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Sample records for valid therapeutic option

  1. Central venous catheters: detection of catheter complications and therapeutical options

    International Nuclear Information System (INIS)

    Gebauer, B.; Beck, A.; Wagner, H.J.; Vivantes-Kliniken, Hellersdorf und Prenzlauer Berg

    2008-01-01

    For modern medicine central venous catheters play an important role for diagnostic and therapeutic options. Catheter implantation, complication detection and therapy of catheter complications are an increasing demand for the radiologist. The review article provides an overview of different catheter types, their indications, advantages and disadvantages. Catheter malpositions are usually detectable in conventional X-ray. Most malpositions are correctable using interventional-radiological techniques. In addition therapeutical options for thrombotic complications (venous thrombosis, catheter occlusion, fibrin sheath) are discussed. In case of an infectious catheter complication, usually a catheter extraction and re-implantation is necessary

  2. Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

    Science.gov (United States)

    Cataland, S R; Wu, H M

    2015-06-01

    Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

  3. Therapeutic Options in Idiopathic Burning Mouth Syndrome: Literature Review

    Science.gov (United States)

    Miziara, Ivan; Chagury, Azis; Vargas, Camila; Freitas, Ludmila; Mahmoud, Ali

    2014-01-01

    Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders. Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years. Data Synthesis We conducted a literature review on PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and only selected studies comparing different therapeutic options in idiopathic BMS, with preference for randomized and double-blind controlled studies. Final Comments Topical clonazepam showed good short-term results for the relief of pain, although this was not presented as a definitive cure. Similarly, α-lipoic acid showed good results, but there are few randomized controlled studies that showed the long-term results and complete remission of symptoms. On the other hand, cognitive therapy is reported as a good and lasting therapeutic option with the advantage of not having side effects, and it can be combined with pharmacologic therapy. PMID:25992157

  4. Therapeutic Options in Idiopathic Burning Mouth Syndrome: Literature Review

    Directory of Open Access Journals (Sweden)

    Miziara, Ivan

    2014-07-01

    Full Text Available Introduction Burning mouth syndrome (BMS is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders. Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years. Data Synthesis We conducted a literature review on PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and only selected studies comparing different therapeutic options in idiopathic BMS, with preference for randomized and double-blind controlled studies. Final Comments Topical clonazepam showed good short-term results for the relief of pain, although this was not presented as a definitive cure. Similarly, α-lipoic acid showed good results, but there are few randomized controlled studies that showed the long-term results and complete remission of symptoms. On the other hand, cognitive therapy is reported as a good and lasting therapeutic option with the advantage of not having side effects, and it can be combined with pharmacologic therapy.

  5. Therapeutic options for lip augmentation.

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    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  6. Therapeutic options in chronic heart failure. Findings on chest X-ray

    International Nuclear Information System (INIS)

    Granitz, M.R.; Meissnitzer, T.; Meissnitzer, M.W.; Hergan, K.; Altenberger, J.; Granitz, C.

    2016-01-01

    The contribution covers drugless therapeutic options for chronic heart failure: the implantable cardioverter/defibrillator (ICD), the cardiac resynchronization therapy (CRT), the interventional catheter treatment of functional mitral insufficiency, and mechanical heart supporting systems and heart transplantation.

  7. Therapeutic options to manage bleeding in a dentist’s office

    Science.gov (United States)

    Rostetter, Claudio; Finkenstädt, Tim; Rücker, Martin; Lübbers, Heinz-Theo

    2018-06-18

    This manuscript provides an overview of therapeutic options for the problem of bleeding in a dentist’s office. Bleeding after tooth extraction is a very common finding in dental medicine and persistent blood in the mouth is obviously uncomfortable and sometimes terrifying for the patient. Most bleedings can be stopped simply with compression, in some cases a homeostatic therapy is necessary. For local compression, a swab with tranexamic acid is useful. If local compression is not sufficient, sutures are often an option. A very effective therapy would also be Tabotamp®, a local hemostypticum which is placed onto the bleeding and should increase the thrombocytic aggregation. In the worst case Floseal®, a human Thrombin, can be placed locally. It stops the bleeding very fast and sufficiently.

  8. Therapeutic Options for the Management of the Cardiorenal Syndrome

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    Katerina Koniari

    2011-01-01

    Full Text Available Patients with heart failure often present with impaired renal function, which is a predictor of poor outcome. The cardiorenal syndrome is the worsening of renal function, which is accelerated by worsening of heart failure or acute decompensated heart failure. Although it is a frequent clinical entity due to the improved survival of heart failure patients, still its pathophysiology is not well understood, and thus its therapeutic approach remains controversial and sometimes ineffective. Established therapeutic strategies, such as diuretics and inotropes, are often associated with resistance and limited clinical success. That leads to an increasing concern about novel options, such as the use of vasopressin antagonists, adenosine A1 receptor antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of the cardiorenal syndrome remains quite empirical.

  9. Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

    Science.gov (United States)

    Li, Hai-feng; Zou, Yan; Ding, Gangqiang

    2013-01-01

    Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

  10. Skewed Epigenetics: An Alternative Therapeutic Option for Diabetes Complications

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    Gabriele Togliatto

    2015-01-01

    Full Text Available Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called “metabolic memory.”

  11. Therapeutic options in pediatric non alcoholic fatty liver disease: current status and future directions

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    Vajro Pietro

    2012-10-01

    Full Text Available Abstract The epidemics of overweight and obesity has resulted in a significant increase of non alcoholic fatty liver disease (NAFLD, a potentially progressive condition. Currently, obesity related hepatopathy represents therefore the main cause of pediatric chronic liver disease. The first choice treatment at all ages is weight loss and/or lifestyle changes, however compliance is very poor and a pharmacological approach has become necessary. In the present article we present a systematic literature review focusing on established pediatric NALFD drugs (ursodeoxycholic acid, insulin sensitizers, and antioxidants and on innovative therapeutic options as well. Regarding the former ones, a pediatric pilot study highlighted that ursodeoxycholic acid is not efficient on transaminases levels and bright liver. Similarly, a recent large scale, multicenter randomized clinical trial (TONIC study showed that also insulin sensitizers and antioxidant vitamin E have scarce effects on serum transaminase levels. Among a large series of novel therapeutic approaches acting on recently proposed different pathomechanisms, probiotics seem hitherto the most interesting and reasonable option for their safety and tolerability. Toll-like receptors modifiers, Pentoxifylline, and Farnesoid X receptors agonists have been still poorly investigated, and will need further studies before becoming possible promising innovative therapeutic strategies.

  12. Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma.

    Science.gov (United States)

    Chen, Shao-Ru; Qiu, Hong-Cong; Hu, Yang; Wang, Ying; Wang, Yi-Tao

    2016-06-01

    Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/β-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Merkel Cell Carcinoma: Chemotherapy and Emerging New Therapeutic Options

    International Nuclear Information System (INIS)

    Desch, L.; Kunstfeld, R.

    2013-01-01

    Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor that typically occurs in elderly, immunosuppressed patients. Infection with Merkel cell virus (MCV) and immunosuppression play an important role in the development of MCC. Different staging systems make it difficult to compare the existing clinical data. Furthermore, there predominantly exist single case reports and case series, but no randomized controlled trials. However, it is necessary to develop further therapy options because MCC tends to grow rapidly and metastasizes early. In the metastatic disease, therapeutic attempts were made with various chemotherapeutic combination regimens. Because of the high toxicity of these combinations, especially those established in SCLC, and regarding the unsatisfying results, the challenge is to balance the pros and cons of chemotherapy individually and carefully. Up to now, emerging new therapy options as molecular-targeted agents, for example, pipebuzone, imatinib, or somatostatin analogues as well as immunologic als, for example, imiquimod and interferons, also showed less success concerning the disease-free response rates. According to the literature, neither chemotherapy nor molecular-targeted agents or immunotherapeutic strategies have shown promising effects in the therapy of the metastatic disease of MCC so far. There is a great demand for randomized controlled studies and a need for an MCC registry and multicenter clinical trials due to the tumors curiosity.

  14. Validation of limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring - is a separate validation group required?

    NARCIS (Netherlands)

    Proost, J. H.

    Objective: Limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring are usually validated in a separate group of patients, according to published guidelines. The aim of this study is to evaluate the validation of LSM by comparing independent validation with cross-validation

  15. [Usher syndrome: clinical features, diagnostic options, and therapeutic prospects].

    Science.gov (United States)

    Seeliger, M W; Fischer, M D; Pfister, M

    2009-06-01

    Usher syndrome denotes a clinically and genetically heterogeneous combination of retinitis pigmentosa and sensorineural deafness. The division into subtypes I, II, and III is based on the degree of hearing loss: Type I is characterized by deafness from birth together with ataxia and retarded motor development, type II by a stationary deafness of a moderate degree, and type III by a progressive deafness with adult onset. In Germany, Usher syndrome currently bears particular relevance because in January 2009 a new compulsory screening of auditory function in newborn infants was introduced. Consequently, it can be expected that a higher number of patients with Usher syndrome will be identified in early childhood and referred to ophthalmologists. The focus of this work is to introduce the typical clinical picture of Usher syndrome, summarize diagnostic options, and give an overview of therapeutic strategies.

  16. Factors associated with therapeutic inertia in hypertension: validation of a predictive model.

    Science.gov (United States)

    Redón, Josep; Coca, Antonio; Lázaro, Pablo; Aguilar, Ma Dolores; Cabañas, Mercedes; Gil, Natividad; Sánchez-Zamorano, Miguel Angel; Aranda, Pedro

    2010-08-01

    To study factors associated with therapeutic inertia in treating hypertension and to develop a predictive model to estimate the probability of therapeutic inertia in a given medical consultation, based on variables related to the consultation, patient, physician, clinical characteristics, and level of care. National, multicentre, observational, cross-sectional study in primary care and specialist (hospital) physicians who each completed a questionnaire on therapeutic inertia, provided professional data and collected clinical data on four patients. Therapeutic inertia was defined as a consultation in which treatment change was indicated (i.e., SBP >or= 140 or DBP >or= 90 mmHg in all patients; SBP >or= 130 or DBP >or= 80 in patients with diabetes or stroke), but did not occur. A predictive model was constructed and validated according to the factors associated with therapeutic inertia. Data were collected on 2595 patients and 13,792 visits. Therapeutic inertia occurred in 7546 (75%) of the 10,041 consultations in which treatment change was indicated. Factors associated with therapeutic inertia were primary care setting, male sex, older age, SPB and/or DBP values close to normal, treatment with more than one antihypertensive drug, treatment with an ARB II, and more than six visits/year. Physician characteristics did not weigh heavily in the association. The predictive model was valid internally and externally, with acceptable calibration, discrimination and reproducibility, and explained one-third of the variability in therapeutic inertia. Although therapeutic inertia is frequent in the management of hypertension, the factors explaining it are not completely clear. Whereas some aspects of the consultations were associated with therapeutic inertia, physician characteristics were not a decisive factor.

  17. Emerging techniques for the discovery and validation of therapeutic targets for skeletal diseases.

    Science.gov (United States)

    Cho, Christine H; Nuttall, Mark E

    2002-12-01

    Advances in genomics and proteomics have revolutionised the drug discovery process and target validation. Identification of novel therapeutic targets for chronic skeletal diseases is an extremely challenging process based on the difficulty of obtaining high-quality human diseased versus normal tissue samples. The quality of tissue and genomic information obtained from the sample is critical to identifying disease-related genes. Using a genomics-based approach, novel genes or genes with similar homology to existing genes can be identified from cDNA libraries generated from normal versus diseased tissue. High-quality cDNA libraries are prepared from uncontaminated homogeneous cell populations harvested from tissue sections of interest. Localised gene expression analysis and confirmation are obtained through in situ hybridisation or immunohistochemical studies. Cells overexpressing the recombinant protein are subsequently designed for primary cell-based high-throughput assays that are capable of screening large compound banks for potential hits. Afterwards, secondary functional assays are used to test promising compounds. The same overexpressing cells are used in the secondary assay to test protein activity and functionality as well as screen for small-molecule agonists or antagonists. Once a hit is generated, a structure-activity relationship of the compound is optimised for better oral bioavailability and pharmacokinetics allowing the compound to progress into development. Parallel efforts from proteomics, as well as genetics/transgenics, bioinformatics and combinatorial chemistry, and improvements in high-throughput automation technologies, allow the drug discovery process to meet the demands of the medicinal market. This review discusses and illustrates how different approaches are incorporated into the discovery and validation of novel targets and, consequently, the development of potentially therapeutic agents in the areas of osteoporosis and osteoarthritis

  18. Micro - Focused Phototherapy Associated To Janus Kinase Inhibitor: A Promising Valid Therapeutic Option for Patients with Localized Vitiligo

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    Serena Gianfaldoni

    2018-01-01

    Full Text Available BACKGROUND: Vitiligo is an acquired pigmentary cutaneous disease, characterised by the progressive loss of melanocytes, resulting in hypopigmented skin areas which progressively become amelanotic. Classically, vitiligo treatments are unsatisfactory and challenging. Despite the continuous introduction of new therapies, phototherapy is still the mainstay for vitiligo repigmentation. AIM: The aim of this multicenter observational retrospective study was to evaluate the efficacy and safety of the nb - UVB micro - phototherapy (BIOSKIN EVOLUTION®, used alone or in associations with an oral Janus kinase inhibitor (Tofacitinib citrate, in the treatment of stable or active forms of localised vitiligo. MATERIAL AND METHODS: Fifty eight patients had been treated with n-UVB micro-photootherapy (Group A; 9 patients had been treated with phototherapy plus Tofacitinb citrate (Group B. RESULTS: Among Group A, 42 patients (72% obtained a re-pigmentation rate higher than 75%, with a medium value of 77%. 11 patients (19% achieved a marked improvement of the clinical findings with a repigmentation rate between 50-75%; 4 patients (8% showed a moderate response with a lesional repigmentation of 25-50%. Only one patient (1% had a poor response to the phototherapeutic treatment CONCLUSION: Nb - UVB micro-focused phototherapy is one of the most effective therapeutic options for vitiligo treatment. The association of micro-focused phototherapy to Tofacitinib citrate seems to provide better clinical results in term of repigmentation rate.

  19. Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis.

    NARCIS (Netherlands)

    Hoogeboom, T.J.; Oosting, E.; Vriezekolk, J.E.; Veenhof, C.; Siemonsma, P.C.; Bie, R.A. de; Ende, C.H.M. van den; Meeteren, N.L.U. van

    2012-01-01

    Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the

  20. IFN-αα induced psoriatic arthritis and HCV-related liver cirrhosis. Therapeutic options and patient’s opinion

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    M. Piga

    2011-09-01

    Full Text Available Hepatitis C virus (HCV infection in the setting of Psoriatic Arthritis is an additional variable to be considered in the therapeutic approach to the disease because of the complications of an immunosuppressive treatment in the course of a chronic infection and the possible hepatotoxicity of many drugs conventionally used to treat psoriatic arthritis. The case reported explores the therapeutic options in a patient with IFN-α induced psoriatic arthritis, characterised by severe arthritis and psoriasis but also the concomitant presence of HCV chronic hepatitis, in light of the patient’s concerns

  1. [Epigenetic regulations and cerebral plasticity: towards new therapeutic options in neurodegenerative diseases?

    Science.gov (United States)

    Merienne, Karine; Boutillier, Anne-Laurence

    2016-01-01

    Although revealed in the 1950's, epigenetics is still a fast-growing field. Its delineations continuously evolve and become clarified. In particular, "neuroepigenetics", a notion that encompasses epigenetic regulations associated with neuronal processes, appears very promising. Indeed, the challenge to be undertaken in this sub-field is double. On the one hand, it should bring molecular comprehension of specific neuronal processes, some of them falling within the long term regulations, such as learning and memory. On the other hand, it could bring therapeutic options for brain diseases, e.g. neurodegenerative diseases such as Alzheimer's or Huntington's diseases. © Société de Biologie, 2017.

  2. Studies on nonsense mediated decay reveal novel therapeutic options for genetic diseases.

    Science.gov (United States)

    Bashyam, Murali D

    2009-01-01

    Scientific breakthroughs have often led to commercially viable patents mainly in the field of engineering. Commercialization in the field of medicine has been restricted mostly to machinery and engineering on the one hand and therapeutic drugs for common chronic ailments such as cough, cold, headache, etc, on the other. Sequencing of the human genome has attracted the attention of pharmaceutical companies and now biotechnology has become a goldmine for commercialization of products and processes. Recent advances in our understanding of basic biological processes have resulted in the opening of new avenues for treatment of human genetic diseases, especially single gene disorders. A significant proportion of human genetic disorders have been shown to be caused due to degradation of transcripts for specific genes through a process called nonsense mediated decay (NMD). The modulation of NMD provides a viable therapeutic option for treatment of several genetic disorders and therefore has been a good prospect for patenting and commercialization. In this review the molecular basis for NMD and attempts to treat genetic diseases which result from NMD are discussed.

  3. Acupuncture as a therapeutic treatment option for threatened miscarriage

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    Betts Debra

    2012-03-01

    Full Text Available Abstract Background Threatened miscarriage involves vaginal bleeding in a pregnancy that remains viable. This is a common early pregnancy complication with increased risk factors for early pregnancy loss, preterm premature rupture of membranes (PPROM, preterm delivery, low birth weight babies and maternal antepartum haemorrhage. Currently there are no recommended medical treatment options, rather women receive advice that centres on a 'wait and see' approach. For women with a history of unexplained recurrent miscarriage providing supportive care in a subsequent pregnancy improves live birthing outcomes, but the provision of supportive care to women experiencing threatened miscarriage has to date not been examined. Discussion While it is known that 50-70% of miscarriages occur due to chromosomal abnormalities, the potential for therapeutic intervention amongst the remaining percentage of women remains unknown. Complementary and alternative medicine (CAM therapies have the potential to provide supportive care for women presenting with threatened miscarriage. Within fertility research, acupuncture demonstrates beneficial hormonal responses with decreased miscarriage rates, raising the possibility acupuncture may promote specific beneficial effects in early pregnancy. With the lack of current medical options for women presenting with threatened miscarriage it is timely to examine the possible treatment benefits of providing CAM therapies such as acupuncture. Summary Despite vaginal bleeding being a common complication of early pregnancy there is often reluctance from practitioners to discuss with women and medical personal how and why CAM may be beneficial. In this debate article, the physiological processes of early pregnancy together with the concept of providing supportive care and acupuncture are examined. The aim is to raise awareness and promote discussion as to the beneficial role CAM may have for women presenting with threatened miscarriage.

  4. Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

    Science.gov (United States)

    Zerbib, Frank; Roman, Sabine

    2015-07-01

    With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.

  5. Hereditary angioedema as a metabolic liver disorder: novel therapeutic options and prospects for cure

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    Rohan Ameratuga

    2016-11-01

    Full Text Available Hereditary angioedema (HAE is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder. In spite of mutations of the SERPING1 gene, autoimmunity and infections are not prominent features of the condition. Here we present the argument that HAE should be viewed primarily as a metabolic liver disorder. This conceptual paradigm shift will stimulate basic research and may facilitate new therapeutic approaches to HAE outlined in this paper. We suggest several novel potential treatment options for HAE from the perspectives of clinical immunology, molecular biology and liver transplantation. Many of these offer the prospect of curing the disorder. The effectiveness of these options are rapidly improving in many cases and their risks are decreasing. Given the very high costs of treating HAE, some of these curative options may become feasible in the next decade.

  6. Comparison between three option, four option and five option multiple choice question tests for quality parameters: A randomized study.

    Science.gov (United States)

    Vegada, Bhavisha; Shukla, Apexa; Khilnani, Ajeetkumar; Charan, Jaykaran; Desai, Chetna

    2016-01-01

    Most of the academic teachers use four or five options per item of multiple choice question (MCQ) test as formative and summative assessment. Optimal number of options in MCQ item is a matter of considerable debate among academic teachers of various educational fields. There is a scarcity of the published literature regarding the optimum number of option in each item of MCQ in the field of medical education. To compare three options, four options, and five options MCQs test for the quality parameters - reliability, validity, item analysis, distracter analysis, and time analysis. Participants were 3 rd semester M.B.B.S. students. Students were divided randomly into three groups. Each group was given one set of MCQ test out of three options, four options, and five option randomly. Following the marking of the multiple choice tests, the participants' option selections were analyzed and comparisons were conducted of the mean marks, mean time, validity, reliability and facility value, discrimination index, point biserial value, distracter analysis of three different option formats. Students score more ( P = 0.000) and took less time ( P = 0.009) for the completion of three options as compared to four options and five options groups. Facility value was more ( P = 0.004) in three options group as compared to four and five options groups. There was no significant difference between three groups for the validity, reliability, and item discrimination. Nonfunctioning distracters were more in the four and five options group as compared to three option group. Assessment based on three option MCQs is can be preferred over four option and five option MCQs.

  7. Burden to importance ratio as a quantitative measure to validate the RISC-3 SSC in OPTION-2

    International Nuclear Information System (INIS)

    Ha, J. S.; Sung, P. H.

    2004-01-01

    A Risk-Informed Safety Significance Categorization (RISSC) is to categorize structures, systems, or components (SSCs) of a Nuclear Power Plant (NPP) into two or more groups, according to their safety significance using both probabilistic and deterministic insights. Recently, OPTION-2 (which is an emerging risk-informed paradigm) recommends that SSCs should be categorized into four groups according to whether they are safety-related or not as well as their safety significance. With the change of 10 CFR 50, safety-related components which categorized into low safety significant SSC (RISC-3 SSC) can be exempted from the existing conservative requirements. Consequently, as OPTION-2 paradigm is applied, a validation process focused on the RISC-3 SSC is needed to assure the categorization results, because most of existing RISSC methods focused on the categorization of the whole SSCs of NPPs based on importance measures obtained from probabilistic and deterministic insights. In this work, Burden to Importance Ratio (BIR) is utilized as a measure for the validation of RISC-3 SSC in OPTION-2. To demonstrate the usefulness of the proposed approach, the approach is applied to 22 components selected from 512 In-Service Test (IST) components of Ulchin unit 3. The results of the application show that the proposed approach is useful for the validation of RISC-3 SSC in OPTION-2

  8. Graves' disease. Manifestations and therapeutic options

    International Nuclear Information System (INIS)

    McFarland, K.F.; Saleeby, G.

    1988-01-01

    Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan

  9. [Are therapeutics decisions homogeneous in multidisciplinary onco-urology staff meeting? Comparison of therapeutic options taken in four departments from Paris].

    Science.gov (United States)

    Audenet, F; Lejay, V; Mejean, A; De La Taille, A; Abbou, C-C; Lebret, T; Botto, H; Bitker, M-O; Roupret, M

    2012-06-01

    One of the priorities of the "Plan against the Cancer" in France is to ensure the discussion of all cancer cases in a multidisciplinary meeting staff (RCP). The multidisciplinary collaboration is proposed to guarantee a discussion between specialists in every cases, particularly in complex cases. The aim of this study was to compare the therapeutic decision taken in four RCP in Paris Île-de-France academic centres for three identical cases. Three cases of urological oncology (prostate cancer [PCa], renal cell carcinoma [RCC] and bladder tumour) were selected by a single urologist, not involved in further discussion. These cases were blindly presented in four academic urology department from Paris: Pitié-Salpêtrière Hospital, Mondor Hospital, the Georges-Pompidou European Hospital and Foch Hospital. The four centres met the criteria of quality of RCP in terms of multidisciplinarity, frequency and standardization. The therapeutic suggestions were similar in the RCC cases, there were differences in the surgical approaches and preoperative work-up in the PCa case and, lastly, the proposals were different for the bladder cancer case. The decisions relies on clinical data and preoperative work-up but also on the experience and habits of the centre of excellence. For complex cases that does not fit with current guidelines, the panel discussion can lead to different therapeutic options from a centre to another and is largely influenced by the local organisation of the RCP. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Settlement-date Accounting for Equity Share Options - Conceptual Validity and Numerical Effects

    DEFF Research Database (Denmark)

    Møller, Peder Fredslund

    -date accounting are fully conceptually valid. They represent measurements of one partner group's share of total equity with effect for another group's share of total equity and income: the shareholders' part. Partially, this equity and income sharing model is already the basis for existing accounting standards......This paper demonstrates that settlement-date accounting for equity share options can be seen as an accounting method which implements a shareholder focused residually rewarded partners' equity view. This equity view represents a simple, natural extension of the shareholder proprietary view....... It implicates an equity and income sharing model for accounting which is characterized by specification of both shareholders' and non-shareholders' parts of total equity and income. When using this equity and income sharing model, the remeasurements of equity share option obligations made by settlement...

  11. Therapeutic options in chronic heart failure. Findings on chest X-ray; Nicht medikamentoese Therapieoptionen der chronischen Herzinsuffizienz. Befunde in der Projektionsradiografie des Thorax

    Energy Technology Data Exchange (ETDEWEB)

    Granitz, M.R.; Meissnitzer, T.; Meissnitzer, M.W.; Hergan, K.; Altenberger, J.; Granitz, C. [Uniklinikum Salzburg - Landeskrankenhaus (Austria)

    2016-05-15

    The contribution covers drugless therapeutic options for chronic heart failure: the implantable cardioverter/defibrillator (ICD), the cardiac resynchronization therapy (CRT), the interventional catheter treatment of functional mitral insufficiency, and mechanical heart supporting systems and heart transplantation.

  12. Development of a compassion-focused and contextual behavioural environment and validation of the Therapeutic Environment Scales (TESS).

    Science.gov (United States)

    Veale, David; Miles, Sarah; Naismith, Iona; Pieta, Maria; Gilbert, Paul

    2016-02-01

    Aims and method The aims of the study were to develop a scale sensitive enough to measure the interpersonal processes within a therapeutic environment, and to explore whether the new scale was sensitive enough to detect differences between settings, including a community based on compassionate mind and contextual behaviourism. The Therapeutic Environment Scales (TESS) were validated with 81 participants in three different settings: a specialist service for anxiety disorders, a specialist in-patient ward and a psychodynamic therapeutic community. Results TESS was found to be reliable and valid. Significant differences were seen between the services on the dimensions of compassion, belongingness, feeling safe, positive reinforcement of members' acts of courage, extinction and accommodation of unhelpful behaviours, inconsistency and high expressed emotion. These processes were over time associated with improved outcomes on a specialist service for anxiety disorders. Clinical implications The TESS offers a first step in exploring important interpersonal relationships in therapeutic environments and communities. An environment based on a compassionate mind and contextual behaviourism offers promise for the running of a therapeutic community.

  13. Graves' disease. Manifestations and therapeutic options

    Energy Technology Data Exchange (ETDEWEB)

    McFarland, K.F.; Saleeby, G.

    1988-03-01

    Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan.

  14. Rectal cancer and Fournier's gangrene - current knowledge and therapeutic options.

    Science.gov (United States)

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-08-14

    Fournier's gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects.

  15. Lumbar sympathectomy under CT guidance: therapeutic option in critical limb ischaemia

    International Nuclear Information System (INIS)

    Pieri, Stefano; Agresti, Paolo; Di Cesare, Fabio; Ricci, Guiseppe

    2005-01-01

    Purpose: Lumbar sympathectomy is a complementary therapeutic option for patients with severe peripheral vascular occlusive disease presenting rest pain or gangrene and not eligible for surgical revascularisation. Traditional surgical sympathectomy was widely used in the past. However, due to its invasive character, it has increasingly been replaced by percutaneous techniques and, in some recent cases, by laparoscopic procedures. Percutaneous lumbar sympathectomy is a safe, cost-effective and widely available treatment option. We report our experience on 19 patients subjected to percutaneous sympathectomy under CT guidance. Materials and methods: Between 1998 and 2000, 19 patients underwent percutaneous sympathectomy under CT guidance. All patients had severe vascular disease of the lower extremities (Fontaine stage IV), with rest pain and gangrene. They were not eligible for surgical revascularization. Phenol was injected at the level of L2 and L4 using two 22 G needles (15 cm long). Signs of interrupted sympathetic activity usually occur 2'-15' after the procedure with warmth and flushing and dryness of the lower extremities. Results: Percutaneous sympathectomy under CT guidance is a simple, safe and well-tolerated procedure with a low rate of complications. Of the 19 patients, 9 (47.3%) showed clinical improvement, whereas 5 experienced a worsening of ischaemia in the month immediately following the procedure. Discussion: Results suggest that percutaneous lumbar sympathectomy causes a sympathetic blockade in patients with advanced vascular disease of the limb. CT guidance ensures a high level of precision in drug dosing, thus lowering the risk of complications. Although the results are demoralizing. the impossibility of achieving surgical revascularisation in advanced peripheral arteriosclerosis enhances the role of Ct-guided percutaneous sympathectomy in relieving rest pain and healing ulcers in order to postpone the amputation [it

  16. A validation study of the BURNUP and associated options of the MONTE CARLO neutronics code MONK5W

    International Nuclear Information System (INIS)

    Howard, E.A.

    1985-11-01

    This is a report on the validation of the burnup option of the Monte Carlo Neutronics Code MONK5W, together with the associated facilities which allow for control rod movements and power changes. The validation uses reference solutions produced by the Deterministic Neutronics Code LWR-WIMS for a 2D model which represents a whole reactor calculation with control rod movements. (author)

  17. Comparison of different options for harvest of a therapeutic protein product from high cell density yeast fermentation broth.

    Science.gov (United States)

    Wang, Alice; Lewus, Rachael; Rathore, Anurag S

    2006-05-05

    Recovery of therapeutic protein from high cell density yeast fermentations at commercial scale is a challenging task. In this study, we investigate and compare three different harvest approaches, namely centrifugation followed by depth filtration, centrifugation followed by filter-aid enhanced depth filtration, and microfiltration. This is achieved by presenting a case study involving recovery of a therapeutic protein from Pichia pastoris fermentation broth. The focus of this study is on performance of the depth filtration and the microfiltration steps. The experimental data has been fitted to the conventional models for cake filtration to evaluate specific cake resistance and cake compressibility. In the case of microfiltration, the experimental data agrees well with flux predicted by shear induced diffusion model. It is shown that, under optimal conditions, all three options can deliver the desired product recovery ( >80%), harvest time ( making a final decision on a harvesting approach.

  18. Effect of response format on cognitive reflection: Validating a two- and four-option multiple choice question version of the Cognitive Reflection Test.

    Science.gov (United States)

    Sirota, Miroslav; Juanchich, Marie

    2018-03-27

    The Cognitive Reflection Test, measuring intuition inhibition and cognitive reflection, has become extremely popular because it reliably predicts reasoning performance, decision-making, and beliefs. Across studies, the response format of CRT items sometimes differs, based on the assumed construct equivalence of tests with open-ended versus multiple-choice items (the equivalence hypothesis). Evidence and theoretical reasons, however, suggest that the cognitive processes measured by these response formats and their associated performances might differ (the nonequivalence hypothesis). We tested the two hypotheses experimentally by assessing the performance in tests with different response formats and by comparing their predictive and construct validity. In a between-subjects experiment (n = 452), participants answered stem-equivalent CRT items in an open-ended, a two-option, or a four-option response format and then completed tasks on belief bias, denominator neglect, and paranormal beliefs (benchmark indicators of predictive validity), as well as on actively open-minded thinking and numeracy (benchmark indicators of construct validity). We found no significant differences between the three response formats in the numbers of correct responses, the numbers of intuitive responses (with the exception of the two-option version, which had a higher number than the other tests), and the correlational patterns of the indicators of predictive and construct validity. All three test versions were similarly reliable, but the multiple-choice formats were completed more quickly. We speculate that the specific nature of the CRT items helps build construct equivalence among the different response formats. We recommend using the validated multiple-choice version of the CRT presented here, particularly the four-option CRT, for practical and methodological reasons. Supplementary materials and data are available at https://osf.io/mzhyc/ .

  19. Therapeutic antibodies as a treatment option for dengue fever.

    Science.gov (United States)

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

    2013-11-01

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

  20. Rectal cancer and Fournier’s gangrene - current knowledge and therapeutic options

    Science.gov (United States)

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-01-01

    Fournier’s gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects. PMID:26290629

  1. automated (centrifugal) therapeutic plasma exchange option for ...

    African Journals Online (AJOL)

    Therapeutic plasma exchange (TPE) is performed frequently and effectively in developed countries, whereas the reverse is the case in developing countries. Guillain‑Barre syndrome (GBS), synonymous with acute inflammatory demyelinating polyneuropathy, is an important indication for TPE, but this is rarely administered ...

  2. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Misra, Monika

    2013-03-01

    Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

  3. Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    Juan-Juan Du; Sheng-Di Chen

    2017-01-01

    Objective:The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).Data Sources:Papers in English published in PubMed,Cochrane,and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords:PD,nondopaminergic therapy,adenosine,glutamatergic,adrenergic,serotoninergic,histaminic,and iron chelator.We also reviewed the ongoing clinical trials in the website of clinicaltrials.gov.Study Selection:Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.Results:PD is conventionally treated with dopamine replacement strategies,which are effective in the early stages of PD.Long-term use oflevodopa could result in motor complications.Recent studies revealed that nondopaminergic systems such as adenosine,glutamatergic,adrenergic,serotoninergic,histaminic,and iron chelator pathways could include potential therapeutic targets for motor symptoms,including motor fluctuations,levodopa-induced dyskinesia,and gait disorders.Some nondopaminergic drugs,such as istradefylline and amantadine,are currently used clinically,while most such drugs are in preclinical testing stages.Transitioning of these agents into clinically beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite positive findings at the preclinical level.Conclusions:Targeting nondopaminergic transmission could improve some motor symptoms in PD,especially the discomfort ofdyskinesia.Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa,further investigation is required to ensure their success.

  4. Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

    Directory of Open Access Journals (Sweden)

    Moizza Mansoor

    2008-01-01

    Full Text Available Antisense oligonucleotides (As-ODNs are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt, 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.

  5. Changing Profiles of Diagnostic and Treatment Options in Subclavian Artery Aneurysms

    NARCIS (Netherlands)

    Vierhout, B. P.; Zeebregts, C. J.; van den Dungen, J. J. A. M.; Reijnen, M. M. P. J.

    Background: Subclavian artery aneurysms (SAAs) are rare and may cause life- and limb-threatening complications. Therapeutic options greatly differ as do access alternatives. The aim of the study was to assess its clinical presentation, diagnostics and therapeutic options as reported in the

  6. Emerging therapeutic options for sporadic inclusion body myositis

    Directory of Open Access Journals (Sweden)

    Alfano LN

    2015-09-01

    Full Text Available Lindsay N Alfano, Linda P Lowes Nationwide Children’s Hospital, Center for Gene Therapy, Columbus, OH, USA Abstract: Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. Keywords: myositis, inclusion body myositis, inflammatory myopathy, treatment, function, outcomes

  7. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks.

    Science.gov (United States)

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

    Science.gov (United States)

    Smith, William J

    2009-09-01

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

  9. Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics.

    Science.gov (United States)

    Gupta, Shalini; Devanarayan, Viswanath; Finco, Deborah; Gunn, George R; Kirshner, Susan; Richards, Susan; Rup, Bonita; Song, An; Subramanyam, Meena

    2011-07-15

    The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  11. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species.

    Science.gov (United States)

    Sobel, J D; Sobel, R

    2018-06-22

    Clinicians are increasingly challenged by patients with refractory vulvovaginal candidiasis (VVC) caused by azole-resistant Candida species. Fluconazole resistant C.albicans is a growing and perplexing problem following years of indiscriminate drug prescription and unnecessary drug exposure and for which there are few therapeutic alternatives. Regrettably, although the azole class of drugs has expanded, new classes of antifungal drugs have not been forthcoming, limiting effective treatment options in patients with azole resistant Candida vaginitis. Areas covered: This review covers published data on epidemiology, pathophysiology and treatment options for women with azole-resistant refractory VVC. Expert opinion: Fluconazole resistant C.albicans adds to the challenge of azole resistant non-albicans Candida spp. Both issues follow years of indiscriminate drug prescription and unnecessary fluconazole exposure. Although an understanding of azole resistance in yeast has been established, this knowledge has not translated into useful therapeutic advantage. Treatment options for such women with refractory symptoms are extremely limited. New therapeutic options and strategies are urgently needed to meet this challenge of azole drug resistance.

  12. Retrospective insights from real options in R&D

    NARCIS (Netherlands)

    Lint, L.J.O.

    2000-01-01

    Absent empirical validation of real option pricing in R&D, we discuss the evolution of three cases in R&D option valuation. The first case concerns an option on conversion of an existing production process. The other two cases concern R&D to develop new product technology in the consumer electronics

  13. Achalasia: Treatment Options Revisited

    Directory of Open Access Journals (Sweden)

    Willemijntje A Hoogerwerf

    2000-01-01

    Full Text Available The aim of all current forms of treatment of achalasia is to enable the patient to eat without disabling symptoms such as dysphagia, regurgitation, coughing or choking. Historically, this has been accomplished by mechanical disruption of the lower esophageal sphincter fibres, either by means of pneumatic dilation (PD or by open surgical myotomy. The addition of laparoscopic myotomy and botulinum toxin (BTX injection to the therapeutic armamentarium has triggered a recent series of reviews to determine the optimal therapeutic approach. Both PD and BTX have excellent short term (less than three months efficacy in the majority of patients. New data have been published that suggest that PD and BTX (with repeat injections can potentially obtain long term efficacy. PD is still considered the first-line treatment by most physicians; its main disadvantage is risk of perforation. BTX injection is evolving as an excellent, safe option for patients who are considered high risk for more invasive procedures. Laparoscopic myotomy with combined antireflux surgery is an increasingly attractive option in younger patients with achalasia, but long term follow-up studies are required to establish its efficacy and the potential for reflux-related sequelae.

  14. CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application

    Directory of Open Access Journals (Sweden)

    Brigitte Sophia Winkler

    2015-02-01

    Full Text Available The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.

  15. Tadalafil - a therapeutic option in the management of BPH-LUTS.

    Science.gov (United States)

    Carson, C C; Rosenberg, M; Kissel, J; Wong, D G

    2014-01-01

    Men with signs of benign prostatic hyperplasia (BPH) may experience lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, intermittence, nocturia, straining, incomplete emptying or a weak urinary stream. The effective management of LUTS suggestive of BPH (BPH-LUTS) requires careful consideration of several factors, including the severity of a patient's symptoms, concurrent or other coexisting medical conditions, the ability to improve symptoms and impact quality of life (QOL), as well as the potential side effects of available treatment options. Several clinical studies have assessed phosphodiesterase type 5 (PDE5) inhibitors in reducing LUTS; however, tadalafil is the only PDE5 inhibitor approved for the treatment of signs and symptoms of BPH, as well as in men with both erectile dysfunction (ED) and the signs and symptoms of BPH. This review examined articles that assessed tadalafil in patients with signs and symptoms of BPH, with or without erectile dysfunction (ED), which led to regulatory approval in the United States and Europe. In dose-ranging and confirmatory studies, results demonstrate that tadalafil significantly improved total International Prostate Symptom Score (IPSS) following 12 weeks of treatment with once daily tadalafil 5 mg. Statistically significant improvements in Benign Prostatic Hyperplasia Impact Index (BII), IPSS subscores, IPSS QOL and International Index of Erectile Function (IIEF) were also observed. Improvement in urinary symptoms occurred regardless of age, previous treatment with an α1 -adrenergic blocker, BPH-LUTS severity at baseline or ED status. While tadalafil is most frequently recognised as a standard treatment option for men with ED, it also represents a well-tolerated and effective treatment option in men with moderate to severe BPH-LUTS. © 2013 John Wiley & Sons Ltd.

  16. Therapeutic Options in Idiopathic Burning Mouth Syndrome: Literature Review

    OpenAIRE

    Miziara, Ivan; Chagury, Azis; Vargas, Camila; Freitas, Ludmila; Mahmoud, Ali

    2014-01-01

    Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders.Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years....

  17. Freud's Therapeutic Mistake with Jung's Disclosure of Childhood Sexual Abuse: Narrative Lessons in the Do's and Don'ts of Validation.

    Science.gov (United States)

    Gasker, Janice

    1999-01-01

    Examines the life narratives of over 25 "victims" and "survivors" of sexual victimization, including that of Carl Jung, as revealed in his letters to Sigmund Freud. Looks at the devastating results of Freud's invalidating response. Discusses categories of successful therapeutic validation. (SR)

  18. Intermittent Massage as a Therapeutic Option for Compartment Syndrome after Embolectomy of the Lower Limbs

    Directory of Open Access Journals (Sweden)

    José Maria Pereira de Godoy

    2018-01-01

    Full Text Available The case of a 54-year-old cardiac patient is reported, who was admitted to hospital with a complaint of sudden pain in the legs associated with edema, paresthesia, and coldness. Arterial embolism of the lower limbs was diagnosed and the patient was submitted to bilateral embolectomy. The patient evolved with a burning sensation, hypersensitivity in the right leg, swelling, and difficulty bending and stretching the sole of the foot and the knee. A physical examination detected edema and increased tension in the anterior, lateral, and posterior compartments. Treatment using intermittent massage of the leg during the evaluation of the patient was chosen in an attempt to stimulate lymphatic and venous drainage. After a few minutes of stimulation, there was significant improvement in the pain and edema. In 40 minutes, there was total reduction of the pain in the posterior and lateral compartments and improvement of over 50% in the anterior compartment. After this, the patient started to bend the knee without pain and bend the sole of the foot with slight pain. On the following day, the patient was walking around the hospital ward without difficulty. It seems that intermittent massage is a therapeutic option in selected cases of compartment syndrome.

  19. Autologous stem-cell transplantation in Hodgkin’s lymphoma: analysis of a therapeutic option

    Directory of Open Access Journals (Sweden)

    Adriano de Moraes Arantes

    2011-06-01

    Full Text Available Objective: To report the clinical progress of patients with Hodgkin’slymphoma treated with autologous transplantation after failure orrelapse of first-line treatment with chemotherapy and/or radiationtherapy. Methods: The results of a retrospective analysis of 31patients submitted to autologous transplantation as second-linetreatment, between April 2000 and December 2008, were analyzed.Fourteen men and seventeen women, with a median age of 27 years,were submitted to autologous transplantation for relapsed (n = 21or refractory (n = 10 Hodgkin’s lymphoma. Results: Mortalityrelated to treatment in the first 100 days after transplant was 3.2%.With a mean follow-up period of 18 months (range: 1 to 88 months,the probability of global survival and progression-free survival in18 months was 84 and 80%, respectively. The probability of globalsurvival and progression-free survival at 18 months for patients withchemosensitive relapses (n = 21 was 95 and 90%, respectively,versus 60 and 45% for patients with relapses resistant to chemotherapy(n = 10 (p = 0.001 for global survival; p = 0.003 for progressionfreesurvival. In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85 and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78. Conclusion: Autologous transplantation of stem-cells is a therapeutic option for Hodgkin’s lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

  20. Intravaginal boric acid: is it an alternative therapeutic option for vaginal trichomoniasis?

    Science.gov (United States)

    Thorley, Nicola; Ross, Jonathan

    2017-12-09

    Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common curable sexually transmitted infection worldwide. Current guidance in the UK is to treat TV with a nitroimidazole antibiotic. The high prevalence of TV, high rate of antibiotic resistance and limited tolerability to nitroimidazoles suggest that alternative treatment regimens are needed. Intravaginal boric acid (BA) has been used safely for the treatment of candida vulvovaginitis and bacterial vaginosis, and in vitro studies suggest BA is active against TV. We review the evidence for the efficacy of BA in patients with TV. MEDLINE, EMBASE, CINAHL, AMED, HMIC and BNI and Grey literature databases, The Cochrane Library, Trial Registers, conference abstracts and proceedings were searched. Inclusion criteria were women aged 16 years or over with microbiological confirmation of TV infection and using BA as treatment. There were no restrictions on language, publication date or study design. The in vitro evidence for BA activity against TV was also reviewed. No randomised controlled trials or case series were found. Four case reports demonstrated TV clearance with BA using a variety of dose regimens (dose 600 mg alternate nights to 600 mg two times per day; duration 1-5 months). In vitro studies suggest that BA has activity against TV which is independent of its effect on pH. Further evaluation of BA for the treatment of uncomplicated TV is required, but it may be useful when therapeutic options are limited. If shown to be safe and effective, intravaginal BA might provide a well-tolerated alternative anti-infective treatment which reduces community exposure to systemic antibiotics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. THERAPEUTIC DECISION-MAKING OF PHYSICIANS

    NARCIS (Netherlands)

    DENIG, P; HAAIJER-RUSKAMP, FM

    1992-01-01

    In this review the therapeutic decision-making process of physicians is described. This process is divided into two steps: the generation of a limited set of possible options (the 'evoked set') and the selection from this evoked set of a treatment for a specific patient. Factors that are important

  2. Conservative therapeutic management of carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Roberto Sérgio Martins

    Full Text Available ABSTRACT Carpal tunnel syndrome is the most prevalent nerve compression and can be clinically or surgically treated. In most cases, the first therapeutic alternative is conservative treatment but there is still much controversy regarding the most effective modality of this treatment. In this study, we critically evaluated the options of conservative treatment for carpal tunnel syndrome, aiming to guide the reader through the conventional options used in this therapy.

  3. The DUNDRUM-1 structured professional judgment for triage to appropriate levels of therapeutic security: retrospective-cohort validation study.

    LENUS (Irish Health Repository)

    Flynn, Grainne

    2011-01-01

    The assessment of those presenting to prison in-reach and court diversion services and those referred for admission to mental health services is a triage decision, allocating the patient to the appropriate level of therapeutic security. This is a critical clinical decision. We set out to improve on unstructured clinical judgement. We collated qualitative information and devised an 11 item structured professional judgment instrument for this purpose then tested for validity.

  4. Phytotherapy: emerging therapeutic option in urologic disease

    Science.gov (United States)

    2012-01-01

    Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists. PMID:26816707

  5. Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients?

    Directory of Open Access Journals (Sweden)

    Alberto Francisco Rubio-Guerra

    2010-09-01

    Full Text Available Alberto Francisco Rubio-Guerra1, Hilda Vargas-Robles2, Luz Maria Ramos-Brizuela1, Bruno Alfonso Escalante-Acosta21Metabolic Clinic, Hospital General de Ticomán SS DF, Mexico; 2Department of Molecular Biomedicine, Centro de Investigacion y de Estudios Avanzados del IPN, MexicoAbstract: Nitric oxide (NO is an important regulator of vascular tone, and is also an antithrombotic, anti-inflammatory, antiproliferative, and antiatherogenic factor. Endothelial function is altered in patients with coronary artery disease, stroke, and peripheral artery disease, and endothelial dysfunction correlates with the risk factor profile for a patient. Hypertension and type 2 diabetes are risk factors for vascular disease, and are both pathologies characterized by loss of NO activity. Indeed, endothelial dysfunction is usually present in diabetic and/or hypertensive patients. Tetrahydrobiopterin is an essential cofactor for the NO synthase enzyme, and insufficiency of this cofactor leads to uncoupling of the enzyme, release of superoxide, endothelial dysfunction, progression of hypertension, and finally, proatherogenic effects. Tetrahydrobiopterin is also an important mediator of NO synthase regulation in type 2 diabetes and hypertension, and may be a rational therapeutic target to restore endothelial function and prevent vascular disease in these patients. The aim of this paper is to review the rationale for therapeutic strategies directed to biopterins as a target for vascular disease in type 2 diabetic hypertensive patients.Keywords: tetrahydrobiopterin, endothelial dysfunction, diabetes, hypertension, oxidative stress, nitric oxide, eNOS synthase uncoupling

  6. Phase 3 Oncology Clinical Trials in South Africa: Experimentation or Therapeutic Misconception?

    Science.gov (United States)

    Malan, Tina; Moodley, Keymanthri

    2016-02-01

    Although clinical research in oncology is vital to improve current understanding of cancer and to validate new treatment options, voluntary informed consent is a critical component. Oncology research participants are a particularly vulnerable population; hence, therapeutic misconception often leads to ethical and legal challenges. We conducted a qualitative study administering semi-structured questionnaires on 29 adult, Phase 3, oncology clinical trial participants at three different private oncology clinical trial sites in South Africa. A descriptive content analysis was performed to identify perceptions of these participants regarding Phase 3 clinical trials. We found that most participants provided consent to be included in the trial for self-benefit. More than half of the participants had a poor understanding of Phase 3 clinical trials, and almost half the participants believed the clinical trial did not pose any significant risk to them. The word "hope" was used frequently by participants, displaying clear optimism with regard to the clinical trial and its outcome. This indicated that therapeutic misconception does occur in the South African oncology research setting and has the potential to lead to underestimation of the risks of a Phase 3 clinical trial. Emphasizing the experimental nature of a clinical trial during the consent process is critical to address therapeutic misconception in oncology research. © The Author(s) 2016.

  7. Indications and interventional options for non-resectable tracheal stenosis

    Science.gov (United States)

    Bacon, Jenny Louise; Patterson, Caroline Marie

    2014-01-01

    Non-specific presentation and normal examination findings in early disease often result in tracheal obstruction being overlooked as a diagnosis until patients present acutely. Once diagnosed, surgical options should be considered, but often patient co-morbidity necessitates other interventional options. Non-resectable tracheal stenosis can be successfully managed by interventional bronchoscopy, with therapeutic options including airway dilatation, local tissue destruction and airway stenting. There are common aspects to the management of tracheal obstruction, tracheomalacia and tracheal fistulae. This paper reviews the pathogenesis, presentation, investigation and management of tracheal disease, with a focus on tracheal obstruction and the role of endotracheal intervention in management. PMID:24624290

  8. Pain and endometriosis: Etiology, impact, and therapeutics

    Directory of Open Access Journals (Sweden)

    Robert N. Taylor

    2012-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Shuai Zhen

    2017-12-01

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

  10. Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options.

    Science.gov (United States)

    Brown, Robert E; Naqvi, Syed; McGuire, Mary F; Buryanek, Jamie; Karni, Ron J

    2017-08-17

    biomedical analytics as consistent with published literature. This is significant because the biology lends itself to targeted therapeutic options using metformin, curcumin, celecoxib and sulforaphane as therapeutic strategies to prevent progression or recurrence of disease.

  11. Therapeutic decisions in ALS patients: cross-cultural differences and clinical implications.

    Science.gov (United States)

    Andersen, Peter M; Kuzma-Kozakiewicz, Magdalena; Keller, Jürgen; Aho-Oezhan, Helena E A; Ciecwierska, Katarzyna; Szejko, Natalia; Vázquez, Cynthia; Böhm, Sarah; Badura-Lotter, Gisela; Meyer, Thomas; Petri, Susanne; Linse, Katharina; Hermann, Andreas; Semb, Olof; Stenberg, Erica; Nackberg, Simona; Dorst, Johannes; Uttner, Ingo; Häggström, Ann-Cristin; Ludolph, Albert C; Lulé, Dorothée

    2018-05-04

    Quantitative analysis of decision-making on therapeutic options in different sociocultural context in amyotrophic lateral sclerosis (ALS). ALS patients (n = 244) were consecutively recruited in Germany (n = 83), Poland (n = 83), and Sweden (n = 78) in a prospective cross-cultural study ( www.NEEDSinALS.com ). They were interviewed on preferences for therapeutic techniques including invasive (IV) and non-invasive ventilation (NIV), as well as percutaneous endoscopic gastrostomy (PEG) and on hypothetical termination of these using quantitative questions. Using standardized questionnaires, religiousness, personal values, quality of life, and depressiveness were assessed. NIV was most frequently used in Germany and PEG in Sweden. Swedish patients were most liberal on initiation and termination of PEG, NIV and IV. Polish patients were mostly undecided and were least likely to consider discontinuing supportive management. Current use was partly associated with age, gender and state of physical function; also, financial support explained some variance. Future preferences on therapeutic options from the patient's perspective were also closely associated with cultural factors. The more oriented towards traditional and conservative values, the less likely patients were to decide for invasive therapeutic devices (IV, PEG), the least likely to have ideations to discontinue any device and the more likely to have an undecided attitude. Current use of therapeutic options is determined by medical condition in analogy to clinical guidelines. For future considerations, other factors such as cultural background are crucial, yielding hurdles to be regarded in the implementation of advanced directives in a multicultural environment.

  12. Options for modulation of drug resistance in ovarian cancer

    NARCIS (Netherlands)

    Arts, HJG; Van der Zee, AGJ; De Jong, S; De Vries, EGE

    2000-01-01

    The objective of this paper is to present an update of mechanisms responsible for drug resistance in ovarian cancer and the possible therapeutic options to modulate this resistance using literature review with emphasis on data acquired in studies comprising ovarian tumor samples. The classic

  13. Novel therapeutic options for relapsed hairy cell leukemia.

    Science.gov (United States)

    Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

    2015-01-01

    The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

  14. New therapeutic options for allergic rhinitis: back to the future with intranasal corticosteroid aerosols.

    Science.gov (United States)

    Carr, Warner W

    2013-01-01

    Under current guidelines, intranasal corticosteroids (INSs) are considered the most effective first-line therapy to improve allergic rhinitis (AR) symptoms and burden of disease. In the late 1980s-1990s, chlorofluorocarbon (CFC)-propelled corticosteroid aerosol nasal sprays formed the standard of care for the treatment of AR. Because of environmental concerns, CFC aerosols were gradually phased out, and aqueous INS formulations of nasal sprays became the standard of care. Although many aqueous INS sprays are available, specific product-related factors can reduce patient adherence to an INS and subsequently reduce treatment efficacy. The purpose of this paper was to review the evolution of AR therapeutics and drug devices and how it may have an effect on patient adherence/compliance and patient satisfaction with current available therapies and show the unmet need to improve INS delivery systems. Although aqueous INSs are effective and well tolerated, use in some patients may be compromised because of patient sensory perception and device preference. A historical review of the evolution of intranasal delivery of INSs was undertaken to provide further insight into improving treatment options for patients with AR. Although the various approved INSs appear to be equivalent in terms of reducing AR disease burden, the method in which an INS is delivered to a patient has significant bearing on the overall success of each specific drug product. Hydrofluoroalkane-propelled INS drug products offer a back-to-the-future delivery approach that may be further tailored to the individual patient's needs. Past experiences and the development of new devices are paving the way toward further therapy choices, ultimately affording health care providers access to the most effective treatments for patients with AR.

  15. Polymyxins: Antimicrobial susceptibility concerns and therapeutic options

    Directory of Open Access Journals (Sweden)

    V Balaji

    2011-01-01

    Full Text Available The increasing prevalence of multidrug-resistant nosocomial pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae poses a great challenge to the treating physicians. The paucity of newer effective antimicrobials has led to renewed interest in the polymyxin group of drugs, as a last resort for treatment of gram-negative bacterial infections. There is a dearth of information on the pharmacological properties of colistin, leading to difficulties in selecting the right dose, dosing interval, and route of administration for treatment, especially in critically-ill patients. The increasing use of colistin over the last few years necessitates the need for accurate and reliable in vitro susceptibility testing methods. Development of heteroresistant strains as a result of colistin monotherapy is also a growing concern. There is a compelling need from the clinicians to provide options for probable and possible colistin combination therapy for multidrug-resistant bacterial infections in the ICU setting. Newer combination drug synergy determination tests are being developed and reported. There are no standardized recommendations from antimicrobial susceptibility testing reference agencies for the testing and interpretation of these drug combinations. Comparison and analysis of these reported methodologies may help to understand and assist the microbiologist to choose the best method that produces accurate results at the earliest. This will help clinicians to select the appropriate combination therapy. In this era of multidrug resistance it is important for the microbiology laboratory to be prepared, by default, to provide timely synergistic susceptibility results in addition to routine susceptibility, if warranted. Not as a favour or at request, but as a responsibility.

  16. [Female androgenetic alopecia, a survey of causes and therapeutic options].

    Science.gov (United States)

    Duchková, Hana; Hašková, Marta

    2015-01-01

    Mesotherapy is one of the options for the treatment of androgenetic alopecia. Testing 24 women with androgenetic alopecia has demonstrated a positive effect of mesotherapy on the hair growth, hair thickness, with only insignificant increase of hair density. It is known that androgenetic alopecia represents a localized aging of hair follicles. We therefore decided to examine the different effects of mesotherapy on hair density in younger and in elderly women. In younger women mesotherapy significantly increased hair density compared with older women. For mesotherapy we used a combination of micronutrients and antioxidants. Mesotherapy achievements were evident for 6-12 months. Treatment requires a long-term care.

  17. Option valuation for energy issues

    International Nuclear Information System (INIS)

    Ostertag, K.; Llerena, P.; Richard, A.

    2004-01-01

    In many industrial and economic situations, decision processes, both individual and collective, have to simultaneously face uncertainty and irreversibility of some kind. This is particularly valid for energy choices if they are linked to technological alternatives. The purpose of this book is to highlight specific aspects of these situations. This is done from the particular perspective of option valuation. The contributions to this book grew out of an international workshop on ''Option valuation in energy and environmental issues'' held at the Fraunhofer ISI in February 2003. This workshop brought together reseachers from energy economics, but also researchers working on option valuation in other empirical fields or with a more theoretical perspective. This is reflected in the organisation of the book, which starts with some theory-oriented contributions and subsequently presents more applied contributions in the field of energy economics with an extension to water infrastructure in the annex. (orig.)

  18. Therapeutic validity and effectiveness of supervised physical exercise training on exercise capacity in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

    NARCIS (Netherlands)

    Vooijs, M.; Siemonsma, P.C.; Heus, I.; Sont, J.K.; Rövekamp, T.A.; Meeteren, N.L. van

    2016-01-01

    Objective: Our aim was to determine the effectiveness of supervised physical exercise training on exercise capacity in patients with chronic obstructive pulmonary disease taken into consideration indices such as therapeutic validity of interventions, methodological quality of studies, and exercise

  19. Metabolic syndrome: nature, therapeutic solutions and options.

    Science.gov (United States)

    Onat, Altan

    2011-08-01

    Metabolic syndrome (MetS) defines the clustering in an individual of multiple metabolic abnormalities, based on central obesity and insulin resistance. In addition to its five components, prothrombotic and proinflammatory states are essential features. The significance of MetS lies in its close association with the risk of type 2 diabetes and cardiovascular disease (CVD). This field being an evolving one necessitated the current review. The areas covered in this review include the so far unproven concept that enhanced low-grade inflammation often leads to dysfunction of the anti-inflammatory and atheroprotective properties of apolipoprotein A-I (apoA-I) and HDL particles, which further increases the risk of diabetes and CVD. It was emphasized that lifestyle modification is essential in the prevention and management of MetS, which includes maintenance of optimal weight by caloric restriction, adherence to a diet that minimizes postprandial glucose and triglyceride fluctuations, restricting alcohol consumption, smoking cessation and engaging in regular exercise. Drug therapy should target the dyslipoproteinemia and the often associated hypertension or dysglycemia.Statins are the drugs of first choice, to be initiated in patients with MetS at high 10-year cardiovascular risk. Such treatment is inadequate if fasting serum triglycerides remain at > 150 mg/dl, when niacin should be combined. Fibrates, omega 3 fatty acids, metformin, angiotensin-converting enzyme inhibitors and pioglitazone are additional options in drug therapy. Research on MetS in subpopulations prone to impaired glucose tolerance and insulin resistance has indicated that proinflammatory state and oxidative stress are often prominently involved in MetS, to the extent that evidence of impaired function of HDL and apo A-I particles is discernible by biological evidence of functional defectiveness via outcomes studies and/or correlations with inflammatory and anti-inflammatory biomarkers. A sex difference

  20. New therapeutic options for the metabolic syndrome: what's next?

    Science.gov (United States)

    Flordellis, Christodoulos S; Ilias, Ioannis; Papavassiliou, Athanasios G

    2005-08-01

    The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.

  1. Splenomegaly in myelofibrosis—new options for therapy and the therapeutic potential of Janus kinase 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Randhawa Jasleen

    2012-08-01

    Full Text Available Abstract Splenomegaly is a common sign of primary myelofibrosis (PMF, post-polycythemia vera myelofibrosis (post-PV MF, and post-essential thrombocythemia myelofibrosis (post-ET MF that is associated with bothersome symptoms, which have a significant negative impact on patients’ quality of life. It may also be present in patients with advanced polycythemia vera (PV or essential thrombocythemia (ET. Until recently, none of the therapies used to treat MF were particularly effective in reducing splenomegaly. The discovery of an activating Janus kinase 2 (JAK2 activating mutation (JAK2V617F that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2 inhibitors for the treatment of patients with ET, PV, and MF. Some of these trials have documented significant clinical benefit of JAK inhibitors, particularly in terms of regression of splenomegaly. In November 2011, the US Food and Drug Administration approved the use of the JAK1- and JAK2-selective inhibitor ruxolitinib for the treatment of patients with intermediate or high-risk myelofibrosis, including PMF, post-PV MF, and post-ET MF. This review discusses current therapeutic options for splenomegaly associated with primary or secondary MF and the treatment potential of the JAK inhibitors in this setting.

  2. Membrana amniótica como alternativa de tratamiento en superficie ocular Amniotic membrane as a therapeutic option for the ocular surface

    Directory of Open Access Journals (Sweden)

    Keyly Fernández García

    2012-12-01

    Full Text Available Se realizó una revisión bibliográfica con el objetivo de conocer la utilidad de la membrana amniótica como alternativa de tratamiento en la superficie ocular. Son abordados tópicos como las diferentes formas de obtención, preparación y conservación de la misma, sus mecanismos de acción y aplicaciones. Se consultó una bibliografía que abarca un periodo de varios años para conocer los resultados publicados sobre el trasplante de membrana amniótica humana en la superficie ocular.A literature review was made to learn about the usefulness of the amniotic membrane as a therapeutic option for the ocular surface. The different ways for obtaining, preparing, and conserving this membrane, its mechanism of action and its applications were also addressed. Literature covering several years was reviewed in order to be acquainted with the published results of the human amniotic membrane transplantation on the ocular surface.

  3. Novel treatment options for portal hypertension

    Science.gov (United States)

    Laleman, Wim

    2017-01-01

    Abstract Portal hypertension is most frequently associated with cirrhosis and is a major driver for associated complications, such as variceal bleeding, ascites or hepatic encephalopathy. As such, clinically significant portal hypertension forms the prelude to decompensation and impacts significantly on the prognosis of patients with liver cirrhosis. At present, non-selective β-blockers, vasopressin analogues and somatostatin analogues are the mainstay of treatment but these strategies are far from satisfactory and only target splanchnic hyperemia. In contrast, safe and reliable strategies to reduce the increased intrahepatic resistance in cirrhotic patients still represent a pending issue. In recent years, several preclinical and clinical trials have focused on this latter component and other therapeutic avenues. In this review, we highlight novel data in this context and address potentially interesting therapeutic options for the future. PMID:28533907

  4. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays

    Directory of Open Access Journals (Sweden)

    Rezende VM

    2013-08-01

    Full Text Available Vinicius Marcondes Rezende,1 Ariane Rivellis,1 Mafalda Megumi Yoshinaga Novaes,1 Dalton de Alencar Fisher Chamone,2 Israel Bendit1,21Laboratory of Tumor Biology, 2Department of Hematology, School of Medicine, University of São Paulo, São Paulo, BrazilBackground: Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring.Methods: A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The method was validated according to the requirements of the US Food and Drug Administration and Brazilian National Health Surveillance Agency within the range of 0.500–10.0 µg/mL with a limit of detection of 0.155 µg/mL. Stability data for the analyte are also presented.Conclusion: Given that the validated method has proved to be linear, accurate, precise, and robust, it is suitable for pharmacokinetic assays, such as bioavailability and bioequivalence, and is being successfully applied in routine therapeutic drug monitoring in the hospital service.Keywords: imatinib, high-performance liquid chromatography-mass spectrometry, therapeutic

  5. Intuition, subjectivity, and Le bricoleur: cancer patients' accounts of negotiating a plurality of therapeutic options.

    Science.gov (United States)

    Broom, Alex

    2009-08-01

    Cancer patients are now combining complementary and alternative medicine (CAM) with biomedical cancer treatments, reflecting an increasingly pluralistic health care environment. However, there has been little research done on the ways in which cancer patients juggle multiplicity in claims to expertise, models of disease, and therapeutic practice. Drawing on the accounts of cancer patients who use CAM, in this article I develop a conceptualization of therapeutic decision making, utilizing the notion of bricolage as a key point of departure. The patient accounts illustrate the "piecing together" (or bricolage) of therapeutic trajectories, drawing on intuitive, embodied knowledge, as well as formalized "objective" scientific expertise. Le bricoleur, as characterized here, actively mediates, rather than accepts or rejects CAM or biomedicine, and utilizes a combination of scientific expertise, embodied physicality, and social knowledge to make decisions and assess therapeutic effectiveness. Although these "border crossings" are potentially subversive of established biomedical expertise, the analysis also illustrates the structural constraints (and penalties) associated with bricolage, and furthermore, the interplay of a repositioning of responsibility with neoliberal forms of self-governance.

  6. Knowledge, attitudes and practices regarding gemstone therapeutics in a selected adult population in Pakistan

    Directory of Open Access Journals (Sweden)

    Qidwai Waris

    2009-08-01

    Full Text Available Abstract Background Gemstones have been in use as part of alternative and complementary medicine for years. However, our understanding of the perceived healing powers of gemstones is limited. An extensive literature search revealed that there is a dearth of validated information on this subject. This study was therefore undertaken to explore the various aspects of the knowledge, attitudes, and practices of the public towards gemstone therapeutics. Methods A survey was performed in the Community Health Centre of a tertiary care teaching hospital in Pakistan. Data collection was done via a face-to-face interview based on a structured, pre-tested questionnaire. Participants included all willing persons between 18–75 years of age approached prior to their appointments at the Community Health Centre. Results The survey response rate was 86% (400/465. More than half (63% of the study population was aware of the use of gemstone therapy. One hundred fifty-six individuals believed that gemstone use impacts health. Of this group, 39% believed that gemstone use increases physical strength. 62% believed that gemstone use is based on superstitious beliefs, whereas 28% opined that it is based on religious beliefs. 38% had used gemstones therapeutics formerly, while 24% were current users. Multiple logistic regression analysis revealed that age status and education status were significant (p Conclusion More than half of our sample population is aware of the use of the gemstones for their various effects. Willingness to use gemstones is associated with the beliefs about the impact of gemstone therapy on health. Friends and family seem to be the major role players influencing people's willingness to use gemstones. CAM modalities should be recognized and considered as an important therapeutic option. We feel that gemstone therapy is a relatively unexplored area and more studies should, therefore, be conducted to gather more validated information on the subject.

  7. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

    Science.gov (United States)

    Sortino, Maria A.; Salomone, Salvatore; Carruba, Michele O.; Drago, Filippo

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios. PMID:28642705

  8. Left atrial appendage occlusion with Amplatzer Cardio Plug is an acceptable therapeutic option for prevention of stroke recurrence in patients with non-valvular atrial fibrillation and contraindication or failure of oral anticoagulation with acenocumarol

    OpenAIRE

    Hawkes, Maximiliano A.; Pertierra, Lucía; Rodriguez-Lucci, Federico; Pujol-Lereis, Virginia A.; Ameriso, Sebastián F.

    2016-01-01

    ABSTRACT Left atrial appendage occlusion (LAAO) appears as a therapeutic option for some atrial fibrillation patients not suitable for oral anticoagulation because an increased hemorrhagic risk or recurrent ischemic events despite anticoagulant treatment. Methods Report of consecutive atrial fibrillation patients treated with LAAO with Amplatzer Cardio Plug because contraindication or failure of oral anticoagulation with acenocumarol. CHA2DS2VASC, HAS-BLED, NIHSS, mRS, procedural complicati...

  9. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    Science.gov (United States)

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.

  10. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  11. Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction.

    Science.gov (United States)

    Inatomi, Osamu; Bamba, Shigeki; Shioya, Makoto; Mochizuki, Yosuke; Ban, Hiromitsu; Tsujikawa, Tomoyuki; Saito, Yasuharu; Andoh, Akira; Fujiyama, Yoshihide

    2013-02-14

    Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy.

  12. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  13. Novel Therapeutic Approaches to the Treatment of Chronic Abdominal Visceral Pain

    Directory of Open Access Journals (Sweden)

    Franca Patrizi

    2006-01-01

    Full Text Available Chronic abdominal visceral pain (CAVP has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS, might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

  14. The potential for emerging therapeutic options for Clostridium difficile infection

    Science.gov (United States)

    Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2014-01-01

    Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review. PMID:25564777

  15. Optimization and validation of an existing, surgical and robust dry eye rat model for the evaluation of therapeutic compounds.

    Science.gov (United States)

    Joossen, Cedric; Lanckacker, Ellen; Zakaria, Nadia; Koppen, Carina; Joossens, Jurgen; Cools, Nathalie; De Meester, Ingrid; Lambeir, Anne-Marie; Delputte, Peter; Maes, Louis; Cos, Paul

    2016-05-01

    The aim of this research was to optimize and validate an animal model for dry eye, adopting clinically relevant evaluation parameters. Dry eye was induced in female Wistar rats by surgical removal of the exorbital lacrimal gland. The clinical manifestations of dry eye were evaluated by tear volume measurements, corneal fluorescein staining, cytokine measurements in tear fluid, MMP-9 mRNA expression and CD3(+) cell infiltration in the conjunctiva. The animal model was validated by treatment with Restasis(®) (4 weeks) and commercial dexamethasone eye drops (2 weeks). Removal of the exorbital lacrimal gland resulted in 50% decrease in tear volume and a gradual increase in corneal fluorescein staining. Elevated levels of TNF-α and IL-1α have been registered in tear fluid together with an increase in CD3(+) cells in the palpebral conjunctiva when compared to control animals. Additionally, an increase in MMP-9 mRNA expression was recorded in conjunctival tissue. Reference treatment with Restasis(®) and dexamethasone eye drops had a positive effect on all evaluation parameters, except on tear volume. This rat dry eye model was validated extensively and judged appropriate for the evaluation of novel compounds and therapeutic preparations for dry eye disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2016-01-01

    Full Text Available Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.

  17. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Paola Savoia

    2015-09-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer in individuals with fair skin type (I–II and steadily increasing in incidence (70% of skin malignancy. It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC.

  18. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Science.gov (United States)

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  19. Energy options

    International Nuclear Information System (INIS)

    Hampton, Michael

    1999-01-01

    This chapter focuses on energy options as a means of managing exposure to energy prices. An intuitive approach to energy options is presented, and traditional definitions of call and put options are given. The relationship between options and swaps, option value and option exercises, commodity options, and option pricing are described. An end-user's guide to energy option strategy is outlined, and straight options, collars, participating swaps and collars, bull and bear spreads, and swaption are examined. Panels explaining the defining of basis risk, and discussing option pricing and the Greeks, delta hedging, managing oil options using the Black-Scholes model, caps, floors and collars, and guidelines on hedging versus speculation with options are included in the paper

  20. Ethical considerations when using video games as therapeutic tools

    OpenAIRE

    Colman, Jason; Gnanayutham, Paul

    2010-01-01

    Video games have been used in a variety of therapeutic and rehabilitative contexts. However, there are health risks associated with playing video games, including the risk of epileptic seizure. Additionally, video games have been criticised for reasons including their portrayal of women and minorities. For games to be accepted as an ethically valid therapeutic tool, these concerns must be addressed. The authors believe that video games can be used as therapeutic tools when used responsibly

  1. Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

    Science.gov (United States)

    Abreu, Soraia C; Weiss, Daniel J; Rocco, Patricia R M

    2016-04-14

    Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.

  2. Breast cancer. Nuclear medicine in diagnosis and therapeutic options

    International Nuclear Information System (INIS)

    Bombardieri, E.; Bonadonna, G.; Gianni, L.

    2008-01-01

    Brings up-to-date nuclear medical knowledge in breast cancer. Includes vital information on advances in the field of diagnosis. Supplies data on the development of some new modalities. Offers a general overview of the available tools for breast cancer treatment. There can never be enough material in the public domain about cancers, and particularly breast cancer. This book adds much to the literature. It provides general information on breast cancer management and considers all new methods of diagnosis and therapy. It focuses on nuclear medicine modalities by comparing their results with other diagnostic and therapeutic approaches. The coverage provides readers with up-to-date knowledge on breast cancer as well as information on the advances in the field of diagnosis. It also details data on the development of some new modalities and provides a general overview of the available tools for breast cancer treatment. In sum, it is a hugely useful text that performs a dual function. Not only does it provide practitioners of all descriptions with a vital overview of the current state of play in breast cancer treatment, but it also lays out in a beautifully structured way the latest diagnostic methodologies. (orig.)

  3. 2008 update of standards, options: recommendations for management of patients with salivary gland malignant tumours (excluding lymphoma, sarcoma and melanoma), summary report

    International Nuclear Information System (INIS)

    Bensadoun, R.J.; Dassonville, O.; Rousmans, S.

    2008-01-01

    Context: An update of the S.O.R.-C.P.G. for management of patients with salivary gland malignant tumours has been initiated by the French National Federation of Cancer Centres (F.N.C.L.C.C.) in collaboration with French league against cancer, specialists from university or general hospitals and private clinics, and with the French National Cancer Institute. This work performed is based on the methodology developed and used in the 'Standards, Options: Recommendations' program (S.O.R.). Objectives. To update the S.O.R. guideline for the management of patients with salivary gland malignant tumors (excluding lymphoma, sarcoma and melanoma) previously validated in 1997 and 2003. Method: The guideline development process is based on literature review and critical appraisal by a multidisciplinary group of experts. The methodological approach combines systematic review with expert judgement. Recommendations take into account the effectiveness and toxicity of the different therapeutic alternatives and the levels of evidence. Following their development and prior to publication, S.O.R.-guidelines are reviewed by independent practitioners in cancer care delivery. Results: This paper is a summary version of the full clinical practice guideline presenting the updated recommendations. Recommendations on radiotherapy have been updated to underline new Options on more and more accessible emerging techniques including 'intensity-modulated radiotherapy', '3-D conformational radiotherapy', 'Cyber-knife', 'Tomotherapy', 'Proton therapy' and 'particle accelerators producing carbon ions' (e.g. last generation hadron therapy). Therapeutical modalities have also been specified. (authors)

  4. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

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

  5. The potential usefulness of the Response Index in positron emission tomography assessing the therapeutic effect of pre-operative chemotherapy for advanced colorectal cancer.

    Science.gov (United States)

    Nomura, Masatoshi; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Ikenaga, Masakazu; Yamamoto, Hirofumi; Murata, Kohei; Doki, Yuichiro; Mori, Masaki; Mizushima, Tsunekazu

    2017-12-01

    Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUV max ) in 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUV max in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was effect of chemotherapy on advanced colorectal cancer. Thus, RI is potentially useful for predicting the therapeutic effect in advanced colorectal cancer.

  6. 48 CFR 552.217-71 - Notice Regarding Option(s).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Notice Regarding Option(s... Notice Regarding Option(s). As prescribed in 517.208(b), insert the following provision: Notice Regarding Option(s) (NOV 1992) The General Services Administration (GSA) has included an option to [Insert...

  7. Option generation in decision making: ideation beyond memory retrieval.

    Science.gov (United States)

    Del Missier, Fabio; Visentini, Mimì; Mäntylä, Timo

    2014-01-01

    According to prescriptive decision theories, the generation of options for choice is a central aspect of decision making. A too narrow representation of the problem may indeed limit the opportunity to evaluate promising options. However, despite the theoretical and applied significance of this topic, the cognitive processes underlying option generation are still unclear. In particular, while a cued recall account of option generation emphasizes the role of memory and executive control, other theoretical proposals stress the importance of ideation processes based on various search and thinking processes. Unfortunately, relevant behavioral evidence on the cognitive processes underlying option generation is scattered and inconclusive. In order to reach a better understanding, we carried out an individual-differences study employing a wide array of cognitive predictors, including measures of episodic memory, semantic memory, cognitive control, and ideation fluency. The criterion tasks consisted of three different poorly-structured decision-making scenarios, and the participants were asked to generate options to solve these problems. The main criterion variable of the study was the number of valid options generated, but also the diversity and the quality of generated options were examined. The results showed that option generation fluency and diversity in the context of ill-structured decision making are supported by ideation ability even after taking into account the effects of individual differences in several other aspects of cognitive functioning. Thus, ideation processes, possibly supported by search and thinking processes, seem to contribute to option generation beyond basic associative memory retrieval. The findings of the study also indicate that generating more options may have multifaceted consequences for choice, increasing the quality of the best option generated but decreasing the mean quality of the options in the generated set.

  8. Option generation in decision making: Ideation beyond memory retrieval

    Directory of Open Access Journals (Sweden)

    Fabio eDel Missier

    2015-01-01

    Full Text Available According to prescriptive decision theories, the generation of options for choice is a central aspect of decision making. A too narrow representation of the problem may indeed limit the opportunity to evaluate promising options. However, despite the theoretical and applied significance of this topic, the cognitive processes underlying option generation are still unclear. In particular, while a cued recall account of option generation emphasizes the role of memory and executive control, other theoretical proposals stress the importance of ideation processes based on various search and thinking processes. Unfortunately, relevant behavioral evidence on the cognitive processes underlying option generation is scattered and inconclusive. In order to reach a better understanding, we carried out an individual-differences study employing a wide array of cognitive predictors, including measures of episodic memory, semantic memory, cognitive control, and ideation fluency. The criterion tasks consisted of three different poorly-structured decision-making scenarios, and the participants were asked to generate options to solve these problems. The main criterion variable of the study was the number of valid options generated, but also the diversity and the quality of generated options were examined. The results showed that option generation fluency and diversity in the context of ill-structured decision making are supported by ideation ability even after taking into account the effects of individual differences in several other aspects of cognitive functioning. Thus, ideation processes, possibly supported by search and thinking processes, seem to contribute to option generation beyond basic associative memory retrieval. The findings of the study also indicate that generating more options may have multifaceted consequences for choice, increasing the quality of the best option generated but decreasing the mean quality of the options in the generated set.

  9. Imaging enabled platforms for development of therapeutics

    Science.gov (United States)

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

    2011-03-01

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

  10. Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

    OpenAIRE

    Lamb, Ruth; Rohrer, Jonathan D.; Lees, Andrew J.; Morris, Huw R.

    2016-01-01

    Opinion statement There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specif...

  11. Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

    OpenAIRE

    Lamb, R.; Rohrer, J. D.; Lees, A. J.; Morris, H. R.

    2016-01-01

    There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesi...

  12. Current options for the treatment of pathological scarring.

    Science.gov (United States)

    Poetschke, Julian; Gauglitz, Gerd G

    2016-05-01

    Scarring is the consequence of surgery, trauma or different skin diseases. Apart from fresh, immature scars,that transform into mature scars over the course of would healing and that do not require further treatment,linear hypertrophic scars, widespread hypertrophic scars, keloids and atrophic scars exist. Symptoms like pruritusand pain, stigmatization as well as functional and aesthetic impairments that are very disturbing for the affected patients can bethe basis for the desire for treatment. Today, a multitude of options for the treatment and prevention of scars exists. Topical agents based on silicone or onion extract, intralesional injections of cristalline glucocorticoids (oftentimes in combinationwith cryotherapy) or 5-Fluorouracil as well as ablative and nonablative laser treatment are used. Current guidelines summarize the multitude of available treatment options and the currently available datafor the treating physicians, allowing them to make clear therapy recommendations for every single scar type. Relieving patients of their discomfort and doing their aesthetic demands justice is thus possible. Apart from scar prevention becoming more and more important, the increased use of modernlaser treatment options constitutes a key point in clinical scar treatment. At the same time the attention is turned to evaluating current therapeutic options with the help of contemporary study designs so as to graduallyimprove the level of evidence in scar treatment. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  13. Therapeutic Options for the Treatment of Hypertension in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Mary M. Stephens MD, MPH

    2012-01-01

    Full Text Available Primary hypertension in children is increasing in prevalence with many cases likely going undiagnosed. The prevalence is currently estimated at between 3%-5% in the United States and may be higher in certain ethnic groups. Primary hypertension, once felt to be rare in children, is now considered to be about five times more common than secondary hypertension. This review provides information to guide physicians through an organized approach to: 1 screening children and adolescents for hypertension during routine visits; 2 using normative percentile data for diagnosis and classification; 3 performing a clinical evaluation to identify the presence of co-morbidities; 4 initiating a plan of care including subsequent follow-up blood pressure measurements, therapeutic lifestyle changes and pharmacologic therapies.

  14. Energy exotic options

    International Nuclear Information System (INIS)

    Kaminski, V.; Gibner, S.; Pinnamaneni, K.

    1999-01-01

    This chapter with 88 references focuses on the use of exotic options to control exposure to energy prices. Exotic options are defined, and the conversion of a standard option into an exotic option and pricing models are examined. Pricing and hedging exotic options, path-dependent options, multi-commodity options, options on the minimum-or-maximum of two commodities, compound options, digital options, hybrid and complex structures, and natural gas daily options are described. Formulas for option pricing for vanilla, barrier, compound, options on minimum or maximum of two assets, and look back options are given in an appendix

  15. [Extracorporeal shockwave therapy (ESWT) as therapeutic option in supraspinatus tendon syndrome? One year results of a placebo controlled study].

    Science.gov (United States)

    Schmitt, J; Tosch, A; Hünerkopf, M; Haake, M

    2002-07-01

    Extracorporeal shock wave therapy (ESWT) is seen as a therapeutic option in the treatment of chronic supraspinatus tendinitis by some authors. To test whether ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33 mJ/mm2 is clinically superior to a sham ESWT treatment, a prospective, randomized, single-blinded, placebo-controlled study with an independent observer was performed. Forty patients were treated either by verum ESWT or sham ESWT under local anesthesia. Target criteria were the age-corrected Constant score, pain at rest and during activity on a visual analogue scale, and subjective improvement. Patients who reported no subjective improvement after 12 weeks were deblinded and received verum ESWT if they had belonged to the placebo group (partial crossover). The results of the verum group lie within the range of results for ESWT published by other authors. Patients in the placebo group with local anesthetic showed equally good results. At 12 weeks, and 1 year after intervention, no difference could be found between the verum and placebo groups regarding Constant score, pain, shoulder function, or subjective improvement. The nonresponders to the placebo ESWT continued to show no improvement after receiving verum ESWT. This contradicts a specific ESWT effect. Based on the results of this placebo-controlled study, ESWT appears to have no clinically relevant effect on supraspinatus tendinitis. The study underlines the importance of a control group in evaluating new treatment methods for diseases with unknown natural history.

  16. The validity and clinical utility of purging disorder.

    Science.gov (United States)

    Keel, Pamela K; Striegel-Moore, Ruth H

    2009-12-01

    To review evidence of the validity and clinical utility of Purging Disorder and examine options for the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V). Articles were identified by computerized and manual searches and reviewed to address five questions about Purging Disorder: Is there "ample" literature? Is the syndrome clearly defined? Can it be measured and diagnosed reliably? Can it be differentiated from other eating disorders? Is there evidence of syndrome validity? Although empirical classification and concurrent validity studies provide emerging support for the distinctiveness of Purging Disorder, questions remain about definition, diagnostic reliability in clinical settings, and clinical utility (i.e., prognostic validity). We discuss strengths and weaknesses associated with various options for the status of Purging Disorder in the DSM-V ranging from making no changes from DSM-IV to designating Purging Disorder a diagnosis on equal footing with Anorexia Nervosa and Bulimia Nervosa.

  17. The use of radiotherapy as a therapeutic option in the juvenile nasopharyngeal angiofibroma: An update of results in 11 patients

    International Nuclear Information System (INIS)

    Alert Silva, Jose; Perez Penna, Lourdes; Caballero Aguirrechu, Iraida; Reno Cespedes, Jesus; Garcia Socarras, Debora; Perez Trejo, Migdalia

    2009-01-01

    The juvenile nasopharyngeal angiofibroma is a rare benign tumor composed of fibrous connective tissue and abundant vascular spaces lined with endothelium, almost exclusively male and adolescence. The recommended treatment of choice is surgical excision of the tumor after embolization, however, in patients with bulky tumors, in which no surgical treatment is possible or it is refused, or where excision was incomplete, or the case of recurrence, radiation therapy (RT) is a therapeutic option. Results are presented in a series of 11 patients suffering from juvenile nasopharyngeal angiofibroma, all male, between 9 and 16 years of age, treated at INOR from 1990 to 2005. Nine patients were used as initial therapy irradiated and 2 relapse treated. The radiation treatment was applied in the irradiation of the entire tumor volume with a margin of safety, dose between 40 and 60 Gy, 1.8 Gy per session, associated with RT, was used postirradiation interferon from 3 to 6 months in 10 poly chemotherapy patients and in 1 patient. They keep 10 of the 11 patients with sustained complete remission (90.9%) without recurrence. In one patient only partial remission was achieved, using then surgical treatment. Early complications were all patients, and late in some. In the management of juvenile nasopharyngeal angiofibroma, RT is a treatment that maintains its usefulness, with their specific indications. (Author)

  18. Microneedle physical contact as a therapeutic for abnormal scars

    OpenAIRE

    Yeo, David C.; Balmayor, Elizabeth R.; Schantz, Jan-Thorsten; Xu, Chenjie

    2017-01-01

    Background Abnormal (keloid and hypertrophic) scars are a significant affliction with no satisfactory single modality therapy to-date. Available options are often ineffective, painful, potentially hazardous, and require healthcare personnel involvement. Herein a self-administered microneedle device based on drug-free physical contact for inhibiting abnormal scars is reported. Its therapeutic activity through microneedle contact eliminates hazards associated with toxic anti-scarring drugs whil...

  19. Cyclic peptides as potential therapeutic agents for skin disorders.

    Science.gov (United States)

    Namjoshi, Sarika; Benson, Heather A E

    2010-01-01

    There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

  20. Therapeutic Options for Controlling Fluids in the Visual System

    Science.gov (United States)

    Curry, Kristina M.; Wotring, Virginia E.

    2014-01-01

    Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

  1. ROCK as a therapeutic target for ischemic stroke.

    Science.gov (United States)

    Sladojevic, Nikola; Yu, Brian; Liao, James K

    2017-12-01

    Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK is a major regulator of cell contractility, motility, and proliferation. Many of these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells, pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in stroke pathophysiology, and the inhibition of such processes could improve stroke outcome. Expert commentary: ROCK is a potential therapeutic target for cardiovascular disease and ROCK inhibitors have already been approved for human use in Japan and China for the treatment of acute stroke. Further studies are needed to determine the role of ROCK isoforms in the pathophysiology of cerebral ischemia and whether there are further therapeutic benefits with selective ROCK inhibitors.

  2. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State or...

  3. Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.

    Science.gov (United States)

    Carmeli, Y; Akova, M; Cornaglia, G; Daikos, G L; Garau, J; Harbarth, S; Rossolini, G M; Souli, M; Giamarellou, H

    2010-02-01

    Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

  4. Analysis of Options Contract, Option Pricing in Agricultural Products

    Directory of Open Access Journals (Sweden)

    H. Tamidy

    2016-03-01

    Full Text Available Introduction: Risk is an essential component in the production and sale of agricultural products. Due to the nature of agricultural products, the people who act in this area including farmers and businesspersons encounter unpredictable fluctuations of prices. On the other hand, the firms that process agricultural products also face fluctuation of price of agricultural inputs. Given that the Canola is considered as one of the inputs of product processing factories, control of unpredictable fluctuations of the price of this product would increase the possibility of correct decision making for farmers and managers of food processing industries. The best available tool for control and management of the price risk is the use of future markets and options. It is evident that the pricing is the main pillar in every trade. Therefore, offering a fair price for the options will be very important. In fact, options trading in the options market create cost insurance stopped. In this way, which can reduce the risks of deflation created in the future, if the person entitled to the benefits of the price increase occurs in the future. Unlike the futures, market where the seller had to deliver the product on time, in the options market, there is no such compulsion. In addition, this is one of the strengths of this option contract, because if there is not enough product for delivery to the futures market as result of chilling, in due course, the farmers suffer, but in the options market there will be a loss. In this study, the setup options of rape, as a product, as well as inputs has been paid for industry. Materials and Methods: In this section. The selection criteria of the disposal of asset base for valuation of European put options and call option is been introduced. That for obtain this purpose, some characteristics of the goods must considered: 1-Unpredictable fluctuations price of underlying asset 2 -large underlying asset cash market 3- The possibility

  5. Acquired hemophilia A: a review of recent data and new therapeutic options.

    Science.gov (United States)

    Franchini, Massimo; Vaglio, Stefania; Marano, Giuseppe; Mengoli, Carlo; Gentili, Sara; Pupella, Simonetta; Liumbruno, Giancarlo Maria

    2017-10-01

    Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

  6. A Proposed Solution for the Chicken-Egg Dilemma in Pricing Currency Options

    Directory of Open Access Journals (Sweden)

    Ariful Hoque

    2013-06-01

    Full Text Available The implied volatility (IV estimation process suffers from an obvious chicken-egg dilemma: obtaining an unbiased IV requires the options to be priced correctly and calculating an accurate option price (OP requires an unbiased IV. We address this critical issue in two steps. First, the Granger causality test is employed, whichconfirms the chicken-and-egg problem in the IV computing process. Secondly, the concept of “moneyness volatility (MV” is introduced as an alternative to IV. MV is modelled based on an option’s moneyness (OM during the life of the option’s contract. The F-test, Granger-Newbold test and Diebold-Mariano test results consistently show that MV outperforms IV in estimating the exchange rate volatility for pricing options. Further, these series of tests across six major currency options substantiate the validity as well as the reliability of the results. We posit that MV offers a unique solution for pricing currency options accurately.

  7. Therapeutic inertia amongst general practitioners with interest in diabetes.

    Science.gov (United States)

    Seidu, Samuel; Than, Tun; Kar, Deb; Lamba, Amrit; Brown, Pam; Zafar, Azhar; Hussain, Rizwan; Amjad, Ahmed; Capehorn, Mathew; Martin, Elizabeth; Fernando, Kevin; McMoran, Jim; Millar-Jones, David; Kahn, Shahzada; Campbell, Nigel; Brice, Richard; Mohan, Rahul; Mistry, Mukesh; Kanumilli, Naresh; St John, Joan; Quigley, Richard; Kenny, Colin; Khunti, Kamlesh

    2018-02-01

    As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  8. Innovative thin silicon detectors for monitoring of therapeutic proton beams: preliminary beam tests

    Science.gov (United States)

    Vignati, A.; Monaco, V.; Attili, A.; Cartiglia, N.; Donetti, M.; Fadavi Mazinani, M.; Fausti, F.; Ferrero, M.; Giordanengo, S.; Hammad Ali, O.; Mandurrino, M.; Manganaro, L.; Mazza, G.; Sacchi, R.; Sola, V.; Staiano, A.; Cirio, R.; Boscardin, M.; Paternoster, G.; Ficorella, F.

    2017-12-01

    To fully exploit the physics potentials of particle therapy in delivering dose with high accuracy and selectivity, charged particle therapy needs further improvement. To this scope, a multidisciplinary project (MoVeIT) of the Italian National Institute for Nuclear Physics (INFN) aims at translating research in charged particle therapy into clinical outcome. New models in the treatment planning system are being developed and validated, using dedicated devices for beam characterization and monitoring in radiobiological and clinical irradiations. Innovative silicon detectors with internal gain layer (LGAD) represent a promising option, overcoming the limits of currently used ionization chambers. Two devices are being developed: one to directly count individual protons at high rates, exploiting the large signal-to-noise ratio and fast collection time in small thicknesses (1 ns in 50 μm) of LGADs, the second to measure the beam energy with time-of-flight techniques, using LGADs optimized for excellent time resolutions (Ultra Fast Silicon Detectors, UFSDs). The preliminary results of first beam tests with therapeutic beam will be presented and discussed.

  9. Therapeutic options for lymphangioleiomyomatosis (LAM): where we are and where we are going

    Science.gov (United States)

    Steagall, Wendy K; Moss, Joel

    2009-01-01

    Lymphangioleiomyomatosis (LAM), a multisystem disease affecting predominantly premenopausal and middle-aged women, causes progressive respiratory failure due to cystic lung destruction and is associated with lymphatic and kidney tumors. In the past, the treatment of LAM comprised exclusively anti-estrogen and related hormonal therapies. These treatments, however, have not been proven effective. In this article, we discuss new findings regarding the molecular mechanisms involved in the regulation of LAM cell growth, which may offer opportunities to develop effective and targeted therapeutic agents. PMID:20948684

  10. Surgical Options for the Refractive Correction of Keratoconus: Myth or Reality

    Directory of Open Access Journals (Sweden)

    L. Fernández-Vega-Cueto

    2017-01-01

    Full Text Available Keratoconus provides a decrease of quality of life to the patients who suffer from it. The treatment used as well as the method to correct the refractive error of these patients may influence on the impact of the disease on their quality of life. The purpose of this review is to describe the evidence about the conservative surgical treatment for keratoconus aiming to therapeutic and refractive effect. The visual rehabilitation for keratoconic corneas requires addressing three concerns: halting the ectatic process, improving corneal shape, and minimizing the residual refractive error. Cross-linking can halt the disease progression, intrastromal corneal ring segments can improve the corneal shape and hence the visual quality and reduce the refractive error, PRK can correct mild-moderate refractive error, and intraocular lenses can correct from low to high refractive error associated with keratoconus. Any of these surgical options can be performed alone or combined with the other techniques depending on what the case requires. Although it could be considered that the surgical option for the refracto-therapeutic treatment of the keratoconus is a reality, controlled, randomized studies with larger cohorts and longer follow-up periods are needed to determine which refractive procedure and/or sequence are most suitable for each case.

  11. CDK4/6 dual inhibitor abemaciclib demonstrates compelling preclinical activity against esophageal adenocarcinoma: a novel therapeutic option for a deadly disease.

    Science.gov (United States)

    Kosovec, Juliann E; Zaidi, Ali H; Omstead, Ashten N; Matsui, Daisuke; Biedka, Mark J; Cox, Erin J; Campbell, Patrick T; Biederman, Robert W W; Kelly, Ronan J; Jobe, Blair A

    2017-11-21

    Esophageal adenocarcinoma (EAC) is a deadly disease with limited therapeutic options. In the present study, we determined the preclinical efficacy of CDK4/6 inhibitor abemaciclib for treatment of EAC. In vitro , apoptosis, proliferation, and pathway regulation were evaluated in OE19, OE33, and FLO1 EAC cell lines. In vivo , esophagojejunostomy was performed on rats to induce EAC. At 36 weeks post-surgery, MRI and endoscopic biopsy established baseline tumor volume and molecular correlates, respectively. Next, the study animals were randomized to 26mg/kg intraperitoneal abemaciclib treatment or vehicle control for 28 days. Pre and post treatment MRIs, histopathology, and qRT-PCR were utilized to determine response. Our results demonstrated treatment with abemaciclib lead to increased apoptosis, and decreased proliferation in OE19 (p=0.185), OE33 (p=0.048), and FLO1 (p=0.043) with anticipated downstream molecular inhibition. In vivo , 78.9% of treatment animals demonstrated >20% tumor volume decrease (placebo 0%). Mean tumor volume changed in the treatment arm by -65.5% (placebo +133.5%) (p<0.01), and prevalence changed by -37.5% (placebo +16.7%) (p<0.01). Pre vs post treatment qRT-PCR demonstrated significant inhibition of all downstream molecular correlates. Overall our findings suggest potent antitumor efficacy of abemaciclib against EAC with evident molecular pathway inhibition and reasonable safety, establishing the rationale for future clinical development.

  12. Date Palm Tree (Phoenix dactylifera L.: Natural Products and Therapeutic Options

    Directory of Open Access Journals (Sweden)

    Reem A. Al-Alawi

    2017-05-01

    Full Text Available Many plants, including some of the commonly consumed herbs and spices in our daily food, can be safely and effectively used to prevent and/or treat some health concerns. For example, caffeine the active ingredient found in coffee beans (Coffea, shows biological activity in the treatment of the central nervous system (CNS disorders, indole-3-carbinol, and 3,3′-diindolylmethane are both broccoli (Brassica oleracea derived phytochemicals with potential anti-cancer activity, and resveratrol, isolated from grape (Vitis vinifera, is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects. Date palm fruits possess high nutritional and therapeutic value with significant antioxidant, antibacterial, antifungal, and anti-proliferative properties. This review focuses on the date fruit extracts and their benefits in individual health promoting conditions and highlights their applications as useful to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial products.

  13. Knowledge, attitudes and practices regarding gemstone therapeutics in a selected adult population in Pakistan.

    Science.gov (United States)

    Ishaque, Sidra; Saleem, Taimur; Qidwai, Waris

    2009-08-26

    recognized and considered as an important therapeutic option. We feel that gemstone therapy is a relatively unexplored area and more studies should, therefore, be conducted to gather more validated information on the subject.

  14. Do follow-on therapeutic substitutes induce price competition between hospital medicines? Evidence from the Danish hospital sector

    DEFF Research Database (Denmark)

    Hostenkamp, Gisela

    2013-01-01

    Objective The pricing of follow-on drugs, that offer only limited health benefits over existing therapeutic alternatives, is a recurring health policy debate. This study investigates whether follow-on therapeutic substitutes create price competition between branded hospital medicines. Methods New...... pioneer products were significantly reduced as a reaction to competition from follow-on drugs. Conclusion Competition between patented therapeutic substitutes did not seem to increase price competition and containment of pharmaceutical expenditures in the Danish hospital market. Strengthening hospitals......’ incentives to consider the price of alternative treatment options paired with a more active formulary management may increase price competition between therapeutic substitutes in the Danish hospital sector in the future....

  15. Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring

    Science.gov (United States)

    Manicke, Nicholas Edward; Abu-Rabie, Paul; Spooner, Neil; Ouyang, Zheng; Cooks, R. Graham

    2011-09-01

    A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

  16. Reducing the number of options on multiple-choice questions: response time, psychometrics and standard setting.

    Science.gov (United States)

    Schneid, Stephen D; Armour, Chris; Park, Yoon Soo; Yudkowsky, Rachel; Bordage, Georges

    2014-10-01

    Despite significant evidence supporting the use of three-option multiple-choice questions (MCQs), these are rarely used in written examinations for health professions students. The purpose of this study was to examine the effects of reducing four- and five-option MCQs to three-option MCQs on response times, psychometric characteristics, and absolute standard setting judgements in a pharmacology examination administered to health professions students. We administered two versions of a computerised examination containing 98 MCQs to 38 Year 2 medical students and 39 Year 3 pharmacy students. Four- and five-option MCQs were converted into three-option MCQs to create two versions of the examination. Differences in response time, item difficulty and discrimination, and reliability were evaluated. Medical and pharmacy faculty judges provided three-level Angoff (TLA) ratings for all MCQs for both versions of the examination to allow the assessment of differences in cut scores. Students answered three-option MCQs an average of 5 seconds faster than they answered four- and five-option MCQs (36 seconds versus 41 seconds; p = 0.008). There were no significant differences in item difficulty and discrimination, or test reliability. Overall, the cut scores generated for three-option MCQs using the TLA ratings were 8 percentage points higher (p = 0.04). The use of three-option MCQs in a health professions examination resulted in a time saving equivalent to the completion of 16% more MCQs per 1-hour testing period, which may increase content validity and test score reliability, and minimise construct under-representation. The higher cut scores may result in higher failure rates if an absolute standard setting method, such as the TLA method, is used. The results from this study provide a cautious indication to health professions educators that using three-option MCQs does not threaten validity and may strengthen it by allowing additional MCQs to be tested in a fixed amount

  17. Generalized worry disorder: a review of DSM-IV generalized anxiety disorder and options for DSM-V.

    Science.gov (United States)

    Andrews, Gavin; Hobbs, Megan J; Borkovec, Thomas D; Beesdo, Katja; Craske, Michelle G; Heimberg, Richard G; Rapee, Ronald M; Ruscio, Ayelet Meron; Stanley, Melinda A

    2010-02-01

    Generalized anxiety disorder (GAD) has undergone a series of substantial classificatory changes since its first inclusion in DSM-III. The majority of these revisions have been in response to its poor inter-rater reliability and concerns that it may lack diagnostic validity. This article provides options for the revision of the DSM-IV GAD criteria for DSM-V. First, searches were conducted to identify the evidence that previous DSM Work Groups relied upon when revising the DSM-III-R GAD and the overanxious disorder classifications. Second, the literature pertaining to the DSM-IV criteria for GAD was examined. The review presents a number of options to be considered for DSM-V. One option is for GAD to be re-labeled in DSM-V as generalized worry disorder. This would reflect its hallmark feature. Proposed revisions would result in a disorder that is characterized by excessive anxiety and worry generalized to a number of events or activities for 3 months or more. Worry acts as a cognitive coping strategy that manifests in avoidant behaviors. The reliability and validity of the proposed changes could be investigated in DSM-V validity tests and field trials.

  18. Novel therapeutic approaches in chondrosarcoma.

    Science.gov (United States)

    Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

    2017-03-01

    Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

  19. The current treatment options for epilepsy

    International Nuclear Information System (INIS)

    Sykora, P.; Svecova, L.

    2014-01-01

    Epilepsy is the most prevalent chronic brain disease manifesting with epileptic seizures. Epilepsy itself is not one nosological entity, it rather includes several diseases with various etiology, clinics, course and therapy. Antiepileptic therapy aims seizure freedom without affecting psychical and physical functions. The therapy is in first line pharmacological. The choice of antiepileptic drug depends not only on the seizure phenomenology, but also on the respective type of epilepsy syndrome. Most patients achieve seizure freedom or at least significant seizure frequency reduction. In 20-30% of the patients is the pharmacotherapy ineffective. In these cases of refractory epilepsy therapeutical options include epilepsy surgery, vagal stimulation or ketogenic diet. Despite recent advances in the diagnostics and therapy, epilepsy remains a serious medical and social issue. (author)

  20. Biofeedback as complementary treatment in patients with epilepsy – an underestimated therapeutic option? Review, results, discussion

    Directory of Open Access Journals (Sweden)

    Uhlmann Carmen

    2016-12-01

    Full Text Available Background. Biofeedback methods represent side effect free complementary options in the treatment of epilepsy. In this paper we review the current status of these methods in terms of clinical study results and their evaluation by systematic review papers. Possible mechanisms of action in biofeedback methods are discussed.

  1. Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

    Science.gov (United States)

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-10-01

    High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

  2. Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sudhakar R. Subramaniam

    2017-06-01

    Full Text Available Parkinson’s disease (PD is a chronic and progressive disorder characterized neuropathologically by loss of dopamine neurons in the substantia nigra, intracellular proteinaceous inclusions, reduction of dopaminergic terminals in the striatum, and increased neuroinflammatory cells. The consequent reduction of dopamine in the basal ganglia results in the classical parkinsonian motor phenotype. A growing body of evidence suggest that neuroinflammation mediated by microglia, the resident macrophage-like immune cells in the brain, play a contributory role in PD pathogenesis. Microglia participate in both physiological and pathological conditions. In the former, microglia restore the integrity of the central nervous system and, in the latter, they promote disease progression. Microglia acquire different activation states to modulate these cellular functions. Upon activation to the M1 phenotype, microglia elaborate pro-inflammatory cytokines and neurotoxic molecules promoting inflammation and cytotoxic responses. In contrast, when adopting the M2 phenotype microglia secrete anti-inflammatory gene products and trophic factors that promote repair, regeneration, and restore homeostasis. Relatively little is known about the different microglial activation states in PD and a better understanding is essential for developing putative neuroprotective agents. Targeting microglial activation states by suppressing their deleterious pro-inflammatory neurotoxicity and/or simultaneously enhancing their beneficial anti-inflammatory protective functions appear as a valid therapeutic approach for PD treatment. In this review, we summarize microglial functions and, their dual neurotoxic and neuroprotective role in PD. We also review molecules that modulate microglial activation states as a therapeutic option for PD treatment.

  3. A numerical approach to the study of the perpetual case of Ameripean options

    Science.gov (United States)

    Kandilarov, J.

    2013-12-01

    A new numerical method for solving the perpetual case of Ameripean options is proposed. The Ameripean delayed exercise model analyzes a new class of option model with American and ParAsian features. The model is mathematically described by ultraparabolic and parabolic PDE's which are valid over different regions. The perpetual case leads to the parabolic-elliptic two-phase Stefan problem with free internal boundary. To deal with the obtained nonlinear problem an iterative numerical method is proposed. Numerical analysis are presented and discussed.

  4. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  5. Binge-eating disorder: Clinical and therapeutic advances.

    Science.gov (United States)

    Hutson, Peter H; Balodis, Iris M; Potenza, Marc N

    2018-02-01

    Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology and pharmacology, drawing from clinical therapeutic, neuroimaging, cognitive, human genetic and animal model studies. These studies, which are still in their infancy, indicate that while there are many gaps in our knowledge, several key neural substrates appear to underpin binge-eating and may be conserved between human and animals. This observation suggests that behavioral intermediate phenotypes or endophenotypes relevant to BED may be modeled in animals, facilitating the identification and testing of novel pharmacological targets. The development of novel, safe and effective pharmacological therapies for the treatment of BED will enhance the ability of clinicians to provide optimal care for people with BED. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Dry eye syndrome. Etiological and therapeutic aspects.

    Science.gov (United States)

    Apostol, Silvia; Filip, M; Dragne, Carmen; Filip, A

    2003-01-01

    "Dry eye syndrome" is a common disorder of the tear film that results from inadequate tear production, excessive tear evaporation or abnormality in mucin or lipid components of the tear film. A number of 53 patients suffering from dry eye syndrome were followed up for a period of 18 months. The study group was heterogeneous, including a lot of conditions accompanied by dry eye syndrome: Syogren's syndrome, lupus erythematous, ocular rosacea, patients with systemic treatments with antidepressants, betablockers, diuretics, oral contraceptives, glaucomatous patients with topical beta-blockers, postmenopausal women, aging people, computer users and long-term contact lens wearers. The therapeutical options were dictated by the severity of the syndrome: substitution therapy, treatment of the underlying eyelid diseases, modifying of the environmental conditions and treatment of the complications in the most severe cases. The new pathological approach is innovative and it may provide a real therapeutical measure for this condition: topical A Cyclosporine and androgen drops.

  7. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays.

    Science.gov (United States)

    Rezende, Vinicius Marcondes; Rivellis, Ariane; Novaes, Mafalda Megumi Yoshinaga; de Alencar Fisher Chamone, Dalton; Bendit, Israel

    2013-01-01

    Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring. A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The method was validated according to the requirements of the US Food and Drug Administration and Brazilian National Health Surveillance Agency within the range of 0.500-10.0 μg/mL with a limit of detection of 0.155 μg/mL. Stability data for the analyte are also presented. Given that the validated method has proved to be linear, accurate, precise, and robust, it is suitable for pharmacokinetic assays, such as bioavailability and bioequivalence, and is being successfully applied in routine therapeutic drug monitoring in the hospital service.

  8. SGLT2 inhibitors provide an effective therapeutic option for diabetes complicated with insulin antibodies.

    Science.gov (United States)

    Hayashi, Akinori; Takano, Koji; Kawai, Sayuki; Shichiri, Masayoshi

    2016-01-01

    Diabetes mellitus complicated with insulin antibodies is rare in clinical practice but usually difficult to control. A high amount of insulin antibodies, especially with low affinity and high binding capacity, leads to unstable glycemic control characterized by hyperglycemia unresponsive to large volume of insulin and unanticipated hypoglycemia. There are several treatment options, such as changing insulin preparation, immunosupression with glucocorticoids, and plasmapheresis, most of which are of limited efficacy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drug which decrease renal glucose reabsorption and lowers plasma glucose level independent of insulin action. We report here a case with diabetes complicated with insulin antibodies who was effectively controlled by an SGLT2 inhibitor. A 47-year-old man with type 2 diabetes treated with insulin had very poor glycemic control characterized by postprandial hyperglycemia unresponsive to insulin therapy and repetitive hypoglycemia due to insulin antibodies. Treatment with ipragliflozin, an SGLT2 inhibitor, improved HbA1c from 8.4% to 6.0% and glycated albumin from 29.4% to 17.9%. Continuous glucose monitoring revealed improvement of glycemic profile (average glucose level from 212 mg/dL to 99 mg/dL and glycemic standard deviation from 92 mg/dL to 14 mg/dL) with disappearance of hypoglycemic events. This treatment further ameliorated the characteristics of insulin antibodies and resulted in reduced insulin requirement. SGLT2 inhibitors may offer an effective treatment option for managing the poor glycemic control in diabetes complicated with insulin antibodies.

  9. Trend of extensively drug-resistant Acinetobacter baumannii and the remaining therapeutic options: a multicenter study in Tehran, Iran over a 3-year period.

    Science.gov (United States)

    Jasemi, S; Douraghi, M; Adibhesami, H; Zeraati, H; Rahbar, M; Boroumand, M A; Aliramezani, A; Ghourchian, S; Mohammadzadeh, M

    2016-12-01

    Comprehensive data on drug-resistant patterns of Acinetobacter baumannii isolates in developing countries is limited. We conducted a multihospital study to assess the rate and trend of drug-resistant phenotypes in Ac. baumannii using standardized definitions and to determine the remaining therapeutic options against resistant phenotypes. The 401 nonduplicate isolates were collected from six hospitals which are geographically distributed across Tehran, Iran over a 3-year period. Following PCR of bla OXA -51-like gene, susceptibility testing was performed against nine antimicrobial agent categories. Three hundred and ninety (97%) isolates were resistant to least two carbapenems; carbapenem-resistant Ac. baumannii. The majority of isolates (366, 91·3%) were extensively drug resistant (XDR) and the rest of the isolates were classified as multidrug resistant (26, 6·8%) and susceptible (9, 2·2%). The rate of XDR-AB slightly decreased from 93·8% in 2011 to 89·8% in 2013. A considerable decrease in resistance to doxycycline, minocycline and tigecycline was demonstrated. The XDR-AB isolates showed susceptibility to gentamicin (10·4%), tobramycin (23%), ampicilin-sulbactam (30·1%), minocycline (32·8%), tigecycline (10·7%), doxycycline (21·6%), colistin (100%) and polymixin B (100%). We demonstrated the rising trend of resistance to all antibiotic categories except tetracyclines and folate pathway inhibitors. We found that the treatment options against XDR-AB are extremely limited and each treatment alternative including even old, but safe, antibiotics might be considered. The high frequency of drug-resistant phenotypes including carbapenem-resistant Acinetobacter baumannii, multidrug-resistant, and extensively resistant has been demonstrated in Ac. baumannii isolates tested here. As the antibiotic resistance pattern of isolates varies in different geographical regions, this study can provide comprehensive information about the antibiotic resistance profile of Ac

  10. Design, development, and clinical validation of therapeutic toys for autistic children.

    Science.gov (United States)

    Tseng, Kevin C; Tseng, Sung-Hui; Cheng, Hsin-Yi Kathy

    2016-07-01

    [Purpose] One of the characteristics of autistic children is social interaction difficulties. Although therapeutic toys can promote social interaction, however its related research remains insufficient. The aim of the present study was to build a set of cooperative play toys that are suitable for autistic children. [Subjects and Methods] This study used an innovative product design and development approach as the basis for the creation of cooperative play toys. [Results] The present study has successfully developed cooperative play toys. Compared to the traditional game therapy for autism, cooperative play toy therapy can significantly improve the interactions between autistic children and their peers. [Conclusion] The most critical design theme of cooperative play toys focuses on captivating the interest of autistic children. Based on the needs of the individual cases, the design of the therapeutic toy set was specifically tailored, i.e., by reinforcing the sound and light effects to improve the attractiveness of the toys. In the future, different play modes can be combined with this toy set to further enhance the degree of interaction of autistic children and improve their quality of life and social skills.

  11. Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials.

    Science.gov (United States)

    Bhatt, Kunal N; Butler, Javed

    2018-06-01

    Several novel therapeutics being tested in patients with heart failure are based on myocardial energetics. This review will provide a summary of the recent trials in this area, including therapeutic options targeting various aspects of cellular and mitochondrial metabolism. Agents that improve the energetic balance in myocardial cells have the potential to improve clinical heart failure status. The most promising therapies currently under investigation in this arena include (1) elamipretide, a cardiolipin stabilizer; (2) repletion of iron deficiency with intravenous ferrous carboxymaltose; (3) coenzyme Q10; and (4) the partial adenosine receptor antagonists capadenoson and neladenosone. Myocardial energetics-based therapeutics are groundbreaking in that they utilize novel mechanisms of action to improve heart failure symptoms, without causing the adverse neurohormonal side effects associated with current guideline-based therapies. The drugs appear likely to be added to the heart failure therapy armamentarium as adjuncts to current regimens in the near future.

  12. Exotic Options: a Chooser Option and its Pricing

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2012-12-01

    Full Text Available Financial instruments traded in the markets and investors’ situation in such markets are getting more and more complex. This leads to more complex derivative structures used for hedging that are harder to analyze and which risk is harder managed. Because of the complexity of these instruments, the basic characteristics of many exotic options may sometimes be not clearly understood. Most scientific studies have been focused on developing models for pricing various types of exotic options, but it is important to study their unique characteristics and to understand them correctly in order to use them in proper market situations. The paper examines main aspects of options, emphasizing the variety of exotic options and their place in financial markets and risk management process. As the exact valuation of exotic options is quite difficult, the article deals with the theoretical and practical aspects of pricing of chooser options that suggest a broad range of usage and application in different market conditions. The calculations made in the article showed that the price of the chooser is closely correlated with the choice time and low correlated with its strike price. So the first mentioned factor should be taken into consideration when making appropriate hedging and investing decisions.

  13. Split high‐dose oral levothyroxine treatment as a successful therapy option in myxedema coma

    OpenAIRE

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-01-01

    Key Clinical Message High‐dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69‐year‐old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high‐dose oral LT4 as a therapeutic option in myxedema coma.

  14. Treatment options for diabetic foot osteomyelitis.

    Science.gov (United States)

    Senneville, Eric; Robineau, Olivier

    2017-06-01

    Diabetic foot osteomyelitis therapeutical options are based on antibiotic therapy and surgical resection of the infected bone(s). Surgical and medical approaches of patients suffering from a diabetic foot osteomyelitis do not oppose but are complementary and need to be discussed as a tailored manner. Areas covered: The aim of the present article is to discuss data issued from the most recent guidelines of the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot on the management of the diabetic foot infection and from a search in the current literature using the terms diabetic foot osteomyelitis and treatment/therapy/therapeutical in both PubMed and Medline, restricted to the last five years. Expert opinion: Surgical removal of the entire infected bone(s) has been considered in the past as the standard treatment but medical approach of these patients has now proven efficacy in selected situations. The current emergence of bacteria, especially among Gram negative rods, resistant to almost all the available antibiotics gradually augments the complexity of the management of these patients and is likely to decrease the place of the medical approach and to worsen the outcome of these infections in the next future.

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

    Science.gov (United States)

    Khanna, Amardeep; Jones, David E

    2017-10-01

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

  16. COMBINATION THERAPIES OR STANDALONE INTERVENTIONS? INNOVATION OPTIONS FOR PHARMACEUTICAL FIRMS FIGHTING CANCER

    OpenAIRE

    GUNJAN BHARDWAJ; ANSHIT AGRAWAL; RUPESH TYAGI

    2015-01-01

    Innovation is key to the pharma model, from an initial discovery to the final development of a marketable drug. Here, we explore the innovation options in the fiercely contested therapeutic area of Oncology. We studied clinical development of drugs targeting PD-1 and PD-L1 pathway. In this interesting contest, companies seem to be focusing on standalone interventions (exploratory innovation) and combination therapy (exploitative innovation) in clinical development. Merck Sharp and Dohme, havi...

  17. NASA's Asteroid Redirect Mission: The Boulder Capture Option

    Science.gov (United States)

    Abell, Paul A.; Nuth, J.; Mazanek, D.; Merrill, R.; Reeves, D.; Naasz, B.

    2014-01-01

    NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar-electric-propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (approximately 4-10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is examining another option that entails retrieving a boulder (approximately 1-5 m) via robotic manipulators from the surface of a larger (approximately 100+ m) pre-characterized NEA. This option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well-characterized NEAs. For example, the data from the Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. The boulder option is an extremely large sample-return mission with the prospect of bringing back many tons of well-characterized asteroid material to the Earth-Moon system. The candidate boulder from the target NEA can be selected based on inputs from the world-wide science community, ensuring that the most scientifically interesting boulder be returned for subsequent sampling. This boulder option for NASA's ARM can leverage knowledge of previously characterized NEAs from prior robotic missions, which provides more

  18. The psychology of health and addictions: therapeutic perspective

    Directory of Open Access Journals (Sweden)

    Elisardo Becoña Iglesias

    2003-06-01

    Full Text Available The addiction subject is nowadays a valid one, as well as in the past century. Not only because of the increase of people that are addict, but also because of the important effects that cause on people and their environments. There are many theoretical perspectives to approach the addiction problem, but the most convenient because of its therapeutic results is the one that issupported by the psychology of health. lt is based on the integral approach to the person. This paper describes a general therapeutic scheme to work with addicts from the cognitive behaviora lperspective.

  19. Advancing treatment options for chronic idiopathic constipation.

    Science.gov (United States)

    Quigley, Eamonn M M; Neshatian, Leila

    2016-01-01

    Chronic constipation is a global problem affecting all ages and associated with considerable morbidity and significant financial burden for society. Though formerly defined on the basis of a single symptom, infrequent defecation; constipation is now viewed as a syndrome encompassing several complaints such as difficulty with defecation, a sense of incomplete evacuation, hard stools, abdominal discomfort and bloating. The expanded concept of constipation has inevitably led to a significant change in outcomes in clinical trials, as well as in patient expectations from new therapeutic interventions. The past decades have also witnessed a proliferation in therapeutic targets for new agents. Foremost among these have been novel prokinetics, a new category, prosecretory agents and innovative approaches such as inhibitors of bile salt transport. In contrast, relatively few effective therapies exist for the management of those anorectal and pelvic floor problems that result in difficult defecation. Though constipation is a common and often troublesome disorder, many of those affected can resolve their symptoms with relatively simple measures. For those with more resistant symptoms a number of novel, effective and safe options now exist. Those with defecatory difficulty (anismus, pelvic floor dysfunction) continue to represent a significant management challenge.

  20. An update on adjunctive treatment options for bipolar disorder.

    Science.gov (United States)

    Dean, Olivia M; Gliddon, Emma; Van Rheenen, Tamsyn E; Giorlando, Francesco; Davidson, Sandra K; Kaur, Manreena; Ngo, Trung T; Williams, Lana J

    2018-03-01

    Bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. In recent years, there have been significant advancements in a number of therapies for bipolar disorder. It is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes. Publications were identified from PubMed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e-Health and brain stimulation techniques. Relevant articles in these areas were selected for further review. This paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature. A number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. These have varying efficacy but all have shown benefit to people with bipolar disorder. Due to the complex nature of treating the disorder, combination treatments are often required. Adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery. Given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. Correspondingly, psychiatric research is working towards a better understanding of the disorder's underlying biology. Therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. Towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Penalty methods for the numerical solution of American multi-asset option problems

    Science.gov (United States)

    Nielsen, Bjørn Fredrik; Skavhaug, Ola; Tveito, Aslak

    2008-12-01

    We derive and analyze a penalty method for solving American multi-asset option problems. A small, non-linear penalty term is added to the Black-Scholes equation. This approach gives a fixed solution domain, removing the free and moving boundary imposed by the early exercise feature of the contract. Explicit, implicit and semi-implicit finite difference schemes are derived, and in the case of independent assets, we prove that the approximate option prices satisfy some basic properties of the American option problem. Several numerical experiments are carried out in order to investigate the performance of the schemes. We give examples indicating that our results are sharp. Finally, the experiments indicate that in the case of correlated underlying assets, the same properties are valid as in the independent case.

  2. Organizational options for a future Romanian electricity market

    International Nuclear Information System (INIS)

    Constantinescu, J.; Patterson, W.

    1996-01-01

    All over the world the implementation of energy efficient and clean technologies can be hardly considered without opening the way to competition and the involvement of private investment. If such terms are valid for reach countries there are even more adequate for economies in transition like Romania's, which inherited and obsolete productive equipment, can mobilize insufficient resources for development-modernization and exhibits a quasi-unanimous option of adhering at European Union. (author). 3 tabs., 11 refs

  3. Australian Asian Options

    OpenAIRE

    Manuel Moreno; Javier F. Navas

    2003-01-01

    We study European options on the ratio of the stock price to its average and viceversa. Some of these options are traded in the Australian Stock Exchange since 1992, thus we call them Australian Asian options. For geometric averages, we obtain closed-form expressions for option prices. For arithmetic means, we use different approximations that produce very similar results.

  4. Design, development, and clinical validation of therapeutic toys for autistic children

    OpenAIRE

    Tseng, Kevin C.; Tseng, Sung-Hui; Cheng, Hsin-Yi Kathy

    2016-01-01

    [Purpose] One of the characteristics of autistic children is social interaction difficulties. Although therapeutic toys can promote social interaction, however its related research remains insufficient. The aim of the present study was to build a set of cooperative play toys that are suitable for autistic children. [Subjects and Methods] This study used an innovative product design and development approach as the basis for the creation of cooperative play toys. [Results] The present study has...

  5. Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease.

    Science.gov (United States)

    Freitag, Helma; Christen, Friederike; Lewens, Florentine; Grass, Irina; Briest, Franziska; Iwaszkiewicz, Sara; Siegmund, Britta; Grabowski, Patricia

    2017-01-01

    The characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, the current therapy options are not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and mTORC1/C2. We assessed the effects of PKI-587 in different GEP-NEN tumor models, including the poorly differentiated cell line LCC-18, and compared them with those of the established mTORC1 inhibitor everolimus. We treated BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We assessed the impact of the treatments on viability (WST-1 assay), on apoptotic processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow cytometry). We determined alterations in signaling mediators by phosphor-specific Western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology). In all cell lines, PKI-587 dose-dependently inhibited proliferation, whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest and induction of apoptosis and successfully suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this paper. PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials. © 2016 The Author(s) Published by S. Karger AG, Basel.

  6. The results of therapeutic plasma exchange in patients with severe hyperthyroidism: a retrospective multicenter study.

    Science.gov (United States)

    Keklik, Muzaffer; Kaynar, Leylagul; Yilmaz, Mehmet; Sivgin, Serdar; Solmaz, Musa; Pala, Cigdem; Aribas, Sulbiye; Akyol, Gulsah; Unluhizarci, Kursat; Cetin, Mustafa; Eser, Bulent; Unal, Ali

    2013-06-01

    Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (phyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. New innovations: therapeutic opportunities for intellectual disabilities.

    Science.gov (United States)

    Picker, Jonathan D; Walsh, Christopher A

    2013-09-01

    Intellectual disability is common and is associated with significant morbidity. Until the latter half of the 20th century, there were no efficacious treatments. Following initial breakthroughs associated with newborn screening and metabolic corrections, little progress was made until recently. With improved understanding of genetic and cellular mechanisms, novel treatment options are beginning to appear for a number of specific conditions. Fragile X and tuberous sclerosis offer paradigms for the development of targeted therapeutics, but advances in understanding of other disorders such as Down syndrome and Rett syndrome, for example, are also resulting in promising treatment directions. In addition, better understanding of the underlying neurobiology is leading to novel developments in enzyme replacement for storage disorders and adjunctive therapies for metabolic disorders, as well as potentially more generalizable approaches that target dysfunctional cell regulation via RNA and chromatin. Physiologic therapies, including deep brain stimulation and transcranial magnetic stimulation, offer yet another direction to enhance cognitive functioning. Current options and evolving opportunities for the intellectually disabled are reviewed and exemplified. Copyright © 2013 American Neurological Association.

  8. Real Options in Capital Budgeting. Pricing the Option to Delay and the Option to Abandon a Project

    Directory of Open Access Journals (Sweden)

    Nicoleta Vintila

    2007-07-01

    Full Text Available Traditional discounted cash-flows method for assessing projects assumes that investment decision is an irreversible one, which is not correct. Managers can and must reconsider their initial decision as the new information arises during the project life. This is managerial flexibility and it creates strategic value for a project, only if management takes advantage of the opportunities associated with an analyzed project. Real options represent a new approach in capital budgeting, using the theory of pricing financial options for investments in real assets. In this paper, we emphasize the characteristics and valuation methodologies of real options. The objective in the last section is pricing the option to delay and the option to abandon a project in construction materials field.

  9. Therapeutic advancement of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Lu Kang

    2012-09-01

    Full Text Available Abstract Despite the combinations of chemotherapy with monoclonal antibodies have further improved response rates, chronic lymphocytic leukemia (CLL remains an incurable disease with an extremely variable course. This article reviews the ongoing clinical advances in the treatment of CLL in both previously untreated and relapsed disease and focuses on the benefit of different therapeutic strategies, the most effective therapy combinations and the potential activity of novel agents. Novel agents and combination therapies have been investigated by several studies in both the upfront and relapsed setting, particularly for patients with 17p deletion, TP53 mutation and fludarabine-refractory CLL. While these agents and combination therapies have improved initial response rates, ongoing studies are continued to determine and improve the efficacy and safety. Despite advancements in the treatment of CLL have led to high response rates, allogeneic hematopoietic stem cell transplantation (allo-HSCT remains the only curative option and reduced-intensity conditioning (RIC allo-HSCT must be strongly considered whenever feasible. As such, ongoing studies of these agents and other novel approaches in clinical development are needed to expand and improve treatment options for CLL patients.

  10. Stata 8 Graphics: Options, sub-options and sub-sub-options

    OpenAIRE

    Tim Collier

    2005-01-01

    Stata 8 graphics have changed out of all recognition from that available in earlier versions. It was not just that a whole new array of options and sub-options were introduced, but the graph syntax itself completely changed. Just trying to produce a simple plot of x against y using Stata 7 syntax (graph x y) produced bewildering error messages e.g. xgraph_g.new y: class member function not found r(4023) and the like. If you did succeed in working out the new syntax (graph twoway scatter x y) ...

  11. Policy and Validity Prospects for Performance-Based Assessment.

    Science.gov (United States)

    Baker, Eva L.; And Others

    1994-01-01

    This article describes performance-based assessment as expounded by its proponents, comments on these conceptions, reviews evidence regarding the technical quality of performance-based assessment, and considers its validity under various policy options. (JDD)

  12. Genome Engineering for Personalized Arthritis Therapeutics.

    Science.gov (United States)

    Adkar, Shaunak S; Brunger, Jonathan M; Willard, Vincent P; Wu, Chia-Lung; Gersbach, Charles A; Guilak, Farshid

    2017-10-01

    Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Automated (Centrifugal) therapeutic plasma exchange option for guillain-barre syndrome: A report from Calabar, Nigeria.

    Science.gov (United States)

    Iheanacho, O E; Chimeziem, C; Sachais, B S; Shi, P A

    2017-10-01

    Therapeutic plasma exchange (TPE) is performed frequently and effectively in developed countries, whereas the reverse is the case in developing countries. Guillain-Barre syndrome (GBS), synonymous with acute inflammatory demyelinating polyneuropathy, is an important indication for TPE, but this is rarely administered in the treatment of such patients in Nigeria due to lack of such automated facility, limited expertise, and high cost. This report therefore presents an uncommon case of GBS in which automated TPE was utilized in the management, with the aims of highlighting the current status and challenges of therapeutic apheresis services in Nigeria. A 42-year-old male presented with rapidly progressive (in an ascending fashion) paralysis of all four limbs within 24 h without any preceding history of fever or other symptoms. Clinical examination revealed a young man, afebrile, not pale, and also not dehydrated. Central nervous system examination showed a conscious man, alert, and oriented in time, person, and place. There were no signs of meningeal irritation and the cranial nerves were grossly intact. There was no power in the limbs: global hypotonia and areflexia were noted on examination. However, he had intact sensory perceptions to touch and pain. Following a diagnosis of GBS, he was treated with four sessions of plasmapheresis and TPE. The TPE session was done using a discontinuous flow apheresis machine which exchanged one plasma volume (3 L of plasma) and 5% albumin used for replacement. The patient made gradual but steady recovery as return of power to the upper limbs and trunk started by the 2nd week of treatment. TPE is an important treatment modality in the management of GBS as well as several other conditions, and it is becoming increasingly available in Nigeria. However, it is still grossly underutilized, thus the need for more therapeutic apheresis facilities and trained personnel, in addition to concerted efforts to subsidize the cost of accessing

  14. An Assessment of Geological Carbon Storage Options in the Illinois Basin: Validation Phase

    Energy Technology Data Exchange (ETDEWEB)

    Finley, Robert

    2012-12-01

    The Midwest Geological Sequestration Consortium (MGSC) assessed the options for geological carbon dioxide (CO{sub 2}) storage in the 155,400 km{sup 2} (60,000 mi{sup 2}) Illinois Basin, which underlies most of Illinois, western Indiana, and western Kentucky. The region has annual CO{sub 2} emissions of about 265 million metric tonnes (292 million tons), primarily from 122 coal-fired electric generation facilities, some of which burn almost 4.5 million tonnes (5 million tons) of coal per year (U.S. Department of Energy, 2010). Validation Phase (Phase II) field tests gathered pilot data to update the Characterization Phase (Phase I) assessment of options for capture, transportation, and storage of CO{sub 2} emissions in three geological sink types: coal seams, oil fields, and saline reservoirs. Four small-scale field tests were conducted to determine the properties of rock units that control injectivity of CO{sub 2}, assess the total storage resources, examine the security of the overlying rock units that act as seals for the reservoirs, and develop ways to control and measure the safety of injection and storage processes. The MGSC designed field test operational plans for pilot sites based on the site screening process, MVA program needs, the selection of equipment related to CO{sub 2} injection, and design of a data acquisition system. Reservoir modeling, computational simulations, and statistical methods assessed and interpreted data gathered from the field tests. Monitoring, Verification, and Accounting (MVA) programs were established to detect leakage of injected CO{sub 2} and ensure public safety. Public outreach and education remained an important part of the project; meetings and presentations informed public and private regional stakeholders of the results and findings. A miscible (liquid) CO{sub 2} flood pilot project was conducted in the Clore Formation sandstone (Mississippian System, Chesterian Series) at Mumford Hills Field in Posey County, southwestern

  15. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

    Directory of Open Access Journals (Sweden)

    C. L. Hughes

    2015-01-01

    Full Text Available In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.

  16. Validation suite for MCNP

    International Nuclear Information System (INIS)

    Mosteller, Russell D.

    2002-01-01

    Two validation suites, one for criticality and another for radiation shielding, have been defined and tested for the MCNP Monte Carlo code. All of the cases in the validation suites are based on experiments so that calculated and measured results can be compared in a meaningful way. The cases in the validation suites are described, and results from those cases are discussed. For several years, the distribution package for the MCNP Monte Carlo code1 has included an installation test suite to verify that MCNP has been installed correctly. However, the cases in that suite have been constructed primarily to test options within the code and to execute quickly. Consequently, they do not produce well-converged answers, and many of them are physically unrealistic. To remedy these deficiencies, sets of validation suites are being defined and tested for specific types of applications. All of the cases in the validation suites are based on benchmark experiments. Consequently, the results from the measurements are reliable and quantifiable, and calculated results can be compared with them in a meaningful way. Currently, validation suites exist for criticality and radiation-shielding applications.

  17. Translational research in addiction: toward a framework for the development of novel therapeutics.

    Science.gov (United States)

    Paterson, Neil E

    2011-06-15

    The development of novel substance use disorder (SUD) therapeutics is insufficient to meet the medical needs of a growing SUD patient population. The identification of translatable SUD models and tests is a crucial step in establishing a framework for SUD therapeutic development programs. The present review begins by identifying the clinical features of SUDs and highlights the narrow regulatory end-point required for approval of a novel SUD therapeutic. A conceptual overview of dependence is provided, followed by identification of potential intervention targets in the addiction cycle. The main components of the addiction cycle provide the framework for a discussion of preclinical models and their clinical analogs, all of which are focused on isolated behavioral end-points thought to be relevant to the persistence of compulsive drug use. Thus, the greatest obstacle to successful development is the gap between the multiplicity of preclinical and early clinical end-points and the regulatory end-point of sustained abstinence. This review proposes two pathways to bridging this gap: further development and validation of the preclinical extended access self-administration model; inclusion of secondary end-points comprising all of the measures highlighted in the present discussion in Phase 3 trials. Further, completion of the postdictive validation of analogous preclinical and clinical assays is of high priority. Ultimately, demonstration of the relevance and validity of a variety of end-points to the ultimate goal of abstinence will allow researchers to identify truly relevant therapeutic mechanisms and intervention targets, and establish a framework for SUD therapeutic development that allows optimal decision-making and resource allocation. 2011 Elsevier Inc. All rights reserved.

  18. Therapeutic High-Density Barium Enema in a Case of Presumed Diverticular Hemorrhage

    Directory of Open Access Journals (Sweden)

    Nonthalee Pausawasdi

    2011-02-01

    Full Text Available Many patients with lower gastrointestinal bleeding do not have an identifiable source of bleeding at colonoscopy. A significant percentage of these patients will have recurrent bleeding. In many patients, the presence of multiple diverticula leads to a diagnosis of presumed diverticular bleeding. Current treatment options include therapeutic endoscopy, angiography, or surgical resection, all of which depend on the identification of the diverticular source of bleeding. This report describes a case of recurrent bleeding in an elderly patient with diverticula but no identifiable source treated successfully with barium impaction therapy. This therapeutic modality does not depend on the identification of the bleeding diverticular lesion and was well tolerated by our 86-year-old patient.

  19. The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis.

    Science.gov (United States)

    Heijman, Jordi; Algalarrondo, Vincent; Voigt, Niels; Melka, Jonathan; Wehrens, Xander H T; Dobrev, Dobromir; Nattel, Stanley

    2016-04-01

    Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms for arrhythmia initiation and maintenance. However, it has become clear that the clinical factors predisposing to AF and the cellular and molecular mechanisms involved are extremely complex. Moreover, all AF-promoting and maintaining mechanisms are dynamically regulated and subject to remodelling caused by both AF and cardiovascular disease. Accordingly, the initial presentation and clinical progression of AF patients are enormously heterogeneous. An understanding of arrhythmia mechanisms is widely assumed to be the basis of therapeutic innovation, but while this assumption seems self-evident, we are not aware of any papers that have critically examined the practical contributions of basic research into AF mechanisms to arrhythmia management. Here, we review recent insights into the basic mechanisms of AF, critically analyse the role of basic research insights in the development of presently used anti-AF therapeutic options and assess the potential value of contemporary experimental discoveries for future therapeutic innovation. Finally, we highlight some of the important challenges to the translation of basic science findings to clinical application. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  20. An optimal algorithm for configuring delivery options of a one-dimensional intensity-modulated beam

    International Nuclear Information System (INIS)

    Luan Shuang; Chen, Danny Z; Zhang, Li; Wu Xiaodong; Yu, Cedric X

    2003-01-01

    The problem of generating delivery options for one-dimensional intensity-modulated beams (1D IMBs) arises in intensity-modulated radiation therapy. In this paper, we present an algorithm with the optimal running time, based on the 'rightmost-preference' method, for generating all distinct delivery options for an arbitrary 1D IMB. The previously best known method for generating delivery options for a 1D IMB with N left leaf positions and N right leaf positions is a 'brute-force' solution, which first generates all N! possible combinations of the left and right leaf positions and then removes combinations that are not physically allowed delivery options. Compared with the brute-force method, our algorithm has several advantages: (1) our algorithm runs in an optimal time that is linearly proportional to the total number of distinct delivery options that it actually produces. Note that for a 1D IMB with multiple peaks, the total number of distinct delivery options in general tends to be considerably smaller than the worst case N!. (2) Our algorithm can be adapted to generating delivery options subject to additional constraints such as the 'minimum leaf separation' constraint. (3) Our algorithm can also be used to generate random subsets of delivery options; this feature is especially useful when the 1D IMBs in question have too many delivery options for a computer to store and process. The key idea of our method is that we impose an order on how left leaf positions should be paired with right leaf positions. Experiments indicated that our rightmost-preference algorithm runs dramatically faster than the brute-force algorithm. This implies that our algorithm can handle 1D IMBs whose sizes are substantially larger than those handled by the brute-force method. Applications of our algorithm in therapeutic techniques such as intensity-modulated arc therapy and 2D modulations are also discussed

  1. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™

    Directory of Open Access Journals (Sweden)

    Martin Henkes

    2008-03-01

    Full Text Available 1Martin Henkes, 2Heiko van der Kuip, 1Walter E Aulitzky12nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital, Auerbachstr. 110, Stuttgart, Germany; 2Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, Stuttgart, and University of Tuebingen, GermanyAbstract: Treatment options for chronic myeloid leukemia (CML have changed dramatically during the last decades. Interferon-α treatment and stem cell transplantation (SCT clearly improved survival over conventional chemotherapy and offered the possibility of complete and durable responses. With the advent of the small molecule inhibitor imatinib mesylate (Glivec®, GleevecTM targeting the causative Bcr-Abl oncoprotein, the era of molecular cancer therapy began with remarkable success especially in chronic phase patients. Today, imatinib is the first-line treatment for CML. However, imatinib does not appear to be capable to eliminate all leukemia cells in the patients and pre-existing as well as acquired resistance to the drug has been increasingly recognized. To overcome these problems, several strategies involving dose escalation, combinations with other agents, and novel Bcr-Abl inhibitors have been developed.Keywords: CML therapy, imatinib, SCT, novel kinase inhibitors

  2. ACCOUNTING FOR OPTIONS AND ANALYSIS OF USE OF OPTION COMBINATION STRATEGIES

    Directory of Open Access Journals (Sweden)

    I. Derun

    2016-08-01

    Full Text Available The article deals with problems of accounting for options in Ukraine, namely: value expression of initial cost of options, their revaluation, accounting of premiums, financial assets and financial liabilities and variation margin. The paper offers ways of solution of these problems which based on harmonization with IAS 32, IAS 39, IFRS 7 and IFRS 9. The study considers option combination strategies (straddle, strangle, strap, strip and approaches of identification of possible financial results for investors which use these strategies. Examples of possible financial results are provided for buyers and sellers of options which use option combination strategies.

  3. Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Odiba Arome

    2017-09-01

    Full Text Available Science always strives to find an improved way of doing things and nanoscience is one such approach. Nanomaterials are suitable for pharmaceutical applications mostly because of their size which facilitates absorption, distribution, metabolism and excretion of the nanoparticles. Whether labile or insoluble nanoparticles, their cytotoxic effect on malignant cells has moved the use of nanomedicine into focus. Since nanomedicine can be described as the science and technology of diagnosing, treating and preventing diseases towards ultimately improving human health, a lot of nanotechnology options have received approval by various regulatory agencies. Nanodrugs also have been discovered to be more precise in targeting the desired site, hence maximizing the therapeutic effects, while minimizing side-effects on the rest of the body. This unique property and more has made nanomedicine popular in therapeutic medicine employing nanotechnology in genetic therapy, drug encapsulation, enzyme manipulation and control, tissue engineering, target drug delivery, pharmacogenomics, stem cell and cloning, and even virus-based hybrids. This review highlights nanoproducts that are in development and have gained approval through one clinical trial stage or the other.

  4. Verification and Validation of RADTRAN 5.5.

    Energy Technology Data Exchange (ETDEWEB)

    Osborn, Douglas.; Weiner, Ruth F.; Mills, George Scott; Hamp, Steve C.

    2005-02-01

    This document contains a description of the verification and validation process used for the RADTRAN 5.5 code. The verification and validation process ensured the proper calculational models and mathematical and numerical methods were used in the RADTRAN 5.5 code for the determination of risk and consequence assessments. The differences between RADTRAN 5 and RADTRAN 5.5 are the addition of tables, an expanded isotope library, and the additional User-Defined meteorological option for accident dispersion. 3

  5. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    Energy Technology Data Exchange (ETDEWEB)

    Gruber-Rouh, Tatjana, E-mail: tgruberrouh@googlemail.com [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt); Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Tsaur, Igor [Department of Urology, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main (Germany); Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

    2014-12-15

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate.

  6. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    International Nuclear Information System (INIS)

    Gruber-Rouh, Tatjana; Naguib, Nagy N.N.; Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin; Tsaur, Igor; Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar

    2014-01-01

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate

  7. Microsoft Visio 2013 business process diagramming and validation

    CERN Document Server

    Parker, David

    2013-01-01

    Microsoft Visio 2013 Business Process Diagramming and Validation provides a comprehensive and practical tutorial including example code and demonstrations for creating validation rules, writing ShapeSheet formulae, and much more.If you are a Microsoft Visio 2013 Professional Edition power user or developer who wants to get to grips with both the essential features of Visio 2013 and the validation rules in this edition, then this book is for you. A working knowledge of Microsoft Visio and optionally .NET for the add-on code is required, though previous knowledge of business process diagramming

  8. Rehabilitation Options

    Science.gov (United States)

    ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ...

  9. 5 CFR 870.705 - Amount and election of Option B and Option C.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Amount and election of Option B and Option C. 870.705 Section 870.705 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED... Compensationers § 870.705 Amount and election of Option B and Option C. (a) The number of multiples of Option B...

  10. Identifying therapeutic targets in gastric cancer: the current status and future direction

    Science.gov (United States)

    Yu, Beiqin; Xie, Jingwu

    2016-01-01

    Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID:26373844

  11. Construction of Valid and Reliable Test for Assessment of Students

    Science.gov (United States)

    Osadebe, P. U.

    2015-01-01

    The study was carried out to construct a valid and reliable test in Economics for secondary school students. Two research questions were drawn to guide the establishment of validity and reliability for the Economics Achievement Test (EAT). It is a multiple choice objective test of five options with 100 items. A sample of 1000 students was randomly…

  12. Management options for cholestatic liver disease in children.

    Science.gov (United States)

    Catzola, Andrea; Vajro, Pietro

    2017-11-01

    Due to a peculiar age-dependent increased susceptibility, neonatal cholestasis affects the liver of approximately 1 in every 2500 term infants. A high index of suspicion is the key to an early diagnosis, and to implement timely, often life-saving treatments. Even when specific treatment is not available or curative, prompt medical management and optimization of nutrition are of paramount importance to survival and avoidance of complications. Areas covered: The present article will prominently focus on a series of newer diagnostic and therapeutic options of cholestasis in neonates and infants blended with consolidated established paradigms. The overview of strategies for the management reported here is based on a systematic literature search published in English using accessible databases (PubMed, MEDLINE) with the keywords biliary atresia, choleretics and neonatal cholestasis. References lists from retrieved articles were also reviewed. Expert commentary: A large number of uncommon and rare hepatobiliary disorders may present with cholestasis during the neonatal and infantile period. Potentially life-saving disease-specific pharmacological and surgical therapeutic approaches are currently available. Advances in hepatobiliary transport mechanisms have started clarifying fundamental aspects of inherited and acquired cholestasis, laying the foundation for the development of possibly more effective specific therapies.

  13. The state-of-play and future of antibody therapeutics.

    Science.gov (United States)

    Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

    2017-12-01

    It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. The Amnesiac Lookback Option: Selectively Monitored Lookback Options and Cryptocurrencies

    Directory of Open Access Journals (Sweden)

    Ho-Chun Herbert Chang

    2018-05-01

    Full Text Available This study proposes a strategy to make the lookback option cheaper and more practical, and suggests the use of its properties to reduce risk exposure in cryptocurrency markets through blockchain enforced smart contracts and correct for informational inefficiencies surrounding prices and volatility. This paper generalizes partial, discretely-monitored lookback options that dilute premiums by selecting a subset of specified periods to determine payoff, which we call amnesiac lookback options. Prior literature on discretely-monitored lookback options considers the number of periods and assumes equidistant lookback periods in pricing partial lookback options. This study by contrast considers random sampling of lookback periods and compares resulting payoff of the call, put and spread options under floating and fixed strikes. Amnesiac lookbacks are priced with Monte Carlo simulations of Gaussian random walks under equidistant and random periods. Results are compared to analytic and binomial pricing models for the same derivatives. Simulations show diminishing marginal increases to the fair price as the number of selected periods is increased. The returns correspond to a Hill curve whose parameters are set by interest rate and volatility. We demonstrate over-pricing under equidistant monitoring assumptions with error increasing as the lookback periods decrease. An example of a direct implication for event trading is when shock is forecasted but its timing uncertain, equidistant sampling produces a lower error on the true maximum than random choice. We conclude that the instrument provides an ideal space for investors to balance their risk, and as a prime candidate to hedge extreme volatility. We discuss the application of the amnesiac lookback option and path-dependent options to cryptocurrencies and blockchain commodities in the context of smart contracts.

  15. Option pricing under stochastic volatility: the exponential Ornstein–Uhlenbeck model

    International Nuclear Information System (INIS)

    Perelló, Josep; Masoliver, Jaume; Sircar, Ronnie

    2008-01-01

    We study the pricing problem for a European call option when the volatility of the underlying asset is random and follows the exponential Ornstein–Uhlenbeck model. The random diffusion model proposed is a two-dimensional market process that takes a log-Brownian motion to describe price dynamics and an Ornstein–Uhlenbeck subordinated process describing the randomness of the log-volatility. We derive an approximate option price that is valid when (i) the fluctuations of the volatility are larger than its normal level, (ii) the volatility presents a slow driving force, toward its normal level and, finally, (iii) the market price of risk is a linear function of the log-volatility. We study the resulting European call price and its implied volatility for a range of parameters consistent with daily Dow Jones index data

  16. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Science.gov (United States)

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  17. Potential Therapeutic Effects of Psilocybin.

    Science.gov (United States)

    Johnson, Matthew W; Griffiths, Roland R

    2017-07-01

    Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

  18. Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

    Science.gov (United States)

    Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

    2013-05-01

    During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

  19. Realizing the therapeutic potential of rare earth elements in designing nanoparticles to target and treat glioblastoma.

    Science.gov (United States)

    Lu, Victor M; McDonald, Kerrie L; Townley, Helen E

    2017-10-01

    The prognosis of brain cancer glioblastoma (GBM) is poor, and despite intense research, there have been no significant improvements within the last decade. This stasis implicates the need for more novel therapeutic investigation. One such option is the use of nanoparticles (NPs), which can be beneficial due to their ability to penetrate the brain, overcome the blood-brain barrier and take advantage of the enhanced permeation and retention effect of GBM to improve specificity. Rare earth elements possess a number of interesting natural properties due to their unique electronic configuration, which may prove therapeutically advantageous in an NP formulation. The underexplored exciting potential for rare earth elements to augment the therapeutic potential of NPs in GBM treatment is discussed in this review.

  20. A Decision Support Framework for Feasibility Analysis of International Space Station (ISS) Research Capability Enhancing Options

    Science.gov (United States)

    Ortiz, James N.; Scott,Kelly; Smith, Harold

    2004-01-01

    The assembly and operation of the ISS has generated significant challenges that have ultimately impacted resources available to the program's primary mission: research. To address this, program personnel routinely perform trade-off studies on alternative options to enhance research. The approach, content level of analysis and resulting outputs of these studies vary due to many factors, however, complicating the Program Manager's job of selecting the best option. To address this, the program requested a framework be developed to evaluate multiple research-enhancing options in a thorough, disciplined and repeatable manner, and to identify the best option on the basis of cost, benefit and risk. The resulting framework consisted of a systematic methodology and a decision-support toolset. The framework provides quantifiable and repeatable means for ranking research-enhancing options for the complex and multiple-constraint domain of the space research laboratory. This paper describes the development, verification and validation of this framework and provides observations on its operational use.

  1. The option to expand a project: its assessment with the binomial options pricing model

    Directory of Open Access Journals (Sweden)

    Salvador Cruz Rambaud

    Full Text Available Traditional methods of investment appraisal, like the Net Present Value, are not able to include the value of the operational flexibility of the project. In this paper, real options, and more specifically the option to expand, are assumed to be included in the project information in addition to the expected cash flows. Thus, to calculate the total value of the project, we are going to apply the methodology of the Net Present Value to the different scenarios derived from the existence of the real option to expand. Taking into account the analogy between real and financial options, the value of including an option to expand is explored by using the binomial options pricing model. In this way, estimating the value of the option to expand is a tool which facilitates the control of the uncertainty element implicit in the project. Keywords: Real options, Option to expand, Binomial options pricing model, Investment project appraisal

  2. DBS-LC-MS/MS assay for caffeine: validation and neonatal application.

    Science.gov (United States)

    Bruschettini, Matteo; Barco, Sebastiano; Romantsik, Olga; Risso, Francesco; Gennai, Iulian; Chinea, Benito; Ramenghi, Luca A; Tripodi, Gino; Cangemi, Giuliana

    2016-09-01

    DBS might be an appropriate microsampling technique for therapeutic drug monitoring of caffeine in infants. Nevertheless, its application presents several issues that still limit its use. This paper describes a validated DBS-LC-MS/MS method for caffeine. The results of the method validation showed an hematocrit dependence. In the analysis of 96 paired plasma and DBS clinical samples, caffeine levels measured in DBS were statistically significantly lower than in plasma but the observed differences were independent from hematocrit. These results clearly showed the need for extensive validation with real-life samples for DBS-based methods. DBS-LC-MS/MS can be considered to be a good alternative to traditional methods for therapeutic drug monitoring or PK studies in preterm infants.

  3. Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

    International Nuclear Information System (INIS)

    Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

    2011-01-01

    Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

  4. [Recurrent vulvovaginitis: diagnostic assessment and therapeutic management].

    Science.gov (United States)

    Ramírez-Santos, A; Pereiro, M; Toribio, J

    2008-04-01

    Recurrent vulvovaginitis is a common problem in clinical practice. Management is often complicated by a long history of inappropriate treatments based on tentative diagnoses after an incomplete diagnostic workup. We review the most common causes of recurrent vulvovaginitis; the appropriate steps with which to establish a diagnosis, from the medical history through to the additional tests needed; and, finally, the best therapeutic options. We will focus on infectious, irritant, allergic, and hormonal causes as the ones of most interest to the dermatologist. Given that infection is the most frequent cause of these processes and also a common reason for inopportune treatment, we will pay particular attention to infectious etiologies and their differential diagnosis.

  5. Aversion to ambiguity and willingness to take risks affect therapeutic decisions in managing atrial fibrillation for stroke prevention: results of a pilot study in family physicians.

    Science.gov (United States)

    Raptis, Stavroula; Chen, Jia Ning; Saposnik, Florencia; Pelyavskyy, Roman; Liuni, Andrew; Saposnik, Gustavo

    2017-01-01

    Anticoagulation is the therapeutic paradigm for stroke prevention in patients with atrial fibrillation (AF). It is unknown how physicians make treatment decisions in primary stroke prevention for patients with AF. To evaluate the association between family physicians' risk preferences (aversion risk and ambiguity) and therapeutic recommendations (anticoagulation) in the management of AF for primary stroke prevention by applying concepts from behavioral economics. Overall, 73 family physicians participated and completed the study. Our study comprised seven simulated case vignettes, three behavioral experiments, and two validated surveys. Behavioral experiments and surveys incorporated an economic framework to determine risk preferences and biases (e.g., ambiguity aversion, willingness to take risks). The primary outcome was making the correct decision of anticoagulation therapy. Secondary outcomes included medical errors in the management of AF for stroke prevention. Overall, 23.3% (17/73) of the family physicians elected not to escalate the therapy from antiplatelets to anticoagulation when recommended by best practice guidelines. A total of 67.1% of physicians selected the correct therapeutic options in two or more of the three simulated case vignettes. Multivariate analysis showed that aversion to ambiguity was associated with appropriate change to anticoagulation therapy in the management of AF (OR 5.48, 95% CI 1.08-27.85). Physicians' willingness to take individual risk in multiple domains was associated with lower errors (OR 0.16, 95% CI 0.03-0.86). Physicians' aversion to ambiguity and willingness to take risks are associated with appropriate therapeutic decisions in the management of AF for primary stroke prevention. Further large scale studies are needed.

  6. Traffic Light Options

    DEFF Research Database (Denmark)

    Jørgensen, Peter Løchte

    This paper introduces, prices, and analyzes traffic light options. The traffic light option is an innovative structured OTC derivative developed independently by several London-based investment banks to suit the needs of Danish life and pension (L&P) companies, which must comply with the traffic...... 2006, and supervisory authorities in many other European countries have implemented similar regulation. Traffic light options are therefore likely to attract the attention of a wider audience of pension fund managers in the future. Focusing on the valuation of the traffic light option we set up a Black...... light scenarios. These stress scenarios entail drops in interest rates as well as in stock prices, and traffic light options are thus designed to pay off and preserve sufficient capital when interest rates and stock prices fall simultaneously. Sweden's FSA implemented a traffic light system in January...

  7. Traffic Light Options

    DEFF Research Database (Denmark)

    Jørgensen, Peter Løchte

    2007-01-01

    This paper introduces, prices, and analyzes traffic light options. The traffic light option is an innovative structured OTC derivative developed independently by several London-based investment banks to suit the needs of Danish life and pension (L&P) companies, which must comply with the traffic...... 2006, and supervisory authorities in many other European countries have implemented similar regulation. Traffic light options are therefore likely to attract the attention of a wider audience of pension fund managers in the future. Focusing on the valuation of the traffic light option we set up a Black...... light scenarios. These stress scenarios entail drops in interest rates as well as in stock prices, and traffic light options are thus designed to pay off and preserve sufficient capital when interest rates and stock prices fall simultaneously. Sweden's FSA implemented a traffic light system in January...

  8. Preclinical models used for immunogenicity prediction of therapeutic proteins.

    Science.gov (United States)

    Brinks, Vera; Weinbuch, Daniel; Baker, Matthew; Dean, Yann; Stas, Philippe; Kostense, Stefan; Rup, Bonita; Jiskoot, Wim

    2013-07-01

    All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.

  9. The origins of options.

    Science.gov (United States)

    Smaldino, Paul E; Richerson, Peter J

    2012-01-01

    Most research on decision making has focused on how human or animal decision makers choose between two or more options, posed in advance by the researchers. The mechanisms by which options are generated for most decisions, however, are not well understood. Models of sequential search have examined the trade-off between continued exploration and choosing one's current best option, but still cannot explain the processes by which new options are generated. We argue that understanding the origins of options is a crucial but untapped area for decision making research. We explore a number of factors which influence the generation of options, which fall broadly into two categories: psycho-biological and socio-cultural. The former category includes factors such as perceptual biases and associative memory networks. The latter category relies on the incredible human capacity for culture and social learning, which doubtless shape not only our choices but the options available for choice. Our intention is to start a discussion that brings us closer toward understanding the origins of options.

  10. Novel treatment options in depression and psychosis

    Directory of Open Access Journals (Sweden)

    Ceskova E

    2018-03-01

    Full Text Available Eva Ceskova, Petr Silhan Department of Psychiatry, University Hospital Ostrava, Ostrava, Czech Republic Abstract: In spite of tremendous development in central nervous system research, current treatment is suboptimal, especially in severe mental disorders. In medicine, there are two main methods of improving the health care provided: seeking new treatment procedures and perfecting (optimizing the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring but also implementation of general trends in the clinical practice. New pharmacological options include new more sophisticated forms of monoaminergic drugs, old drugs rediscovered on the base of a better understanding of pathophysiology of mental illnesses, and drugs aimed at new treatment targets. In depression, treatment resistance to antidepressive pharmacotherapy represents one of the most important clinical challenges. Switching to monotherapy with new multimodal/multifunctional antidepressants and augmentation with new atypical antipsychotics (aripiprazole and brexpiprazole may be promising options. Further, current evidence supports utility and safety of adjunctive treatment of nutraceuticals. Novel approaches being studied include ketamine and opioids. Recent advances in technology and emerging knowledge about dysfunctional brain circuits and neuroplasticity have led to the development of different new neuromodulation techniques usually used as add-on therapy. Antipsychotics are still the cornerstone of the current treatment of schizophrenia. Two new partial dopamine agonists, brexpiprazole and cariprazine, are now available in addition to aripiprazole. Although the mechanisms of action are similar, the two agents differ in terms of their pharmacodynamic profiles. Further, two new formulations of long-acting injections of second-generation antipsychotics (aripiprazole lauroxil and 3-month paliperidone palmitate were introduced into

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

    Science.gov (United States)

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

    2016-03-01

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

  12. 30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Part 90 option; notice of eligibility; exercise of option. 90.3 Section 90.3 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a...

  13. Semi-Analytical method for the pricing of barrier options in case of time-dependent parameters (with Matlab® codes

    Directory of Open Access Journals (Sweden)

    Guardasoni C.

    2018-03-01

    Full Text Available A Semi-Analytical method for pricing of Barrier Options (SABO is presented. The method is based on the foundations of Boundary Integral Methods which is recast here for the application to barrier option pricing in the Black-Scholes model with time-dependent interest rate, volatility and dividend yield. The validity of the numerical method is illustrated by several numerical examples and comparisons.

  14. Options with Extreme Strikes

    Directory of Open Access Journals (Sweden)

    Lingjiong Zhu

    2015-07-01

    Full Text Available In this short paper, we study the asymptotics for the price of call options for very large strikes and put options for very small strikes. The stock price is assumed to follow the Black–Scholes models. We analyze European, Asian, American, Parisian and perpetual options and conclude that the tail asymptotics for these option types fall into four scenarios.

  15. Total recall: Reconsolidation theory unifies cognitive psychology and neuroscience and creates new therapeutic options for memory-related disorders

    OpenAIRE

    Hunter, Philip

    2011-01-01

    New research reveals that long-term memory is not entirely stable and can be modified or potentially erased. These insights open new therapeutic possibilities for a range of memory-related diseases and disorders.

  16. New testing options for diagnosing and grading dry eye disease.

    Science.gov (United States)

    Foulks, Gary N; Pflugfelder, Stephen C

    2014-06-01

    To describe new options for diagnosis and severity grading of dry eye disease. Perspective on technological advancements to identify tear dysfunction and their value in diagnosing and grading dry eye disease. Evidence is presented on new and evolving technologies to measure tear stability, composition, and meniscus height and their role in dry eye diagnosis and therapeutic efficacy grading is assessed. Evolving concepts regarding pathogenesis and new technologies to evaluate the tears and ocular surface have improved the ability to diagnose, classify, and grade the severity of dry eye disease. New technologies include noninvasive imaging of tear stability and tear meniscus height as a measure of tear volume and tear composition (osmolarity, lacrimal factors, inflammatory mediators, growth and differentiation factors). Approved tests, such as tear osmolarity and tear imaging, are being integrated into clinical practice and may eventually supplant certain traditional tests that have greater variability and less sensitivity. Other tests, such as molecular assays of tears and conjunctival cells, are currently being used in studies investigating pathogenesis and therapeutic mechanism of action. They may eventually translate to routine clinical practice. New technologies have emerged that can noninvasively evaluate the tears and measure disease-associated compositional changes. These tests are being integrated into clinical practice and therapeutic trials for diagnosis, classification, and severity grading of dry eye disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Therapeutic Effects of Horseback Riding Interventions: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Stergiou, Alexandra; Tzoufi, Meropi; Ntzani, Evangelia; Varvarousis, Dimitrios; Beris, Alexandros; Ploumis, Avraam

    2017-10-01

    Equine-assisted therapies, such as therapeutic riding and hippotherapy, are believed to have positive physical and emotional effects in individuals with neuromotor, developmental, and physical disabilities. The purpose of this review was to determine whether therapeutic riding and hippotherapy improve balance, motor function, gait, muscle symmetry, pelvic movement, psychosocial parameters, and the patients' overall quality of life. In this study, a literature search was conducted on MEDLINE, CINAHL, MBASE, SportDiscus, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, PEDro, DARE, Google Scholar, and Dissertation Abstracts. Only studies with a control/comparison group or self-controlled studies performing preintervention and postintervention assessment were included. Excluded were (1) studies not providing data on baseline score or end-point outcome, (2) single-subject studies, (3) studies providing only qualitative data, and (4) studies that used a mechanical horse. Sixteen trials were included. The methodologic quality of each study was evaluated using Downs and Black quality assessment tool. Most of the studies showed a trend toward a beneficial effect of therapeutic riding and hippotherapy on balance and gross motor function. The meta-analysis showed improvement in both the Berg Balance Scale and the Gross Motor Function Measure in therapeutic riding and hippotherapy programs. Programs such as therapeutic riding and hippotherapy are a viable intervention option for patients with balance, gait, and psychomotor disorders.

  18. Treatment Options for Retinoblastoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other places in the body. Treatment Option Overview Key Points There are different types of ...

  19. Polish Toxic Currency Options

    Directory of Open Access Journals (Sweden)

    Waldemar Gontarski

    2009-06-01

    Full Text Available Toxic currency options are defined on the basis of the opposition to the nature (essence of an option contract, which is justified in terms of norms founded on the general law clause of characteristics (nature of a relation (which represents an independent premise for imposing restrictions on the freedom of contracts. So-understood toxic currency options are unlawful. Indeed they contravene iuris cogentis regulations. These include for instance option contracts, which are concluded with a bank, if the bank has not informed about option risk before concluding the contract; or the barrier options, which focus only on the protection of bank’s interests. Therefore, such options may appear to be invalid. Therefore, performing contracts for toxic currency options may be qualified as a criminal mismanagement. For the sake of security, the manager should then take into consideration filing a claim for stating invalidity (which can be made in a court verdict. At the same time, if the supervisory board member in a commercial company, who can also be a subject to mismanagement offences, commits an omission involving lack of reaction (for example, if he/she fails to notify of the suspected offence committed by the management board members acting to the company’s detriment when the management board makes the company conclude option contracts which are charged with absolute invalidity the supervisory board member so acting may be considered to act to the company’s detriment. In the most recent Polish jurisprudence and judicature the standard of a “good host” is treated to be the last resort for determining whether the manager’s powers resulting from criminal regulations were performed. The manager of the exporter should not, as a rule, issue any options. Issuing options always means assuming an obligation. In the case of currency put options it is an absolute obligation to purchase a given amount in euro at exchange rate set in advance. On the

  20. Pelvic radiation disease: Updates on treatment options

    Science.gov (United States)

    Frazzoni, Leonardo; La Marca, Marina; Guido, Alessandra; Morganti, Alessio Giuseppe; Bazzoli, Franco; Fuccio, Lorenzo

    2015-01-01

    Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments. PMID:26677440

  1. Surgical options for lumbosacral fusion: biomechanical stability, advantage, disadvantage and affecting factors in selecting options.

    Science.gov (United States)

    Yoshihara, Hiroyuki

    2014-07-01

    Numerous surgical procedures and instrumentation techniques for lumbosacral fusion (LSF) have been developed. This is probably because of its high mechanical demand and unique anatomy. Surgical options include anterior column support (ACS) and posterior stabilization procedures. Biomechanical studies have been performed to verify the stability of those options. The options have their own advantage but also disadvantage aspects. This review article reports the surgical options for lumbosacral fusion, their biomechanical stability, advantages/disadvantages, and affecting factors in option selection. Review of literature. LSF has lots of options both for ACS and posterior stabilization procedures. Combination of posterior stabilization procedures is an option. Furthermore, combinations of ACS and posterior stabilization procedures are other options. It is difficult to make a recommendation or treatment algorithm of LSF from the current literature. However, it is important to know all aspects of the options and decision-making of surgical options for LSF needs to be tailored for each patient, considering factors such as biomechanical stress and osteoporosis.

  2. Cachexia and pancreatic cancer: Are there treatment options?

    Science.gov (United States)

    Mueller, Tara C; Burmeister, Marc A; Bachmann, Jeannine; Martignoni, Marc E

    2014-01-01

    Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods. PMID:25071331

  3. TANK SPACE OPTIONS REPORT

    International Nuclear Information System (INIS)

    Willis, W.L.; Ahrendt, M.R.

    2009-01-01

    Since this report was originally issued in 2001, several options proposed for increasing double-shell tank (DST) storage space were implemented or are in the process of implementation. Changes to the single-shell tank (SST) waste retrieval schedule, completion of DST space saving options, and the DST space saving options in progress have delayed the projected shortfall of DST storage space from the 2007-2011 to the 2018-2025 timeframe (ORP-11242, River Protection Project System Plan). This report reevaluates options from Rev. 0 and includes evaluations of new options for alleviating projected restrictions on SST waste retrieval beginning in 2018 because of the lack of DST storage space.

  4. Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

    Science.gov (United States)

    Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

    2017-08-15

    Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Dynamique jointe stock/option et application aux stratégies de trading sur options

    OpenAIRE

    El Aoud , Sofiene

    2015-01-01

    This thesis explores theoretically and empirically the implications of the stock/option joint dynamics on applications related to option trading. In the first part of the thesis, we look into the relations between stock options and index options under the risk-neutral measure. The Capital Asset Pricing Model offers an adequate mathematical framework for this study as it provides a modeling approach for the joint dynamics between the stock and the index. As we compute option prices according t...

  6. Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

    Science.gov (United States)

    Witcher, Mark R; Ellis, Thomas L

    2012-01-01

    Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

  7. Assessing the Option to Abandon an Investment Project by the Binomial Options Pricing Model

    Directory of Open Access Journals (Sweden)

    Salvador Cruz Rambaud

    2016-01-01

    Full Text Available Usually, traditional methods for investment project appraisal such as the net present value (hereinafter NPV do not incorporate in their values the operational flexibility offered by including a real option included in the project. In this paper, real options, and more specifically the option to abandon, are analysed as a complement to cash flow sequence which quantifies the project. In this way, by considering the existing analogy with financial options, a mathematical expression is derived by using the binomial options pricing model. This methodology provides the value of the option to abandon the project within one, two, and in general n periods. Therefore, this paper aims to be a useful tool in determining the value of the option to abandon according to its residual value, thus making easier the control of the uncertainty element within the project.

  8. Forecasting with Option-Implied Information

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Chang, Bo Young

    2013-01-01

    This chapter surveys the methods available for extracting information from option prices that can be used in forecasting. We consider option-implied volatilities, skewness, kurtosis, and densities. More generally, we discuss how any forecasting object that is a twice differentiable function...... of the future realization of the underlying risky asset price can utilize option-implied information in a well-defined manner. Going beyond the univariate option-implied density, we also consider results on option-implied covariance, correlation and beta forecasting, as well as the use of option......-implied information in cross-sectional forecasting of equity returns. We discuss how option-implied information can be adjusted for risk premia to remove biases in forecasting regressions....

  9. Method validation in pharmaceutical analysis: from theory to practical optimization

    Directory of Open Access Journals (Sweden)

    Jaqueline Kaleian Eserian

    2015-01-01

    Full Text Available The validation of analytical methods is required to obtain high-quality data. For the pharmaceutical industry, method validation is crucial to ensure the product quality as regards both therapeutic efficacy and patient safety. The most critical step in validating a method is to establish a protocol containing well-defined procedures and criteria. A well planned and organized protocol, such as the one proposed in this paper, results in a rapid and concise method validation procedure for quantitative high performance liquid chromatography (HPLC analysis.   Type: Commentary

  10. Option price and market instability

    Science.gov (United States)

    Baaquie, Belal E.; Yu, Miao

    2017-04-01

    An option pricing formula, for which the price of an option depends on both the value of the underlying security as well as the velocity of the security, has been proposed in Baaquie and Yang (2014). The FX (foreign exchange) options price was empirically studied in Baaquie et al., (2014), and it was found that the model in general provides an excellent fit for all strike prices with a fixed model parameters-unlike the Black-Scholes option price Hull and White (1987) that requires the empirically determined implied volatility surface to fit the option data. The option price proposed in Baaquie and Cao Yang (2014) did not fit the data during the crisis of 2007-2008. We make a hypothesis that the failure of the option price to fit data is an indication of the market's large deviation from its near equilibrium behavior due to the market's instability. Furthermore, our indicator of market's instability is shown to be more accurate than the option's observed volatility. The market prices of the FX option for various currencies are studied in the light of our hypothesis.

  11. Options Study - Phase II

    Energy Technology Data Exchange (ETDEWEB)

    R. Wigeland; T. Taiwo; M. Todosow; W. Halsey; J. Gehin

    2010-09-01

    The Options Study has been conducted for the purpose of evaluating the potential of alternative integrated nuclear fuel cycle options to favorably address the issues associated with a continuing or expanding use of nuclear power in the United States. The study produced information that can be used to inform decisions identifying potential directions for research and development on such fuel cycle options. An integrated nuclear fuel cycle option is defined in this study as including all aspects of the entire nuclear fuel cycle, from obtaining natural resources for fuel to the ultimate disposal of used nuclear fuel (UNF) or radioactive wastes. Issues such as nuclear waste management, especially the increasing inventory of used nuclear fuel, the current uncertainty about used fuel disposal, and the risk of nuclear weapons proliferation have contributed to the reluctance to expand the use of nuclear power, even though it is recognized that nuclear power is a safe and reliable method of producing electricity. In this Options Study, current, evolutionary, and revolutionary nuclear energy options were all considered, including the use of uranium and thorium, and both once-through and recycle approaches. Available information has been collected and reviewed in order to evaluate the ability of an option to clearly address the challenges associated with the current implementation and potential expansion of commercial nuclear power in the United States. This Options Study is a comprehensive consideration and review of fuel cycle and technology options, including those for disposal, and is not constrained by any limitations that may be imposed by economics, technical maturity, past policy, or speculated future conditions. This Phase II report is intended to be used in conjunction with the Phase I report, and much information in that report is not repeated here, although some information has been updated to reflect recent developments. The focus in this Options Study was to

  12. Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

    Science.gov (United States)

    Griffith, Gina L; Kasus-Jacobi, Anne; Pereira, H Anne

    2017-06-01

    Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit.

  13. [Psychological aspects of pruritus and therapy options].

    Science.gov (United States)

    Stumpf, A; Schut, C; Schneider, G

    2016-08-01

    Besides biological factors, which cause or influence chronic pruritus, more and more attention has recently also been paid to psychological and psychoneuroimmunological factors which uphold the symptom. This review article gives an overview of the state of research regarding psychological and psychoneuroimmunological factors and the resulting therapeutic options. The article is based on a literature search in the PubMed database. Under experimental conditions, pruritus can be induced by verbal instructions and modulated by placebo and nocebo effects. Stressful life events can also induce pruritus or its exacerbation. This can also be demonstrated on a cellular level. The knowledge that pruritus intensity is modulated by cognitions, behavioral factors, and stress is important for the development and application of psychological interventions. More research should be done regarding psychological interventions in the treatment of chronic itch and they should be applied clinically more often.

  14. Current and future treatment options in osteoporosis.

    LENUS (Irish Health Repository)

    Brewer, Linda

    2012-02-01

    PURPOSE: The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population. METHODS: When prescribing for older patients the effectiveness profile of drugs needs to be balanced against their tolerability in individual patients. RESULTS: Currently we have good anti-fracture data to support the use of many available anti-resorptive and anabolic drugs including bisphosphonates, strontium ranelate and recombinant human parathyroid hormone. We also have evidence to demonstrate the importance of calcium and vitamin D repletion in these patients. However, in recent years our understanding of normal bone physiology and the mechanisms underlying the development of osteoporosis has significantly advanced and this has led to the development of new therapies. Novel agents, particularly denosumab, but also inhibitors of cathepsin K and anabolic agents that act on Wnt signalling, will increase the therapeutic options for clinicians in the coming years. CONCLUSION: This review discusses the evidence supporting the use of currently available treatment options for osteoporosis and potential future advances in drug therapy. Particular consideration should be given when prescribing for certain older patients who have issues with compliance or tolerance and also in those with co-morbidities or levels of frailty that may restrict the choice of therapy. Understanding the evidence for the benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.

  15. Efficient Trajectory Options Allocation for the Collaborative Trajectory Options Program

    Science.gov (United States)

    Rodionova, Olga; Arneson, Heather; Sridhar, Banavar; Evans, Antony

    2017-01-01

    The Collaborative Trajectory Options Program (CTOP) is a Traffic Management Initiative (TMI) intended to control the air traffic flow rates at multiple specified Flow Constrained Areas (FCAs), where demand exceeds capacity. CTOP allows flight operators to submit the desired Trajectory Options Set (TOS) for each affected flight with associated Relative Trajectory Cost (RTC) for each option. CTOP then creates a feasible schedule that complies with capacity constraints by assigning affected flights with routes and departure delays in such a way as to minimize the total cost while maintaining equity across flight operators. The current version of CTOP implements a Ration-by-Schedule (RBS) scheme, which assigns the best available options to flights based on a First-Scheduled-First-Served heuristic. In the present study, an alternative flight scheduling approach is developed based on linear optimization. Results suggest that such an approach can significantly reduce flight delays, in the deterministic case, while maintaining equity as defined using a Max-Min fairness scheme.

  16. Investigative and therapeutic uses of Transcranial magnetic stimulation (TMS) in Attention Deficit Hyperactivity Disorder (ADHD).

    Science.gov (United States)

    Zaman, Rashid

    2016-09-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that affects children and young adults. It results in significant impairment of their educational, social and occupational functioning and is associated economic societal burden. Whilst there are effective medications (such as methylphenidate) as well as some psychobehavioural therapies that can help with management of symptoms of ADHD, the former can have significant cardiac side effects, which limit their use. For number of patients these treatment options lack efficacy or are not acceptable. There is need to improve our understanding of neurobiology of ADHD as well as explore other treatment options. Transcranial magnetic stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) are safe and non-invasive investigative and therapeutic tools respectively. In this short paper, I will explore the potential role of TMS and rTMS in further improving our understanding of the neurobiology of ADHD as well as possible treatment option.

  17. Update on therapeutic interventions for the management of achalasia.

    Science.gov (United States)

    Gunasingam, Nishmi; Perczuk, Adam; Talbot, Michael; Kaffes, Arthur; Saxena, Payal

    2016-08-01

    Achalasia is a primary esophageal motility disorder. It is the absence of peristalsis in the esophageal body and inability of the lower esophageal sphincter to relax, which characterizes this rare condition. Its features typically include dysphagia, regurgitation, chest pain, and weight loss. The ultimate goal in treating achalasia is to relieve the patient's symptoms, improve esophageal emptying, and prevent further dilatation of the esophagus. Current treatment modalities targeted at achalasia include pharmacological therapy, endoscopic therapy, and surgery. This review focuses on the current therapeutic options and explores the role of peroral endoscopic myotomy in the management armamentarium. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  18. THERAPEUTIC OPTIONS FOR BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Milena Georgescu

    2011-12-01

    Full Text Available Breast cancer remains a major public health problem, being the second cause of cancer death in women. There is a marked tendency to restrict the extension of surgical gesture, which directly leads to two different attitudes: radical surgery and conservative surgery, to which, at least in our country, there are still some delays. Prospective and retrospective studies have shown that, in 20 years, conservative and radical therapy had about the same rate of survival and disease-free interval, at least for stage I and II breast cancer, the only real counterargument against conservative surgery being that, in principle, the higher rate of recurrence local constraint can be solved by postoperative radiotherapy. Finally, the survival rate is the main parameter of evaluation, assessing the effectiveness of the treatment in breast cancer, and in all its other forms.

  19. Radiation caries: a therapeutical option

    International Nuclear Information System (INIS)

    Biazolla, E.R.; Miziara, T.C.

    1988-01-01

    It is showed a clinical report about radiation caries. As the tooth destruction was, mainly, of the majority of the teeth, was made a therapy where, besides avoiding the osteoradiomielite, also is possible to reability the patient. (author)

  20. Clinical and therapeutic aspects of childhood kerosene poisoning in Djibouti.

    Science.gov (United States)

    Benois, Alain; Petitjeans, Fabrice; Raynaud, Laurent; Dardare, Eric; Sergent, Hervé

    2009-10-01

    We report a prospective and descriptive study about childhood acute poisoning with kerosene in Djibouti. Acute poisoning is a common and stable occurrence in low socioeconomic groups in Africa, where negligence is the main cause of poisoning. The respiratory system was the main target, with 41% of patients having pneumonia, which may become life-threatening, but with low mortality rate. Asymptomatic patients (35%) can be discharged, while those with pulmonary or neurological signs must be admitted for observation and supportive treatment based on oxygen administration. Our study suggests management and provides a discussion for therapeutic options and emphasizes the importance of prevention.

  1. Preemptive Renal Transplantation-The Best Treatment Option for Terminal Chronic Renal Failure.

    Science.gov (United States)

    Arze Aimaretti, L; Arze, S

    2016-03-01

    Renal transplantation is the best therapeutic option for end-stage chronic renal disease. Assuming that it is more advisable if performed early, we aimed to show the clinical, social, and economic advantages in 70% of our patients who were dialyzed only for a short period. For this purpose, we retrospectively collected data over 28 years in 142 kidney transplants performed in patients with renal transplantation with renal failure, especially in developing countries such as Bolivia, where until last year, full public support for renal replacement therapy was unavailable. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Extracorporeal shockwave therapy and therapeutic exercise for supraspinatus and biceps tendinopathies in 29 dogs.

    Science.gov (United States)

    Leeman, J J; Shaw, K K; Mison, M B; Perry, J A; Carr, A; Shultz, R

    2016-10-15

    Supraspinatus tendinopathy (ST) and biceps tendinopathy (BT) are common causes of forelimb lameness in large-breed dogs and have historically been treated with conservative management or surgery. Extracorporeal shockwave therapy (ESWT) and therapeutic exercise (TE) are thought to be treatment options for these conditions. The objectives of this study were to report the clinical presentations of dogs treated with ESWT for shoulder tendinopathies, to determine the association between shoulder lesion severity identified on ultrasonography or MRI and outcome, and to compare the outcomes of dogs treated with ESWT with and without TE. Medical records of 29 dogs diagnosed with shoulder tendinopathies and treated with ESWT were reviewed, and 24 dogs were diagnosed with either unilateral BT or BT and ST. None were found to have unilateral ST. Five dogs were diagnosed with bilateral disease. Eighty-five per cent of dogs had good or excellent outcomes determined by owner assessment 11-220 weeks after therapy. Outcomes were found to be better as tendon lesion severity increased (P=0.0497), regardless if ESWT was performed with or without TE (P=0.92). ESWT should be considered a safe primary therapeutic option for canine shoulder tendinopathies. Larger controlled prospective studies are needed to adequately assess these findings. British Veterinary Association.

  3. A study of the effects of therapeutic doses of ionizing radiation in vitro on Lactobacillus isolates originating from the vagina - a pilot study

    OpenAIRE

    Gosiewski, Tomasz; Mr?z, Tomasz; Ocho?ska, Dorota; Pabian, Wojciech; Bulanda, Malgorzata; Brzychczy-Wloch, Monika

    2016-01-01

    Background Ionizing radiation is used as a therapeutic option in the treatment of certain neoplastic lesions located, among others, in the pelvic region. The therapeutic doses of radiation employed often result in adverse effects manifesting themselves primarily in the form of genital tract infections in patients or diarrhea. The data available in the literature indicate disorders in the microbial ecosystem caused by ionizing radiation, which leads to the problems mentioned above. In the pres...

  4. Early Option Exercise

    DEFF Research Database (Denmark)

    Heje Pedersen, Lasse; Jensen, Mads Vestergaard

    A classic result by Merton (1973) is that, except just before expiration or dividend payments, one should never exercise a call option and never convert a convertible bond. We show theoretically that this result is overturned when investors face frictions. Early option exercise can be optimal when...... it reduces short-sale costs, transaction costs, or funding costs. We provide consistent empirical evidence, documenting billions of dollars of early exercise for options and convertible bonds using unique data on actual exercise decisions and frictions. Our model can explain as much as 98% of early exercises...

  5. Early Option Exercise

    DEFF Research Database (Denmark)

    Jensen, Mads Vestergaard; Heje Pedersen, Lasse

    2016-01-01

    A classic result by Merton (1973) is that, except just before expiration or dividend payments, one should never exercise a call option and never convert a convertible bond. We show theoretically that this result is overturned when investors face frictions. Early option exercise can be optimal when...... it reduces short-sale costs, transaction costs, or funding costs. We provide consistent empirical evidence, documenting billions of dollars of early exercise for options and convertible bonds using unique data on actual exercise decisions and frictions. Our model can explain as much as 98% of early exercises...

  6. Nevada Transportation Options Study

    International Nuclear Information System (INIS)

    P. GEHNER; E.M. WEAVER; L. FOSSUM

    2006-01-01

    This study performs a cost and schedule analysis of three Nevada Transportation options that support waste receipt at the repository. Based on the U.S. Department of Energy preference for rail transportation in Nevada (given in the Final Environmental Impact Statement), it has been assumed that a branch rail line would be constructed to support waste receipt at the repository. However, due to potential funding constraints, it is uncertain when rail will be available. The three Nevada Transportation options have been developed to meet a varying degree of requirements for transportation and to provide cost variations used in meeting the funding constraints given in the Technical Direction Letter guidelines for this study. The options include combinations of legal-weight truck, heavy-haul truck, and rail. Option 1 uses a branch rail line that would support initial waste receipt at the repository in 2010. Rail transportation would be the primary mode, supplemented by legal weight trucks. This option provides the highest level of confidence in cost and schedule, lowest public visibility, greatest public acceptability, lowest public dose, and is the recommended option for support of waste receipt. The completion of rail by 2010 will require spending approximately $800 million prior to 2010. Option 2 uses a phased rail approach to address a constrained funding scenario. To meet funding constraints, Option 2 uses a phased approach to delay high cost activities (final design and construction) until after initial waste receipt in 2010. By doing this, approximately 95 percent of the cost associated with completion of a branch rail line is deferred until after 2010. To support waste receipt until a branch rail line is constructed in Nevada, additional legal-weight truck shipments and heavy-haul truck shipments (on a limited basis for naval spent nuclear fuel) would be used to meet the same initial waste receipt rates as in Option 1. Use of heavy-haul shipments in the absence

  7. Evaluation of transcranial surgical decompression of the optic canal as a treatment option for traumatic optic neuropathy.

    Science.gov (United States)

    He, Zhenhua; Li, Qiang; Yuan, Jingmin; Zhang, Xinding; Gao, Ruiping; Han, Yanming; Yang, Wenzhen; Shi, Xuefeng; Lan, Zhengbo

    2015-07-01

    Traumatic optic neuropathy (TON) is a serious complication of head trauma, with the incidence rate ranging from 0.5% to 5%. The two treatment options widely practiced for TON are: (i) high-dose corticosteroid therapy and (ii) surgical decompression. However, till date, there is no consensus on the treatment protocol. This study aimed to evaluate the therapeutic efficacy of transcranial decompression of optic canal in TON patients. A total of 39 patients with visual loss resulting from TON between January 2005 and June 2013 were retrospectively reviewed for preoperative vision, preoperative image, visual evoked potential (VEP), surgical approach, postoperative visual acuity, complications, and follow-up results. All these patients underwent transcranial decompression of optic canal. During the three-month follow-up period, among the 39 patients, 21 showed an improvement in their eyesight, 6 recovered to standard logarithmic visual acuity chart "visible," 10 could count fingers, 2 could see hand movement, and 3 regained light sensation. Visual evoked potential could be used as an important preoperative and prognostic evaluation parameter for TON patients. Once TON was diagnosed, surgery is a promising therapeutic option, especially when a VEP wave is detected, irrespective of the HRCT scan findings. Operative time between trauma and operation is not necessary reference to assess the therapeutic effect of surgical decompression. The poor results of this procedure may be related to the severity of optic nerve injury. The patient's age is an important factor affecting the surgical outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Expensing options solves nothing.

    Science.gov (United States)

    Sahlman, William A

    2002-12-01

    The use of stock options for executive compensation has become a lightning rod for public anger, and it's easy to see why. Many top executives grew hugely rich on the back of the gains they made on their options, profits they've been able to keep even as the value they were supposed to create disappeared. The supposed scam works like this: Current accounting regulations let companies ignore the cost of option grants on their income statements, so they can award valuable option packages without affecting reported earnings. Not charging the cost of the grants supposedly leads to overstated earnings, which purportedly translate into unrealistically high share prices, permitting top executives to realize big gains when they exercise their options. If an accounting anomaly is the problem, then the solution seems obvious: Write off executive share options against the current year's revenues. The trouble is, Sahlman writes, expensing option grants won't give us a more accurate view of earnings, won't add any information not already included in the financial statements, and won't even lead to equal treatment of different forms of executive pay. Far worse, expensing evades the real issue, which is whether compensation (options and other-wise) does what it's supposed to do--namely, help a company recruit, retain, and provide the right people with appropriate performance incentives. Any performance-based compensation system has the potential to encourage cheating. Only ethical management, sensible governance, adequate internal control systems, and comprehensive disclosure will save the investor from disaster. If, Sahlman warns, we pass laws that require the expensing of options, thinking that's fixed the fundamental flaws in corporate America's accounting, we will have missed a golden opportunity to focus on the much more extensive defects in the present system.

  9. MicroRNAs as Therapeutic Targets for Alzheimer's Disease.

    Science.gov (United States)

    Di Meco, Antonio; Praticò, Domenico

    2016-05-07

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly. With increasing longevity and the absence of a cure, AD has become not only a major health problem but also a heavy social and economic burden worldwide. Given this public health challenge, and that the current approved therapy for AD is limited to symptomatic treatment (i.e., cholinesterase inhibitors and NMDA receptor antagonists), exploration of new molecular pathways as novel therapeutic targets remains an attractive option for disease modifying drug development. microRNAs (miRNAs) are short non-coding RNA that control gene expression at the post-translational level by inhibiting translation of specific mRNAs or degrading them. Dysregulation of several miRNAs has been described in AD brains. Interestingly, their molecular targets are pathways that are well-established functional players in the onset and development of AD pathogenesis. Today several molecular tools have been developed to modulate miRNA levels in vitro and in vivo. These scientific advancements are affording us for the first time with the real possibility of targeting in vivo these dysregulated miRNAs as a novel therapeutic approach against AD.

  10. Distributed Energy Implementation Options

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Chandralata N [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-13

    This presentation covers the options for implementing distributed energy projects. It distinguishes between options available for distributed energy that is government owned versus privately owned, with a focus on the privately owned options including Energy Savings Performance Contract Energy Sales Agreements (ESPC ESAs). The presentation covers the new ESPC ESA Toolkit and other Federal Energy Management Program resources.

  11. New and exploratory therapeutic agents for asthma

    National Research Council Canada - National Science Library

    Yeadon, Michael; Diamant, Zuzana

    2000-01-01

    ... been accomplished. It is well recognized that new drugs are essentially the result of basic and applied research. Early in this century, the advent of a chemical approach to medicine led to many extraordinary developments. The past few decades have been characterized by a search to understand the mechanisms of disease- a quest spurred by the recognition that if pathogenic processes were known, new therapeutic opportunities would ensue. The validity of this concept is beautifully illustrated in the case of asthma. Here is a d...

  12. Consumer satisfaction with psychiatric services: The role of shared decision making and the therapeutic relationship.

    Science.gov (United States)

    Klingaman, Elizabeth A; Medoff, Deborah R; Park, Stephanie G; Brown, Clayton H; Fang, Lijuan; Dixon, Lisa B; Hack, Samantha M; Tapscott, Stephanie L; Walsh, Mary Brighid; Kreyenbuhl, Julie A

    2015-09-01

    Although dissatisfaction is a primary reason for disengagement from outpatient psychiatric care among consumers with serious mental illnesses, little is known about predictors of their satisfaction with medication management visits. The primary purpose of this study was to explore how dimensions of consumer preferences for shared decision making (i.e., preferences for obtaining knowledge about one's mental illness, being offered and asked one's opinion about treatment options, and involvement in treatment decisions) and the therapeutic relationship (i.e., positive collaboration and type of clinician input) were related to visit satisfaction. Participants were 228 Veterans with serious mental illnesses who completed a 19-item self-report questionnaire assessing satisfaction with visits to prescribers (524 assessments) immediately after visits. In this correlational design, a 3-level mixed model with the restricted maximum likelihood estimation procedure was used to examine shared decision-making preferences and therapeutic alliance as predictors of visit satisfaction. Preferences for involvement in treatment decisions was the unique component of shared decision making associated with satisfaction, such that the more consumers desired involvement, the less satisfied they were. Positive collaboration and prescriber input were associated with greater visit satisfaction. When consumers with serious mental illnesses express preferences to be involved in shared decision making, it may not be sufficient to only provide information and treatment options; prescribers should attend to consumers' interest in involvement in actual treatment decisions. Assessment and tailoring of treatment approaches to consumer preferences for shared decision making should occur within the context of a strong therapeutic relationship. (c) 2015 APA, all rights reserved).

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

    Science.gov (United States)

    Bianchi-Demicheli, F

    2006-02-08

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

  14. Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option

    Directory of Open Access Journals (Sweden)

    Joshua P. H. Neale

    2017-12-01

    Full Text Available Critical limb ischemia (CLI is the most severe manifestation of peripheral artery disease. It is characterized by chronic pain at rest, skin ulcerations, and gangrene tissue loss. CLI is a highly morbid condition, resulting in a severely diminished quality of life and a significant risk of mortality. The primary goal of therapy for CLI is to restore blood flow to the affected limb, which is only possible by surgery, but is inadvisable in up to 50% of patients. This subset of patients who are not candidates for revascularisation are referred to as “no-option” patients and are the focus of investigation for novel therapeutic strategies. Angiogenesis, arteriogenesis and vasculogenesis are the processes whereby new blood vessel networks form from the pre-existing vasculature and primordial cells, respectively. In therapeutic angiogenesis, exogenous stimulants are administered to promote angiogenesis and augment limb perfusion, offering a potential treatment option for “no option” patients. However, to date, very few clinical trials of therapeutic angiogenesis in patients with CLI have reported clinically significant results, and it remains a major challenge. Ghrelin, a 28-amino acid peptide, is emerging as a potential novel therapeutic for CLI. In pre-clinical models, exogenous ghrelin has been shown to induce therapeutic angiogenesis, promote muscle regeneration, and reduce oxidative stress via the modulation of microRNAs (miRs. miRs are endogenous, small, non-coding ribonucleic acids of ~20–22 nucleotides which regulate gene expression at the post-transcriptional level by either translational inhibition or by messenger ribonucleic acid cleavage. This review focuses on the mounting evidence for the use of ghrelin as a novel therapeutic for CLI, and highlights the miRs which orchestrate these physiological events.

  15. In silico prediction of novel therapeutic targets using gene-disease association data.

    Science.gov (United States)

    Ferrero, Enrico; Dunham, Ian; Sanseau, Philippe

    2017-08-29

    Target identification and validation is a pressing challenge in the pharmaceutical industry, with many of the programmes that fail for efficacy reasons showing poor association between the drug target and the disease. Computational prediction of successful targets could have a considerable impact on attrition rates in the drug discovery pipeline by significantly reducing the initial search space. Here, we explore whether gene-disease association data from the Open Targets platform is sufficient to predict therapeutic targets that are actively being pursued by pharmaceutical companies or are already on the market. To test our hypothesis, we train four different classifiers (a random forest, a support vector machine, a neural network and a gradient boosting machine) on partially labelled data and evaluate their performance using nested cross-validation and testing on an independent set. We then select the best performing model and use it to make predictions on more than 15,000 genes. Finally, we validate our predictions by mining the scientific literature for proposed therapeutic targets. We observe that the data types with the best predictive power are animal models showing a disease-relevant phenotype, differential expression in diseased tissue and genetic association with the disease under investigation. On a test set, the neural network classifier achieves over 71% accuracy with an AUC of 0.76 when predicting therapeutic targets in a semi-supervised learning setting. We use this model to gain insights into current and failed programmes and to predict 1431 novel targets, of which a highly significant proportion has been independently proposed in the literature. Our in silico approach shows that data linking genes and diseases is sufficient to predict novel therapeutic targets effectively and confirms that this type of evidence is essential for formulating or strengthening hypotheses in the target discovery process. Ultimately, more rapid and automated target

  16. A comparison in therapeutic efficacy of several time points of intravenous StemBell administration in a rat model of acute myocardial infarction

    NARCIS (Netherlands)

    Emmens, Reindert W.; Oedayrajsingh-Varma, Maikel; Woudstra, Linde; Kamp, Otto; Meinster, Elisa; van Dijk, Annemieke; Helder, Marco N.; Wouters, Diana; Zeerleder, Sacha; van Ham, S. Marieke; de Jong, Nico; Niessen, Hans W. M.; Juffermans, Lynda J. M.; Krijnen, Paul A. J.

    2017-01-01

    Adipose-derived stromal cells (ASCs) are a promising new therapeutic option for patients with acute myocardial infarction (AMI). Previously, we found that ASCs coupled to antibody-targeted microbubbles (StemBells [StBs]) improved cardiac function when administered intravenously 7 days post-AMI in

  17. Validation Test Report For The CRWMS Analysis and Logistics Visually Interactive Model Version 3.0, 10074-Vtr-3.0-00

    International Nuclear Information System (INIS)

    Gillespie, S.

    2000-01-01

    This report describes the tests performed to validate the CRWMS ''Analysis and Logistics Visually Interactive'' Model (CALVIN) Version 3.0 (V3.0) computer code (STN: 10074-3.0-00). To validate the code, a series of test cases was developed in the CALVIN V3.0 Validation Test Plan (CRWMS M and O 1999a) that exercises the principal calculation models and options of CALVIN V3.0. Twenty-five test cases were developed: 18 logistics test cases and 7 cost test cases. These cases test the features of CALVIN in a sequential manner, so that the validation of each test case is used to demonstrate the accuracy of the input to subsequent calculations. Where necessary, the test cases utilize reduced-size data tables to make the hand calculations used to verify the results more tractable, while still adequately testing the code's capabilities. Acceptance criteria, were established for the logistics and cost test cases in the Validation Test Plan (CRWMS M and O 1999a). The Logistics test cases were developed to test the following CALVIN calculation models: Spent nuclear fuel (SNF) and reactivity calculations; Options for altering reactor life; Adjustment of commercial SNF (CSNF) acceptance rates for fiscal year calculations and mid-year acceptance start; Fuel selection, transportation cask loading, and shipping to the Monitored Geologic Repository (MGR); Transportation cask shipping to and storage at an Interim Storage Facility (ISF); Reactor pool allocation options; and Disposal options at the MGR. Two types of cost test cases were developed: cases to validate the detailed transportation costs, and cases to validate the costs associated with the Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) and Regional Servicing Contractors (RSCs). For each test case, values calculated using Microsoft Excel 97 worksheets were compared to CALVIN V3.0 scenarios with the same input data and assumptions. All of the test case results compare with

  18. 32 CFR 48.201 - Options.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Options. 48.201 Section 48.201 National Defense...'S FAMILY PROTECTION PLAN Election of Options § 48.201 Options. As provided in § 48.203, a member may... amount equal to such 121/2 per centum. (a) Option 1 is an annuity payable to or on behalf of his widow...

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

    Science.gov (United States)

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

    2016-02-21

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

  20. Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients.

    Science.gov (United States)

    Rommer, Paulus S; Zettl, Uwe K

    2018-04-01

    Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review. The authors also provide suggestions for monitoring therapy. For all approved DMDs the pivotal studies have been included for possible side effects, as well as reports by health authorities. For this manuscript, PubMed was checked for reports on side effects for various drugs. Expert opinion: Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Presently, the long-term experience for some of these therapies is missing and this must be addressed.

  1. [Adapting and validating the generic instrument CollaboRATE™ to measure women's participation in health related decision-making during the reproductive process].

    Science.gov (United States)

    Bravo, Paulina; Contreras, Aixa; Dois, Angelina; Villarroel, Luis

    2018-05-01

    There is a worldwide interest in involving patients in health related decisions, so patients can actively search for therapeutic options and choose course of action that allows them to have better quality of life and wellbeing. The majority of the instruments available to capture the degree of participation in medical decision-making are in English and have been developed in high income countries. To adapt and validate for the Chilean context the instrument CollaboRATE™, to measure women's participation in medical decisions during the reproductive process. Cross-sectional study to adapt and validate the instrument CollaboRATE™. Maternity units in Santiago, Chile. Puerperal women in maternity units of three public hospitals. Translation and back-translation, cultural and linguistic relevance with service users and final revision by experts. Study for validation with 90 puerperal women. The Chilean version of CollaboRATE™ demonstrated to be a reliable instrument to capture the degree of patients' participation in medical decision-making. Cronbach alpha was above 0.89. This study provides the first instrument to capture the prevalence of SDM in a Latin American country. This instrument will be critical in future research efforts that seek to explore to what extent people are being involved in the decisions related to their healthcare. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  2. Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation

    NARCIS (Netherlands)

    Steinmetz, Caroline; Kashyap, Anubha; Zhivkova, Nataliya; Alizor, Henry; Ernst, Isabell; Gottfried-Brand, Daniela; Janssen, Henning; Teufel, Andreas; Schulze-Bergkamen, Henning; Lotz, Johannes; Kuball, Jürgen; Theobald, Matthias; Heise, Michael; Lang, Hauke; Galle, Peter R; Strand, Dennis; Strand, Susanne

    2017-01-01

    Incidence and prevalence of inflammatory liver diseases has increased over the last years, but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune

  3. 48 CFR 570.401 - Renewal options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Renewal options. 570.401... Requirements 570.401 Renewal options. (a) Exercise of options. Before exercising an option to renew, follow the... survey. Before exercising an option to renew a lease, review current market information to ensure the...

  4. Treatment Options for Wilms Tumor

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... come back) after it has been treated. Treatment Option Overview Key Points There are different types of ...

  5. Treatment Options for Myelodysplastic Syndromes

    Science.gov (United States)

    ... special light. Certain factors affect prognosis and treatment options. The prognosis (chance of recovery) and treatment options ... age and general health of the patient. Treatment Option Overview Key Points There are different types of ...

  6. Treatment Option Overview (Prostate Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  7. Treatment Option Overview (Myelodysplastic Syndromes)

    Science.gov (United States)

    ... special light. Certain factors affect prognosis and treatment options. The prognosis (chance of recovery) and treatment options ... age and general health of the patient. Treatment Option Overview Key Points There are different types of ...

  8. Treatment Option Overview (Esophageal Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  9. Treatment Option Overview (Childhood Rhabdomyosarcoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  10. Treatment Option Overview (Penile Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  11. Treatment Option Overview (Vulvar Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  12. Treatment Option Overview (Pancreatic Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  13. Treatment Option Overview (Adrenocortical Carcinoma)

    Science.gov (United States)

    ... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  14. Treatment Options for Childhood Rhabdomyosarcoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  15. Treatment Options for Kaposi Sarcoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  16. Treatment Options for Childhood Craniopharyngioma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... the brain where it was first found. Treatment Option Overview Key Points There are different types of ...

  17. Nelson Syndrome: Update on Therapeutic Approaches.

    Science.gov (United States)

    Azad, Tej D; Veeravagu, Anand; Kumar, Sunny; Katznelson, Laurence

    2015-06-01

    To review the pathophysiology and therapeutic modalities availble for Nelson syndrome. We reviewed the current literature including managment for Nelson syndrome. For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS. An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Characterization of ion exchange resins for nuclear power plants: Application and validation of a dedicated model

    International Nuclear Information System (INIS)

    Mabrouk, A.

    2012-01-01

    In pressurized water reactor, ion exchange resins (IER) are used in systems purification. In this thesis, a qualitative study has been performed to predict the behavior of IER while used in nuclear plants conditions. Then, we searched to characterize the IER behavior in column through a quantitative study using analytical solutions. But these solutions worked only for particular cases. In order to find a general solution, we used a new numerical solution: OPTIPUR. To validate this general solution and get a better understanding of the kinetic in column, we performed an experimental study to characterize the resistance to mass transfer in column and to study the sensibility on the parameters influencing this phenomenon. This study is based on the characterization of the initial leakage (initial pollutant concentration at the column outlet). We tested numerous parameters on the initial leakage. We understood the importance of the superficial velocity and indeed of the hydrodynamic conditions on the initial leakage. These numerous results about initial leakage were modeled with an empirical correlation of Dwivedi and Upadhyay in order to validate it. Then, we modeled our results with the two options of OPTIPUR software: option Mass Transfer Coefficient (MTC) and Nernst-Planck (NP). These options encircle experimental results. The MTC option of OPTIPUR gives lower results while those obtained with the NP option are higher than the experimental results. We observed also that only the NP option was valid for a ternary exchange. We proposed solutions to get a better fit with the results obtained with OPTIPUR. We performed other simulations to check the prediction abilities of the software for longer experiments (until the IER saturation). The tendencies were those expected. The OPTIPUR software showed is accuracy and robustness to study column kinetic. (author)

  19. Bee Pollen: Chemical Composition and Therapeutic Application

    Directory of Open Access Journals (Sweden)

    Katarzyna Komosinska-Vassev

    2015-01-01

    Full Text Available Bee pollen is a valuable apitherapeutic product greatly appreciated by the natural medicine because of its potential medical and nutritional applications. It demonstrates a series of actions such as antifungal, antimicrobial, antiviral, anti-inflammatory, hepatoprotective, anticancer immunostimulating, and local analgesic. Its radical scavenging potential has also been reported. Beneficial properties of bee pollen and the validity for their therapeutic use in various pathological condition have been discussed in this study and with the currently known mechanisms, by which bee pollen modulates burn wound healing process.

  20. Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors

    Directory of Open Access Journals (Sweden)

    Anna L Olsen

    2012-01-01

    Full Text Available RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB of non-small cell lung cancer (NSCLC patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO (LY2181308, we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies.

  1. Option-implied term structures

    OpenAIRE

    Vogt, Erik

    2014-01-01

    The illiquidity of long-maturity options has made it difficult to study the term structures of option spanning portfolios. This paper proposes a new estimation and inference framework for these option-implied term structures that addresses long-maturity illiquidity. By building a sieve estimator around the risk-neutral valuation equation, the framework theoretically justifies (fat-tailed) extrapolations beyond truncated strikes and between observed maturities while remaining nonparametric. Ne...

  2. Therapeutic challenge in brain metastases: chemotherapy, surgery or radiotherapy

    International Nuclear Information System (INIS)

    Mena, Ivan; Contreras, Manuel; Ceballos Francisco

    1998-01-01

    Metastases to the brain occur in 25 to 35% of patients with systemic cancer. Cerebral metastatic is the most common intracranial tumor in adults and occur up to 10 times more frequently than primary tumors in the central nervous system. Significant advances have occurred in the diagnosis and treatment of metastases to the brain, and the therapeutic nihilism of the past is now no longer warranted for most patients. With the currently available treatments, most patients do not die of their brain metastases and usually experience effective palliation of neurologic symptoms and meaning full extension of life. As a trial to limit the cerebral metastatic disease, many and diverse therapy options have been developed such as: chemotherapy, surgery plus whole-brain radiotherapy, only radiation therapy, therapy with neutron, intersticial brachytherapy and stereotactic radiosurgery. In selected cases, surgery plus whole-brain radiotherapy is the conventional treatment for single metastases. However, recurrence usually limits the quality of life and greatly decrease the patients time life, and the therapy options are scarce. This piece of writing also includes a review of the available therapy forms to manage this kind of lesions. (The author)

  3. Astroglial networks and implications for therapeutic neuromodulation of epilepsy

    Directory of Open Access Journals (Sweden)

    Mark R Witcher

    2012-08-01

    Full Text Available Epilepsy is a common chronic neurologic disorder affecting approximately 1 percent of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

  4. New options in the management of tendinopathy

    Science.gov (United States)

    Maffulli, Nicola; Longo, Umile Giuseppe; Loppini, Mattia; Spiezia, Filippo; Denaro, Vincenzo

    2010-01-01

    Tendon injuries can be acute or chronic, and caused by intrinsic or extrinsic factors, either alone or in combination. Tendinopathies are a common cause of disability in occupational medicine and account for a substantial proportion of overuse injuries in sports. Tendinopathy is essentially a failed healing response, with haphazard proliferation of tenocytes, abnormalities in tenocytes, with disruption of collagen fibres and subsequent increase in noncollagenous matrix. The scientific evidence base for managing tendinopathies is limited. What may appear clinically as an “acute tendinopathy” is actually a well advanced failure of a chronic healing response in which there is neither histologic nor biochemical evidence of inflammation. In this review we report the new options for the management of tendinopathy, including eccentric exercises, extracorporeal shockwave therapy, injections (intratendinous injections of corticosteroids, aprotinin, polidocanol platelet-rich plasma, autologous blood injection, high-volume injections) and surgery. Open surgery aims to excise fibrotic adhesions, remove areas of failed healing and make multiple longitudinal incisions in the tendon to detect intratendinous lesions, and to restore vascularity and possibly stimulate the remaining viable cells to initiate cell matrix response and healing. New surgical techniques aim to disrupt the abnormal neoinnervation to interfere with the pain sensation caused by tendinopathy. These procedures are intrinsically different from the classical ones in present use, because they do not attempt to address directly the pathologic lesion, but act only to denervate them. They include endoscopy, electrocoagulation, and minimally invasive stripping. Further randomized controlled trials are necessary to clarify better the best therapeutic options for the management of tendinopathy. PMID:24198540

  5. Clinical trials as treatment option: bioethics and health care disparities in substance dependency.

    Science.gov (United States)

    Timmermans, Stefan; McKay, Tara

    2009-12-01

    Bioethicists have warned against the dangers of mixing research with treatment. They are concerned that research priorities may take precedence over individual patient needs and that research subjects tend to misunderstand the purpose of research or overestimate the direct medical benefits of participating in studies. Yet, other work has questioned whether clinical research can always be separated from therapeutic benefit for participants. Using in-depth interviews with participants in two phase III randomized U.S. clinical trials for methamphetamine dependency, we examine the treatment options available to participants, their experiences with participating in the trials, and potential problems of trial participation. We find that while participants have experience with four alternative treatment modalities - quitting alone, support groups, in-patient treatment facilities, and consulting primary care physicians - the randomized clinical trials compare favorably to alternatives because they provide access to evidence-based behavioral treatments, specialized medical professionals, non-judgmental staff, and the possibility of receiving an experimental drug. We conclude that while randomized clinical trials are imperfect substitutes for clinical care, they constitute a fragile and sporadic therapeutic niche in a country with fundamental problems in access to health care, a mixed punitive-therapeutic drug addiction policy, and a profit-driven pharmaceutical development and approval process.

  6. Treatment Option Overview (Myelodysplastic/Myeloproliferative Neoplasms)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ...

  7. Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

    Science.gov (United States)

    Irwin, Nigel; Gault, Victor; Flatt, Peter R

    2010-09-01

    Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

  8. Efficient option valuation of single and double barrier options

    Science.gov (United States)

    Kabaivanov, Stanimir; Milev, Mariyan; Koleva-Petkova, Dessislava; Vladev, Veselin

    2017-12-01

    In this paper we present an implementation of pricing algorithm for single and double barrier options using Mellin transformation with Maximum Entropy Inversion and its suitability for real-world applications. A detailed analysis of the applied algorithm is accompanied by implementation in C++ that is then compared to existing solutions in terms of efficiency and computational power. We then compare the applied method with existing closed-form solutions and well known methods of pricing barrier options that are based on finite differences.

  9. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    Directory of Open Access Journals (Sweden)

    Pranshu eBansal

    2016-05-01

    Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

  10. 2005 resource options report

    International Nuclear Information System (INIS)

    Morris, T.

    2005-01-01

    This resource options report (ROR) fulfils regulatory requirements in British Columbia's two-year resource planning process. It identifies a wide range of resources and technologies that could be used to meet BC Hydro's future electricity demand. As such, it facilitates a transparent public review of resource options which include both supply-side and demand-side options. The resource options that will be used in the 2005 integrated electricity plan (IEP) were characterized. This ROR also documents where there is a general agreement or disagreement on the resource type characterization, based on the First Nations and Stakeholder engagement. BC Hydro used current information to provide realistic ranges on volume and cost to characterize environmental and social attributes. The BC Hydro system was modelled to assess the benefit and cost of various resource options. The information resulting from this ROR and IEP will help in making decisions on how to structure competitive acquisition calls and to determine the level of transmission services needed to advance certain BC Hydro projects. The IEP forecasts the nature and quantity of domestic resources required over the next 20 years. A strategic direction on how those needs will be met has been created to guide the management of BC Hydro's energy resources. Supply-side options include near-commercial technologies such as energy storage, ocean waves, tidal, fuel cells and integrated coal gasification combined cycle technology. Supply-side options also include natural gas, coal, biomass, geothermal, wind, and hydro. 120 refs., 39 tabs., 21 figs., 6 appendices

  11. Probabilistic methods in exotic option pricing

    NARCIS (Netherlands)

    Anderluh, J.H.M.

    2007-01-01

    The thesis presents three ways of calculating the Parisian option price as an illustration of probabilistic methods in exotic option pricing. Moreover options on commidities are considered and double-sided barrier options in a compound Poisson framework.

  12. Preventing Mitochondrial Diseases: Embryo-Sparing Donor-Independent Options.

    Science.gov (United States)

    Adashi, Eli Y; Cohen, I Glenn

    2018-05-01

    Mutant mitochondrial DNA gives rise to a broad range of incurable inborn maladies. Prevention may now be possible by replacing the mutation-carrying mitochondria of zygotes or oocytes at risk with donated unaffected counterparts. However, mitochondrial replacement therapy is being held back by theological, ethical, and safety concerns over the loss of human zygotes and the involvement of a donor. These concerns make it plain that the identification, validation, and regulatory adjudication of novel embryo-sparing donor-independent technologies remains a pressing imperative. This Opinion highlights three emerging embryo-sparing donor-independent options that stand to markedly allay theological, ethical, and safety concerns raised by mitochondrial replacement therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Dopamine Modulates Option Generation for Behavior.

    Science.gov (United States)

    Ang, Yuen-Siang; Manohar, Sanjay; Plant, Olivia; Kienast, Annika; Le Heron, Campbell; Muhammed, Kinan; Hu, Michele; Husain, Masud

    2018-05-21

    Animals make innumerable decisions every day, each of which involves evaluating potential options for action. But how are options generated? Although much is now known about decision making when a fixed set of potential options is provided, surprisingly little progress has been made on self-generated options. Some researchers have proposed that such abilities might be modulated by dopamine. Here, we used a new measure of option generation that is quantitative, objective, and culture fair to investigate how humans generate different behavioral options. Participants were asked to draw as many different paths (options) as they could between two points within a fixed time. Healthy individuals (n = 96) exhibited a trade-off between uniqueness (how individually different their options were) and fluency (number of options), generating either many similar or few unique options. To assess influence of dopamine, we first examined patients with Parkinson's disease (n = 35) ON and OFF their dopaminergic medication and compared them to elderly healthy controls (n = 34). Then we conducted a double-blind, placebo-controlled crossover study of the D2 agonist cabergoline in healthy older people (n = 29). Across both studies, dopamine increased fluency but diminished overall uniqueness of options generated, due to the effect of fluency trading off with uniqueness. Crucially, however, when this trade-off was corrected for, dopamine was found to increase uniqueness for any given fluency. Three carefully designed control studies showed that performance on our option-generation task was not related to executing movements, planning actions, or selecting between generated options. These findings show that dopamine plays an important role in modulating option generation. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. Therapeutic approaches to preventing cell death in Huntington disease.

    Science.gov (United States)

    Kaplan, Anna; Stockwell, Brent R

    2012-12-01

    Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. The Factor Structure in Equity Options

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Fournier, Mathieu; Jacobs, Kris

    Principal component analysis of equity options on Dow-Jones firms reveals a strong factor structure. The first principal component explains 77% of the variation in the equity volatility level, 77% of the variation in the equity option skew, and 60% of the implied volatility term structure across...... equities. Furthermore, the first principal component has a 92% correlation with S&P500 index option volatility, a 64% correlation with the index option skew, and a 80% correlation with the index option term structure. We develop an equity option valuation model that captures this factor structure...

  16. The information content of options

    OpenAIRE

    Navon, Yonatan

    2017-01-01

    The objective of this thesis is to examine the information content of stock options in financial markets. A key question in financial economics is how information diffuses across markets and how quickly it is reflected in security prices. This thesis aims at exploring this question by investigating the informational role that options play in financial markets. This is achieved by exploring the joint cross section of option and bond prices, the informational role of options in seasoned equity ...

  17. Challenges of therapeutic substitution of drugs for economic reasons: focus on CVD prevention.

    Science.gov (United States)

    Johnston, Atholl

    2010-04-01

    Healthcare systems throughout the world are under increasing pressure to control and minimise costs. The substitution of initially-prescribed drugs with cheaper equivalents is an obvious option which presents a rapid and visible means to reduce these costs. Whether the substitution improves patient and/or population outcomes must be appraised and this paper highlights the conditions under which therapeutic substitution may require additional thought and consideration. In this paper, some of the medical evidence and the regulatory environment for and against the three types of therapeutic substitution - generic, within-class and between-class - are discussed. This article is not an exhaustive review of the literature, but captures some of the key clinical, pharmacological, economic, policy and ethical issues regarding generic and therapeutic substitution. Search criteria of the most commonly used terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence, were applied to Embase, PubMed and Google Scholar to identify relevant publications. Although population studies support therapeutic substitution in principle, there is evidence that substitution may not always result in therapeutic equivalence in individual patients, with the consequent potential for greater risks of decreased efficacy and/or increased safety concerns. Factors such as patient choice and therapeutic equivalence also play an important role in the effectiveness of the treatment and overall management of the patient. The pan-European regulatory environment provides another contradiction, encouraging widespread cost containment through reduction in drug acquisition costs, while simultaneously promoting an increased role for patients in defining and managing their own treatment. There is a strong rationale for careful management in some patients with cardiovascular disease. Treatment decisions should be transparent and based on strong clinical evidence. If not, drug substitution on

  18. [Validation of the German Version of Tinnitus Functional Index (TFI)].

    Science.gov (United States)

    Brüggemann, Petra; Szczepek, Agnieszka J; Kleinjung, Tobias; Ojo, Michael; Mazurek, Birgit

    2017-09-01

    Tinnitus belongs to seriously debilitating auditory conditions and is often complicated by comorbidities such as insomnia, difficulties with concentration, depression, frustration and irritability. To facilitate the grading of symptoms and the effects of therapeutic strategies, we validated a German-version Tinnitus Functional Index (TFI) in 229 subjects suffering from chronic tinnitus. Outcome validity was assessed using the Tinnitus Questionnaire (TQ, German adaptation by Goebel u. Hiller [1998]). Construct validity was assessed using the "Hamburger Allgemeine Depressionsskala" (HADS). The German TFI featured excellent internal consistency (total score Cronbach's α=0.93). Factor analysis disclosed eight TFI subscales as proposed earlier by Meikle et al. [2012]. Intercorrelations were strong both between the TFI and the TQ (r=0.83), and between the TFI and the HADS (depression r=0.49, anxiety r=0.51). The German-version TFI qualifies as a rapid and statistically robust tool for grading the impact of tinnitus on daily living and for the measurements of therapeutic effects. Regarding depressive symptomatology, sensitivity of the TFI was comparable to that of the TQ. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Decision-making model of generation technology under uncertainty based on real option theory

    International Nuclear Information System (INIS)

    Ming, Zeng; Ping, Zhang; Shunkun, Yu; Ge, Zhang

    2016-01-01

    Highlights: • A decision-making model of generation technology investment is proposed. • The irreversible investment concept and real option theory is introduced. • Practical data was used to prove the validity of the model. • Impact of electricity and fuel price fluctuation on investment was analyzed. - Abstract: The introduction of market competition and the increased uncertainty factors makes the generators have to decide not only on whether to invest generation capacity or not but also on what kind of generation technology to choose. In this paper, a decision-making model of generation technology investment is proposed. The irreversible investment concept and real option theory is introduced as the fundamental of the model. In order to explain the decision-making process of generator’s investment, the decision-making optimization model was built considering two generation technologies, i.e., the heat-only system and the combined heat and power generation. Also, we discussed the theory deducing process, which explained how to eliminate the overrated economic potential caused by risk hazard, based on economic evaluation of both generation technologies. Finally, practical data from electricity market of Inner Mongolia was used to prove the validity of the model and the impact of uncertainties of electricity and fuel price fluctuation on investment was analyzed according to the simulated results.

  20. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2016-01-01

    Full Text Available Colorectal cancer (CRC is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy.

  1. Consumer Satisfaction with Psychiatric Services: The Role of Shared Decision-Making and the Therapeutic Relationship

    Science.gov (United States)

    Klingaman, Elizabeth A.; Medoff, Deborah R.; Park, Stephanie G.; Brown, Clayton H.; Fang, Lijuan; Dixon, Lisa B.; Hack, Samantha M.; Tapscott, Stephanie L.; Walsh, Mary Brighid; Kreyenbuhl, Julie A.

    2017-01-01

    Objective Although dissatisfaction is a primary reason for disengagement from outpatient psychiatric care among consumers with serious mental illnesses, little is known about predictors of their satisfaction with medication management visits. The primary purpose of the present study was to explore how dimensions of consumer preferences for shared decision-making (i.e., preferences for obtaining knowledge about one’s mental illness, being offered and asked one’s opinion about treatment options, and involvement in treatment decisions) and the therapeutic relationship (i.e., positive collaboration and type of clinician input) were related to visit satisfaction. Methods Participants were 228 Veterans with serious mental illnesses who completed a 19-item self-report questionnaire assessing satisfaction with visits to prescribers (n=524 assessments) immediately after visits. In this correlational design, a 3-level mixed model with the restricted maximum likelihood estimation procedure was used to examine shared decision-making preferences and therapeutic alliance as predictors of visit satisfaction. Results Preferences for involvement in treatment decisions was the unique component of shared decision-making associated with satisfaction, such that the more consumers desired involvement, the less satisfied they were. Positive collaboration and prescriber input were associated with greater visit satisfaction. Conclusions and Implications for Practice When consumers with serious mental illnesses express preferences to be involved in shared decision-making, it may not be sufficient to only provide information and treatment options; prescribers should attend to consumers’ interest in involvement in actual treatment decisions. Assessment and tailoring of treatment approaches to consumer preferences for shared decision-making should occur within the context of a strong therapeutic relationship. PMID:25664755

  2. Therapeutic exercises for the control of temporomandibular disorders

    Directory of Open Access Journals (Sweden)

    Alberto da Rocha Moraes

    2013-10-01

    Full Text Available INTRODUCTION: Temporomandibular disorder (TMD is a multifactorial disease. For this reason, it is difficult to obtain an accurate and correct diagnosis. In this context, conservative treatments, including therapeutic exercises classified as stretching, relaxation, coordination, strengthening and endurance, are oftentimes prescribed. OBJECTIVE: Thus, the aim of the present article was to conduct a literature review concerning the types of exercises available and the efficacy for the treatment of muscular TMD. METHODS: The review included researches carried out between 2000 and 2010, indexed on Web of Science, PubMed, LILACS and BBO. Moreover, the following keywords were used: Exercise, physical therapy, facial pain, myofascial pain syndrome, and temporomandibular joint dysfunction syndrome. Studies that did not consider the subject "TMD and exercises", used post-surgery exercises and did not use validated criteria for the diagnosis of TMD (RDC/TMD were not included. RESULTS: The results comprised seven articles which proved therapeutic exercises to be effective for the treatment of muscular TMD. However, these studies are seen as limited, since therapeutic exercises were not applied alone, but in association with other conservative procedures. In addition, they present some drawbacks such as: Small samples, lack of control group and no detailed exercise description which should have included intensity, repetition, frequency and duration. CONCLUSION: Although therapeutic exercises are considered effective in the management of muscular TMD, the development of randomized clinical trials is necessary, since many existing studies are still based on the clinical experience of professionals.

  3. 48 CFR 17.107 - Options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Options. 17.107 Section 17... CONTRACT TYPES SPECIAL CONTRACTING METHODS Multiyear Contracting 17.107 Options. Benefits may accrue by including options in a multiyear contract. In that event, contracting officers must follow the requirements...

  4. Balancing of solar heating options

    NARCIS (Netherlands)

    Veltkamp, W.B.; van Koppen, C.W.J.; Ouden, den C.

    1984-01-01

    In the field of energy conservation many options are presently competing. This study aims at providing more rational criteria for selection between these options.The options considered are; insulation of the walls, regeneration of the heat in the waste air, double glazing, attached sunspace at the

  5. Stock option repricing in Europe

    NARCIS (Netherlands)

    Sauer, M.; Sautner, Z.

    2008-01-01

    This paper investigates the link between option repricing, firm performance and corporate governance in Europe. Our sample consists of 77 European firms that repriced their stock option between 1987 and 2003. We document that option repricing is mainly a phenomenon for young and fast growing firms

  6. 48 CFR 2917.207 - Exercising options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Exercising options. 2917... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 2917.207 Exercising options. The contracting officer must use a standardized determination and finding before exercising an option in accordance with...

  7. Simplified Therapeutic Intervention Scoring System : The TISS-28 items - Results from a multicenter study

    NARCIS (Netherlands)

    Miranda, DR; deRijk, A; Schaufeli, W

    Objectives: To validate a simplified version of the Therapeutic Intervention Scoring System, the TISS-28, and to determine the association of TISS-28 with the time spent on scored and nonscored nursing activities. Design: Prospective, multicenter study. Setting: Twenty-two adult medical, surgical,

  8. Dipole Magnets for the LHeC Ring-Ring Option

    CERN Document Server

    Tommasini, D; Chritin, R

    2012-01-01

    The Ring-Ring option of a Large Hadron electron Collider (LHeC) requires 3080 bending magnets, 5.35-meter-long each providing a magnetic field ranging from 0.0127 T at 10 GeV to 0.0763 T at 60 GeV. Main issues in the design of these magnets are the very low injection field, constituting a challenge in achieving a satisfactory field reproducibility from cycle to cycle, and the required compactness to fit in the existing LHC tunnel. This paper describes and discusses a design meeting these requirements, together with its experimental validation by the manufacture and measurement of a 400-mm-long magnet model.

  9. PAX6 aniridia syndrome: clinics, genetics, and therapeutics.

    Science.gov (United States)

    Lim, Hyun Taek; Kim, Dae Hee; Kim, Hyuna

    2017-09-01

    Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe the clinical features, genetics, and therapeutic options for this disease and to provide an update of current knowledge and latest research findings. Aside from the ocular features, a variety of associated systemic abnormalities, including hormonal, metabolic, gastrointestinal, genitourinary, and neurologic pathologies have been reported in children with aniridia. Although mutations in PAX6 are a major cause of aniridia, genetic defects in nearby genes, such as TRIM44 or ELP4, have also been reported to cause aniridia. Recent improvement in genetic testing technique will help more rapid and precise diagnosis for aniridia. A promising therapeutic approach called nonsense suppression therapy has been introduced and successfully used in an animal model. Aniridia is a challenging disease. The progressive nature of this condition and its potential complications require continuous and life-long ophthalmologic care. Genetic diagnosis for aniridia is important for establishing definitive molecular characterization as well as identifying individuals at high risk for Wilms tumor. Recent advancement in understanding the genetic pathogenesis of this disease offers promise for the approaches to treatment.

  10. Old and new challenges in Parkinson's disease therapeutics.

    Science.gov (United States)

    Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

    2017-09-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Therapeutic Use of Cannabis in Inflammatory Bowel Disease

    Science.gov (United States)

    Katz, Seymour

    2016-01-01

    The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

  12. Current issues of RNAi therapeutics delivery and development.

    Science.gov (United States)

    Haussecker, D

    2014-12-10

    12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that

  13. 38 CFR 6.10 - Options.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Options. 6.10 Section 6.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS UNITED STATES GOVERNMENT LIFE INSURANCE Optional Settlement § 6.10 Options. Insurance will be payable in one sum only when...

  14. Perpetual Cancellable American Call Option

    OpenAIRE

    Emmerling, Thomas J.

    2010-01-01

    This paper examines the valuation of a generalized American-style option known as a Game-style call option in an infinite time horizon setting. The specifications of this contract allow the writer to terminate the call option at any point in time for a fixed penalty amount paid directly to the holder. Valuation of a perpetual Game-style put option was addressed by Kyprianou (2004) in a Black-Scholes setting on a non-dividend paying asset. Here, we undertake a similar analysis for the perpetua...

  15. Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter pylori eradication.

    Science.gov (United States)

    Jeong, Su Jin; Kim, Jie-Hyun; Jung, Da Hyun; Lee, Kyoung Hwa; Park, Soon Young; Song, Yungoo; Kang, Il-Mo; Song, Young Goo

    2018-02-12

    Novel antibacterial strategies against Helicobacter pylori are needed because H. pylori strains are acquiring resistance to antibiotics. We evaluated the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment regimens in a murine model of H. pylori infection. Two groups of 10 rats were administered either smectite or S-GEN to measure coverage of the gastric mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups of 10 mice each given different treatments, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces. The levels of proinflammatory cytokines were examined. S-GEN was retained in the gastric mucosal layer with a >60% distribution ratio for up to 1 h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared with that of untreated mice or mice treated with other regimens. The cure rates in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%, 60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the faeces of mice were 90% and 100% in Group III with standard therapy and Group V with triple therapy including S-GEN, respectively. S-GEN triple therapy also reduced the levels of proinflammatory cytokines. These results suggest that S-GEN is a promising and effective therapeutic agent for the treatment of H. pylori infection. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Therapeutic Symptomatic Strategies in the Parasomnias.

    Science.gov (United States)

    Manni, Raffaele; Toscano, Gianpaolo; Terzaghi, Michele

    2018-06-05

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

  17. 48 CFR 317.107 - Options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Options. 317.107 Section... CONTRACT TYPES SPECIAL CONTRACTING METHODS Multi-year Contracting 317.107 Options. When used as part of a multi-year contract, options shall not be used to extend the performance of the original requirement for...

  18. 38 CFR 8.25 - Options.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Options. 8.25 Section 8.25 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS NATIONAL SERVICE LIFE INSURANCE Optional Settlements § 8.25 Options. Insurance will be paid in a lump sum only when selected by...

  19. Bounds for Asian basket options

    Science.gov (United States)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  20. Validation of a virtual reality-based simulator for shoulder arthroscopy.

    Science.gov (United States)

    Rahm, Stefan; Germann, Marco; Hingsammer, Andreas; Wieser, Karl; Gerber, Christian

    2016-05-01

    This study was to determine face and construct validity of a new virtual reality-based shoulder arthroscopy simulator which uses passive haptic feedback. Fifty-one participants including 25 novices (100 shoulder arthroscopies) completed two tests: for assessment of face validity, a questionnaire was filled out concerning quality of simulated reality and training potential using a 7-point Likert scale (range 1-7). Construct validity was tested by comparing simulator metrics (operation time in seconds, camera and grasper pathway in centimetre and grasper openings) between novices and experts test results. Overall simulated reality was rated high with a median value of 5.5 (range 2.8-7) points. Training capacity scored a median value of 5.8 (range 3-7) points. Experts were significantly faster in the diagnostic test with a median of 91 (range 37-208) s than novices with 1177 (range 81-383) s (p < 0.0001) and in the therapeutic test 102 (range 58-283) s versus 229 (range 114-399) s (p < 0.0001). Similar results were seen in the other metric values except in the camera pathway in the therapeutic test. The tested simulator achieved high scores in terms of realism and training capability. It reliably discriminated between novices and experts. Further improvements of the simulator, especially in the field of therapeutic arthroscopy, might improve its value as training and assessment tool for shoulder arthroscopy skills. II.

  1. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... can be addressed as quickly as possible. Recurrent breast cancer If the cancer does return after treatment for ...

  2. Milrinone therapeutic drug monitoring in a pediatric population: Development and validation of a quantitative liquid chromatography-tandem mass spectrometry method.

    Science.gov (United States)

    Raizman, Joshua E; Taylor, Katherine; Parshuram, Christopher; Colantonio, David A

    2017-05-01

    Milrinone is a potent selective phosphodiesterase type III inhibitor which stimulates myocardial function and improves myocardial relaxation. Although therapeutic monitoring is crucial to maintain therapeutic outcome, little data is available. A proof-of-principle study has been initiated in our institution to evaluate the clinical impact of optimizing milrinone dosing through therapeutic drug monitoring (TDM) in children following cardiac surgery. We developed a robust LC-MS/MS method to quantify milrinone in serum from pediatric patients in real-time. A liquid-liquid extraction procedure was used to prepare samples for analysis prior to measurement by LC-MS/MS. Performance characteristics, such as linearity, limit of quantitation (LOQ) and precision, were assessed. Patient samples were acquired post-surgery and analyzed to determine the concentration-time profile of the drug as well as to track turn-around-times. Within day precision was milrinone levels were either sub-therapeutic or in the toxic range, highlighting the importance for milrinone TDM. This simplified and quick method proved to be analytically robust and able to provide therapeutic monitoring of milrinone in real-time in patients post-cardiac surgery. Copyright © 2017. Published by Elsevier B.V.

  3. OPTION(5) versus OPTION(12) instruments to appreciate the extent to which healthcare providers involve patients in decision-making.

    Science.gov (United States)

    Stubenrouch, Fabienne E; Pieterse, Arwen H; Falkenberg, Rijan; Santema, T Katrien B; Stiggelbout, Anne M; van der Weijden, Trudy; Aarts, J Annemijn W M; Ubbink, Dirk T

    2016-06-01

    The 12-item "observing patient involvement" (OPTION(12))-instrument is commonly used to assess the extent to which healthcare providers involve patients in health-related decision-making. The five-item version (OPTION(5)) claims to be a more efficient measure. In this study we compared the Dutch versions of the OPTION-instruments in terms of inter-rater agreement and correlation in outpatient doctor-patient consultations in various settings, to learn if we can safely switch to the shorter OPTION(5)-instrument. Two raters coded 60 audiotaped vascular surgery and oncology patient consultations using OPTION(12) and OPTION(5). Unweighted Cohen's kappa was used to compute inter-rater agreement on item-level. The association between the total scores of the two OPTION-instruments was investigated using Pearson's correlation coefficient (r) and a Bland & Altman plot. After fine-tuning the OPTION-manuals, inter-rater agreement for OPTION(12) and OPTION(5) was good to excellent (kappa range 0.69-0.85 and 0.63-0.72, respectively). Mean total scores were 23.7 (OPTION(12); SD=7.8) and 39.3 (OPTION(5); SD=12.7). Correlation between the total scores was high (r=0.71; p=0.01). OPTION(5) scored systematically higher with a wider range than OPTION(12). Both OPTION-instruments had a good inter-rater agreement and correlated well. OPTION(5) seems to differentiate better between various levels of patient involvement. The OPTION(5)-instrument is recommended for clinical application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Jessica Roelands

    2017-10-01

    Full Text Available The immune system has a substantial effect on colorectal cancer (CRC progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies is influenced by the immune system. The molecular characterization of colorectal cancer (CRC has led to the identification of favorable and unfavorable immunological attributes linked to clinical outcome. With the definition of consensus molecular subtypes (CMSs based on transcriptomic profiles, multiple characteristics have been proposed to be responsible for the development of the tumor immune microenvironment and corresponding mechanisms of immune escape. In this review, a detailed description of proposed immune phenotypes as well as their interaction with different therapeutic modalities will be provided. Finally, possible strategies to shift the CRC immune phenotype towards a reactive, anti-tumor orientation are proposed per CMS.

  5. 24 CFR 206.19 - Payment options.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Payment options. 206.19 Section 206... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgages § 206.19 Payment options. (a) Term payment option. Under the term payment option, equal monthly payments are made by the mortgagee to the...

  6. A web-based resource for designing therapeutics against Ebola Virus

    OpenAIRE

    Sandeep Kumar Dhanda; Kumardeep Chaudhary; Sudheer Gupta; Samir Kumar Brahmachari; Gajendra P. S. Raghava

    2016-01-01

    In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus. Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses. Secondly, we generated all the possible overlapping 9mer peptides from the proteins of ebolaviruses. Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with ...

  7. Traditional preventive treatment options

    DEFF Research Database (Denmark)

    Longbottom, C; Ekstrand, K; Zero, D

    2009-01-01

    Preventive treatment options can be divided into primary, secondary and tertiary prevention techniques, which can involve patient- or professionally applied methods. These include: oral hygiene (instruction), pit and fissure sealants ('temporary' or 'permanent'), fluoride applications (patient...... options....

  8. 24 CFR 35.120 - Options.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Options. 35.120 Section 35.120... and Definitions for All Programs. § 35.120 Options. (a) Standard treatments. Where interim controls are required by this part, the designated party has the option to presume that lead-based paint or...

  9. Mediterranean diet and non-alcoholic fatty liver disease: New therapeutic option around the corner?

    Science.gov (United States)

    Sofi, Francesco; Casini, Alessandro

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in Western countries, being considered as the hepatic manifestation of metabolic syndrome. NAFLD has a common pathogenic background to that of metabolic syndrome, and shares many risk factors such as obesity, hypertension, insulin resistance and dyslipidemia. Although there is no currently available evidence-based established treatment for NAFLD, all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications. Diet, indeed, plays a key role in the management of NAFLD patients, as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease. Among all the diets that have been proposed, a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD. Over the last few years, research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD. In this review, we will examine all the available data on the association between diet, nutrients and the Mediterranean diet in association with onset and severity of NAFLD. PMID:24966604

  10. Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

    Science.gov (United States)

    Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

    2015-01-01

    Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

  11. Patients' experiences with technology during inpatient rehabilitation: opportunities to support independence and therapeutic engagement.

    Science.gov (United States)

    Fager, Susan Koch; Burnfield, Judith M

    2014-03-01

    To understand individuals' perceptions of technology use during inpatient rehabilitation. A qualitative phenomenological study using semi-structured interviews of 10 individuals with diverse underlying diagnoses and/or a close family member who participated in inpatient rehabilitation. Core themes focused on assistive technology usage (equipment set-up, reliability and fragility of equipment, expertise required to use assistive technology and use of mainstream technologies) and opportunities for using technology to increase therapeutic engagement (opportunities for practice outside of therapy, goals for therapeutic exercises and technology for therapeutic exercises: motivation and social interaction). Interviews revealed the need for durable, reliable and intuitive technology without requiring a high level of expertise to install and implement. A strong desire for the continued use of mainstream devices (e.g. cell phones, tablet computers) reinforces the need for a wider range of access options for those with limited physical function. Finally, opportunities to engage in therapeutically meaningful activities beyond the traditional treatment hours were identified as valuable for patients to not only improve function but to also promote social interaction. Assistive technology increases functional independence of severely disabled individuals. End-users (patients and families) identified a need for designs that are durable, reliable, intuitive, easy to consistently install and use. Technology use (adaptive or commercially available) provides a mechanism to extend therapeutic practice beyond the traditional therapy day. Adapting skeletal tracking technology used in gaming software could automate exercise tracking, documentation and feedback for patient motivation and clinical treatment planning and interventions.

  12. FTR-option formulation and pricing

    International Nuclear Information System (INIS)

    Parmeshwaran, Vijay; Muthuraman, Kumar

    2009-01-01

    Recent changes in electricity markets have advocated the use of Local Marginal Prices (LMP) for congestion management and pricing. From the perspective of market participants, the LMPs pose a risk since they are not known before a transaction on the grid is made. Financial transmission rights (FTR) are instruments that help market participants hedge this risk and are issuable in two flavors - obligations and options. While pricing obligations are much easier, pricing FTR options pose a significant challenge. In this paper we develop a computational method for pricing FTR options. We also discuss the problem of designing financial instrument sets that assure revenue adequacy for the issuer. We point out the difficulty in assuring revenue adequacy when FTR options are present and propose a scheme for overcoming the difficulty. The proposed pricing method can be used to compute prices of options and obligations in the primary market or as a reliable pricing tool to compute option prices in the secondary market. Finally using a test network we present and discuss numerical results. (author)

  13. Valuing real options: frequently made errors

    OpenAIRE

    Fernández, Pablo

    2002-01-01

    In this paper we analyze frequently made errors when valuing real options. The best way of doing it is through examples. We start by analyzing Damodaran's proposal to value the option to expand the business of Home Depot. Some of the errors and problems of this and other approaches are: - Assuming that the option is replicable and using Black and Scholes' formula. - The estimation of the option's volatility is arbitrary and has a decisive effect on the option's value. - As there is no riskles...

  14. 26 CFR 1.544-4 - Options.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Options. 1.544-4 Section 1.544-4 Internal Revenue... (CONTINUED) Personal Holding Companies § 1.544-4 Options. The shares of stock which may be acquired by reason of an option shall be considered to be constructively owned by the individual having the option to...

  15. Non-Clinical Models for Neurodegenerative Diseases: Therapeutic Approach and Drug Validation in Animal Models

    Directory of Open Access Journals (Sweden)

    Caridad Ivette Fernandez

    2017-12-01

    Full Text Available In 2016, 19.8% of the Cuban population was aged 60 or over. As a result, age-associated degenerative diseases and other diseases have become priority targets from a prophylactic, diagnostic and therapeutic perspective. As a result, the Cuban biomedical scientific community has addressed its basic, preclinical and epidemiological research in order to rise up to the challenge. A firm step in this direction has been the international congress “State of the art in non-clinical models for neurodegenerative diseases” which has brought together preclinical and clinical researchers, technicians and regulatory staff members from different countries to review the state of the art in neurodegenerations, find unifying ideas, objectives and collaborations or partnership. The objective is to expose the perspectives of new biotechnological products from Cuba and other countries from the diagnostic, therapeutic and neuroprotective point of view. It is crucial, therefore, that the irreplaceable role of laboratory animals in achieving these objectives is understood but they must be used in rational, adequate and ethical manner. We expose the current development trends in this field, being of common interest to the work directed to the search for potential drugs, diagnostic tools and the promotion of changes in lifestyle as a preventive projection.

  16. Imaging of athletic pubalgia and core muscle injuries: clinical and therapeutic correlations.

    Science.gov (United States)

    Palisch, Andrew; Zoga, Adam C; Meyers, William C

    2013-07-01

    Athletes frequently injure their hips and core muscles. Accurate diagnosis and proper treatment of groin pain in the athlete can be tricky, frequently posing vexing problem for trainers and physicians. Clinical presentations of the various hip problems overlap with respect to history and physical examination. This article reviews clinical presentations and magnetic resonance imaging findings specific to the various causes of groin pain in the athlete. The focus is on the core muscle injuries (athletic pubalgia or "sports hernia"). The goal is to raise awareness about the variety of injuries that occur and therapeutic options. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Current options for the treatment of optic neuritis

    Directory of Open Access Journals (Sweden)

    Pula JH

    2012-07-01

    Full Text Available John H Pula,1 Christopher J MacDonald21Division of Neuro-ophthalmology, University of Illinois College of Medicine at Peoria, Peoria; 2University of Illinois College of Medicine at Urbana-Champaign, Champaign, IL, USAAbstract: Optic neuritis can be defined as typical (associated with multiple sclerosis, improving independent of steroid treatment, or atypical (not associated with multiple sclerosis, steroid-dependent improvement. Causes of atypical optic neuritis include connective tissue diseases (eg, lupus, vasculitis, sarcoidosis, or neuromyelitis optica. In this manuscript, updated treatment options for both typical and atypical optic neuritis are reviewed. Conventional treatments, such as corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin therapy are all discussed with commentary regarding evidence-based outcomes. Less commonly used treatments and novel purported therapies for optic neuritis are also reviewed. Special scenarios in the treatment of optic neuritis – pediatric optic neuritis, acute demyelinating encephalomyelitis, and optic neuritis occurring during pregnancy – are specifically examined.Keywords: optic neuritis, optic neuropathy, treatment, neuroophthalmology

  18. Hypertension in pregnancy: natural history and treatment options.

    Science.gov (United States)

    Foo, L; Tay, J; Lees, C C; McEniery, C M; Wilkinson, I B

    2015-05-01

    Hypertensive disorders of pregnancy affect approximately 5-10% of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored.

  19. Illiquidity Premia in the Equity Options Market

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Goyenko, Ruslan; Jacobs, Kris

    Illiquidity is well-known to be a significant determinant of stock and bond returns. We report on illiquidity premia in the equity options market. An increase in option illiquidity decreases the current option price and implies higher expected option returns. This effect is statistically and econ......Illiquidity is well-known to be a significant determinant of stock and bond returns. We report on illiquidity premia in the equity options market. An increase in option illiquidity decreases the current option price and implies higher expected option returns. This effect is statistically...... and economically signifi…cant. It is robust across different empirical approaches and when including various control variables. The illiquidity of the underlying stock affects the option return negatively, consistent with a hedging argument: When stock market illiquidity increases, the cost of replicating...

  20. Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Donatella Conconi

    2016-02-01

    Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

  1. Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

    Directory of Open Access Journals (Sweden)

    Kaludov Nikola

    2011-09-01

    Full Text Available Abstract Background Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds. Methods A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular design. Results Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 ≤ 10 μM, with six being very effective (IC50 ≤ 1 μM, and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a

  2. 45 CFR 1306.34 - Combination program option.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Combination program option. 1306.34 Section 1306... START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.34 Combination program option. (a) Combination program option requirements: (1) Grantees implementing a...

  3. 48 CFR 517.207 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Exercise of options. 517... METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 517.207 Exercise of options. Before exercising an option, you must: (a) Synopsize it unless you meet of the following conditions: (1) The option...

  4. 24 CFR 982.625 - Homeownership option: General.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: General. 982... Types Homeownership Option § 982.625 Homeownership option: General. (a) The homeownership option is used... family assisted under the homeownership option may be a newly admitted or existing participant in the...

  5. Facial Pores: Definition, Causes, and Treatment Options.

    Science.gov (United States)

    Lee, Sang Ju; Seok, Joon; Jeong, Se Yeong; Park, Kui Young; Li, Kapsok; Seo, Seong Jun

    2016-03-01

    Enlarged skin pores refer to conditions that present with visible topographic changes of skin surfaces. Although not a medical concern, enlarged pores are a cosmetic concern for a large number of individuals. Moreover, clear definition and possible causes of enlarged pores have not been elucidated. To review the possible causes and treatment options for skin pores. This article is based on a review of the medical literature and the authors' clinical experience in investigating and treating skin pores. There are 3 major clinical causes of enlarged facial pores, namely high sebum excretion, decreased elasticity around pores, and increased hair follicle volume. In addition, chronic recurrent acne, sex hormones, and skin care regimen can affect pore size. Given the different possible causes for enlarged pores, therapeutic modalities must be individualized for each patient. Potential factors that contribute to enlarged skin pores include excessive sebum, decreased elasticity around pores, and increased hair follicle volume. Because various factors cause enlarged facial pores, it might be useful to identify the underlying causes to be able to select the appropriate treatment.

  6. Option Derivatives in Electricity Hedging

    Directory of Open Access Journals (Sweden)

    P. Pavlátka

    2010-01-01

    Full Text Available Despite the high volatility of electricity prices, there is still little demand for electricity power options, and the liquidity on the power exchanges of these power derivatives is quite low. One of the reasons is the uncertainty about how to evaluate these electricity options and about finding the right fair value of this product. Hedging of electricity is associated mainly with products such as futures and forwards. However, due to new trends in electricity trading and hedging, it is also useful to think more about options and the principles for working with them in hedging various portfolio positions and counterparties. We can quite often encounter a situation when we need to have a perfect hedge for our customer’s (end user consuming electricity portfolio, or we have to evaluate the volumetric risk (inability of a customer to predict consumption, which is very similar to selling options. Now comes the moment to compare the effects of using options or futures to hedge these open positions. From a practical viewpoint, the Black-Scholes prices appear to be the best available and the simplest method for evaluating option premiums, but there are some limitations that we have to consider.

  7. Analytic American Option Pricing and Applications

    OpenAIRE

    Sbuelz, A.

    2003-01-01

    I use a convenient value breakdown in order to obtain analytic solutions for finitematurity American option prices.Such a barrier-option-based breakdown yields an analytic lower bound for the American option price, which is as price-tight as the Barone-Adesi and Whaley (1987) analytic value proxy for short and medium maturities and exhibits good convergence to the Merton (1973) perpetual option price for large maturities.

  8. Option-implied measures of equity risk

    DEFF Research Database (Denmark)

    Chang, Bo-Young; Christoffersen, Peter; Vainberg, Gregory

    2012-01-01

    Equity risk measured by beta is of great interest to both academics and practitioners. Existing estimates of beta use historical returns. Many studies have found option-implied volatility to be a strong predictor of future realized volatility. We find that option-implied volatility and skewness...... are also good predictors of future realized beta. Motivated by this finding, we establish a set of assumptions needed to construct a beta estimate from option-implied return moments using equity and index options. This beta can be computed using only option data on a single day. It is therefore potentially...

  9. Study of Agricultural Product Options Pricing

    Science.gov (United States)

    HONG, Qiu

    2017-09-01

    China is a large agricultural country, and the healthy development of agriculture is related to the stability of the whole society. The agricultural production and management of agricultural products are confronted with many risks, especially the market risks. Option contract is the object of option market transaction, so it is very important to study the option contract of agricultural products. Option trading separates the risk and profit, so that the trader can avoid the risk while retaining the opportunity to obtain income. The option has the characteristics of low transaction cost, simple and efficient, so it is suitable for small and medium investors.

  10. Treatment Options by Stage (Pancreatic Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  11. Treatment Options by Stage (Esophageal Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  12. Treatment Options by Stage (Vulvar Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  13. Treatment Options by Stage (Penile Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  14. Treatment Options for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... lymphoma may come back as indolent lymphoma. Treatment Option Overview Key Points There are different types of ...

  15. Treatment Options by Stage (Prostate Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  16. Treatment Options by Stage (Adrenocortical Carcinoma)

    Science.gov (United States)

    ... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  17. Treatment Options for Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... the lungs , liver , bones, or bone marrow . Treatment Option Overview Key Points There are different types of ...

  18. Treatment Options for Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  19. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... examination under a microscope. Certain factors affect treatment options and prognosis (chance of recovery). Treatment options depend ... that does not get better with treatment. Treatment Option Overview Key Points There are different types of ...

  20. Hairy Cell Leukemia Treatment Option Overview

    Science.gov (United States)

    ... or a swollen spleen. Certain factors affect treatment options and prognosis (chance of recovery). The treatment options ... cell leukemia has not responded to treatment. Treatment Option Overview Key Points There are different types of ...

  1. Treatment Option Overview (Small Intestine Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  2. Treatment Option Overview (Adult Hodgkin Lymphoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  3. Treatment Option Overview (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  4. Treatment Option Overview (Childhood Hodgkin Lymphoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... the lungs , liver , bones, or bone marrow . Treatment Option Overview Key Points There are different types of ...

  5. Treatment Options for AIDS-Related Lymphoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... nervous system is not primary CNS lymphoma. Treatment Option Overview Key Points There are different types of ...

  6. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  7. Treatment Options for Gastrointestinal Carcinoid Tumors

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... body. Has not gotten better with treatment. Treatment Option Overview Key Points There are different types of ...

  8. Treatment Options by Stage (Gastric Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... such as the liver or lymph nodes . Treatment Option Overview Key Points There are different types of ...

  9. Treatment Options by Stage (Thyroid Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  10. Treatment Options for Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... of blast cells increases after a remission . Treatment Option Overview Key Points There are different types of ...

  11. Evaluating Domestic Hot Water Distribution System Options with Validated Analysis Models

    Energy Technology Data Exchange (ETDEWEB)

    Weitzel, E. [Alliance for Residential Building Innovation, Davis, CA (United States); Hoeschele, E. [Alliance for Residential Building Innovation, Davis, CA (United States)

    2014-09-01

    A developing body of work is forming that collects data on domestic hot water consumption, water use behaviors, and energy efficiency of various distribution systems. Transient System Simulation Tool (TRNSYS) is a full distribution system developed that has been validated using field monitoring data and then exercised in a number of climates to understand climate impact on performance. In this study, the Building America team built upon previous analysis modeling work to evaluate differing distribution systems and the sensitivities of water heating energy and water use efficiency to variations of climate, load, distribution type, insulation and compact plumbing practices. Overall, 124 different TRNSYS models were simulated. The results of this work are useful in informing future development of water heating best practices guides as well as more accurate (and simulation time efficient) distribution models for annual whole house simulation programs.

  12. Validation of TEMP: A finite line heat transfer code for geologic repositories for nuclear waste

    International Nuclear Information System (INIS)

    Atterbury, W.G.; Hetteburg, J.R.; Wurm, K.J.

    1987-09-01

    TEMP is a FORTRAN computer code for calculating temperatures in a geologic repository for nuclear waste. A previous report discusses the structure, usage, verification, and benchmarking of TEMP V1.0 (Wurm et al., 1987). This report discusses modifications to the program in the development of TEMP V1.1 and documents the validation of TEMP. The development of TEMP V1.1 from TEMP V1.0 consisted of two major efforts. The first was to recode several of the subroutines to improve logic flow and to allow for geometry-independent temperature calculation routines which, in turn, allowed for the addition of the geometry-independent validation option. The validation option provides TEMP with the ability to model any geometry of temperature sources with any step-wise heat release rate. This capability allows TEMP to model the geometry and heat release characteristics of the validation problems. The validation of TEMP V1.1 consists of the comparison of TEMP to three in-ground heater tests. The three tests chosen were Avery Island, Louisiana, Site A; Avery Island, Louisiana, Site C; and Asse Mine, Federal Republic of Germany, Site 2. TEMP shows marginal comparison with the two Avery Island sites and good comparison with the Asse Mine Site. 8 refs., 25 figs., 14 tabs

  13. Generalised pustular psoriasis – a case report and review of therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Agnieszka Osmola-Mańkowska

    2014-11-01

    Full Text Available Introduction. Generalised pustular psoriasis (GPP is regarded as a rare clinical subtype of psoriasis. The severity of GPP varies from a benign, chronic course to severe and widespread, life-threatening disease. Due to the uncommon nature of GPP, establishing treatment guidelines for this variant of psoriasis is challenging. Objective. To present the case of a patient with GPP with a short review of therapeutic approaches. Case report. Our patient was treated with standard methods such as acitretin, then cyclosporine and methotrexate as well as with biologic drug – infliximab. During the last and the most severe flare, combination therapy with systemic retinoid and PUVA (Re-PUVA was used. Conclusions. The treatment in GPP should be determined individually according to the severity of the disease, age, gender and comorbidities, as well as according to the physician’s experience with particular methods and their side effects. In addition, the availability of therapeutic options should be taken into consideration.

  14. Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD in midlife and older women

    Directory of Open Access Journals (Sweden)

    Chiara Borghi

    2017-03-01

    Full Text Available Female Sexual Disorders (FSD include a complex, multidimensional, individual experience that can change as an individual age, suggesting that these problems are caused by multiple factors including psychosocial factors, personal relationships, pathologic changes caused by diseases, and pharmacologic influences. Menopause is an important time for middle aged women and postmenopausal physiological changes could have a significant role in the development of FSD. Few is still known about their correct definition and treatment. Their incidence, prevalence and risk factors are difficult to define because of a high level of overlap in the experience of problems with desire, arousal, and orgasm. Little evidences are known about the best therapeutic approach, and both non-pharmacological and pharmacological treatment options have been described. Among these, phosphodiesterase type 5 inhibitors could be an effective option for many subtypes of female sexual disorders, with an improvement in different aspects of sexual function, such as desire, arousal, orgasm and sexual satisfaction. In this paper authors reviewed what is already known about the use of these vasoactive agents, particularly tadalafil, as a treatment option for female sexual disturbances.

  15. Generalized Aggressive Periodontitis and Its Treatment Options: Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    T. Roshna

    2012-01-01

    Full Text Available Generalized aggressive periodontitis results in rapid destruction of the periodontium and can lead to early tooth loss in the affected individuals if not diagnosed early and treated appropriately. The diagnostic features of the disease are characteristic, but the clinical presentation and patterns of destructions may vary between patients. Successful management of the disease is challenging especially if diagnosed at advanced stages of the disease, but not impossible with the current therapeutic choices for the disease. A vast array of treatment modalities is available which can be employed in the treatment of generalized aggressive periodontitis with varying success rates, but a definite guideline for the management is yet to be formulated. However, with the exponential rate of developments in periodontal research, regenerative therapy, tissue engineering, and genetic technologies, the future seems promising in regard to options at managing the disease. This paper attempts to describe the clinical and radiographic diagnostic features and the current treatment options along with a suggested protocol for comprehensive management of generalized aggressive periodontitis patients with case reports and a brief review.

  16. Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2013-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.

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

    Science.gov (United States)

    Guijarro, Carlos; García-Díaz, Juan de Dios

    2013-01-01

    The European Guidelines on Dyslipidaemias (2011) and Cardiovascular Prevention (2012) have incorporated important changes. Firstly, it highlights the identification of a group of "very high risk" patients: patients with atherosclerotic disease in any vascular area, diabetes with associated risk factors, advanced chronic renal failure, or a SCORE estimate >10%. Patients with diabetes and no other risk factors, moderate renal failure, severe hypertension, genetic dyslipidaemias, or a SCORE estimate 5-10%, are considered as "high risk". The HDL cholesterol and triglycerides levels are considered as modulators of risks, but not therapeutic objectives per se. The therapeutic objectives are set at LDL cholesterol levels < 70 mg/dl (or at least a reduction of at least 50%) for patients at very high risk, and an LDL < 100 mg/dl for high risk patients. As well as the changes in lifestyle, pharmacological treatment with statins is the focal point of lipid lowering treatments. Other pharmacological options may be considered if the treatment with the maximum tolerable doses of statins do not achieve the therapeutic objectives. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  18. Assessing climate adaptation options and uncertainties for cereal systems in West Africa

    Science.gov (United States)

    Guan, K.; Sultan, B.; Biasutti, M.; Lobell, D. B.

    2015-12-01

    The already fragile agriculture production system in West Africa faces further challenges in meeting food security in the coming decades, primarily due to a fast increasing population and risks of climate change. Successful adaptation of agriculture should not only benefit in the current climate but should also reduce negative (or enhance positive) impacts for climate change. Assessment of various possible adaptation options and their uncertainties provides key information for prioritizing adaptation investments. Here, based on the several robust aspects of climate projections in this region (i.e. temperature increases and rainfall pattern shifts), we use two well-validated crop models (i.e. APSIM and SARRA-H) and an ensemble of downscaled climate forcing to assess five possible and realistic adaptation options (late sowing, intensification, thermal time increase, water harvesting and increased resilience to heat stress) in West Africa for the staple crop production of sorghum. We adopt a new assessment framework to account for both the impacts of adaptation options in current climate and their ability to reduce impacts of future climate change, and also consider changes in both mean yield and its variability. Our results reveal that most proposed "adaptation options" are not more beneficial in the future than in the current climate, i.e. not really reduce the climate change impacts. Increased temperature resilience during grain number formation period is the main adaptation that emerges. We also find that changing from the traditional to modern cultivar, and later sowing in West Sahel appear to be robust adaptations.

  19. Microneedle physical contact as a therapeutic for abnormal scars.

    Science.gov (United States)

    Yeo, David C; Balmayor, Elizabeth R; Schantz, Jan-Thorsten; Xu, Chenjie

    2017-08-14

    Abnormal (keloid and hypertrophic) scars are a significant affliction with no satisfactory single modality therapy to-date. Available options are often ineffective, painful, potentially hazardous, and require healthcare personnel involvement. Herein a self-administered microneedle device based on drug-free physical contact for inhibiting abnormal scars is reported. Its therapeutic activity through microneedle contact eliminates hazards associated with toxic anti-scarring drugs while self-treatment enables administration flexibility. The microneedle patch was fabricated with FDA-approved liquid crystalline polymer under good manufacturing practice. It was first tested to ascertain its ability to inhibit (keloid) fibroblast proliferation. Later the microneedle patch was examined on the rabbit ear hypertrophic scar model to explore its potential in inhibiting the generation of abnormal scars post-injury. Finally, the microneedle patch was applied to the caudal region of a hypertrophic scar located on a female patient's dorsum to verify clinical efficacy. On untreated control cultures, barely any non-viable fibroblasts could be seen. After 12-h treatment with the microneedle patch, the non-viable proportion increased to 83.8 ± 11.96%. In rabbit ear hypertrophic scar model, 100% of the control wounds without the presence of patches on rabbit ears generated regions of raised dermis originating from the wound site (3/3), whereas microneedle treatment prevented dermis tissue thickening in 83.33% of the wounds (15/18). In the clinical test, the microneedle patch was well tolerated by the patient. Compared to the untreated region, microneedle treatment decreased the number of infiltrated inflammatory cells, with less disrupted dermis tissue architecture and more flattened appearance. A self-administered, drug-free microneedle patch appears highly promising in reducing abnormal scarring as observed from in vitro, in vivo and clinical experiments. Larger cohort clinical

  20. Margin Requirements and Equity Option Returns

    DEFF Research Database (Denmark)

    Hitzemann, Steffen; Hofmann, Michael; Uhrig-Homburg, Marliese

    In equity option markets, traders face margin requirements both for the options themselves and for hedging-related positions in the underlying stock market. We show that these requirements carry a significant margin premium in the cross-section of equity option returns. The sign of the margin...... premium depends on demand pressure: If end-users are on the long side of the market, option returns decrease with margins, while they increase otherwise. Our results are statistically and economically significant and robust to different margin specifications and various control variables. We explain our...... findings by a model of funding-constrained derivatives dealers that require compensation for satisfying end-users’ option demand....

  1. Margin Requirements and Equity Option Returns

    DEFF Research Database (Denmark)

    Hitzemann, Steffen; Hofmann, Michael; Uhrig-Homburg, Marliese

    In equity option markets, traders face margin requirements both for the options themselves and for hedging-related positions in the underlying stock market. We show that these requirements carry a significant "margin premium" in the cross-section of equity option returns. The sign of the margin...... premium depends on demand pressure: If end-users are on the long side of the market, option returns decrease with margins, while they increase otherwise. Our results are statistically and economically significant and robust to different margin specifications and various control variables. We explain our...... findings by a model of funding-constrained derivatives dealers that require compensation for satisfying end-users’ option demand....

  2. Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine

    Science.gov (United States)

    Pauli, Chantal; Hopkins, Benjamin D.; Prandi, Davide; Shaw, Reid; Fedrizzi, Tarcisio; Sboner, Andrea; Sailer, Verena; Augello, Michael; Puca, Loredana; Rosati, Rachele; McNary, Terra J.; Churakova, Yelena; Cheung, Cynthia; Triscott, Joanna; Pisapia, David; Rao, Rema; Mosquera, Juan Miguel; Robinson, Brian; Faltas, Bishoy M.; Emerling, Brooke E.; Gadi, Vijayakrishna K.; Bernard, Brady; Elemento, Olivier; Beltran, Himisha; Dimichelis, Francesca; Kemp, Christopher J.; Grandori, Carla; Cantley, Lewis C.; Rubin, Mark A.

    2017-01-01

    Precision Medicine is an approach that takes into account the influence of individuals' genes, environment and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform, which integrates whole exome sequencing (WES) with a living biobank that enables high throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures, and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an IRB approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high throughput drug screening effective strategies. Analysis of tumor derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted. PMID:28331002

  3. An analysis of international nuclear fuel supply options

    Science.gov (United States)

    Taylor, J'tia Patrice

    . The material movement module is the largest of the three, and the two other modules that assess nonproliferation and economics of the options are dependent on its output. Proliferation resistance measures from literature are modified and incorporated in MEPAT. The module to assess the nonproliferation of the supply options allows the user to specify defining attributes for the fuel cycle processes, and determines significant quantities of materials as well as measures of proliferation resistance. The measure is dependent on user-input and material information. The economics module allows the user to specify costs associated with different processes and other aspects of the fuel cycle. The simulation tool then calculates economic measures that relate the cost of the fuel cycle to electricity production. The second part of this dissertation consists of an examination of four scenarios of fuel supply option using MEPAT. The first is a simple scenario illustrating the modules and basic functions of MEPAT. The second scenario recreates a fuel supply study reported earlier in literature, and compares MEPAT results with those reported earlier for validation. The third, and a rather realistic, scenario includes four nuclear programs with one program entering the nuclear energy market. The fourth scenario assesses the reactor options available to the Hashemite Kingdom of Jordan, which is currently assessing available options to introduce nuclear power in the country. The methodology developed and implemented in MEPAT to analyze the material, proliferation and economics of nuclear fuel supply options is expected to help simplify and assess different reactor and fuel options available to utilities, government agencies and international organizations.

  4. Option Pricing using Realized Volatility

    DEFF Research Database (Denmark)

    Stentoft, Lars Peter

    dynamics to be used for option pricing purposes in this framework, and we show that our model explains some of the mispricings found when using traditional option pricing models based on interdaily data. We then show explicitly that a Generalized Autoregressive Conditional Heteroskedastic model with Normal...... Inverse Gaussian distributed innovations is the corresponding benchmark model when only daily data is used. Finally, we perform an empirical analysis using stock options for three large American companies, and we show that in all cases our model performs significantly better than the corresponding...... benchmark model estimated on return data alone. Hence the paper provides evidence on the value of using high frequency data for option pricing purposes....

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

    Directory of Open Access Journals (Sweden)

    Christopher M. Mahoney

    2018-05-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  7. Americal options analyzed differently

    NARCIS (Netherlands)

    Nieuwenhuis, J.W.

    2003-01-01

    In this note we analyze in a discrete-time context and with a finite outcome space American options starting with the idea that every tradable should be a martingale under a certain measure. We believe that in this way American options become more understandable to people with a good working

  8. Alternative Fuels Data Center: Biodiesel Equipment Options

    Science.gov (United States)

    Equipment Options to someone by E-mail Share Alternative Fuels Data Center: Biodiesel Equipment Options on Facebook Tweet about Alternative Fuels Data Center: Biodiesel Equipment Options on Twitter Bookmark Alternative Fuels Data Center: Biodiesel Equipment Options on Google Bookmark Alternative Fuels

  9. 78 FR 7997 - Noncompensatory Partnership Options

    Science.gov (United States)

    2013-02-05

    ... Noncompensatory Partnership Options AGENCY: Internal Revenue Service (IRS), Department of the Treasury. ACTION... noncompensatory options and convertible instruments issued by a partnership. The final regulations generally provide that the exercise of a noncompensatory option does not cause the recognition of immediate income...

  10. Portfolio insurance using traded options

    OpenAIRE

    Machado-Santos, Carlos

    2001-01-01

    Literature concerning the institutional use of options indicates that the main purpose of option trading is to provide investors with the opportunity to create return distributions previously unavailable, considering that options provide the means to manipulate portfolio returns. In such a context, this study intends to analyse the returns of insured portfolios generated by hedging strategies on underlying stock portfolios. Because dynamic hedging is too expensive, we have hedged the stock po...

  11. 48 CFR 3017.202 - Use of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Use of options. 3017.202... ACQUISITION REGULATION (HSAR) CONTRACT METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options. 3017.202 Use of options. (a) Contracting officers shall not use unpriced options. ...

  12. Equity Portfolio Management Using Option Price Information

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Pan, Xuhui (Nick)

    We survey the recent academic literature that uses option-implied information to construct equity portfolios. Studies show that equity managers can earn a positive alpha by using information in individual equity options, by using stocks' exposure to information in market index options, and by using...... stocks' exposure to crude oil option information. Option-implied information can also help construct better mean-variance portfolios and better estimates of market beta....

  13. Fourier and wavelet option pricing methods

    NARCIS (Netherlands)

    S.C. Maree (Stef); L. Ortiz Gracia (Luis); C.W. Oosterlee (Cornelis); M.A.H. Dempster; J. Kanniainen (Juho); J. Keane (John); E. Vynckier (Erik)

    2018-01-01

    textabstractIn this overview chapter, we will discuss the use of exponentially converging option pricing techniques for option valuation. We will focus on the pricing of European options, and they are the basic instruments within a calibration procedure when fitting the parameters in asset dynamics.

  14. Option trading and individual investor performance

    NARCIS (Netherlands)

    Bauer, R.; Cosemans, M.; Eichholtz, P.

    2009-01-01

    This paper examines the impact of option trading on individual investor performance. The results show that most investors incur substantial losses on their option investments, which are much larger than the losses from equity trading. We attribute the detrimental impact of option trading on investor

  15. American option pricing with stochastic volatility processes

    Directory of Open Access Journals (Sweden)

    Ping LI

    2017-12-01

    Full Text Available In order to solve the problem of option pricing more perfectly, the option pricing problem with Heston stochastic volatility model is considered. The optimal implementation boundary of American option and the conditions for its early execution are analyzed and discussed. In view of the fact that there is no analytical American option pricing formula, through the space discretization parameters, the stochastic partial differential equation satisfied by American options with Heston stochastic volatility is transformed into the corresponding differential equations, and then using high order compact finite difference method, numerical solutions are obtained for the option price. The numerical experiments are carried out to verify the theoretical results and simulation. The two kinds of optimal exercise boundaries under the conditions of the constant volatility and the stochastic volatility are compared, and the results show that the optimal exercise boundary also has stochastic volatility. Under the setting of parameters, the behavior and the nature of volatility are analyzed, the volatility curve is simulated, the calculation results of high order compact difference method are compared, and the numerical option solution is obtained, so that the method is verified. The research result provides reference for solving the problems of option pricing under stochastic volatility such as multiple underlying asset option pricing and barrier option pricing.

  16. The Pricing of Foreign Currency Futures Options

    OpenAIRE

    Chang Mo Ahn

    1996-01-01

    We derive semi-closed form solutions for the forward and futures exchange rates, European foreign currency options, currency forward options, and currency futures options when the domestic and foreign interest rate movements follow mean reverting diffusion processes. These solutions are consistent with the Black-Scholes option formula so that they can be easily applied. The impact of interest rate uncertainty on theoretical prices of currency futures options is too significant to be neglected.

  17. Sporotrichosis: An Overview and Therapeutic Options

    Science.gov (United States)

    Mahajan, Vikram K.

    2014-01-01

    Sporotrichosis is a chronic granulomatous mycotic infection caused by Sporothrix schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss, that is endemic in tropical/subtropical areas. The recent phylogenetic studies have delineated the geographic distribution of multiple distinct Sporothrix species causing sporotrichosis. It characteristically involves the skin and subcutaneous tissue following traumatic inoculation of the pathogen. After a variable incubation period, progressively enlarging papulo-nodule at the inoculation site develops that may ulcerate (fixed cutaneous sporotrichosis) or multiple nodules appear proximally along lymphatics (lymphocutaneous sporotrichosis). Osteoarticular sporotrichosis or primary pulmonary sporotrichosis are rare and occur from direct inoculation or inhalation of conidia, respectively. Disseminated cutaneous sporotrichosis or involvement of multiple visceral organs, particularly the central nervous system, occurs most commonly in persons with immunosuppression. Saturated solution of potassium iodide remains a first line treatment choice for uncomplicated cutaneous sporotrichosis in resource poor countries but itraconazole is currently used/recommended for the treatment of all forms of sporotrichosis. Terbinafine has been observed to be effective in the treatment of cutaneous sporotrichosis. Amphotericin B is used initially for the treatment of severe, systemic disease, during pregnancy and in immunosuppressed patients until recovery, then followed by itraconazole for the rest of the therapy. PMID:25614735

  18. Sporotrichosis: An Overview and Therapeutic Options

    OpenAIRE

    Mahajan, Vikram K.

    2014-01-01

    Sporotrichosis is a chronic granulomatous mycotic infection caused by Sporothrix schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss, that is endemic in tropical/subtropical areas. The recent phylogenetic studies have delineated the geographic distribution of multiple distinct Sporothrix species causing sporotrichosis. It characteristically involves the skin and subcutaneous tissue following traumatic inoculation of the pathogen. After a variable incubation period, p...

  19. 48 CFR 317.207 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Exercise of options. 317... METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 317.207 Exercise of options. (h) Before exercising an option for a subsequent performance period/additional quantity under a multiple-year contract...

  20. 48 CFR 1517.207 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Exercise of options. 1517... CONTRACTING METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 1517.207 Exercise of options. (a) Unless otherwise approved by the Chief of the Contracting Office, contracts for services employing option...

  1. 24 CFR 982.636 - Homeownership option: Portability.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Portability... Types Homeownership Option § 982.636 Homeownership option: Portability. (a) General. A family may... described in §§ 982.353 and 982.355 apply to the homeownership option and the administrative...

  2. Hematopoietic stem cells transplant in patients with common variable immunodeficiency. Is a therapeutic option?

    Directory of Open Access Journals (Sweden)

    Julio César Cambray-Gutiérrez

    2017-02-01

    Full Text Available Background: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality. Clinical case: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood. At adolescence, she was diagnosed with common variable immunodeficiency; she was prescribed intravenous gamma-globulin, broad-spectrum antimicrobials and macrolides. At 22 years of age, she underwent hematopoietic stem cell transplantation owing to continued severe infections. At 4 months, post-transplantation she was diagnosed with hypothyroidism and ovarian insufficiency. During the following 3 years, she had no infections, but at 25 years of age she had immune thrombocytopenic purpura diagnosed, which persists together with Raynaud’s disease and upper respiratory tract persistent infections. At the moment of this report she is being treated with intravenous gamma-globulin and receiving prophylaxis with clarithromycin, without steroids or danazol. Conclusions: Given the high rate of morbidity and mortality associated and immune reconstitution failure, hematopoietic stem cell transplantation should be carefully evaluated in patients with treatment-unresponsive infections or lymphoproliferative disorders.

  3. Heterogeneous Beliefs, Public Information, and Option Markets

    DEFF Research Database (Denmark)

    Qin, Zhenjiang

    In an incomplete market setting with heterogeneous prior beliefs, I show that public information and strike price of option have substantial infl‡uence on asset pricing in option markets, by investigating an absolute option pricing model with negative exponential utility investors and normally...... distributed dividend. I demonstrate that heterogeneous prior variances give rise to the economic value of option markets. Investors speculate in option market and public information improves allocational efficiency of markets only when there is heterogeneity in prior variance. Heterogeneity in mean is neither...... a necessary nor sufficient condition for generating speculations in option markets. With heterogeneous beliefs, options are non-redundant assets which can facilitate side-betting and enable investors to take advantage of the disagreements and the differences in con…dence. This fact leads to a higher growth...

  4. 48 CFR 3417.207 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Exercise of options. 3417... REGULATION CONTRACTING METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 3417.207 Exercise of options. If any provision in a contract requires that an option may only be exercised within a specified...

  5. 48 CFR 17.207 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Exercise of options. 17... METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 17.207 Exercise of options. (a) When exercising an option, the contracting officer shall provide written notice to the contractor within the time...

  6. 48 CFR 817.202 - Use of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Use of options. 817.202... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 817.202 Use of options. All solicitations... four one-year renewal options as prescribed in FAR Subpart 17.2. The contracting officer must forward...

  7. 48 CFR 536.270 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Exercise of options. 536... Construction 536.270 Exercise of options. (a) If exercising an option, notify the contractor, in writing, within the time period specified in the contract. (b) Exercise options only after determining that all...

  8. Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.

    Science.gov (United States)

    Jung, Jinmyung; Kwon, Mijin; Bae, Sunghwa; Yim, Soorin; Lee, Doheon

    2018-03-05

    Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards

  9. Analytic American Option Pricing and Applications

    NARCIS (Netherlands)

    Sbuelz, A.

    2003-01-01

    I use a convenient value breakdown in order to obtain analytic solutions for finitematurity American option prices.Such a barrier-option-based breakdown yields an analytic lower bound for the American option price, which is as price-tight as the Barone-Adesi and Whaley (1987) analytic value proxy

  10. 48 CFR 517.202 - Use of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Use of options. 517.202... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 517.202 Use of options. (a) Supplies or services. (1) You should use options when they meet one or more of the following objectives: (i) Reduce...

  11. 48 CFR 217.207 - Exercise of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Exercise of options. 217..., DEPARTMENT OF DEFENSE CONTRACTING METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 217.207 Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only after...

  12. 48 CFR 17.202 - Use of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Use of options. 17.202... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 17.202 Use of options. (a) Subject to the..., the contracting officer may include options in contracts when it is in the Government's interest. When...

  13. 32 CFR 644.168 - Exercise of options.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Exercise of options. 644.168 Section 644.168... ESTATE HANDBOOK Acquisition Procurement of Options Prior to Real Estate Directives (military) § 644.168 Exercise of options. Upon issuance of a real estate directive for acquisition of the optioned real property...

  14. Tank Space Options Report

    International Nuclear Information System (INIS)

    BOYLES, V.C.

    2001-01-01

    A risk-based priority for the retrieval of Hanford Site waste from the 149 single-shell tanks (SSTs) has been adopted as a result of changes to the Hanford Federal Facility Agreement and Consent Order (HFFACO) (Ecology et al. 1997) negotiated in 2000. Retrieval of the first three tanks in the retrieval sequence fills available capacity in the double-shell tanks (DSTs) by 2007. As a result, the HFFACO change established a milestone (M-45-12-TO1) requiring the determination of options that could increase waste storage capacity for single-shell tank waste retrieval. The information will be considered in future negotiations. This document fulfills the milestone requirement. This study presents options that were reviewed for the purpose of increasing waste storage capacity. Eight options are identified that have the potential for increasing capacity from 5 to 10 million gallons, thus allowing uninterrupted single-shell tank retrieval until the planned Waste Treatment Plant begins processing substantial volumes of waste from the double-shell tanks in 2009. The cost of implementing these options is estimated to range from less than $1 per gallon to more than $14 per gallon. Construction of new double-shell tanks is estimated to cost about $63 per gallon. Providing 5 to 10 million gallons of available double-shell tank space could enable early retrieval of 5 to 9 high-risk single-shell tanks beyond those identified for retrieval by 2007. These tanks are A-101, AX-101, AX-103, BY-102, C-107, S-105, S-106, S-108, and S-109 (Garfield et al. 2000). This represents a potential to retrieve approximately 14 million total curies, including 3,200 curies of long-lived mobile radionuclides. The results of the study reflect qualitative analyses conducted to identify promising options. The estimated costs are rough-order-of magnitude and, therefore, subject to change. Implementing some of the options would represent a departure from the current baseline and may adversely impact the

  15. Budget Options

    National Research Council Canada - National Science Library

    2000-01-01

    This volume-part of the Congressional Budget Office's (CBO's) annual report to the House and Senate Committees on the Budget-is intended to help inform policymakers about options for the federal budget...

  16. Treatment Options for Actinic Keratosis

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends mostly on ... helped by lip balm or petroleum jelly . Treatment Option Overview Key Points There are different types of ...

  17. Treatment Option Overview (Vaginal Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on the ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  18. Treatment Option Overview (Anal Cancer)

    Science.gov (United States)

    ... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on the ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  19. 24 CFR 221.775 - Option period.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Option period. 221.775 Section 221.775 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... § 221.775 Option period. The mortgagee may exercise its option to assign within one year following the...

  20. 24 CFR 221.770 - Assignment option.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Assignment option. 221.770 Section... § 221.770 Assignment option. A mortgagee holding a conditional or firm commitment issued on or before... mortgagee's approved underwriter on or before November 30, 1983) has the option to assign, transfer and...

  1. 48 CFR 2917.202 - Use of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Use of options. 2917.202... CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 2917.202 Use of options. The HCA may, in unusual circumstances, approve option quantities in excess of the 50 percent limit prescribed in FAR 17.203(g)(2). The...

  2. Alternative energy options

    International Nuclear Information System (INIS)

    Bennett, K.F.

    1983-01-01

    It is accepted that coal will continue to play the major role in the supply of energy to the country for the remainder of the century. In this paper, however, emphasis has been directed to those options which could supplement coal in an economic and technically sound manner. The general conclusion is that certain forms of solar energy hold the most promise and it is in this direction that research, development and implementation programmes should be directed. Tidal energy, fusion energy, geothermal energy, hydrogen energy and fuel cells are also discussed as alternative energy options

  3. Validating data quality during wet weather monitoring of wastewater treatment plant influents

    DEFF Research Database (Denmark)

    Alferes, Janelcy; Lynggaard-Jensen, Anders; Munk-Nielsen, Thomas

    Efficient monitoring of water systems and proper use of the collected data in further applications such as modelling, forecasting influent water quality and real-time control depends on careful data quality control. Given the size of the data sets produced nowadays in online water quality...... monitoring schemes, automated data validation is the only feasible option. In this paper, software tools for automatic data quality assessment with a practical orientation are presented. The developments from three organizations ranging from simple to more complex methods for automated data validation...

  4. 42 CFR 457.70 - Program options.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Program options. 457.70 Section 457.70 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.70 Program options. (a) Health benefits coverage options. A State may elect to obtain health benefits coverage under its plan through— (1...

  5. 24 CFR 221.255 - Assignment option.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Assignment option. 221.255 Section... Assignment option. (a) A mortgagee holding a mortgage insured pursuant to a conditional or firm commitment issued on or before November 30, 1983 has the option to assign, transfer and deliver to the Commissioner...

  6. Expensing stock options: a fair-value approach.

    Science.gov (United States)

    Kaplan, Robert S; Palepu, Krishna G

    2003-12-01

    Now that companies such as General Electric and Citigroup have accepted the premise that employee stock options are an expense, the debate is shifting from whether to report options on income statements to how to report them. The authors present a new accounting mechanism that maintains the rationale underlying stock option expensing while addressing critics' concerns about measurement error and the lack of reconciliation to actual experience. A procedure they call fair-value expensing adjusts and eventually reconciles cost estimates made at grant date with subsequent changes in the value of the options, and it does so in a way that eliminates forecasting and measurement errors over time. The method captures the chief characteristic of stock option compensation--that employees receive part of their compensation in the form of a contingent claim on the value they are helping to produce. The mechanism involves creating entries on both the asset and equity sides of the balance sheet. On the asset side, companies create a prepaid-compensation account equal to the estimated cost of the options granted; on the owners'-equity side, they create a paid-in capital stock-option account for the same amount. The prepaid-compensation account is then expensed through the income statement, and the stock option account is adjusted on the balance sheet to reflect changes in the estimated fair value of the granted options. The amortization of prepaid compensation is added to the change in the option grant's value to provide the total reported expense of the options grant for the year. At the end of the vesting period, the company uses the fair value of the vested option to make a final adjustment on the income statement to reconcile any difference between that fair value and the total of the amounts already reported.

  7. 48 CFR 217.202 - Use of options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Use of options. 217.202... OF DEFENSE CONTRACTING METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 217.202 Use of options. (1) See PGI 217.202 for guidance on the use of options. (2) See 234.005-1 for limitations on the...

  8. 48 CFR 252.217-7001 - Surge option.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Surge option. 252.217-7001... Clauses 252.217-7001 Surge option. As prescribed in 217.208-70(b), use the following clause: Surge Option (AUG 1992) (a) General. The Government has the option to— (1) Increase the quantity of supplies or...

  9. Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma.

    Science.gov (United States)

    Jensen, D H; Dabelsteen, E; Specht, L; Fiehn, A M K; Therkildsen, M H; Jønson, L; Vikesaa, J; Nielsen, F C; von Buchwald, C

    2015-08-01

    Although tumour budding is an adverse prognostic factor for many cancer types, the molecular mechanisms governing this phenomenon are incompletely understood. Therefore, understanding the molecular basis of tumour budding may provide new therapeutic and diagnostic options. We employ digital image analysis to demonstrate that the number of tumour buds in cytokeratin-stained sections correlates with patients having lymph node metastases at diagnosis. The tumour bud count was also a predictor of overall survival, independent of TNM stage. Tumour buds and paired central tumour areas were subsequently collected from oral squamous cell carcinoma (OSCC) specimens, using laser capture microdissection, and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature, comprising factors involved in epithelial-mesenchymal transition (EMT) and activated TGFβ signalling. Transcription factors ZEB1 and PRRX1 were up-regulated concomitantly with the decreased expression of mesenchymal-epithelial (MET) transcription factors (eg OVOL1) in addition to Krüppel-like factors and Grainyhead-like factors. Moreover, miR-200 family members were down-regulated in budding tumour cells. We used immunohistochemistry to validate five markers of the EMT/MET process in 199 OSCC tumours, as well as in situ hybridization in 20 OSCC samples. Given the strong relationship between tumour budding and the development of lymph node metastases and an adverse prognosis, therapeutics based on inhibiting the activation of TGFβ signalling may prove useful in the treatment of OSCC. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

    Directory of Open Access Journals (Sweden)

    Kyeung Min Joo

    Full Text Available Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

  11. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles

    Directory of Open Access Journals (Sweden)

    Jingga Morry

    2017-04-01

    Full Text Available Oxidative stress, mainly contributed by reactive oxygen species (ROS, has been implicated in pathogenesis of several diseases. We review two primary examples; fibrosis and cancer. In fibrosis, ROS promote activation and proliferation of fibroblasts and myofibroblasts, activating TGF-β pathway in an autocrine manner. In cancer, ROS account for its genomic instability, resistance to apoptosis, proliferation, and angiogenesis. Importantly, ROS trigger cancer cell invasion through invadopodia formation as well as extravasation into a distant metastasis site. Use of antioxidant supplements, enzymes, and inhibitors for ROS-generating NADPH oxidases (NOX is a logical therapeutic intervention for fibrosis and cancer. We review such attempts, progress, and challenges. Lastly, we review how nanoparticles with inherent antioxidant activity can also be a promising therapeutic option, considering their additional feature as a delivery platform for drugs, genes, and imaging agents.

  12. Ozone-augmented percutaneous discectomy: a novel treatment option for refractory discogenic sciatica.

    Science.gov (United States)

    Crockett, M T; Moynagh, M; Long, N; Kilcoyne, A; Dicker, P; Synnott, K; Eustace, S J

    2014-12-01

    To assess the short and medium-term efficacy and safety of a novel, minimally invasive therapeutic option combining automated percutaneous lumbar discectomy, intradiscal ozone injection, and caudal epidural: ozone-augmented percutaneous discectomy (OPLD). One hundred and forty-seven patients with a clinical and radiological diagnosis of discogenic sciatica who were refractory to initial therapy were included. Fifty patients underwent OPLD whilst 97 underwent a further caudal epidural. Outcomes were evaluated using McNab's score, improvement in visual analogue score (VAS) pain score, and requirement for further intervention. Follow-up occurred at 1 and 6 months, and comparison was made between groups. OPLD achieved successful outcomes in almost three-quarters of patients in the short and medium term. OPLD achieved superior outcomes at 1 and 6 months compared to caudal epidural. There was a reduced requirement for further intervention in the OPLD group. No significant complications occurred in either group. OPLD is a safe and effective treatment for patients with refractory discogenic sciatica in the short and medium term. OPLD has the potential to offer an alternative second-line minimally invasive treatment option that could reduce the requirement for surgery in this patient cohort. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  13. Recomendaciones terapéuticas en la insuficiencia cardíaca Therapeutic recommendations in heart failure

    Directory of Open Access Journals (Sweden)

    Annery Luis Martínez

    2003-12-01

    Full Text Available Se presentan algunas recomendaciones terapéuticas para el tratamiento de la insuficiencia cardíaca (IC. Esta se ha convertido en un creciente problema de salud, debido al envejecimiento poblacional y al aumento de la supervivencia de las pacientes cardiópatas. Las opciones terapéuticas que se aconsejan están encaminadas a lograr una mejor calidad de vida del paciente, para lo cual es vital el entendimiento de los procesos fisiopatológicos de esta enfermedad.Some therapeutic recommendations for the treatment of heart failure are made. It has become an increasing health problem due to the population aging and to the rise of survival among cardiopathic patients. The recommended therapeutic options are directed to attain a better quality of life of the patients, for which the comprehension of the physiopathological processes of this disease is vital.

  14. Transportation Options | Climate Neutral Research Campuses | NREL

    Science.gov (United States)

    Transportation Options Transportation Options Transportation to, from, and within a research campus from business travel often enlarge the footprint more than expected. To understand options for climate

  15. Non conventional psychiatric rehabilitation in schizophrenia using therapeutic riding: the FISE multicentre Pindar project

    Directory of Open Access Journals (Sweden)

    Stefania Cerino

    2011-12-01

    Full Text Available The FISE (Federazione Italiana Sport Equestri Pindar is a multicentre research project aimed at testing the potential effects of therapeutic riding on schizophrenic patients. Twenty-four subjects with a diagnosis of schizophrenia were enrolled for a 1 year-treatment involving therapeutic riding sessions. All subjects were tested at the beginning and at the end of treatment with a series of validated test batteries (BPRS and 8 items-PANSS. The results discussed in this paper point out an improvement in negative symptoms, a constant disease remission in both early onset and chronic disease subjects, as well as a reduced rate of hospitalization.

  16. Westinghouse Owners Group Risk-Informed Regulation Efforts: Options 2 and 3

    International Nuclear Information System (INIS)

    Brown, Jason A.; Osterrieder, Robert A.; Lutz, Robert J.; Dingler, Maurice; Ward, Lewis A.

    2002-01-01

    The U.S. Nuclear Regulatory Commission (NRC) has initiated efforts to incorporate risk-informed methods to redefine the scope of the existing 10 CFR 50 regulations (Option 2) and to change the technical requirements of the regulations (Option 3). The overall objectives of these efforts are to enhance plant safety, provide a framework for risk-informed regulations, add flexibility to plant operations, and reduce regulatory burden. The Westinghouse Owners Group (WOG) has a variety of active programs in the risk-informed area, including a program in the Option 2 and Option 3 areas. These two programs will be summarized including the benefits and the technical approach. The purpose of Option 2 is to make changes to the overall scope of structures, systems and components (SSCs) covered by 10 CFR 50 requiring special treatment by formulating new risk-informed safety classification categories that are linked to current definitions of safety-related and important-to-safety. This initiative would permit possible changes to the current special treatment requirements based on risk insights. The Nuclear Energy Institute (NEI) has developed an Option 2 implementation guideline (NEI 00-04 Draft Revision B). The WOG has initiated a program to validate the NEI guideline and to provide an initial cost-benefit assessment of the revised categorization and treatment under Option 2 via trial application to two systems at both Surry Unit 1 and Wolf Creek. The WOG Option 2 program includes consideration of all of the components in the selected systems, regardless of whether or not they are modeled in the respective plant probabilistic risk assessment (PRA) studies. As a result, quantitative risk measures are not available for many of the components being considered. In this case, the WOG program will provide valuable input to the NEI guideline. Additionally, the WOG program extends the use of both of the dominant methodologies for risk-informed ISI (RI-ISI) to address repair and

  17. Pricing American and Asian Options

    OpenAIRE

    Pat Muldowney

    2015-01-01

    An analytic method for pricing American call options is provided; followed by an empirical method for pricing Asian call options. The methodology is the pricing theory presented in "A Modern Theory of Random Variation", by Patrick Muldowney, 2012.

  18. Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

    Science.gov (United States)

    Alsharif, Naser Z.; And Others

    1997-01-01

    Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

  19. THE REAL OPTIONS OF CAPITAL BUDGET

    Directory of Open Access Journals (Sweden)

    Antonio Lopo Martins

    2008-07-01

    Full Text Available The traditional techniques of capital budget, as the deducted cash flow and the net value present, do not incorporate existing flexibilities in an investment project, they tend to distort the value of certain investments, mainly those that are considered in scenes of uncertainty and risk. Therefore, this study intends to demonstrate that the Real Options Theory (TOR is a useful methodology to evaluate and to indicate the best option for project of expansion investment. To reach the considered objective the procedure method was used a case study, having as unit of case the Resort Praia Hotel do Litoral Norte of Salvador. This study was developed of the following form: first it identified the traditional net value present and later it was incorporated the volatileness of each analyzed uncertainty. Second, as the real options are analogous to the financial options, it was necessary to identify elements that composed the terminologies of the financial options with intention to get the value of the real option. For this model of options pricing of Black & Scholes jointly with a computational simulator was used (SLS to get the expanded net value present. As a result of this study it was possible to evidence that using the traditional tool of capital budget Net Value Present (VPL is negative, therefore the project of expansion of the Hotel would be rejected. While for the application of methodology TOR the project presents positive Expanded Present Value which would represent an excellent chance of investment. Key-word: Capital budget, Real options, Analysis of investments.

  20. Management of hypertriglyceridemia induced acute pancreatitis and therapeutic plasmapheresis : Report of nine cases and review of literature.

    Science.gov (United States)

    Uyar, S; Harmandar, F; Kök, M; Taș, Z; Dolu, S; Tokuç, A; Köker, G; Görar, S; Çekin, A H

    2017-01-01

    Hypertriglyceridemia is one of the rare causes of the acute pancreatitis. The prevalance of hypertriglyceridemia has increased recently due to the changing eating habits, sedentary lifestyle, alcohol consumption, obesity and concomitant diabetes mellitus. Therefore, the frequency of the acute pancreatitis due to hypertriglyceridemia may increase in coming years. Diagnosis of the acute pancreatitis by hypertriglyceridemia can be overlooked easily and may be very severe if untreated accurately on time. In addition to the standard management of pancreatitis, specific treatment for hypertriglyceridemia that is insulin, heparin and anti-hypertriglyceridemic drugs are used. Therapeutic plasmapheresis is the last treatment option and seems the most effective one in this subject through developing device and membrane technologies when we review the current literature. Not only triglycerides but also proinflammatory cytokines and adhesion molecules that play an active role in pathogenesis are removed by plasmapheresis. So, the effectiveness of treatment appears promising. However, the exact pathophysiology of hypertriglyceridemia-induced pancreatitis could not be fully understood and the majority of published experience comes from the case reports and the benefit of randomized clinical trials is not available. Therefore, there are no data about what are the exact indications and when we start therapeutic plasmapheresis in literature. This manuscript describes our hospital experience with treatment options and analyzes reports published recently about plasmapheresis as a treatment modality for hypertriglyceridemia induced acute pancreatitis. © Acta Gastro-Enterologica Belgica.

  1. 45 CFR 1306.33 - Home-based program option.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Home-based program option. 1306.33 Section 1306.33... PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.33 Home-based program option. (a) Grantees implementing a home-based program option must: (1) Provide one home...

  2. Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches?

    Science.gov (United States)

    Phillip, Harris; Okewole, Idris; Chilaka, Victor

    2014-06-01

    Urethral pain syndrome has had several sobriquets, which have led to much confusion over the existence of this pathological condition and the useful options in the care of the afflicted patient. Our aim was to explore the proposed etiologies of this syndrome, and to provide a critical analysis of each proposed etiology and present a balanced argument on the plausibility of the proposed etiology and therapeutic approaches. We carried out an English language electronic search in the following databases: Medline, Embase, Amed, Cinahl, Pubmed, Cochrane Library, Trip Database and SUMSearch using the following search terms: urethral syndrome, urethral diseases, urethra, urologic diseases etiology/etiology, presentation, treatment, outcome, therapeutics and treatment from 1951 to 2011. In excess of 200 articles were recovered. With the clearly defined objectives of analyzing the proposed etiologies and therapeutic regimes, two author(s) (HP and IO) perused the abstracts of all the recovered articles, selecting those that addressed the etiologies and therapeutic approaches to treating the urethral pain syndrome. The number of articles was reduced to 25. The full text of all 25 articles were retrieved and reviewed. Through the present article, we hope to elucidate the most probable etiology of this condition whilst simultaneously, advance a logical explanation for the apparent success in the treatment of this condition using a range of different therapeutic modalities. We have carried out a narrative review, which we hope will reduce some of the confusion around this clinical entity by combining the known facts about the disease. © 2014 The Japanese Urological Association.

  3. Lumbar sympathectomy under CT guidance: therapeutic option in critical limb ischaemia; la simpaticolisi TC guidata: alternativa terapeutica delle ischemie critiche

    Energy Technology Data Exchange (ETDEWEB)

    Pieri, Stefano; Agresti, Paolo [Az. Osp. S. Camillo-Forlanini, Roma (Italy). U.O. di radiologia vascolare ed interventistica; Ialongo, Pasquale; Fedeli, Stefano [Radiologia diagnostica Busi, Roma (Italy); Di Cesare, Fabio; Ricci, Guiseppe [Az. Osp. S. Camillo-Forlanini, Roma (Italy). Chirurgia vascolare

    2005-04-01

    Purpose: Lumbar sympathectomy is a complementary therapeutic option for patients with severe peripheral vascular occlusive disease presenting rest pain or gangrene and not eligible for surgical revascularisation. Traditional surgical sympathectomy was widely used in the past. However, due to its invasive character, it has increasingly been replaced by percutaneous techniques and, in some recent cases, by laparoscopic procedures. Percutaneous lumbar sympathectomy is a safe, cost-effective and widely available treatment option. We report our experience on 19 patients subjected to percutaneous sympathectomy under CT guidance. Materials and methods: Between 1998 and 2000, 19 patients underwent percutaneous sympathectomy under CT guidance. All patients had severe vascular disease of the lower extremities (Fontaine stage IV), with rest pain and gangrene. They were not eligible for surgical revascularization. Phenol was injected at the level of L2 and L4 using two 22 G needles (15 cm long). Signs of interrupted sympathetic activity usually occur 2'-15' after the procedure with warmth and flushing and dryness of the lower extremities. Results: Percutaneous sympathectomy under CT guidance is a simple, safe and well-tolerated procedure with a low rate of complications. Of the 19 patients, 9 (47.3%) showed clinical improvement, whereas 5 experienced a worsening of ischaemia in the month immediately following the procedure. Discussion: Results suggest that percutaneous lumbar sympathectomy causes a sympathetic blockade in patients with advanced vascular disease of the limb. CT guidance ensures a high level of precision in drug dosing, thus lowering the risk of complications. Although the results are demoralizing. the impossibility of achieving surgical revascularisation in advanced peripheral arteriosclerosis enhances the role of Ct-guided percutaneous sympathectomy in relieving rest pain and healing ulcers in order to postpone the amputation. [Italian] Scopo: La

  4. Validity of the Working Alliance Inventory within Child Protection Services

    Science.gov (United States)

    Killian, Michael; Forrester, Donald; Westlake, David; Antonopoulou, Paraskevi

    2017-01-01

    The Working Alliance Inventory remains a widely studied measure of quality of therapeutic relationships between the practitioner and client. No prior study has examined the psychometrics and validity of the Working Alliance Inventory-Short (WAI-S) in a sample of families, social workers, and trained observers within child protection services.…

  5. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    failure, due to bacteria with coexistent macrolide-associated and fluoroquinolone-associated resistance mutations, were recently published by Australian investigators. Pristinamycin and solithromycin may be of clinical benefit for such multidrug-resistant infections. Further clinical studies are required to determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. Keywords: Mycoplasma genitalium, non-gonococcal urethritis, macrolide, fluoroquinolone, resistance, treatment failure

  6. The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Giuseppe Campolongo

    2016-06-01

    Conclusions: The association of a nutraceutical and simvastatin 20 mg may be a valid therapeutic option for the treatment of hyperlipidemia in patients with ischemic heart disease intolerant to statin at high doses, in the absence of side effects. Further studies are needed to clarify the mechanisms of action of nutraceuticals.

  7. Taxing Options: Do Ceos Respond To Favorable Tax Treatment Of Stock Options?

    OpenAIRE

    Martin Gritsch; Tricia Coxwell Snyder

    2007-01-01

    CEO stock option compensation increased tremendously during the 1990s. During this period, the spread between the marginal income and capital gains tax rates increased substantially, creating the potential for tax avoidance. Using ExecuComp data from 1992-2000, we estimate CEOs’ responsiveness to changes in these tax rates. Our findings show that an increase in the marginal income and a decrease in the capital gains tax rate create a significant increase in stock option compensation. Furtherm...

  8. Thermal test options

    International Nuclear Information System (INIS)

    Koski, J.A.; Keltner, N.R.; Sobolik, K.B.

    1993-02-01

    Shipping containers for radioactive materials must be qualified to meet a thermal accident environment specified in regulations, such at Title 10, Code of Federal Regulations, Part 71. Aimed primarily at the shipping container design, this report discusses the thermal testing options available for meeting the regulatory requirements, and states the advantages and disadvantages of each approach. The principal options considered are testing with radiant heat, furnaces, and open pool fires. The report also identifies some of the facilities available and current contacts. Finally, the report makes some recommendations on the appropriate use of these different testing methods

  9. Reasoning with Inductive Argument Test: A Study of Validity and Reliability

    Directory of Open Access Journals (Sweden)

    Mehmet Emrah Karadere

    2013-11-01

    Full Text Available Reasoning with Inductive Argument Test:A Study of Validity and Reliability Objective: The aim of our study is to research reliability and validity and to evaluate the usability of Turkish version of Reasoning with Inductive Argument Test (RIAT in Turkish healty population. Method: 51 healty volunteers who work in Ankara Dıskapi Yildirim Beyazit Research and Training Hospital participated in this study. Reasoning with Inductive Argument Test (RIAT was translated into Turkish by three clinical good knowledge of English. Participants were given a sociodemographic data form, and RIAT were performed by clinicians. To test the reliability of the Turkish version of RIAT, Cronbach’s alpha coefficient was calculated and the halving method was used for the test. Results: The internal consistency of the Reasoning with Inductive Argument Test (RIAT items, Cronbach’s alpha internal consistency coefficient measurements of 0.73 was found to be statistically significant. Spearman-Brown coefficient that determines the reliability of the whole test r=0.74 was found. Kurtosis values of all the items was below 1.5 and the percentages in the second evaluation were mainly lower. At the same time, both change in belief between self produced RIAT options and given RIAT options (p=0.02, z=-2296 as well as changes in beliefs between related and unrelated items for Obsessive Compulsive Disorder (OCD difference (p=0.03, z=-2.199 were significant. Conclusion: The preliminary data obtained from the study of reliability and validity of the scale shows that ‘Reasoning with Inductive Argument Test’ supports reliability and validity in Turkish population.

  10. Systematic Review of the Diagnostic Accuracy and Therapeutic Effectiveness of Sacroiliac Joint Interventions.

    Science.gov (United States)

    Simopoulos, Thomas T; Manchikanti, Laxmaiah; Gupta, Sanjeeva; Aydin, Steve M; Kim, Chong Hwan; Solanki, Daneshvari; Nampiaparampil, Devi E; Singh, Vijay; Staats, Peter S; Hirsch, Joshua A

    2015-01-01

    The sacroiliac joint is well known as a cause of low back and lower extremity pain. Prevalence estimates are 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis based on multiple diagnostic studies and systematic reviews. However, at present there are no definitive management options for treating sacroiliac joint pain. To evaluate the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. A systematic review of the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. The available literature on diagnostic and therapeutic sacroiliac joint interventions was reviewed. The quality assessment criteria utilized were the Quality Appraisal of Reliability Studies (QAREL) checklist for diagnostic accuracy studies, Cochrane review criteria to assess sources of risk of bias, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) criteria for randomized therapeutic trials and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for observational therapeutic assessments. The level of evidence was based on a best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data sources included relevant literature published from 1966 through March 2015 that were identified through searches of PubMed and EMBASE, manual searches of the bibliographies of known primary and review articles, and all other sources. For the diagnostic accuracy assessment, and for the therapeutic modalities, the primary outcome measure of pain relief and improvement in functional status were utilized. A total of 11 diagnostic accuracy studies and 14 therapeutic studies were included. The evidence for diagnostic accuracy is Level II for dual diagnostic blocks with at least 70% pain relief as the criterion

  11. Pricing and Applications of Digital Installment Options

    Directory of Open Access Journals (Sweden)

    Pierangelo Ciurlia

    2012-01-01

    Full Text Available For its theoretical interest and strong impact on financial markets, option valuation is considered one of the cornerstones of contemporary mathematical finance. This paper specifically studies the valuation of exotic options with digital payoff and flexible payment plan. By means of the Incomplete Fourier Transform, the pricing problem is solved in order to find integral representations of the upfront price for European call and put options. Several applications in the areas of corporate finance, insurance, and real options are discussed. Finally, a new type of digital derivative named supercash option is introduced and some payment schemes are also presented.

  12. Treatment Options for Adult Soft Tissue Sarcoma

    Science.gov (United States)

    ... reacts to the light. Certain factors affect treatment options and prognosis (chance of recovery). The treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  13. Treatment Options by Stage (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  14. Treatment Options by Stage (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... examination under a microscope. Certain factors affect treatment options and prognosis (chance of recovery). Treatment options depend ... that does not get better with treatment. Treatment Option Overview Key Points There are different types of ...

  15. Treatment Options for Hodgkin Lymphoma during Pregnancy

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  16. Treatment Option Overview (Adult Soft Tissue Sarcoma)

    Science.gov (United States)

    ... reacts to the light. Certain factors affect treatment options and prognosis (chance of recovery). The treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  17. Treatment Option Overview (Adult Non-Hodgkin Lymphoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... lymphoma may come back as indolent lymphoma. Treatment Option Overview Key Points There are different types of ...

  18. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  19. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... marrow , or other parts of the body. Treatment Option Overview Key Points There are different types of ...

  20. Treatment Options for Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... marrow , or other parts of the body. Treatment Option Overview Key Points There are different types of ...

  1. Treatment Options for Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... back in the blood or bone marrow . Treatment Option Overview Key Points There are different types of ...

  2. Options for human intrusion

    International Nuclear Information System (INIS)

    Bauser, M.; Williams, R.

    1993-01-01

    This paper addresses options for dealing with human intrusion in terms of performance requirements and repository siting and design requirements. Options are presented, along with the advantages and disadvantages of certain approaches. At the conclusion, a conceptual approach is offered emphasizing both the minimization of subjective judgements concerning future human activity, and specification of repository requirements to minimize the likelihood of human intrusion and any resulting, harmful effects should intrusion occur

  3. Aversion to ambiguity and willingness to take risks affect therapeutic decisions in managing atrial fibrillation for stroke prevention: results of a pilot study in family physicians

    Directory of Open Access Journals (Sweden)

    Raptis S

    2017-09-01

    Full Text Available Stavroula Raptis,1,* Jia Ning Chen,2,* Florencia Saposnik,2 Roman Pelyavskyy,2 Andrew Liuni,3 Gustavo Saposnik2,4 On behalf of the Stroke Outcomes Research Canada Working Group (SORCan- www.sorcan.ca 1Applied Health Research Centre, Li Ka Shing Knowledge Institute, 2Stroke Outcomes and Decision Neuroscience Research Unit, Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, 3Medical Department, Boehringer Ingelheim (Canada Ltd., Burlington, ON, Canada; 4Neuroeconomics and Decision Neuroscience, Department of Economics, University of Zurich, Zurich, Switzerland *These authors contributed equally to this work Background: Anticoagulation is the therapeutic paradigm for stroke prevention in patients with atrial fibrillation (AF. It is unknown how physicians make treatment decisions in primary stroke prevention for patients with AF. Objectives: To evaluate the association between family physicians’ risk preferences (aversion risk and ambiguity and therapeutic recommendations (anticoagulation in the management of AF for primary stroke prevention by applying concepts from behavioral economics. Methods: Overall, 73 family physicians participated and completed the study. Our study comprised seven simulated case vignettes, three behavioral experiments, and two validated surveys. Behavioral experiments and surveys incorporated an economic framework to determine risk preferences and biases (e.g., ambiguity aversion, willingness to take risks. The primary outcome was making the correct decision of anticoagulation therapy. Secondary outcomes included medical errors in the management of AF for stroke prevention. Results: Overall, 23.3% (17/73 of the family physicians elected not to escalate the therapy from antiplatelets to anticoagulation when recommended by best practice guidelines. A total of 67.1% of physicians selected the correct therapeutic options in two or more of the three simulated case vignettes. Multivariate

  4. Life on the line: the therapeutic potentials of computer-mediated conversation.

    Science.gov (United States)

    Miller, J K; Gergen, K J

    1998-04-01

    In what ways are computer networking practices comparable to face-to-face therapy? With the exponential increase in computer-mediated communication and the increasing numbers of people joining topically based computer networks, the potential for grass-roots therapeutic (or antitherapeutic) interchange is greatly augmented. Here we report the results of research into exchanges on an electronic bulletin board devoted to the topic of suicide. Over an 11-month period participants offered each other valuable resources in terms of validation of experience, sympathy, acceptance, and encouragement. They also asked provocative questions and furnished broad-ranging advice. Hostile entries were rare. However, there were few communiques that parallel the change-inducing practices more frequent within many therapeutic settings. In effect, on-line dialogues seemed more sustaining than transforming. Further limits and potentials of on-line communication are explored.

  5. Option Panels in Pure-Jump Settings

    DEFF Research Database (Denmark)

    Andersen, Torben Gustav; Fusari, Nicola; Todorov, Viktor

    We develop parametric inference procedures for large panels of noisy option data in the setting where the underlying process is of pure-jump type, i.e., evolve only through a sequence of jumps. The panel consists of options written on the underlying asset with a (different) set of strikes...... specification for the risk-neutral asset return dynamics, the option prices are nonlinear functions of a time-invariant parameter vector and a time-varying latent state vector (or factors). Furthermore, no-arbitrage restrictions impose a direct link between some of the quantities that may be identified from...... the return and option data. These include the so-called jump activity index as well as the time-varying jump intensity. We propose penalized least squares estimation in which we minimize L_2 distance between observed and model-implied options and further penalize for the deviation of model-implied quantities...

  6. Options contracts in the nuclear fuel industry

    International Nuclear Information System (INIS)

    Fuller, D.M.

    1995-01-01

    This article discusses options trading in the nuclear fuels industry. Although there now exists no formal options market in the nuclear industry, flexibilities, or embedded options, are actually quite common in the long-term supply contracts. The value of these flexibilities can be estimated by applying the methods used to evaluate options. The method used is the Black-Scholes Model, and it is applied to a number of examples

  7. An ill-posed problem for the Black-Scholes equation for a profitable forecast of prices of stock options on real market data

    Science.gov (United States)

    Klibanov, Michael V.; Kuzhuget, Andrey V.; Golubnichiy, Kirill V.

    2016-01-01

    A new empirical mathematical model for the Black-Scholes equation is proposed to forecast option prices. This model includes new interval for the price of the underlying stock, new initial and new boundary conditions. Conventional notions of maturity time and strike prices are not used. The Black-Scholes equation is solved as a parabolic equation with the reversed time, which is an ill-posed problem. Thus, a regularization method is used to solve it. To verify the validity of our model, real market data for 368 randomly selected liquid options are used. A new trading strategy is proposed. Our results indicates that our method is profitable on those options. Furthermore, it is shown that the performance of two simple extrapolation-based techniques is much worse. We conjecture that our method might lead to significant profits of those financial insitutions which trade large amounts of options. We caution, however, that further studies are necessary to verify this conjecture.

  8. Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

    NARCIS (Netherlands)

    Garner, C.R.; Park, K.B.; French, N.S.; Earnshaw, C.; Schipani, A.; Selby, A.M.; Byrne, L.; Siner, S.; Crawley, F.P.; Vaes, W.H.J.; Duijn, E. van; ligt, R. de; Varendi, H.; Lass, J.; Grynkiewicz, G.; Maruszak, W.; Turner, M.A.

    2015-01-01

    Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group.

  9. Report on "American Option Pricing and Hedging Strategies"

    OpenAIRE

    Zhang, Jinshan

    2007-01-01

    This paper mainly discusses the American option's hedging strategies via binomialmodel and the basic idea of pricing and hedging American option. Although the essential scheme of hedging is almost the same as European option, small differences may arise when simulating the process for American option holder has more rights, spelling that the option can be exercised at anytime before its maturity. Our method is dynamic-hedging method.

  10. Monte Carlo Simulation of an American Option

    Directory of Open Access Journals (Sweden)

    Gikiri Thuo

    2007-04-01

    Full Text Available We implement gradient estimation techniques for sensitivity analysis of option pricing which can be efficiently employed in Monte Carlo simulation. Using these techniques we can simultaneously obtain an estimate of the option value together with the estimates of sensitivities of the option value to various parameters of the model. After deriving the gradient estimates we incorporate them in an iterative stochastic approximation algorithm for pricing an option with early exercise features. We illustrate the procedure using an example of an American call option with a single dividend that is analytically tractable. In particular we incorporate estimates for the gradient with respect to the early exercise threshold level.

  11. Observing Optional Number in DDC Edition 23

    Directory of Open Access Journals (Sweden)

    Rotmianto Mohamad

    2018-01-01

    Full Text Available Dewey Decimal Classification is a most popular classification system in the world because of its completeness and most up-to-date. There are many optional number in this classification system, although it rarely to be discussed even it is important to known well about that optional number, especially for a librarian as classifier. This paper is a literature study about Dewey Decimal Classification Edition 23, to describe about optional numbers, particularly the number in relationship with Indonesia’s subject and discipline. This paper is to avoid misunderstanding in interpreted about optional number among librarians, especially for who that does not understand well about optional numbers.

  12. Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation

    Science.gov (United States)

    Chang, Katherine; Merideth, Melissa A.; Stratton, Pamela

    2015-01-01

    There is a growing population of women who have or will undergo hematopoietic stem cell transplant for a variety of malignant and benign conditions. Gynecologists play an important role in addressing the gynecologic and reproductive health concerns for these women throughout the transplant process. As women undergo cell transplantation, they should avoid becoming pregnant and are at risk of uterine bleeding. Thus, counseling about and implementing hormonal treatments such as gonadotropin-releasing hormone agonists, combined hormonal contraceptives, and progestin-only methods help to achieve therapeutic amenorrhea and can serve as contraception during the peritransplant period. In this commentary, we summarize the timing, risks and benefits of the hormonal options just prior, during and for the year after hematopoietic stem cell transplantation. PMID:26348182

  13. Acquisitions Through a Behavioral and Real Options Lens

    NARCIS (Netherlands)

    J.C.M. Kil (Joris)

    2013-01-01

    textabstractThis thesis combines four studies that contribute to our understanding of corporate acquisitions by taking a behavioral and real options perspective. Chapter 2 classifies acquisitions based on real option characteristics and shows option type (single vs. compound) and option nature

  14. Quality assurance after process changes of the production of a therapeutic antibody.

    Science.gov (United States)

    Brass, J M; Krummen, K; Moll-Kaufmann, C

    1996-12-01

    Process development for the production of a therapeutic humanised antibody is a very complex operation. It involves recombinant genetics, verification of a strong expression system, gene amplification, characterisation of a stable host cell expression system, optimisation and design of the mammalian cell culture fermentation system and development of an efficient recovery process resulting in high yields and product quality. Rapid progress in the field and the wish of some pharmaceutical companies for outsourcing their production are the driving forces for process changes relatively late in the development phase. This literature survey is aimed at identifying the limits of acceptable process changes in up scaling of the fermentation and down stream processing of biopharmaceuticals and defining the demand in production validation to prove product equivalency and identity of the isolated, purified therapeutic antibody.

  15. Trace levels of innate immune response modulating impurities (IIRMIs synergize to break tolerance to therapeutic proteins.

    Directory of Open Access Journals (Sweden)

    Daniela Verthelyi

    Full Text Available Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

  16. Trace levels of innate immune response modulating impurities (IIRMIs) synergize to break tolerance to therapeutic proteins.

    Science.gov (United States)

    Verthelyi, Daniela; Wang, Vivian

    2010-12-22

    Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs) that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS) and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st) dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

  17. Advances in the proteomic discovery of novel therapeutic targets in cancer

    Directory of Open Access Journals (Sweden)

    Guo S

    2013-10-01

    Full Text Available Shanchun Guo,1 Jin Zou,2 Guangdi Wang3 1Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 2Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA; 3Research Centers in Minority Institutions Cancer Research Program, Xavier University of Louisiana, New Orleans, LA, USA Abstract: Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed. Keywords: proteomics, cancer, therapeutic target, signaling network, tumorigenesis

  18. Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics.

    Science.gov (United States)

    Collongues, Nicolas; Patte-Mensah, Christine; De Seze, Jérôme; Mensah-Nyagan, Ayikoe-Guy; Derfuss, Tobias

    2018-06-01

    Neuroprotection and remyelination are two unmet needs in the treatment of multiple sclerosis (MS). Therapeutic potential has been identified with sexual hormones, supported in women by a decrease in MS activity during the pregnancy, in men by a greater severity of symptoms and a faster progression than in women. Areas covered: The therapeutic effect of testosterone and estrogens is reviewed. Both hormones have demonstrated an anti-inflammatory effect. Testosterone has an effect in protecting neurons in culture against glutamate-induced toxicity and oxidative stress, and stimulates myelin formation and regeneration mediated through the neural androgen receptor. In experimental autoimmune encephalomyelitis model, estrogens significantly decrease inflammation in the central nervous system via ERα, while its action on ERβ leads to myelin and axon reparation. Estriol therapy in two phase 2 trials showed a decrease in clinical disease activity and inflammatory parameters in MRI. However, evidence of a therapeutic effect of testosterone is scarce. Expert commentary: Phase 3 trials with estriol as an add-on supplementation are now mandatory. Testosterone is another candidate to be tested in phase 2 trials. These hormones should be considered as an adjunctive therapy. New validated tools are needed to assess their effect on neuroprotection and remyelination.

  19. Validation of equilibrium tools on the COMPASS tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Urban, J., E-mail: urban@ipp.cas.cz [Institute of Plasma Physics ASCR, Za Slovankou 3, 182 00 Praha 8 (Czech Republic); Appel, L.C. [CCFE, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom); Artaud, J.F. [CEA, IRFM, F-13108 Saint Paul Lez Durance (France); Faugeras, B. [Laboratoire J.A. Dieudonné, UMR 7351, Université de Nice Sophia-Antipolis, Parc Valrose, 06108 Nice Cedex 02 (France); Havlicek, J. [Institute of Plasma Physics ASCR, Za Slovankou 3, 182 00 Praha 8 (Czech Republic); Department of Surface and Plasma Science, Faculty of Mathematics and Physics, Charles University in Prague, V Holešovičkách 2, 180 00 Praha 8 (Czech Republic); Komm, M. [Institute of Plasma Physics ASCR, Za Slovankou 3, 182 00 Praha 8 (Czech Republic); Lupelli, I. [CCFE, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom); Peterka, M. [Institute of Plasma Physics ASCR, Za Slovankou 3, 182 00 Praha 8 (Czech Republic); Department of Surface and Plasma Science, Faculty of Mathematics and Physics, Charles University in Prague, V Holešovičkách 2, 180 00 Praha 8 (Czech Republic)

    2015-10-15

    Highlights: • Three equilibrium codes—EFIT++, FREEBIE and VacTH—have been successfully set up and validated on COMPASS. • FREEBIE can predictively calculate the equilibrium and corresponding poloidal field coil currents. • EFIT++ can reconstruct equilibria generated by FREEBIE from synthetic, optionally noisy diagnostic data. • VacTH is a promising tool for real time plasma shape reconstruction. • Optimized parameters are estimated for EFIT++ and VacTH by a statistical analysis. - Abstract: Various MHD (magnetohydrodynamic) equilibrium tools, some of which being recently developed or considerably updated, are used on the COMPASS tokamak at IPP Prague. MHD equilibrium is a fundamental property of the tokamak plasma, whose knowledge is required for many diagnostics and modelling tools. Proper benchmarking and validation of equilibrium tools is thus key for interpreting and planning tokamak experiments. We present here benchmarks and comparisons to experimental data of the EFIT++ reconstruction code (Appel et al., 2006), the free-boundary equilibrium code FREEBIE (Artaud and Kim, 2012), and a rapid plasma boundary reconstruction code VacTH (Faugeras et al., 2014). We demonstrate that FREEBIE can calculate the equilibrium and corresponding poloidal field (PF) coils currents consistently with EFIT++ reconstructions from experimental data. Both EFIT++ and VacTH can reconstruct equilibria generated by FREEBIE from synthetic, optionally noisy diagnostic data. Hence, VacTH is suitable for real-time control. Optimum reconstruction parameters are estimated.

  20. Evaluation of long-term natural gas marketing agreements: An application of commodity forward and option pricing theory

    International Nuclear Information System (INIS)

    Salahor, G.S.; Laughton, D.G.

    1993-01-01

    Methods that have been empirically validated in the analysis of short-term traded securities are adapted to evaluate long-term natural gas direct-sale contracts. A sample contract is examined from the perspective of the producer, and analyzed as a series of forward and option contracts. The assessment of contract value is based on the gas price forecast, the volatility in that forecast, and the valuation of risk caused by that volatility. The method presented allows the gas producer to quantify these elements, and to evaluate the variety of terms encountered in direct-sale natural gas agreements, including features such as load factors and penalty charges. The analysis uses as inputs a probabilistic price forecast and a determination of a price of risk for gas prices. Once the forecast volatility is derived from the probabilistic forecast, the forward contracts imbedded in the long-term gas contract can be valued with a risk-discounting model, and optional aspects can be evaluated using the Black-Scholes option pricing method. 10 refs., 3 figs., 2 tabs

  1. Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

    Directory of Open Access Journals (Sweden)

    Fiebich Bernd L

    2011-03-01

    the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.

  2. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    2011-01-01

    options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies. PMID:21453539

  3. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

    2011-03-31

    Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

  4. Energy options for residential buildings assessment

    International Nuclear Information System (INIS)

    Rezaie, Behnaz; Dincer, Ibrahim; Esmailzadeh, Ebrahim

    2013-01-01

    Highlights: ► Studying various building energy options. ► Assessing these options from various points. ► Comparing these options for better environment and sustainability. ► Proposing renewable energy options as potential solutions. - Abstract: The building sector, as one of the major energy consumers, demands most of the energy research to assess different energy options from various aspects. In this paper, two similar residential buildings, with either low or high energy consumption patterns, are chosen as case studies. For these case studies, three different renewable energy technology and three different hybrid systems are designed for a specified size. Then, the environmental impact indices, renewable energy indices, and the renewable exergy indices have been estimated for every energy options. Results obtained show that the hybrid systems (without considering the economics factors) are superior and having top indices. The importance of the energy consumption patterns in buildings are proven by the indices. By cutting the energy consumption to about 40% the environment index would increase by more than twice (2.1). Utilization of the non-fossil fuels is one part of the solution to environmental problems while energy conservation being the other. It has been shown that the re-design of the energy consumption model is less complex but more achievable for buildings.

  5. The therapeutic factor inventory-8: Using item response theory to create a brief scale for continuous process monitoring for group psychotherapy.

    Science.gov (United States)

    Tasca, Giorgio A; Cabrera, Christine; Kristjansson, Elizabeth; MacNair-Semands, Rebecca; Joyce, Anthony S; Ogrodniczuk, John S

    2016-01-01

    We tested a very brief version of the 23-item Therapeutic Factors Inventory-Short Form (TFI-S), and describe the use of Item Response Theory (IRT) for the purpose of developing short and reliable scales for group psychotherapy. Group therapy patients (N = 578) completed the TFI-S on one occasion, and their data were used for the IRT analysis. Of those, 304 completed the TFI-S and other measures on more than one occasion to assess sensitivity to change, concurrent, and predictive validity of the brief version. Results suggest that the new TFI-8 is a brief, reliable, and valid measure of a higher-order group therapeutic factor. The TFI-8 may be used for continuous process measurement and feedback to improve the functioning of therapy groups.

  6. Reducing therapeutic misconception: A randomized intervention trial in hypothetical clinical trials.

    Directory of Open Access Journals (Sweden)

    Paul P Christopher

    Full Text Available Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials.This prospective randomized trial was conducted from 2015 to 2016 to test the efficacy of an informed consent intervention based on scientific reframing compared to a traditional informed consent procedure (control in reducing therapeutic misconception among patients considering enrollment in hypothetical clinical trials modeled on real-world studies for one of five disease categories. Patients with diabetes mellitus, hypertension, coronary artery disease, head/neck cancer, breast cancer, and major depression were recruited from medical clinics and a clinical research volunteer database. The primary outcomes were therapeutic misconception, as measured by a validated, ten-item Therapeutic Misconception Scale (range = 10-50, and willingness to participate in the clinical trial.154 participants completed the study (age range, 23-87 years; 92.3% white, 56.5% female; 74 (48.1% had been randomized to receive the experimental intervention. Therapeutic misconception was significantly lower (p = 0.004 in the scientific reframing group (26.4, 95% CI [23.7 to 29.1] compared to the control group (30.9, 95% CI [28.4 to 33.5], and remained so after controlling for education (p = 0.017. Willingness to participate in the hypothetical trial was not significantly different (p = 0.603 between intervention (52.1%, 95% CI [40.2% to 62.4%] and control (56.3%, 95% CI [45.3% to 66.6%] groups.An enhanced educational intervention augmenting

  7. Design Evolution Study - Aging Options

    International Nuclear Information System (INIS)

    McDaniel, P.

    2002-01-01

    The purpose of this study is to identify options and issues for aging commercial spent nuclear fuel received for disposal at the Yucca Mountain Mined Geologic Repository. Some early shipments of commercial spent nuclear fuel to the repository may be received with high-heat-output (younger) fuel assemblies that will need to be managed to meet thermal goals for emplacement. The capability to age as much as 40,000 metric tons of heavy metal of commercial spent nuclear he1 would provide more flexibility in the design to manage this younger fuel and to decouple waste receipt and waste emplacement. The following potential aging location options are evaluated: (1) Surface aging at four locations near the North Portal; (2) Subsurface aging in the permanent emplacement drifts; and (3) Subsurface aging in a new subsurface area. The following aging container options are evaluated: (1) Complete Waste Package; (2) Stainless Steel inner liner of the waste package; (3) Dual Purpose Canisters; (4) Multi-Purpose Canisters; and (5) New disposable canister for uncanistered commercial spent nuclear fuel. Each option is compared to a ''Base Case,'' which is the expected normal waste packaging process without aging. A Value Engineering approach is used to score each option against nine technical criteria and rank the options. Open issues with each of the options and suggested future actions are also presented. Costs for aging containers and aging locations are evaluated separately. Capital costs are developed for direct costs and distributable field costs. To the extent practical, unit costs are presented. Indirect costs, operating costs, and total system life cycle costs will be evaluated outside of this study. Three recommendations for aging commercial spent nuclear fuel--subsurface, surface, and combined surface and subsurface are presented for further review in the overall design re-evaluation effort. Options that were evaluated but not recommended are: subsurface aging in a new

  8. 17 CFR 33.3 - Unlawful commodity option transactions.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Unlawful commodity option... REGULATION OF DOMESTIC EXCHANGE-TRADED COMMODITY OPTION TRANSACTIONS § 33.3 Unlawful commodity option... of, or maintain a position in, any commodity option transaction subject to the provisions of this...

  9. Equity Portfolio Management Using Option Price Information

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Pan, Xuhui (Nick)

    We survey the recent academic literature that uses option-implied information to construct equity portfolios. Studies show that equity managers can earn a positive alpha by using information in individual equity options, by using stocks' exposure to information in market index options, and by usi...

  10. The Real Options Attached to an Investment Project

    Directory of Open Access Journals (Sweden)

    Mihai-Cristian DINICĂ

    2011-12-01

    Full Text Available The real options capture the importance of the managerial team’s role in creating value through investment projects. The investments in real assets have a set of options that managers can exercise during the period of the project to increase the value of the assets or to limit the eventual losses. This options have their own value.The traditional methods for investment project evaluatioan, based on discounted cash flows, have some major disadvantages: they assume the irreversibility of a decision, do not take into account the interactions between decisions in several periods and treat the investment as pasive. The evaluation using real options undertake this disadvantage. The paper shows the main types of real options, together with their elements and captures the impact of these options on the value of the investment. The main two models used to evaluate real options, the binomial model and Black-Scholes model, are explained and used to compute the value of real options attached to an investment project.

  11. Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm.

    Science.gov (United States)

    Josephy-Hernandez, Sylvia; Jmaeff, Sean; Pirvulescu, Iulia; Aboulkassim, Tahar; Saragovi, H Uri

    2017-01-01

    Neurodegenerative disorders are prevalent, complex and devastating conditions, with very limited treatment options currently available. While they manifest in many forms, there are commonalities that link them together. In this review, we will focus on neurotrophins - a family of related factors involved in neuronal development and maintenance. Neurodegenerative diseases often present with a neurotrophin imbalance, in which there may be decreases in trophic signaling through Trk receptors for example, and/or increases in pro-apoptotic activity through p75. Clinical trials with neurotrophins have continuously failed due to their poor pharmacological properties as well as the unavoidable activation of p75. Thus, there is a need for drugs without such setbacks. Small molecule neurotrophin mimetics are favorable options since they can selectively activate Trks or inactivate p75. In this review, we will initially present a brief outline of how these molecules are synthesized and their mechanisms of action; followed by an update in the current state of neurotrophins and small molecules in major neurodegenerative diseases. Although there has been significant progress in the development of potential therapeutics, more studies are needed to establish clear mechanisms of action and target specificity in order to transition from animal models to the assessment of safety and use in humans. Copyright © 2016. Published by Elsevier Inc.

  12. VALIDATION AND THERAPEUTIC USE OF SUCCULENT PLANT PARTS - OPENING OF A NEW HORIZON OF ALTERNATIVE MEDICINE

    Directory of Open Access Journals (Sweden)

    Shibabrata Pattanayak

    2016-06-01

    Full Text Available The history of use of plants for medicinal purposes is very old. In the ancient civilizations, the crude plant parts were mostly used in such purposes. In the ongoing research, solvent extracted parts of the plants are validated for their reported efficacy with an intention to identify the active principles for production of those at a large scale to use them commercially as medicines. This contemporary method may be added with validation of reported medicinal plants at their fresh, succulent form with all the available principles within them. The validated medicinal plants may be used in many purposes after performing studies related with toxicity, dose etc. Organic animal farms may be created by using fresh inputs of the added medicinal plant garden, replacing the inorganic medicines. Commercialization of succulent medicinal plant part extracts may be performed by export oriented agro-medicine business with the assistance of different cooling systems.

  13. [Pathogenetic and therapeutic aspects of secondary anorexia].

    Science.gov (United States)

    Laviano, A; Cascino, A; Muscaritoli, M; Rossi Fanelli, F

    2000-01-01

    Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.

  14. Therapeutic Uses of Triphala in Ayurvedic Medicine.

    Science.gov (United States)

    Peterson, Christine Tara; Denniston, Kate; Chopra, Deepak

    2017-08-01

    The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. A search of the PubMed database was conducted. In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.

  15. 17 CFR 32.3 - Unlawful commodity option transactions.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Unlawful commodity option... REGULATION OF COMMODITY OPTION TRANSACTIONS § 32.3 Unlawful commodity option transactions. (a) On and after... extend credit in lieu thereof) from an option customer as payment of the purchase price in connection...

  16. 40 CFR 35.6345 - Equipment disposal options.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Equipment disposal options. 35.6345 Section 35.6345 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL... options. The following disposal options are available: (a) Use the equipment on another CERCLA project and...

  17. Incentive effects of performance-vested stock options

    NARCIS (Netherlands)

    Kuang, Y.

    2007-01-01

    The vesting of traditional stock options (TSOs) only depends on the passage of time and managerial compensation might merely reflect price increases in a rising market. As a reform on traditional stock option plans, performance targets have been introduced as a condition for option vesting. The use

  18. [Does therapeutic privilege have a place in modern medicine?

    Science.gov (United States)

    Salinas, Rodrigo R; Echeverría B, Carlos; Arriagada U, Anamaría; Goic G, Alejandro; Quintana V, Carlos; Rojas O, Alberto; Serani M, Alejandro; Taboada R, Paulina; Vacarezza Y, Ricardo

    2017-09-01

    During the last years, bioethical discussion has highlighted the role of the patients' autonomy, being informed consent its particular expression, about decisions that they should make about their own health. The Hippocratic tradition, the deontological positions of the Geneva Declaration of the World Medical Association and numerous codes of ethics in various countries, require that the physician, above all, should ensure patients' health. In this context the discussion on pros and cons for the so-called "therapeutic privilege" are discussed. The "therapeutic privilege" refers to the withholding of information by the clinician during the consent process in the belief that disclosure of this information would lead to harm or suffering of the patient. The circumstances and conditions in which this privilege can become valid are discussed. Special reference is made in order to respect multiculturalism and to the possibility of obtaining advice from health care ethics committees. The role of prudence in the doctor-patient relation must be highlighted. Disclosure of information should be subordinated and oriented to the integral well-being of the patient.

  19. Economic and financial approaches to planning relatively high capital cost energy options such as hydroelectric power development

    Energy Technology Data Exchange (ETDEWEB)

    Warnock, J.G.; Merrett, A.J.

    1984-04-01

    The need for levelization has been widely recognized as desirable on grounds of equity. This paper points that it is also essential to the validity of the long-term present value criterion for capital investment. Yet the advocated methods of levelization are generally unacceptable or inefficient. These methods could be made more efficient - for example by the interest differential guarantee proposal outlined above. Until such time as effective and efficient levelization measures are implemented it has to be recognized that under present day inflationary conditions the conventional criteria of long-term present value may well be devoid of any economic validity. These issues can be of very significant importance in judging those energy options for future electrical generator modes.

  20. Mixed waste management options

    International Nuclear Information System (INIS)

    Owens, C.B.; Kirner, N.P.

    1992-01-01

    Currently, limited storage and treatment capacity exists for commercial mixed waste streams. No commercial mixed waste disposal is available, and it has been estimated that if and when commercial mixed waste disposal becomes available, the costs will be high. If high disposal fees are imposed, generators may be willing to apply extraordinary treatment or regulatory approaches to properly dispose of their mixed waste. This paper explores the feasibility of several waste management scenarios and management options. Existing data on commercially generated mixed waste streams are used to identify the realm of mixed waste known to be generated. Each waste stream is evaluated from both a regulatory and technical perspective in order to convert the waste into a strictly low-level radioactive or a hazardous waste. Alternative regulatory approaches evaluated in this paper include a delisting petition) no migration petition) and a treatability variance. For each waste stream, potentially available treatment options are identified that could lead to these variances. Waste minimization methodology and storage for decay are also considered. Economic feasibility of each option is discussed broadly. Another option for mixed waste management that is being explored is the feasibility of Department of Energy (DOE) accepting commercial mixed waste for treatment, storage, and disposal. A study has been completed that analyzes DOE treatment capacity in comparison with commercial mixed waste streams. (author)