide to management in the health care system].

    Science.gov (United States)

    Kudlacek, Stefan; Meran, Johannes G

    2006-06-01

    Management and leadership are an integral part of any organisation, to optimise procedures and increase efficiency. Aims, ideals and structures first need to be defined for tasks to be carried out successfully, particularly in difficult times. A good example for the way communities can effectively and with conviction pass on their values and standpoints from generation to generation, grow in strength and also influence their surroundings is provided by religion. This paper focuses leadership provided by charismatic personalities within the Jewish and Christian religions. Monasteries have run hospitals without governmental support ever since the Middle Ages. Leadership within today's health care system calls for a variety of strategies in the different phases of development. In times of limited resources and multifarious societies, leadership implies both a scientific as well as an ethical challenge.

  9. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

    Science.gov (United States)

    Carson, Jeffrey L; Carless, Paul A; Hebert, Paul C

    2012-04-18

    Most clinical practice guidelines recommend restrictive red cell transfusion practices, with the goal of minimising exposure to allogeneic blood. The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). To examine the evidence for the effect of transfusion thresholds on the use of allogeneic and/or autologous red cell transfusion, and the evidence for any effect on clinical outcomes. We identified trials by searching; The Cochrane Injuries Group Specialised Register (searched 01 Feb 2011), Cochrane Central Register of Controlled Trials 2011, issue 1 (The Cochrane Library), MEDLINE (Ovid) 1948 to January Week 3 2011, EMBASE (Ovid) 1980 to 2011 (Week 04), ISI Web of Science: Science Citation Index Expanded (1970 to Feb 2011), ISI Web of Science: Conference Proceedings Citation Index- Science (1990 to Feb 2011). We checked reference lists of other published reviews and relevant papers to identify any additional trials. Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered. Risk ratios of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials, using a random effects model. Data extraction and assessment of the risk of bias was performed by two people. Nineteen trials involving a total of 6264 patients were identified, and were similar enough that the results could be combined. Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 39% (RR 0.61, 95% CI 0.52 to 0.72). This equates to an average absolute risk reduction (ARR) of 34% (95% CI 24% to 45%). The volume of RBCs transfused was reduced on average by 1

  10. Development of a pharmacokinetic‐guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia

    Science.gov (United States)

    Dong, Min; McGann, Patrick T.; Mizuno, Tomoyuki; Ware, Russell E.

    2016-01-01

    AIMS Hydroxyurea has emerged as the primary disease‐modifying therapy for patients with sickle cell anaemia (SCA). The laboratory and clinical benefits of hydroxyurea are optimal at maximum tolerated dose (MTD), but the current empirical dose escalation process often takes up to 12 months. The purpose of this study was to develop a pharmacokinetic‐guided dosing strategy to reduce the time required to reach hydroxyurea MTD in children with SCA. Methods Pharmacokinetic (PK) data from the HUSTLE trial (NCT00305175) were used to develop a population PK model using non‐linear mixed effects modelling (nonmem 7.2). A D‐optimal sampling strategy was developed to estimate individual PK and hydroxyurea exposure (area under the concentration–time curve (AUC)). The initial AUC target was derived from HUSTLE clinical data and defined as the mean AUC at MTD. Results PK profiles were best described by a one compartment with Michaelis–Menten elimination and a transit absorption model. Body weight and cystatin C were identified as significant predictors of hydroxyurea clearance. The following clinically feasible sampling times are included in a new prospective protocol: pre‐dose (baseline), 15–20 min, 50–60 min and 3 h after an initial 20 mg kg–1 oral dose. The mean target AUC(0,∞) for initial dose titration was 115 mg l–1 h. Conclusion We developed a PK model‐based individualized dosing strategy for the prospective Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154). This approach has the potential to optimize the dose titration of hydroxyurea therapy for children with SCA, such that the clinical benefits at MTD are achieved more quickly. PMID:26615061

  11. Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia.

    Science.gov (United States)

    Dong, Min; McGann, Patrick T; Mizuno, Tomoyuki; Ware, Russell E; Vinks, Alexander A

    2016-04-01

    Hydroxyurea has emerged as the primary disease-modifying therapy for patients with sickle cell anaemia (SCA). The laboratory and clinical benefits of hydroxyurea are optimal at maximum tolerated dose (MTD), but the current empirical dose escalation process often takes up to 12 months. The purpose of this study was to develop a pharmacokinetic-guided dosing strategy to reduce the time required to reach hydroxyurea MTD in children with SCA. Pharmacokinetic (PK) data from the HUSTLE trial (NCT00305175) were used to develop a population PK model using non-linear mixed effects modelling (nonmem 7.2). A D-optimal sampling strategy was developed to estimate individual PK and hydroxyurea exposure (area under the concentration-time curve (AUC)). The initial AUC target was derived from HUSTLE clinical data and defined as the mean AUC at MTD. PK profiles were best described by a one compartment with Michaelis-Menten elimination and a transit absorption model. Body weight and cystatin C were identified as significant predictors of hydroxyurea clearance. The following clinically feasible sampling times are included in a new prospective protocol: pre-dose (baseline), 15-20 min, 50-60 min and 3 h after an initial 20 mg kg(-1) oral dose. The mean target AUC(0,∞) for initial dose titration was 115 mg l(-1)  h. We developed a PK model-based individualized dosing strategy for the prospective Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154). This approach has the potential to optimize the dose titration of hydroxyurea therapy for children with SCA, such that the clinical benefits at MTD are achieved more quickly. © 2015 The British Pharmacological Society.

  12. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    International Nuclear Information System (INIS)

    Shusharina, N; Khan, F; Choi, N; Sharp, G

    2014-01-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart

  13. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    Energy Technology Data Exchange (ETDEWEB)

    Shusharina, N; Khan, F; Choi, N; Sharp, G [Massachusetts General Hospital, Boston, MA (United States)

    2014-06-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

  14. Demographic drivers of a refugee species: Large‐scale experiments guide strategies for reintroductions of hirola

    Science.gov (United States)

    Ali, Abdullahi H.; Kauffman, Matthew J.; Amin, Rajan; Kibara, Amos; King, Juliet; Mallon, David P.; Musyoki, Charles; Goheen, Jacob R.

    2018-01-01

    Effective reintroduction strategies require accurate estimates of vital rates and the factors that influence them. The hirola (Beatragus hunteri) is the rarest antelope on Earth, with a global population size of <500 individuals restricted to the Kenya–Somali border. We estimated vital rates of hirola populations exposed to varying levels of predation and rangeland quality from 2012 to 2015, and then built population matrices to estimate the finite rate of population change (λ) and demographic sensitivities. Mean survival for all age classes and population growth was highest in the low‐predation–high‐rangeland‐quality setting (λ = 1.08 ± 0.03 [mean ± SE]), and lowest in the high‐predation–low‐rangeland‐quality setting (λ = 0.70 ± 0.22). Retrospective demographic analyses revealed that increased fecundity (the number of female calves born to adult females annually) and female calf survival were responsible for higher population growth where large carnivores were absent. In contrast, variation in adult female survival was the primary contributor to differences in population growth attributable to rangeland quality. Our analyses suggest that hirola demography is driven by a combination of top‐down (predation) and bottom‐up (rangeland quality) forces, with populations in the contemporary geographic range impacted both by declining rangeland quality and predation. To enhance the chances of successful reintroductions, conservationists can consider rangeland restoration to boost both the survival and fecundity of adult females within the hirola's historical range.

  15. Physical exercise during adjuvant chemotherapy

    NARCIS (Netherlands)

    van Waart, H.

    2017-01-01

    This thesis evaluates the effect of physical exercise during chemotherapy. In chapter two the study design, rationale and methods of the Physical exercise during Adjuvant Chemotherapy Study (PACES) are described. Chapter three presents the effects of the randomized controlled trial evaluating a

  16. Pricing Strategy. Unit 10. Level 2. Instructor Guide. PACE: Program for Acquiring Competence in Entrepreneurship. Third Edition. Research & Development Series No. 302-10.

    Science.gov (United States)

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This instructor guide for a unit on pricing strategy in the PACE (Program for Acquiring Competence in Entrepreneurship) curriculum includes the full text of the student module and lesson plans, instructional suggestions, and other teacher resources. The competencies that are incorporated into this module are at Level 2 of learning--planning for a…

  17. Pricing Strategy. Unit 10. Level 3. Instructor Guide. PACE: Program for Acquiring Competence in Entrepreneurship. Third Edition. Research & Development Series No. 303-10.

    Science.gov (United States)

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This instructor guide for a unit on pricing strategy in the PACE (Program for Acquiring Competence in Entrepreneurship) curriculum includes the full text of the student module and lesson plans, instructional suggestions, and other teacher resources. The competencies that are incorporated into this module are at Level 3 of learning--starting and…

  18. Pricing Strategy. Unit 10. Level 1. Instructor Guide. PACE: Program for Acquiring Competence in Entrepreneurship. Third Edition. Research & Development Series No. 301-10.

    Science.gov (United States)

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This instructor guide for a unit on pricing strategy in the PACE (Program for Acquiring Competence in Entrepreneurship) curriculum includes the full text of the student module and lesson plans, instructional suggestions, and other teacher resources. The competencies that are incorporated into this module are at Level 1 of learning--understanding…

  19. Treatment outcomes of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis in daily clinical practice.

    NARCIS (Netherlands)

    Snijders, G.F.; Ende, C.H.M. van den; Bemt, B.J.F van den; Riel, P.L.C.M. van; Hoogen, F.H.J. van den; Broeder, A. den

    2012-01-01

    OBJECTIVES: To describe the results of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis (OA) in daily clinical practice. METHODS: In this observational cohort study, standardised conservative treatment was offered to patients

  20. Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Wang Q

    2015-07-01

    Full Text Available Qingbing Wang,1,2 Jianfeng Li,3 Sai An,3 Yi Chen,1 Chen Jiang,3 Xiaolin Wang1,2 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, 2Shanghai Institute of Medical Imaging, 3Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China Background: Gene therapy is a very promising technology for treatment of pancreatic ductal adenocarcinoma (PDAC. However, its application has been limited by the abundant stromal response in the tumor microenvironment. The aim of this study was to prepare a dendrimer-based gene-free loading vector with high permeability in the tumor stroma and explore an imaging-guided local gene delivery strategy for PDAC to promote the efficiency of targeted gene delivery.Methods: The experimental protocol was approved by the animal ethics committee of Zhongshan Hospital, Fudan University. Third-generation dendrigraft poly-L-lysines was selected as the nanocarrier scaffold, which was modified by cell-penetrating peptides and gadolinium (Gd chelates. DNA plasmids were loaded with these nanocarriers via electrostatic interaction. The cellular uptake and loaded gene expression were examined in MIA PaCa-2 cell lines in vitro. Permeability of the nanoparticles in the tumor stroma and transfected gene distribution in vivo were studied using a magnetic resonance imaging-guided delivery strategy in an orthotopic nude mouse model of PDAC.Results: The nanocarriers were synthesized with a dendrigraft poly-L-lysine to polyethylene glycol to DTPA ratio of 1:3.4:8.3 and a mean diameter of 110.9±7.7 nm. The luciferases were strictly expressed in the tumor, and the luminescence intensity in mice treated by Gd-DPT/plasmid luciferase (1.04×104±9.75×102 p/s/cm2/sr was significantly (P<0.05 higher than in those treated with Gd-DTPA (9.56×102±6.15×10 p/s/cm2/sr and Gd-DP (5.75×103± 7.45×102 p/s/cm2/sr

  1. Genomic diversity guides conservation strategies among rare terrestrial orchid species when taxonomy remains uncertain.

    Science.gov (United States)

    Ahrens, Collin W; Supple, Megan A; Aitken, Nicola C; Cantrill, David J; Borevitz, Justin O; James, Elizabeth A

    2017-06-01

    Species are often used as the unit for conservation, but may not be suitable for species complexes where taxa are difficult to distinguish. Under such circumstances, it may be more appropriate to consider species groups or populations as evolutionarily significant units (ESUs). A population genomic approach was employed to investigate the diversity within and among closely related species to create a more robust, lineage-specific conservation strategy for a nationally endangered terrestrial orchid and its relatives from south-eastern Australia. Four putative species were sampled from a total of 16 populations in the Victorian Volcanic Plain (VVP) bioregion and one population of a sub-alpine outgroup in south-eastern Australia. Morphological measurements were taken in situ along with leaf material for genotyping by sequencing (GBS) and microsatellite analyses. Species could not be differentiated using morphological measurements. Microsatellite and GBS markers confirmed the outgroup as distinct, but only GBS markers provided resolution of population genetic structure. The nationally endangered Diuris basaltica was indistinguishable from two related species ( D. chryseopsis and D. behrii ), while the state-protected D. gregaria showed genomic differentiation. Genomic diversity identified among the four Diuris species suggests that conservation of this taxonomically complex group will be best served by considering them as one ESU rather than separately aligned with species as currently recognized. This approach will maximize evolutionary potential among all species during increased isolation and environmental change. The methods used here can be applied generally to conserve evolutionary processes for groups where taxonomic uncertainty hinders the use of species as conservation units. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  2. Integrated Testing Strategy (ITS) - Opportunities to better use existing data and guide future testing in toxicology.

    Science.gov (United States)

    Jaworska, Joanna; Hoffmann, Sebastian

    2010-01-01

    The topic of Integrated Testing Strategies (ITS) has attracted considerable attention, and not only because it is supposed to be a central element of REACH, the ambitious European chemical regulation effort. Although what ITSs are supposed to do seems unambiguous, i.e. speeding up hazard and risk assessment while reducing testing costs, not much has been said, except basic conceptual proposals, about the methodologies that would allow execution of these concepts. Although a pressing concern, the topic of ITS has drawn mostly general reviews, broad concepts, and the expression of a clear need for more research on ITS. Published research in the field remains scarce. Solutions for ITS design emerge slowly, most likely due to the methodological challenges of the task, and perhaps also to it its complexity and the need for multidisciplinary collaboration. Along with the challenge, ITS offer a unique opportunity to contribute to the Toxicology of the 21st century by providing frameworks and tools to actually implement 21st century toxicology data in the chemical management and decision making processes. Further, ITS have the potential to significantly contribute to a modernization of the science of risk assessment. Therefore, to advance ITS research we propose a methodical approach to their design and will discuss currently available approaches as well as challenges to overcome. To this end, we define a framework for ITS that will inform toxicological decisions in a systematic, transparent, and consistent way. We review conceptual requirements for ITS developed earlier and present a roadmap to an operational framework that should be probabilistic, hypothesis-driven, and adaptive. Furthermore, we define properties an ITS should have in order to meet the identified requirements and differentiate them from evidence synthesis. Making use of an ITS for skin sensitization, we demonstrate how the proposed ITS concepts can be implemented.

  3. Guiding Design of University STEM Courses Based on Gifted Status and Strategies for Success

    Science.gov (United States)

    Hawthorne Allen, A. M.

    2016-12-01

    attained. For example, modern STEM teaching utilizes pedagogical interventions that typically involve active learning. The success of such interventions will interact with the gifted profile of students in a given class. In this presentation, I describe strategies, frameworks, and concrete examples that work for such students.

  4. Use of an Innovative Personality-Mindset Profiling Tool to Guide Culture-Change Strategies among Different Healthcare Worker Groups.

    Science.gov (United States)

    Grayson, M Lindsay; Macesic, Nenad; Huang, G Khai; Bond, Katherine; Fletcher, Jason; Gilbert, Gwendolyn L; Gordon, David L; Hellsten, Jane F; Iredell, Jonathan; Keighley, Caitlin; Stuart, Rhonda L; Xuereb, Charles S; Cruickshank, Marilyn

    2015-01-01

    Important culture-change initiatives (e.g. improving hand hygiene compliance) are frequently associated with variable uptake among different healthcare worker (HCW) categories. Inherent personality differences between these groups may explain change uptake and help improve future intervention design. We used an innovative personality-profiling tool (ColourGrid®) to assess personality differences among standard HCW categories at five large Australian hospitals using two data sources (HCW participant surveys [PS] and generic institution-wide human resource [HR] data) to: a) compare the relative accuracy of these two sources; b) identify differences between HCW groups and c) use the observed profiles to guide design strategies to improve uptake of three clinically-important initiatives (improved hand hygiene, antimicrobial stewardship and isolation procedure adherence). Results from 34,243 HCWs (HR data) and 1045 survey participants (PS data) suggest that HCWs were different from the general population, displaying more individualism, lower power distance, less uncertainty avoidance and greater cynicism about advertising messages. HR and PS data were highly concordant in identifying differences between the three key HCW categories (doctors, nursing/allied-health, support services) and predicting appropriate implementation strategies. Among doctors, the data suggest that key messaging should differ between full-time vs part-time (visiting) senior medical officers (SMO, VMO) and junior hospital medical officers (HMO), with SMO messaging focused on evidence-based compliance, VMO initiatives emphasising structured mandatory controls and prestige loss for non-adherence, and for HMOs focusing on leadership opportunity and future career risk for non-adherence. Compared to current standardised approaches, targeted interventions based on personality differences between HCW categories should result in improved infection control-related culture-change uptake. Personality

  5. Use of an Innovative Personality-Mindset Profiling Tool to Guide Culture-Change Strategies among Different Healthcare Worker Groups.

    Directory of Open Access Journals (Sweden)

    M Lindsay Grayson

    Full Text Available Important culture-change initiatives (e.g. improving hand hygiene compliance are frequently associated with variable uptake among different healthcare worker (HCW categories. Inherent personality differences between these groups may explain change uptake and help improve future intervention design.We used an innovative personality-profiling tool (ColourGrid® to assess personality differences among standard HCW categories at five large Australian hospitals using two data sources (HCW participant surveys [PS] and generic institution-wide human resource [HR] data to: a compare the relative accuracy of these two sources; b identify differences between HCW groups and c use the observed profiles to guide design strategies to improve uptake of three clinically-important initiatives (improved hand hygiene, antimicrobial stewardship and isolation procedure adherence.Results from 34,243 HCWs (HR data and 1045 survey participants (PS data suggest that HCWs were different from the general population, displaying more individualism, lower power distance, less uncertainty avoidance and greater cynicism about advertising messages. HR and PS data were highly concordant in identifying differences between the three key HCW categories (doctors, nursing/allied-health, support services and predicting appropriate implementation strategies. Among doctors, the data suggest that key messaging should differ between full-time vs part-time (visiting senior medical officers (SMO, VMO and junior hospital medical officers (HMO, with SMO messaging focused on evidence-based compliance, VMO initiatives emphasising structured mandatory controls and prestige loss for non-adherence, and for HMOs focusing on leadership opportunity and future career risk for non-adherence.Compared to current standardised approaches, targeted interventions based on personality differences between HCW categories should result in improved infection control-related culture-change uptake. Personality

  6. A tool for validating MRI-guided strategies: a digital breathing CT/MRI phantom of the abdominal site.

    Science.gov (United States)

    Paganelli, Chiara; Summers, Paul; Gianoli, Chiara; Bellomi, Massimo; Baroni, Guido; Riboldi, Marco

    2017-11-01

    Dynamic magnetic resonance imaging (MRI) is emerging as the elected image modality for organ motion quantification and management in image-guided radiotherapy. However, the lack of validation tools is an open issue for image guidance in the abdominal and thoracic organs affected by organ motion due to respiration. We therefore present an abdominal four-dimensional (4D) CT/MRI digital phantom, including the estimation of MR tissue parameters, simulation of dedicated abdominal MR sequences, modeling of radiofrequency coil response and noise, followed by k-space sampling and image reconstruction. The phantom allows the realistic simulation of images generated by MR pulse sequences with control of scan and tissue parameters, combined with co-registered CT images. In order to demonstrate the potential of the phantom in a clinical scenario, we describe the validation of a virtual T1-weighted 4D MRI strategy. Specifically, the motion extracted from a T2-weighted 4D MRI is used to warp a T1-weighted breath-hold acquisition, with the aim of overcoming trade-offs that limit T1-weighted acquisitions. Such an application shows the applicability of the digital CT/MRI phantom as a validation tool, which should be especially useful for cases unsuited to obtain real imaging data.

  7. Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy.

    Science.gov (United States)

    Empey, Philip E; Stevenson, James M; Tuteja, Sony; Weitzel, Kristin W; Angiolillo, Dominick J; Beitelshees, Amber L; Coons, James C; Duarte, Julio D; Franchi, Francesco; Jeng, Linda J B; Johnson, Julie A; Kreutz, Rolf P; Limdi, Nita A; Maloney, Kristin A; Owusu Obeng, Aniwaa; Peterson, Josh F; Petry, Natasha; Pratt, Victoria M; Rollini, Fabiana; Scott, Stuart A; Skaar, Todd C; Vesely, Mark R; Stouffer, George A; Wilke, Russell A; Cavallari, Larisa H; Lee, Craig R

    2017-12-26

    CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions. © 2018, The American Society for Clinical Pharmacology and Therapeutics.

  8. A comparison of individualized treatment guided by VeriStrat with standard of care treatment strategies in patients receiving second-line treatment for advanced non-small cell lung cancer: A cost-utility analysis.

    Science.gov (United States)

    Nelson, Richard E; Stenehjem, David; Akerley, Wallace

    2013-12-01

    Two therapies are appropriate as 2nd-line treatment of non-small cell lung cancer (NSCLC) patients: chemotherapy and epidermal growth factor receptor (EGFR) inhibitor therapy. VeriStrat, a serum proteomic test, can be used to guide treatment decisions for NSCLC patients. The test classifies patients as likely to benefit from either of these two treatment options. The objective of this research was to model the anticipated survival and cost-effectiveness of four different treatment strategies: chemotherapy for all patients (C-all), EGFR inhibitor for all (E-all), a performance status guided selection strategy (PS-guided), and a strategy guided by VeriStrat test results (V-guided). We developed a Markov model with the perspective of the U.S. health care system. Model inputs were taken from published literature for the base-case analysis. One-way and probabilistic sensitivity analyses were performed. The C-all treatment strategy showed the best overall survival outcome (10.1 months), followed by V-guided (9.6 months), PS-guided (9.2 months), and E-all (8.2 months) strategies. The incremental cost-effectiveness ratio (ICER) of a V-guided treatment strategy was $91,111 (vs. E-all) and $8462 (vs. PS-guided) per quality-adjusted life year (QALY). The ICER for C-all compared to V-guided was $105,616. This cost-utility analysis indicates that a treatment strategy guided by the VeriStrat test in patients receiving second-line therapy for NSCLC may experience an overall survival benefit at an incremental cost-effectiveness ratio that is reasonable when compared with other practices, including cancer treatments, generally covered in the U.S. health care system. However, treating all patients with chemotherapy yielded the greatest expected survival. Copyright © 2013. Published by Elsevier Ireland Ltd.

  9. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

    Directory of Open Access Journals (Sweden)

    Karen A.O. Martins

    2016-01-01

    Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

  10. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

    Science.gov (United States)

    Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

    2016-01-01

    Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

  11. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  12. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    Science.gov (United States)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

  13. Optimization of Adjuvant Radiation in Breast Conservation Therapy: Can We Minimize without Compromise?

    International Nuclear Information System (INIS)

    Edwards-Bennett, S.M.; Correa, C.R.; Harris, E.E.

    2011-01-01

    Adjuvant breast radiation therapy after breast conservation surgery is recommended as it yields significant reduction in the risk of local recurrence, and confers a potential overall survival benefit. Although the standard breast radiation regimen has historically been delivered over 57 weeks; more novel, shorter courses of breast radiation are currently being employed, offering the advantage of more convenience and less time-commitment. Herein, we review the recent literature substantiating these abbreviated radiation treatment approaches and the methods of delivery thereof. In addition, we discuss imaged guided techniques currently being utilized to further refine the delivery of adjuvant breast radiation therapy

  14. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

    2016-01-01

    Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

  15. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably

  16. Adjuvants and Their Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Masoumeh Foumani

    2012-09-01

    Full Text Available Adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in experimental and commercial vaccines include aluminum salts (alum, oil emulsions, saponins, immune-stimulating complexes (ISCOMs, liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds are different. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed. In this paper we review the current adjuvant types, structure and mechanism of action and their application in the design and production of animal and human vaccines to provide a source for students and researchers in related fields .

  17. SEE Action Guide for States: Energy Efficiency as a Least-Cost Strategy to Reduce Greenhouse Gases and Air Pollution and Meet Energy Needs in the Power Sector

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Lisa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Leventis, Greg [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schiller, Steven R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fadrhonc, Emily Martin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); shenot, John [US Department of Energy, Washington, DC (United States); Colburn, Ken [US Department of Energy, Washington, DC (United States); James, Chris [US Department of Energy, Washington, DC (United States); Zetterberg, Johanna [US Department of Energy, Washington, DC (United States); Roy, Molly [US Department of Energy, Washington, DC (United States)

    2016-02-01

    This guide is designed to provide information to state decision makers and staff on options to advance energy efficiency through strategies designed or implemented at the state and local levels of government and in the private sector.1 The information in this guide is intended to be useful to a wide variety of partners and stakeholders involved in energy-related discussions and decision-making at state and local levels. These energy efficiency options, or “pathways” as they are identified in this guide, can assist states in using energy efficiency to meet air pollution reduction and other policy objectives such as energy affordability and reliability. A pathway is a set of interdependent actions that results in measurable energy savings streams and associated avoided air emissions and other benefits over a period of time. These activities can include state, local, or private sector regulations, policies, programs and other activities. For each of five broad pathways that offer sizable cost-effective energy savings, the guide addresses likely questions policy makers and regulators face when screening for the best opportunities to advance energy efficiency in their state.

  18. Characterization of the antigen-specific CD4+ T cell response induced by prime-boost strategies with CAF01 and CpG adjuvants administered by the intranasal and subcutaneous routes

    Directory of Open Access Journals (Sweden)

    Annalisa eCiabattini

    2015-08-01

    Full Text Available The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1821 adjuvants, administered by the parenteral and nasal routes. By using peptide-MHC class II tetramers, antigen-specific CD4+ T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4+ tetramer-positive T cells in the spleen, however only parenterally primed cells responded to booster immunization. Subcutaneous priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4+ tetramer-positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4+ T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that subcutaneous priming is fundamental for eliciting CD4+ T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses.

  19. Adjuvant therapy for gastric cancer: what have we learned since INT0116?

    Science.gov (United States)

    Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

    2015-04-07

    Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

  20. Adjuvants are key factors for the development of future vaccines: Lessons from the Finlay Adjuvant platform

    Directory of Open Access Journals (Sweden)

    Oliver ePérez

    2013-12-01

    Full Text Available The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs, AFPL (proteoliposome and AFCo (cochleate, were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.

  1. Effect of Roy's Adaptation Model-Guided Education on Coping Strategies of the Veterans with Lower Extremities Amputation: A Double-Blind Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Farsi, Zahra; Azarmi, Somayeh

    2016-04-01

    Any defect in the extremities of the body can affect different life aspects. The purpose of this study was to investigate the effect of Roy's adaptation model-guided education on coping strategies of the veterans with lower extremities amputation. In a double-blind randomized controlled clinical trial, 60 veterans with lower extremities amputation referring to Kowsar Orthotics and Prosthetics Center of Veterans Clinic in Tehran, Iran were recruited using convenience method and randomly assigned to intervention and control groups in 2013-2014. Lazarus and Folkman coping strategies questionnaire was used to collect the data. After completing the questionnaires in both groups, maladaptive behaviours were determined in the intervention group and an education program based on Roy's adaptation model was implemented. After 2 months, both groups completed the questionnaires again. Data were analyzed using SPSS software. Independent T-test showed that the score of the dimensions of coping strategies did not have a statistically significant difference between the intervention and control groups in the pre-intervention stage (P>0.05). This test showed a statistically significant difference between the two groups in the post-intervention stage in terms of the scores of different dimensions of coping strategies (P>0.05), except in dimensions of social support seeking and positive appraisal (P>0.05). The findings of this research indicated that the Roy's adaptation model-guided education improved the majority of coping strategies in veterans with lower extremities amputation. It is recommended that further interventions based on Roy's adaptation model should be performed to improve the coping of the veterans with lower extremities amputation. IRCT2014081118763N1.

  2. Mathematical Challenges to Secondary School Students in a Guided Reinvention Teaching-Learning Strategy towards the Concept of Energy Conservation

    NARCIS (Netherlands)

    Logman, P.S.W.M.; Kaper, W.H.; Ellermeijer, A.L.; Taşar, M.F.

    2014-01-01

    Guiding sixteen-year-old students to rediscover the concept of energy conservation may be done in three distinct learning steps. First, we have chosen for the students to reinvent what we call partial laws of energy conservation (e.g. Σm∙g∙h = k1). Secondly, the students are asked to combine these

  3. The Maritime Strategy Debates: A Guide to the Renaissance of U.S. Naval Strategic Thinking in the 1980s.

    Science.gov (United States)

    1988-02-24

    strategy, as well as strike warfare and tactical innovations). ** Gray, Colin , "Maritime Strategy", Proceedings, February 1986, pp 34-42. (Supportive...driven document). ** Gray, Colin S., "Keeping the Soviets Landlocked: Geostrategy for a Maritime America", The National Interest, Summer 1986, pp 24-36...latter on the role of U.S. and allied submarines in the Maritime Strategy: "We dare not go it alone"). ** Drury , F., "Naval Strike Warfare and the

  4. Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) is an effective and safe strategy for the management of non-lifting large laterally spreading colonic lesions.

    Science.gov (United States)

    Tate, David J; Bahin, Farzan F; Desomer, Lobke; Sidhu, Mayenaaz; Gupta, Vikas; Bourke, Michael J

    2018-01-01

     Non-lifting large laterally spreading colorectal lesions (LSLs) are challenging to resect endoscopically and often necessitate surgery. A safe, simple technique to treat non-lifting LSLs endoscopically with robust long-term outcomes has not been described.  In this single-center prospective observational study of consecutive patients referred for endoscopic mucosal resection (EMR) of LSLs ≥ 20 mm, LSLs not completely resectable by snare because of non-lifting underwent standardized completion of resection with cold-forceps avulsion and adjuvant snare-tip soft coagulation (CAST). Scheduled surveillance colonoscopies were performed at 4 - 6 months (SC1) and 18 months (SC2). Primary outcomes were endoscopic evidence of adenoma clearance and avoidance of surgery. The secondary outcome was safety.  From January 2012 to October 2016, 540 lifting LSLs (82.2 %) underwent complete snare excision at EMR. CAST was required for complete removal in 101 non-lifting LSLs (17.8 %): 63 naïve non-lifting lesions (NNLs; 62.7 %) and 38 previously attempted non-lifting lesions (PANLs; 37.3 %). PANLs were smaller ( P  < 0.001) and more likely to be non-granular ( P  = 0.001) than the lifting LSLs. NNLs were of similar size ( P  = 0.77) and morphology ( P  = 0.10) to the lifting LSLs. CAST was successful in all cases and adverse events were comparable to lifting LSLs resected by complete snare excision. Recurrence at SC1 was comparable for PANLs (15.2 %) and lifting LSLs (15.3 %; P  = 0.99), whereas NNLs recurred more frequently (27.5 %; P  = 0.049); however, surgery was no more common for either type of non-lifting LSL than for lifting LSLs.  CAST is a safe, effective, and surgery-sparing therapy for the majority of non-lifting LSLs. It is easy to use, inexpensive, and does not require additional equipment. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Does lipophilicity per se induce adjuvant effects?

    DEFF Research Database (Denmark)

    Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.

    2007-01-01

    Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is...

  6. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity

    Science.gov (United States)

    Cooper, P. D.; Barclay, T. G.; Ginic-Markovic, M.; Petrovsky, N.

    2014-01-01

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of 60Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25 kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants. PMID:24342245

  7. Impact of Guided Reflection with Peers on the Development of Effective Problem Solving Strategies and Physics Learning

    Science.gov (United States)

    Mason, Andrew J.; Singh, Chandralekha

    2016-01-01

    Students must learn effective problem solving strategies in order to develop expertise in physics. Effective problem solving strategies include a conceptual analysis of the problem followed by planning of the solution, and then implementation, evaluation, and reflection upon the process. Research suggests that converting a problem from the initial…

  8. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

    Science.gov (United States)

    Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

    2018-05-22

    Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

  9. Enterprise iPhone and iPad Administrator's Guide Strategies for iPhone Deployment, Integration, and Control

    CERN Document Server

    Edge, Charles

    2010-01-01

    Are you an IT professional involved in deploying the iPhone and or iPad in your company or organization? Do you have fellow employees who are eager to use their iPhones and iPads for work? Then this is the book for you. Enterprise iPhone and iPad Administrator's Guide provides step-by-step instructions on how to deploy and integrate the iPhone within a range of professional environments - from large businesses and educational institutions to medium-sized offices. This book ensures that the process is achieved in a streamlined, efficient, and cost-effective manner. The guide begins with an intr

  10. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  11. Surgical strategy for malignant gliomas involving pyramidal tracts guided by functional neuronavigation and 5-ALA fluorescence navigation

    International Nuclear Information System (INIS)

    Sato, Ken-ichi; Ito, Tamio; Seo, Yoshinobu; Sunohara, Tadashi; Maeda, Masana; Sasaki, Takehiko; Nakagawara, Jyoji; Nakamura, Hirohiko

    2009-01-01

    For patients with malignant glioma invading pyramidal tracts, maximal resections are difficult to accomplish while preserving their motor function. We used tractography-integrated functional neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence-guided resection for removal of malignant gliomas involving pyramidal tract. In this study, we analyzed postoperative motor function and extent of resection in a series of patients who underwent surgery in our department. Ten patients with malignant glioma invading pyramidal tracts underwent radical surgery. To preserve pyramidal tracts, we developed a functional neuronavigation-guided fence-post procedure to avoid the problem of brain shift, a disadvantage of the existing neuronavigation systems. Furthermore we have achieved precise resection of tumors using 5-ALA fluorescence navigation. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. All fluorescing tumor tissue was resected. Motor function was preserved after appropriate tumor resection in all cases. Postoperatively, improvement of motor weakness was observed in seven patients, whereas transient mild motor weakness occurred in two patients. Gross total removals were accomplished in seven patients, and subtotal removal was accomplished in one patient, and partial removal was accomplished in two patients. Combined use of tractography-integrated functional neuronavigation and 5-ALA fluorescence-guided resection contributes to maximal safe resection of malignant gliomas with pyramidal tract involvement. (author)

  12. Extended Adjuvant Therapy for Breast Cancer

    Science.gov (United States)

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  13. Proteoliposome derived cochleate as novel adjuvant.

    Science.gov (United States)

    Bracho, Gustavo; Lastre, Miriam; del Campo, Judith; Zayas, Caridad; González, Domingo; Gil, Danay; Acevedo, Reinaldo; Taboada, Carlos; Solís, Rosa L; Pérez, Oliver

    2006-04-12

    Cochleate structures (CS) consist in a highly stable lipid structures that have been reported to be a good antigen delivery system. The incorporation of pathogen associated molecular pattern (PAMP) from bacterial membranes into CS became in a promising approach to develop adjuvants, particularly mucosal adjuvants. Therefore, we prepare CS from proteoliposome (PL) obtained from Neisseria meningitidis B (PLCS) and evaluated it for its capability to stimulate the immune system as well as the adjuvant activity. The ability of PLCS to induce Thl polarization was also explored. The results and the easy capability for new antigen incorporation on CS support its use as adjuvant for immunization with a large variety of pathogen derived antigens and different routes of immunization.

  14. Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

    Science.gov (United States)

    Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

    2016-01-01

    Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

  15. The promise and challenge of practice-research collaborations: Guiding principles and strategies for initiating, designing, and implementing program evaluation research.

    Science.gov (United States)

    Secret, Mary; Abell, Melissa L; Berlin, Trey

    2011-01-01

    The authors present a set of guiding principles and strategies to facilitate the collaborative efforts of social work researchers and practitioners as they initiate, design, and implement outcome evaluations of human service interventions and programs. Beginning with an exploration of the interpersonal barriers to practice-research collaborations, and building on their experiences in successfully completing a community-based research evaluation, the authors identify specific relationship-focused principles and strategies and illustrate how these approaches can guide practice-research teams through the various sequential activities of the evaluation research process. In particular, it is suggested that practice-research collaborations can be formed, strengthened, and sustained by emphasis on a spirit of discovery and shared leadership at the start of the relationship, use of a comprehensive evaluation model to clarify and frame the evaluation and program goals, beginning where the client is when selecting research methodology and measurement tools, commitment to keeping the program first and recording everything during the implementation and data-collection stages, discussion of emerging findings and presentation of findings in graphic format at the data-analysis stage, and a total team approach at the dissemination stage.

  16. OCTAVE(Federal Registration)-S Implementation Guide, Version 1.0, Volume 9: Strategy and Plan Worksheets

    National Research Council Canada - National Science Library

    Alberts, Christopher; Dorofee, Audrey; Stevens, James; Woody, Carol

    2005-01-01

    ...) approach defines a risk-based strategic assessment and planning technique for security. OCTAVE is a self-directed approach, meaning that people from an organization assume responsibility for setting the organization's security strategy...

  17. Applications of nanomaterials as vaccine adjuvants

    Science.gov (United States)

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

  18. Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

    Science.gov (United States)

    El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

    2018-01-01

    Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Impact of guided reflection with peers on the development of effective problem solving strategies and physics learning

    OpenAIRE

    Mason, Andrew J.; Singh, Chandralekha

    2016-01-01

    Students must learn effective problem solving strategies in order to develop expertise in physics. Effective problem solving strategies include a conceptual analysis of the problem followed by planning of the solution, and then implementation, evaluation and reflection upon the process. Research suggests that converting a problem from the initial verbal representation to other suitable representation, e.g., diagrammatic representation, during the initial conceptual analysis can facilitate fur...

  20. Adjuvant chemoradiotherapy in gastric cancer

    International Nuclear Information System (INIS)

    Gonzalez Herrera, Ileana

    2002-01-01

    The main objetives of this work are to determine the tolerability of the adjuvant chemo-radiotherapy's treatment in Costa Rican patients in the Hospital San Juan de Dios, as well as to value the toxicity's level presented. A bibliographic review is realized to justify the use of this treatment's type and to determine the feasibility of its performance with the different services that are involved. The treatment's plan consisted on: after an undergoing of a gastrectomy, the patients were appointed to receive post-operative treatment combined of 5-F U plus leucovorin and radiation. The fluoracil was injected intravenous in continue infusion. The obtained results prove that the use of a lineal accelerator must be recommended as a standard treatment for this pathology by the region to treat and the complexity of the fields. The ganglion dissection performed with more frequency is inferior to one D 2, and the treatment with radiotherapy cobalt 60 and infusion al 5-F U is well tolerated with moderate-light toxicity and easily manageable [es

  1. A comparison of methodological guides for creating microregional strategies of Central European rural areas. Case study: Czech Republic

    Directory of Open Access Journals (Sweden)

    Jakub Trojan

    2012-05-01

    Full Text Available This paper discusses the complementarity of methodological guides dealing with microregional development in Central Europe. As an example, the Czech Republic framework has been selected. This study compares seven common methodologies written in Czech, which the author has divided into three groups, namely manual-like methodologies, semi-scientific texts and hybrid texts dealing with other complementary aspects. The result is a comparison of methodologies, their usage and implications for the practices of regional development. The paper also includes a brief analysis of sustainable development elements incorporated into the methodological texts. The final part outlines links to the four-capital model of regional development.

  2. COLLABORATIVE GUIDE: A REEF MANAGER'S GUIDE TO ...

    Science.gov (United States)

    Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental organizations, and academic institutions. Referred to as A Reef Manager's Guide to Coral Bleaching, the guide will provide coral reef managers with the latest scientific information on the causes of coral bleaching and new management strategies for responding to this significant threat to coral reef ecosystems. Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental organizations, and academic institutions. Dr. Jordan West, of the National Center for Environmental Assessment, was a major contributor to the guide. Referred to as

  3. Impact of Guided Reflection with Peers on the Development of Effective Problem Solving Strategies and Physics Learning

    Science.gov (United States)

    Mason, Andrew J.; Singh, Chandralekha

    2016-05-01

    Students must learn effective problem solving strategies in order to develop expertise in physics. Effective problem solving strategies include a conceptual analysis of the problem followed by planning of the solution, and then implementation, evaluation, and reflection upon the process. Research suggests that converting a problem from the initial verbal representation to other suitable representation, e.g., diagrammatic representation, during the initial conceptual analysis can facilitate further analysis of the problem. But without guidance, many introductory physics students solve problems using superficial clues and cues and do not perceive problem solving as an opportunity for learning. Here, we describe a study that suggests that engaging students in reflection with peers about effective problem solving strategies while effective approaches are modeled for them and prompt feedback is provided may enhance desirable skills.

  4. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  5. Academic Game Changers: A Study of the Social Networking Strategies of Leaders Guiding Disruptive Innovations in Higher Education

    Science.gov (United States)

    Langteau, Paula T.

    2017-01-01

    This study examines the internal and external networking strategies of leaders furthering potentially disruptive innovations in higher education. The goal of the research was to understand specifically what types of networks they develop, activate, and leverage; the functions of those networks; and the ways they engage them to further their…

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

    Science.gov (United States)

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

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

  7. Impact of residual and intrafractional errors on strategy of correction for image-guided accelerated partial breast irradiation

    Directory of Open Access Journals (Sweden)

    Guo Xiao-Mao

    2010-10-01

    Full Text Available Abstract Background The cone beam CT (CBCT guided radiation can reduce the systematic and random setup errors as compared to the skin-mark setup. However, the residual and intrafractional (RAIF errors are still unknown. The purpose of this paper is to investigate the magnitude of RAIF errors and correction action levels needed in cone beam computed tomography (CBCT guided accelerated partial breast irradiation (APBI. Methods Ten patients were enrolled in the prospective study of CBCT guided APBI. The postoperative tumor bed was irradiated with 38.5 Gy in 10 fractions over 5 days. Two cone-beam CT data sets were obtained with one before and one after the treatment delivery. The CBCT images were registered online to the planning CT images using the automatic algorithm followed by a fine manual adjustment. An action level of 3 mm, meaning that corrections were performed for translations exceeding 3 mm, was implemented in clinical treatments. Based on the acquired data, different correction action levels were simulated, and random RAIF errors, systematic RAIF errors and related margins before and after the treatments were determined for varying correction action levels. Results A total of 75 pairs of CBCT data sets were analyzed. The systematic and random setup errors based on skin-mark setup prior to treatment delivery were 2.1 mm and 1.8 mm in the lateral (LR, 3.1 mm and 2.3 mm in the superior-inferior (SI, and 2.3 mm and 2.0 mm in the anterior-posterior (AP directions. With the 3 mm correction action level, the systematic and random RAIF errors were 2.5 mm and 2.3 mm in the LR direction, 2.3 mm and 2.3 mm in the SI direction, and 2.3 mm and 2.2 mm in the AP direction after treatments delivery. Accordingly, the margins for correction action levels of 3 mm, 4 mm, 5 mm, 6 mm and no correction were 7.9 mm, 8.0 mm, 8.0 mm, 7.9 mm and 8.0 mm in the LR direction; 6.4 mm, 7.1 mm, 7.9 mm, 9.2 mm and 10.5 mm in the SI direction; 7.6 mm, 7.9 mm, 9.4 mm, 10

  8. Impact of residual and intrafractional errors on strategy of correction for image-guided accelerated partial breast irradiation

    International Nuclear Information System (INIS)

    Cai, Gang; Hu, Wei-Gang; Chen, Jia-Yi; Yu, Xiao-Li; Pan, Zi-Qiang; Yang, Zhao-Zhi; Guo, Xiao-Mao; Shao, Zhi-Min; Jiang, Guo-Liang

    2010-01-01

    The cone beam CT (CBCT) guided radiation can reduce the systematic and random setup errors as compared to the skin-mark setup. However, the residual and intrafractional (RAIF) errors are still unknown. The purpose of this paper is to investigate the magnitude of RAIF errors and correction action levels needed in cone beam computed tomography (CBCT) guided accelerated partial breast irradiation (APBI). Ten patients were enrolled in the prospective study of CBCT guided APBI. The postoperative tumor bed was irradiated with 38.5 Gy in 10 fractions over 5 days. Two cone-beam CT data sets were obtained with one before and one after the treatment delivery. The CBCT images were registered online to the planning CT images using the automatic algorithm followed by a fine manual adjustment. An action level of 3 mm, meaning that corrections were performed for translations exceeding 3 mm, was implemented in clinical treatments. Based on the acquired data, different correction action levels were simulated, and random RAIF errors, systematic RAIF errors and related margins before and after the treatments were determined for varying correction action levels. A total of 75 pairs of CBCT data sets were analyzed. The systematic and random setup errors based on skin-mark setup prior to treatment delivery were 2.1 mm and 1.8 mm in the lateral (LR), 3.1 mm and 2.3 mm in the superior-inferior (SI), and 2.3 mm and 2.0 mm in the anterior-posterior (AP) directions. With the 3 mm correction action level, the systematic and random RAIF errors were 2.5 mm and 2.3 mm in the LR direction, 2.3 mm and 2.3 mm in the SI direction, and 2.3 mm and 2.2 mm in the AP direction after treatments delivery. Accordingly, the margins for correction action levels of 3 mm, 4 mm, 5 mm, 6 mm and no correction were 7.9 mm, 8.0 mm, 8.0 mm, 7.9 mm and 8.0 mm in the LR direction; 6.4 mm, 7.1 mm, 7.9 mm, 9.2 mm and 10.5 mm in the SI direction; 7.6 mm, 7.9 mm, 9.4 mm, 10.1 mm and 12.7 mm in the AP direction

  9. Results of adjuvant chemo radiation after curative surgery for gastric cancer. A retrospective study

    International Nuclear Information System (INIS)

    Muller, Bettina; Balbontin, Paulina; Trujillo, Cristian; Becerra, Sergio; Sola, Antonio; Neveu, Rodrigo; Fernandez, Roberto; Buchholtz, Martin; Villanueva, Luis; Cerda, Berta

    2009-01-01

    Background: Survival rates after curative surgery for gastric cancer are disappointing. Therefore adjuvant therapeutic strategies are required. Aim: To analyze survival and side effects of treatment among gastric cancer patients treated with adjuvant chemoradiotherapy after curative resection of gastric adenocarcinoma. Material and methods: Retrospective review of medical records of 74 patients aged 20 to 74 years, treated with complete resection of gastric adenocarcinoma followed by adjuvant chemo radiation. Survival analysis was based on the records and information from the National Mortality Registry. Results: Five years survival fluctuated from 50% among patients in stage 1B to 25% among those is stage IV. Significant acute toxicity was observed in 23 patients (31%). No patients died due to acute toxicity. Eleven patients (16.4%) developed significant late toxicity, with two possible deaths related to treatment. Conclusions: Postoperative chemoradiotherapy is feasible in our experience. Continuos infusion of 5- fluoruracil is recommended to reduce toxicity

  10. Adjuvant solution for pandemic influenza vaccine production.

    Science.gov (United States)

    Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G

    2012-10-23

    Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

  11. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Science.gov (United States)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  12. The adjuvant potential of synthetic alkylglycerols.

    Science.gov (United States)

    Acevedo, Reinaldo; Gil, Danay; del Campo, Judith; Bracho, Gustavo; Valdés, Yolanda; Pérez, Oliver

    2006-04-12

    Alkylglycerols (AGs) have shown immune stimulant and adjuvant activity in many studies, but natural sources are not so accessible and their extraction from them is very complicated. Therefore, a group of chemists at IFAL have synthesized AG analogs. The aim of this work was to evaluate the adjuvant potential of different synthetic AGs. A mix of ovoalbumin (Ova) and AGs increase anti-Ova IgG antibodies production in sera of immunized mice. The predominant subclass was IgG1 although higher levels of IgG2a were observed as the carbon chain length of AGs increased. AGs also induced the production of IL-12 and nitric oxide (NO) in the U937 human histiocyte and J774 mouse macrophage cell lines, respectively. These results indicate that synthetic AGs are effective adjuvants for the standardized antigen, Ova.

  13. PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Dool-Ri Oh

    2014-01-01

    Full Text Available Toll-like receptor (TLR ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.

  14. Adjuvanted vaccines: Aspects of immunosafety and modes of action

    NARCIS (Netherlands)

    Aalst, Susan van

    2017-01-01

    New developments in vaccine design shift towards safe, though sometimes less immunogenic, subunit and synthetic antigens. Therefore, the majority of current vaccines require adjuvants to increase immunogenicity. Most adjuvants available were developed empirically and their mode of action is only

  15. Repository Integration Program: RIP performance assessment and strategy evaluation model theory manual and user`s guide

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    This report describes the theory and capabilities of RIP (Repository Integration Program). RIP is a powerful and flexible computational tool for carrying out probabilistic integrated total system performance assessments for geologic repositories. The primary purpose of RIP is to provide a management tool for guiding system design and site characterization. In addition, the performance assessment model (and the process of eliciting model input) can act as a mechanism for integrating the large amount of available information into a meaningful whole (in a sense, allowing one to keep the ``big picture`` and the ultimate aims of the project clearly in focus). Such an integration is useful both for project managers and project scientists. RIP is based on a `` top down`` approach to performance assessment that concentrates on the integration of the entire system, and utilizes relatively high-level descriptive models and parameters. The key point in the application of such a ``top down`` approach is that the simplified models and associated high-level parameters must incorporate an accurate representation of their uncertainty. RIP is designed in a very flexible manner such that details can be readily added to various components of the model without modifying the computer code. Uncertainty is also handled in a very flexible manner, and both parameter and model (process) uncertainty can be explicitly considered. Uncertainty is propagated through the integrated PA model using an enhanced Monte Carlo method. RIP must rely heavily on subjective assessment (expert opinion) for much of its input. The process of eliciting the high-level input parameters required for RIP is critical to its successful application. As a result, in order for any project to successfully apply a tool such as RIP, an enormous amount of communication and cooperation must exist between the data collectors, the process modelers, and the performance. assessment modelers.

  16. A review of the nature and effectiveness of nutrition interventions in adult males--a guide for intervention strategies.

    Science.gov (United States)

    Taylor, Pennie J; Kolt, Gregory S; Vandelanotte, Corneel; Caperchione, Cristina M; Mummery, W Kerry; George, Emma S; Karunanithi, Mohanraj; Noakes, Manny J

    2013-01-29

    Energy excess, low fruit and vegetable intake and other suboptimal dietary habits contribute to an increased poor health and the burden of disease in males. However the best way to engage males into nutrition programs remains unclear. This review provides a critical evaluation of the nature and effectiveness of nutrition interventions that target the adult male population. A search for full-text publications was conducted using The Cochrane Library; Web of Science; SCOPUS; MEDLINE and CINAHL. Studies were included if 1) published from January 1990 to August 2011 and 2) male only studies (≥18 years) or 3) where males contributed to >90% of the active cohort. A study must have described, (i) a significant change (pstudies were included. Sample sizes ranged from 53 to 5042 male participants, with study durations ranging from 12 weeks to 24 months. Overlap was seen with eight of the nine studies including a weight management component whilst six studies focused on achieving changes in dietary intake patterns relating to modifications of fruit, vegetable, dairy and total fat intakes and three studies primarily focused on achieving weight loss through caloric restriction. Intervention effectiveness was identified for seven of the nine studies. Five studies reported significant positive changes in weight (kg) and/or BMI (kg/m2) changes (p≤0.05). Four studies had effective interventions (pself-monitoring and tailored feedback. Uncertainty remains as to the features of successful nutrition interventions for males due to limited details provided for nutrition intervention protocols, variability in mode of delivery and comparisons between delivery modes as well as content of information provided to participants between studies. This review offers knowledge to guide researchers in making informed decisions on how to best utilise resources in interventions to engage adult males while highlighting the need for improved reporting of intervention protocols.

  17. Environmental impacts of the deep-water oil and gas industry: a review to guide management strategies

    Directory of Open Access Journals (Sweden)

    Erik E. Cordes

    2016-09-01

    Full Text Available The industrialization of the deep sea is expanding worldwide. Expanding oil and gas exploration activities in the absence of sufficient baseline data in these ecosystems has made environmental management challenging. Here, we review the types of activities that are associated with global offshore oil and gas development in water depths over 200 m, the typical impacts of these activities, some of the more extreme impacts of accidental oil and gas releases, and the current state of management in the major regions of offshore industrial activity including 18 exclusive economic zones. Direct impacts of infrastructure installation, including sediment resuspension and burial by seafloor anchors and pipelines, are typically restricted to a radius of approximately 100 m on from the installation on the seafloor. Discharges of water-based and low-toxicity oil-based drilling muds and produced water can extend over 2 km, while the ecological impacts at the population and community levels on the seafloor are most commonly on the order of 200-300 m from their source. These impacts may persist in the deep sea for many years and likely longer for its more fragile ecosystems, such as cold-water corals. This synthesis of information provides the basis for a series of recommendations for the management of offshore oil and gas development. An effective management strategy, aimed at minimizing risk of significant environmental harm, will typically encompass regulations of the activity itself (e.g. discharge practices, materials used, combined with spatial (e.g. avoidance rules and marine protected areas and temporal measures (e.g. restricted activities during peak reproductive periods. Spatial management measures that encompass representatives of all of the regional deep-sea community types is important in this context. Implementation of these management strategies should consider minimum buffer zones to displace industrial activity beyond the range of typical

  18. A fast inverse treatment planning strategy facilitating optimized catheter selection in image-guided high-dose-rate interstitial gynecologic brachytherapy.

    Science.gov (United States)

    Guthier, Christian V; Damato, Antonio L; Hesser, Juergen W; Viswanathan, Akila N; Cormack, Robert A

    2017-12-01

    Interstitial high-dose rate (HDR) brachytherapy is an important therapeutic strategy for the treatment of locally advanced gynecologic (GYN) cancers. The outcome of this therapy is determined by the quality of dose distribution achieved. This paper focuses on a novel yet simple heuristic for catheter selection for GYN HDR brachytherapy and their comparison against state of the art optimization strategies. The proposed technique is intended to act as a decision-supporting tool to select a favorable needle configuration. The presented heuristic for catheter optimization is based on a shrinkage-type algorithm (SACO). It is compared against state of the art planning in a retrospective study of 20 patients who previously received image-guided interstitial HDR brachytherapy using a Syed Neblett template. From those plans, template orientation and position are estimated via a rigid registration of the template with the actual catheter trajectories. All potential straight trajectories intersecting the contoured clinical target volume (CTV) are considered for catheter optimization. Retrospectively generated plans and clinical plans are compared with respect to dosimetric performance and optimization time. All plans were generated with one single run of the optimizer lasting 0.6-97.4 s. Compared to manual optimization, SACO yields a statistically significant (P ≤ 0.05) improved target coverage while at the same time fulfilling all dosimetric constraints for organs at risk (OARs). Comparing inverse planning strategies, dosimetric evaluation for SACO and "hybrid inverse planning and optimization" (HIPO), as gold standard, shows no statistically significant difference (P > 0.05). However, SACO provides the potential to reduce the number of used catheters without compromising plan quality. The proposed heuristic for needle selection provides fast catheter selection with optimization times suited for intraoperative treatment planning. Compared to manual optimization, the

  19. A review of the nature and effectiveness of nutrition interventions in adult males – a guide for intervention strategies

    Directory of Open Access Journals (Sweden)

    Taylor Pennie J

    2013-01-01

    guide researchers in making informed decisions on how to best utilise resources in interventions to engage adult males while highlighting the need for improved reporting of intervention protocols.

  20. Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

    Directory of Open Access Journals (Sweden)

    Christopher J. D. Wallis MD

    2017-05-01

    Full Text Available Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence. Methods: We constructed a health state transition (Markov model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer–specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE (58.3 months as compared with adjuvant radiotherapy (53.7 months, a difference of 4.6 months (standard deviation 8.8. Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months. Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized

  1. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    International Nuclear Information System (INIS)

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-01-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  2. Validation of the Risk Prediction Models STATE-Score and START-Strategy to Guide TACE Treatment in Patients with Hepatocellular Carcinoma.

    Science.gov (United States)

    Mähringer-Kunz, Aline; Kloeckner, Roman; Pitton, Michael B; Düber, Christoph; Schmidtmann, Irene; Galle, Peter R; Koch, Sandra; Weinmann, Arndt

    2017-07-01

    Several scoring systems that guide patients' treatment regimen for transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) have been introduced, but none have gained widespread acceptance in clinical practice. The purpose of this study is to externally validate the Selection for TrAnsarterial chemoembolization TrEatment (STATE)-score and START-strategy [i.e., sequential use of the STATE-score and Assessment for Retreatment with TACE (ART)-score]. From January 2000 to September 2015, 933 patients with HCC underwent TACE at our institution. All variables needed to calculate the STATE-score and implement the START-strategy were determined. STATE comprised serum albumin, up-to-seven criteria, and C-reactive protein (CRP). ART comprised an increase in aspartate aminotransferase, the Child-Pugh score, and a radiological tumor response. Overall survival was calculated, and multivariate analysis performed. In addition, the STATE-score and START-strategy were validated using the Harrell's C-index and integrated Brier score (IBS). The STATE-score was calculated in 228 patients. Low and high STATE-scores corresponded to median survival of 14.3 and 20.2 months, respectively. Harrell's C was 0.558 and IBS 0.133. For the STATE-score, significant predictors of survival were up-to-seven criteria (p = 0.006) and albumin (p = 0.022). CRP values were not predictive (p = 0.367). The ART-score was calculated in 207 patients. Combining the STATE-score and ART-score led to a Harrell's C of 0.580 and IBS of 0.132. The STATE-score was unable to reliably determine the suitability for initial TACE. The START-strategy only slightly improved the predictive ability compared to the ART-score alone. Therefore, neither the STATE-score nor START-strategy alone provides sufficient certainty for clear-cut clinical decisions.

  3. Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists.

    Science.gov (United States)

    Ouyang, Pamela; Wenger, Nanette K; Taylor, Doris; Rich-Edwards, Janet W; Steiner, Meir; Shaw, Leslee J; Berga, Sarah L; Miller, Virginia M; Merz, Noel Bairey

    2016-01-01

    In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex

  4. Laser vaccine adjuvants. History, progress, and potential.

    Science.gov (United States)

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.

  5. Hospitality Services. Curriculum Guide.

    Science.gov (United States)

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This guide, which was developed as part of Texas' home economics education program, is intended to assist teachers of a hospitality services course focusing on the food and lodging segments of the hospitality and tourism industry. The first 40% of the approximately 600-page guide consists of strategies for teaching each of 29 essential…

  6. Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Teik Hin Tan

    2016-07-01

    Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

  7. Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

    Directory of Open Access Journals (Sweden)

    Qamar J. Khan

    2010-01-01

    Full Text Available Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW with breast cancer, third-generation aromatase inhibitors (AIs as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence.

  8. Bromelain: A potential strategy for the adjuvant treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Felipe Rodolfo Pereira da Silva

    2016-01-01

    Full Text Available Introduction: Bromelain, a mixture of proteases derived from different parts of pineapple, has been described to have therapeutic benefits in a diversity of inflammatory diseases. Such effects are associated to its proteolytic activity. As one of the most common and multifactorial diseases, periodontitis is a bacterial infection that results from the damage to the integrity of the tissues around the tooth, which includes gingiva, periodontal ligament, and alveolar bone. In periodontitis, the recruitment of defense cells occurs, which releases several pro-inflammatory cytokines. At elevated levels, they can potentiate the alveolar bone loss. Studies have been conducted trying to alleviate the damage to the periodontium, however, the regeneration of the periodontal tissues is still limited. The Hypotheses: Based on previous studies showing that bromelain can act by decreasing the periodontal microorganism growth by proteolytically cleaving important cell surface molecules in leucocytes, by reducing neutrophils migration to periodontal sites, by downregulating the inflammation mediator levels, and by decreasing alveolar bone loss in the periodontitis. Evaluation of the Hypothesis: In a first moment, to evaluate this hypothesis, could be used two animal models: the ligature or bacteria inoculation induced periodontitis. If studies using animal models show encouraging results, appropriate clinical trials should be designed to evaluate the effect of bromelain as a complementary treatment for periodontal disease in humans, during the active phase or after the healing phase of mechanical therapy could be tested; to conduct a placebo-controlled study where health and periodontitis patients could be used.

  9. Cost-effectiveness of the Decipher Genomic Classifier to Guide Individualized Decisions for Early Radiation Therapy After Prostatectomy for Prostate Cancer.

    Science.gov (United States)

    Lobo, Jennifer M; Trifiletti, Daniel M; Sturz, Vanessa N; Dicker, Adam P; Buerki, Christine; Davicioni, Elai; Cooperberg, Matthew R; Karnes, R Jeffrey; Jenkins, Robert B; Den, Robert B; Showalter, Timothy N

    2017-06-01

    Controversy exists regarding the effectiveness of early adjuvant versus salvage radiation therapy after prostatectomy for prostate cancer. Estimates of prostate cancer progression from the Decipher genomic classifier (GC) could guide informed decision-making and improve the outcomes for patients. We developed a Markov model to compare the costs and quality-adjusted life years (QALYs) associated with GC-based treatment decisions regarding adjuvant therapy after prostatectomy with those of 2 control strategies: usual care (determined from patterns of care studies) and the alternative of 100% adjuvant radiation therapy. Using the bootstrapping method of sampling with replacement, the cases of 10,000 patients were simulated during a 10-year time horizon, with each subject having individual estimates for cancer progression (according to GC findings) and noncancer mortality (according to age). GC-based care was more effective and less costly than 100% adjuvant radiation therapy and resulted in cost savings up to an assay cost of $11,402. Compared with usual care, GC-based care resulted in more QALYs. Assuming a $4000 assay cost, the incremental cost-effectiveness ratio was $90,833 per QALY, assuming a 7% usage rate of adjuvant radiation therapy. GC-based care was also associated with a 16% reduction in the percentage of patients with distant metastasis at 5 years compared with usual care. The Decipher GC could be a cost-effective approach for genomics-driven cancer treatment decisions after prostatectomy, with improvements in estimated clinical outcomes compared with usual care. The individualized decision analytic framework applied in the present study offers a flexible approach to estimate the potential utility of genomic assays for personalized cancer medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  11. Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy.

    Science.gov (United States)

    Jang, Hoon; Hong, Kwonho; Choi, Youngsok

    2017-06-07

    Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients.

  12. DNA Vaccine Electroporation and Molecular Adjuvants

    Science.gov (United States)

    2016-03-16

    Suschak and Schmaljohn DNA Vaccine Electroporation and Molecular Adjuvants 1 Abstract To date, there is no protective vaccine for Ebola virus...the formulation of DNA launched virus-like particles (VLP). In this case, the antigen is encoded in one DNA plasmid, while structural proteins are...Virol, 2010. 155(12): p. 2083-103. 2. Feldmann, H. and T.W. Geisbert, Ebola haemorrhagic fever. Lancet, 2011. 377(9768): p. 849-62. 3. Hart, M.K

  13. Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

    Science.gov (United States)

    Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

    2017-01-01

    Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Impact of adjuvant chemotherapy for gliomatosis cerebri

    International Nuclear Information System (INIS)

    Kong, Doo-Sik; Nam, Do-Hyun; Kim, Sung Tae; Lee, Jung-Il; Suh, Yeon-Lim; Lim, Do Hoon; Kim, Won Seog; Kwon, Ki-Hoon; Park, Kwan; Kim, Jong Hyun

    2010-01-01

    Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

  15. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

    Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H

    2007-04-18

    The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

  16. Postoperative adjuvant therapy of colorectal carcinoma

    International Nuclear Information System (INIS)

    Scheithauer, W.

    1989-01-01

    Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

  17. Counterfeit Parts Prevention Strategies Guide

    Science.gov (United States)

    2014-06-24

    requirements of 252.211-7003, Item Unique Identification and Valuation .” This section establishes a recommended approach for requirements, polices, and...7003 Item Unique Identification and Valuation DoDI 4140.67 DoD Counterfeit Prevention Policy DoDI 5200.39 Critical Program Information (CPI...Deborah Valley deborah.valley@ll.mit.edu MIT Fred Van Milligen fvanmilligen@jdsu.com JDSU Marvin VanderWeg marvin.vanderwag@spacex.c om SpaceX Gerrit

  18. Adjuvant chemotherapy for rectal cancer: Is it needed?

    Science.gov (United States)

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  19. Overview of Vaccine Adjuvants: Introduction, History, and Current Status.

    Science.gov (United States)

    Shah, Ruchi R; Hassett, Kimberly J; Brito, Luis A

    2017-01-01

    Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response. Additionally, these new techniques help the field learn about our existing vaccines and what makes them safe, and effective, allowing us to leverage that in the next generation of vaccines. Our goal in this chapter is to define the concept, need, and mechanism of adjuvants in the vaccine field while describing its history, present use, and future prospects. More details on individual adjuvants and their formulation, development, mechanism, and use will be covered in depth in the next chapters.

  20. Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

    Directory of Open Access Journals (Sweden)

    Vincent Fagan

    2014-07-01

    Full Text Available A novel convergent synthetic strategy for the construction of multicomponent self-adjuvanting lipopeptide vaccines was developed. A tetraalkyne-functionalized glucose derivative and lipidated Fmoc-lysine were prepared by novel efficient and convenient syntheses. The carbohydrate building block was coupled to the self-adjuvanting lipidic moiety (three lipidated Fmoc-lysines on solid support. Four copies of a group A streptococcal B cell epitope (J8 were then conjugated to the glyco-lipopeptide using a copper-catalyzed cycloaddition reaction. The approach was elaborated by the preparation of a second vaccine candidate which incorporated an additional promiscuous T-helper epitope.

  1. An exploration of counterfeit medicine surveillance strategies guided by geospatial analysis: lessons learned from counterfeit Avastin detection in the US drug supply chain.

    Science.gov (United States)

    Cuomo, Raphael E; Mackey, Tim K

    2014-12-02

    To explore healthcare policy and system improvements that would more proactively respond to future penetration of counterfeit cancer medications in the USA drug supply chain using geospatial analysis. A statistical and geospatial analysis of areas that received notices from the Food and Drug Administration (FDA) about the possibility of counterfeit Avastin penetrating the US drug supply chain. Data from FDA warning notices were compared to data from 44 demographic variables available from the US Census Bureau via correlation, means testing and geospatial visualisation. Results were interpreted in light of existing literature in order to recommend improvements to surveillance of counterfeit medicines. This study analysed 791 distinct healthcare provider addresses that received FDA warning notices across 30,431 zip codes in the USA. Statistical outputs were Pearson's correlation coefficients and t values. Geospatial outputs were cartographic visualisations. These data were used to generate the overarching study outcome, which was a recommendation for a strategy for drug safety surveillance congruent with existing literature on counterfeit medication. Zip codes with greater numbers of individuals age 65+ and greater numbers of ethnic white individuals were most correlated with receipt of a counterfeit Avastin notice. Geospatial visualisations designed in conjunction with statistical analysis of demographic variables appeared more capable of suggesting areas and populations that may be at risk for undetected counterfeit Avastin penetration. This study suggests that dual incorporation of statistical and geospatial analysis in surveillance of counterfeit medicine may be helpful in guiding efforts to prevent, detect and visualise counterfeit medicines penetrations in the US drug supply chain and other settings. Importantly, the information generated by these analyses could be utilised to identify at-risk populations associated with demographic characteristics

  2. Adjuvant chemo- and radiotherapy in gastrointestinal tumors; Adjuvante Chemo- und Strahlentherapie bei gastrointestinalen Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Sendler, A. [Technische Univ. Muenchen (Germany). Chirurgische Klinik und Poliklinik; Feldmann, H.J. [Technische Univ. Muenchen (Germany). Inst. und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Fink, U. [Technische Univ. Muenchen (Germany). Chirurgische Klinik und Poliklinik; Molls, M. [Technische Univ. Muenchen (Germany). Inst. und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Siewert, J.R. [Technische Univ. Muenchen (Germany). Chirurgische Klinik und Poliklinik

    1995-04-21

    In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R{sub 0} resection) and additive therapies following incomplete tumor resections (UICC R{sub 1} or R{sub 2} resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R{sub 0} resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [Deutsch] Adjuvante Therapiestrategien sind wichtige flankierende Massnahmen der modernen onkologischen Chirurgie, da u.a. die 5-Jahres-Ueberlebensquoten bei lokal fortgeschrittenen Tumoren des Gastrointestinaltraktes nach wie vor unbefriedingend sind. Dabei muss grundsaetzlich zwischen adjuvanten Behandlungen nach kompletter Tumorexstirpation (UICC-R{sub 0}-Resektion) und der additiven Therapie nach palliativer Resektion (UICC-R{sub 1}- oder -R{sub 2}-Resektion) unterschieden werden. Als Modalitaeten kommen Chemotherapie, Strahlentherapie und ihre Kombination in Frage. Bei Oesophagus- und Magenkarzinomen kann derzeit keine gueltige Empfehlung zur adjuvanten Therapie gegeben werden. Die Radio

  3. Modern Vaccines/Adjuvants Formulation—Session 2 (Plenary II)

    Science.gov (United States)

    Collin, Nicolas

    2013-01-01

    On the 15–17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies. PMID:23966098

  4. Towards an understanding of the adjuvant action of aluminium

    Science.gov (United States)

    Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

    2011-01-01

    The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

  5. Mechanisms of, and Adjuvants for, Bone Pain.

    Science.gov (United States)

    Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

    2018-06-01

    Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

    Directory of Open Access Journals (Sweden)

    Hanna L. Thim

    2014-03-01

    receptor (PRR ligands, such as CpG/polyI:C, increases both adaptive and innate responses and represents a promising adjuvant strategy for enhancing the protection of future viral vaccines.

  7. Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

    Science.gov (United States)

    Bennett, Marsha; Bonanno, Laura; Kuhn, William

    2016-10-01

    The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

  8. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...... of dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB)....

  9. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  10. Immune adjuvant activity of the olive, soybean and corn oils

    Directory of Open Access Journals (Sweden)

    Ana Claudia Marinho da Silva

    2016-08-01

    Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

  11. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  12. Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

    Science.gov (United States)

    Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

  13. CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization.

    Science.gov (United States)

    Sundling, Christopher; Schön, Karin; Mörner, Andreas; Forsell, Mattias N E; Wyatt, Richard T; Thorstensson, Rigmor; Karlsson Hedestam, Gunilla B; Lycke, Nils Y

    2008-12-01

    Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in non-human primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env.

  14. Quadrantectomy and adjuvant radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Gabriele, A.M.; Boidi Trotti, A.; Tardy, A.

    1987-01-01

    The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4,4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted

  15. Adjuvant bisphosphonates in early breast cancer

    DEFF Research Database (Denmark)

    Hadji, P; Coleman, R E; Wilson, C

    2016-01-01

    Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have...... regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature...... was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus...

  16. Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

    Science.gov (United States)

    Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

    2015-08-01

    Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

  17. Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

    Directory of Open Access Journals (Sweden)

    Mark G. Bowden

    2011-01-01

    Full Text Available Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1 walking specific motor control; (2 dynamic balance; (3 cardiorespiratory fitness and (4 muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance.

  18. Implementation Guide: Leading School Change

    Science.gov (United States)

    Whitaker, Todd

    2010-01-01

    This two-part "Implementation Guide" will help to deepen your understanding and sharpen your ability to implement each of the strategies discussed in "Leading School Change: Nine Strategies to Bring Everybody on Board" (ED509821). Part One offers discussion questions and activities which focus on each of the nine strategies. They can be completed…

  19. Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

    Science.gov (United States)

    Mathew, Aju; Davidson, Nancy E

    2015-11-01

    Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Adjuvants for vaccines to drugs of abuse and addiction.

    Science.gov (United States)

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. Copyright © 2014. Published by Elsevier Ltd.

  1. Adjuvant radiation for vulvar carcinoma: improved local control

    International Nuclear Information System (INIS)

    Faul, Clare M.; Mirmow, Dwight; Huang Qingshon; Gerszten, Kristina; Day, Roger; Jones, Mirka W.

    1997-01-01

    Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

  2. Adjuvant Treatment for Older Women with Invasive Breast Cancer

    Science.gov (United States)

    Jolly, Trevor A; Williams, Grant R; Bushan, Sita; Pergolotti, Mackenzi; Nyrop, Kirsten A; Jones, Ellen L; Muss, Hyman B

    2016-01-01

    Older women experience a large share of breast cancer incidence and death. With the projected rise in the number of older cancer patients, adjuvant chemo-, radiation and endocrine therapy management will become a key component of breast cancer treatment in older women. Many factors influence adjuvant treatment decisions including patient preferences, life expectancy and tumor biology. Geriatric assessment predicts important outcomes, identifies key deficits, and can aid in the decision making process. This review utilizes clinical vignettes to illustrate core principles in adjuvant management of breast cancer in older women and suggests an approach incorporating life expectancy and geriatric assessment. PMID:26767315

  3. Potential of Cationic Liposomes as Adjuvants/Delivery Systems for Tuberculosis Subunit Vaccines.

    Science.gov (United States)

    Khademi, Farzad; Taheri, Ramezan Ali; Momtazi-Borojeni, Amir Abbas; Farnoosh, Gholamreza; Johnston, Thomas P; Sahebkar, Amirhossein

    2018-04-27

    The weakness of the BCG vaccine and its highly variable protective efficacy in controlling tuberculosis (TB) in different age groups as well as in different geographic areas has led to intense efforts towards the development and design of novel vaccines. Currently, there are several strategies to develop novel TB vaccines. Each strategy has its advantages and disadvantages. However, the most important of these strategies is the development of subunit vaccines. In recent years, the use of cationic liposome-based vaccines has been considered due to their capacity to elicit strong humoral and cellular immune responses against TB infections. In this review, we aim to evaluate the potential for cationic liposomes to be used as adjuvants/delivery systems for eliciting immune responses against TB subunit vaccines. The present review shows that cationic liposomes have extensive applications either as adjuvants or delivery systems, to promote immune responses against Mycobacterium tuberculosis (Mtb) subunit vaccines. To overcome several limitations of these particles, they were used in combination with other immunostimulatory factors such as TDB, MPL, TDM, and Poly I:C. Cationic liposomes can provide long-term storage of subunit TB vaccines at the injection site, confer strong electrostatic interactions with APCs, potentiate both humoral and cellular (CD4 and CD8) immune responses, and induce a strong memory response by the immune system. Therefore, cationic liposomes can increase the potential of different TB subunit vaccines by serving as adjuvants/delivery systems. These properties suggest the use of cationic liposomes to produce an efficient vaccine against TB infections.

  4. Adjuvant chemotherapy in early breast cancer.

    Science.gov (United States)

    Ejlertsen, Bent

    2016-05-01

    these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS

  5. An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

    Science.gov (United States)

    Fox, Christopher B; Haensler, Jean

    2013-07-01

    With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

  6. Adjuvant Therapy: Treatment to Keep Cancer from Returning

    Science.gov (United States)

    ... significant side effects, and these treatments don't benefit everyone. Types of cancer treatment that are used as adjuvant therapy include: Chemotherapy. Chemotherapy uses drugs to kill cancer cells throughout ...

  7. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  8. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  9. Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

    International Nuclear Information System (INIS)

    Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

    2009-01-01

    Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

  10. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

    OpenAIRE

    Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

    2014-01-01

    Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemoth...

  11. Learning impairment in honey bees caused by agricultural spray adjuvants.

    Directory of Open Access Journals (Sweden)

    Timothy J Ciarlo

    Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

  12. Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

    Science.gov (United States)

    Skedgel, Chris; Rayson, Daniel; Younis, Tallal

    2016-01-01

    Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

  13. Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

    Science.gov (United States)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

    2013-05-10

    Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    International Nuclear Information System (INIS)

    Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-01-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

  15. The study protocol for a non-randomized controlled clinical trial using a genotype-guided strategy in a dataset of patients who undergone percutaneous coronary intervention with stent

    Directory of Open Access Journals (Sweden)

    Cristina Lucía Dávila-Fajardo

    2017-02-01

    Full Text Available This article contains data related to the research article entitled “Results of genotype–guided antiplatelet therapy in patients undergone percutaneous coronary intervention with stent” (J. Sánchez-Ramos, C.L. Dávila-Fajardo, P. Toledo Frías, X. Díaz Villamarín, L.J. Martínez-González, S. Martínez Huertas, F. Burillo Gómez, J. Caballero Borrego, A. Bautista Pavés, M.C. Marín Guzmán, J.A. Ramirez Hernández, C. Correa Vilches, J. Cabeza Barrera, 2016 (1. This data article reports, for the first time, about the non-randomized clinical trial protocol that check if CYP2C19/ABCB1 genotype–guided strategy in which the choice of antiplatelet therapy is based on the genetic test, reduces the rates of cardiovascular events and bleeding compared to a non-tailored strategy in patients undergone percutaneous coronary intervention (PCI with stent. The data included in this article are: design and setting of the study, study population, inclusion and exclusion criteria, definition of the intervention, objectives, variables (baseline characteristics and during the follow-up, study procedures, collection and treatment of the biological sample, genotyping, withdrawal criteria, sample size, statistic analysis, ethical aspects, information sheet and consent form. The authors confirm that this study has been registered in Eudra CT (Eudra CT: 2016-001294-33.

  16. The Maritime Strategy Debates: A Guide to the Renaissance of U.S. Naval Strategic in the 1980s. Revision 2

    Science.gov (United States)

    1989-09-30

    1986, there’s always 10 percent who don’t get the word. ** Drury , F., "Naval Strike Warfare and the Outer Air Battle," Naya1 Forces IV/1986, pp 46-52...debate. * Gray, Colin S., "Keeping the Soviets Landlocked: Geostrategy for a Maritime America," The National Interest, Summer 1986, pp 24-36. Masterful...discussion of the relationships between geopolitics and the Maritime Strategy. ** Gray, Colin S., Maritime Strategy, Geopolitics, and the Defense of the

  17. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  18. Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

    Science.gov (United States)

    Bogani, Giorgio; Fucà, Giovanni; Maltese, Giuseppa; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Lecce, Francesca; Raspagliesi, Francesco; Lorusso, Domenica

    2016-11-01

    We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The path to memory is guided by strategy: distinct networks are engaged in associative encoding under visual and verbal strategy and influence memory performance in healthy and impaired individuals

    Science.gov (United States)

    Hales, J. B.; Brewer, J. B.

    2018-01-01

    Given the diversity of stimuli encountered in daily life, a variety of strategies must be used for learning new information. Relating and encoding visual and verbal stimuli into memory has been probed using various tasks and stimulus-types. Engagement of specific subsequent memory and cortical processing regions depends on the stimulus modality of studied material; however, it remains unclear whether different encoding strategies similarly influence regional activity when stimulus-type is held constant. In this study, subjects encoded object pairs using a visual or verbal associative strategy during functional magnetic resonance imaging (fMRI), and subsequent memory was assessed for pairs encoded under each strategy. Each strategy elicited distinct regional processing and subsequent memory effects: middle / superior frontal, lateral parietal, and lateral occipital for visually-associated pairs and inferior frontal, medial frontal, and medial occipital for verbally-associated pairs. This regional selectivity mimics the effects of stimulus modality, suggesting that cortical involvement in associative encoding is driven by strategy, and not simply by stimulus-type. The clinical relevance of these findings, probed in two patients with recent aphasic strokes, suggest that training with strategies utilizing unaffected cortical regions might improve memory ability in patients with brain damage. PMID:22390467

  20. Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial

    International Nuclear Information System (INIS)

    Wang, Jianhua; Shi, Mei; Ling, Rui; Xia Yuesheng; Luo Shanquan; Fu Xuehai; Xiao Feng; Li Jianping; Long Xiaoli; Wang Jianguo; Hou Zengxia; Chen Yunxia; Zhou Bin; Xu, Man

    2011-01-01

    Background and purpose: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. Patients and methods: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I-II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. Results: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03). No severe toxicity was reported. Conclusions: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

  1. Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

    Science.gov (United States)

    Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

    2014-01-01

    BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

  2. Guided labworks

    DEFF Research Database (Denmark)

    Jacobsen, Lærke Bang

    For the last 40 years physics education research has shown poor learning outcomes of guided labs. Still this is found to be a very used teaching method in the upper secodary schools. This study explains the teacher's choice of guided labs throught the concept of redesign as obstacle dislodgement...

  3. Strategy Instruction in Mathematics.

    Science.gov (United States)

    Goldman, Susan R.

    1989-01-01

    Experiments in strategy instruction for mathematics have been conducted using three models (direct instruction, self-instruction, and guided learning) applied to the tasks of computation and word problem solving. Results have implications for effective strategy instruction for learning disabled students. It is recommended that strategy instruction…

  4. Energy Efficiency Programs in K-12 Schools: A Guide to Developing and Implementing Greenhouse Gas Reduction Programs. Local Government Climate and Energy Strategy Series

    Science.gov (United States)

    US Environmental Protection Agency, 2011

    2011-01-01

    Saving energy through energy efficiency improvements can cost less than generating, transmitting, and distributing energy from power plants, and provides multiple economic and environmental benefits. Local governments can promote energy efficiency in their jurisdictions by developing and implementing strategies that improve the efficiency of…

  5. Cardiac computed tomography guided treatment strategy in patients with recent acute-onset chest pain ☆ ☆☆: Results from the randomised, controlled trial

    DEFF Research Database (Denmark)

    Linde, Jesper James; Kofoed, Klaus Fuglsang; Sørgaard, Mathias

    2013-01-01

    In patients admitted on suspicion of acute coronary syndrome, with normal electrocardiogram and troponines, we evaluated the clinical impact of a Coronary CT angiography (CCTA)-strategy on referral rate for invasive coronary angiography (ICA), detection of significant coronary stenoses (positive...

  6. A clinically applicable adjuvant for an atherosclerosis vaccine in mice.

    Science.gov (United States)

    Kobiyama, Kouji; Vassallo, Melanie; Mitzi, Jessica; Winkels, Holger; Pei, Hong; Kimura, Takayuki; Miller, Jacqueline; Wolf, Dennis; Ley, Klaus

    2018-06-22

    Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Predictive markers of safety and immunogenicity of adjuvanted vaccines.

    Science.gov (United States)

    Mastelic, Beatris; Garçon, Nathalie; Del Giudice, Giuseppe; Golding, Hana; Gruber, Marion; Neels, Pieter; Fritzell, Bernard

    2013-11-01

    Vaccination represents one of the greatest public health triumphs; in part due to the effect of adjuvants that have been included in vaccine preparations to boost the immune responses through different mechanisms. Although a variety of novel adjuvants have been under development, only a limited number have been approved by regulatory authorities for human vaccines. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the current state of the art in the adjuvant field. Held at the U.S. Pharmacopeial Convention (USP) in Rockville, Maryland, USA, from 18 to 19 April 2013 and organized by the International Association for Biologicals (IABS), the conference focused particularly on the future development of effective adjuvants and adjuvanted vaccines and on overcoming major hurdles, such as safety and immunogenicity assessment, as well as regulatory scrutiny. More information on the conference output can be found on the IABS website, http://www.iabs.org/. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  8. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

    Science.gov (United States)

    Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

    2014-01-01

    Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

  9. Environmental adjuvants, apoptosis and the censorship over autoimmunity.

    Science.gov (United States)

    Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

    2005-11-01

    Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

  10. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Science.gov (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  11. HBR guides

    CERN Document Server

    Duarte, Nancy; Dillon, Karen

    2015-01-01

    Master your most pressing professional challenges with this seven-volume set that collects the smartest best practices from leading experts all in one place. "HBR Guide to Better Business Writing" and "HBR Guide to Persuasive Presentations" help you perfect your communication skills; "HBR Guide to Managing Up and Across" and "HBR Guide to Office Politics" show you how to build the best professional relationships; "HBR Guide to Finance Basics for Managers" is the one book you'll ever need to teach you about the numbers; "HBR Guide to Project Management" addresses tough questions such as how to manage stakeholder expectations and how to manage uncertainty in a complex project; and "HBR Guide to Getting the Right Work Done" goes beyond basic productivity tips to teach you how to prioritize and focus on your work. This specially priced set of the most popular books in the series makes a perfect gift for aspiring leaders looking for trusted advice. Arm yourself with the advice you need to succeed on the job, from ...

  12. Designing CAF-adjuvanted dry powder vaccines: Spray drying preserves the adjuvant activity of CAF01

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis

    2013-01-01

    spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol...... parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray...... drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome...

  13. Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice

    NARCIS (Netherlands)

    Leenaars, P.P.A.M.; Koedam, M.A.; Wester, P.W.; Baumans, V.; Claassen, E.; Hendriksen, C.F.M.

    1998-01-01

    We evaluated the side effects induced by injection of Freund's adjuvant (FA) and alternative adjuvants combined with different antigens. Rabbits and mice were injected subcutaneously, intramuscularly (rabbits) and intraperitoneally (mice) with different adjuvants (FA, Specol, RIBI, TiterMax,

  14. Clinical development of a novel CD1d-binding NKT cell ligand as a vaccine adjuvant.

    Science.gov (United States)

    Padte, Neal N; Li, Xiangming; Tsuji, Moriya; Vasan, Sandhya

    2011-08-01

    Natural killer T (NKT) cells are known to play a role against certain microbial infections, including malaria and HIV, two major global infectious diseases. Strategies that can harness and amplify the immunotherapeutic potential of NKT cells can serve as powerful tools in the fight against such diseases. 7DW8-5, a novel glycolipid, may be one such tool. The interaction of 7DW8-5 with CD1d molecules induces activation of NKT cells, thereby activating various immune-competent cells including dendritic cells (DCs) to provide a significant adjuvant effect for several vaccines. This review discusses the discovery and characterization of 7DW8-5 and the practical considerations of its preclinical and clinical development as a potential glycolipid adjuvant for candidate malaria and HIV vaccines. Copyright © 2010. Published by Elsevier Inc.

  15. Some Aspects Of Adjuvant Treatment Of Colorectal Cancer

    International Nuclear Information System (INIS)

    Hlavata, Z.

    2008-01-01

    Colorectal cancer is one of the most common cancers in Europe and in North America. Cornerstone of the treatment of localized colorectal cancer is surgical resection followed by chemotherapy or radio-chemotherapy in indicated cases. For patients with Stage III colon cancer recent data have shown efficacy through the combining fluorouracil-based chemotherapy with oxaliplatin into adjuvant treatment program. For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at high risk for disease recurrence. Current randomized clinical trials in the adjuvant therapy of colorectal cancer are examining the value of adding agents known to be active in metastatic disease, including those that modify specific molecular targets. (author)

  16. Old and new adjuvants for hepatitis B vaccines.

    Science.gov (United States)

    Leroux-Roels, Geert

    2015-02-01

    The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

  17. Cognitive function after adjuvant treatment for early breast cancer

    DEFF Research Database (Denmark)

    Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer

    2010-01-01

    The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged ... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...... themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients....

  18. Production, purification and immunogenicity of recombinant Ebola virus proteins - A comparison of Freund's adjuvant and adjuvant system 03.

    Science.gov (United States)

    Melén, Krister; Kakkola, Laura; He, Felix; Airenne, Kari; Vapalahti, Olli; Karlberg, Helen; Mirazimi, Ali; Julkunen, Ilkka

    2017-04-01

    There is an urgent need for Ebola virus (EBOV) proteins, EBOV-specific antibodies and recombinant antigens to be used in diagnostics and as potential vaccine candidates. Our objective was to produce and purify recombinant proteins for immunological assays and for the production of polyclonal EBOV specific antibodies. In addition, a limited comparison of the adjuvant effects of Freund's complete adjuvant (FCA) and adjuvant system 03 (AS03) was carried out. Recombinant EBOV GST-VP24, -VP30, -VP35, -VP40 and -NP were produced in E. coli and purified with affinity chromatography followed by preparative gel electrophoresis. Recombinant EBOV GP-His was produced in Sf9 insect cells and purified by preparative gel electrophoresis. To compare the adjuvant effect of FCA and AS03, 12 rabbits were immunized four times with one of the six recombinant EBOV proteins using FCA or AS03. In addition, three guinea pigs were immunized with EBOV VP24 using FCA. With the exception of sera from two rabbits immunized with GST-VP24, the antisera against all other EBOV proteins showed very high and specific antibody responses after three to four immunizations. The adjuvant effect of AS03 was comparable to that of FCA. The produced antibodies recognized the corresponding EBOV proteins in wild type EBOV-infected cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    Science.gov (United States)

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

  20. Adjuvant treatment and outcomes of stage III endometrial carcinoma

    International Nuclear Information System (INIS)

    Connell, C.; Ludbrook, J.; Davy, M.; Yeoh, E

    2003-01-01

    Surgery with staging using FIGO (1988) classification is accepted management for stage III endometrial carcinoma. The delivery of adjuvant therapy is controversial and tends to be individualised. Retrospective review of stage III endometrial carcinoma patients who underwent radical surgery at the Royal Adelaide and Queen Elizabeth Hospitals from 1984 to 2003 was carried out. Medical records were reviewed for details of patient characteristics, surgery, histopathology, adjuvant therapy and recurrence/survival. Sixty-six patients with a median age of 69 (37-97), had a median follow-up of 26 months (1-188 ). For all stage III patients, the actuarial 5-year disease-free and overall survivals were 50 and 43% respectively. Thirty-five patients received pelvic +/- paraaortic radiotherapy, 5 whole abdominal radiotherapy, 14 vaginal brachytherapy boost, 10 chemotherapy and 13 adjuvant hormones. Forty-six percent of patients recurred in a median time of 13 months (0-95). For these patients, the sites of first recurrence were pelvis in 27%, pelvis and abdomen in 23%, abdomen alone in 13%, distant alone in 27%, distant and abdominal in 7% and all three sites in 3%. On univariate analysis disease-free survival was impacted by; age, grade, parametrial involvement, number of extrauterine sites, lymphovascular invasion, adjuvant radiotherapy to the pelvis alone and postoperative macroscopic residual disease. Lymphovascular invasion, post-operative residual disease and adjuvant pelvic radiotherapy remained significant on multivariate analysis. These outcomes for stage III endometrial carcinoma are comparable to the current literature. Ongoing research is required to establish the most appropriate adjuvant therapy in these high risk patients

  1. Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Agbahiwe, Harold C.; Wharam, Moody [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Batra, Sachin [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cohen, Kenneth [Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: sterezak@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-02-01

    Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

  2. Medication Guide

    Science.gov (United States)

    ... Size Small Text Medium Text Large Text Contrast Dark on Light Light on Dark Donate Search Menu Donate What is Glaucoma? Care ... Low Vision Resources Medication Guide Resources on the Web » See All Articles Where the Money Goes Have ...

  3. Long span DNA paired-end-tag (DNA-PET sequencing strategy for the interrogation of genomic structural mutations and fusion-point-guided reconstruction of amplicons.

    Directory of Open Access Journals (Sweden)

    Fei Yao

    Full Text Available Structural variations (SVs contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. While genomic DNA paired-end-tag (DNA-PET sequencing is an attractive approach to identify genomic SVs, the current application of PET sequencing with short insert size DNA can be insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We employed a recently developed procedure to generate PET sequencing data using large DNA inserts of 10-20 kb and compared their characteristics with short insert (1 kb libraries for their ability to identify SVs. Our results suggest that although short insert libraries bear an advantage in identifying small deletions, they do not provide significantly better breakpoint resolution. In contrast, large inserts are superior to short inserts in providing higher physical genome coverage for the same sequencing cost and achieve greater sensitivity, in practice, for the identification of several classes of SVs, such as copy number neutral and complex events. Furthermore, our results confirm that large insert libraries allow for the identification of SVs within repetitive sequences, which cannot be spanned by short inserts. This provides a key advantage in studying rearrangements in cancer, and we show how it can be used in a fusion-point-guided-concatenation algorithm to study focally amplified regions in cancer.

  4. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients.

    Science.gov (United States)

    Vees, Hansjörg; Senthamizhchelvan, Srinivasan; Miralbell, Raymond; Weber, Damien C; Ratib, Osman; Zaidi, Habib

    2009-02-01

    The purpose of the study is to assess the contribution of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate (18)F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV(MRI)). PET image segmentation techniques included manual delineation of contours (GTV(man)), a 2.5 standardized uptake value (SUV) cutoff (GTV(2.5)), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio (SBR)-based adaptive thresholding (GTV(SBR)), gradient find (GTV(GF)), and region growing (GTV(RG)). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Contours defined using GTV(2.5) failed to provide successful delineation technically in three patients (18% of cases) as SUV(max) segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation.

  5. Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Zerahn, Bo; Møller, Susanne

    2012-01-01

    Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.......Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

  6. A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens

    Directory of Open Access Journals (Sweden)

    Xue Xiangyang

    2009-05-01

    Full Text Available Abstract Background Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4 via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice. Methods The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3+CD8-IFN-γ+ cells and CD3+CD8-IL-4+ cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge. Results Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced

  7. A strategy for the use of image-guided radiotherapy (IGRT) on linear accelerators and its impact on treatment margins for prostate cancer patients

    International Nuclear Information System (INIS)

    Nairz, Olaf; Deutschmann, Heinz; Zehentmayr, Franz; Sedlmayer, Felix; Paracelsus Medical University Salzburg; Merz, Florian; Kopp, Peter; Schoeller, Helmut; Wurstbauer, Karl; Kametriser, Gerhard

    2008-01-01

    In external beam radiotherapy of prostate cancer, the consideration of various systematic error types leads to wide treatment margins compromising normal tissue tolerance. We investigated if systematic set-up errors can be reduced by a set of initial image-guided radiotherapy (IGRT) sessions. 27 patients received daily IGRT resulting in a set of 882 cone-beam computed tomographies (CBCTs). After matching to bony structures, we analyzed the dimensions of remaining systematic errors from zero up to six initial IGRT sessions and aimed at a restriction of daily IGRT for 10% of all patients. For threshold definition, we determined the standard deviations (SD) of the shift corrections and selected patients out of this range for daily image guidance. To calculate total treatment margins, we demanded for a cumulative clinical target volume (CTV) coverage of at least 95% of the specified dose in 90% of all patients. The gain of accuracy was largest during the first three IGRTs. In order to match precision and workload criteria, thresholds for the SD of the corrections of 3.5 mm, 2.0 mm and 4.5 mm in the left-right (L-R), cranial-caudal (C-C), and anterior-posterior (A-P) direction, respectively, were identified. Including all other error types, the total margins added to the CTV amounted to 8.6 mm in L-R, 10.4 mm in C-C, and 14.4 mm in A-P direction. Only initially performed IGRT might be helpful for eliminating gross systematic errors especially after virtual simulation. However, even with daily IGRT performance, a substantial PTV margin reduction is only achievable by matching internal markers instead of bony anatomical structures. (orig.)

  8. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients

    International Nuclear Information System (INIS)

    Vees, Hansjoerg; Senthamizhchelvan, Srinivasan; Ratib, Osman; Miralbell, Raymond; Weber, Damien C.; Zaidi, Habib

    2009-01-01

    The purpose of the study is to assess the contribution of 18 F-fluoro-ethyl-tyrosine ( 18 F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate 18 F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV MRI ). PET image segmentation techniques included manual delineation of contours (GTV man ), a 2.5 standardized uptake value (SUV) cutoff (GTV 2.5 ), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV 40% and GTV 50% ), signal-to-background ratio (SBR)-based adaptive thresholding (GTV SBR ), gradient find (GTV GF ), and region growing (GTV RG ). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Contours defined using GTV 2.5 failed to provide successful delineation technically in three patients (18% of cases) as SUV max MRI (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTV MRI in six patients (33% of cases). The selection of the most appropriate 18 F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation. (orig.)

  9. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  10. Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas

    2011-01-01

    Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

  11. Comparison of adjuvants for immune potentiating properties and side effects in mice

    NARCIS (Netherlands)

    Leenaars, P.P.A.M.; Hendriksen, C.F.M.; Koedam, M.A.; Claassen, I.; Claassen, E.

    1995-01-01

    Four types of adjuvants were evaluated as alternatives to the use of Freund's complete adjuvant in mice. The adjuvants evaluated included a water-in-oil emulsion (Specol), a microorganism (Lactobacillus), preformed immune-stimulating complexes (ISCOM) containing rabies virus glycoprotein and a

  12. How to combine hormonotherapy and radiation treatment in adjuvant breast cancer?

    International Nuclear Information System (INIS)

    Azria, D.; Llacer Moscardo, C.; Lemanski, C.; Ozsahin, M.; Gligorov, J.; Zaman, K.; Jacot, W.; Belkacemi, Y.

    2008-01-01

    Combined radiation and hormone therapies have become common clinical practice in recent years for locally-advanced prostate cancers. The use of such concomitant therapy in the treatment of breast disease has been infrequently reported in the literature, but seems justified given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities. As adjuvant therapy, two strategies are used in daily clinical practice: up front aromatase inhibitors or sequentially after a variable delay of tamoxifen. These molecules may, thus, interact with radiotherapy. Retrospective studies recently published did not show any differences in terms of locoregional recurrences between concurrent or sequential radio hormonotherapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side effects appeared to be increased by such a treatment, particularly in hypersensitive patients identified at risk by the lymphocyte predictive test. Concurrent radio hormonotherapy should, thus, be delivered cautiously at least for these patients. This article details the potent advantages and risks of concurrent use of adjuvant hormonotherapy and radiotherapy in localized breast cancers. (authors)

  13. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

    2017-08-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

  14. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need

  15. Benefits of adjuvant chemotherapy in high-grade gliomas.

    Science.gov (United States)

    DeAngelis, Lisa M

    2003-12-01

    The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

  16. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky

    2012-01-01

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Du...

  17. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA

  18. Effects of processing adjuvants on traditional Chinese herbs

    Directory of Open Access Journals (Sweden)

    Lin-Lin Chen

    2018-04-01

    Full Text Available Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs. Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs. Keywords: Adjuvant, Processing, Synergism, Traditional Chinese medicine

  19. Efficacy of Killed Adjuvanted FMD Vaccine Developed with ...

    African Journals Online (AJOL)

    In this study the potency of killed Foot and Mouth Disease (FMD) vaccines serotypes SAT1 (Nig 1/98) and SAT 2 (Nig 2/97) virus isolates, formulated with montanide ISA 206 adjuvant was determined in guinea pigs and cattle by antibody assay using Complement Fixation and Serum Neutralization tests. The antibody titres ...

  20. A randomised controlled trial comparing the effect of adjuvant ...

    African Journals Online (AJOL)

    Background: Intrathecal adjuvants are added to local anaesthetics to improve the quality of neuraxial blockade and prolong the duration of analgesia during spinal anaesthesia. Used intrathecally, fentanyl improves the quality of spinal blockade as compared to plain bupivacaine and confers a short duration of post ...

  1. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Science.gov (United States)

    2010-04-01

    ... Section 172.710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The...

  2. Adjuvant chemotherapy for stage I non-seminomatous testicular ...

    African Journals Online (AJOL)

    Adjuvant chemotherapy for stage I non-seminomatous testicular cancer. R. P. Abratt, A. R. Pontin, R. D. Barnes, B. V. Reddi. Developments in the treatment of stage I ... taxing for patients.·. Analysis of tumour histology in the orchidectomy specimen in patients entered into surveillance studies led to the identification of risk ...

  3. Complications following surgery and adjuvant irradiation in rectal carcinoma

    International Nuclear Information System (INIS)

    Suhr, P.; Limmer, J.

    1991-01-01

    Colorectal cancer is one of the most common human malignancies. Adjuvant irradiation can decrease the risk of recurrence and subsequently the associated morbidity compared with surgery alone. The rate of radiation-induced complications amounts to approximately 10%, which is substantially lower than the frequency of observed local failure. (orig.) [de

  4. Role of chemoradiotherapy in oesophageal cancer -- adjuvant and neoadjuvant therapy

    NARCIS (Netherlands)

    Gwynne, S.; Wijnhoven, B. P. L.; Hulshof, M.; Bateman, A.

    2014-01-01

    Despite low postoperative mortality rates, the long-term outcomes from surgical-based treatment for oesophageal cancer remain poor. Chemoradiotherapy (CRT), either given before surgical resection as neoadjuvant therapy or after resection as adjuvant therapy, has been postulated to improve these

  5. TLR4 and TLR7/8 Adjuvant Combinations Generate Different Vaccine Antigen-Specific Immune Outcomes in Minipigs when Administered via the ID or IN Routes.

    Directory of Open Access Journals (Sweden)

    Paul F McKay

    Full Text Available The induction of high levels of systemic and mucosal humoral immunity is a key goal for many prophylactic vaccines. However, adjuvant strategies developed in mice have often performed poorly in the clinic. Due to their closer similarity to humans, minipigs may provide a more accurate picture of adjuvant performance. Based on their complementary signalling pathways, we assessed humoral immune responses to model antigens after co-administration with the toll-like receptor 4 (TLR4 stimulator glucopyranosyl lipid adjuvant (GLA-AF or the TLR7/8 agonist resiquimod (R848 (alone and in combination via the intradermal (ID, intranasal (IN or combined routes in the Gottingen minipig animal model. Surprisingly, we discovered that while GLA-AF additively enhanced the adjuvant effect of R848 when injected ID, it abrogated the adjuvant activity of R848 after IN inoculation. We then performed a route comparison study using a CN54 gp140 HIV Envelope model antigen adjuvanted with R848 + GLA-AF (ID or R848 alone (IN. Animals receiving priming inoculations via one route were then boosted by the alternate route. Although differences were observed in the priming phase (IN or ID, responses converged upon boosting by the alternative route with no observable impact resultant from the order of administration (ID/IN vs IN/ID. Specific IgG responses were measured at a distal mucosal site (vaginal, although there was no evidence of mucosal linkage as these closely reflected serum antibody levels. These data indicate that the complex in vivo cross-talk between innate pathways are likely tissue specific and cannot be predicted by simple in vitro models.

  6.   Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E.

    tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however...... Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006......) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen. Patients...

  7. Guide device

    International Nuclear Information System (INIS)

    Brammer, C.M. Jr.

    1977-01-01

    Disclosed is a fuel handling guide tube centering device for use in nuclear reactors during fuel assembly handling operations. The device comprises an outer ring secured to the flange of a nuclear reactor pressure vessel, a rotatable table rotatably coupled to the outer ring, and a plurality of openings through the table. Truncated locating cones are positioned in each of the openings in the table, and the locating cones center the guide tube during fuel handling operations. The openings in the table are located such that each fuel assembly in the nuclear core may be aligned with one of the openings by a suitable rotation of the table. The locating cones thereby provide alignment between the fuel handling mechanism located in the guide tube and the individual fuel assemblies of the cone. The need for a device to provide alignment is especially critical for floating nuclear power plants, where wave motion may exist during fuel handling operations. 5 claims, 4 figures

  8. [Vacuum sealing drainage as an adjuvant treatment of penile and scrotal gangrene: Clinical analysis of 4 cases].

    Science.gov (United States)

    Zhu, Tong; Liao, Liang-Gong; Li, Yan-Feng; Liu, Xu-Dong; Hu, Ming; Zhang, Yong; Li, Zhong-Tai; Cao, Quan-Fu; Jiang, Jun

    2017-03-01

    To search for an optimal strategy for the treatment of penile and scrotal gangrene by analyzing the clinical effect of vacuum sealing drainage (VSD) as an adjuvant treatment on this disease. We retrospectively analyzed the clinical data about 4 cases of penile and scrotal gangrene treated by VSD as an adjuvant treatment from January 2015 to June 2016. The 4 patients all underwent early extensive and radical debridement of gangrene of the scrotum and penis and received intravenous injection of two broad-spectrum antibiotics, followed by VSD for wound drainage and irrigation. Adequate wound drainage was achieved in all the 4 cases, the gangrene range rapidly localized and testicular necrosis avoided. The wound surface healed satisfactorily after cleansing and suturing. The patients were followed up for 3 months after discharged from the hospital and none experienced recurrence. VSD combined with early adequate debridement can effectively localize the gangrene range, significantly reduce the frequency of changing dressings and shorten the hospitalization time of the patient, and therefore is a very effective adjuvant treatment of penile and scrotal gangrene.

  9. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    Science.gov (United States)

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation.

  10. Towards personal health care with model-guided medicine: long-term PPPM-related strategies and realisation opportunities within 'Horizon 2020'.

    Science.gov (United States)

    Lemke, Heinz U; Golubnitschaja, Olga

    2014-01-01

    At the international EPMA Summit carried out in the EU Parliament (September 2013), the main challenges in Predictive, Preventive and Personalised Medicine have been discussed and strategies outlined in order to implement scientific and technological innovation in medicine and healthcare utilising new strategic programmes such as 'Horizon 2020'. The joint EPMA (European Association for Predictive, Preventive and Personalised Medicine) / IFCARS (International Foundation for Computer Assisted Radiology and Surgery) paper emphasises the consolidate position of the leading experts who are aware of the great responsibility of being on a forefront of predictive, preventive and personalised medicine. Both societies consider long-term international partnerships and multidisciplinary projects to create PPPM relevant innovation in science, technological tools and practical implementation in healthcare. Personalisation in healthcare urgently needs innovation in design of PPPM-related medical services, new products, research, education, didactic materials, propagation of targeted prevention in the society and treatments tailored to the person. For the paradigm shift from delayed reactive to predictive, preventive and personalised medicine, a new culture should be created in communication between individual professional domains, between doctor and patient, as well as in communication with individual social (sub)groups and patient cohorts. This is a long-term mission in personalised healthcare with the whole spectrum of instruments available and to be created in the field.

  11. 76 FR 71577 - Guidance for Industry on Medication Guide Distribution Requirements and Inclusion of Medication...

    Science.gov (United States)

    2011-11-18

    ...] Guidance for Industry on Medication Guide Distribution Requirements and Inclusion of Medication Guides in... guidance for industry entitled ``Medication Guides-- Distribution Requirements and Inclusion in Risk... Requirements and Inclusion in Risk Evaluation and Mitigation Strategies (REMS).'' This guidance provides...

  12. Homebuyer's Guide.

    Science.gov (United States)

    Sindt, Roger P.; Harris, Jack

    Designed to assist prospective buyers in making such important decisions as whether to buy a new or older home and within what price range, the guide provides information on the purchase process. Discussion of the purchase process covers the life-cycle costs (recurring homeownership costs that must be met every month); selection of a home;…

  13. [Status and suggestions for adjuvant standard for Chinese materia medica processing in China].

    Science.gov (United States)

    Yang, Chun-Yu; Cao, Hui; Wang, Xiao-Tao; Tu, Jia-Sheng; Qian, Zhong-Zhi; Yu, Zhi-Ling; Shang, Yue; Zhang, Bao-Xian

    2017-04-01

    In this paper, the status of adjuvant standard for Chinese materia medica processing in the Chinese Pharmacopoeia 2015 edition, the National Specification of Chinese Materia Medica Processing, and the 29 provincial specification of Chinese materia medica was summarized, and the the status including general requirements, specific requirements, and quality standard in the three grade official specifications was collected and analyzed according to the "medicine-adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper also introduced the research situation of adjuvant standard for Chinese materia medica processing in China; In addition, analyzed and discussed the problems existing in the standard system of adjuvant for Chinese materia medica processing, such as lack of general requirements, low level of standard, inconsistent standard references, and lack of research on the standard, and provided suggestions for the further establishment of the national standards system of adjuvant for Chinese materia medica processing. Copyright© by the Chinese Pharmaceutical Association.

  14. Effect of different adjuvant formulations on the immunogenicity and protective effect of a live Mycoplasma hyopneumoniae vaccine after intramuscular inoculation.

    Science.gov (United States)

    Xiong, Qiyan; Wei, Yanna; Xie, Haidong; Feng, Zhixin; Gan, Yuan; Wang, Chunlai; Liu, Maojun; Bai, Fangfang; Xie, Fang; Shao, Guoqing

    2014-06-05

    Mycoplasma hyopneumoniae (M. hyopneumoniae) vaccine strain 168 is an intrapulmonically injected attenuated live vaccine that is available in the Chinese market. The aim of this study was to develop suitable adjuvants for this live vaccine to provide effective protection after intramuscular inoculation. Several adjuvant components were screened to assess their toxicity for the live vaccine, and various adjuvant formulations were then designed and prepared. Vaccines supplemented with these adjuvants were used to immunize mice intramuscularly to assess the capacity of the adjuvants to induce a specific immune response. The screened formulations were then evaluated in pigs. Seven of the eight adjuvant components did not affect the viability of the live vaccine, and seven different adjuvant formulations were then designed. In mice, the ISCOM-matrix adjuvant and the levamisole-chitosan mixture adjuvant significantly enhanced serum IgG responses against M. hyopneumoniae, while lymphocyte proliferation was enhanced by the ISCOM-matrix adjuvant, the carbomer-astragalus polysaccharide mixture adjuvant and an oil-in-water emulsion adjuvant. These four adjuvants were evaluated in pigs. Enhancement of specific lymphocyte proliferation responses was observed in the groups vaccinated with the ISCOM-matrix adjuvant and the carbomer-astragalus polysaccharide mixture adjuvant. Significant enhancement of serum IgG antibody production was observed before challenge in pigs vaccinated with the carbomer-astragalus polysaccharide mixture adjuvant and the levamisole-chitosan mixture adjuvant, while after challenge, all of the animals that received vaccines containing adjuvants had higher antibody concentrations against M. hyopneumoniae than unvaccinated animals. Animals inoculated with a vaccine containing the ISCOM-matrix adjuvant (median score 3.57) or the carbomer-astragalus polysaccharide mixture adjuvant (median score 5.28) had reduced lesion scores compared to unvaccinated animals

  15. Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series.

    Science.gov (United States)

    Goetz, Matthew B; Bowman, Candice; Hoang, Tuyen; Anaya, Henry; Osborn, Teresa; Gifford, Allen L; Asch, Steven M

    2008-03-19

    We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis - a point of substantial importance to the VA, which is the largest provider of HIV care in the United States. Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA.Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation. Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3-5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations. This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of

  16. Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Nancy, E-mail: leen2@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Schoder, Heiko [Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beattie, Brad [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lanning, Ryan; Riaz, Nadeem; McBride, Sean [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katabi, Nora [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Li, Duan [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yarusi, Brett; Chan, Susie; Mitrani, Lindsey [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pfister, David G.; Sherman, Eric; Baxi, Shrujal [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Boyle, Jay; Morris, Luc G.T.; Ganly, Ian; Wong, Richard [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Humm, John [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2016-09-01

    confirmed pathologically. Conclusions: Hypoxia is present in HPV{sup +} tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

  17. Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Lee, Nancy; Schoder, Heiko; Beattie, Brad; Lanning, Ryan; Riaz, Nadeem; McBride, Sean; Katabi, Nora; Li, Duan; Yarusi, Brett; Chan, Susie; Mitrani, Lindsey; Zhang, Zhigang; Pfister, David G.; Sherman, Eric; Baxi, Shrujal; Boyle, Jay; Morris, Luc G.T.; Ganly, Ian; Wong, Richard; Humm, John

    2016-01-01

    . Conclusions: Hypoxia is present in HPV"+ tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

  18. Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series

    Directory of Open Access Journals (Sweden)

    Osborn Teresa

    2008-03-01

    Full Text Available Abstract Background We describe how we used the framework of the U.S. Department of Veterans Affairs (VA Quality Enhancement Research Initiative (QUERI to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV. This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis – a point of substantial importance to the VA, which is the largest provider of HIV care in the United States. Methods Following the QUERI steps (or process, we evaluated: 1 whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2 whether there are evidence-based recommendations for HIV testing, 3 whether there are gaps in the performance of VA HIV testing, and 4 the barriers and facilitators to improving current practice in the VA. Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation. Results Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3–5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations where the pilot project has been undertaken; no change was seen at control stations. Discussion This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates

  19. Feasibility of an Adaptive Strategy in Preoperative Radiochemotherapy for Rectal Cancer With Image-Guided Tomotherapy: Boosting the Dose to the Shrinking Tumor

    International Nuclear Information System (INIS)

    Passoni, Paolo; Fiorino, Claudio; Slim, Najla; Ronzoni, Monica; Ricci, Vincenzo; Di Palo, Saverio; De Nardi, Paola; Orsenigo, Elena; Tamburini, Andrea; De Cobelli, Francesco; Losio, Claudio; Iacovelli, Nicola A.; Broggi, Sara; Staudacher, Carlo; Calandrino, Riccardo; Di Muzio, Nadia

    2013-01-01

    Purpose: To investigate the feasibility of preoperative adaptive radiochemotherapy by delivering a concomitant boost to the residual tumor during the last 6 fractions of treatment. Methods and Materials: Twenty-five patients with T3/T4N0 or N+ rectal cancer were enrolled. Concomitant chemotherapy consisted of oxaliplatin 100 mg/m 2 on days −14, 0, and +14, and 5-fluorouracil 200 mg/m 2 /d from day −14 to the end of radiation therapy (day 0 is the start of radiation therapy). Radiation therapy consisted of 41.4 Gy in 18 fractions (2.3 Gy per fraction) with Tomotherapy to the tumor and regional lymph nodes (planning target volume, PTV) defined on simulation CT and MRI. After 9 fractions simulation CT and MRI were repeated for the planning of the adaptive phase: PTV adapt was generated by adding a 5-mm margin to the residual tumor. In the last 6 fractions a boost of 3.0 Gy per fraction (in total 45.6 Gy in 18 fractions) was delivered to PTV adapt while concomitantly delivering 2.3 Gy per fraction to PTV outside PTV adapt . Results: Three patients experienced grade 3 gastrointestinal toxicity; 2 of 3 showed toxicity before the adaptive phase. Full dose of radiation therapy, oxaliplatin, and 5-fluorouracil was delivered in 96%, 96%, and 88% of patients, respectively. Two patients with clinical complete response (cCR) refused surgery and were still cCR at 17 and 29 months. For the remaining 23 resected patients, 15 of 23 (65%) showed tumor regression grade 3 response, and 7 of 23 (30%) had pathologic complete response; 8 (35%) and 12 (52%) tumor regression grade 3 patients had ≤5% and 10% residual viable cells, respectively. Conclusions: An adaptive boost strategy is feasible, with an acceptable grade 3 gastrointestinal toxicity rate and a very encouraging tumor response rate. The results suggest that there should still be room for further dose escalation of the residual tumor with the aim of increasing pathologic complete response and/or cCR rates

  20. Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when in association with the recombinant LiHyp1 protein, to protect against visceral leishmaniasis.

    Science.gov (United States)

    de Jesus Pereira, Nathália Cristina; Régis, Wiliam César Bento; Costa, Lourena Emanuele; de Oliveira, Jamil Silvano; da Silva, Alanna Gomes; Martins, Vivian Tamietti; Duarte, Mariana Costa; de Souza, José Roberto Rodrigues; Lage, Paula Sousa; Schneider, Mônica Santos; Melo, Maria Norma; Soto, Manuel; Soares, Sandra Aguiar; Tavares, Carlos Alberto Pereira; Chávez-Fumagalli, Miguel Angel; Coelho, Eduardo Antonio Ferraz

    2015-06-01

    The development of effective prophylactic strategies to prevent leishmaniasis has become a high priority. No less important than the choice of an antigen, the association of an appropriate adjuvant is necessary to achieve a successful vaccination, as the majority of the tested antigens contain limited immunogenic properties, and need to be supplemented with immune response adjuvants in order to boost their immunogenicity. However, few effective adjuvants that can be used against leishmaniasis exist on the market today; therefore, it is possible to speculate that the research aiming to identify new adjuvants could be considered relevant. Recently, Agaricus blazei extracts have proved to be useful in enhancing the immune response to DNA vaccines against some diseases. This was based on the Th1 adjuvant activity of the polysaccharide-rich fractions from this mushroom. In this context, the present study evaluated purified fractions derived from Agaricus blazei as Th1 adjuvants through in vitro assays of their immune stimulation of spleen cells derived from naive BALB/c mice. Two of the tested six fractions (namely F2 and F4) were characterized as polysaccharide-rich fractions, and were able to induce high levels of IFN-γ, and low levels of IL-4 and IL-10 in the spleen cells. The efficacy of adjuvant action against L. infantum was evaluated in BALB/c mice, with these fractions being administered together with a recombinant antigen, LiHyp1, which was previously evaluated as a vaccine candidate, associated with saponin, against visceral leishmaniasis (VL). The associations between LiHyp1/F2 and LiHyp1/F4 were able to induce an in vivo Th1 response, which was primed by high levels of IFN-γ, IL-12, and GM-CSF, by low levels of IL-4 and IL-10; as well as by a predominance of IgG2a antibodies in the vaccinated animals. After infection, the immune profile was maintained, and the vaccines proved to be effective against L. infantum. The immune stimulatory effects in the

  1. A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

    Science.gov (United States)

    Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

    2016-02-03

    New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

    Science.gov (United States)

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

    2012-01-01

    Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

  3. Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

  4. Skull base meningioma. Surgical and adjuvant treatment with clinical and PET evaluation

    International Nuclear Information System (INIS)

    Gudjonsson, O.

    2001-01-01

    The treatment strategy for skull base meningiomas remains a controversial issue. Because of the proximity of these tumours to critical neurovascular structures, the risk for vascular damage and new cranial neuropathies postoperatively is significant. To avoid unacceptable neurological deficits the surgical treatment strategy includes different surgical approaches and a subtotal removal of these tumours in some cases. However, because the rate of recurrence and progression is significant in these patients, a demand for adjuvant treatment and better prognostic methods is called for so that treatment and follow-up can be tailored to each patient. Accordingly, we have chosen to evaluate general outcome and facial nerve function after translabyrinthine and transcochlear approaches for cerebellopontine angle (CPA) meningiomas. Furthermore, we have evaluated two adjuvant treatments, namely, irradiation by high-energy proton beams and medical treatment with interferon-alpha as well as evaluation of the treatment effect with 11 C-L-methionine PET. In addition, we have evaluated a new PET tracer ( 76 Br-BrdU) for 'in vivo' determination of the growth potential of intracranial tumours. Conclusion: The translabyrinthine and transcochlear approaches are apparently safe surgical procedures in the treatment of CPA meningiomas. Proton beam therapy is technically feasible as suggested by the fact that only minimal side effects were observed. Moreover, none of the meningiomas treated have shown progression during a 36-month follow-up. Our results indicate that IFN-alpha can be an effective oncostatic treatment for certain patients with meningiomas. The 11 C-L-methionine PET method might be used as a complement to CT or MRI in the evaluation of the effect of proton beam and IFN-alpha treatment in meningiomas. The present attempt failed to demonstrate that the PET tracer 76 Br-BrdU could be used for the non-invasive characterisation of growth potential in brain, tumours

  5. Skull base meningioma. Surgical and adjuvant treatment with clinical and PET evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Gudjonsson, O

    2001-05-01

    The treatment strategy for skull base meningiomas remains a controversial issue. Because of the proximity of these tumours to critical neurovascular structures, the risk for vascular damage and new cranial neuropathies postoperatively is significant. To avoid unacceptable neurological deficits the surgical treatment strategy includes different surgical approaches and a subtotal removal of these tumours in some cases. However, because the rate of recurrence and progression is significant in these patients, a demand for adjuvant treatment and better prognostic methods is called for so that treatment and follow-up can be tailored to each patient. Accordingly, we have chosen to evaluate general outcome and facial nerve function after translabyrinthine and transcochlear approaches for cerebellopontine angle (CPA) meningiomas. Furthermore, we have evaluated two adjuvant treatments, namely, irradiation by high-energy proton beams and medical treatment with interferon-alpha as well as evaluation of the treatment effect with {sup 11}C-L-methionine PET. In addition, we have evaluated a new PET tracer ({sup 76}Br-BrdU) for 'in vivo' determination of the growth potential of intracranial tumours. Conclusion: The translabyrinthine and transcochlear approaches are apparently safe surgical procedures in the treatment of CPA meningiomas. Proton beam therapy is technically feasible as suggested by the fact that only minimal side effects were observed. Moreover, none of the meningiomas treated have shown progression during a 36-month follow-up. Our results indicate that IFN-alpha can be an effective oncostatic treatment for certain patients with meningiomas. The {sup 11}C-L-methionine PET method might be used as a complement to CT or MRI in the evaluation of the effect of proton beam and IFN-alpha treatment in meningiomas. The present attempt failed to demonstrate that the PET tracer {sup 76}Br-BrdU could be used for the non-invasive characterisation of growth potential in

  6. Managing information risk a director's guide

    CERN Document Server

    Mitchell, Stewart

    2009-01-01

    This pocket guide addresses the scope of risks involved in a modern IT system, and outlines strategies for working through the process of putting risk management at the heart of your corporate culture. Given that no two companies are the same, this pocket guide should not be taken as a step-by-step guide, but should provide decision makers with a solid overview of the factors they need to consider and a framework for implementing a regime that suits their needs.

  7. Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan

    OpenAIRE

    Urushiyama, Hirokazu; Jo, Taisuke; Yasunaga, Hideo; Yamauchi, Yasuhiro; Matsui, Hiroki; Hasegawa, Wakae; Takeshima, Hideyuki; Hiraishi, Yoshihisa; Mitani, Akihisa; Fushimi, Kiyohide; Nagase, Takahide

    2017-01-01

    Background The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. Methods We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, be...

  8. Preparation and evaluation of functional foods in adjuvant arthritis

    OpenAIRE

    Al-Okbi, S. Y.; Mohamed, D. A.

    2012-01-01

    Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functio...

  9. Tocotrienols are good adjuvants for developing cancer vaccines

    International Nuclear Information System (INIS)

    Abdul Hafid, Sitti Rahma; Radhakrishnan, Ammu Kutty; Nesaretnam, Kalanithi

    2010-01-01

    Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy

  10. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  11. Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

    International Nuclear Information System (INIS)

    Welz, Stefan; Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

    2007-01-01

    Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m 2 ), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m 2 /24 h). A dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m 2 in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m 2 administered before and after simultaneous 5-FU and radiotherapy

  12. The identification of plant lectins with mucosal adjuvant activity

    Science.gov (United States)

    Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

    2001-01-01

    To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

  13. AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial

    NARCIS (Netherlands)

    McElhaney, J.E.; Beran, J.; Devaster, J.M.; Esen, M.; Launay, O.; Leroux-Roels, G.; Ruiz-Palacios, G.M.; Essen, G.A. van; Caplanusi, A.; Claeys, C.; Durand, C.; Duval, X.; Idrissi, M. El; Falsey, A.R.; Feldman, G.; Frey, S.E.; Galtier, F.; Hwang, S.J.; Innis, B.L.; Kovac, M.; Kremsner, P.; McNeil, S.; Nowakowski, A.; Richardus, J.H.; Trofa, A.; Oostvogels, L.; Verheugt, F.W.; et al.,

    2013-01-01

    BACKGROUND: We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS: We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons.

  14. Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

    Directory of Open Access Journals (Sweden)

    Mridula Krishnan

    2017-08-01

    Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

  15. Analysis of adjuvant treatment with chemoradiation in gastric cancer

    International Nuclear Information System (INIS)

    Fallas Solis, Elias

    2008-01-01

    The Hospital San Juan de Dios has analyzed the benefit of patients with gastric cancer who undergo surgery after receiving adjuvant chemoradiation. A retrospective study was performed reviewing records of patients during the period 1 January 2001 to December 31, 2005. These patients have been discharged with a diagnosis of gastric cancer and have received a complete resection with curative gastric malignancy and adjuvant chemoradiation according to the protocol established by Dr. MacDonald. In the study 0116. 743 patients were discharged to Hospital San Juan de Dios, 1 in 20 has been possible to diagnose gastric cancer at early stages for a total of 28 patients. The results obtained were compared at the Hospital San Juan de Dios with those published by Dr. MacDonald. The over-life of 3 years in the chemoradiation group in Hospital San Juan de Dios has been of 42.9% and 50% in the study MacDonald. The group that has not received adjuvant the over-life in the same period has been of 20 % in HSJD and 41% in the study MacDonald, being lower percentage of patients with this over-life, but greater range of difference. [es

  16. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  17. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Science.gov (United States)

    Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  18. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Licht, Peter B; Schytte, Tine; Jakobsen, Erik

    2014-01-01

    BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p....02). No significant difference between video-assisted thoracoscopic surgery and thoracotomy was seen regarding chemotherapy compliance (p=0.17), number of chemotherapy cycles (p=0.60), or time from surgery to chemotherapy (p = 0.41). CONCLUSIONS: Complete national data do not support the widespread assumption...

  19. Antinociceptive effect of chlorphenesin carbamate in adjuvant arthritic rats.

    Science.gov (United States)

    Okuyama, S; Aihara, H

    1987-02-01

    The antinociceptive effect of chlorphenesin carbamate (CPC) and mephenesin were examined in adjuvant arthritic rats. In the behavioral study, CPC (100-400 mg/kg, p.o.) but not mephenesin (100-400 mg/kg, p.o.) had a dose-dependent antinociceptive effect, determined using the flexion test. In the electrophysiological study, CPC (25-50 mg/kg, i.v.) but not mephenesin (50 mg/kg, i.v.) depressed the evoked neuronal responses of nociceptive neurons in the ventrobasal thalamus (VB), while the evoked responses of non-nociceptive neurons were not depressed by either CPC (50 mg/kg, i.v.) or mephenesin (50 mg/kg, i.v.). The spontaneous firings of the VB nociceptive neurons were depressed by both CPC (50 mg/kg, i.v.) and mephenesin (50 mg/kg, i.v.). However, mephenesin (50 mg/kg, i.v.) but not CPC (50 mg/kg, i.v.) also depressed the spontaneous firings of the mesencephalic reticular formation (RF), in these adjuvant arthritic rats. These results indicate that CPC but not mephenesin, has an antinociceptive action in adjuvant arthritic rats.

  20. Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

    Science.gov (United States)

    Turánek, Jaroslav; Ledvina, Miroslav; Kasná, Andrea; Vacek, Antonín; Hríbalova, Vera; Krejcí, Josef; Miller, Andrew D

    2006-04-12

    The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

  1. Neonatal Vaccination: Challenges and Intervention Strategies.

    Science.gov (United States)

    Morris, Matthew C; Surendran, Naveen

    2016-01-01

    While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.

  2. Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

    Science.gov (United States)

    Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

    2005-03-01

    The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

  3. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  4. Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

    Directory of Open Access Journals (Sweden)

    Cheng Tsui

    2012-01-01

    Full Text Available Abstract Background Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer. Methods In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0, and to obtain the utility value by the standard gamble (SG and visual scale (VS methods. Total medical cost was assessed from the (National Health Insurance NHI payer's perspective. Results Survival at 11 years was significantly better in the groserelin group (P Conclusions Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

  5. Adjuvant endocrine and chemotherapy for early breast cancer

    International Nuclear Information System (INIS)

    Henderson, I. Craig

    1996-01-01

    Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

  6. An observer-blind, randomized, multi-center trial assessing long-term safety and immunogenicity of AS03-adjuvanted or unadjuvanted H1N1/2009 influenza vaccines in children 10-17 years of age.

    Science.gov (United States)

    Poder, Airi; Simurka, Pavol; Li, Ping; Roy-Ghanta, Sumita; Vaughn, David

    2014-02-19

    Vaccination is an effective strategy to prevent influenza. This observer-blind, randomized study in children 10-17 years of age assessed whether the hemagglutination inhibition (HI) antibody responses elicited by H1N1/2009 vaccines adjuvanted with AS03 (an adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion) or without adjuvant, met the European regulatory immunogenicity criteria at Days 21 and 182. Three hundred and ten healthy children were randomized (3:3:3:5) to receive one dose of 3.75 μg hemagglutinin (HA) AS03A-adjuvanted vaccine, one or two doses of 1.9 μg HA AS03B-adjuvanted vaccine, or one dose of 15 μg HA pandemic vaccine. All children received a booster dose of the allocated vaccine at Day 182. Serum samples were tested for HI antibody response at Days 21, 42, 182 and 189. All vaccination regimens elicited HI antibody responses that met the European regulatory criteria at Days 21 and 42. HI antibody responses fulfilling European regulatory criteria were still observed six months after the first vaccine dose in all study vaccines groups. Two doses of 1.9 μg HA AS03B-adjuvanted vaccine elicited the strongest HI antibody response throughout the study. The non-adjuvanted 15 μg HA vaccine elicited a lower HI antibody response than the AS03-adjuvanted vaccines. At Day 189, the European regulatory criteria were met for all vaccines with baseline HI antibody titers as reference. An anamnestic response for all vaccines was suggested at Day 189, based on the rapid increase in HI antibody geometric mean titers (1.5-2.5-fold increase). Injection site reactogenicity was higher following the AS03-adjuvanted vaccines compared with the non-adjuvanted vaccine. No safety concerns were identified for any study vaccine. All study vaccines elicited HI antibody responses that persisted at purported protective levels through six months after vaccination and fulfilled the European regulatory criteria. Copyright © 2013 The Authors. Published

  7. Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine.

    Science.gov (United States)

    Durando, Paolo; Iudici, Rocco; Alicino, Cristiano; Alberti, Marisa; de Florentis, Daniela; Ansaldi, Filippo; Icardi, Giancarlo

    2011-01-01

    Vaccination is universally considered as the principal measure for the control of influenza, which represents a significant burden worldwide, both from a health-care and a socio-economic viewpoint. Conventional non-adjuvanted trivalent influenza vaccines (TIVs) have been recognized as having some deficiencies, such as suboptimal immunogenicity particularly in the elderly, in patients with severe chronic diseases and immunocompromized, indeed, those groups of the population at higher risk of developing severe complications following influenza infection, when compared to healthy adults. Moreover, the protection offered by conventional vaccines may be reduced by periodic antigenic drifts, resulting in a mismatch between the circulating and vaccinal viral strains. Another gap regarding currently available vaccines is related to the egg-based manufacturing system for their production: not only the length of time involved with the latter but also the limited capacity of this platform technology represent a major limitation for the active prevention of influenza, which is particularly important in the case of a new pandemic strain. New technologies used in vaccine composition, administration and manufacture have led to major advances during the last few years, and clinical researchers have continued to work hard, investigating several different strategies to improve the performance of influenza vaccines: namely, the addition of different adjuvants (i.e., MF59- and AS03-vaccines, virosomal formulations), the use of alternative routes of administration or manufacture (i.e., intradermal, nasal and oral vaccines and cell culture- and reverse genetic-based vaccines) or of high doses of antigen, and the development of DNA-vaccines, or the use of conserved viral epitopes (i.e., the extracellular portion of the M2 protein, the nucleoprotein and some domains of the hemagglutinin), in the attempt to produce a "universal target" antigen vaccine. The knowledge acquired represents a

  8. Expert Guide

    DEFF Research Database (Denmark)

    Heiselberg, Per

    , their benefits and limitations, economical feasibility and impact on energy savings, company image, comfort, productivity, building functionality and flexibility and gives guidance on design of these concepts, including integration of responsive building elements and HVAC-systems and build examples......This guide summarizes the work of Subtask B of IEA-ECBCS Annex 44 “Integrating Environmentally Responsive Elements in Buildings” and is based on the contributions from the participating countries. The publication is an official Annex report. With a focus on innovative building concepts...

  9. Development of a minimal saponin vaccine adjuvant based on QS-21

    Science.gov (United States)

    Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

    2014-07-01

    Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

  10. Guide to National Security Policy and Strategy

    Science.gov (United States)

    2006-06-01

    a part of contemporary post- structuralist and social constructivist approaches to international theory , often accompanied by quasi-indifference to...Richard Langhorne, The Practice of Diplomacy: Its Evolution, Theory , and Administration , London and New York: Routledge, 1995; David Jablonsky, Paradigm...61 II. Strategic Theory and Formulation

  11. Control Strategies for Guided Collective Motion

    Science.gov (United States)

    2015-02-27

    J.K. Parrish , “Oscillator models and collective motion,” IEEE Control Systems Magzine, Vol. 27, 2007, pp. 89-105. [18] S. H. Strogatz , “From Kuramoto...Automatic Control, 54(2), 2009, pp. 353-357. [21] H. Hong and S. H. Strogatz , “Kuramoto Model of Coupled Oscillators with Positive and Negative...2013) provided similar results by utilizing a modified Kuramoto model ( Strogatz (2000)). Paley (2008) proposed a Lyapunov-based design methodology to

  12. Counterfeit Parts Prevention Strategy Guide Product Overview

    Science.gov (United States)

    2014-05-08

    avoidance • Develop a risk assessment methodology when using unauthorized or non- franchised suppliers • Identify methods to ensure and verify sub-tier...comments received – Obtain endorsement across team members for product and follow-on recommendations • Workshop Accomplishments – Obtained buy -in

  13. Interferon alpha for the adjuvant treatment of cutaneous melanoma.

    Science.gov (United States)

    Mocellin, Simone; Lens, Marko B; Pasquali, Sandro; Pilati, Pierluigi; Chiarion Sileni, Vanna

    2013-06-18

    Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates

  14. Guider des stratégies de compréhension de l'oral en ALAO : le cas de l'inférence Guiding oral comprehension strategies with CALL: the case of inference

    Directory of Open Access Journals (Sweden)

    Cécile Poussard

    2003-06-01

    Full Text Available L'inférence est une des stratégies à l'oeuvre dans le processus de compréhension de l'oral. Quelques exemples de tâches d'inférence extraites de la trame pédagogique que nous avons conçue pour un projet de didacticiel d'anglais, montrent comment on peut susciter l'activité interprétative de l'apprenant, en ciblant les tâches sur des passages opaques d'interviews et en guidant l'identification des obstacles (traits de l'oralité et la combinaison d'éléments facilitateurs (éléments discursifs, prosodiques... pour lui permettre de reconstruire ou compenser ce qui peut poser problème à  l'écoute. En proposant un travail conscient et systématique de l'inférence, notre objectif est que cette capacité devienne opératoire chez l'apprenant, qu'elle soit largement automatisée.Inferring is one of the strategies at work in the comprehension process. A few examples of inferring tasks, taken from the pedagogical script that we created for a future CALL (Computer Assisted Language Learning product, show how the learner interpretation can be elicited, by focusing the tasks on opaque interview extracts and by guiding the identification of obstacles (oral features and the combination of facilitating elements (discursive, prosodic..., elements in order to enable the learner to rebuild or compensate for what can be difficult to listen to. By offering conscious and systematic work on inference, our goal is to help the learner build an operating (i.e. mainly automatized capacity.

  15. Use of chemical and biological adjuvants to achieve the optimum application of radiological techniques

    International Nuclear Information System (INIS)

    Azab, K.S.

    2010-01-01

    Nowadays, the optimization and attainment of maximum guarantee are representing the real challenge for the nuclear technology exercise. The Adjuvant techniques might be considered one of the available tactics for the developing, reducing risk and facilitating secure clearing of nuclear waste in the field of radiation technology applications. The history describes the belief that an adjuvant is required for immunity because the immune system evolved to respond to dangerous situations such as infections, and the presence of an adjuvant is the mechanism used to identify these situations. In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect. Adjuvants are coming increasingly into focus for vaccine developers since many novel split and subunit vaccines are insufficiently immunogenic on their own. Among the used today are alum (aluminum hydroxide) and Glycosyl ceramides. It is worth mentioning that manufacturers already had produced thousands of different adjuvants, for both industrial and agricultural purposes. Today, the agricultural and horticultural industries are being overwhelmed by adjuvant choices. Complete Freunds adjuvant is the adjuvant used in animal research studies of basic and applied immunology. (author)

  16. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    Science.gov (United States)

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Context-dependent neural activation: internally and externally guided rhythmic lower limb movement in individuals with and without neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Madeleine Eve Hackney

    2015-12-01

    Full Text Available Parkinson’s Disease (PD is a neurodegenerative disorder that has received considerable attention in allopathic medicine over the past decades. However, it is clear that, to date, pharmacological and surgical interventions do not fully address symptoms of PD and patients’ quality of life. As both an alternative therapy and as an adjuvant to conventional approaches, several types of rhythmic movement (e.g., movement strategies, dance, tandem biking, tai chi have shown improvements to motor symptoms, lower limb control and postural stability in people with PD (Amano, Nocera, Vallabhajosula, Juncos, Gregor, Waddell et al., 2013; Earhart, 2009; M. E. Hackney & Earhart, 2008; Kadivar, Corcos, Foto, & Hondzinski, 2011; Morris, Iansek, & Kirkwood, 2009; Ridgel, Vitek, & Alberts, 2009. However, while these programs are increasing in number, still little is known about the neural mechanisms underlying motor improvements attained with such interventions. Studying limb motor control under task specific contexts can help determine the mechanisms of rehabilitation effectiveness. Both internally guided (IG and externally guided (EG movement strategies have evidence to support their use in rehabilitative programs. However, there appears to be a degree of differentiation in the neural substrates involved in IG versus EG designs. Because of the potential task specific benefits of rhythmic training within a rehabilitative context, this report will consider the use of IG and EG movement strategies, and observations produced by functional magnetic resonance imaging (fMRI and other imaging techniques. This review will present findings from lower limb imaging studies, under IG and EG conditions for populations with and without movement disorders. We will discuss how these studies might inform movement disorders rehabilitation (in the form of rhythmic, music-based movement training and highlight research gaps. We believe better understanding of lower limb neural

  18. A case of delayed anastomotic fistula occurred nine years after adjuvant radiotherapy following rectal cancer surgery

    International Nuclear Information System (INIS)

    Matsumoto, Tomoko; Fukao, Takashi; Kuriyama, Shiho; Ohtawa, Yasuyuki; Waku Toshihiko

    2017-01-01

    The patient was a 72-year-old man who underwent a low anterior resection for rectal cancer in 2007 (RbRa, pT4a, pN1, cM0, pStage 3a). With the surgically stripped surface testing positive, the pelvic cavity was subjected to 50 Gy of radiation as part of adjuvant radiotherapy. In December 2015, the patient presented with anal pain and bloody stool.A CT scan revealed a pelvic abscess accompanied by gas patterns around the anastomotic site, and a colonoscopy detected formation of a fistula at the anastomotic site. Although CT-guided drainage was performed in response, a new abscess was formed promptly. In April 2016, laparoscopic colostomy with double orifices was performed on the transverse colon. Thereafter the abscesses in the buttocks required four sessions of incision and drainage. The condition improved with no purulent discharge after December 2016. As of 11 months after the colostomy, the pelvic abscess is gradually contracting, though some fistulas have remained. The patient has been followed up on an ambulatory basis.This case is considered to be of an intrapelvic abscess associated with the delayed anastomotic fistula occurred after a lapse of 9 years following irradiation. (author)

  19. Adjuvant radiotherapy for phyllodes tumor of the breast

    International Nuclear Information System (INIS)

    Chaney, Arthur W.; Pollack, Alan; Zagars, Gunar K.

    1997-01-01

    Purpose/Objective: The role of radiotherapy for the treatment of phyllodes tumors of the breast remains controversial. Adjuvant radiotherapy is often cited in the existing literature as not providing any benefit over surgical treatment alone. The data supporting this belief are anecdotal. There are also anecdotal reports that radiotherapy may have a role in cases wherein the risk of local failure is high. As with breast carcinomas, conservative surgery (wide local excision) for phyllodes tumors is associated with about a 50% local recurrence rate; diffuse or bulky disease and/or malignant histology are also associated with high local failure rates. We are unaware of any series that examines the role of adjuvant radiotherapy in the management of phyllodes tumor of the breast. We present here a retrospective study of eight patients so treated at MD Anderson Cancer Center. Materials and Methods: Eight patients have been treated with radiotherapy for non-metastatic phyllodes tumor of the breast at MD Anderson Cancer Center between December 1988 and August 1993. All patients were female; the median age was 43 years, with a range of 19 to 62 years. All patients presented with a breast mass, which was associated with pain in one patient, and was ulcerative in three. Results: Tumor size ranged from 3.5 to 16 cm, with a median diameter of 10.4 cm. Six patients had tumors in the upper outer quadrant, and two patients had upper inner tumors. Five patients had malignant tumors, two patients were classified as benign, and one was of indeterminate malignant potential. All five of the malignant tumors displayed stromal overgrowth on pathologic review. The remaining benign and indeterminate tumors lacked this feature. One patient with a benign tumor had a history of two prior recurrences. Primary surgery consisted of either lumpectomy in two patients or mastectomy in six patients. Axillary level I/II lymph node dissections were performed in 5 patients and no involvement was seen

  20. PFP functional development planning guide

    International Nuclear Information System (INIS)

    SINCLAIR, J.C.

    1999-01-01

    The PFP Functional Development Planning Guide presents the strategy and process used for the identification, development, and analysis of functions (activities) necessary to satisfy the requirements within the Plutonium Finishing Plant (PFP) integrated project baseline. The functional analysis will provide the basis for the development of a function driven work breakdown structure. Future revisions to this document will include as attachments the results of the PFP Functional Analysis resulting from this approach. This document is intended be a Project-owned management tool. As such, the guide will periodically require revisions resulting from improvements of the information, processes, and techniques as now described

  1. Selective use of adjuvant radiation therapy in resectable colorectal adenocarcinoma

    International Nuclear Information System (INIS)

    Cohen, A.M.; Gunderson, L.L.; Welch, C.E.

    1981-01-01

    Colorectal cancer recurs within the operative field in 10-20 per cent of patients undergoing potentially curative surgery. In certain subgroups, the recurrence rate is 20-50 per cent. There are some data to suggest either preoperative or postoperative radiation therapy as an adjuvant to potentially curative surgery can reduce the local operative failure rate. However, since radiation therapy has significant side effects, patient selection to maximize the therapeutic ratio is important. This report defines the criteria at the Massachusetts General Hospital for selection of patients with colorectal cancer for adjuvant radiation therapy, defines radiation therapy-surgery sequencing alternatives used, and describes techniques to reduce radiation side effects. Over a period of three and a half years, 196 patients received adjuvant radiation therapy: 51 patients received either moderate or low dose preoperative radiation therapy to rectal or rectosigmoid cancers, and 161 patients received postoperative radiation therapy to the pelvis or extrapelvic colonic tumor-lymph node beds. Some patients who received low-dose preoperative radiation therapy also received moderate-dose postoperative radiation therapy. We prefer moderate-dose postoperative radiation therapy as the approach most likely to decrease the local recurrence rate with minimal interference with surgical procedures and late small-bowel complications. Patients who received postoperative radiation therapy were those without distant metastases, whose primary tumor pathology revealed macroscopic or extensive microscopic transmural tumor penetration into extraperitoneal tissues. Careful case selection, multiple field techniques, the use of reperitonealization, omental flaps, and retroversion of the uterus into the pelvis were combined with postoperative small-bowel x-rays, bladder distention, and lateral portals to minimize radiation damage to normal structures

  2. Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

    Science.gov (United States)

    Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

    2017-06-01

    This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Melanoma Metastases to the Neck Nodes: Role of Adjuvant Irradiation

    International Nuclear Information System (INIS)

    Strojan, Primoz; Jancar, Boris; Cemazar, Maja; Perme, Maja Pohar; Hocevar, Marko

    2010-01-01

    Purpose: To review experiences in the treatment of regionally advanced melanoma to the neck and/or parotid with emphasis on the role of adjuvant radiotherapy. Patients and Methods: Clinical and histopathologic data, treatment details, and outcomes in patients treated during the period 2000-2006 at the Institute of Oncology, Ljubljana, Slovenia, were reviewed. Results: A total of 40 patients with 42 dissections underwent surgery, and 43 patients with 45 dissections received irradiation postoperatively to a median equivalent dose (eqTD 2 : 2 Gy/fraction, 1 fraction/day, 5 fractions/week) of 60 Gy (range, 47.8-78.8). Regional control 2 years after surgery was 56% (95% confidence interval [CI] 40-72%) and after postoperative radiotherapy 78% (CI 63-92%) (p = 0.015). On multivariate analysis, postoperative radiotherapy (yes vs. no: hazard ratio [HR] 6.3, CI 2.0-20.6) and sum of the risk factors present (i.e., risk factor score; HR 1.7 per score point, CI 1.2-2.6) were predictive for regional control. On logistic regression testing, the number of involved nodes was associated with the probability of distant metastases (p = 0.021). The incidence of late toxicity did not correlate with the mode of therapy, eqTD 2 , or fractionation pattern. Conclusions: Adjuvant radiotherapy has the potential to compensate effectively for the negative impact of adverse histopatologic features to disease control in a dissected nodal basin. More conventionally fractionated radiotherapy regimens using fraction doses of 2-2.5 Gy, with cumulative eqTD 2 ≥60 Gy, are recommended. The number of involved lymph nodes is proposed as an additional criterion for limiting the implementation of adjuvant irradiation.

  4. Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

    Directory of Open Access Journals (Sweden)

    Annalisa Cortesi

    2017-06-01

    Full Text Available Purpose: The standard primary treatment for soft tissue sarcoma (STS is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT plus postoperative external beam radiation therapy (EBRT in patients with intermediate-high risk STS. Material and methods : BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS and local control (LC in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS, and OS. Results : From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015, and in lower limb tumors vs. other sites (p = 0.027. An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034. Conclusions : The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC.

  5. Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

    Science.gov (United States)

    Cortesi, Annalisa; Galuppi, Andrea; Arcelli, Alessandra; Romani, Fabrizio; Mattiucci, Gian Carlo; Bianchi, Giuseppe; Ferrari, Stefano; Ferraro, Andrea; Farioli, Andrea; Gambarotti, Marco; Righi, Alberto; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Buwenge, Milly; Valentini, Vincenzo; Morganti, Alessio Giuseppe; Donati, Davide; Cammelli, Silvia

    2017-01-01

    Purpose The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC. PMID:28725250

  6. Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation

    International Nuclear Information System (INIS)

    Chang, Daniel T.; Amdur, Robert J.; Morris, Christopher G. M.S.; Mendenhall, William M.

    2006-01-01

    Purpose: To examine locoregional control after adjuvant radiotherapy (RT) for cutaneous melanoma and compare outcomes between conventional fractionation and hypofractionation. Methods and Materials: Between January 1980 and June 2004, 56 patients with high-risk disease were treated with adjuvant RT. Indications for RT included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm, more than three lymph nodes involved, extracapsular extension, gross residual disease, close or positive margins, or satellitosis. Hypofractionation was used in 41 patients (73%) and conventional fractionation was used in 15 patients (27%). Results: The median age was 61 years (21->90). The median follow-up among living patients was 4.4 years (range, 0.6-14.4 years). The primary site was located in the head and neck in 49 patients (87%) and below the clavicles in 7 patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field regional failures (5%), and 24 (43%) distant failures. The 5-year in-field locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall survival (OS) was 57% and 46%, respectively. The only factor associated with ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two patients (4%) who experienced severe late complications, osteoradionecrosis of the temporal bone and radiation plexopathy, and both received hypofractionation (5%). Conclusions: Although surgery and adjuvant RT provides excellent locoregional control, distant metastases remain the major cause of mortality. Hypofractionation and conventional fractionation are equally efficacious

  7. Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

    Science.gov (United States)

    Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

    2016-01-01

    Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

  8. Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

    OpenAIRE

    Škrnjug, Ivana; Guzmán, Carlos Alberto; Ruecker, Christine

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice....

  9. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    International Nuclear Information System (INIS)

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy

  10. Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, M M; Dallow, K C; Zietman, A L; Althausen, A F; Heney, N M; McGovern, F J; Shipley, W U

    1995-07-01

    Purpose: To assess the ability of adjuvant irradiation to prevent PSA failure in cases of pT3N0 disease, and of salvage irradiation to durably suppress a rising PSA following radical prostatectomy. Methods and Materials: 62 patients treated by post-operative radiation therapy (60-64Gy in 1.8Gy fractions to the tumor bed) between 1988 and 1993 were evaluated. All had complete pre- and post-radiation PSA data. Median follow up was 3.2 years from time of surgery and 2.2 years from irradiation. 20 patients had Gleason grade 3 disease (moderately differentiated) and 41 Gleason 4-5 (poorly differentiated). 46 had positive inked surgical margins, 18 involved seminal vesicles and 5 had palpable recurrent disease. None had known nodal or metastatic disease. 32 patients underwent adjuvant treatment (undetectable PSA at time of irradiation) and 30 salvage (detectable PSA at time of irradiation). Kaplan-Meier life table analysis was employed. The endpoint studied was freedom from biochemical failure. This was defined as a rise in the PSA of greater than 10% (intra laboratory error <8%) or a previously undetectable PSA becoming detectable. Results: The overall actuarial freedom from biochemical failure at 4 years from radiotherapy was 59%. A significant difference was seen between those receiving adjuvant and those receiving salvage irradiation (71% vs 51%, p=0.03). Amongst those in the salvage group neither the PSA prior to surgery, the PSA at the time of irradiation, the seminal vesicle status, nor the Gleason score (3 vs 4-5) correlated significantly with outcome. The time interval between surgery and irradiation was, however, significant. Those being treated within 6 months fared better than those treated later (60% vs 36%, p=0.04). Further, those treated early were more likely to achieve an undetectable nadir PSA level (94% vs 71%). Conclusion: The addition of adjuvant irradiation appears to improve the 4 year biochemical disease-free survival of patients with poor

  11. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    International Nuclear Information System (INIS)

    Aftimos, Philippe G; Nasr, Elie A; Nasr, Dolly I; Noun, Roger J; Nasr, Fady L; Ghosn, Marwan G; El Helou, Joelle A; Chahine, Georges Y

    2010-01-01

    Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to

  12. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Directory of Open Access Journals (Sweden)

    Ghosn Marwan G

    2010-06-01

    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  13. Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

    Science.gov (United States)

    Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

    2015-08-01

    Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. © 2015 Poultry Science Association Inc.

  14. A linear maglev guide for machine tools

    Energy Technology Data Exchange (ETDEWEB)

    Tieste, K D [Inst. of Mechanics, Univ. of Hannover (Germany); Popp, K [Inst. of Mechanics, Univ. of Hannover (Germany)

    1996-12-31

    Machine tools require linear guides with high slide velocity and very high position accuracy. The three tasks of a linear guide - supporting, guiding and driving - shall be realised by means of active magnetic bearings (AMB). The resulting linear magnetically levitated (maglev) guide has to accomplish the following characteristics: High stiffness, good damping and low noise as well as low heat production. First research on a one degree-of-freedom (DOF) support magnet unit aimed at the development of components and efficient control strategies for the linear maglev guide. The actual research is directed to realise a five DOF linear maglev guide for machine tools without drive to answer the question whether the maglev principle can be used for a linear axis in a machine tool. (orig.)

  15. Development of Novel Protocol for Preclinical Monitoring the Release of Adjuvants Encapsulated Mucosal Delivery Carriers

    Directory of Open Access Journals (Sweden)

    Mohamed Ibrahim-Saeed

    2015-12-01

    Full Text Available This work contributes in vaccines down-stream process by introducing a novel platform for in-vitro monitoring of vaccine-adjuvant delivery profile as a crucial preclinical optimizing step in mucosal vaccines. Nano and micro particles of Calcium phosphate (Cap vaccine-adjuvant were encapsulated in Chitosan and Alginate polymeric carriers. Adjuvants release profiles monitored in a permeable bag at 37°C, pH 2, incubated in isotonic buffer for 96 hours. The released Calcium in the outer buffer was monitored and compared in-addition to the carrier’s swelling and biophysical properties. The adjuvants and carriers did not interfere with the proliferation of cultured hepatocytes an indicator of their safe use; Chitosan’s viscosity and swelling were higher than Alginate. Chitosan’s Zeta-potential was significantly high positive, while Cap and Alginate were negative. The prepared CaP and Chitosan particles were in nano-size, while the ready-made CaP adjuvant and Alginate were in micro-size using zeta-seizer and scanning electron-micrograph. The release of nano-size particle was in ascending, extended and controlled manner compared to micro-size adjuvant. Moreover, nano-adjuvant release profile from Chitosan was superior compared to Alginate. The core controlling factors in vaccine-adjuvant sustained release includes; smaller adjuvant particles (nano-size, carrier’s low swelling, high viscosity and importantly carrier-adjuvant entrapment reversibility. Chitosan offers sustained ascending superior capacity in releasing Nano-Cap adjuvant. This novel in-vitro pre-clinical study answer a crucial downstream preparative step for optimizing mucosal vaccines before their direct routine in-vivo trial on animal regardless of adjuvant’s particle size or delivery kinetics.

  16. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    International Nuclear Information System (INIS)

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-01-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

  17. Adaptive radiotherapy for long course neo-adjuvant treatment of rectal cancer

    International Nuclear Information System (INIS)

    Nijkamp, Jasper; Marijnen, Corrie; Herk, Marcel van; Triest, Baukelien van; Sonke, Jan-Jakob

    2012-01-01

    Purpose: To quantify the potential margin reduction with adaptive radiotherapy (ART) during neo-adjuvant treatment of locally-advanced rectal cancer. Methods and materials: Repeat CT scans were acquired for 28 patients treated with 25 × 2 Gy, daily during the first week, and followed by weekly scans. The CTV was delineated on all scans, and shape variation was estimated. Five ART strategies were tested, consisting of an average CTV over the planning CT and one to five repeat CTs. Required PTV margins were calculated for adapted and non-adapted treatment. The strategy with the least PTV volume over the whole treatment was selected and bowel area dose reduction was estimated. Results: Substantial systematic and random shape variation demanded for a PTV margin up to 2.4 cm at the upper-anterior part of the CTV. Plan adaptation after fraction 4 resulted in a maximum 0.7 cm margin reduction and a significant PTV reduction from 1185 to 1023 cc (p < 0.0001). The bowel area volume receiving 15, 45, and 50 Gy was reduced from 436 to 402 cc, 111 to 81 cc, and 49 to 29 cc, respectively (p < 0.0001). Conclusions: With adaptive radiotherapy, maximum required PTV margins can be reduced from 2.4 to 1.7 cm, resulting in significantly less dose to the bowel area.

  18. Which prognostic factors influence the outcome of patients with surgically staged endometrial cancer treated with adjuvant radiation?

    International Nuclear Information System (INIS)

    Greven, Kathryn M.; Corn, Benjamin W.; Case, Douglas; Purser, Phillip; Lanciano, Rachelle M.

    1997-01-01

    Purpose: Despite the fact that retrospective reviews have documented pelvic failure rates ranging from 15-20% in patients with high-risk uterine-confined endometrial cancer who have received no or 'inadequate' RT, the role of RT has been questioned. We sought to analyze pelvic control and disease-free survival for a large data base of women with corpus cancers managed with initial surgery followed by adjuvant irradiation. Methods and Materials: Between 1983 and 1993, 294 patients received adjuvant postoperative RT from one of three academic radiation practices. RT consisted of vaginal brachytherapy alone in 28 patients, pelvic RT in 173 patients, pelvic RT with vaginal brachytherapy in 97 patients, and whole abdominal RT in 2 patients. Lymph nodes were evaluated in 49%. The median number of pelvic and periaortic LN in the pathology specimen were 6 and 4, respectively. Median follow up was 63 months. Results: 5-year disease-free survival (DFS) rate and pelvic control rates were 86 and 95%, respectively. Patient-related, treatment-related, and tumor-related characteristics were assessed for the effect on time to relapse. Unfavorable histology, older age, and capillary space invasion were univariately associated with decreased DFS and pelvic control. Pathologic Stage II patients had significantly worse DFS than Stage I patients. Multivariate analysis revealed that age, capillary space invasion, and histology were jointly predictive of disease free survival. Conclusion: The excellent pelvic control and disease-free survival of patients with uterine-confined disease in this series suggest that adjuvant RT should continue for patients with high risk disease. This analysis of a large group of postoperatively treated patients will provide a basis for determining alternative treatment strategies for patients who have an increased risk of disease recurrence despite RT

  19. A Guide to Effective School Leadership Theories

    Science.gov (United States)

    Lynch, Matthew

    2012-01-01

    Educational administrators know that leadership requires hundreds of judgments each day that require a sensitivity and understanding of various leadership strategies. Bridging the gap between the academic and practical world, "A Guide to Effective School Leadership Theories" provides an exploration of ten dominant leadership strategies to give…

  20. Adjuvant activity of peptidoglycan monomer and its metabolic products.

    Science.gov (United States)

    Halassy, Beata; Krstanović, Marina; Frkanec, Ruza; Tomasić, Jelka

    2003-02-14

    Peptidoglycan monomer (PGM) is a natural compound of bacterial origin. It is a non-toxic, non-pyrogenic, water-soluble immunostimulator potentiating humoral immune response to ovalbumin (OVA) in mice. It is fast degraded and its metabolic products-the pentapeptide (PP) and the disaccharide (DS)-are excreted from the mammalian organism upon parenteral administration. The present study investigates: (a). whether PGM could influence the long-living memory generation; (b). whether metabolic products retain adjuvant properties of the parent compound and contribute to its adjuvanticity. We report now that mice immunised twice with OVA+PGM had significantly higher anti-OVA IgG levels upon challenge with antigen alone 6 months later in comparison to control group immunised with OVA only. PP and DS were prepared enzymatically in vitro as apyrogenic and chemically pure compounds. When mice were immunised with OVA plus PP and DS, respectively, the level of anti-OVA IgGs in sera was not higher than in mice immunised with OVA alone, while PGM raised the level of specific antibodies. Results implicate that the adjuvant active molecule, capable of enhancing long-living memory generation, is PGM itself, and none of its metabolic products.

  1. Preparation and evaluation of functional foods in adjuvant arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Al-Okbi, S. Y.; Mohamed, D. A.

    2012-07-01

    Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended. (Author) 42 refs.

  2. [Environmental pollutants as adjuvant factors of immune system derived diseases].

    Science.gov (United States)

    Lehmann, Irina

    2017-06-01

    The main task of the immune system is to protect the body against invading pathogens. To be able to do so, immune cells must be able to recognize and combat exogenous challenges and at the same time tolerate body-borne structures. A complex regulatory network controls the sensitive balance between defense and tolerance. Perturbation of this network ultimately leads to the development of chronic inflammation, such as allergies, autoimmune reactions, and infections, because the immune system is no longer able to efficiently eliminate invading pathogens. Environmental pollutants can cause such perturbations by affecting the function of immune cells in such a way that they would react hypersensitively against allergens and the body's own structures, respectively, or that they would be no longer able to adequately combat pathogens. This indirect effect is also known as adjuvant effect. For pesticides, heavy metals, wood preservatives, or volatile organic compounds such adjuvant effects are well known. Examples of the mechanism by which environmental toxins contribute to chronic inflammatory diseases are manifold and will be discussed along asthma and allergies.While the immune system of healthy adults is typically well able to distinguish between foreign and endogenous substances even under adverse environmental conditions, that of children would react much more sensible upon comparable environmental challenges. To prevent priming for diseases by environmental cues during that highly sensitive period of early childhood children are to be particularly protected.

  3. Controversies in breast cancer: adjuvant and neoadjuvant therapy.

    Science.gov (United States)

    Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

    2005-06-01

    Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

  4. Adjuvant chemotherapy followed by conformal chemoradiotherapy in gastric carcinoma

    International Nuclear Information System (INIS)

    Bouchbika, Z.; Quero, L.; Kouto, H.; Hennequin-Baruch, V.; Sergent, G.; Maylin, C.; Hennequin, C.; Gornet, J.M.; Munoz, N.; Cojean-Zelek, I.; Houdart, R.; Panis, Y.; Valleur, P.

    2008-01-01

    Purpose: Analysis of the feasibility and results of adjuvant chemotherapy followed by conformal chemoradiotherapy after surgery for gastric carcinoma. Patients and methods Twenty-six patients (R0 or R1) were treated postoperatively by three cycles of 5-fluorouracil (5-FU) and cisplatin, followed by a concomitant association of LV5FU2 chemotherapy with a conformal radiotherapy of 45 Gy. Results: The tumor was classified pT3-T4 in 77% of the patients and 92.5% had a nodal involvement (pN1: 54%; pN2: 31%). Feasibility (1) Adjuvant chemotherapy: nausea/vomiting grade II/III: 12 patients (48%); neutropenia grade III/IV: two patients; completed in all patients, except one. (2) Chemoradiotherapy: nausea/vomiting grade II/III: 10 patients; diarrhea grade II/3: two patients; oesophagitis grade II/III: two patients; myocardial infarction/pulmonary embolism: two patients. All patients except one received the planned dose of 45 Gy. Radiotherapy was interrupted in six cases, with a median duration of 14 days. Survival: with a median follow-up of 30 months, 65% of the patients were alive without disease; median survival was 32 months. Conclusion: This postoperative schedule was judged feasible. It allowed the deliverance of a more intensified chemotherapy than the classical schedule. Its clinical benefit must be evaluated in a phase III trial. (authors)

  5. Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma.

    Science.gov (United States)

    Kannarkatt, Joseph; Joseph, Joe; Kurniali, Peter C; Al-Janadi, Anas; Hrinczenko, Borys

    2017-04-01

    The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patient's risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

  6. Cloud computing strategies

    CERN Document Server

    Chorafas, Dimitris N

    2011-01-01

    A guide to managing cloud projects, Cloud Computing Strategies provides the understanding required to evaluate the technology and determine how it can be best applied to improve business and enhance your overall corporate strategy. Based on extensive research, it examines the opportunities and challenges that loom in the cloud. It explains exactly what cloud computing is, what it has to offer, and calls attention to the important issues management needs to consider before passing the point of no return regarding financial commitments.

  7. Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival?

    NARCIS (Netherlands)

    Eggermont, Alexander M. M.; Punt, Cornelis J. A.

    2003-01-01

    The experience with interferon-alpha in malignant melanoma resembles, to some degree, the experience with various kinds of adjuvant immunotherapeutic agents where 25 years of phase III trials of adjuvant therapy in stage II-IIII melanoma have not defined a standard therapy. Most trials failed to

  8. Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

    NARCIS (Netherlands)

    Brok, M.H. den; Bull, C.; Wassink, M.; Graaf, A.M.A. de; Wagenaars, J.A.L.; Minderman, M.; Thakur, M.; Amigorena, S.; Rijke, E.O.; Schrier, C.C.; Adema, G.J.

    2016-01-01

    Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is

  9. Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

    Science.gov (United States)

    Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

    2017-07-01

    Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  10. Current adjuvant treatment modalities for gastric cancer: From history to the future

    Science.gov (United States)

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  11. Cardiac monitoring during adjuvant trastuzumab therapy: Guideline adherence in clinical practice

    NARCIS (Netherlands)

    Visser, Annemiek; van de Ven, Eline M. W.; Ruczynski, Larissa I. A.; Blaisse, Reinoud J. B.; van Halteren, Henk K.; Aben, Katja; van Laarhoven, Hanneke W. M.

    2016-01-01

    Cardiotoxicity is an important adverse effect of adjuvant breast cancer treatment with trastuzumab and three monthly left ventricular ejection fraction (LVEF) monitoring is considered mandatory. The purpose of this study was to gain insight into LVEF monitoring during adjuvant trastuzumab treatment

  12. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

    NARCIS (Netherlands)

    Suter, Thomas M.; Procter, Marion; van Veldhuisen, Dirk J.; Muscholl, Michael; Bergh, Jonas; Carlomagno, Chiara; Perren, Timothy; Passalacqua, Rodolfo; Bighin, Claudia; Klijn, Jan G. M.; Ageev, Fail T.; Hitre, Erika; Groetz, Juergen; Iwata, Hiroji; Knap, Malgorzata; Gnant, Michael; Muehlbauer, Susanne; Spence, Alison; Gelber, Richard D.; Piccart-Gebhart, Martine J.

    2007-01-01

    Purpose The purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant ( HERA) trial is a three- group, multicenter,

  13. Canadian Adjuvant Initiative Workshop, March 26–27, 2013—Ottawa, Canada

    Science.gov (United States)

    Krishnan, Lakshmi; Twine, Susan; Gerdts, Volker; Barreto, Luis; Richards, James C

    2014-01-01

    Novel adjuvants hold the promise for developing effective modern subunit vaccines capable of appropriately modulating the immune response against challenging diseases such as those caused by chronic and/or intracellular pathogens and cancer. Over the past decade there has been intensive research into discovering new adjuvants, however, their translation into routine clinical use is lagging. To stimulate discussion and identify opportunities for networking and collaboration among various stakeholders, a Canadian Adjuvant Initiative Workshop was held in Ottawa. Sponsored by the National Research Council Canada, Canadian Institutes of Health Research and the Vaccine Industry Committee, a two day workshop was held that brought together key Canadian and international stakeholders in adjuvant research from industry, academia and government. To discover innovation gaps and unmet needs, the presentations covered a board range of topics in adjuvant development; criteria for selection of lead adjuvant candidates from an industry perspective, discovery research across Canada, bioprocessing needs and challenges, veterinary vaccines, Canadian vaccine trial capabilities, the Canadian regulatory framework and WHO formulation laboratory experience. The workshop concluded with a discussion on the opportunity to create a Canadian Adjuvant Development Network. This report details the key discussion points and steps forward identified for facilitating adjuvant development research in Canada. PMID:24192752

  14. Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

    Science.gov (United States)

    Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

    2013-11-01

    Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles. © 2013.

  15. 21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvant substances used in the manufacture of... substances used in the manufacture of foamed plastics. The following substances may be safely used as adjuvants in the manufacture of foamed plastics intended for use in contact with food, subject to any...

  16. COATING ALTERNATIVES GUIDE (CAGE) USER'S GUIDE

    Science.gov (United States)

    The guide provides instructions for using the Coating Alternatives GuidE (CAGE) software program, version 1.0. It assumes that the user is familiar with the fundamentals of operating an IBM-compatible personal computer (PC) under the Microsoft disk operating system (MS-DOS). CAGE...

  17. First Clinical Release of an Online, Adaptive, Aperture-Based Image-Guided Radiotherapy Strategy in Intensity-Modulated Radiotherapy to Correct for Inter- and Intrafractional Rotations of the Prostate

    International Nuclear Information System (INIS)

    Deutschmann, Heinz; Kametriser, Gerhard; Steininger, Philipp; Scherer, Philipp; Schöller, Helmut; Gaisberger, Christoph; Mooslechner, Michaela; Mitterlechner, Bernhard; Weichenberger, Harald; Fastner, Gert; Wurstbauer, Karl; Jeschke, Stephan; Forstner, Rosemarie; Sedlmayer, Felix

    2012-01-01

    Purpose: We developed and evaluated a correction strategy for prostate rotations using direct adaptation of segments in intensity-modulated radiotherapy (IMRT). Method and Materials: Implanted fiducials (four gold markers) were used to determine interfractional translations, rotations, and dilations of the prostate. We used hybrid imaging: The markers were automatically detected in two pretreatment planar X-ray projections; their actual position in three-dimensional space was reconstructed from these images at first. The structure set comprising prostate, seminal vesicles, and adjacent rectum wall was transformed accordingly in 6 degrees of freedom. Shapes of IMRT segments were geometrically adapted in a class solution forward-planning approach, derived within seconds on-site and treated immediately. Intrafractional movements were followed in MV electronic portal images captured on the fly. Results: In 31 of 39 patients, for 833 of 1013 fractions (supine, flat couch, knee support, comfortably full bladder, empty rectum, no intraprostatic marker migrations >2 mm of more than one marker), the online aperture adaptation allowed safe reduction of margins clinical target volume–planning target volume (prostate) down to 5 mm when only interfractional corrections were applied: Dominant L-R rotations were found to be 5.3° (mean of means), standard deviation of means ±4.9°, maximum at 30.7°. Three-dimensional vector translations relative to skin markings were 9.3 ± 4.4 mm (maximum, 23.6 mm). Intrafractional movements in 7.7 ± 1.5 min (maximum, 15.1 min) between kV imaging and last beam’s electronic portal images showed further L-R rotations of 2.5° ± 2.3° (maximum, 26.9°), and three-dimensional vector translations of 3.0 ±3.7 mm (maximum, 10.2 mm). Addressing intrafractional errors could further reduce margins to 3 mm. Conclusion: We demonstrated the clinical feasibility of an online adaptive image-guided, intensity-modulated prostate protocol on a standard

  18. First clinical release of an online, adaptive, aperture-based image-guided radiotherapy strategy in intensity-modulated radiotherapy to correct for inter- and intrafractional rotations of the prostate.

    Science.gov (United States)

    Deutschmann, Heinz; Kametriser, Gerhard; Steininger, Philipp; Scherer, Philipp; Schöller, Helmut; Gaisberger, Christoph; Mooslechner, Michaela; Mitterlechner, Bernhard; Weichenberger, Harald; Fastner, Gert; Wurstbauer, Karl; Jeschke, Stephan; Forstner, Rosemarie; Sedlmayer, Felix

    2012-08-01

    We developed and evaluated a correction strategy for prostate rotations using direct adaptation of segments in intensity-modulated radiotherapy (IMRT). Implanted fiducials (four gold markers) were used to determine interfractional translations, rotations, and dilations of the prostate. We used hybrid imaging: The markers were automatically detected in two pretreatment planar X-ray projections; their actual position in three-dimensional space was reconstructed from these images at first. The structure set comprising prostate, seminal vesicles, and adjacent rectum wall was transformed accordingly in 6 degrees of freedom. Shapes of IMRT segments were geometrically adapted in a class solution forward-planning approach, derived within seconds on-site and treated immediately. Intrafractional movements were followed in MV electronic portal images captured on the fly. In 31 of 39 patients, for 833 of 1013 fractions (supine, flat couch, knee support, comfortably full bladder, empty rectum, no intraprostatic marker migrations >2 mm of more than one marker), the online aperture adaptation allowed safe reduction of margins clinical target volume-planning target volume (prostate) down to 5 mm when only interfractional corrections were applied: Dominant L-R rotations were found to be 5.3° (mean of means), standard deviation of means ±4.9°, maximum at 30.7°. Three-dimensional vector translations relative to skin markings were 9.3 ± 4.4 mm (maximum, 23.6 mm). Intrafractional movements in 7.7 ± 1.5 min (maximum, 15.1 min) between kV imaging and last beam's electronic portal images showed further L-R rotations of 2.5° ± 2.3° (maximum, 26.9°), and three-dimensional vector translations of 3.0 ±3.7 mm (maximum, 10.2 mm). Addressing intrafractional errors could further reduce margins to 3 mm. We demonstrated the clinical feasibility of an online adaptive image-guided, intensity-modulated prostate protocol on a standard linear accelerator to correct 6 degrees of freedom of

  19. Antigen sparing with adjuvanted inactivated polio vaccine based on Sabin strains.

    Science.gov (United States)

    Westdijk, Janny; Koedam, Patrick; Barro, Mario; Steil, Benjamin P; Collin, Nicolas; Vedvick, Thomas S; Bakker, Wilfried A M; van der Ley, Peter; Kersten, Gideon

    2013-02-18

    Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titres (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotypes 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7-20-27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Adjuvant whole brain radiotherapy: strong emotions decide but rational studies are needed.

    Science.gov (United States)

    Brown, Paul D; Asher, Anthony L; Farace, Elana

    2008-04-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

  1. Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: brown.paul@mayo.edu; Asher, Anthony L [Brain and Spinal Cord Tumors Programs, Carolinas Medical Center and Presbyterian Hospital, Charlotte, NC (United States); Farace, Elana [Department of Neurosurgery, Pennsylvania State University, Penn State Milton S. Hershey Medical Center, Hershey, PA (United States)

    2008-04-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

  2. Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

    International Nuclear Information System (INIS)

    Brown, Paul D.; Asher, Anthony L.; Farace, Elana

    2008-01-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival

  3. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine

    Directory of Open Access Journals (Sweden)

    Sun HW

    2015-12-01

    robust generator of an effective intramuscular systemic and nasal mucosal immune response without the need for an additional adjuvant. Thus, the present study serves as a sound scientific foundation for future strategies in the development of this novel nanoemulsion adjuvant vaccine to enhance both the intramuscular systemic and nasal mucosal immune responses. Keywords: nanotechnology, adjuvant, methicillin-resistant Staphylococcus aureus, recombination protein, immune responses

  4. Enhancement of the Immunogenicity and Protective Efficacy of a Mucosal Influenza Subunit Vaccine by the Saponin Adjuvant GPI-0100

    NARCIS (Netherlands)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2012-01-01

    Identification of safe and effective adjuvants remains an urgent need for the development of inactivated influenza vaccines for mucosal administration. Here, we used a murine challenge model to evaluate the adjuvant activity of GPI-0100, a saponin-derived adjuvant, on influenza subunit vaccine

  5. Experimental study on oral sulfhydryl as an adjuvant for improving nitrate ester tolerance in an animal model.

    Science.gov (United States)

    Chen, L; Jiang, J-Q; Zhang, Y; Feng, H

    2018-03-01

    As an initial step in exploring the feasibility of oral sulfhydryl as an adjuvant for improving nitrate ester tolerance, this study was designed to experimentally test the adjuvant therapy in a rabbit model of atherosclerosis (AS). New Zealand white rabbits with induced AS were randomly divided into four groups: AS group, AS + nitrate ester group, AS + nitrate ester tolerance group, and AS + drug combination group. Additionally, four equivalent groups with healthy New Zealand white rabbits without AS were also conformed. After feeding the animals for 5 days, the concentrations of superoxide anion (•O2-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) in blood and the relaxation response of the aortic ring were determined in each subject. The vascular plaques in different treatment groups were assessed by Hematoxylin and eosin (HE) staining to investigate the therapeutic value of sulfhydryl as coadjuvant for improving nitrate ester tolerance, and changes in blood vessels in different treatment groups were studied by immunohistochemical assays. Our results showed no significant differences through time in the concentrations of •O2-, SOD, MDA, NO, ET-1 between the healthy control and the nitrate ester groups (p > 0.05). The levels of SOD and MDA in the nitrate ester tolerance group increased with time, however, the levels of •O2-, NO and ET-1 decreased gradually (p tolerance groups were significantly decreased, but SOD and MDA were significantly increased (p tolerance, and this strategy was safe and looks promising for humans.

  6. The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment.

    Science.gov (United States)

    Lundgren, Sebastian; Warfvinge, Carl Fredrik; Elebro, Jacob; Heby, Margareta; Nodin, Björn; Krzyzanowska, Agnieszka; Bjartell, Anders; Leandersson, Karin; Eberhard, Jakob; Jirström, Karin

    2016-01-01

    Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29-0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers.

  7. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom.

    Science.gov (United States)

    Olmedo, Hidekel; Herrera, María; Rojas, Leonardo; Villalta, Mauren; Vargas, Mariángela; Leiguez, Elbio; Teixeira, Catarina; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo; Montero, Mavis L

    2014-01-01

    The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.

  8. Enhancement of human immunodeficiency virus type 1-DNA vaccine potency through incorporation of T-helper 1 molecular adjuvants.

    Science.gov (United States)

    Calarota, Sandra A; Weiner, David B

    2004-06-01

    It is clear that the development of a safe and effective vaccine for human immunodeficiency virus type 1 (HIV-1) remains a crucial goal for controlling the acquired immunodeficiency syndrome epidemic. At present, it is not clear what arm of the immune response correlates with protection from HIV-1 infection or disease. Therefore, a strong cellular and humoral immune response will likely be needed to control this infection. Among different vaccine alternatives, DNA vaccines appeared more than a decade ago, demonstrating important qualities of inducing both humoral and cellular immune responses in animal models. However, after several years and various clinical studies in humans, supporting the safety of the HIV-DNA vaccine strategies, it has become clear that their potency should be improved. One way to modulate and enhance the immune responses induced by a DNA vaccine is by including genetic adjuvants such as cytokines, chemokines, or T-cell costimulatory molecules as part of the vaccine itself. Particularly, vaccine immunogenicity can be modulated by factors that attract professional antigen-presenting cells, provide additional costimulation, or enhance the uptake of plasmid DNA. This review focuses on developments in the coadministration of molecular adjuvants for the enhancement of HIV-1 DNA-vaccine potency.

  9. A basic guide to investing.

    Science.gov (United States)

    Smith, Michael C

    2006-03-01

    Today's investors have many choices. From seemingly simple investments, such as stocks, bonds and cash, to more complicated option strategies, there is a dizzying array of investment vehicles that can leave even the most seasoned investor a bit confused. In discussions with our clients, one common thread is the desire to learn more about the various types of investments available. Following is a basic guide to the most common investments and the risks inherent in those choices.

  10. IMMUNOGENICITY OF ADJUVANT INFLUENZA VACCINE FOR PREGNANT WOMEN

    Directory of Open Access Journals (Sweden)

    M. P. Kostinov

    2017-01-01

    Full Text Available Recent epidemiological events showed that pregnant women are the most vulnerable part of population if there is the flu in the country and they die much more often than the rest part of people. That is why influenza vaccination of population including pregnant women is one of the priorities of public health service in our state. Worldwide experience of influenza vaccination of either adults or children by new adjuvant vaccine has caused our research of its efficiency among pregnant women. The aim of the study was to investigate the level of antibodies to influenza virus strain A/H1N1/v, A/H3N2 and B in pregnant women vaccinated adjuvant trivalent subunit vaccine. Our research is randomized and comparative on parallel groups. It was carried out within the demands of Russian Federation and International ethic norms adapted to such kind of researches. Evaluation of the immunogenicity of the vaccine was conducted in 27 pregnant women in the II trimester of gestation, and in 23 pregnant women in the III trimester of gestation, 19 non-pregnant women was in the control group. The level of antibodies in the serum was determined using a reaction of hemagglutination inhibition before and 1, 3, 6, 9 and 12 months after the vaccination. Revealed that influenza vaccination of pregnant women in the II and III trimester, causes the increase in titers of antibodies to vaccine influenza strains A and B, to fully meet the required criteria CPMP, and does not differ from the nonpregnant group. In a month after vaccination the level of seroprotective against A/H1N1/v was 77.0%, A/H3N2 — 88.9%, B — 85.2% after vaccination in II trimester, and 87.0; 87.0; 91.35% in III trimester of gestation. The factor of seroconversion after vaccination in II trimester for A/H1N1/v was equal to 6.5, A/H3N2 — 7.2, B — 6.5, after vaccination in III trimester of pregnancy: 7.1, 6.5 and 5.1 correspondingly. At the same time revealed accelerated decline in antibody titer against

  11. Adjuvant psychological therapy in long-term endocrine conditions.

    Science.gov (United States)

    Daniels, J; Turner-Cobb, J M

    2017-06-01

    Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome. © 2017 John Wiley & Sons Ltd.

  12. Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

    DEFF Research Database (Denmark)

    Nielsen, Karin; Polk, Anne; Nielsen, Dorte Lisbet

    2014-01-01

    Evolving evidence of cardiotoxicity in cancer patients treated with 5-fluorouracil (5-FU) has been reported. We report two different clinical manifestations of asymptomatic 5-FU-associated cardiotoxicity in patients operated for colorectal cancer and treated with adjuvant chemotherapy of 5-FU...... (bolus-injection and continuous infusion for 46 hours), folinic acid and oxaliplatin (FOLFOX). For a research study evaluating cardiac events during 5-FU treatment, Holter monitoring, electrocardiogram (ECG) and echocardiography were done and cardiac markers monitored before and during the first...... and hyperlipidemia as well as an incidental finding of negative T-waves in electrocardiogram years before 5-FU treatment. No subjective cardiac symptoms were described during infusion, but approximately 12 hours after infusion she suffered from cardiac arrest but was revived. Subsequent analysis of the Holter...

  13. Effect of synthetic adjuvants of biological activity of spleen proteins

    International Nuclear Information System (INIS)

    Kartasheva, A.L.; Yuferova, N.V.; Drozhennikov, V.A.; Orlova, E.B.; Perevezentseva, O.S.; Filatov, P.P.

    1981-01-01

    Intraperitoneal administration to mice of synthetic adjuvants of a polyanion type increases the spleen mass by 500% and rises the content of proteins with activity of inhibitor of DNAase 1. A protein fraction isolated from the spleen of treated animals administered to exposed (7.7 Gy) mice alone or in a combination with exogenous DNA increases survival up to 61.1 and 80.5%, respectively, as opposed to 36.6% in the case of administration of proteins from intact animals, or 8.3% in the control (no treatment). The protein fraction from treated animals administered to mice exposed to 5.1-5.5 Gy accelerates the recovery of hemopoesis and immune response better than proteins of intact animals

  14. Hypofractionated Adjuvant Whole Breast Radiotherapy: Progress and Prospects

    International Nuclear Information System (INIS)

    Yarnold, John; Haviland, Joanne

    2010-01-01

    Published results of randomised trials involving >7000 women confirm the safety and efficacy of hypofractionated schedules of adjuvant radiotherapy for women with early breast cancer using fraction sizes between 2 and 3 Gy assuming appropriate downward adjustments to total dose. Unnecessary concerns relating to heart tolerance, suboptimal dose distribution and duration of follow up need not discourage the routine adoption of 15- or 16-fraction schedules in women treated by breast conservation surgery for early breast cancer. Regardless of fractionation regimen, dose escalation to the index quadrant in high risk subgroups will result in a greater relative increase in late adverse effects than tumour control, a therapeutic disadvantage that can only be overcome by exploiting a marked dose-volume effect. A 15-fraction schedule of whole breast radiotherapy is unlikely to represent the lower limits of hypofractionation, and the preliminary results of a 5-fraction regimen are encouraging

  15. The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

    Science.gov (United States)

    Lesiuk, Teresa

    2015-05-01

    To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

  16. Utilization pattern and survival outcomes of adjuvant therapies in high-grade nonretroperitoneal abdominal soft tissue sarcoma: A population-based study.

    Science.gov (United States)

    Green, William Ross; Chokshi, Ravi; Jabbour, Salma K; DeLaney, Thomas F; Mahmoud, Omar

    2018-02-01

    Nonretroperitoneal abdominal soft tissue sarcoma (NRA-STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. The analysis included patients with resected high-grade NRA-STS. Chi-square analysis was used to evaluate distribution of patient and tumor-related factors within treatment groups. The Kaplan-Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients' outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. At median follow-up of 49 months, 5-year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58-0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Adjuvant radiotherapy was associated with improved survival in high-grade NRA-STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. © 2017 John Wiley & Sons Australia, Ltd.

  17. Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online.

    Science.gov (United States)

    Jahn, Beate; Rochau, Ursula; Kurzthaler, Christina; Hubalek, Michael; Miksad, Rebecca; Sroczynski, Gaby; Paulden, Mike; Bundo, Marvin; Stenehjem, David; Brixner, Diana; Krahn, Murray; Siebert, Uwe

    2017-10-16

    Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high

  18. The Role of Adjuvant Radiation in Uterine Sarcomas

    International Nuclear Information System (INIS)

    Sampath, Sagus; Schultheiss, Timothy E.; Ryu, Janice K.; Wong, Jeffrey Y.C.

    2010-01-01

    Purpose: To determine clinical and pathological factors significant for overall survival (OS) and local-regional failure-free survival (LRFFS) in uterine sarcoma as they relate to adjuvant radiotherapy (AR). Methods and Materials: A retrospective analysis of 3,650 patients with uterine sarcoma was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by Impac Medical Systems (Sunnyvale, CA). Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis, with or without brachytherapy. Prognostic factors were identified by multivariate analysis (MVA) using the Cox proportional hazards model. The Kaplan-Meier method was used to estimate survival, with significant differences (p < 0.05) determined using the log-rank test. Results: The median follow-up time was 59 months, with a 5-year OS of 37%. Significant prognostic factors for OS were stage, race/ethnicity, grade, age, histology, lymph node status, and surgical treatment (p < 0.01 for all factors). Use of AR was not predictive for OS. For nonmetastatic cancer patients receiving definitive surgery (n = 2,206), the 5-year LRFFS was 87%. In this group, stage, grade, histology, and AR were prognostic for LRFFS (p < 0.05), with AR associated with improved outcome compared with surgery alone (hazard ratio = 0.4, p < 0.001). Patients with carcinosarcoma, endometrial stromal sarcoma, leiomyosarcoma, poorly differentiated tumors, and negative lymph nodes had reduced local-regional failure (LRF) with AR (log-rank, p < 0.05 for all). Conclusion: In the largest retrospective analysis of uterine sarcoma published thus far, AR conferred a 53% reduction in the risk of LRF at 5 years. Use of AR may have broader indications than what are currently accepted in clinical practice.

  19. Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

    Science.gov (United States)

    Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

    2018-01-01

    Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the

  20. THE USE OF ADJUVANTS IN STUDIES ON INFLUENZA IMMUNIZATION

    Science.gov (United States)

    Salk, Jonas E.; Laurent, Angela M.

    1952-01-01

    Untoward reactions at the site of inoculation were not observed in monkeys vaccinated with influenza virus incorporated in a water-in-oil emulsion without acid-fast bacilli. Studies were then made to measure some of the dimensions of antigenicity of these emulsions to evaluate the extent of the immunologic adjuvant effect. This included measurements of height and persistence of the antibody response to inoculation and measurements of the extent to which the vaccine could be diluted and still induce antibody formation; i.e., antigenic extinction. In addition, comparisons were made of the rates of development of hemagglutination-inhibiting, virus-neutralizing, and complement-fixing antibody activities to determine the relationship among these three properties of the serum of immunized animals. It was found that levels of antibody many fold higher were induced by the virus-adjuvant mixtures as compared with virus in an aqueous menstruum, and that the level of antibody induced was related to the quantity of antigen incorporated in the emulsion. The stock vaccine when emulsified could be diluted 100,000-fold and was still active in antibody formation whereas a 100-fold dilution of the antigen without emulsification was essentially ineffective. Equivalent quantities of virus in 0.1 ml. or 1.0 ml. of emulsion induced antibody responses that were indistinguishable with respect to level or persistence. In comparing the course of antibody development it was found that hemagglutination-inhibiting, virus-neutralizing, and complement-fixing antibodies develop at different rates; careful analysis of the data derived from the present study together with other observations warrant the conclusion that these antibody activities are not present in constant proportion and are independent of one another. The implications of this observation and of the others mentioned above are discussed. PMID:14927797

  1. Effect of DETOX as an adjuvant for melanoma vaccine.

    Science.gov (United States)

    Schultz, N; Oratz, R; Chen, D; Zeleniuch-Jacquotte, A; Abeles, G; Bystryn, J C

    1995-04-01

    The identification of effective adjuvants is critical for tumor vaccine development. Towards this end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX, an adjuvant consisting of monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS). Nineteen patients with resected stage III melanoma were immunized with a polyvalent melanoma antigen vaccine (40 micrograms) admixed with DETOX, q3 wks x 4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100 micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL + 200 micrograms CWS). A non-randomized control group of 35 patients was treated similarly with 40 micrograms vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 7/7 (100%) patients treated with vaccine + low-dose DETOX, 8/12 (67%) patients treated with vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19 (21%) in the alum group (p or = 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX group was 17.8 months compared with 32.1 months in the alum group (p DETOX markedly potentiated antibody but had little effect on DTH responses to melanoma vaccine immunization. It did not appear to improve disease-free survival in comparison to alum in this non-randomized study.

  2. Rationally Designed TLR4 Ligands for Vaccine Adjuvant Discovery

    Directory of Open Access Journals (Sweden)

    Kelsey A. Gregg

    2017-05-01

    Full Text Available Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS, altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC as a method to generate rationally designed, functionally diverse lipid A. BECC removes endogenous or introduces exogenous lipid A-modifying enzymes to bacteria, effectively reprogramming the lipid A biosynthetic pathway. In this study, BECC is applied within an avirulent strain of Yersinia pestis to develop structurally distinct LOS molecules that elicit differential Toll-like receptor 4 (TLR4 activation. Using reporter cell lines that measure NF-κB activation, BECC-derived molecules were screened for the ability to induce a lower proinflammatory response than Escherichia coli LOS. Their structures exhibit varied, dose-dependent, TLR4-driven NF-κB activation with both human and mouse TLR4 complexes. Additional cytokine secretion screening identified molecules that induce levels of tumor necrosis factor alpha (TNF-α and interleukin-8 (IL-8 comparable to the levels induced by phosphorylated hexa-acyl disaccharide (PHAD. The lead candidates demonstrated potent immunostimulation in mouse splenocytes, human primary blood mononuclear cells (PBMCs, and human monocyte-derived dendritic cells (DCs. This newly described system allows directed programming of lipid A synthesis and has the potential to generate a diverse array of TLR4 agonist candidates.

  3. Adjuvant radiation therapy versus surgery alone in operable breast cancer

    International Nuclear Information System (INIS)

    Rutqvist, L.E.; Pettersson, D.; Johansson, H.

    1993-01-01

    This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference - corresponding to 16% reduction of deaths - in favour of the irradiated patients which, however, was not statistically significant (p=0.09). Among those 169 patients who developed loco-regional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p<0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients. (author) 5 tabs

  4. Adjuvant radiation therapy for pancreatic cancer: a 15-year experience

    International Nuclear Information System (INIS)

    Dobelbower, Ralph R.; Merrick, Hollis W.; Khuder, Sadik; Battle, Joyce A.; Herron, Lisa M.; Pawlicki, Todd

    1997-01-01

    Purpose: A retrospective analysis to determine differences in survival of patients with pancreatic aden carcinoma treated by radical surgery with and without adjuvant radiation therapy. Methods and Materials: Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups. Results: The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate. Conclusion: The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time

  5. Preclosure Safety Analysis Guide

    International Nuclear Information System (INIS)

    D.D. Orvis

    2003-01-01

    A preclosure safety analysis (PSA) is a required element of the License Application (LA) for the high- level radioactive waste repository at Yucca Mountain. This guide provides analysts and other Yucca Mountain Repository Project (the Project) personnel with standardized methods for developing and documenting the PSA. The definition of the PSA is provided in 10 CFR 63.2, while more specific requirements for the PSA are provided in 10 CFR 63.112, as described in Sections 1.2 and 2. The PSA requirements described in 10 CFR Part 63 were developed as risk-informed performance-based regulations. These requirements must be met for the LA. The PSA addresses the safety of the Geologic Repository Operations Area (GROA) for the preclosure period (the time up to permanent closure) in accordance with the radiological performance objectives of 10 CFR 63.111. Performance objectives for the repository after permanent closure (described in 10 CFR 63.113) are not mentioned in the requirements for the PSA and they are not considered in this guide. The LA will be comprised of two phases: the LA for construction authorization (CA) and the LA amendment to receive and possess (R and P) high-level radioactive waste (HLW). PSA methods must support the safety analyses that will be based on the differing degrees of design detail in the two phases. The methods described herein combine elements of probabilistic risk assessment (PRA) and deterministic analyses that comprise a risk-informed performance-based safety analysis. This revision to the PSA guide was prepared for the following objectives: (1) To correct factual and typographical errors. (2) To provide additional material suggested from reviews by the Project, the U.S. Department of Energy (DOE), and U.S. Nuclear Regulatory Commission (NRC) Staffs. (3) To update material in accordance with approaches and/or strategies adopted by the Project. In addition, a principal objective for the planned revision was to ensure that the methods and

  6. Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

    Directory of Open Access Journals (Sweden)

    Shu-Ting Ren

    Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

  7. De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

    Science.gov (United States)

    Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

    2017-09-10

    Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

  8. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    Science.gov (United States)

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

  9. Neoadjuvant chemoradiation (modified Eilber protocol) versus adjuvant radiotherapy in the treatment of extremity soft tissue sarcoma

    International Nuclear Information System (INIS)

    Lehane, Chris; Parasyn, Andrew; Ho, Frederick; Thompson, Stephen R.; Smee, Robert; Links, David; Crowe, Phil; Lewis, Craig; Friedlander, Michael; Williams, Janet

    2016-01-01

    Local control for extremity soft tissue sarcomas (STS) requires surgery combined with radiotherapy, usually given pre-operatively or post-operatively. The modified Eilber protocol, a neoadjuvant chemoradiation regimen, has been reported with excellent local control rates. This retrospective single-centre study compared outcomes for patients treated with the modified Eilber protocol with those treated with standard adjuvant radiotherapy. Twenty-nine patients were treated with modified Eilber protocol. Thirty-four patients received adjuvant radiotherapy. Three patients (10%) in the Eilber group and five patients (15%) in the Adjuvant group developed local recurrence (P = 0.87). Major acute wound complications were noted in four patients in each group (P = 0.55). One patient (3.4%) in the Eilber group developed Grade 3 or 4 late toxicities after 1 year compared with nine patients (27%) in the Adjuvant group (P = 0.02). Patients with a diagnosis of extremity STS were retrospectively reviewed from the Prince of Wales Hospital Sarcoma Database from 1995 to 2012. Sixty-three patients underwent curative surgery with either neoadjuvant Eilber chemoradiotherapy (Eilber) or adjuvant radiotherapy (Adjuvant). Neoadjuvant chemoradiation (Eilber protocol) provided similar rates of local control when compared with adjuvant radiotherapy. Acute wound complication rates were similar but there was less severe late toxicity in the Eilber group.

  10. Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

    Science.gov (United States)

    Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

    2015-05-20

    Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

  11. Accounting for adjuvant-induced artifacts in the characterization of vaccine formulations by polyacrylamide gel electrophoresis.

    Science.gov (United States)

    Jakob, Virginie; Brunner, Livia; Barnier-Quer, Christophe; Blust, Molly; Collin, Nicolas; Carter, Lauren; Carter, Darrick; Rausch, Kelly M; Fox, Christopher B

    2017-04-01

    Several vaccine adjuvants comprise complex nano- or micro-particle formulations, such as oil-in-water emulsions. In order to characterize interactions and compatibility of oil-in-water emulsion adjuvants with protein antigens in vaccines, effective protein characterization methods that can accommodate potential interference from high concentrations of lipid-based particles are needed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is a standard protein characterization technique which is affected by the presence of adjuvants such as oil-in-water emulsions. In this article, we investigate variations in SDS-PAGE methods that result in a reduction of adjuvant-induced staining artifacts. We have investigated whether the SDS method or the adjuvant composition were the reason for these artifacts and succeeded in reducing the artifacts with a modified sample preparation and different staining procedures. The best results were obtained by using gold staining or silver staining instead of a Coomassie Blue staining procedure. Moreover, the replacement of the dilution buffer (20% SDS to disrupt emulsion) by alternative detergents such as Tween® 80 and Triton® X-100 removed adjuvant-induced streaking artifacts at the top of the gel. These methods may be useful for improving characterization approaches of antigen-adjuvant mixtures by SDS-PAGE.

  12. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

    Science.gov (United States)

    Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

    2016-01-01

    Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

  13. An overview of adjuvants utilized in prophylactic vaccine formulation as immunomodulators.

    Science.gov (United States)

    Chauhan, Nidhi; Tiwari, Sukirti; Iype, Tessy; Jain, Utkarsh

    2017-05-01

    Development of efficient and cost effective vaccines have been recognized as the primary concern to improve the overall healthcare in a country. In order to achieve this goal, more improved and powerful adjuvants need to be developed. Lacking in the self-adjuvanting immuno-modulatory constituents, vaccines exhibit lower immunogenicity. Combining potent adjuvants with vaccines is the most appropriate method to enhance the efficacy of the vaccines. Hence, this review is focussed on the most potent adjuvants for the formulation of vaccines. Areas covered: This review focuses on Oil-based emulsions, Mineral compounds, Liposomes, Bacterial products, ISCOMs and most recently used nanomaterials as adjuvants for enhancing the antigenicity of vaccines. Furthermore, this review explains the immunological response elicited by various particles. Moreover, case studies are incorporated providing an in depth analyses of various adjuvant-containing vaccines which are currently used. Expert commentary: Enhanced fundamental knowledge about the adjuvants and their immuno-stimulatory capabilities and delivery mechanisms will facilitate the rational designing of prophylactic vaccines with better efficacy.

  14. Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

    Science.gov (United States)

    Miladi, Imen; Vivier, Magali; Dauplat, Marie-Mélanie; Chatard, Morgane; Besse, Sophie; Vidal, Aurélien; Chassain, Karine; Jean, Betty; Forestier, Christiane; Chezal, Jean-Michel; Rédini, Francoise; Degoul, Francoise; Miot-Noirault, Elisabeth

    2017-09-01

    This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management.

  15. Identification of distinct fatigue trajectories in patients with breast cancer undergoing adjuvant chemotherapy.

    Science.gov (United States)

    Junghaenel, Doerte U; Cohen, Jules; Schneider, Stefan; Neerukonda, Anu R; Broderick, Joan E

    2015-09-01

    The goal of this study was to characterize changes in daily fatigue in women undergoing chemotherapy for breast cancer. We examined whether there are subgroups of patients with distinct fatigue trajectories and explored potential psychosocial and biomedical predictors of these subgroups. Participants were 77 women with breast cancer receiving adjuvant chemotherapy with AC-T (2-week cycle) and TC or TCH (3-week cycle) regimens. They completed 28 daily ratings online using an adapted version of the Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue instrument. Both regimens followed an "inverted-U-shaped" fatigue pattern over approximately 2 weeks. Growth mixture modeling identified three patient subgroups with distinct trajectories. Fatigue scores in the "low fatigue" group (23 %) increased following the infusion and quickly abated. The "transient fatigue" (27 %) group had a very pronounced increase. Patients in the "high fatigue" (50 %) group reported consistently elevated fatigue with a relatively small increase. Demographic and medical variables were not associated with fatigue trajectory. Patients in the "high fatigue" group reported significantly poorer physical, emotional, and social functioning, poorer general health, and more depressed mood than patients in the "low fatigue" group. The "transient fatigue" group reported significantly better physical and social functioning than the "high fatigue" group, but emotional distress and depression similar to the "high fatigue" group. The identification of patient subgroups with distinct fatigue trajectories during chemotherapy is an essential step for developing preventative strategies and tailored interventions. Our results suggest that different trajectories are associated with patients' psychosocial and general health.

  16. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    DEFF Research Database (Denmark)

    Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith

    2016-01-01

    be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit...

  17. Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization.

    Science.gov (United States)

    Li, Hui-Shan; Piao, Da-Chuan; Jiang, Tao; Bok, Jin-Duck; Cho, Chong-Su; Lee, Yoon-Seok; Kang, Sang-Kee; Choi, Yun-Jaie

    2015-04-15

    Development and application of safe and effective mucosal adjuvants are important to improve immunization efficiency in oral vaccine. Here, we report a novel mucosal adjuvant, IL-6-CKS9, a recombinant cytokine generated by conjugating an M cell-targeting peptide (CKS9) with c-terminus of the murine interleukin 6 (IL-6), which facilitated enhancement of mucosal immune response. Lactococcus lactis IL1403, a food-grade strain of lactic acid bacteria (LAB) which is widely used in dairy industry, was used as a host cell to express and secrete the IL-6-CKS9 for a mucosal vaccine adjuvant. The recombinant L. lactis IL1403 secreting IL-6-CKS9 was orally administered with a model antigen protein, M-BmpB (Brachyspira membrane protein B conjugated with CKS9), to BALB/c mice for mucosal immunization. ELISA analyses showed consistent enhancement tendencies in induction of anti-M-BmpB antibody levels both with mucosal (IgA) and systemic (IgG) immune responses in IL-6-CKS9-LAB treated group compared with other groups tested by conducting two separated mice immunization assays. In addition, we characterized that the oral administration of model protein antigen with live LAB producing IL-6-CKS9 could induce both Th1 and Th2 type immune responses by analysis of the specific anti-BmpB IgG1 and IgG2a isotypes in the sera and also investigated possible oral tolerance in our vaccine strategy. Collectively, our results showed successful production and secretion of recombinant murine IL-6 with M cell-targeting moiety (IL-6-CKS9) from L. lactis IL1403 and demonstrated the live recombinant LAB producing IL-6-CKS9 could have a potential to be used as an efficient adjuvant for peroral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Guide to Closing and Conditioning Ventilated Crawlspaces

    Energy Technology Data Exchange (ETDEWEB)

    Dickson, Bruce [IBACOS, Inc., Pittsburgh, PA (United States)

    2013-01-01

    This how-to guide explains the issues and concerns with conventional ventilated crawlspaces and provides prescriptive measures for improvements that will create healthier and more durable spaces. The methods described in this guide are not the only acceptable ways to treat a crawlspace but represent a proven strategy that works in many areas of the United States. The designs discussed in this guide may or may not meet the local building codes and as such will need to be researched before beginning the project.

  19. DOE groundwater protection strategy

    International Nuclear Information System (INIS)

    Lichtman, S.

    1988-01-01

    EH is developing a DOE-wide Groundwater Quality Protection Strategy to express DOE's commitment to the protection of groundwater quality at or near its facilities. This strategy responds to a September 1986 recommendation of the General Accounting Office. It builds on EPA's August 1984 Ground-Water Protection Strategy, which establishes a classification system designed to protect groundwater according to its value and vulnerability. The purposes of DOE's strategy are to highlight groundwater protection as part of current DOE programs and future Departmental planning, to guide DOE managers in developing site-specific groundwater protection practices where DOE has discretion, and to guide DOE's approach to negotiations with EPA/states where regulatory processes apply to groundwater protection at Departmental facilities. The strategy calls for the prevention of groundwater contamination and the cleanup of groundwater commensurate with its usefulness. It would require long-term groundwater protection with reliance on physical rather than institutional control methods. The strategy provides guidance on providing long-term protection of groundwater resources; standards for new remedial actions;guidance on establishing points of compliance; requirements for establishing classification review area; and general guidance on obtaining variances, where applicable, from regulatory requirements. It also outlines management tools to implement this strategy

  20. Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

    Science.gov (United States)

    Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

    2012-12-01

    Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

  1. Transient anorexia, hyper-nociception and cognitive impairment in early adjuvant arthritis in rats.

    Science.gov (United States)

    Skurlova, M; Stofkova, A; Kiss, A; Belacek, J; Pecha, O; Deykun, K; Jurcovicova, J

    2010-10-01

    Rheumatoid arthritis (RA) is associated with enhanced pro-inflammatory cytokine levels, pain, anorexia, and cognitive changes. The enhanced production of cytokines appears before the full manifestation of the disease. So far, any experimental data on behavioral effects of early arthritis are lacking. In the present series we describe anorexia early changes in, pain hyper-sensitivity and altered cognitive behavior during the first four days of adjuvant arthritis in rats (AA), when no clinical signs are yet apparent. AA was induced to male Lewis rats by a single injection of complete Freund's adjuvant (cFA) at the base of the tail. Plasma leptin and ghrelin were measured using specific RIA methods. Gene expressions for food-regulatory peptides, neuropeptide-Y (NPY) and interleukin-1β (IL-1β) in the hypothalamic arcuate nuclei (nARC), were quantitated by TaqMan real-time PCR. Pain sensation was measured on all four limbs and tail by the plantar test. Cognitive functions were tested in the Morris water maze (MWM). Levels of orexigenic ghrelin as well as mRNA expression of orexigenic NPY in nucleus arcuatus (nRC)re significantly enhanced on day 2 of AA only. Reduced body weight and food intake persisted by day 4 with the most profound reduction on day 2. The mRNA for anorexigenic IL-1β in the nARC was significantly enhanced on days 2 and 4. Enhanced pain sensitivity was observed on day 2, as was the cognitive impairment given by longer time to find the hidden platform, longer time spent in thigmotaxis zone, and longer trajectory. The less effective strategy used to find the hidden platform was observed up to the day 4 of AA. Early stage of AA brings about reduced body weight, food intake, and activation of central orexigenic pathways. The observed anorexia could be ascribed to the over-expression of anorexigenic IL-1β which dominates over the NPY orexigenic effects. On day 2 of AA higher pain sensitivity and cognitive impairment appear. All the observed change tend

  2. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

    Science.gov (United States)

    Lee, Hyung-Sik; Choi, Youngmin; Hur, Won-Joo; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Kim, Sung-Hyun; Kim, Jae-Seok; Lee, Jong-Hoon; Jung, Ghap-Joong; Kim, Min-Chan

    2006-01-01

    AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival. PMID:16489675

  3. CpG oligodeoxynucleotides are a potent adjuvant for an inactivated polio vaccine produced from Sabin strains of poliovirus.

    Science.gov (United States)

    Yang, Chunting; Shi, Huiying; Zhou, Jun; Liang, Yanwen; Xu, Honglin

    2009-11-05

    Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.

  4. Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial

    NARCIS (Netherlands)

    Bouman, Chantal Am; van Herwaarden, Noortje; van den Hoogen, Frank Hj; Fransen, Jaap; van Vollenhoven, Ronald F.; Bijlsma, Johannes Wj; Maas, Aatke van der; den Broeder, Alfons A.

    2017-01-01

    Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from

  5. Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial

    NARCIS (Netherlands)

    Bouman, C.A.M.; Herwaarden, N. van; Hoogen, F.H.J. van den; Fransen, J.; Vollenhoven, R.F. van; Bijlsma, J.W.; Maas, A.V.; Broeder, A.A. den

    2017-01-01

    OBJECTIVE: Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year

  6. A Glycolipid Adjuvant, 7DW8-5, Enhances CD8+ T Cell Responses Induced by an Adenovirus-Vectored Malaria Vaccine in Non-Human Primates

    OpenAIRE

    Padte, Neal N.; Boente-Carrera, Mar; Andrews, Chasity D.; McManus, Jenny; Grasperge, Brooke F.; Gettie, Agegnehu; Coelho-dos-Reis, Jordana G.; Li, Xiangming; Wu, Douglass; Bruder, Joseph T.; Sedegah, Martha; Patterson, Noelle; Richie, Thomas L.; Wong, Chi-Huey; Ho, David D.

    2013-01-01

    A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent ad...

  7. Tratamento adjuvante nos GISTs Adjuvant treatment in GISTs

    Directory of Open Access Journals (Sweden)

    Laercio Gomes Lourenço

    2011-09-01

    Full Text Available INTRODUÇÃO: O tumor estromal gastrointestinal (GIST é o sarcoma mais comum do aparelho digestivo. Essa neoplasia ocorre devido à mutação do gene KIT com consequente ativação constitutiva da proteína KIT. O tratamento primário é cirúrgico e consiste na sua ressecção completa. Entretanto, alguns grupos de pacientes apresentam risco elevado de recorrência mesmo após operação com ressecção completa (R0, indicando diferenças no comportamento biológico. Estudos clínicos comprovaram a atividade clínica do mesilato de imatinibe, fazendo dele a primeira linha de tratamento padrão nos GISTs metastáticos ou irressecáveis, mudando muito o desfecho clínico dessa doença em relação aos benefícios anteriormente obtidos com a quimioterapia antineoplásica. MÉTODO: Foi realizada revisão da literatura com consulta nos periódicos das bases Medline/Pubmed, Scielo e Lilacs cruzando os descritores: tumor estromal gastrointestinal, Gist, tratamento, adjuvância. Além desta revisão foi adicionada a experiência pessoal dos autores. CONCLUSÃO: Melhor refinamento dos critérios de prognóstico tem permitido selecionar de forma mais adequada pacientes para o tratamento adjuvante com imatinibe. Os resultados de maior evidência até o momento respaldam o tratamento adjuvante por um ano, o que produz benefício significativo na sobrevida livre de recidiva, mas não na sobrevida global desses pacientes.INTRODUCTION: Gastrointestinal stromal tumor (GIST is the most common sarcoma of the digestive tract. This cancer occurs due to mutation of the KIT gene resulting in constitutive activation of KIT protein. The primary treatment is surgical and consists of complete resection. However, some groups of patients at high risk of recurrence even after surgery with complete resection (R0, indicate differences in biological behavior. Clinical studies have demonstrated the clinical activity of imatinib mesylate, making it the standard first

  8. Psidium guajava leaves decrease arthritic symptoms in adjuvant-induced arthritic rats

    Directory of Open Access Journals (Sweden)

    Hanif Nasiatul Baroroh

    2016-04-01

    Psidium guajava leaf extract is effective in decreasing the inflammatory response and arthritic symptoms in rats with adjuvant-induced arthritis. Psidium guajava leaves can be developed into an alternative anti-arthritis treatment.

  9. Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a randomized controlled trial

    DEFF Research Database (Denmark)

    Bernateck, M.; Becker, M.; Schwacke, C.

    2008-01-01

    BACKGROUND: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. OBJECTIVE: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). METHODS: Patients...

  10. Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA)

    DEFF Research Database (Denmark)

    Ameratunga, Rohan; Gillis, David; Gold, Michael

    2017-01-01

    Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis...

  11. Curative effect of ganglioside sodium for adjuvant therapy on acute severe craniocerebral injury

    Directory of Open Access Journals (Sweden)

    Yun-Liang Deng

    2017-01-01

    >Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduce ICP, improve PbtO2 and alleviate the injuries of neurons and glial cells caused by oxidative stress.

  12. Radioimmunoassay of adjuvant-associated porcine parvovirus using a monoclonal antibody in a nitrocellulose membrane system

    International Nuclear Information System (INIS)

    Katz, J.B.; Van Deusen, R.A.

    1985-01-01

    A quantitative and simple indirect radioimmunoassay (IRIA) was developed for porcine parvovirus (PPV), employing a monoclonal antibody directed against PPV adsorbed to nitrocellulose membrane. The IRIA was equally sensitive to live or inactivated PPV. There was a linear relationship between membrane-bound radioactivity and PPV quantity within a range of 10-80 hemagglutinating (HA) units of virus. Two commercially used adjuvants, aluminum hydroxide (AH) and carboxyvinyl polymer (CP), reduced bound radioactivity in a concentration-dependent manner. At fixed adjuvant concentrations, there were, nevertheless, linear relationships between bound radioactivity and HA units of PPV. Known amounts of PPV were prepared in adjuvants according to commercial vaccine formulations. Using these standards, the PPV content of 16 commercial PPV vaccines was estimated by IRIA. The IRIA may be one practical method of in vitro estimation of antigenic mass in adjuvanted vaccines. (Auth.)

  13. Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

    NARCIS (Netherlands)

    Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

    Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

  14. A Controlled Study Using Acupuncture as an Adjuvant to Treat Chemotherapy-Induced Nausea and Vomiting

    National Research Council Canada - National Science Library

    Lao, Lixing

    2001-01-01

    ...) on nausea and vomiting induced by chemotherapy in cancer patients. The primary aim of this study is to evaluate the usefulness of EA as an adjuvant on N/V in chemotherapy patients who do not respond to conventional antiemetics...

  15. [Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

    Science.gov (United States)

    Russo, P; Vitu, C; Fontaine, J J; Vignoni, M

    1993-04-01

    In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

  16. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene

    2014-01-01

    is generally known about how antigens and adjuvants interact at the molecular level. The aim of this study was to elucidate the mechanisms of interactions between the equally sized, but oppositely charged model protein antigens α-lactalbumin and lysozyme, and i) the clinically tested cationic liposomal...... antigens are presented to antigen-presenting cells, and may play an important role for the efficacy of the vaccine-induced immune response. These studies thus exemplify the importance of characterizing the molecular interactions between the vaccine antigen and adjuvant along with immunogenicity......The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...

  17. Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review

    Directory of Open Access Journals (Sweden)

    Gustavo Arruda Viani

    Full Text Available ABSTRACT In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN. The findings were: (i adjuvant 5-fluorouracil (5-FU reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR A]. (ii Primary topical mitomycin (MMC produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A. (iii Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B. (iv Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C. (v Primary topical 5-FU versus MMC versus interferon (IFN showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C.

  18. Effects of 3% trehalose as an adjuvant treatment after LASIK

    Directory of Open Access Journals (Sweden)

    Mateo Orobia AJ

    2017-02-01

    Full Text Available Antonio J Mateo Orobia,1–3 Paula Casas Pascual,1,4 José Á Cristóbal Bescós,1 Diana Perez García,1,4 Carlos Peiro Embid,1,4 M Ángeles del Buey Sayas,1,4 Valentyna Korobko Kulikova,1 Noelia Lafuente Ojeda5 1Department of Ophthalmology, Hospital Quirón, 2Department of Ophthalmology, Hospital Universitario Miguel Servet, 3Instituto de Investigación Sanitaria de Aragón (IIS, 4Department of Ophthalmology, Hospital Clínico Universitario Lozano-Blesa, 5Department of Anesthesiology, Hospital Universitario Miguel Servet, Zaragoza, Spain Purpose: To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis.Design: Interventional prospective comparative single-blind study.Setting: Department of Ophthalmology, Hospital Quirón Zaragoza, Spain.Methods: A total of 26 eyes (13 patients were included, of which 12 eyes (group 1 received conventional treatment with lubricant drops of hyaluronic acid (0.15% and 14 eyes (group 2 received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made.Results: We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001, and in the National Eye Institute scale in day 30 (P=0.02.Conclusion: The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality. Keywords: dry eye syndrome, trehalose

  19. IMRT for adjuvant radiation in gastric cancer: A preferred plan?

    International Nuclear Information System (INIS)

    Ringash, Jolie; Perkins, Greg; Brierley, James; Lockwood, Gina; Islam, Mohammad; Catton, Pamela; Cummings, Bernard; Kim, John; Wong, Rebecca; Dawson, Laura

    2005-01-01

    Purpose: To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over conformal planning for postoperative adjuvant radiotherapy in patients with gastric carcinoma. Methods and Materials: Twenty patients who had undergone treatment planning with conformal beam arrangements for 4500 cGy adjuvant radiotherapy between 2000 and 2001 underwent repeat planning using IMRT techniques. Conformal five-field plans were compared with seven- to nine-field coplanar sliding-window IMRT plans. For each patient, the cumulative dose-volume histograms and organ-dose summaries (without distributions or digitally reconstructed radiographs) were provided to two independent, 'blinded' GI radiation oncologists. The oncologists indicated which plan provided better planning target volume coverage and critical organ sparing, any safety concerns with either plan, and which plan they would choose to treat the patient. Results: In 18 (90%) of 20 cases, both oncologists chose the same plan. Cases with disagreement were given to a third 'blinded' reviewer. A 'preferred plan' could be determined in 19 (95%) of 20 cases. IMRT was preferred in 17 (89%) of 19 cases. In 4 (20%) of 20 IMRT plans at least one radiation oncologist had safety concerns because of the spinal cord dose (3 cases) or small bowel dose (2 cases). Of 42 ratings, IMRT was thought to provide better planning target volume coverage in 36 (86%) and better sparing of the spinal cord in 31 (74%) of 42, kidneys in 29 (69%), liver in 30 (71%), and heart in 29 (69%) of 42 ratings. The median underdose volume (1.7 vs. 4.1 cm 3 ), maximal dose to the spinal cord (36.85 vs. 45.65 Gy), and dose to 50% of the liver (17.29 vs. 27.97), heart (12.89 vs. 15.50 Gy), and left kidney (15.50 vs. 16.06 Gy) were lower with IMRT than with the conformal plans. Conclusion: Compared with the conformal plans, oncologists frequently preferred IMRT plans when using dose-volume histogram data. The advantages of IMRT plans include both

  20. Adjuvant and salvage therapy following radical prostatectomy for prostate cancer: effect of combined transient androgen deprivation and irradiation

    International Nuclear Information System (INIS)

    Eulau, Stephen M.; Tate, David J.; Cox, Richard S.; Bagshaw, Malcolm A.; Hancock, Steven L.

    1996-01-01

    . Biochemical relapse was defined as rising PSA >0.07 on 2 consecutive measurements. Results: Overall actuarial survival was 91% at 5 years and 75% at 7 years after radiotherapy. The overall 5 year actuarial biochemical disease free survival was 44%. Although their follow-up is shorter, patients who received adjuvant androgen blockade had significantly better freedom from biochemical recurrence than those receiving radiotherapy alone (p=.0099) with 5 year actuarial biochemical disease free survivals of 67% and 38% respectively. None of 12 patients at risk greater than 5 years after irradiation have developed a biochemical recurrence. Indication for treatment (adjuvant, rising PSA, or clinical local recurrence) did not significantly affect biochemical control (52%, 50%, and 31% at 5 years, p≥ .7147). Conclusion: In this retrospective study, combined transient androgen deprivation and irradiation improves actuarial biochemical disease free survival compared with irradiation alone in patients with involved surgical margins, seminal vesicle involvement, or capsular penetration. Whether this outcome will translate into improved local control and overall survival awaits further follow-up. Nonetheless, this combined modality strategy is encouraging and should be considered for randomized prospective evaluation

  1. Manual on brachytherapy. Incorporating: Applications guide, procedures guide, basics guide

    International Nuclear Information System (INIS)

    1992-01-01

    In addition to a basic guide to the principles of the production of ionizing radiation and to methods of radiation protection and dosimetry, this booklet includes information about radiation protection procedures for brachytherapy

  2. Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0268 TITLE: Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Eric Winer CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: OCTOBER 2017 TYPE OF REPORT: ANNUAL PREPARED FOR...CONTRACT NUMBER Randomized Trial of Asprin as Adjuvant Therapy for Node- Positive Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  3. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-02-01

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  4. Effects of Formulated Glyphosate and Adjuvant Tank Mixes on Atomization from Aerial Application Flat Fan Nozzles

    Science.gov (United States)

    2012-01-01

    Bradley K. Fritz,1 W. Clint Hoffmann,1 and W. E. Bagley2 Effects of Formulated Glyphosate and Adjuvant Tank Mixes on Atomization from Aerial...Application Flat Fan Nozzles REFERENCE: Fritz, Bradley K., Hoffmann, W. Clint, and Bagley, W. E., “Effects of Formulated Glyphosate and Adjuvant Tank Mixes on...factors. Twelve spray-solution treatments were evaluated, ten of which contained a formulated glyphosate product and nine of these con- tained an

  5. Systemic antibody response to nano-size calcium phospate biocompatible adjuvant adsorbed HEV-71 killed vaccine

    OpenAIRE

    Saeed, Mohamed Ibrahim; Omar, Abd Rahaman; Hussein, Mohd Zobir; Elkhidir, Isam Mohamed; Sekawi, Zamberi

    2015-01-01

    Purpose Since 1980s, human enterovirus-71 virus (HEV-71) is one of the common infectious disease in Asian Pacific region since late 1970s without effective commercial antiviral or protective vaccine is unavailable yet. The work examines the role of vaccine adjuvant particle size and the route of administration on postvaccination antibody response towards HEV-71 vaccine adsorbed to calcium phosphate (CaP) adjuvant. Materials and Methods First, CaP nano-particles were compared to a commercial m...

  6. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

    International Nuclear Information System (INIS)

    Showalter, Timothy N.; Ohri, Nitin; Teti, Kristopher G.; Foley, Kathleen A.; Keith, Scott W.; Trabulsi, Edouard J.; Lallas, Costas D.; Dicker, Adam P.; Hoffman-Censits, Jean; Pizzi, Laura T.; Gomella, Leonard G.

    2012-01-01

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  7. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA)

    DEFF Research Database (Denmark)

    Goldhirsch, Aron; Gelber, Richard D; Piccart-Gebhart, Martine J

    2013-01-01

    Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment......, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial....

  8. STRAP Is a Strong Predictive Marker of Adjuvant Chemotherapy Benefit in Colorectal Cancer

    OpenAIRE

    Buess, Martin; Terracciano, Luigi; Reuter, Jurgen; Ballabeni, Pierluigi; Boulay, Jean-Louis; Laffer, Urban; Metzger, Urs; Herrmann, Richard; Rochlitz, Christoph

    2004-01-01

    BACKGROUND: Molecular predictors for the effectiveness of adjuvant chemotherapy in colorectal cancer are of considerable clinical interest. To this aim, we analyzed the serine threonine receptor-associated protein (STRAP), an inhibitor of TGF-βsignaling, with regard to prognosis and prediction of adjuvant 5-FU chemotherapy benefit. i The gene copy status of STRAP was determined using quantitative realtime polymerase chain reaction in 166 colorectal tumor biopsies, which had been collected fro...

  9. Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction

    DEFF Research Database (Denmark)

    Kofoed, Steen Christian; Muhic, A; Jensen, Lene Bæksgaard

    2012-01-01

    Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected pa...... patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy....

  10. Visualizing guided tours

    DEFF Research Database (Denmark)

    Poulsen, Signe Herbers; Fjord-Larsen, Mads; Hansen, Frank Allan

    This paper identifies several problems with navigating and visualizing guided tours in traditional hypermedia systems. We discuss solutions to these problems, including the representation of guided tours as 3D metro maps with content preview. Issues regarding navigation and disorientation...

  11. Electromagnetic ultrasonic guided waves

    CERN Document Server

    Huang, Songling; Li, Weibin; Wang, Qing

    2016-01-01

    This book introduces the fundamental theory of electromagnetic ultrasonic guided waves, together with its applications. It includes the dispersion characteristics and matching theory of guided waves; the mechanism of production and theoretical model of electromagnetic ultrasonic guided waves; the effect mechanism between guided waves and defects; the simulation method for the entire process of electromagnetic ultrasonic guided wave propagation; electromagnetic ultrasonic thickness measurement; pipeline axial guided wave defect detection; and electromagnetic ultrasonic guided wave detection of gas pipeline cracks. This theory and findings on applications draw on the author’s intensive research over the past eight years. The book can be used for nondestructive testing technology and as an engineering reference work. The specific implementation of the electromagnetic ultrasonic guided wave system presented here will also be of value for other nondestructive test developers.

  12. Apparatus for guiding workpieces

    International Nuclear Information System (INIS)

    Misty, G.C.

    1984-01-01

    Workpieces are guided to the tool by a resiliently mounted support guide which accommodates irregularities in the profiles of the workpieces to maintain the axes of the workpieces in alignment with the centre line of the tool. (author)

  13. The effect of several adjuvants on glufosinate effectiveness in Conyza species.

    Science.gov (United States)

    Fernandez-Cerejido, M C; Bastida, F; Menendez, J

    2009-01-01

    The effect of several adjuvants on the effectiveness of glufosinate and the role of adherence and contact angle modifications due to the presence of these adjuvants in the spraying solution on the increase in efficacy observed on the broadleaved weeds Conyza albida and Conyza bonariensis has been determined under laboratory controlled conditions. The adjuvants used on the experiment were a mixture of methyl oleate and palmitate (MO/MP), a dodecylbenzene ammonium sulphonate (DBAS), a paraffinic oil (PO), an alkylglycol ester (AGE), and a lecithin + propionic acid + non ionic surfactant based product (LI-700). Dose-response experiments showed that C. albida displayed higher susceptibility to glufosinate than C. bonariensis, no matter the adjuvant tested. However, none of the mixtures increased the herbicide effectiveness on C. atlbida, with LI 700 and PO showing an antagonistic effect on the herbicide efficacy. On C. bonariensis, MO/MP and DBAS showed significant better results than non-amended glufosinate controls, with LI 700 showing again an antagonistic effect. Both adherence and contact angle studies were inconclusive, since adjuvants with best adherence and contact angle values were not the most effective ones. Therefore, other unknown parameters putatively modified by adjuvants such as herbicide penetration should be questioned.

  14. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.

    Science.gov (United States)

    Bos, A C R K; van Erning, F N; van Gestel, Y R B M; Creemers, G J M; Punt, C J A; van Oijen, M G H; Lemmens, V E P P

    2015-11-01

    Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus colon cancer patients within 8 weeks post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

    Science.gov (United States)

    Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

    2011-03-01

    To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  16. Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

    Science.gov (United States)

    Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

    2018-02-01

    The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

  17. Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine.

    Directory of Open Access Journals (Sweden)

    William C Weldon

    Full Text Available Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

  18. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-12

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  19. Ketamine as an adjuvant to opioids for cancer pain.

    Science.gov (United States)

    Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

    2017-06-28

    This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The

  20. NKT-cell glycolipid agonist as adjuvant in synthetic vaccine.

    Science.gov (United States)

    Liu, Zheng; Guo, Jun

    2017-11-27

    NKT cells are CD1d-restricted, glycolipid antigen-reactive, immunoregulatory T lymphocytes that can serve as a bridge between the innate and adaptive immunities. NKT cells have a wide range of therapeutic application in autoimmunity, transplant biology, infectious disease, cancer, and vaccinology. Rather than triggering "danger signal" and eliciting an innate immune response, αGalCer-based NKT-cell agonist act via a unique mechanism, recruiting NKT cells which play a T helper-like role even without peptide as Th epitope. Importantly, the non-polymorphism of CD1d render glycolipid a universal helper epitope, offering the potential to simplify the vaccine construct capable of eliciting consistent immune response in different individuals. This review details recent advances in the design of synthetic vaccines using NKT-cell agonist as adjuvant, highlighting the role of organic synthesis and conjugation technique to enhance the immunological actives and to simplify the vaccine constructs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Adjuvant radiotherapy and risk of contralateral breast cancer

    International Nuclear Information System (INIS)

    Storm, H.H.; Blettner, M.; Pedersen, J.

    1992-01-01

    To evaluate the relationship between high-dose radiotherapy and secondary breast cancer, a nested and matched case-control study in the cohort of breast cancer patients in Denmark was conducted. Radiation dose to the contralateral breast was reconstructed by medical physicists for each of the 529 cases and 529 controls, 82.4% of each group was treated with radiation. The average breast dose was 2.51 Gy, and a 20% increased risk was expected for this population at average age 51 years. There was no evidence that radiotherapy increased the overall risk of second breast cancer (RR=1.04), although the possibility of a RR as high as 1.46 could not be excluded. There was little indication that the risk varied over categories of radiation dose, time since exposure, or age at exposure. Thus, data provides additional evidence that there is little if any risk of radiation induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic X-rays or adjuvant radiotherapy) in later life. (author). 9 refs., 1 fig., 1 tab

  2. ADJUVANT PROPERTIES OF NANOPARTICLES IMMOBILIZED RECOMBINANT DIPHTHERIA TOXOID FRAGMENT

    Directory of Open Access Journals (Sweden)

    T. O. Chudina

    2017-08-01

    Full Text Available The aim of the research was to compare the characteristics of nanoparticles with different chemical structure and size (colloidal gold Gold 1 and Gold 2, calcium phosphate CaP and poly(lactideco-glykolid PLGA 1 and 2 to find the most efficient carriers of antigen — recombinant diphtheria toxoid for per os immunization. According to the MTT test, all studied particles show no significant cytotoxic impact on the studied cells in vitro, with the exception of CaP nanoparticles, which in high concentrations have cytotoxic effect on the U937 cells, and Gold nanoparticles 1 and 2, that are able to inhibit growth of the L929 cells. The most effective phagocytosis by macrophage-like cells J774 is observed for PLGA nanoparticles 1 and 2 with the immobilized antigen, while Gold nanoparticles 1 and 2 with antigen can interact with the surface of these cells without being phagocytated by them. In BALB/c mice immunized per os with antigen immobilized on PLGA 1 and 2 as well as Gold 2 carriers, the concentration of specific IgA antibodies in blood significantly increases after the second immunization, compared with controls. In the group of mice treated with PLGA 2 conjugated antigen, the concentration of specific IgG in blood after the third immunization also increases. These results show the promise of nanoparticles PLGA 1 and 2 as adjuvant for immunization per os.

  3. [Adjuvant cryosurgery in the treatment of unicameral bone cysts].

    Science.gov (United States)

    Tena-Sanabria, Mario Edgar; Hernández-Hernández, Melissa Jesús; Tena-González, Mario Edgar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Multiple treatments have been used for the unicameral bone cyst lesion, such as steroid application, multiple perforations, bone curettages, partial resection and bone grafting. The purpose of this study was to describe the evolution of children with unicameral bone cyst who were treated with cryosurgery as coadjuvant therapy. Cross-sectional descriptive study over the period between January 2001 and December 2006. Twelve patients were studied and treated at the Pediatric Orthopedics Department of the Pediatrics Hospital at the Centro Médico Nacional Siglo XXI. Twelve patients were analyzed; all of them were treated with curettage, cryotherapy and bone grafting. In 7 patients, the lesions were located in the humerus (58.3 %), in 3 in the tibia (25 %), in 1 in the ilio-ischiopubic branch (8.3 %), and in 1 in the clavicle (8.3 %). Follow-up ranged from 12 to 36 months. Bone healing required 2 to 3 months after the surgery; the response was complete in 9 (75 %) patients and partial in 3 (25 %). Function was restored in all cases, without recurrences. Cryosurgery as an adjuvant treatment and autologous or homologous bone grafting prevented local recurrence of unicameral bone cyst lesions, favored bone healing and allowed for a full range of motion functionality without complications.

  4. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    Science.gov (United States)

    Zhu, Xin Yan; Liu, Fei

    2017-04-01

    Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  5. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Adjuvant radiotherapy in high-grade extremity sarcomas

    International Nuclear Information System (INIS)

    Franca, Carlos Antonio da Silva; Penna, Antonio Belmiro Rodrigues Campbell; Carvalho, Antonio Carlos Pires; Vieira, Sergio Lannes

    2010-01-01

    Objective: to evaluate the therapies utilized in the authors' institution for management of high-grade extremity sarcomas, analyzing the overall survival rates following multidisciplinary treatment. Materials and methods: retrospective study developed in the period from 1993 to 2007 with 36 patients diagnosed with stages IIb/III, submitted to postoperative external beam radiotherapy, with or without boost dose, utilizing high-dose brachytherapy. Results: thirty-six patients underwent surgery followed by adjuvant external beam radiation therapy. Four patients (11%) received boost dose with brachytherapy, and seven (19%) received chemotherapy. The average dose for radiotherapy was 50 Gy (CI 95%: 47-53 Gy), and the four patients with brachytherapy boost received doses ranging from 16.2 to 35 Gy. Chemotherapy was indicated for seven patients (19%) with positive margins. Fifteen patients (42%) presented local or distant recurrence, and all of them progressed to death. Twenty-one patients (58%) remain with no clinical/radiological evidence of local/distant recurrence. The mean follow-up time was 88 months (IC 95%: 74-102). The overall seven years survival rate was 80%. Conclusion: combined surgery and radiotherapy is an effective treatment with excellent outcomes in cases where brachytherapy is associated, with improved overall survival rates. (author)

  7. Physical activity for women with breast cancer after adjuvant therapy.

    Science.gov (United States)

    Lahart, Ian M; Metsios, George S; Nevill, Alan M; Carmichael, Amtul R

    2018-01-29

    Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy. To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer. We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases. We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer. Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes. We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic

  8. Pocket Spending Guide

    OpenAIRE

    Poff, Karen

    2015-01-01

    Provides an example for how to set up a pocket spending guide. By filling out the guide and keeping it with you, you can easily see at any time how much money you have available to spend in each category. A pocket spending guide will help you adjust your spending plan to make your money go where you really want it to go.

  9. Managerial Accounting. Study Guide.

    Science.gov (United States)

    Plachta, Leonard E.

    This self-instructional study guide is part of the materials for a college-level programmed course in managerial accounting. The study guide is intended for use by students in conjuction with a separate textbook, Horngren's "Accounting for Management Control: An Introduction," and a workbook, Curry's "Student Guide to Accounting for Management…

  10. Long-term results of 2 adjuvant trials reveal differences in chemosensitivity and the pattern of metastases between colon cancer and rectal cancer.

    Science.gov (United States)

    Kornmann, Marko; Staib, Ludger; Wiegel, Thomas; Kron, Martina; Henne-Bruns, Doris; Link, Karl-Heinrich; Formentini, Andrea

    2013-03-01

    Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not in RC and revealed different patterns of recurrence in patients with CC and those with RC. Our aim was to compare long-term results of adjuvant treatment of colon cancer (CC) and rectal cancer (RC). Adjuvant chemotherapy of CC improved overall survival (OS), whereas that of RC remained at the level achieved by 5-fluorouracil (5-FU). We separately conducted 2 identically designed adjuvant trials in CC and RC. Patients were assigned to adjuvant chemotherapy with 5-FU alone, 5-FU + folinic acid (FA), or 5-FU + interferon-alfa. The first study enrolled patients with stage IIb/III CC, and the second study enrolled patients with stage II/III RC. All patients with RC received postoperative irradiation. Median follow-up for all patients with CC (n = 855) and RC (n = 796) was 4.9 years. The pattern and frequency of recurrence differed significantly, especially lung metastases, which occurred more frequently in RC (12.7%) than in CC (7.3%; P < .001). Seven-year OS rates for 5-FU, 5-FU + FA, and 5-FU + IFN-alfa were 54.1% (95% confidence interval [CI], 46.5-61.0), 66.8% (95% CI, 59.4-73.1), and 56.7% (95% CI, 49.3-63.4) in CC and 50.6% (95% CI, 43.0-57.7), 56.3% (95% CI, 49.4-62.7), and 54.8% (95% CI, 46.7-62.2) in RC, respectively. A subgroup analysis pointed to a reduced local recurrence (LR) rate and an increased OS by the addition of FA in stage II RC (n = 271) but not in stage III RC (n = 525). FA increased 7-year OS by 12.7 percentage points in CC but was not effective in RC. Based on these results and the pattern of metastases, our results suggest that the chemosensitivity of CC and RC may be different. Strategies different from those used in CC may be successful to

  11. Intelligent National Strategy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    China has unveiled a strategic plan aimed at strengthening I PR protection and enhancing the country’s overall competitiveness China’s State Council published the Outline of the National Intellectual Property Strategy in early June, taking on one of the country’s major bugbears. The plan aims to improve the use of intellectual property rights (IPR) by 2020 and consists of a preface, guiding prin- ciples and strategic goals, strategic focuses,

  12. Agile practice guide

    CERN Document Server

    2017-01-01

    Agile Practice Guide – First Edition has been developed as a resource to understand, evaluate, and use agile and hybrid agile approaches. This practice guide provides guidance on when, where, and how to apply agile approaches and provides practical tools for practitioners and organizations wanting to increase agility. This practice guide is aligned with other PMI standards, including A Guide to the Project Management Body of Knowledge (PMBOK® Guide) – Sixth Edition, and was developed as the result of collaboration between the Project Management Institute and the Agile Alliance.

  13. Augmenting Guided-Inquiry Learning with a Blended Classroom Approach

    Science.gov (United States)

    Baum, Edward J.

    2013-01-01

    Teaching strategies such as guided inquiry have long been reported to produce superior learning outcomes in postsecondary science education. Yet many teachers cite obstacles that prevent them from implementing the method. Students also often report negative attitudes toward guided inquiry, leading to a lack of student engagement and other…

  14. SEAPOWER: A GUIDE FOR THE TWENTY- FIRST CENTURY

    African Journals Online (AJOL)

    Abel

    $154,37 (amazon.com hardback). With the publication of Seapower: A Guide for the Twenty-First Century. Geoffrey Till has set the standard for publications on all things maritime. The updated and expanded new edition of the book is an essential guide for students of naval history and maritime strategy and provides ...

  15. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is

  16. Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: impact of distinct additional adjuvants

    NARCIS (Netherlands)

    Radosević, Katarina; Rodriguez, Ariane; Mintardjo, Ratna; Tax, Dennis; Bengtsson, Karin Lövgren; Thompson, Catherine; Zambon, Maria; Weverling, Gerrit Jan; Uytdehaag, Fons; Goudsmit, Jaap

    2008-01-01

    A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic. Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to

  17. Integrated corridor management : implementation guide and lessons learned.

    Science.gov (United States)

    2012-02-01

    This implementation guide is intended for use by adopters of integrated corridor management (ICM) approaches and strategies to address congestion and travel time reliability issues within specific travel corridors. It introduces the topic of ICM and ...

  18. Double-shell tank emergency pumping guide

    International Nuclear Information System (INIS)

    BROWN, M.H.

    1999-01-01

    This Double-Shell Tank Emergency Pumping Guide provides the preplanning necessary to expeditiously remove any waste that may leak from the primary tank to the secondary tank for Hanfords 28 DSTs. The strategy is described, applicable emergency procedures are referenced, and transfer routes and pumping equipment for each tank are identified

  19. Double-shell tank emergency pumping guide

    International Nuclear Information System (INIS)

    BROWN, M.H.

    1999-01-01

    This Double-Shell Tank Emergency Pumping Guide provides the preplanning necessary to expeditiously remove any waste that may leak from the primary tank to the secondary tank for Hanford's 28 DSTS. The strategy is described, applicable emergency procedures are referenced, and transfer routes and pumping equipment for each tank are identified

  20. Social Marketing. A Guide. First Draft.

    Science.gov (United States)

    Rosenau, Fred S.

    This introductory guide to nonprofit social marketing provides marketing techniques and guidelines in seven chapters. Topics covered include a general discussion of social marketing, with several definitions; market research, including factors to be considered in planning a marketing strategy, forces for and against educational changes, cluster…

  1. Food Production, Management, and Services: Curriculum Guide.

    Science.gov (United States)

    Mumme, Debbie; Koukel, Sonja

    This curriculum guide provides occupationally specific training designed to develop knowledge and skills for employment in the area of food production, management, and services. Contents include the Texas Essential Knowledge and Skills (TEAKS); sample course outlines; instructional strategies organized topically by chapters, each containing a…

  2. A Guide to the Field Guides.

    Science.gov (United States)

    Natural History, 1987

    1987-01-01

    Provides a compilation of recommended field guides which deal with birds, mammals, trees, and wildflowers. Each recommended volume is described, noting its distinguishing features and evaluating its organization, photography, and text. Includes the author, publisher, and suggested retail price. (TW)

  3. Novel strategies in immunotherapy for allergic diseases.

    Science.gov (United States)

    Rajakulendran, Mohana; Tham, Elizabeth Huiwen; Soh, Jian Yi; Van Bever, H P

    2018-04-01

    Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended.

  4. How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey

    OpenAIRE

    Acevedo, Francisco; Sanchez, Cesar; Jans, Jaime; Rivera, Solange; Camus, Mauricio; Besa, Pelayo

    2014-01-01

    Background: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the H...

  5. Recruitment to and pilot results of the PACES randomized trial of physical exercise during adjuvant chemotherapy for colon cancer.

    Science.gov (United States)

    van Waart, Hanna; Stuiver, Martijn M; van Harten, Wim H; Geleijn, Edwin; de Maaker-Berkhof, Marianne; Schrama, Jolanda; Geenen, Maud M; Meerum Terwogt, Jetske M; van den Heiligenberg, Simone M; Hellendoorn-van Vreeswijk, Jeannette A J H; Sonke, Gabe S; Aaronson, Neil K

    2018-01-01

    We report the recruitment rate, reasons for and factors influencing non-participation, and descriptive results of a randomized controlled trial of two different exercise programs for patients with colon cancer undergoing adjuvant chemotherapy. Participants were randomized to a low-intensity, home-based program (Onco-Move), a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack), or Usual Care. Non-participants provided reasons for non-participation and were asked to complete a questionnaire assessing behavioral and attitudinal variables. Trial participants completed performance-based and self-reported outcome measures prior to randomization, at the end of chemotherapy, and at the 6-month follow-up. Twenty-three of 63 referred patients agreed to participate in the trial. All 40 non-participants provided reasons for non-participation. Forty-five percent of the non-participants completed the questionnaire. Those who did not want to exercise had higher fatigue scores at baseline and a more negative attitude toward exercise. Compliance to both programs was high and no adverse events occurred. On average, the colon cancer participants were able to maintain or improve their physical fitness levels and maintain or decrease their fatigue levels during chemotherapy and follow-up. Recruitment of patients with colon cancer to a physical exercise trial during adjuvant chemotherapy proved to be difficult, underscoring the need to develop more effective strategies to increase participation rates. Both home-based and supervised programs are safe and feasible in patients with colon cancer undergoing chemotherapy. Effectiveness needs to be established in a larger trial. Netherlands Trial Register - NTR2159.

  6. Effect of Different Adjuvants on Protection and Side-Effects Induced by Helicobacter suis Whole-Cell Lysate Vaccination.

    Directory of Open Access Journals (Sweden)

    Iris Bosschem

    Full Text Available Helicobacter suis (H. suis is a widespread porcine gastric pathogen, which is also of zoonotic importance. The first goal of this study was to investigate the efficacy of several vaccine adjuvants (CpG-DNA, Curdlan, Freund's Complete and Incomplete, Cholera toxin, administered either subcutaneously or intranasally along with H. suis whole-cell lysate, to protect against subsequent H. suis challenge in a BALB/c infection model. Subcutaneous immunization with Freund's complete (FC/lysate and intranasal immunization with Cholera toxin (CT/lysate were shown to be the best options for vaccination against H. suis, as determined by the amount of colonizing H. suis bacteria in the stomach, although adverse effects such as post-immunization gastritis/pseudo-pyloric metaplasia and increased mortality were observed, respectively. Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects. A CCR4 antagonist that transiently inhibits the migration of regulatory T cells was also included as a new adjuvant in this second study. Results confirmed that immunization with CT (intranasally or sublingually is among the most effective vaccination protocols, but increased mortality was still observed. In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed. Compared to the FC/lysate immunized group, gastric pseudo-pyloric metaplasia was less severe or even absent in the CCR4 antagonist/lysate immunized group. In general, an inverse correlation was observed between IFN-γ, IL-4, IL-17, KC, MIP-2 and LIX mRNA expression and H. suis colonization density, whereas lower IL-10 expression levels were observed in partially protected animals.

  7. Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Petrina Kapewangolo

    2017-10-01

    Full Text Available Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs of infected patients on combination antiretroviral therapy (cART. The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC inhibition, and protein kinase C (PKC activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC, significantly (p < 0.05 induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL-2, IL-6, tumour necrosis factor (TNF-α, and interferon (IFN-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here.

  8. ERCC1 as a biomarker for bladder cancer patients likely to benefit from adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Sun, Jong-Mu; Choi, Han Yong; Lim, Ho Yeong; Sung, Ji-Youn; Park, Se Hoon; Kwon, Ghee Young; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Jo, Jisuk

    2012-01-01

    The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair cross-complementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer. A retrospective analysis was performed on 93 patients with completely resected transitional cell carcinoma of the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1 expression was analyzed in 57 patients treated with adjuvant gemcitabine plus cisplatin chemotherapy and 36 who were not treated. Among 93 patients, ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1 positivity was significantly associated with longer survival (adjusted hazard ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the group without adjuvant chemotherapy while ERCC1 positivity was associated with shorter survival among patients who have received adjuvant chemotherapy (adjusted hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical benefit from adjuvant chemotherapy was associated with ERCC1 negativity as measured by overall survival (test for interaction, P = 0.034) and by disease-free survival (test for interaction, P = 0.20). Among patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors. Future prospective, randomized studies are warranted to confirm our findings

  9. The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

    Science.gov (United States)

    Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

    2016-11-01

    To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-01-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

  11. Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer.

    Science.gov (United States)

    Park, Hyung Soon; Jung, Minkyu; Shin, Sang Joon; Heo, Su Jin; Kim, Chang Gon; Lee, Min Goo; Beom, Seung Hoon; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Ahn, Joong Bae

    2016-03-01

    The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain. We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy. Among all patients, 176 (79.6%) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95% confidence interval (95% CI), 7.4-90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0-1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95% CI 0.32-0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95% CI 0.48-2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833). CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.

  12. Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer

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    Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

    2015-01-01

    Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a “high-risk situation” (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12 %); 77 of all T4 patients received postoperative chemotherapy (33 %). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (p < 0.001) and recurrence-free survival (p = 0.008). However, no difference was observed between oxaliplatin-containing and non-oxaliplatin-containing treatment regimens. G2 and G3 tumors were found to particularly benefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients. The online version of this article (doi:10.1186/s12885-015-1404-9) contains supplementary material, which is available to authorized users

  13. Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

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    Denicar Lina Nascimento Fabris Maeda

    2017-09-01

    Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

  14. Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

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    Chung, Ki-Young Y; Kelsen, David

    2006-06-01

    The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

  15. Preparation and evaluation of functional foods in adjuvant arthritis

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    Al-Okbi, S. Y.

    2012-10-01

    Full Text Available Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended.

    La artritis adyuvante es un modelo utilizado en animales y se caracteriza por ser muy parecida a la artritis reumatoide en humanos. Se trata de un modelo de trabajo utilizado con éxito para estudiar nuevos agentes anti-inflamatorios. En estudios previos (animales y clínica hemos demostrado que

  16. Weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Hu Wei; Ding Weijun; Yang Haihua; Shao Minghai; Wang Biyun; Wang Jianhua; Wu Sufang; Wu Shixiu; Jin Lihui; Ma, Charlie C.-M.

    2009-01-01

    Purpose: To evaluate the efficacy and toxicity of weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy (AC) in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Between 2004 and 2007, 54 patients with locally advanced NPC were included in this protocol. Patient characteristics: median age 48; 69% male; 52% World Health Organization (WHO) III; 50% stage III, 50% stage IV. The patients underwent a course of definitive conventional radiotherapy (70 Gy in 7 weeks with 2 Gy/fraction), with concurrent weekly paclitaxel 35 mg/m 2 from the first to the sixth week of radiation. AC was started 4 weeks after the end of the radiotherapy (RT), paclitaxel 135 mg/m 2 on day 1 and cisplatin 30 mg/m 2 on days 1-3 were administered every 4 weeks for two cycles. Results: Median follow-up was 32 months. Eighty-five percentage of complete response and 15% partial response were achieved at the time of one month after AC. The 3-year actuarial rate of local regional control was 86%; distant metastases-free survival, progression-free survival and overall survival at 3 years were 81%, 69% and 76%, respectively. Forty-nine (91%) patients completed six courses of concurrent chemotherapy with weekly paclitaxel, and 4 (7%) patients delayed at the second cycle of AC. No patient developed severe acute toxicities. Conclusions: Weekly paclitaxel with concurrent RT followed by AC is a potentially effective and toxicity tolerable method for locally advanced NPC. Further studies are needed to identify the optimal dose of weekly paclitaxel in this strategy.

  17. Single nucleotide polymorphisms and unacceptable late toxicity in breast cancer adjuvant radiotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Lazzari G

    2017-05-01

    Full Text Available Grazia Lazzari,1 Maria Iole Natalicchio,2 Angela Terlizzi,3 Francesco Perri,4 Giovanni Silvano1 1Radiation Oncology Unit, San Giuseppe Moscati Hospital, Taranto, 2Molecular Biology Laboratory, Pathological Anatomy Department, Ospedali Riuniti, Foggia, 3Medical Physic Unit, San Giuseppe Moscati Hospital, 4Medical Oncology Unit, Presidio Ospedaliero Centrale - Santissima Annunziata, Taranto, Italy Background: There has recently been a strong interest in the inter-individual variation in normal tissue and tumor response to radiotherapy (RT, because tissue radiosensitivity seems to be under genetic control. Evidence is accumulating on the role of polymorphic genetic variants, such as single nucleotide polymorphisms (SNPs that could influence normal tissue response after radiation. The most studied SNPs include those in genes involved in DNA repair (single- and double-strand breaks, and base excision and those active in the response to oxidative stress.Case report: We present the case report of a 60-year-old woman with early breast cancer who underwent adjuvant hormone therapy and conventional radiotherapy, and subsequently developed unacceptable cosmetic toxicities of the irradiated breast requiring a genetic test of genes involved in DNA repair mechanisms. The patient was found to be heterozygous for G28152A (T/C and C18067T (A/G mutations in X-ray repair cross-complementing group 1 (XRCC1 and 3 (XRCC3, respectively, homozygous for A313G (G/G mutation in glutathione S transferase Pi 1 (GSTP1, and wild-type for A4541G (A/A in XRCC3 and G135C (G/G in RAD51 recombinase.Conclusion: The role of SNPs should be taken into account when a severe phenomenon appears in normal tissues after radiation treatment, because understanding the molecular basis of individual radiosensitivity may be useful for identifying moderately or extremely radiosensitive patients who may need tailored therapeutic strategies. Keywords: radiosensitivity, SNPs, fibrosis, DNA repair

  18. Feasibilty of a sleep intervention during adjuvant breast cancer chemotherapy.

    Science.gov (United States)

    Berger, Ann M; VonEssen, Susanna; Khun, Brett R; Piper, Barbara F; Farr, Lynne; Agrawal, Sangeeta; Lynch, James C; Higginbotham, Patti

    2002-01-01

    To evaluate the feasibility of an intervention designed to promote sleep and modify fatigue during four cycles of adjuvant breast cancer chemotherapy. Prospective, repeated measures, quasi-experimental feasibility study. Midwestern urban oncology clinics. 25 women between the ages of 40-65 (mean = 54.3) with stage I-II breast cancer receiving doxorubicin-based chemotherapy. Each woman developed, reinfo