WorldWideScience

Sample records for drugs current controversies

  1. Teen Addiction. Current Controversies Series.

    Science.gov (United States)

    Winters, Paul A., Ed.

    The Current Controversies series explores social, political, and economic controversies that dominate the national and international scenes today from a variety of perspectives. Recent surveys have shown that, after years of decline, drug use among teenagers has increased during the 1990s, and that alcohol and tobacco use have remained…

  2. Current controversies, is there merit?

    DEFF Research Database (Denmark)

    Twetman, S

    2009-01-01

    Xylitol has become a debated measure in caries prevention. This paper aims to examine and comment on some possible controversies, with emphasis on the most recent literature. A search for clinical trials was conducted through 2007 in PubMed, and papers describing a controlled xylitol intervention...

  3. Drug safety: Pregnancy rating classifications and controversies.

    Science.gov (United States)

    Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

    2016-01-01

    This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Maxillary reconstruction: Current concepts and controversies

    Directory of Open Access Journals (Sweden)

    Subramania Iyer

    2014-01-01

    Full Text Available Maxillary reconstruction is still an evolving art when compared to the reconstruction of the mandible. The defects of maxilla apart from affecting the functions of the speech, swallowing and mastication also cause cosmetic disfigurement. Rehabilitation of the form and function in patients with maxillary defects is either by using an obturator prosthesis or by a surgical reconstruction. Literature is abundant with a variety of reconstructive methods. The classification systems are also varied, with no universal acceptance of any one of them. The oncologic safety of these procedures is still debated, and conclusive evidence in this regard has not emerged yet. Management of the orbit is also not yet addressed properly. Tissue engineering, that has been hyped to be one of the possible solutions for this vexing reconstructive problem, has not come out with reliable and reproducible results so far. This review article discusses the rationale and oncological safety of the reconstructing the maxillary defects, critically analyzes the classification systems, offers the different reconstructive methods and touches upon the controversies in this subject. The management of the retained and exenterated orbit associated with maxillectomy is reviewed. The surgical morbidity, complications and the recent advances in this field are also looked into. An algorithm, based on our experience, is presented.

  5. Maxillary reconstruction: Current concepts and controversies

    Science.gov (United States)

    Iyer, Subramania; Thankappan, Krishnakumar

    2014-01-01

    Maxillary reconstruction is still an evolving art when compared to the reconstruction of the mandible. The defects of maxilla apart from affecting the functions of the speech, swallowing and mastication also cause cosmetic disfigurement. Rehabilitation of the form and function in patients with maxillary defects is either by using an obturator prosthesis or by a surgical reconstruction. Literature is abundant with a variety of reconstructive methods. The classification systems are also varied, with no universal acceptance of any one of them. The oncologic safety of these procedures is still debated, and conclusive evidence in this regard has not emerged yet. Management of the orbit is also not yet addressed properly. Tissue engineering, that has been hyped to be one of the possible solutions for this vexing reconstructive problem, has not come out with reliable and reproducible results so far. This review article discusses the rationale and oncological safety of the reconstructing the maxillary defects, critically analyzes the classification systems, offers the different reconstructive methods and touches upon the controversies in this subject. The management of the retained and exenterated orbit associated with maxillectomy is reviewed. The surgical morbidity, complications and the recent advances in this field are also looked into. An algorithm, based on our experience, is presented. PMID:24987199

  6. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

    OpenAIRE

    Russo, Ethan B.

    2016-01-01

    This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanica...

  7. Ethical Perspectives on the Current Controversy Regarding Openness in Adoption.

    Science.gov (United States)

    Tavis, Timothy M.

    This paper outlines current changes in American adoption practice and the controversies surrounding these changes. It includes a discussion of the role that neo-Kantian and utilitarian perspectives have played in American adoption policy and practice, and offers an alternative, the communitarian perspective, described by Sandel (1984). Adoption…

  8. Radiotherapy in prostate cancer. Innovative techniques and current controversies

    International Nuclear Information System (INIS)

    Geinitz, Hans

    2015-01-01

    Examines in detail the role of innovative radiation techniques in the management of prostate cancer, including IMRT, IGRT, BART, and modern brachytherapy. Explores a range of current controversies in patient treatment. Intended for both radiation oncologists and urologists. Radiation treatment is rapidly evolving owing to the coordinated research of physicists, engineers, computer and imaging specialists, and physicians. Today, the arsenal of ''high-precision'' or ''targeted'' radiotherapy includes multimodal imaging, in vivo dosimetry, Monte Carlo techniques for dose planning, patient immobilization techniques, intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), biologically adapted radiotherapy (BART), quality assurance methods, novel methods of brachytherapy, and, at the far end of the scale, particle beam radiotherapy using protons and carbon ions. These approaches are like pieces of a puzzle that need to be put together to provide the prostate cancer patient with high-level optimized radiation treatment. This book examines in detail the role of the above-mentioned innovative radiation techniques in the management of prostate cancer. In addition, a variety of current controversies regarding treatment are carefully explored, including whether prophylactic treatment of the pelvic lymphatics is essential, the magnitude of the effect of dose escalation, whether a benefit accrues from hypofractionation, and what evidence exists for the superiority of protons or heavy ions. Radiotherapy in Prostate Cancer: Innovative Techniques and Current Controversies is intended for both radiation oncologists and urologists with an interest in the up-to-date capabilities of modern radiation oncology for the treatment of prostate cancer.

  9. Radiotherapy in prostate cancer. Innovative techniques and current controversies

    Energy Technology Data Exchange (ETDEWEB)

    Geinitz, Hans [Krankenhaus der Barmherzigen Schwestern, Linz (Austria). Dept. of Radiation Oncology; Linz Univ. (Austria). Medical Faculty; Roach, Mack III [California Univ., San Francisco, CA (United States). Dept. of Radiation Oncology; Van As, Nicholas (ed.) [The Institute of Cancer Research, Sutton Surrey (United Kingdom)

    2015-04-01

    Examines in detail the role of innovative radiation techniques in the management of prostate cancer, including IMRT, IGRT, BART, and modern brachytherapy. Explores a range of current controversies in patient treatment. Intended for both radiation oncologists and urologists. Radiation treatment is rapidly evolving owing to the coordinated research of physicists, engineers, computer and imaging specialists, and physicians. Today, the arsenal of ''high-precision'' or ''targeted'' radiotherapy includes multimodal imaging, in vivo dosimetry, Monte Carlo techniques for dose planning, patient immobilization techniques, intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), biologically adapted radiotherapy (BART), quality assurance methods, novel methods of brachytherapy, and, at the far end of the scale, particle beam radiotherapy using protons and carbon ions. These approaches are like pieces of a puzzle that need to be put together to provide the prostate cancer patient with high-level optimized radiation treatment. This book examines in detail the role of the above-mentioned innovative radiation techniques in the management of prostate cancer. In addition, a variety of current controversies regarding treatment are carefully explored, including whether prophylactic treatment of the pelvic lymphatics is essential, the magnitude of the effect of dose escalation, whether a benefit accrues from hypofractionation, and what evidence exists for the superiority of protons or heavy ions. Radiotherapy in Prostate Cancer: Innovative Techniques and Current Controversies is intended for both radiation oncologists and urologists with an interest in the up-to-date capabilities of modern radiation oncology for the treatment of prostate cancer.

  10. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues.

    Directory of Open Access Journals (Sweden)

    Ethan Budd Russo

    2016-09-01

    Full Text Available This overview covers a wide range of cannabis topics, initially examining issue in dispensaries and self-administration, plus regulatory requirement for production of cannabis-based medicines, particularly the Food and Drug Administration Botanical Guidance. The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety and public health issues remain.

  11. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

    Science.gov (United States)

    Russo, Ethan B.

    2016-01-01

    This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain. PMID:27683558

  12. Cannabis: a controversial 21st-century drug of antiquity.

    Science.gov (United States)

    Greydanus, D; Holt, M

    2014-05-01

    Cannabis consumption has been popular for thousands of years and its historical use is noted in many parts of the world including ancient China, India, the Middle East. It is currently the most popular illicit drug in the world, is being utilized as a medicinal plant, and many parts of the world are legalizing this drug. This discussion considers various aspects of cannabis use including its prevalence, history, co-morbid drug abuse, designer cannabinoids, psychiatric adverse effects, medical adverse effects, and management options. The youth of the world should be comprehensively taught that cannabis is neither a safe nor a benign drug. Prevention with comprehensive drug education is the best plan for our youth since management of a chronic or heavy cannabis consummer remains difficult and fraught with failure if cessation is the goal. Caveat emptor!

  13. Current controversies and future perspectives in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Agustí, Alvar; Vestbo, Jørgen

    2011-01-01

    Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work. This review discusses these controversies and anticipates...... some of the changes that may occur in the near future in the field of COPD....

  14. Current controversies and future perspectives in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Agustí, Alvar; Vestbo, Jørgen

    2011-01-01

    Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work. This review discusses these controversies and anticipates...

  15. Current controversies in infective endocarditis [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Thomas J. Cahill

    2015-11-01

    Full Text Available Infective endocarditis is a life-threatening disease caused by a focus of infection within the heart. For clinicians and scientists, it has been a moving target that has an evolving microbiology and a changing patient demographic. In the absence of an extensive evidence base to guide clinical practice, controversies abound. Here, we review three main areas of uncertainty: first, in prevention of infective endocarditis, including the role of antibiotic prophylaxis and strategies to reduce health care-associated bacteraemia; second, in diagnosis, specifically the use of multimodality imaging; third, we discuss the optimal timing of surgical intervention and the challenges posed by increasing rates of cardiac device infection.

  16. Spine Trauma-What Are the Current Controversies?

    Science.gov (United States)

    Oner, Cumhur; Rajasekaran, Shanmuganathan; Chapman, Jens R; Fehlings, Michael G; Vaccaro, Alexander R; Schroeder, Gregory D; Sadiqi, Said; Harrop, James

    2017-09-01

    Although less common than other musculoskeletal injuries, spinal trauma may lead to significantly more disability and costs. During the last 2 decades there was substantial improvement in our understanding of the basic patterns of spinal fractures leading to more reliable classification and injury severity assessment systems but also rapid developments in surgical techniques. Despite these advancements, there remain unresolved issues concerning the management of these injuries. At this moment there is persistent controversy within the spinal trauma community, which can be grouped under 6 headings. First of all there is still no unanimity on the role and timing of medical and surgical interventions for patients with associated neurologic injury. The same is also true for type and timing of surgical intervention in multiply injured patients. In some common injury types like odontoid fractures and burst type (A3-A4) fractures in thoracolumbar spine, there is wide variation in practice between operative versus nonoperative management without clear reasons. Also, the role of different surgical approaches and techniques in certain injury types are not clarified yet. Methods of nonoperative management and care of elderly patients with concurrent complex disorders are also areas where there is no consensus. In this overview article the main reasons for these controversies are reviewed and the possible ways for resolutions are discussed.

  17. Drug Establishments Current Registration Site

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Establishments Current Registration Site (DECRS) is a database of current information submitted by drug firms to register establishments (facilities) which...

  18. Oncologic PET/CT: current status and controversies

    International Nuclear Information System (INIS)

    Siegel, B.A.; Dehdashti, F.

    2005-01-01

    The introduction of integrated PET/CT has dramatically increased the worldwide rate of growth for PET, predominantly for oncologic imaging with the glucose analog 18 F-fluorodeoxyglucose (FDG). A rapidly expanding body of literature demonstrates that the use FDG-PET/CT and the resultant ability to interpret coregistered and fused PET and CT images lead to improved observer confidence and improved diagnostic performance by comparison with PET alone, CT alone, and visually correlated PET and CT. The value of PET/CT is likely to be even greater with new PET radiopharmaceuticals under development, many of which produce PET images with even fewer anatomical landmarks than FDG images. PET/CT is also likely to lead to the resurrection of 18 F-fluoride as a principal agent for radionuclide bone imaging. There are a number of controversies related to PET/CT, including minimum training and experience requirements for interpreting physicians and defining new models for technical and professional reimbursement. (orig.)

  19. Zollinger-Ellison syndrome: classical considerations and current controversies.

    Science.gov (United States)

    Epelboym, Irene; Mazeh, Haggi

    2014-01-01

    Zollinger-Ellison syndrome (ZES) is an endocrinopathy characterized by gastrin-secreting tumors, responsible for causing the formation of multiple, refractory, and recurrent peptic ulcers in the distal duodenum and proximal jejunum. Two main variants have been described, sporadic and those found in association with parathyroid and pituitary tumors, a genetic disorder known as multiple endocrine neoplasia-1 (MEN-1). Biochemical serum evaluation for elevated gastrin, followed by radiological or nuclear localization of the primary lesion, is mandated for establishing diagnosis. The mainstays of treatment include management of hypersecretory state with medical suppression of gastric acid production and surgical resection of primary tumor for the prevention of malignant transformation and metastatic complications. Medical therapy with proton pump inhibitors has virtually eliminated the need for acid-reducing surgical procedures. Surgical approach to sporadic and MEN-1-associated ZES varies based on our understanding of the natural history of the condition and the probability of cure; however, resection to a negative microscopic margin is indicated in both cases. Postoperative surveillance involves measurement of gastrin level, followed by imaging if elevation is detected. Re-excision of recurrent or resection of metastatic disease is a subject of controversy; however, at the present time aggressive cytoreductive approach is favored.

  20. Current obesity drug treatment

    Directory of Open Access Journals (Sweden)

    Marcio C. Mancini

    2006-03-01

    Full Text Available Pharmacological treatment of obesity is an area of sudden changes,development of new drugs and treatment propositions. This articlepresents information on physiological agents that are currentlybeing used as well as drugs that were widely used but are nomore available.

  1. Controversy in Purchasing Prescription Drugs Online in China.

    Science.gov (United States)

    Yuan, Peng; Qi, Lin; Wang, Long

    2016-08-01

    China's government is considering legalization of online prescription drugs to increase the pharmaceutical market and enhance access to necessary medicines. However, challenges such as a shortage of licensed pharmacists and drug quality issues have raised concerns and delayed consensus on the proposal. China's government must address the most pressing issues so it can render a decision on online prescription sales. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Current Controversies in Newer Therapies to Treat Birth Asphyxia

    Directory of Open Access Journals (Sweden)

    Pia Wintermark

    2011-01-01

    Full Text Available Despite major advances in monitoring technology and knowledge of fetal and neonatal pathophysiology, neonatal hypoxic-ischemic encephalopathy (HIE remains one of the main causes of severe adverse neurological outcome in children. Until recently, there were no therapies other than supportive measures. Over the past several years, mild hypothermia has been proven to be safe to treat HIE. Unfortunately, this neuroprotective strategy seems efficient in preventing brain injury in some asphyxiated newborns, but not in all of them. Thus, there is increasing interest to rapidly understand how to refine hypothermia therapy and add neuroprotective or neurorestorative strategies. Several promising newer treatments to treat birth asphyxia and prevent its devastating neurological consequences are currently being tested. In this paper, the physiopathology behind HIE, the currently available treatment, the potential alternatives, and the next steps before implementation of these other treatments are reviewed.

  3. Heart failure and atrial fibrillation: current concepts and controversies.

    Science.gov (United States)

    Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

    1997-01-01

    Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

  4. Antiretroviral therapy: current drugs.

    Science.gov (United States)

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

  5. Current concepts and controversies on adolescent idiopathic scoliosis: Part I.

    Science.gov (United States)

    Sud, Alok; Tsirikos, Athanasios I

    2013-03-01

    Adolescent idiopathic scoliosis is the most common spinal deformity encountered by General Orthopaedic Surgeons. Etiology remains unclear and current research focuses on genetic factors that may influence scoliosis development and risk of progression. Delayed diagnosis can result in severe deformities which affect the coronal and sagittal planes, as well as the rib cage, waistline symmetry, and shoulder balance. Patient's dissatisfaction in terms of physical appearance and mechanical back pain, as well as the risk for curve deterioration are usually the reasons for treatment. Conservative management involves mainly bracing with the aim to stop or slow down scoliosis progression during growth and if possible prevent the need for surgical treatment. This is mainly indicated in young compliant patients with a large amount of remaining growth and progressive curvatures. Scoliosis correction is indicated for severe or progressive curves which produce significant cosmetic deformity, muscular pain, and patient discontent. Posterior spinal arthrodesis with Harrington instrumentation and bone grafting was the first attempt to correct the coronal deformity and replace in situ fusion. This was associated with high pseudarthrosis rates, need for postoperative immobilization, and flattening of sagittal spinal contour. Segmental correction techniques were introduced along with the Luque rods, Harri-Luque, and Wisconsin systems. Correction in both coronal and sagittal planes was not satisfactory and high rates of nonunion persisted until Cotrel and Dubousset introduced the concept of global spinal derotation. Development of pedicle screws provided a powerful tool to correct three-dimensional vertebral deformity and opened a new era in the treatment of scoliosis.

  6. Current concepts and controversies on adolescent idiopathic scoliosis: Part I

    Directory of Open Access Journals (Sweden)

    Alok Sud

    2013-01-01

    Full Text Available Adolescent idiopathic scoliosis is the most common spinal deformity encountered by General Orthopaedic Surgeons. Etiology remains unclear and current research focuses on genetic factors that may influence scoliosis development and risk of progression. Delayed diagnosis can result in severe deformities which affect the coronal and sagittal planes, as well as the rib cage, waistline symmetry, and shoulder balance. Patient′s dissatisfaction in terms of physical appearance and mechanical back pain, as well as the risk for curve deterioration are usually the reasons for treatment. Conservative management involves mainly bracing with the aim to stop or slow down scoliosis progression during growth and if possible prevent the need for surgical treatment. This is mainly indicated in young compliant patients with a large amount of remaining growth and progressive curvatures. Scoliosis correction is indicated for severe or progressive curves which produce significant cosmetic deformity, muscular pain, and patient discontent. Posterior spinal arthrodesis with Harrington instrumentation and bone grafting was the first attempt to correct the coronal deformity and replace in situ fusion. This was associated with high pseudarthrosis rates, need for postoperative immobilization, and flattening of sagittal spinal contour. Segmental correction techniques were introduced along with the Luque rods, Harri-Luque, and Wisconsin systems. Correction in both coronal and sagittal planes was not satisfactory and high rates of nonunion persisted until Cotrel and Dubousset introduced the concept of global spinal derotation. Development of pedicle screws provided a powerful tool to correct three-dimensional vertebral deformity and opened a new era in the treatment of scoliosis.

  7. Zohydro approval by food and drug administration: controversial or frightening?

    Science.gov (United States)

    Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

    2014-01-01

    The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health

  8. Biosimilar drugs: Current status.

    Science.gov (United States)

    Kumar, Rajiv; Singh, Jagjit

    2014-07-01

    Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed "abbreviated pathway" for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines "Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online.

  9. Malrotation and midgut volvulus: a historical review and current controversies in diagnosis and management

    Energy Technology Data Exchange (ETDEWEB)

    Lampl, Brooke; Berdon, Walter E. [Morgan Stanley Children' s Hospital of New York-Presbyterian, Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY (United States); Levin, Terry L. [Montefiore Medical Center, Department of Radiology, Mamaroneck, NY (United States); Cowles, Robert A. [Morgan Stanley Children' s Hospital of New York-Presbyterian, Division of Pediatric Surgery, Columbia University College of Physicians and Surgeons, New York, NY (United States)

    2009-04-15

    The complex and sometimes controversial subject of malrotation and midgut volvulus is reviewed commencing with the 19th-century Bohemian anatomist, Vaclav Treitz, who described the suspensory muscle anchoring of the duodenal-jejunal junction in the left upper quadrant, and continuing with William Ladd, the 20th-century American ''father of pediatric surgery'' who pioneered the surgical treatment of midgut volvulus. In this review, we present the interesting history of malrotation and discuss the current radiologic and surgical controversies surrounding its diagnosis and treatment. In the symptomatic patient with malrotation and possible midgut volvulus, prompt diagnosis is critical. The clinical examination and plain film are often confusing, and delayed diagnosis can lead to significant morbidity and death. Despite recent intense interest in the position of the mesenteric vessels on US and CT scans, the upper gastrointestinal series remains the fastest and most accurate method of demonstrating duodenal obstruction, the position of the ligament of Treitz, and, if the contrast agent is followed distally, cecal malposition. Controversy exists over the management of asymptomatic patients with malrotation in whom the diagnosis is made incidentally during evaluation for nonspecific complaints, prior to reflux surgery, and in those with heterotaxy syndromes. (orig.)

  10. Malrotation and midgut volvulus: a historical review and current controversies in diagnosis and management

    International Nuclear Information System (INIS)

    Lampl, Brooke; Berdon, Walter E.; Levin, Terry L.; Cowles, Robert A.

    2009-01-01

    The complex and sometimes controversial subject of malrotation and midgut volvulus is reviewed commencing with the 19th-century Bohemian anatomist, Vaclav Treitz, who described the suspensory muscle anchoring of the duodenal-jejunal junction in the left upper quadrant, and continuing with William Ladd, the 20th-century American ''father of pediatric surgery'' who pioneered the surgical treatment of midgut volvulus. In this review, we present the interesting history of malrotation and discuss the current radiologic and surgical controversies surrounding its diagnosis and treatment. In the symptomatic patient with malrotation and possible midgut volvulus, prompt diagnosis is critical. The clinical examination and plain film are often confusing, and delayed diagnosis can lead to significant morbidity and death. Despite recent intense interest in the position of the mesenteric vessels on US and CT scans, the upper gastrointestinal series remains the fastest and most accurate method of demonstrating duodenal obstruction, the position of the ligament of Treitz, and, if the contrast agent is followed distally, cecal malposition. Controversy exists over the management of asymptomatic patients with malrotation in whom the diagnosis is made incidentally during evaluation for nonspecific complaints, prior to reflux surgery, and in those with heterotaxy syndromes. (orig.)

  11. Trust in the pharmaceutical sector : Analysis of drug safety controversies by means of drug life cycles

    NARCIS (Netherlands)

    Hernández, J.F.

    2015-01-01

    Before obtaining a marketing approval, the efficacy and safety profile of drugs is studied in specific populations and under well-controlled circumstances. After marketing approval, the drug is made available and used in ‘real world conditions’, which are known to deviate from the trial setting.

  12. Current state and controversies in fertility preservation in women with breast cancer.

    Science.gov (United States)

    Taylan, Enes; Oktay, Kutluk H

    2017-06-10

    On average, over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States. Because an increasing number of young women delay childbearing to later life for various reasons, a growing population of women experience breast cancer before completing childbearing. In this context, preservation of fertility potential of breast cancer survivors has become an essential concept in modern cancer care. In this review, we will outline the currently available fertility preservation options for women with breast cancer of reproductive age, discuss the controversy behind hormonal suppression for gonadal protection against chemotherapy and highlight the importance of timely referral by cancer care providers.

  13. Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency

    Science.gov (United States)

    Ysunza, Pablo Antonio; Repetto, Gabriela M.; Pamplona, Maria Carmen; Calderon, Juan F.; Shaheen, Kenneth; Chaiyasate, Konkgrit; Rontal, Matthew

    2015-01-01

    Background. One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI). Objective. This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. Materials and Methods. An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. Results. Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. Conclusion. This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management. PMID:26273595

  14. Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency

    Directory of Open Access Journals (Sweden)

    Pablo Antonio Ysunza

    2015-01-01

    Full Text Available Background. One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI. Objective. This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. Materials and Methods. An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. Results. Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. Conclusion. This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management.

  15. The Immunology of Neuromyelitis Optica-Current Knowledge, Clinical Implications, Controversies and Future Perspectives.

    Science.gov (United States)

    Jasiak-Zatonska, Michalina; Kalinowska-Lyszczarz, Alicja; Michalak, Slawomir; Kozubski, Wojciech

    2016-03-02

    Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%-25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients.

  16. The Immunology of Neuromyelitis Optica—Current Knowledge, Clinical Implications, Controversies and Future Perspectives

    Science.gov (United States)

    Jasiak-Zatonska, Michalina; Kalinowska-Lyszczarz, Alicja; Michalak, Slawomir; Kozubski, Wojciech

    2016-01-01

    Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%–25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients. PMID:26950113

  17. Androgen replacement therapy in late-onset hypogonadism: current concepts and controversies - a mini-review.

    Science.gov (United States)

    Mäkinen, Juuso I; Huhtaniemi, Ilpo

    2011-01-01

    Normal testicular function is essential for the maintenance of male physical strength and behaviour irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone (T) and hypogonadal symptoms in ageing men. The most important testicular hormone, T, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular T production remains stable until around the age of 40 years after which it declines by 1-2% annually. Despite this age-related decline, serum T levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and nonspecific subjective signs and symptoms of ageing. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. A thorough review of the existing literature was performed to evaluate the current concepts and controversies related to ageing men and ART. Although it is intuitively logical that the symptoms of LOH are due to the ageing-related deficiency of T, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in ageing men is largely missing. Despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental. Copyright © 2010 S. Karger AG, Basel.

  18. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment.

    Science.gov (United States)

    Huhtaniemi, Ilpo

    2014-01-01

    Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM). Late-onset hypogonadism (LOH) describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH)) or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH). The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty). A problem with the diagnosis of LOH is that often the symptoms (in 20%-40% of unselected men) and low circulating T (in 20% of men >70 years of age) do not coincide in the same individual. The European Male Ageing Study (EMAS) has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefi ts and short- and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH.

  19. The "Magic Cure" A Review of the Current Controversial Approaches for Treating Learning Disabilities.

    Science.gov (United States)

    Silver, Larry B.

    1987-01-01

    In view of popular press coverage of controversial approaches to treating learning disabilities, the article briefly reviews evidence concerning the following: neurophysiological retraining (patterning, optometric visual training, cerebellar-vestibular remediation, and applied kinesiology); and orthomolecular medicine (concerning megavitamins,…

  20. Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Ilpo Huhtaniemi

    2014-04-01

    short- and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH.

  1. Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

    Science.gov (United States)

    Huhtaniemi, Ilpo

    2014-01-01

    - and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH. PMID:24407185

  2. Update on the surgical management of ulcerative colitis and ulcerative proctitis: current controversies and problems.

    Science.gov (United States)

    Sagar, P M; Pemberton, J H

    1995-01-01

    : The surgical management of ulcerative colitis has been revolutionized in recent years by the development of the ileal pouch-anal procedure. Although it is now the operation of choice for most patients, there remain several controversies. A variety of designs of ileal pouch are available each with advantages and disadvantages. The technique used to anastomose the pouch to the anal canal is also open to debate with some surgeons favoring distal mucosectomy with eradication of all disease and others choosing to perform a stapled anastomosis to achieve better functional results. The main concern for gastroenterologists, however, is the risk of development of pouchitis. The etiology, diagnosis, and treatment of this condition will also be discussed in this review as well as the more classical options for the surgical treatment of ulcerative colitis.

  3. Current controversies in reconstructive surgery of the anterior urethra: a clinical overview

    Directory of Open Access Journals (Sweden)

    Guido Barbagli

    2012-06-01

    Full Text Available We performed an overview of the surgical techniques suggested for the treatment of anterior urethral strictures using MEDLINE. In applying the MEDLINE search, we used the "MeSH" (Medical Subject Heading and "free text" protocols. The MeSH search was conducted by combining the following terms: "urethral stricture", "flap", "graft", "oral mucosa", "urethroplasty", "urethrotomy" and "failed hypospadias". Multiple "free text" searches were performed individually applying the following terms through all fields of the records: "reconstructive urethral surgery", "end-to-end anastomosis", "one-stage", "two stage". Descriptive statistics of the articles were provided. Meta-analyses were not employed. Seventy-eight articles were determined to be germane in this review. Six main topics were identified as controversial in anterior urethra surgery: the use of oral mucosa vs penile skin; the use of free grafts vs pedicled flaps in penile urethroplasty; the use of grafts vs anastomotic repair in bulbar urethral strictures; the use of dorsal vs ventral placement of the graft in bulbar urethroplasty; the use of definitive perineal urethrostomy vs one-stage repair in complex urethral strictures; the surgical options for patients with failed hypospadias repair. Different points of view are documented and presented in the literature by various authors from different countries. The aim of this clinical overview is to survey the main controversial issues in surgical reconstruction of the anterior urethra focusing on the use of flap or graft, substitute material, type of surgery and challenging situations, such as failed hypospadias or complex urethral stricture repair.

  4. Everything You Need To Know To Understand the Current Controversies You Learned from Psychological Research: A Comment on the Rind and Lilienfeld Controversies.

    Science.gov (United States)

    Sternberg, Robert J.

    2002-01-01

    Discusses applications of theories and research in psychology to understand controversies generated by two recent articles, explaining the need to distinguish between rational and intuitive thinking, recognize the power of context, think reflectively, and realize the costs of defying the crowd, and noting steps one can take to be wiser and more…

  5. The Controversy of Applying the Death Sentence for Criminal Acts Related to Drugs

    OpenAIRE

    Hasan Asy’ari, Syamsul Hidayat &

    2013-01-01

    In anticipation of the threat and the dangers of drug abuse and illicit trafficking, Indonesia as a whole has had the law on ratification of the Convention , including the United Nations on combating illicit trafficking in narcotic drugs and psychotropic substances in 1988. Policy is required drug crimes (penal policy). Applicable policies regarding how to commit criminal law legislation in force at the moment and formulated policies that lead to renewal (penal law reform) who formulated the ...

  6. The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy

    Directory of Open Access Journals (Sweden)

    Andrew Bacyinski

    2017-11-01

    Full Text Available The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.

  7. The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy.

    Science.gov (United States)

    Bacyinski, Andrew; Xu, Maosheng; Wang, Wei; Hu, Jiani

    2017-01-01

    The paravascular pathway, also known as the "glymphatic" pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.

  8. Two faces of patient advocacy: the current controversy in newborn screening.

    Science.gov (United States)

    Arnold, Cosby G

    2014-08-01

    Newborn screening programmes began in the 1960s, have traditionally been conducted without parental permission and have grown dramatically in the last decade. Whether these programmes serve patients' best interests has recently become a point of controversy. Privacy advocates, concerned that newborn screening infringes upon individual liberties, are demanding fundamental changes to these programmes. These include parental permission and limiting the research on the blood samples obtained, an agenda at odds with the viewpoints of newborn screening advocates. This essay presents the history of newborn screening in the USA, with attention to factors that have contributed to concerns about these programmes. The essay suggests that the rapid increase in the number of disorders screened for and the addition of research without either public knowledge or informed consent were critical to the development of resistance to mandatory newborn screening and research. Future newborn screening initiatives should include public education and comment to ensure continued support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Current Controversies in the Prediction, Diagnosis, and Management of Cerebral Vasospasm: Where Do We Stand?

    Directory of Open Access Journals (Sweden)

    Young Lee

    2013-01-01

    Full Text Available Aneurysmal subarachnoid hemorrhage occurs in approximately 30,000 persons in the United States each year. Around 30 percent of patients with aneurysmal subarachnoid hemorrhage suffer from cerebral ischemia and infarction due to cerebral vasospasm, a leading cause of treatable death and disability following aneurysmal subarachnoid hemorrhage. Methods used to predict, diagnose, and manage vasospasm are the topic of recent active research. This paper utilizes a comprehensive review of the recent literature to address controversies surrounding these topics. Evidence regarding the effect of age, smoking, and cocaine use on the incidence and outcome of vasospasm is reviewed. The abilities of different computed tomography grading schemes to predict vasospasm in the aftermath of subarachnoid hemorrhage are presented. Additionally, the utility of different diagnostic methods for the detection and visualization of vasospasm, including transcranial Doppler ultrasonography, CT angiography, digital subtraction angiography, and CT perfusion imaging is discussed. Finally, the recent literature regarding interventions for the prophylaxis and treatment of vasospasm, including hyperdynamic therapy, albumin, calcium channel agonists, statins, magnesium sulfate, and endothelin antagonists is summarized. Recent studies regarding each topic were reviewed for consensus recommendations from the literature, which were then presented.

  10. Current controversies in the prediction, diagnosis, and management of cerebral vasospasm: where do we stand?

    Science.gov (United States)

    Lee, Young; Zuckerman, Scott L; Mocco, J

    2013-01-01

    Aneurysmal subarachnoid hemorrhage occurs in approximately 30,000 persons in the United States each year. Around 30 percent of patients with aneurysmal subarachnoid hemorrhage suffer from cerebral ischemia and infarction due to cerebral vasospasm, a leading cause of treatable death and disability following aneurysmal subarachnoid hemorrhage. Methods used to predict, diagnose, and manage vasospasm are the topic of recent active research. This paper utilizes a comprehensive review of the recent literature to address controversies surrounding these topics. Evidence regarding the effect of age, smoking, and cocaine use on the incidence and outcome of vasospasm is reviewed. The abilities of different computed tomography grading schemes to predict vasospasm in the aftermath of subarachnoid hemorrhage are presented. Additionally, the utility of different diagnostic methods for the detection and visualization of vasospasm, including transcranial Doppler ultrasonography, CT angiography, digital subtraction angiography, and CT perfusion imaging is discussed. Finally, the recent literature regarding interventions for the prophylaxis and treatment of vasospasm, including hyperdynamic therapy, albumin, calcium channel agonists, statins, magnesium sulfate, and endothelin antagonists is summarized. Recent studies regarding each topic were reviewed for consensus recommendations from the literature, which were then presented.

  11. Death and dependence: current controversies over the selective serotonin reuptake inhibitors.

    Science.gov (United States)

    Nutt, David J

    2003-12-01

    Recent years have seen a considerable media interest in the adverse effects of the selective serotonin reuptake inhibitors (SSRIs). This has led to claims that these antidepressants may lead to suicide and homicide and that they cause dependence or even addiction. Such claims have caused great concerns to many patients and have confused doctors in both primary care and psychiatric practice. In this article I review the basis of these claims and show that many seem to emerge from the misinterpretation of evidence and the use of imprecise definitions. Although the SSRIs are not free of problems they compare very favourably with other antidepressants and other classes of psychotropic drugs. There is no evidence they are addictive in the formal sense of leading to a drug dependence syndrome. Some suggestions on the way these issues can be more precisely defined and studied in future are given.

  12. Tamsulosin for urolithiasis: a review of the recent literature and current controversies.

    Science.gov (United States)

    Pourmand, Ali; Nadendla, Rahul; Mazer-Amirshahi, Maryann; O'Connell, Francis

    2016-11-01

    In the United States, urolithiasis affects approximately 1 in 11 people, and there is evidence that the prevalence is increasing. A relatively recent treatment strategy for urolithiasis involves using medical expulsive therapy (MET) to increase the likelihood of spontaneous passage of ureteral stones. The 2 leading drug classes for MET are alpha-1-andrenergic receptor blockers and calcium channel blockers. Tamsulosin, an alpha-1-adrenocepter blocking agent, is thought to induce spontaneous stone passage by relaxing ureteral smooth muscle tone. However, tamsulosin has not been proven effective for increasing ureteral stone passage and is not approved by the Food and Drug Administration for this indication. There is a relative paucity of data on the efficacy of tamsulosin for urolithiasis, and of the published results, there are conflicting conclusions from the data. Because of the acute and often severe nature of symptoms from urolithiasis, emergency medicine physicians are frequently the first to diagnose and treat this condition. This has led to tamsulosin being frequently prescribed from the emergency department (ED) for off-label use without the support of high-quality evidence. If tamsulosin is proven effective, its use in the treatment of urolithiasis could offer several important advantages. The number of procedures, length of hospital stay, and health care costs after the initial ED visit could potentially be reduced. Tamsulosin may also increase patient satisfaction by reducing the invasive treatment and decreasing the time to stone passage. This review focuses on the efficacy of tamsulosin based on stone location, after shock wave lithotripsy, compared with other MET drugs and in the acute setting of the ED. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

    Science.gov (United States)

    Benda, Norbert; Brandt, Andreas

    2018-01-01

    Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

  14. Everything you need to know to understand the current controversies you learned from psychological research. A comment on the Rind and Lilienfeld controversies.

    Science.gov (United States)

    Sternberg, Robert J

    2002-03-01

    Psychological theory and research can help explain some of the aspects of the controversies that arose over articles written by B. Rind, P. Tromovitch, and R. Bauserman (1998) and by S. O. Lilienfeld (2002). In particular, one needs to distinguish between rational and intuitive thinking, to recognize the power of context, to be reflective in one's own thinking, and to realize the costs of defying the crowd. There are steps one can take to be wiser and more balanced in one's own thinking than one may have been in the past. One such step is to resolve conflicts among psychologists by attempting to defuse rather than to exacerbate or avoid them.

  15. Current state and controversies in fertility preservation in women with breast cancer

    OpenAIRE

    Taylan, Enes; Oktay, Kutluk H

    2017-01-01

    On average, over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States. Because an increasing number of young women delay childbearing to later life for various reasons, a growing population of women experience breast cancer before completing childbearing. In this context, preservation of fertility potential of breast cancer survivors has become an essential concept in modern cancer care. In this review, we will outline the currently available fertilit...

  16. Current controversies in colorectal surgery: the way to resolve uncertainty and move forward

    DEFF Research Database (Denmark)

    Rosenberg, J; Fischer, A; Haglind, E

    2012-01-01

    for low rectal cancer, robotic surgery for various colorectal procedures, laparoscopic lavage without resection for Hinchey Stage III perforated sigmoid diverticulitis, and the use of the single port technique for laparoscopic surgery. Before general implementation the new modalities should ideally......The are currently a number of unsolved clinical questions in colorectal surgery with new surgical principles being introduced without proper scientific high-level evidence. These include complete mesocolic excision with central ligation for colonic cancer, extralevator abdominoperineal excision...

  17. Current controversies on the role of behavior therapy in Tourette Syndrome

    Science.gov (United States)

    Scahill, Lawrence; Woods, Douglas W.; Himle, Michael B.; Peterson, Alan L.; Wilhelm, Sabine; Piacentini, John C.; McNaught, Kevin; Walkup, John T.; Mink, Jonathan W.

    2014-01-01

    Comprehensive Behavioral Intervention for Tics (CBIT) is a safe and effective treatment for managing the tics of TS. In contrast to most current medications used for the treatment of tics, the efficacy of CBIT has been demonstrated in two relatively large, multisite trials. It also shows durability of benefit over time. Similar to psychopharmacological intervention, skilled practitioners are required to implement the intervention. Despite concerns about the effort required to participate in CBIT, patients with TS and parents of children with TS appear willing to meet the requirements of the CBIT program. Efforts are underway to increase the number of trained CBIT providers in the United States. Based on available evidence, recent published guidelines suggest that CBIT can be considered a first-line treatment for persons with a tic disorders. PMID:23681719

  18. Current trends and controversies in the management of patients with splenic flexure tumours

    Directory of Open Access Journals (Sweden)

    Chan DS

    2013-03-01

    Full Text Available Aim: There exists a variation in practice in the management of tumours around the splenic flexure. We aim to determine the current opinion regarding the management of these tumours. Methods: An anonymised 10-part online questionnaire was sent to all members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI. Results: The response rate was 24% (111/464 with approximately half of respondents performing laparoscopic surgery. Electively, an extended right hemicolectomy is the preferred option by 63% of respondents followed by left hemicolectomy (23% and segmental resection (14%. The upper sigmoid and rectosigmoid is the preferred site of anastomosis by 90% and 10% of respondents respectively. There were no significant differences in the type of operations performed by surgeons who practice laparoscopic or open surgery (p=0.10. A hand-sewn end-to-end anastomosis is most commonly performed (51% followed by a stapled side-to-side (36% and a stapled end-to-end (13% technique. Extended right hemicolectomy is also the preferred option in obstructing tumours. Of surgeons who perform segmental resections, 27% perform an on-table lavage and 9% perform a defunctioning stoma. Internal herniation following laparoscopic resection was only reported by a handful of surgeons. Conclusion: Opinion and practice in the management of patients with tumours around the splenic flexure are divided. Further trials are indicated to determine the best practice.

  19. Computational Controversy

    NARCIS (Netherlands)

    Timmermans, Benjamin; Kuhn, Tobias; Beelen, Kaspar; Aroyo, Lora

    2017-01-01

    Climate change, vaccination, abortion, Trump: Many topics are surrounded by fierce controversies. The nature of such heated debates and their elements have been studied extensively in the social science literature. More recently, various computational approaches to controversy analysis have

  20. Still controversial

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-10-15

    It is some sixty years since the existence of the neutrino was controversially postulated by the controversial Wolfgang Pauli. Today, the neutrino remains controversial. At the Berkeley Conference, summarizer Steve Weinberg kept the spotlight on these enigmatic particles during a considerable portion of his talk.

  1. Still controversial

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    It is some sixty years since the existence of the neutrino was controversially postulated by the controversial Wolfgang Pauli. Today, the neutrino remains controversial. At the Berkeley Conference, summarizer Steve Weinberg kept the spotlight on these enigmatic particles during a considerable portion of his talk

  2. Controversies in the Hydrosphere: an iBook exploring current global water issues for middle school classrooms

    Science.gov (United States)

    Dufoe, A.; Guertin, L. A.

    2012-12-01

    This project looks to help teachers utilize iPad technology in their classrooms as an instructional tool for Earth system science and connections to the Big Ideas in Earth Science. The project is part of Penn State University's National Science Foundation (NSF) Targeted Math Science Partnership grant, with one goal of the grant to help current middle school teachers across Pennsylvania engage students with significant and complex questions of Earth science. The free Apple software iBooks Author was used to create an electronic book for the iPad, focusing on a variety of controversial issues impacting the hydrosphere. The iBook includes image slideshows, embedded videos, interactive images and quizzes, and critical thinking questions along Bloom's Taxonomic Scale of Learning Objectives. Outlined in the introductory iBook chapters are the Big Ideas of Earth System Science and an overview of Earth's spheres. Since the book targets the hydrosphere, each subsequent chapter focuses on specific water issues, including glacial melts, aquifer depletion, coastal oil pollution, marine debris, and fresh-water chemical contamination. Each chapter is presented in a case study format that highlights the history of the issue, the development and current status of the issue, and some solutions that have been generated. The next section includes critical thinking questions in an open-ended discussion format that focus on the Big Ideas, proposing solutions for rectifying the situation, and/or assignments specifically targeting an idea presented in the case study chapter. Short, comprehensive multiple-choice quizzes are also in each chapter. Throughout the iBook, students are free to watch videos, explore the content and form their own opinions. As a result, this iBook fulfills the grant objective by engaging teachers and students with an innovative technological presentation that incorporates Earth system science with current case studies regarding global water issues.

  3. Systematic assessment of the various controversies, difficulties, and current trends in the reestablishment of lost occlusal planes in edentulous patients.

    Science.gov (United States)

    Sahoo, S; Singh, D; Raghav, D; Singh, G; Sarin, A; Kumar, P

    2014-05-01

    Accurate occlusal plane orientation is an essential factor in the fabrication of complete denture prosthesis. Over the years, it has received a number of methodologies by several researchers utilizing various anatomical landmarks however none of them is considered as perfect that could orient ideal occlusal plane. The presented literature review is an attempt to enlighten historical perspectives, pioneer researches, different controversies, difficulties and current trends for re-establishment of lost occlusal plane in edentulous patients. An extensive literature search was performed using Medline/PubMed interface and other scholarly research bibliographic databases using Medical Subject Headings. Studies describing research studies, case series and assorted clinical reports were retrieved and evaluated from 1963 to 2013. Most of the studies have suggest and evidence to consider Camper's plane for artificial orientation of occlusal plane however there is a substantial lack of genuine long term studies and authentic data that could recommend a single reliable landmark for perfect occlusal plane reorientation in a variety of cases.

  4. Investigating onychophoran gas exchange and water balance as a means to inform current controversies in arthropod physiology.

    Science.gov (United States)

    Clusella-Trullas, Susana; Chown, Steven L

    2008-10-01

    Several controversies currently dominate the fields of arthropod metabolic rate, gas exchange and water balance, including the extent to which modulation of gas exchange reduces water loss, the origins of discontinuous gas exchange, the relationship between metabolic rate and life-history strategies, and the causes of Palaeozoic gigantism. In all of these areas, repeated calls have been made for the investigation of groups that might most inform the debates, especially of taxa in key phylogenetic positions. Here we respond to this call by investigating metabolic rate, respiratory water loss and critical oxygen partial pressure (Pc) in the onychophoran Peripatopsis capensis, a member of a group basal to the arthropods, and by synthesizing the available data on the Onychophora. The rate of carbon dioxide release (VCO2) at 20 degrees C in P. capensis is 0.043 ml CO2 h(-1), in keeping with other onychophoran species; suggesting that low metabolic rates in some arthropod groups are derived. Continuous gas exchange suggests that more complex gas exchange patterns are also derived. Total water loss in P. capensis is 57 mg H2O h(-1) at 20 degrees C, similar to modern estimates for another onychophoran species. High relative respiratory water loss rates ( approximately 34%; estimated using a regression technique) suggest that the basal condition in arthropods may be a high respiratory water loss rate. Relatively high Pc values (5-10% O2) suggest that substantial safety margins in insects are also a derived condition. Curling behaviour in P. capensis appears to be a strategy to lower energetic costs when resting, and the concomitant depression of water loss is a proximate consequence of this behaviour.

  5. Plutonium controversy

    International Nuclear Information System (INIS)

    Richmond, C.R.

    1980-01-01

    The toxicity of plutonium is discussed, particularly in relation to controversies surrounding the setting of radiation protection standards. The sources, amounts of, and exposure pathways of plutonium are given and the public risk estimated

  6. Plutonium controversy

    Energy Technology Data Exchange (ETDEWEB)

    Richmond, C.R.

    1980-01-01

    The toxicity of plutonium is discussed, particularly in relation to controversies surrounding the setting of radiation protection standards. The sources, amounts of, and exposure pathways of plutonium are given and the public risk estimated. (ACR)

  7. Computational Controversy

    OpenAIRE

    Timmermans, Benjamin; Kuhn, Tobias; Beelen, Kaspar; Aroyo, Lora

    2017-01-01

    Climate change, vaccination, abortion, Trump: Many topics are surrounded by fierce controversies. The nature of such heated debates and their elements have been studied extensively in the social science literature. More recently, various computational approaches to controversy analysis have appeared, using new data sources such as Wikipedia, which help us now better understand these phenomena. However, compared to what social sciences have discovered about such debates, the existing computati...

  8. Current trends in microsponge drug delivery system.

    Science.gov (United States)

    Gangadharappa, H V; Gupta, N Vishal; Prasad M, Sarat Chandra; Shivakumar, H G

    2013-08-01

    Microsponge is a microscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microsponge having particle size of 10-25 microns in diameter, have wide range of entrapment of various ingredients in a single microsponges system and release them at desired rates. Conventional topical preparations have various disadvantages due to irritancy, odour, greasiness and patient compliance. In many topical dosage forms fail to reach the systemic circulation in sufficient amounts in few cases. These problems overcome by the usage of formulation as microsponge in the areas of research. Drug release in microsponge is done by the external stimuli like pH, temperature and rubbing. It has several advantageous over the other topical preparations in being non-allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are used in the sun screens, creams, ointments, over-the-counter skin care preparations, recently nanosponge were reported in literature used in delivery of drug by the use of cyclodextrins to enhance the solubility of poorly water soluble drugs, which are meant for topical application.

  9. Current manufacturing processes of drug-eluting sutures.

    Science.gov (United States)

    Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

    2017-11-01

    Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

  10. Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs.

    Science.gov (United States)

    Gualtieri, Fulvio; Manetti, Dina; Romanelli, Maria Novella; Ghelardini, Carla

    2002-01-01

    Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes. Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.

  11. Current situation and future usage of anticancer drug databases.

    Science.gov (United States)

    Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei

    2016-07-01

    Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.

  12. Heart Failure with Recovered EF and Heart Failure with Mid-Range EF: Current Recommendations and Controversies.

    Science.gov (United States)

    Unkovic, Peter; Basuray, Anupam

    2018-04-03

    This review explores key features and potential management controversies in two emerging populations in heart failure: heart failure with recovered ejection fraction (HF-recovered EF) and heart failure with mid-range ejection fraction (HFmrEF). While HF-recovered EF patients have better outcomes than heart failure with reduced ejection fraction (HFrEF), they continue to have symptoms, persistent biomarker elevations, and abnormal outcomes suggesting a continued disease process. HFmrEF patients appear to have features of HFrEF and heart failure with preserved ejection fraction (HFpEF), but have a high prevalence of ischemic heart disease and may represent a transitory phase between the HFrEF and HFpEF. Management strategies have insufficient data to warrant standardization at this time. HF-recovered EF and HFmrEF represent new populations with unmet needs and expose the pitfalls of an EF basis for heart failure classification.

  13. Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

    Science.gov (United States)

    Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

    2013-10-01

    Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

  14. Oral transmucosal drug delivery--current status and future prospects.

    Science.gov (United States)

    Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E

    2014-08-25

    Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Caffeine controversies.

    Science.gov (United States)

    Gentle, Samuel J; Travers, Colm P; Carlo, Waldemar A

    2018-04-01

    Caffeine use in preterm infants has endured several paradigms: from standard of care to possible neurotoxin to one of the few medications for which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The purpose of the review is to analyze this dynamic trajectory and discuss controversies that still remain after decades of caffeine use. Following concerns for caffeine safety in preterm infants, a large randomized controlled trial demonstrated a reduction in BPD and treatment for patent ductus arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18-21 months was not statistically different at later timepoints; however, infants in the caffeine group had lower rates of motor impairment at 11-year follow-up. The time of caffeine therapy initiation is now substantially earlier, and doses used are sometimes higher that previously used, but there are limited data to support these practices. Caffeine therapy for apnea of prematurity (AOP) remains one of the pillars of neonatal care, although more evidence to support dosing and timing of initiation and discontinuation are needed.

  16. What hath freud wrought? Current confusion and controversies about the clinical practice of psychoanalysis and psychodynamic psychotherapy.

    Science.gov (United States)

    Chessick, Richard D

    2014-12-01

    This article discusses the current state of psychoanalysis and the challenges to the fundamental premises of Freud's psychoanalysis by those who have shifted to relationship or so-called two-person psychologies in our field. The author begins by briefly describing a parallel to the recent history of psychoanalysis in the sudden rise and fall of scholastic philosophy in the 14th century. He then focuses on contemporary attacks on Freud's psychoanalysis as a science, based on the contention by two-person psychologists that free association by the patient and evenly hovering attention by the analyst are actually impossible. He reviews Freud's idea of psychoanalysis, discusses psychodynamic psychotherapy, both conceived as scientific treatment procedures, and describes the current assault on their metapsychological and epistemological foundations. Returning to the parallel between what happened to medieval scholasticism and what has happened to psychoanalysis, he examines why this happened, and the resulting fragmentation of psychoanalytic practice. The article concludes with suggestions for the integration of various schools of psychoanalysis, reminding us of Benjamin Franklin's warning: "We must, indeed, all hang together or, most assuredly, we shall all hang separately."

  17. [Development of antituberculous drugs: current status and future prospects].

    Science.gov (United States)

    Tomioka, Haruaki; Namba, Kenji

    2006-12-01

    Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are

  18. Inhibition of cardiac inward rectifier currents by cationic amphiphilic drugs.

    Science.gov (United States)

    van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A

    2013-09-01

    Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.

  19. Constructive Controversy

    DEFF Research Database (Denmark)

    Kock, Christian Erik J

    2009-01-01

    Current theories of argumentation underestimate the difference, emphasized already by Aristotle, between theoretical and practical (action-oriented) argumentation. This is exemplified with the argument theories of Toulmin, pragma-dialectics, Habermas, Walton, and Perelman. Since antiquity, rhetor......, but also inside each individual, several conflicting value dimensions are typically involved, not just the dimension of truth-falsity, which makes sustained, reasonable dissensus inevitable....

  20. Guns and Violence. Current Controversies.

    Science.gov (United States)

    Kim, Henny H., Ed.

    This book focuses on gun violence and gun control, presenting both sides of arguments about firearms ownership and gun control. Each of five chapters poses a question about gun control and provides answers for both sides of the question. The following essays are included: (1) "Gun Violence Is Becoming an Epidemic" (Bob Herbert); (2) "Gun Violence…

  1. Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

    Science.gov (United States)

    Milo, Ron

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  4. Emerging drugs of abuse: current perspectives on synthetic cannabinoids

    Directory of Open Access Journals (Sweden)

    Debruyne D

    2015-10-01

    Full Text Available Danièle Debruyne,1,2 Reynald Le Boisselier1 1Centre for Evaluation and Information on Pharmacodependence - Addictovigilance (CEIP-A, 2Toxicology and Pharmacology Laboratory, Department of Pharmacology, University Hospital Centre Côte de Nacre, Caen, France Abstract: New psychoactive drugs that have appeared over the last decade are typically dominated by cathinones and synthetic cannabinoids (SCs. SCs have been emerging as recreational drugs because they mimic the euphoria effect of cannabis while still being legal. Sprayed on natural herb mixtures, SCs have been primarily sold as “herbal smoking blends” or “herbal incense” under brand names like “Spice” or “K2”. Currently, SCs pure compounds are available from websites for the combination with herbal materials or for the use in e-cigarettes. For the past 5 years, an ever increasing number of compounds, representative of different chemical classes, have been promoted and now represent a large assortment of new popular drugs of abuse, which are difficult to properly identify. Their legal status varies by country with many government institutions currently pushing for their control. The in vitro binding to CB1/CB2 receptors is usually well-known and considerable differences have been found in the CB1 versus CB2 selectivity and potency within the different SCs, with several structure-activity relations being evident. Desired effects by CB1 agonist users are relaxation/recreative, however, cardiovascular, gastrointestinal, or psychiatric/neurological side effects are commonly reported. At present there is no specific antidote existing if an overdose of designer drugs was to occur, and no curative treatment has been approved by health authorities. Management of acute toxic effects is mainly symptomatic and extrapolated from experience with cannabis. Keywords: synthetic cannabinoids, chemistry, analysis, pharmacology, toxicology, dependence, medical care

  5. Current status of accreditation for drug testing in hair.

    Science.gov (United States)

    Cooper, Gail; Moeller, Manfred; Kronstrand, Robert

    2008-03-21

    At the annual meeting of the Society of Hair Testing in Vadstena, Sweden in 2006, a committee was appointed to address the issue of guidelines for hair testing and to assess the current status of accreditation amongst laboratories offering drug testing in hair. A short questionnaire was circulated amongst the membership and interested parties. Fifty-two responses were received from hair testing laboratories providing details on the amount and type of hair tests they offered and the status of accreditation within their facilities. Although the vast majority of laboratories follow current guidelines (83%), only nine laboratories were accredited to ISO/IEC 17025 for hair testing. A significant number of laboratories reporting that they were in the process of developing quality systems with a view to accrediting their methods within 2-3 years. This study provides an insight into the status of accreditation in hair testing laboratories and supports the need for guidelines to encourage best practice.

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

    Science.gov (United States)

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

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

  7. Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements.

    Science.gov (United States)

    Mincarone, Pierpaolo; Leo, Carlo Giacomo; Sabina, Saverio; Sarriá-Santamera, Antonio; Taruscio, Domenica; Serrano-Aguilar, Pedro Guillermo; Kanavos, Panos

    2017-01-01

    The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the "regulatory capture" effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases. © 2017 S. Karger AG, Basel.

  8. Orphan drugs in development for urea cycle disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Häberle J

    2014-09-01

    Full Text Available Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of ammonia. The resulting hyperammonemia causes severe brain injury unless aggressive steps are taken to reduce the accumulation of ammonia, which is thought to be the most toxic metabolite. This review describes the current state of chronic management of urea cycle disorders, focusing on new and emerging therapies. Management strategies include the mainstay of treatment, namely dietary protein restriction and supplementation with l-arginine or l-citrulline. Several currently approved medications utilize and enhance alternative pathways of waste nitrogen excretion (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate in several formulations, and glycerol phenylbutyrate, working through conjugation of the drug to either glycine (in the case of benzoate or glutamine, the products of which are excreted in the urine. Carglumic acid activates the first committed step of conversion of ammonia to urea, carbamoylphosphate synthetase, and thus effectively treats defective synthesis of the endogenous activator, N-acetylglutamate, whether due to genetic defects or biochemical inhibition of the N-acetylglutamate synthase enzyme. Approaches to neuroprotection during episodes of hyperammonemia are discussed, including the use of controlled hypothermia (brain cooling, as well as proposed, but as yet untested, pharmacologic therapies. Finally, cell-based therapies, including liver transplantation, infusion of fresh or cryopreserved hepatocytes, use of stem cells, and new approaches to gene

  9. 21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

    Science.gov (United States)

    2010-04-01

    ..., holding, or distribution of PET drugs intended for human use. Current good manufacturing practice is... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What is current good manufacturing practice for... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION...

  10. Adolescent varicocoele management controversies.

    Science.gov (United States)

    Serefoglu, E C; Saitz, T R; La Nasa, J A; Hellstrom, W J

    2013-01-01

    Varicocoele is defined as excessive dilatation of the pampiniform venous plexus of the spermatic cord. Varicocoele frequently appears during early puberty and is recognized to be the most common surgically correctable cause of male infertility. However, the actual incidence in adolescents, pathophysiology and the association with male factor infertility all remain somewhat controversial. The most accurate diagnostic technique for identifying young men who will benefit from surgical treatment has yet to be established. Observations of testicular asymmetry and deteriorating semen quality helped establish current guidelines and recommendations for surgical treatment. Further studies, comparing observation with surgical intervention, are needed to refine the current indications for varicocoele repair in the adolescent male. © 2012 American Society of Andrology and European Academy of Andrology.

  11. Current status of the New Antiepileptic drugs in chronic pain.

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Sidhu

    2016-08-01

    Full Text Available Antiepileptic drugs (AEDs are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various Non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder

  12. Vaginal drug delivery systems: A Review of Current Status | Dobaria ...

    African Journals Online (AJOL)

    Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...

  13. [The costs of new drugs compared to current standard treatment].

    Science.gov (United States)

    Ujeyl, Mariam; Schlegel, Claudia; Gundert-Remy, Ursula

    2013-01-01

    Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions. Copyright © 2013. Published by Elsevier GmbH.

  14. Siting controversial facilities

    International Nuclear Information System (INIS)

    Baird, R.D.; Blacker, P.B.

    1985-01-01

    There is often significant difficulty involved with siting controversial facilities. The social and political problems are frequently far more difficult to resolve than the technical and economic issues. The tendancy for most developing organizations is to address only technical issues in the search for a technically optimal site, to the exclusion of such weighting considerations as the social and political climate associated with potential sites--an approach which often imperils the success of the project. The site selection processes currently suggested is summarized and two contemporary examples of their application are cited. The difference between developers' real objectives and the objectives they have implicitly assumed by adopting the recommended approaches without augmentation are noted. The resulting morass of public opposition is attributed to the failure to consider the needs of individuals and groups who stand to be negatively impacted by the development. A comprehensive implementation strategy which addresses non-technical consideration in parallel with technical ones is presented and evaluated

  15. Access to orphan drugs in Europe: current and future issues.

    Science.gov (United States)

    Michel, Morgane; Toumi, Mondher

    2012-02-01

    Orphan drugs target small populations of patients. In order to make the field more attractive to pharmaceutical companies and encourage R&D in rare diseases, incentives were put forward by the EU, which are discussed in this article. Because they often are the only available option to treat a disease, some orphan drugs are considered to have high value and as such benefit from high prices on national markets. This has made orphan drugs an attractive market for pharmaceutical companies, with approximately 40 approved orphan drugs generating over $200 million each in yearly sales. The resulting burden this puts on national health insurances may lead to a change in regulation and will certainly lead to new national pricing and reimbursement strategies. They will need to be coherent, fair, effective and sustainable so as to be predictable for companies. Reflection on the subject needs to be initiated.

  16. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: CURRENT ASPECTS OF THEIR USE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2014-07-01

    Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.

  17. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: CURRENT ASPECTS OF THEIR USE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2013-01-01

    Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.

  18. Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report.

    Science.gov (United States)

    San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

    2018-01-01

    Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

  19. A survey of current trends in computational drug repositioning.

    Science.gov (United States)

    Li, Jiao; Zheng, Si; Chen, Bin; Butte, Atul J; Swamidass, S Joshua; Lu, Zhiyong

    2016-01-01

    Computational drug repositioning or repurposing is a promising and efficient tool for discovering new uses from existing drugs and holds the great potential for precision medicine in the age of big data. The explosive growth of large-scale genomic and phenotypic data, as well as data of small molecular compounds with granted regulatory approval, is enabling new developments for computational repositioning. To achieve the shortest path toward new drug indications, advanced data processing and analysis strategies are critical for making sense of these heterogeneous molecular measurements. In this review, we show recent advancements in the critical areas of computational drug repositioning from multiple aspects. First, we summarize available data sources and the corresponding computational repositioning strategies. Second, we characterize the commonly used computational techniques. Third, we discuss validation strategies for repositioning studies, including both computational and experimental methods. Finally, we highlight potential opportunities and use-cases, including a few target areas such as cancers. We conclude with a brief discussion of the remaining challenges in computational drug repositioning. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

  20. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  1. Current trend of drug sensitivity in bovine mastitis

    Directory of Open Access Journals (Sweden)

    Rajeev Ranjan

    2010-02-01

    Full Text Available The study was conducted on 190 milk samples of bovine mastitis and 138 samples were confirmed positives for microorganisms. All the 138 samples were subjected to drug sensitivity test. The most effective antibiotic was enrofloxacin (91.67% followed by ciprofloxacin (90.15%, amikacin (87.12%, ceftriaxone (84.10%, chloramphenicol (80.31%, cefotaxime (79.55% and gentamicin (77.27%. Microorganisms were mostly resistant to drugs like streptomycin, penicillinG, ampicillin, cloxacillin, amoxycillin and neomycin in increasing order of resistance. Hence, it is suggested that the line of treatment should be based on antibiogram study of various isolates from bovine mastitis. Further, the selection of drugs after culture and sensitivity test should be based on their ability to cross blood tissue barrier or mammary parenchyma, lipophilicity and ability to work in alkaline pH. [Vet. World 2010; 3(1.000: 17-20

  2. Role of Urine Drug Testing in the Current Opioid Epidemic.

    Science.gov (United States)

    Mahajan, Gagan

    2017-12-01

    While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.

  3. [Harm reduction interventions in drug users: current situation and recommendations].

    Science.gov (United States)

    Bosque-Prous, Marina; Brugal, María Teresa

    2016-11-01

    Harm reduction encompasses interventions, programmes and policies that seek to reduce the negative consequences of the consumption of both legal and illegal drugs on the individual and public health. Harm reduction looks to mitigate the harm suffered by drug users through drug use monitoring and prevention, and promotes initiatives that respect and protect the human rights of this population. The harm reduction policies that have proven effective and efficient are: opioid substitution maintenance therapy (methadone); needle and syringe exchange programmes; supervised drug consumption rooms; and overdose prevention through peer-based naloxone distribution. In order to be effective, these policies must have comprehensive coverage and be implemented in areas where the target population is prevalent. Resident-based opposition to the implementation of these policies is known as the NIMBY (Not In My Back Yard) phenomenon, which is characterised by being against the implementation of new measures in a particular place, but does not question their usefulness. Given that any NIMBY phenomenon is a complex social, cultural and political phenomenon, it is important to conduct a thorough analysis of the situation prior to implementing any of these measures. Harm reduction policies must be extended to other substances such as alcohol and tobacco, as well as to other conditions beyond infectious/contagious diseases and overdose. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Current and future drug targets in weight management

    NARCIS (Netherlands)

    Witkamp, R.F.

    2011-01-01

    Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being

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

    Science.gov (United States)

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

    2011-06-01

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

  6. Current French system of post-marketing drug surveillance.

    Science.gov (United States)

    Albengres, E; Gauthier, F; Tillement, J P

    1990-07-01

    The French system of drug surveillance is characterized by several original features: thirty regional centres are selected to cover all of France to collect, analyze and enter the adverse drug events in the national data bank. The system is based on a bank of well documented files submitted to a decision of imputation; the report of severe events by prescribers is mandatory; cases are collected either by spontaneous reporting (routine) or by direct request (intensive validation study); the system is being involved in studies of epidemiological type as carried out by the national system of health or a few societies of medicine as well as by the centres themselves in cooperative works on defined populations.

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

    OpenAIRE

    Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

    2017-01-01

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

  8. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    International Nuclear Information System (INIS)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-01-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

  9. Drugs currently under investigation for the treatment of invasive candidiasis.

    Science.gov (United States)

    McCarthy, Matthew W; Walsh, Thomas J

    2017-07-01

    The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

  10. Strongyloidiasis Current Status with Emphasis in Diagnosis and Drug Research

    Directory of Open Access Journals (Sweden)

    Tiago Mendes

    2017-01-01

    Full Text Available Strongyloidiasis is a parasitic neglected disease caused by the nematode Strongyloides stercoralis affecting 30 to 100 million people worldwide. Complications, strongly associated with alcoholism, organ transplants, and HTLV-1 virus, often arise due to late diagnosis, frequently leading to patient death. Lack of preemptive diagnosis is not the only difficulty when dealing with this parasite, since there are no gold standard diagnostic techniques, and the ones used have problems associated with sensitivity, resulting in false negatives. Treatment is also an issue as ivermectin and benzimidazoles administration leads to inconsistent cure rates and several side effects. Researching new anti-Strongyloides drugs is a difficult task since S. stercoralis does not develop until the adult stages in Mus musculus (with the exception of SCID mice, the main experimental host model. Fortunately, alternative parasite models can be used, namely, Strongyloides ratti and S. venezuelensis. However, even with these models, there are other complications in finding new drugs, which are associated with specific in vitro assay protocol steps, such as larvae decontamination. In this review, we highlight the challenges associated with new drug search, the compounds tested, and a list of published in vitro assay methodologies. We also point out advances being made in strongyloidiasis diagnosis so far.

  11. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  12. Current approaches for the discovery of drugs that deter substance and drug abuse.

    Science.gov (United States)

    Yasgar, Adam; Simeonov, Anton

    2014-11-01

    Much has been presented and debated on the topic of drug abuse and its multidimensional nature, including the role of society and its customs and laws, economical factors, and the magnitude and nature of the burden. Given the complex nature of the receptors and pathways implicated in regulation of the cognitive and behavioral processes associated with addiction, a large number of molecular targets have been interrogated during recent years to discover starting points for development of small-molecule interventions. This review describes recent developments in the field of early drug discovery for drug abuse interventions with an emphasis on the advances published during the 2012 - 2014 period. Technologically, the processes/platforms utilized in drug abuse drug discovery are nearly identical to those used in the other disease areas. A key complicating factor in drug abuse research is the enormous biological complexity surrounding the brain processes involved and the associated difficulty in finding 'good' targets and achieving exquisite selectivity of treatment agents. While tremendous progress has been made during recent years to use the power of high-throughput technologies to discover proof-of-principle molecules for many new targets, next-generation models will be especially important in this field. Examples include: seeking advantageous drug-drug combinations, the use of automated whole-animal behavioral screening systems, advancing our understanding of the role of epigenetics in drug addiction and the employment of organoid-level 3D test platforms (also referred to as tissue-chip or organs-on-chip).

  13. Cardiovascular effects of current and future anti-obesity drugs

    DEFF Research Database (Denmark)

    Comerma Steffensen, Simon Gabriel; Grann, Martin; Andersen, Charlotte U

    2014-01-01

    cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular...... side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol...

  14. Current knowledge on biodegradable microspheres in drug delivery.

    Science.gov (United States)

    Prajapati, Vipul D; Jani, Girish K; Kapadia, Jinita R

    2015-08-01

    Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery. This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres. There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.

  15. The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

    Directory of Open Access Journals (Sweden)

    Malcolm J. Reid

    2011-12-01

    Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

  16. The nuclear controversy

    International Nuclear Information System (INIS)

    Walske, C.; Dobkin, R.A.

    1984-01-01

    The article deals with the nuclear controversy, especially in the United States. To a certain extent the nuclear debate has become heavily politicised. Public opinion and anti-nuclear groups are mentioned as well as nuclear disarmament

  17. Emerging drugs of abuse: current perspectives on substituted cathinones

    Directory of Open Access Journals (Sweden)

    Paillet-Loilier M

    2014-05-01

    Full Text Available Magalie Paillet-Loilier,1 Alexandre Cesbron,1 Reynald Le Boisselier,2 Joanna Bourgine,1 Danièle Debruyne1,2 1Toxicology and Pharmacology Laboratory, 2Centre d'Evaluation et d'Information sur la Pharmacodépendance – Addictovigilance (CEIP-A, Department of Pharmacology, University Hospital Centre, Caen, France Abstract: Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension and psychiatric

  18. The current status of orphan drug development in Europe and the US

    OpenAIRE

    Hall, Anthony K; Carlson, Marilyn R

    2014-01-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, e...

  19. Purification of drugs from biological fluids by counter-current chromatography.

    Science.gov (United States)

    Hochlowski, Jill E; Pan, Jeffrey Y; Searle, Philip A; Buck, Wayne R; Spanton, Stephen G

    2009-08-21

    Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR.

  20. Energy, controversies and prospects

    International Nuclear Information System (INIS)

    Bertholet, J.-L.; Garbely, M.; Lachal, B.; Romerio, F.; Weber, W.

    2003-01-01

    The energy debate raises deep controversies, as discussions on climate change or electricity markets' deregulation show. In this context, it is very difficult for the citizen to express himself in referendums and for the decision maker to slice between various options. Experts themselves deliver controversial evaluations and interest groups can benefit from them to suggest their own solution. This book enables to get a better insight and better understand energy-related controversies and the environmental and socio-economic impacts of energy. It deals with topics as complex and politically extreme as the exhaustion of fossil fuels, climate change, ionising radiations, renewable energy sources, energy consumption in Southern countries and the reorganisation of electricity markets. It starts with an article on the precaution principle and it ends with a glance on the future, devoted to education in the field of efficient energy use [fr

  1. Obstetric controversies in thyroidology

    Directory of Open Access Journals (Sweden)

    Ambika Gopalakrishnan Unnikrishnan

    2013-01-01

    Full Text Available It is well known that thyroid disorders commonly affect women. The care of pregnant women affected by thyroid disease is an important clinical challenge for endocrinologists. Hypothyroidism is the commonest problem, and maternal hypothyroxinemia has been linked to adverse feto-maternal outcomes. This article would discuss the controversy regarding first-trimester thyroid hormone deficiency and fetal brain development. Certain obstetric controversies in the management of hyperthyroidism in pregnancy, including the indications of TSH receptor antibody measurements and fetal thyroid status monitoring would also be discussed.

  2. Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions.

    Science.gov (United States)

    Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm

    2014-12-01

    With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes. Therefore, approaches employing chromatographic-mass spectrometric, electrophoretic, immunological and combined test methods have been required and developed. These allow detecting the misuse of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs, 'full-length' mechano growth factor, growth hormone, chorionic gonadotropin, erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired specificity and sensitivity. A gap between the technically possible detection and the day-to-day analytical practice, however, still needs to be closed.

  3. Current Situation, Determinants, and Solutions to Drug Shortages in Shaanxi Province, China: A Qualitative Study.

    Science.gov (United States)

    Yang, Caijun; Wu, Lina; Cai, Wenfang; Zhu, Wenwen; Shen, Qian; Li, Zongjie; Fang, Yu

    2016-01-01

    Drug shortages were a complex global problem. The aim of this study was to analyze, characterize, and assess the drug shortages, and identify possible solutions in Shaanxi Province, western China. A qualitative methodological approach was conducted during May-June 2015 and December 2015-January 2016. Semi-structured interviews were performed to gather information from representatives of hospital pharmacists, wholesalers, pharmaceutical producers, and local health authorities. Thirty participants took part in the study. Eight traditional Chinese medicines and 87 types of biologicals and chemicals were reported to be in short supply. Most were essential medicines. Five main determinants of drug shortages were detected: too low prices, too low market demands, Good Manufacturing Practice (GMP) issues, materials issues, and approval issues for imported drugs. Five different solutions were proposed by the participants: 1) let the market decide the drug price; 2) establish an information platform; 3) establish a reserve system; 4) enhance the communication among the three parties in the supply chain; and 5) improve hospital inventory management. Western China was currently experiencing a serious drug shortage. Numerous reasons for the shortage were identified. Most drug shortages in China were currently because of "too low prices." To solve this problem, all of the stakeholders, especially the government, needed to participate in managing the drug shortages.

  4. Fed-state gastric media and drug analysis techniques: Current status and points to consider.

    Science.gov (United States)

    Baxevanis, Fotios; Kuiper, Jesse; Fotaki, Nikoletta

    2016-10-01

    Gastric fed state conditions can have a significant effect on drug dissolution and absorption. In vitro dissolution tests with simple aqueous media cannot usually predict drugs' in vivo response, as several factors such as the meal content, the gastric emptying and possible interactions between food and drug formulations can affect drug's pharmacokinetics. Good understanding of the effect of the in vivo fed gastric conditions on the drug is essential for the development of biorelevant dissolution media simulating the gastric environment after the administration of the standard high fat meal proposed by the FDA and the EMA in bioavailability/bioequivalence (BA/BE) studies. The analysis of drugs in fed state media can be quite challenging as most analytical protocols currently employed are time consuming and labour intensive. In this review, an overview of the in vivo gastric conditions and the biorelevant media used for their in vitro simulation are described. Furthermore an analysis of the physicochemical properties of the drugs and the formulations related to food effect is given. In terms of drug analysis, the protocols currently used for the fed state media sample treatment and analysis and the analytical challenges and needs emerging for more efficient and time saving techniques for a broad spectrum of compounds are being discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery.

    Science.gov (United States)

    Muddineti, Omkara Swami; Ghosh, Balaram; Biswas, Swati

    2017-06-01

    Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years. Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.

  6. Measurement of Drug Craving in Persian Speaking Subjects; a Review on Current Experiences and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Masoomeh Maarefvand

    2012-09-01

    Full Text Available Background: Drug craving is considered as one of the main cores of drug dependency and addiction. Multidimensionality of drug craving, its cultural-bounded features and its intra individual rapidly changing nature makes it difficult to be measured. Nowadays, regarding different psychometric approaches, there are various instruments available for measurement of different aspects of drug craving but mainly for Latin-based languages in North America and European countries. High prevalence and special conditions, and unique subcultures in substance abuse and addiction in many countries, like Iran, make the design of culturally validated instruments for drug craving assessment priority. Materials and Methods: Comprehensive review on drug craving measurement instruments for Persian speaking subjects have been performed by searching in databases (ELSEVIER, Science Direct and Scientific Information Database (SID and investigating of related documents on regional experiences. Results: In this article seven main categories of drug craving instruments have been reviewed focusing on validated versions in Persian language including: self-reports, reinforcement “proxies”, drug self administration, psycho physiological responding, neurobiological responding, cognitive processing and expressive methods. Conclusion: Reviewing on weak and strength points of each instrument group and national and regional experiences shows that designing and validating a new series of ecologically-validated instruments for multidimensional measurement of drug craving in different addiction subcultures should be prioritized to cover current methodological gaps in substance abuse studies in Iran.

  7. Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule.

    Science.gov (United States)

    2008-07-15

    The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.

  8. Controversies in Obesity Treatment

    Directory of Open Access Journals (Sweden)

    Majid Karandish

    2015-06-01

    Full Text Available The markedly high prevalence of obesity contributes to the increased incidence of chronic diseases, such as diabetes, hypertension, sleep apnea, and heart disease. Because of high prevalence of obesity in almost all countries, it has been the focus of many researches throughout the world during the recent decades. Along with increasing researches, new concepts and controversies have been emerged. The existing controversies on the topic are so deep that some researches argue on absolutely philosophical questions such as “Is obesity a disease?” or “Is it correct to treat obesity?” These questions are based on a few theories and real data that explain obesity as a biological adaptation and also the final results of weight loss programs. Many people attempt to lose weight by diet therapy, physical activity and lifestyle modifications. Importantly, weight loss strategies in the long term are ineffective and may have unintended consequences including decreasing energy expenditure, complicated appetite control, eating disorders, reducing self-esteem, increasing the plasma and tissue levels of persistent organic pollutants that promote metabolic complications, and consequently, higher risk of repeated cycles of weight loss and weight regain. In this review, major paradoxes and controversies on obesity including classic obesity paradox, pre-obesity; fat-but-fit theory, and healthy obesity are explained. In addition, the relevant strategies like “Health at Every Size” that emphasize on promotion of global health behaviors rather than weight loss programs are explained.

  9. Current and emerging lipid-based systems for transdermal drug delivery.

    Science.gov (United States)

    Singla, Sumeet K; Sachdeva, Vishal

    2015-01-01

    Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

  10. The current status of orphan drug development in Europe and the US.

    Science.gov (United States)

    Hall, Anthony K; Carlson, Marilyn R

    2014-02-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, explain the incentives and procedures, and touch on the role of patient organisations in the process.

  11. Frontotemporal dementias: Recent advances and current controversies

    Directory of Open Access Journals (Sweden)

    Leyton Cristian

    2010-10-01

    Full Text Available Frontotemporal dementia (FTD syndromes comprise a heterogeneous group of neurodegenerative conditions characterized by atrophy in the frontal and temporal lobes. Three main clinical variants are recognized: Behavioral variant (bv-FTD, Semantic dementia (SD, and Progressive nonfluent aphasia (PNFA. However, logopenic/phonological (LPA variant has been recently described, showing a distinctive pattern of brain atrophy and often associated to Alzheimer′s disease pathology. The diagnosis of FTD is challenging, since there is clinical, pathological, and genetic overlap between the variants and other neurodegenerative diseases, such as motoneuron disease (MND and corticobasal degeneration (CBD. In addition, patients with gene mutations (tau and progranulin display an inconsistent clinical phenotype and the correspondence between the clinical variant and its pathology is unpredictable. New cognitive tests based on social cognition and emotional recognition together with advances in molecular pathology and genetics have contributed to an improved understanding. There is now a real possibility of accurate biomarkers for early diagnosis. The present review concentrates on new insights and debates in FTD.

  12. Current Opinion and Controversies of Dialyser Reuse

    Directory of Open Access Journals (Sweden)

    Brown Colin

    2001-01-01

    Full Text Available Reuse of dialysers has been an integral part of hemodialysis since its inception. Over the past decade, reuse has increased significantly in many countries, most notably in the United States, while vanishing entirely in some other countries, such as Portugal and France. In the United States, which is most widely used as an example because of the large amount of data available, the mortality of dialysis patients has steadily decreased even as reuse has increased. This improvement is probably the result of a complex of factors including understanding the role of comorbidity, treatment unit characteristics, barriers to adequate dialysis, nutrition, anemia, high flux dialysis and dialyser membrane improvements and the desired dialysis dose. Reuse provides a significant economic benefit that allows the use of more efficient and expensive larger biocompatible synthetic membranes to provide high-quality dialysis in the face of cost inflation, limited medical resources and fixed reimbursement. Rather than being legitimized by clinical practice alone, reprocessing, supported by clinical studies, allows the provision of superior treatment to more patients safely and economically. Recent reports concerning dialyser reprocessing have centered not only on morbidity and mortality, but also on questions of the specific effects of different germicides on various types of dialyser membranes (e.g., cellulosic, synthetic, high-flux, etc. and on the possible role of dialyser reprocessing in the transmission of hepatitis C.

  13. Wundt on Introspection: Reflection on Current Controversy.

    Science.gov (United States)

    Leahey, Thomas H.; And Others

    Wilhelm Wundt provided a complete and concise description of his introspective method in a 1907 paper criticizing the thought experiments conducted by the Wurzburg psychologists. This major work is now being translated for the first time. For Wundt, the role of experimental method was to ensure the best conditions for observing and reporting…

  14. Intuitive Physics: Current Research and Controversies.

    Science.gov (United States)

    Kubricht, James R; Holyoak, Keith J; Lu, Hongjing

    2017-10-01

    Early research in the field of intuitive physics provided extensive evidence that humans succumb to common misconceptions and biases when predicting, judging, and explaining activity in the physical world. Recent work has demonstrated that, across a diverse range of situations, some biases can be explained by the application of normative physical principles to noisy perceptual inputs. However, it remains unclear how knowledge of physical principles is learned, represented, and applied to novel situations. In this review we discuss theoretical advances from heuristic models to knowledge-based, probabilistic simulation models, as well as recent deep-learning models. We also consider how recent work may be reconciled with earlier findings that favored heuristic models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Marijuana: Current Concepts†

    OpenAIRE

    Greydanus, Donald E.; Hawver, Elizabeth K.; Greydanus, Megan M.; Merrick, Joav

    2013-01-01

    Marijuana (cannabis) remains a controversial drug in the twenty-first century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mai...

  16. 21 CFR 1404.135 - May the Office of National Drug Control Policy exclude a person who is not currently...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false May the Office of National Drug Control Policy exclude a person who is not currently participating in a nonprocurement transaction? 1404.135 Section 1404.135 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) General § 1404.135 May the...

  17. Structural basis of drugs that increase cardiac inward rectifier Kir2.1 currents.

    Science.gov (United States)

    Gómez, Ricardo; Caballero, Ricardo; Barana, Adriana; Amorós, Irene; De Palm, Sue-Haida; Matamoros, Marcos; Núñez, Mercedes; Pérez-Hernández, Marta; Iriepa, Isabel; Tamargo, Juan; Delpón, Eva

    2014-11-01

    We hypothesize that some drugs, besides flecainide, increase the inward rectifier current (IK1) generated by Kir2.1 homotetramers (IKir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. To test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on Kir2.x channels. Currents were recorded with the patch-clamp technique using whole-cell, inside-out, and cell-attached configurations. Propafenone (0.1 nM-1 µM) did not modify either IK1 recorded in human right atrial myocytes or the current generated by homo- or heterotetramers of Kir2.2 and 2.3 channels recorded in transiently transfected Chinese hamster ovary cells. On the other hand, propafenone increased IKir2.1 (EC50 = 12.0 ± 3.0 nM) as a consequence of its interaction with Cys311, an effect which decreased inward rectification of the current. Propafenone significantly increased mean open time and opening frequency at all the voltages tested, resulting in a significant increase of the mean open probability of the channel. Timolol, which interacted with Cys311, was also able to increase IKir2.1. On the contrary, neither atenolol nor dronedarone modified IKir2.1. Molecular modelling of the Kir2.1-drugs interaction allowed identification of the pharmacophore of drugs that increase IKir2.1. Kir2.1 channels exhibit a binding site determined by Cys311 that is responsible for drug-induced IKir2.1 increase. Drug binding decreases channel affinity for polyamines and current rectification, and can be a mechanism of drug-induced pro- and antiarrhythmic effects not considered until now. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  18. Weak value controversy

    Science.gov (United States)

    Vaidman, L.

    2017-10-01

    Recent controversy regarding the meaning and usefulness of weak values is reviewed. It is argued that in spite of recent statistical arguments by Ferrie and Combes, experiments with anomalous weak values provide useful amplification techniques for precision measurements of small effects in many realistic situations. The statistical nature of weak values is questioned. Although measuring weak values requires an ensemble, it is argued that the weak value, similarly to an eigenvalue, is a property of a single pre- and post-selected quantum system. This article is part of the themed issue `Second quantum revolution: foundational questions'.

  19. Cartography of architectural controversies

    DEFF Research Database (Denmark)

    Lotz, Katrine

    2009-01-01

    on the visual materials and documents produced during the process, and interviews with architects, clients and engineers, I describe the continuous efforts to establish and strengthen architectural motives, and how they eventually gain the ability to align other motives and other actors. I suggest...... that employing the visualising methods of the recent development of Actor-Network-Theory called ‘Cartography of Controversies' might contribute to trans-disciplinary efforts to develop analytic understanding of the conflicting human purposes and power-struggles at stake in the be-coming of architecture....

  20. Mapping Wind Energy Controversies

    DEFF Research Database (Denmark)

    Munk, Anders Kristian

    As part the Wind2050 project funded by the Danish Council for Strategic Research we have mapped controversies on wind energy as they unfold online. Specifically we have collected two purpose built datasets, a web corpus containing information from 758 wind energy websites in 6 different countries......, and a smaller social media corpus containing information from 14 Danish wind energy pages on Facebook. These datasets have been analyzed to answer questions like: How do wind proponents and opponents organize online? Who are the central actors? And what are their matters of concern? The purpose of this report...

  1. Exxon Valdez controversy revived

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Four years after its occurrence rocked the petroleum industry and revitalized the US environmental movement, the Exxon Valdez tanker oil spill off Alaska continues to stir controversy. Conflicting reports abound over whether there is long term damage to the Prince William Sound ecosystem resulting from the March 24, 1989, spill. Government scientists at recent conferences disclosed studies they contend show long term, significant damage to the sound. Exxon this month launched a counteroffensive, disclosing results of studies it funded that it claims show no credible scientific evidence of long term damage. At the same time, the company blasted as flawed the government's data on assessing environmental damage to the sound and charged that test samples from the sound were mishandled. Meantime, Prince William Sound still shows lingering effects from the Exxon Valdez oil spill. But recovery has been so rapid that there is more controversy over how to use $900 million in natural resource recovery funds that Exxon paid than over how badly species are suffering. The paper describes Exxon's studies; faulty data; lingering damage; and an update on tanker safety

  2. The breast implant controversy.

    Science.gov (United States)

    Cook, R R; Harrison, M C; LeVier, R R

    1994-02-01

    The breast implant issue is a "bad news/good news" story. For many women with implants, the controversy has caused a fair degree of anxiety which may or may not be resolved as further information becomes available. It has also taken its toll on Dow Corning. Whole lines of medical products have been eliminated or are being phase out. The development of new medical applications has been terminated. As a consequence, employees have lost their jobs. What the effect will be on the biomedical industry as a whole remains to be seen (11). While silicones have been an important component in various medical devices, it is likely that other materials can be used as replacements. However, suppliers of non-silicone materials are also reevaluating their role in this market. For example, Du Pont, the nation's largest chemical company, has determined that the unpredictable and excessive costs of doing business with manufacturers of implantable medical devices no longer justifies the unrestricted sale of standard raw materials into this industry. Other companies are quietly following suit. On the up side, it is possible that the research being driven by this controversy will result in a greater understanding of the immunologic implications of xenobiotics, of the importance of nonbiased observations, of the need for ready access to valid data sets, and of the opportunity for valid scientific information to guide legal decisions. Only time will tell.

  3. Understanding and Developing Controversial Issues in College Courses.

    Science.gov (United States)

    Payne, Brian K.; Gainey, Randy R.

    2003-01-01

    Discusses common controversial issues in different college disciplines, such as the death penalty and drug legalization. Also suggests useful methods for encouraging enlightening discussions, such as verbal and physical cues, student-centered activities, and text selection. (SLD)

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

    Science.gov (United States)

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

    2013-11-18

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

  5. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

    Science.gov (United States)

    Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

    2017-11-01

    Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

  6. Current prescription status of antihypertensive drugs with special reference to the use of diuretics in Japan.

    Science.gov (United States)

    Ibaraki, Ai; Goto, Wataru; Iura, Rie; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

    2017-02-01

    The guidelines for the management of hypertension recommend the inclusion of diuretics, especially when three or more antihypertensive drugs are used. The present study investigated the current prescription status of antihypertensive drugs with a particular focus on the use of diuretics in a local district in Japan. Prescriptions, including antihypertensive drugs, were collected from a dispensing pharmacy of the Yahata Pharmacist Association, located in Kitakyushu City, in October 2014. Of the 10 585 prescriptions, calcium channel blockers (CCBs) were prescribed in 73.5%, followed by angiotensin II receptor blockers (ARB, 62.7%), diuretics (16.5%) and β-blockers (13.6%). The average number of drugs used was 1.80. The rates of prescription of diuretics for patients with one, two, three and four drugs were 0.6%, 13.1%, 55.2% and 82.6%, respectively. Diuretics were more frequently prescribed in elderly patients, and the prescription rate of doctors in hospitals was significantly higher than that of general practitioners (19.1% vs. 15.7%, Pdiuretics were prescribed combination tablets of hydrochlorothiazide with ARB, whereas trichlormethiazide (34.9%) and indapamide (19.8%) were used in other patients. Based on these findings, the use of diuretics remains limited, even among patients taking multiple antihypertensive drugs.

  7. Current knowledge of microRNA-mediated regulation of drug metabolism in humans.

    Science.gov (United States)

    Nakano, Masataka; Nakajima, Miki

    2018-05-01

    Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.

  8. Controversies in gestational diabetes.

    Science.gov (United States)

    Nolan, Christopher J

    2011-02-01

    Gestational diabetes mellitus (GDM) and controversy are old friends. However, several major studies in the field have clarified some of the main issues. There is now no doubt that hyperglycaemia, at levels less than those that occur in overt diabetes, is associated with adverse pregnancy outcomes, such as large-for-gestational age infants, neonatal hyperinsulinism, neonatal hypoglycaemia and pre-eclampsia. We also have evidence now that a standard approach to GDM with diagnosis at 24-28 weeks, dietary advice, self-monitoring of blood glucose and insulin therapy as needed reduces these adverse perinatal outcomes. Unknown, however, is if this same approach is effective at reducing long-term risks of metabolic syndrome, type 2 diabetes and cardiovascular disease in both the mothers and babies. For example, could our management strategies miss critical time points of fuel-mediated injury to the foetus important for the baby's long-term metabolic health? The implications of a recent international consensus statement on new diagnostic criteria for GDM are discussed, as well as issues relating to the timing of diagnosis. The potential place for a risk calculator for adverse outcomes in GDM pregnancy that takes into account glycaemic and non-glycaemic risk factors is considered. Such a tool could help stratify GDM women to different levels of care. Ongoing issues relating to maternal glycaemic and foetal growth targets, and the use of oral hypoglycaemic agents in GDM are discussed. To resolve some of the remaining controversies, further carefully designed randomised controlled trials in GDM with long-term follow-up of both mothers and babies are necessary. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. The current state of GPCR-based drug discovery to treat metabolic disease.

    Science.gov (United States)

    Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

    2018-02-02

    One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

  10. Controversies in breast cancer: adjuvant and neoadjuvant therapy.

    Science.gov (United States)

    Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

    2005-06-01

    Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

  11. Debating Diversity: Ethics and Controversial Public Issues

    Science.gov (United States)

    Darr, Christopher R.

    2016-01-01

    Courses: Ethics, Organizational Communication, Political Communication. Objectives: After completing this unit activity, students should be able to (1) apply multiple ethical perspectives to real-world diversity issues in a debate format, and (2) explain the role of informational and social category diversity in current controversies.

  12. PREVALENCE OF MULTIPLE ADDICTIONS AND CURRENT TREATMENT BY DRUG TREATMENT CENTRES IN DURBAN, SOUTH AFRICA

    Directory of Open Access Journals (Sweden)

    Keen, Helen

    2015-09-01

    Full Text Available Substance-use disorders (SUD cause severe problems both globally and locally. Research suggests that multiple addictions create a more complex illness. This study investigated whether in-patients admitted for SUD at three drug treatment centres in Durban, South Africa had other, undiagnosed addictions. It utilised a three-phase concurrent mixed-methods design and initially screened for gambling and sex addiction. Results showed that, of the sample of 123 participants, 54% had either sex or gambling and 24% had both addictions which current treatment programmes neither assessed for nor treated. Recommendations include suggestions to update current assessment and treatment approaches and the need to train professional staff at drug treatment centres.

  13. Varicocele: Management and the continuing controversies

    Directory of Open Access Journals (Sweden)

    P S Agbo

    2010-01-01

    Full Text Available Varicoceles have long been associated with infertility. Despite this long history, there remains much controversy regarding their aetiology and management. The aim of this review is to present the most current information on the management of varicoceles and to highlight some of the management controversies: Association of varicocele with male infertility; Management of varicocele in adolescent; safety and effectiveness of varicocele embolization and management of subclinical varicoceles. It is hoped that this review study will stimulate further research into this condition in order to find a more common ground regarding its management.

  14. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  15. Darwinian Controversies: An Historiographical Recounting

    Science.gov (United States)

    Depew, David J.

    2010-05-01

    This essay reviews key controversies in the history of the Darwinian research tradition: the Wilberforce-Huxley debate in 1860, early twentieth-century debates about the heritability of acquired characteristics and the consistency of Mendelian genetics with natural selection; the 1925 Scopes trial about teaching evolution; tensions about race, culture, and eugenics at the 1959 centenary celebration Darwin’s Origin of Species; adaptationism and its critics in the Sociobiology debate of 1970s and, more recently, Evolutionary Psychology; and current disputes about Intelligent Design. These controversies, I argue, are etched into public memory because they occur at the emotionally charged boundaries between public-political, technical-scientific, and personal-religious spheres of discourse. Over most of them falls the shadow of eugenics. The main lesson is that the history of Darwinism cannot be told except by showing the mutual influence of the different norms of discourse that obtain in the personal, technical, and public spheres. Nor can evolutionary biology successfully be taught to citizens and citizens-to-be until the fractious intersections between spheres of discourse have been made explicit. In the course of showing why, I take rival evolutionary approaches to be dynamical historical research traditions rather than static theories. Accordingly, I distinguish Darwin’s version of Darwinism from its later transformations. I pay special attention to the role Darwin assigned to development in evolution, which was marginalized by twentieth-century population genetical Darwinism, but has recently resurfaced in new forms. I also show how the disputed phrases “survival of the fittest” and “social Darwinism” have shaped personal anxieties about “Darwinism,” have provoked public opposition to teaching evolution in public schools, and have cast a shadow over efforts to effectively communicate to the public largely successful technical efforts to make

  16. Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.

    Science.gov (United States)

    Zumla, Alimuddin; Abubakar, Ibrahim; Raviglione, Mario; Hoelscher, Michael; Ditiu, Lucica; McHugh, Timothy D; Squire, S Bertel; Cox, Helen; Ford, Nathan; McNerney, Ruth; Marais, Ben; Grobusch, Martin; Lawn, Stephen D; Migliori, Giovanni-Battista; Mwaba, Peter; O'Grady, Justin; Pletschette, Michel; Ramsay, Andrew; Chakaya, Jeremiah; Schito, Marco; Swaminathan, Soumya; Memish, Ziad; Maeurer, Markus; Atun, Rifat

    2012-05-15

    Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR

  17. Direct-to-consumer marketing of prescription drugs: a current perspective for neurologists and psychiatrists.

    Science.gov (United States)

    Hollon, Matthew F

    2004-01-01

    In the US and New Zealand, the past decade has seen tremendous growth in the marketing of prescription drugs directly to patients. The pharmaceutical industry has applied pressure in other countries to relax regulations governing such marketing although this has not yet been successful. While we still have much to learn about the potential impact on the public's health of direct-to-consumer (DTC) marketing, some data are available. This article summarises the current literature on the benefits and risks of DTC marketing. This marketing strategy has grown substantially in the US, but only select drugs are advertised. Whether there is net benefit or harm to the public's health as a result of DTC marketing depends critically on which drugs are advertised and the quality of the information provided in promotional material. Critical reviews of this promotional material suggest the information is of poor quality. Notably, 18% of the 50 drugs advertised most intensively in the US were medications used to treat psychiatric and neurological disorders. The impairments in decisional capacity often seen in psychiatric and neurological illness leave patients vunerable to the controlling influence of DTC marketing and, thus, undermine the patient autonomy that is said to be promoted by this marketing strategy. If there is any benefit from DTC marketing it is for significantly undertreated conditions. International restrictions on DTC marketing should remain in place until further evidence of net benefit or harm emerges from the DTC marketing experiment that is taking place in the US and New Zealand.

  18. Therapeutic drug monitoring in pediatric IBD: current application and future perspectives.

    Science.gov (United States)

    Lega, Sara; Bramuzzo, Matteo; Dubinsky, Marla

    2017-09-11

    As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies. In the era of biologics, TDM entered the clinical field to assist clinicians managing anti-TNF failure and its role is now moving toward the concept of "proactive" TDM with the goal to optimize drug exposure and prevent loss of response. Research in TDM is rapidly expanding: while the role of TDM with new biologics is under investigation, preliminary data suggest that software-systems support tools could be an opportunity to guide dosing choices and maximize the cost-benefit profile of therapies in the near future. The review discusses the current knowledge that poses the rationale for the use of TDM and the present and future role of TDM-based approaches in the management of pediatric IBD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Current challenges and emerging drug delivery strategies for the treatment of psoriasis.

    Science.gov (United States)

    Hoffman, Melissa B; Hill, Dane; Feldman, Steven R

    2016-10-01

    Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients' psychosocial needs, treatment costs, convenience, and effectiveness with patients' preferences in order to optimize treatment outcomes.

  20. Application of thermally stimulated current measurement to the polymorphic characterization of drug substances

    International Nuclear Information System (INIS)

    Ikeda, Y.; Hirayama, T.; Terada, K.

    2005-01-01

    The thermal stimulated current measurement was used as an innovative analytical equipment to evaluate the polymorphic properties of terfenadine and Compound A, being developed by Takeda Pharmaceutical Company, Limited. At first, terfenadine, which is known to have polymorphs, was used as a model sample for thermally stimulated current (TSC) analyses. The TSC curves of amorphous and two polymorphs were distinctly different from each other. Therefore, it was considered that TSC measurement could be a useful technique to evaluate the crystalline properties of drug substances. The polymorphs of compound A were difficult to distinguish the characteristics of polymorphs from conventional powder X-ray diffractometry and also differential scanning calorimetry. Forms A and B of compound A were clearly differentiated by the thermal stimulated current properties that were adequate to characterize each form. Thus, it was shown that TSC was extremely useful and powerful tool for identification of complicated polymorphs, which were not distinguished by conventional methods

  1. Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes.

    Science.gov (United States)

    Palleria, Caterina; Leporini, Christian; Maida, Francesca; Succurro, Elena; De Sarro, Giovambattista; Arturi, Franco; Russo, Emilio

    2016-07-01

    Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment. We have focused our attention on the possible effect on the brain of antidiabetic drugs, despite their effects on blood glucose levels, giving a brief rationale on the mechanisms (e.g. GLP-1, BDNF, ghrelin) that might be involved. Indeed, GLP-1 agonists are currently clinically studied in other neurodegenerative diseases (i.e. Parkinson's and Alzheimer's disease); furthermore, also other antidiabetic drugs have proven efficacy in preclinical studies. Overall, promising results are already available and finding new intervention strategies represents a current need in this field of research. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    OpenAIRE

    Asija Rajesh; Chaudhari Bharat; Asija Sangeeta

    2012-01-01

    Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...

  3. Current Landscape of Antiviral Drug Discovery [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Wade Blair

    2016-02-01

    Full Text Available Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV and hepatitis B virus (HBV; however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV and influenza (flu. Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.

  4. Ibuprofen in paediatrics: pharmacology, prescribing and controversies.

    Science.gov (United States)

    Moriarty, Camilla; Carroll, Will

    2016-12-01

    Ibuprofen, a propionic acid derivative, is a non-steroidal anti-inflammatory drug. The oral formulation is widely used in paediatric practice and after paracetamol it is one of the most common drugs prescribed for children in hospital. The treatment of fever with antipyretics such as ibuprofen is controversial as fever is the normal response of the body to infection and unless the child becomes distressed or symptomatic, fever alone should not be routinely treated. Combined treatment with paracetamol and ibuprofen is commonly undertaken but almost certainly is not helpful. This article aims to describe the indications and mode of action of the drug, outline its pharmacokinetics and highlight the important key messages regarding its use in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Alternatives to currently used antimalarial drugs: in search of a magic bullet.

    Science.gov (United States)

    Bhagavathula, Akshaya Srikanth; Elnour, Asim Ahmed; Shehab, Abdulla

    2016-11-04

    bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.

  6. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy.

    Science.gov (United States)

    Zhang, Ren; Abou-Samra, Abdul B

    2014-09-13

    Metabolic syndrome includes glucose intolerance and dyslipidemia, both of which are strong risk factors for developing diabetes and atherosclerotic cardiovascular diseases. Recently, multiple groups independently studied a previously uncharacterized gene, officially named C19orf80 (human) and Gm6484 (mouse), but more commonly known as RIFL, Angptl8, betatrophin and lipasin. Both exciting and conflicting results have been obtained, and significant controversy is ongoing. Accumulating evidence from genome wide association studies and mouse genetic studies convincingly shows that lipasin is involved in lipid regulation. However, the mechanism of action, the identity of transcription factors mediating its nutritional regulation, circulating levels, and relationship among lipasin, Angptl3 and Angptl4, remain elusive. Betatrophin represents a promising drug target for replenishing β-cell mass, but current results have not been conclusive regarding its potency and specificity. Here, we summarize the consensus and controversy regarding functions of lipasin/betatrophin based on currently available evidence.

  7. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Prediction of Human Drug Targets and Their Interactions Using Machine Learning Methods: Current and Future Perspectives.

    Science.gov (United States)

    Nath, Abhigyan; Kumari, Priyanka; Chaube, Radha

    2018-01-01

    Identification of drug targets and drug target interactions are important steps in the drug-discovery pipeline. Successful computational prediction methods can reduce the cost and time demanded by the experimental methods. Knowledge of putative drug targets and their interactions can be very useful for drug repurposing. Supervised machine learning methods have been very useful in drug target prediction and in prediction of drug target interactions. Here, we describe the details for developing prediction models using supervised learning techniques for human drug target prediction and their interactions.

  9. A radioactive controversy

    International Nuclear Information System (INIS)

    Engler, Veronica

    2002-01-01

    During 2002, the National Congress of Argentina began discussing the 'Agreement between the Republic of Argentina and Australia on cooperation in the peaceful uses of the nuclear energy'. This document has revived the debate regarding development of a national nuclear industry. The debate was spurred by a commercial contract signed in 2000 by INVAP, an Argentinean company who sold a nuclear reactor to the ANSTO, Australian Nuclear and Technology Organization. More than sixty non-governmental organizations are opposed to the ratification of the agreement, because they interpret that the text leaves the door wide open for the transport and deposit of Australian nuclear waste to Argentina, to be processed in national territory. Article 41 of the Argentinean National Constitution, explicitly prohibits the generation of any income from 'radioactive residues'. Those who support the agreement say that it does not promote the deposit of nuclear waste in Argentina, and argue that environmentalists are hampering efforts of this advanced technological industry to flourish in Argentina. The point of conflict in the agreement lies in article 12, which states that Argentina will continue the process of reactor-driven irradiated fuel outside Argentina. Once the treatment is completed, the fuel conditioned and the resulting waste must return to the country of origin for their storage. The possibility of spent fuel being sent to Argentina lies in the hypothetical case that the French company Cogema, which currently holds treatment responsibility, stops treatment sometime within the next fifteen years, when the fuel must be treated. The non-ratification of the agreement on Argentina part will not imply any sort of impediment in the realization of the reactor, it will only put on hold the possibility that the Australians spent fuels will complete treatment in Argentina. The constitutionality of the agreement lies in the question of waste, but this too is not a simple question. The

  10. Current approaches to enhance CNS delivery of drugs across the brain barriers

    Directory of Open Access Journals (Sweden)

    Lu CT

    2014-05-01

    Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

  11. Comparison of antimalarial activity of Artemisia turanica extract with current drugs in vivo.

    Science.gov (United States)

    Taherkhani, Mahboubeh; Rustaiyan, Abdolhossein; Nahrevanian, Hossein; Naeimi, Sabah; Taherkhani, Tofigh

    2013-03-01

    The purpose of this study was to compare antimalarial activity of Artemisia turanica Krasch as Iranian flora with current antimalarial drugs against Plasmodium berghei in vivo in mice. Air-dried aerial parts of Iranian flora A. turanica were collected from Khorasan, northeastern Iran, extracted with Et2O/MeOH/Petrol and defatted. Toxicity of herbal extracts was assessed on male NMRI mice, and their antimalarial efficacy was compared with antimalarial drugs [artemether, chloroquine and sulfadoxinepyrimethamine (Fansidar)] on infected P. berghei animals. All the groups were investigated for parasitaemia, body weight, hepatomegaly, splenomegaly and anemia. The significance of differences was determined by Analysis of Variances (ANOVA) and Student's t-test using Graph Pad Prism software. The inhibitory effects of A. turanica extract on early decline of P. berghei parasitaemia highlights its antimalarial activity, however, this effect no longer can be observed in the late infection. This may be due to the metabolic process of A. turanica crude extract by mice and reduction of its concentration in the body. Crude extract of A. turanica represented its antisymptomatic effects by stabilization of body, liver and spleen weights. This study confirmed antimalarial effects of A. turanica extracts against murine malaria in vivo during early infection, however, there are more benefits on pathophysiological symptoms by this medication.

  12. Why Map Issues? On Controversy Analysis as a Digital Method.

    Science.gov (United States)

    Marres, Noortje

    2015-09-01

    This article takes stock of recent efforts to implement controversy analysis as a digital method in the study of science, technology, and society (STS) and beyond and outlines a distinctive approach to address the problem of digital bias. Digital media technologies exert significant influence on the enactment of controversy in online settings, and this risks undermining the substantive focus of controversy analysis conducted by digital means. To address this problem, I propose a shift in thematic focus from controversy analysis to issue mapping. The article begins by distinguishing between three broad frameworks that currently guide the development of controversy analysis as a digital method, namely, demarcationist, discursive, and empiricist. Each has been adopted in STS, but only the last one offers a digital "move beyond impartiality." I demonstrate this approach by analyzing issues of Internet governance with the aid of the social media platform Twitter.

  13. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  14. Categorization of psychoactive substances into "hard drugs" and "soft drugs": a critical review of terminology used in current scientific literature.

    Science.gov (United States)

    Janik, Peter; Kosticova, Michaela; Pecenak, Jan; Turcek, Michal

    2017-11-01

    Precise terminology and definitions are important components of scientific language. Although the terms "hard drugs" and "soft drugs" are used widely by professionals, neither the International Classification of Diseases nor the Diagnostic and Statistical Manual classify psychoactive substances into the categories "hard" and "soft." To analyze the occurrence of the terms "hard drugs" and "soft drugs" in recent scientific literature and to establish the degree of consensus in labeling psychoactive substances as "hard" or "soft." A critical review of scientific papers listed in PubMed and Scopus between 2011 and 2015. Three hundred thirty-four articles were initially identified as potentially relevant for review, 132 of which were included in the final analysis. One hundred twenty-four articles used the term "hard drugs" and 84.7% provided examples of substances considered "hard." Forty-four articles used the term "soft drugs" and 90.9% provided examples of substances considered "soft." Citations of relevant articles supporting categorization as "hard" or "soft" were not given in 90% of the articles. The authors often provided no or only very sparse information on their reasons for considering specific drugs as "hard" or "soft." Although it initially appeared that there is substantial agreement as to which psychoactive substances should be regarded as "hard" and "soft," closer inspection shows that the dividing line is blurred without clear criteria for categorization. At this time, it remains uncertain whether these terms should persist in the scientific literature. We therefore recommend these terms should be avoided or, if used, be clearly and precisely defined.

  15. [Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital].

    Science.gov (United States)

    Bedouch, P; Baudrant, M; Detavernier, M; Rey, C; Brudieu, E; Foroni, L; Allenet, B; Calop, J

    2009-01-01

    Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

  16. Penetrating abdominal injuries: management controversies

    Science.gov (United States)

    Butt, Muhammad U; Zacharias, Nikolaos; Velmahos, George C

    2009-01-01

    Penetrating abdominal injuries have been traditionally managed by routine laparotomy. New understanding of trajectories, potential for organ injury, and correlation with advanced radiographic imaging has allowed a shift towards non-operative management of appropriate cases. Although a selective approach has been established for stab wounds, the management of abdominal gunshot wounds remains a matter of controversy. In this chapter we describe the rationale and methodology of selecting patients for non-operative management. We also discuss additional controversial issues, as related to antibiotic prophylaxis, management of asymptomatic thoracoabdominal injuries, and the use of colostomy vs. primary repair for colon injuries. PMID:19374761

  17. Penetrating abdominal injuries: management controversies

    Directory of Open Access Journals (Sweden)

    Velmahos George C

    2009-04-01

    Full Text Available Abstract Penetrating abdominal injuries have been traditionally managed by routine laparotomy. New understanding of trajectories, potential for organ injury, and correlation with advanced radiographic imaging has allowed a shift towards non-operative management of appropriate cases. Although a selective approach has been established for stab wounds, the management of abdominal gunshot wounds remains a matter of controversy. In this chapter we describe the rationale and methodology of selecting patients for non-operative management. We also discuss additional controversial issues, as related to antibiotic prophylaxis, management of asymptomatic thoracoabdominal injuries, and the use of colostomy vs. primary repair for colon injuries.

  18. Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions.

    Science.gov (United States)

    Swain, Suryakanta; Beg, Sarwar; Babu, Sitty M

    2016-01-01

    Researchers are facing challenges to develop robust formulation and to enhance the bioavailability of poorly water-soluble drugs towards clinical applications. The development of new drug molecule alone is not adequate to assure ample pharmacotherapy of various diseases. Considerable results obtained from in vitro studies are not supported by in vivo data due to inadequate plasma drug concentrations. This may occur due to limited drug solubility and absorption. To resolve these problems, development of new drug delivery systems will be a promising approach. One of the promising pharmaceutical strategies is the use of lipospheres drug delivery system to deliver the poorly water-soluble drugs. Therefore, the present review described the methodology for manufacturing of lipospheres and factors influencing the formulation to deliver the drugs to the targeted site. Apart from that, this review also enlisted briefly the various applications of liposphers in medical and biomedical fields and critically discussed the recent patent system.

  19. Neighborhood-level LGBT hate crimes and current illicit drug use among sexual minority youth.

    Science.gov (United States)

    Duncan, Dustin T; Hatzenbuehler, Mark L; Johnson, Renee M

    2014-02-01

    To investigate whether past-30 day illicit drug use among sexual minority youth was more common in neighborhoods with a greater prevalence of hate crimes targeting lesbian, gay, bisexual, and transgender (LGBT, or sexual minority) individuals. We used a population-based survey of public school youth in Boston, Massachusetts, consisting of 1292 9th-12th grade students from the 2008 Boston Youth Survey Geospatial Dataset (sexual minority n=108). Data on LGBT hate crimes involving assaults or assaults and battery between 2005 and 2008 were obtained from the Boston Police Department and linked to youths' residential address. Youth reported past-30 day use of marijuana and other illicit drugs. Wilcoxon-Mann-Whitney tests and corresponding p-values were computed to assess differences in substance use by neighborhood-level LGBT assault hate crime rate among sexual minority youth (n=103). The LGBT assault hate crime rate in the neighborhoods of sexual minority youth who reported current marijuana use was 23.7 per 100,000, compared to 12.9 per 100,000 for sexual minority youth who reported no marijuana use (p=0.04). No associations between LGBT assault hate crimes and marijuana use among heterosexual youth (p>0.05) or between sexual minority marijuana use and overall neighborhood-level violent and property crimes (p>0.05) were detected, providing evidence for result specificity. We found a significantly greater prevalence of marijuana use among sexual minority youth in neighborhoods with a higher prevalence of LGBT assault hate crimes. These results suggest that neighborhood context (i.e., LGBT hate crimes) may contribute to sexual orientation disparities in marijuana use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. "Current Good Manufacturing Practices" and the Federal Food, Drug and Cosmetic Act

    OpenAIRE

    Goldstein, Beth F.

    1995-01-01

    The Food and Drug Administration (hereinafter, FDA) regulates food, drugs, and cosmetics in order to ensure that these products are safe and truthfully labelled. As part of its responsibilities under the Federal Food, Drug, and Cosmetic Act (hereinafter, Act), the FDA monitors the manufacturing practices of companies involved in the production of food, drugs, and medical devices. The manufacturing practices used by these companies must comply with certain standards, identified in the Act as "...

  1. Danish Cartoon Crisis/Controversy

    DEFF Research Database (Denmark)

    Hervik, Peter

    2017-01-01

    The Danish Cartoon Crisis Controversy is one of several terms that refer to the turmoil that associates with the Danish newspaper Morgenavisen Jyllands-Posten’s publication of 12 cartoons on 30 September 2005. “The Muhammad Cartoon Crisis” is an alternative heading used for the violent global rea...

  2. Controversial Issues in Learning Disability.

    Science.gov (United States)

    Sapir, Selma C.

    The author discusses controversial issues in the field of learning disabilities (LD). Among topics addressed are conflicting definitions of LD and the impact of the operational definition accepted by the US Government; etiological questions concerning the separation of neurological, environmental, and emotional factors; approaches used in training…

  3. The Satanic Ritual Abuse Controversy.

    Science.gov (United States)

    Putnam, Frank W.

    1991-01-01

    The issues raised by Jonker and Jonker-Bakker and Young et al (EC 601 187-188) illustrate a major controversy dividing the child abuse community, the alleged existence of a conspiracy of satanic, ritual, sexual abuse of children. No evidence is found to support claims that large numbers of babies and children are being sacrificed or abused in…

  4. Risk controversies. Concepts - conflicts - communication

    International Nuclear Information System (INIS)

    Jungermann, H.

    1991-01-01

    Common arguments and differences in risk communication in connection with the controversial discussion surrounding the fields of genetic engineering, chemistry, nuclear engineering, information techniques, and climate research are investigated. Presented are comparative analyses on subjects, those becoming active, and strategies of risk communication. (DG) [de

  5. Introducing Ethics Using Structured Controversies

    Science.gov (United States)

    Wareham, David; Elefsiniotis, Takis P.; Elms, David

    2006-01-01

    This paper describes a method of introducing ethics to a second-year class of civil engineering students. The method, known as a "structured controversy", takes the form of a workshop where the students assume the identity of stakeholders having an interest in a proposed development in an environmentally sensitive region. The instructor…

  6. Desecuritization as Displacement of Controversy

    DEFF Research Database (Denmark)

    Jacobsen, Marc; Strandsbjerg, Jeppe

    2017-01-01

    By signing the Ilulissat Declaration of May 2008, the five littoral states of the Arctic Ocean pre-emptively desecuritized potential geopolitical controversies in the Arctic Ocean by confirming that international law and geo-science are the defining factors underlying the future delimitation...

  7. Women's Athletics: Coping with Controversy.

    Science.gov (United States)

    Hoepner, Barbara J., Ed.

    This book is a collection of papers discussing controversial topics in women's athletics. Section one, "Overview--Women's Rights," includes articles on women's rights and equal opportunities in sports, the emergence of women in sports, and significant events in a century of American women's sports. Section two, "Women's Intercollegiate…

  8. [The Necessity and the Current Status of Safe Handling of Anticancer Drugs].

    Science.gov (United States)

    Kanda, Kiyoko

    2017-07-01

    Number of people who handle anticancer drugs in their profession is increasing. Anticancer drugs, which are hazardous drugs(HD), exert cytocidal effects on cancer cells, but many have also been shown to have mutagenicity, teratogenicity and carcinogenicity; therefore, safe handling of anticancer drugs is necessary. In July 2015, the first Japanese guidelines for exposure control measures, namely, the "Joint Guidelines for Safe Handling of Cancer Chemotherapy Drugs", were published jointly by 3 societies. Our guideline is the creation of the Japanese Society of Cancer Nursing(JSCN), Japanese Society of Medical Oncology(JSMO)and Japanese Society of Pharmaceutical Oncology(JASPO)and has a historical significance. This paper states the necessity of safe handling of anticancer drugs, Japan's recent movement of safe handling, the introduction of joint guidelines of safe handling of anticancer drugs, and new movement of safe handling of USP chapter 800 in the United States.

  9. Could a revision of the current guidelines for cancer drug use improve the quality of cancer treatment?

    Directory of Open Access Journals (Sweden)

    Lippert TH

    2014-01-01

    Full Text Available Theodor H Lippert,1 Hans-Jörg Ruoff,1 Manfred Volm2 1Medical Faculty, University of Tübingen, Tübingen, Germany; 2Medical Faculty, University of Heidelberg, Heidelberg, Germany Abstract: Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment. Keywords: anticancer drugs, quality of guidelines, critical remarks

  10. Use of toxicogenomics in drug safety evaluation: Current status and an industry perspective.

    Science.gov (United States)

    Vahle, John L; Anderson, Ulf; Blomme, Eric A G; Hoflack, Jean-Christophe; Stiehl, Daniel P

    2018-04-18

    Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time. Survey data were compiled during 2016 from thirteen pharmaceutical companies. Toxicogenomic analyses were infrequently conducted in the development phase and when performed were done to address specific mechanistic questions. Prior to development, toxicogenomics use was more frequent; however, there were significant differences in approaches among companies. Across all phases, gaining mechanistic insight was the most frequent reason cited for pursing toxicogenomics with few companies using toxicogenomics to predict toxicities. These data were consistent with the commentary submitted in response to survey questions asking companies to describe the evolution of their toxicogenomics strategy. Overall, these survey data indicate that toxicogenomics is not widely used as a predictive tool in the pharmaceutical industry but is used regularly by some companies and serves a broader role in mechanistic investigations and as a complement to other technologies. Copyright © 2018. Published by Elsevier Inc.

  11. Currently used and investigational drugs for Cushing´s disease.

    Science.gov (United States)

    Ciato, Denis; Mumbach, Aizhar G; Paez-Pereda, Marcelo; Stalla, Günter K

    2017-01-01

    Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.

  12. Consensus and controversy regarding osteoporosis in the pediatric population.

    Science.gov (United States)

    Bachrach, Laura Keyes

    2007-09-01

    To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence. The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis. Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients. Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood.

  13. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    International Nuclear Information System (INIS)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

    2013-01-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na v 1.5 sodium and Ca v 1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential

  14. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Hilber, Karlheinz, E-mail: karlheinz.hilber@meduniwien.ac.at [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Sandtner, Walter [Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna (Austria)

    2013-12-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on

  15. Current status and future prospects for enabling chemistry technology in the drug discovery process.

    Science.gov (United States)

    Djuric, Stevan W; Hutchins, Charles W; Talaty, Nari N

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of "dangerous" reagents. Also featured are advances in the "computer-assisted drug design" area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

  16. Current status and future prospects for enabling chemistry technology in the drug discovery process

    Science.gov (United States)

    Djuric, Stevan W.; Hutchins, Charles W.; Talaty, Nari N.

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities. PMID:27781094

  17. Classification of prophylactic antiradiation drugs as the consistency of conceptual basis of current radiation pharmacology

    International Nuclear Information System (INIS)

    Vasin, M.F

    1999-01-01

    The consistency of the classification of prophylactic antiradiation drugs have been given consideration as history of their discovery, theory of the radioprotection mechanisms and their use in applied medicine. Prophylactic drugs consists of radioprotectors with short-term of long-term action, drugs stimulating radioresistance, the ones suppressing symptoms of primary radiation reaction, the ones of early detoxication, the ones for adsorption and elimination of radionuclides from an organism [ru

  18. Controversial Science and the Media

    Science.gov (United States)

    Riordon, James

    2012-03-01

    The possibility that the OPERA collaboration has detected superluminal neutrinos was among the most controversial topics in physics news in decades, and one of the most widely covered stories in all of science in 2011. Word of the research initially reached journalists and the public prior to publication in peer-reviewed journals. Understandably, many physicists are concerned that the significance of controversial science may be exaggerated or distorted when news organizations report on science at such an early stage. I will offer an overview of the ways the story was promoted by the media relations personnel, and outline the rationales that motivate media relations efforts along with the associated benefits and drawbacks that can result. Finally, I will examine the accuracy and completeness of the superluminal neutrino news stories that ultimately were made available to the general public.

  19. Nuclear controversy with many undercurrents

    International Nuclear Information System (INIS)

    Lingjaerde, R.O.

    1979-01-01

    The president of the Norwegian Atomic Energy Society presents, in the form of an interview his opinions on the nature of the nuclear controversy in Norway. He is very critical of the emotional and uninformed nature of much of the criticism of nuclear power, and emphasises that nuclear power must be regarded as an alternative to other, less favourable forms of thermal power, as a supplement to hydroelectric power, or to electricity rationing. While a society using less energy is quite feasible, it would hardly be acceptable. The waste disposal controversy is quite artifical, as perfectly safe methods of disposal are available. Finally he regrets that it is the conclusions only in the Nuclear Power Commission's report which have attracted attention, and mainly the comments of the dissident minority. (JIW)

  20. Sexual Orientation, Controversy, and Science.

    Science.gov (United States)

    Bailey, J Michael; Vasey, Paul L; Diamond, Lisa M; Breedlove, S Marc; Vilain, Eric; Epprecht, Marc

    2016-09-01

    SummaryOngoing political controversies around the world exemplify a long-standing and widespread preoccupation with the acceptability of homosexuality. Nonheterosexual people have seen dramatic surges both in their rights and in positive public opinion in many Western countries. In contrast, in much of Africa, the Middle East, the Caribbean, Oceania, and parts of Asia, homosexual behavior remains illegal and severely punishable, with some countries retaining the death penalty for it. Political controversies about sexual orientation have often overlapped with scientific controversies. That is, participants on both sides of the sociopolitical debates have tended to believe that scientific findings-and scientific truths-about sexual orientation matter a great deal in making political decisions. The most contentious scientific issues have concerned the causes of sexual orientation-that is, why are some people heterosexual, others bisexual, and others homosexual? The actual relevance of these issues to social, political, and ethical decisions is often poorly justified, however. © The Author(s) 2016.

  1. Could a revision of the current guidelines for cancer drug use improve the quality of cancer treatment?

    Science.gov (United States)

    Lippert, Theodor H; Ruoff, Hans-Jörg; Volm, Manfred

    2014-01-01

    Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment.

  2. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    NARCIS (Netherlands)

    Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

  3. Valuation of Drug Abuse: A Review of Current Methodologies and Implications for Policy Making

    Science.gov (United States)

    Schori, Maayan

    2011-01-01

    This article reviews the use of several valuation methods as they relate to drug abuse and places them within the context of U.S. policy. First, cost-of-illness (COI) studies are reviewed and their limitations discussed. Second, three additional economic methods of valuing drug abuse are reviewed, including cost-effectiveness analysis (CEA),…

  4. What the History of Drugs Can Teach Us About the Current Cannabis Legalization Process: Unfinished Business.

    Science.gov (United States)

    Adrian, Manuella

    2015-01-01

    Over time, there have been considerable changes in the variety, availability, production, distribution, and use and user(s) of psychoactive substances, the meaning of substance use and its impact on users and their social or physical environment(s). This article reviews the mechanisms of introduction of psychoactive substances such as alcohol, tobacco, coffee, tea and cannabis to populations and communities that did not have them before. It considers the historical tension between early adopters who greet new substances with various levels of enthusiasm in their eagerness to enjoy what they believe to be the benefits of using these substances, and those focused on what they believe to be the negative aspects of use, who decry these new substances with horror. With more nonusers than users in the population, social policies tend to be directed at preventing, restricting, or punishing selected use, users and .drugs., using controls and interventions such regulation, incarceration, death sentence, treatment, prevention, legalization, taxation, among others. Whatever their intent or wished-for impact, all had consequences that produced additional, unplanned for, and (often) negative effects. This paper will consider some of these sequences as they occurred historically with other substances in light of the current shift to legalization and normalization of cannabis, noting the mechanisms of use, controls, and consequences of some types of formal interventions and give some attention to how and what we can learn from our experiences in order to plan ahead and become better prepared to successfully deal with the 'unexpecteds' of that well-known 'hell' paved with good intentions.

  5. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  6. Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges.

    Science.gov (United States)

    Gemal, Andre; Keravec, Joel; Menezes, Alexandre; Trajman, Anete

    2013-03-27

    Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are

  7. Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

    Science.gov (United States)

    Kitamura, Shigeyuki; Sugihara, Kazumi

    2014-01-01

    1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

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

    Science.gov (United States)

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

    2017-11-01

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

  9. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

    Science.gov (United States)

    Bian, Yuemin; Xie, Xiang-Qun Sean

    2018-04-09

    Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

  10. Current position of high-resolution MS for drug quantification in clinical & forensic toxicology.

    Science.gov (United States)

    Meyer, Markus R; Helfer, Andreas G; Maurer, Hans H

    2014-08-01

    This paper reviews high-resolution MS approaches published from January 2011 until March 2014 for the quantification of drugs (of abuse) and/or their metabolites in biosamples using LC-MS with time-of-flight or Orbitrap™ mass analyzers. Corresponding approaches are discussed including sample preparation and mass spectral settings. The advantages and limitations of high-resolution MS for drug quantification, as well as the demand for a certain resolution or a specific mass accuracy are also explored.

  11. The controversy about nuclear power

    International Nuclear Information System (INIS)

    Bethe, H.A.

    1977-01-01

    A short review of the events of the past several years in the conflict in the USA between the groups supporting or opposing nuclear power. Reference is made to publications on both sides of the controversy which the author considers to be well reasoned and useful sources of information. Mention is also made of the legal and legislative actions taken by both sides. The arguments against nuclear power are summarized and solutions to the problems which are the source of these arguments are suggested

  12. Summary report of PQRI Workshop on Nanomaterial in Drug Products: current experience and management of potential risks.

    Science.gov (United States)

    Bartlett, Jeremy A; Brewster, Marcus; Brown, Paul; Cabral-Lilly, Donna; Cruz, Celia N; David, Raymond; Eickhoff, W Mark; Haubenreisser, Sabine; Jacobs, Abigail; Malinoski, Frank; Morefield, Elaine; Nalubola, Ritu; Prud'homme, Robert K; Sadrieh, Nakissa; Sayes, Christie M; Shahbazian, Hripsime; Subbarao, Nanda; Tamarkin, Lawrence; Tyner, Katherine; Uppoor, Rajendra; Whittaker-Caulk, Margaret; Zamboni, William

    2015-01-01

    At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

  13. Can we resolve the radiation controversy

    International Nuclear Information System (INIS)

    Webster, E.W.

    1983-01-01

    The past 20 years has seen an intensification of anxieties about potential harm, specifically cancer, from low levels of x or gamma rays. The idea that radiation is more damaging than previously estimated, says the author, is a central theme in current radiation phobia and probably the principal prop of the antinuclear movement. A current law-suit decision in Salt Lake City will settle the issue for the present. Historical data from Japanese A-bomb survivors and other studies are reviewed, the need for further epidemiologic work pointed out, and 20 years more of data collection from the Japanese survivors indicated as the final arbiter of the controversy. 18 references, 8 figures, 11 tables

  14. Hormonal and antimicrobial therapy in theriogenology practice: currently approved drugs in the USA and possible future directions.

    Science.gov (United States)

    Modric, T; Momcilovic, D; Gwin, W E; Peter, A T

    2011-08-01

    Hormonal and antimicrobial therapies are essential to regulate and maintain healthy reproduction in domestic animals. The appropriate and legal use of these compounds is ultimately the responsibility of the veterinarian and other users, with a primary mission to directly protect and promote the health of animals, and indirectly the health of people. The appropriate use of these products is defined by the Federal Food, Drug, and Cosmetic Act, 21 United States of America § 301 et seq and implementing regulations in the Code of Federal Regulations. In the past, use of a drug in an animal for an unapproved use violated this Act. However, passage of the Animal Medicinal Drug Use Clarification Act 1994 legalized the extra-label use of certain animal and human drugs in veterinary practice for treating diseases. This manuscript reviews currently approved hormonal and antimicrobial drugs for use in theriogenology. Considering the ever increasing knowledge in the area of veterinary reproduction, particularly in the treatment and control of reproduction using antimicrobials and hormones, it would be beneficial to widen the therapeutic options in these categories. The potential for widening the therapeutic options is also discussed in this review, by providing a non-exhaustive but essential list of potential new drugs for use in clinical animal reproduction (theriogenology). Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Doctrinal controversies and ecumenical councils | Ogbonnaya ...

    African Journals Online (AJOL)

    This work focused on the doctrinal controversies that have confronted the Church in the course of its development and the accompanying councils that sought to resolve these theological controversies. The paper did this historically, by showing the origin of the problems, the factors and features involved in the controversies ...

  16. Current applications of miniaturized chromatographic and electrophoretic techniques in drug analysis.

    Science.gov (United States)

    Aturki, Zeineb; Rocco, Anna; Rocchi, Silvia; Fanali, Salvatore

    2014-12-01

    In the last decade, miniaturized separation techniques have become greatly popular in pharmaceutical analysis. Miniaturized separation methods are increasingly utilized in all processes of drug discovery as well as quality control of pharmaceutical preparation. The great advantages presented by the analytical miniaturized techniques, including high separation efficiency and resolution, rapid analysis and minimal consumption of reagents and samples, make them an attractive alternative to the conventional chromatographic methods for drug analysis. The purpose of this review is to give a general overview of the applicability of capillary electrophoresis (CE), capillary electrochromatography (CEC) and micro/capillary/nano-liquid chromatography (micro-LC/CLC/nano-LC) for the analysis of pharmaceutical formulations, active pharmaceutical ingredients (API), drug impurity testing, chiral drug separation, determination of drugs and metabolites in biological fluids. The results concerning the use of CEC, micro-LC, CLC, and nano-LC in the period 2009-2013, while for CE, those from 2012 up to the review draft are here summarized and some specific examples are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Glaciers in Patagonia: Controversy and prospects

    Science.gov (United States)

    Kargel, J. S.; Alho, P.; Buytaert, W.; Célleri, R.; Cogley, J. G.; Dussaillant, A.; Guido, Z.; Haeberli, W.; Harrison, S.; Leonard, G.; Maxwell, A.; Meier, C.; Poveda, G.; Reid, B.; Reynolds, J.; Rodríguez, C. A. Portocarrero; Romero, H.; Schneider, J.

    2012-05-01

    Lately, glaciers have been subjects of unceasing controversy. Current debate about planned hydroelectric facilities—a US7- to 10-billion megaproject—in a pristine glacierized area of Patagonia, Chile [Romero Toledo et al., 2009; Vince, 2010], has raised anew the matter of how glaciologists and global change experts can contribute their knowledge to civic debates on important issues. There has been greater respect for science in this controversy than in some previous debates over projects that pertain to glaciers, although valid economic motivations again could trump science and drive a solution to the energy supply problem before the associated safety and environmental problems are understood. The connection between glaciers and climate change—both anthropogenic and natural—is fundamental to glaciology and to glaciers' practical importance for water and hydropower resources, agriculture, tourism, mining, natural hazards, ecosystem conservation, and sea level [Buytaert et al., 2010; Glasser et al., 2011]. The conflict between conservation and development can be sharper in glacierized regions than almost anywhere else. Glaciers occur in spectacular natural landscapes, but they also supply prodigious exploitable meltwater.

  18. Managing Controversies in the Fuzzy Front End

    DEFF Research Database (Denmark)

    Christiansen, John K.; Gasparin, Marta

    2016-01-01

    This research investigates the controversies that emerge in the fuzzy front end (FFE) and how they are closed so the innovation process can move on. The fuzzy front has been characterized in the literature as a very critical phase, but controversies in the FFE have not been studied before....... The analysis investigates the microprocesses around the controversies that emerge during the fuzzy front end of four products. Five different types of controversies are identified: profit, production, design, brand and customers/market. Each controversy represents a threat, but also an opportunity to search...

  19. Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

    Directory of Open Access Journals (Sweden)

    Panoraia I. Siafaka

    2016-08-01

    Full Text Available Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

  20. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    Science.gov (United States)

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

  1. The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?

    Science.gov (United States)

    Rodenhizer, Darren; Dean, Teresa; D'Arcangelo, Elisa; McGuigan, Alison P

    2018-04-01

    Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted. Then, an overview of the cancer hallmarks that drive clinical progression is provided, and the range of available clinical therapies within the context of these hallmarks is categorized. Specifically, it is found that historically, the development of therapies is limited to a subset of possible targets. This provides evidence for the opportunities offered by novel disease-relevant in vitro models that enable identification of novel targets that facilitate interactions between the tumor cells and their surrounding microenvironment. Next, an overview of the models currently reported in literature is provided, and the cancer biology they have been used to explore is highlighted. Finally, four priority areas are suggested for the field to accelerate adoption of in vitro tumour models for cancer drug discovery. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Nuclear power. The Windscale controversy

    International Nuclear Information System (INIS)

    Boyle, G.

    1978-01-01

    The aims of this unit are: (1) to provide a basic understanding of nuclear technology and of the associated technical and environmental problems; (2) to provide an understanding of: (a) the historical growth of the nuclear industry; (b) the arguments for the continued development of nuclear power, and the institutions promoting that development; (3) to provide a basic understanding of the mechanisms and institutions which officially regulate the nuclear power programme in the UK; (4) to provide an understanding of the main issues - technical, economic, social and political - involved in the controversy over the proposed expansion of British Nuclear Fuels Ltd's reprocessing facilities at Windscale, and the events leading up to the Public Inquiry on the proposal which began in June 1977; and (5) to examine (a) the reason for the growth in opposition to nuclear power in various countries and the different approaches taken by the opposition groups; (b) the political impact and effectiveness of that opposition. (author)

  3. Subclinical hypothyroidism: Controversies to consensus

    Directory of Open Access Journals (Sweden)

    Syed Abbas Raza

    2013-01-01

    Full Text Available Diagnoses of subclinicaal hypothyroidism (SCH is biochemically made, when serum thyroid stimulating hormone (TSH levels is elevated while free thyroid hormone levels are within normal reference range. SCH is diagnosed after excluding all other causes of elevated TSH levels. Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms. The risk of progression to overt hypothyroidism is related to number of factors including initial serum TSH concentration, presence of auto antibodies, family history and presence goiter. Various screening recommendations for thyroid function assessment are in practice. There are still controversies surrounding SCH and associated risk of various cardiovascular diseases (CVDs, pregnancy outcomes, neuropsychiatric issues, metabolic syndrome, and dyslipidemia. Consensus will require more large randomized clinical studies involving various age groups and medical condition, especially in developing countries. All these efforts will definitely improve our understanding of disease and ultimately patient outcomes.

  4. Partisan Scholarship in Technoscientific Controversies

    DEFF Research Database (Denmark)

    Galis, Vasilis; Hansson, Anders

    2012-01-01

    of who controls, manipulates, and establishes decisions, facts, and knowledge. With this in mind, it is possible to identify different forms of partisan research including capture by participants, de facto and overt partisanship, and mercenary scholarship. These different forms of partisan scholarship...... are characterised by differences in the motives underlying epistemological choices of research topic and method, personal commitments to the fields studied, use of research findings in controversies, and positioning of results in wider debates. Two examples help to illustrate partisan scholarship: first, a study...... of new technologies for managing climate change (carbon dioxide capture and storage); and second, the construction of the new underground metro system in Athens and its accommodation of accessibility standards. Both cases entail partisan positions and raise similar concerns about the orthodox...

  5. Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls. Final rule.

    Science.gov (United States)

    2012-03-20

    The Food and Drug Administration (FDA) is amending the packaging and labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and veterinary drug products by limiting the application of special control procedures for the use of cut labeling to immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons. FDA is also permitting the use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment when cut labeling is used. This action is intended to protect consumers from labeling errors more likely to cause adverse health consequences, while eliminating the regulatory burden of applying the rule to labeling unlikely to reach or adversely affect consumers. This action is also intended to permit manufacturers to use a broader range of error prevention and labeling control techniques than permitted by current CGMPs.

  6. Estimating the effect of current, previous and never use of drugs in studies based on prescription registries

    DEFF Research Database (Denmark)

    Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify......PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do...... not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...

  7. Management of endometrial cancer: issues and controversies.

    Science.gov (United States)

    Bogani, G; Dowdy, S C; Cliby, W A; Ghezzi, F; Rossetti, D; Frigerio, L; Mariani, A

    2016-01-01

    Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.

  8. [Treatment of typical trigeminus neuralgias. Overview of the current state of drug and surgical therapy].

    Science.gov (United States)

    Möbius, E; Leopold, H C; Paulus, W M

    1984-10-11

    Carbamazepine continues to be the most useful drug in the treatment of trigeminal neuralgia. Diphenylhydantoin may be given in addition to or instead of Carbamazepine. Refractory cases may benefit from combination with Baclofen or Chlorphenesin. In cases of persistent pain the concomitant use of tricyclic antidepressant drugs is recommended. If pain continues in spite of multiple medical therapies or if serious side effects develop, then surgical procedures such as percutaneous controlled thermocoagulation or microvascular decompression are indicated. Percutaneous thermocoagulation is associated with the lowest mortality and morbidity rate and can easily be repeated. Microvascular decompression should especially be offered to young patients, who want to avoid any sensory disturbance of the face, and recommended for other patients for whom all other forms of therapy including percutaneous thermocoagulation have failed.

  9. Understanding the agreements and controversies surrounding childhood psychopharmacology

    Directory of Open Access Journals (Sweden)

    Johnston Josephine

    2008-02-01

    Full Text Available Abstract The number of children in the US taking prescription drugs for emotional and behavioral disturbances is growing dramatically. This growth in the use of psychotropic drugs in pediatric populations has given rise to multiple controversies, ranging from concerns over off-label use and long-term safety to debates about the societal value and cultural meaning of pharmacological treatment of childhood behavioral and emotional disorders. This commentary summarizes the authors' eight main findings from the first of five workshops that seek to understand and produce descriptions of these controversies. The workshop series is convened by The Hastings Center, a bioethics research institute located in Garrison, New York, U.S.A.

  10. Drug-Loaded Microspheres for the Treatment of Liver Cancer: Review of Current Results

    International Nuclear Information System (INIS)

    Kettenbach, Joachim; Stadler, Alfred; Katzler, Isabella v.; Schernthaner, Ruediger; Blum, Melanie; Lammer, Johannes; Rand, Thomas

    2008-01-01

    Transarterial chemoembolization (TACE) involves the emulsification of a chemotherapeutic agent in a viscous drug carrier, delivered intra-arterially to liver tumor for maximum effect. TACE reduces arterial inflow, diminishes washout of the chemotherapeutic agent, and decreases systemic exposure. Despite evidence of some clinical success with TACE, a new type of microspheres with drug-eluting capabilities may offer a precisely controlled and sustainable release of the chemotherapeutic agent into the tumor bed. In animal trials tumor necrosis (approaching 100%) was greatest at 7 days, with significantly lower plasma concentrations of doxorubicin than in control animals treated with doxorubicin intra-arterially. Clinically, drug-eluting microspheres loaded with doxorubicin, either at 75 mg/m 2 or at a fixed dose of 150 mg, were used recently and no severe disorders of the hepatic function were observed postprocedure, while a substantial reduction of the fetoprotein levels occurred. An interim analysis of the first 15 patients from the Hong Kong group at 3 months showed an objective response rate of 61.54% and 53.84% according to EASL criteria and RECIST criteria, respectively, and a survival rate of 93.3%. In this paper we present how to use microspheres loaded with doxorubicin and review their clinical value and preliminary performance for treatment of unresectable liver cancer

  11. The controversy on chronic cerebrospinal venous insufficiency

    Directory of Open Access Journals (Sweden)

    Paolo Zamboni

    2013-08-01

    Full Text Available The objective of this review is to analyze the actual scientific controversy on chronic cerebrospinal venous insufficiency (CCSVI and its association with both neurodegenerative disorders and multiple sclerosis (MS. We revised all published studies on prevalence of CCSVI in MS patients, including ultrasound and catheter venography series. Furthermore, we take into consideration other publications dealing with the pathophysiologic consequences of CCSVI in the brain, as well as ecent data characterizing the pathology of the venous wall in course of CCSVI. Finally, safety and pilot data on effectiveness of endovascular CCSVI treatment were further updated. Studies of prevalence show a big variability in prevalence of CCSVI in MS patients assessed by established ultrasonographic criteria. This could be related to high operator dependency of ultrasound. However, 12 studies, by the means of more objective catheter venography, show a prevalence >90% of CCSVI in MS. Global hypo-hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Postmortem studies and histology corroborate the 2009 International Union of Phlebology (UIP Consensus decision to insert CCSVI among venous malformations. Finally, safety of balloon angioplasty of the extracranial veins was certainly demonstrated, while prospective data on the potential effectiveness of endovascular treatment of CCSVI support to increase the level of evidence by proceeding with a randomized control trial (RCT. Taking into account the current epidemiological data, including studies on catheter venography, the autoptic findings, and the relationship between CCSVI and both hypo-perfusion and cerebro-spinal fluid flow, we conclude that CCSVI can be definitively inserted among the medical entities. Research is still inconclusive in elucidating the CCSVI role in the pathogenesis of neurological disorders. The controversy between the vascular and the

  12. 77 FR 16158 - Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs...

    Science.gov (United States)

    2012-03-20

    .... FDA-1997-N-0518] (formerly 97N-0300) Current Good Manufacturing Practice in Manufacturing, Processing... labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and... GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS 0 1. The authority citation for 21 CFR part...

  13. Marijuana: Current concepts

    Directory of Open Access Journals (Sweden)

    Donald eGreydanus

    2013-10-01

    Full Text Available Marijuana (cannabis remains a controversial drug in the 21st century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed as the 21st century matures. However, potential dangerous adverse effects from smoking marijuana are well known and should be clearly taught to a public often confused by a media-driven, though false message and promise of benign pot consumption.

  14. Marijuana: Current Concepts†

    Science.gov (United States)

    Greydanus, Donald E.; Hawver, Elizabeth K.; Greydanus, Megan M.; Merrick, Joav

    2013-01-01

    Marijuana (cannabis) remains a controversial drug in the twenty-first century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed as the twenty-first century matures. However, potential dangerous adverse effects from smoking marijuana are well known and should be clearly taught to a public that is often confused by a media-driven, though false message and promise of benign pot consumption. PMID:24350211

  15. Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

    Science.gov (United States)

    Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

    2011-10-30

    Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

  16. Current Trends of Drug Resistance Patterns of Acinetobacter baumannii Infection in Blood Transfusion-dependent Thalassemia Patients.

    Science.gov (United States)

    Almani, Suhail Ahmed; Naseer, Ali; Maheshwari, Sanjay Kumar; Maroof, Pir; Naseer, Raza; Khoharo, Haji Khan

    2017-01-01

    The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female ( P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii . Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

  17. The impact of currently used oral antihyperglycemic drugs on dysfunctional adipose tissue

    Directory of Open Access Journals (Sweden)

    Tomić-Naglić Dragana

    2017-01-01

    Full Text Available Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.

  18. Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

    Science.gov (United States)

    Feldman, Steven R; Huang, William W; Huynh, Tu T

    2014-06-01

    Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

  19. Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

    Science.gov (United States)

    Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

    2014-06-01

    Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

  20. HPV vaccines: a controversial issue?

    Science.gov (United States)

    Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  1. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  2. CONTROVERSIAL ASPECTS REGARDING TAX EVASION

    Directory of Open Access Journals (Sweden)

    Mircea-Constantin SINESCU

    2018-05-01

    Full Text Available Throughout the paper, we have highlighted some controversial aspects regarding the crime of tax evasion, referring to some important decisions of the High Court of Cassation and Justice and also of the Bucharest Court of Appeal. Debating upon the impunity provision stated by art. 10 of Law no. 241/2005, the study also sheds light upon the issue of the perspective of the judicial organs regarding the juridical regime of the tax due for dividends. The main focus of the paper leads to the situations when there is legal ground for the tax due for dividends to be considered part of the damage caused by tax evasion crime. The study includes a short analysis of some relevant provisions of the Romanian Fiscal Code and also some aspects deriving from decisions issued by the Administrative and Tax Litigation Chamber of The High Court of Cassation and Justice concerning the legal regime of dividends. Consequently, the authors are presenting both perspectives of the interpretation of the issue regarding the tax due for dividends to be considered part of the damage caused by tax evasion crime, resulting from two decisions of the two Criminal Sections of The Bucharest Court of Appeal, also arguing in favour of the most solid interpretation among them

  3. Lyme disease: why the controversy?

    Science.gov (United States)

    Beaman, M H

    2016-12-01

    Some Australians have become convinced of the existence of locally acquired Lyme disease (LD). The history of LD, since its recognition in the early 1970s, is reviewed as a model for investigative approaches to unknown syndromes. Australian Management Guidelines for LD include the requirement for diagnostic testing by National Association of Testing Authorities-accredited laboratories using Therapeutic Goods Administration-licensed tests, which result in the efficient diagnosis of LD in overseas travellers. Despite this, patients who have not left Australia pay many thousands of dollars for non-specialist consultations and testing at overseas laboratories. Unproven long-term therapy with multiple antibiotics has resulted in serious complications, including allergies, line sepsis, pancreatitis and pseudomembranous colitis. Studies have shown that LD vectors are not found in Australia, and Lyme Borrelia has not been found in Australian vectors, animals or patients with autochthonous illnesses. I propose that (i) A non-controversial name for the chronic syndrome should be adopted, 'Australian Multisystem Disorder'. (ii) Research funding should enable the development of a consensus case definition and studies of the epidemiology of this syndrome with laboratory investigations to identify an aetiology and surrogate markers of disease. Prospective, randomised treatment studies could then be undertaken using ethical protocols. © 2016 Royal Australasian College of Physicians.

  4. Controversies in presacral tumors management

    Directory of Open Access Journals (Sweden)

    Nidal Issa

    2017-10-01

    Full Text Available Presacral tumors are rare lesions of the retrorectal space that can present diagnostic and therapeutic difficulty because of their anatomic location and the different tissue types and etiology. Although the diagnosis and management of these tumors has evolved in recent years, several points still to be addressed in order to improve perioperative diagnosis and treatment. In the upcoming we will try to highlight some controversial points; the pre-operative biopsies, neoadjuvant therapy, the necessity of surgery and the role of minimally invasive surgeries of presacral tumors. Resumo: Tumores pré-sacrais são lesões raras do espaço retrorretal que podem trazer dificuldades diagnósticas e terapêuticas por causa de sua localização anatômica e também pelos diferentes tipos de tecidos e etiologia. Embora nos últimos anos o diagnóstico e tratamento desses tumores tenham evoluído, diversos pontos ainda devem ser estudados com vistas à melhora do diagnóstico e tratamento no perioperatório. Mais adiante, tentaremos esclarecer alguns pontos controversos; biópsias pré-operatórias, terapia neoadjuvante, a necessidade de cirurgia e o papel das cirurgias minimamente invasivas para os tumores pré-sacrais. Keywords: Presacral tumor, Preoperative biopsy, Neoadjuvant therapy, Palavras-chave: Tumor pré-sacral, Biópsia pré-operatória, Terapia neoadjuvante

  5. Empowerment in healthcare policy making: three domains of substantive controversy.

    Science.gov (United States)

    Chiapperino, Luca; Tengland, Per-Anders

    2015-12-01

    This paper distinguishes between the uses of empowerment across different contexts in healthcare policy and health promotion, providing a model for the ethical and political scrutiny of those uses. We argue that the controversies currently engendered by empowerment are better understood by means of a historical distinction between two concepts of empowerment, namely, what we call the radical empowerment approach and the new wave of empowerment. Building on this distinction, we present a research agenda for ethicists and policy makers, highlighting three domains of controversy raised by the new wave of empowerment, namely: (1) the relationship between empowerment and paternalistic interferences on the part of professionals; (2) the evaluative commitment of empowerment strategies to the achievement of health-related goals; and (3) the problems arising from the emphasis on responsibility for health in recent uses of empowerment. Finally, we encourage the explicit theorisation of these moral controversies as a necessary step for the development and implementation of ethically legitimate empowerment processes.

  6. Six controversial issues on subclinical Cushing's syndrome.

    Science.gov (United States)

    Chiodini, Iacopo; Albani, Adriana; Ambrogio, Alberto Giacinto; Campo, Michela; De Martino, Maria Cristina; Marcelli, Giorgia; Morelli, Valentina; Zampetti, Benedetta; Colao, Annamaria; Pivonello, Rosario

    2017-05-01

    Subclinical Cushing's syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality. The subclinical Cushing's syndrome is not rare, being estimated to be between 0.2-2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing's syndrome screening, diagnosis and treatment. The Altogether to Beat Cushing's syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing's syndrome viewpoint regarding the following controversial issues on Subclinical Cushing's syndrome (SCS): (1) Who has to be screened for subclinical Cushing's syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushing's syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushing's syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushing's syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushing's syndrome surgically or conservatively treated? Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing's syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing's syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing's syndrome.

  7. Phytosynthesis of nanoparticles: concept, controversy and application

    Science.gov (United States)

    2014-01-01

    Nanotechnology is an exciting and powerful discipline of science; the altered properties of which have offered many new and profitable products and applications. Agriculture, food and medicine sector industries have been investing more in nanotechnology research. Plants or their extracts provide a biological synthesis route of several metallic nanoparticles which is more eco-friendly and allows a controlled synthesis with well-defined size and shape. The rapid drug delivery in the presence of a carrier is a recent development to treat patients with nanoparticles of certain metals. The engineered nanoparticles are more useful in increasing the crop production, although this issue is still in infancy. This is simply due to the unprecedented and unforeseen health hazard and environmental concern. The well-known metal ions such as zinc, iron and copper are essential constituents of several enzymes found in the human system even though the indiscriminate use of similar other metal nanoparticle in food and medicine without clinical trial is not advisable. This review is intended to describe the novel phytosynthesis of metal and metal oxide nanoparticles with regard to their shape, size, structure and diverse application in almost all fields of medicine, agriculture and technology. We have also emphasized the concept and controversial mechanism of green synthesis of nanoparticles. PMID:24910577

  8. Phytosynthesis of nanoparticles: concept, controversy and application

    Science.gov (United States)

    Husen, Azamal; Siddiqi, Khwaja Salahuddin

    2014-05-01

    Nanotechnology is an exciting and powerful discipline of science; the altered properties of which have offered many new and profitable products and applications. Agriculture, food and medicine sector industries have been investing more in nanotechnology research. Plants or their extracts provide a biological synthesis route of several metallic nanoparticles which is more eco-friendly and allows a controlled synthesis with well-defined size and shape. The rapid drug delivery in the presence of a carrier is a recent development to treat patients with nanoparticles of certain metals. The engineered nanoparticles are more useful in increasing the crop production, although this issue is still in infancy. This is simply due to the unprecedented and unforeseen health hazard and environmental concern. The well-known metal ions such as zinc, iron and copper are essential constituents of several enzymes found in the human system even though the indiscriminate use of similar other metal nanoparticle in food and medicine without clinical trial is not advisable. This review is intended to describe the novel phytosynthesis of metal and metal oxide nanoparticles with regard to their shape, size, structure and diverse application in almost all fields of medicine, agriculture and technology. We have also emphasized the concept and controversial mechanism of green synthesis of nanoparticles.

  9. VIRTUAL CURRENCY "BITCOIN" – CHALLENGES AND CONTROVERSIES

    Directory of Open Access Journals (Sweden)

    ȘOAVĂ GEORGETA

    2016-06-01

    Full Text Available In the knowledge society, when there is a rapidly evolving information technology, the virtual markets, namely the online transactions, have created the premises emergence and development of new technologies of using of finances, namely virtual coin (Bitcoin. Use of this coin appears as an alternative to traditional currencies, but they are not under the control of no body, are devoid of inflation and maintain the anonymity of users. Following the evolution of this new type of coin, we proposed in this paper to present some general aspects of this coin focusing on global controversies on using Bitcoin. We have reviewed several myths that have arisen with the development and penetration of its on market and because it is a volatile coin can generate huge gains but and huge losses, we have studied fluctuation and implications for users and investors and the attraction of the drug dealers and criminals for using virtual currency, Bitcoin. At the end of the paper, based on the analysis we have tried to outline the future of this modern payment system. Thus, we found that lately, in that its value has fluctuated strongly, and increased buyer confidence, but appeared and increased cyber attacks, and the fear that if the state has no a role in protecting citizens from fraud, we can assist at the development of financial schemes extremely dangerous. The financial experts believe that if the world banks would jointly solve all the problems, the virtual money will have a real chance of life.

  10. HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment.

    Science.gov (United States)

    Baker, A; Kochan, N; Dixon, J; Wodak, A; Heather, N

    1995-04-01

    This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.

  11. New insights into the use of currently available non-steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Brune K

    2015-02-01

    Full Text Available Kay Brune,1 Paola Patrignani2 1Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; 2Department of Neuroscience, Imaging and Clinical Sciences, Center of Excellence on Aging, G d’Annunzio University, Chieti, Italy Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs, which act via inhibition of the cyclooxygenase (COX isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination, and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (~80% inhibition of COX-2 while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while

  12. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases.

    Science.gov (United States)

    Felder, Christian C; Goldsmith, Paul J; Jackson, Kimberley; Sanger, Helen E; Evans, David A; Mogg, Adrian J; Broad, Lisa M

    2018-01-25

    The cholinergic signalling system has been an attractive pathway to seek targets for modulation of arousal, cognition, and attention which are compromised in neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic receptor M1 and M4 subtypes which are highly expressed in the central nervous system, in cortex, hippocampus and striatum, key areas of cognitive and neuropsychiatric control, have received particular attention. Historical muscarinic drug development yielded first generation agonists with modest selectivity for these two receptor targets over M2 and M3 receptors, the major peripheral sub-types hypothesised to underlie the dose-limiting clinical side effects. More recent compound screening and medicinal chemistry optimization of orthosteric and allosteric agonists, and positive allosteric modulators binding to sites distinct from the highly homologous acetylcholine binding pocket have yielded a collection of highly selective tool compounds for preclinical validation studies. Several M1 selective ligands have progressed to early clinical development and in time will hopefully lead to useful therapeutics for treating symptoms of Alzheimer's disease and related disorders. Copyright © 2018. Published by Elsevier Ltd.

  13. Treatment and Controversies in Paraesophageal Hernia Repair

    Directory of Open Access Journals (Sweden)

    P. Marco eFisichella

    2015-04-01

    Full Text Available Background: Historically all paraesophageal hernias were repaired surgically, today intervention is reserved for symptomatic paraesophageal hernias. In this review, we describe the indications for repair and explore the controversies in paraesophageal hernia repair, which include a comparison of open to laparoscopic paraesophageal hernia repair, the necessity of complete sac excision, the routine performance of fundoplication, and the use of mesh for hernia repair.Methods: We searched Pubmed for papers published between 1980 and 2015 using the following keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia, gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH monitoring, proton pump inhibitors, anemia, iron deficiency anemia, Nissen fundoplication, sac excision, mesh, mesh repair. Results: Indications for paraesophageal hernia repair have changed, and currently symptomatic paraesophageal hernias are recommended for repair. In addition, it is important not to overlook iron-deficiency anemia and pulmonary complaints, which tend to improve with repair. Current practice favors a laparoscopic approach, complete sac excision, primary crural repair with or without use of mesh, and a routine fundoplication.

  14. Understanding Controversies in Urban Climate Change Adaptation

    DEFF Research Database (Denmark)

    Baron, Nina; Petersen, Lars Kjerulf

    2015-01-01

    This article explores the controversies that exist in urban climate change adaptation and how these controversies influence the role of homeowners in urban adaptation planning. A concrete SUDS project in a housing cooperative in Copenhagen has been used as a case study thereby investigating the m...

  15. Stress Mediates the Relationship Between Past Drug Addiction and Current Risky Sexual Behaviour Among Low-income Women.

    Science.gov (United States)

    Wu, Z Helen; Tennen, Howard; Hosain, G M Monawar; Coman, Emil; Cullum, Jerry; Berenson, Abbey B

    2016-04-01

    This study examined the role of stress as a mediator of the relationship between prior drug addiction and current high-risk sexual behaviour. Eight hundred twenty women aged 18 to 30 years, who received care at community-based family planning clinics, were interviewed using the Composite International Diagnostic Interview and the Sexual Risk Behavior Assessment Schedule. They also completed the brief version of the Self-Control Scale as a measure of problem-solving strategies and measures of recent stressful events, daily hassles and ongoing chronic stress. Regardless of addiction history, stress exposure during the previous 12 months was associated with risky sexual behaviour during the previous 12 months. Structural equation modelling revealed that 12-month stress levels mediated the relationship between past drug addiction and 12-month high-risk sexual behaviours, as well as the negative relationship between problem-solving strategies and high-risk sexual behaviours. Problem-solving strategies did not moderate the relationship between drug addiction and high-risk sexual behaviours. These findings suggest that stress management training may help reduce risky behaviour among young, low-income women. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Current Trends of Using Antimicrobial Drugs in the ICU at a Tertiary Level Teaching Hospital in Mymensingh.

    Science.gov (United States)

    Saha, S K; Shaha, K C; Haque, M F; Khatun, S; Akhter, S M; Akhter, H

    2016-10-01

    The aim of the present study was to investigate the current trends of using antimicrobial drugs in the ICU at a tertiary level teaching hospital in Mymensingh. The study of prescribing patterns seeks to monitor, evaluate and suggest modifications in clinicians prescribing habits so as to make medical care rational. It was an observational type of descriptive study, conducted in the Mymensingh medical college hospital, Mymensingh, during the study period of June 2016 to September 2016.The study was approved by the institutional ethical committee. Most patients in the ICU belonged to the older age group >60 years. Male patients were more than the female patients in ICU. Average duration of stay in ICU was 4.35 days. Admissions in ICU were common due to respiratory system related diseases and the present study showed that 31.68% of the reported cases belong to the respiratory system. Average number of drugs per prescription was 6.46. Average number of anti-microbial drugs per prescription was 1.38. Cephalosporin group and individually ceftriaxone was the most frequently prescribed antimicrobial group and agent respectively in the ICU. Most commonly used antimicrobial combination was Cephalosporin and Metronidazole (43.33%) followed by Carbapenem (Meropenem) and Metronidazole (13.33%). Most antimicrobial agents were prescribed without bacteriological culture and sensivity testing evidence. There is a need for motivating the physicians to prescribe antimicrobial agents with supportive bacteriological evidences.

  17. From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    LEONARDO G. FERREIRA

    2018-02-01

    Full Text Available ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry’s striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

  18. Managing Controversies in the Fuzzy Front End

    DEFF Research Database (Denmark)

    Christiansen, John K.; Gasparin, Marta

    2016-01-01

    . The analysis investigates the microprocesses around the controversies that emerge during the fuzzy front end of four products. Five different types of controversies are identified: profit, production, design, brand and customers/market. Each controversy represents a threat, but also an opportunity to search...... for new solutions in the unpredictable non-linear processes. The study uses an ethnographic approach using qualitative data from interviews, company documents, external communication and marketing material, minutes of meetings, informal conversations and observations. The analysis of four FFE processes...... demonstrates how the fuzzy front requires managers to deal with controversies that emerge from many different places and involve both human and non-human actors. Closing the controversies requires managers to take account of the situation, identify the problem that needs to be addressed, and initiate a search...

  19. The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

    Science.gov (United States)

    Yazdanian, Mehran; Briggs, Katherine; Jankovsky, Corinne; Hawi, Amale

    2004-02-01

    The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in biorelevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0. and 7.4 relative to marketed dose strengths in 250 ml. The pKa values for the acidic NSAIDs studied were between 3.5 and 5.1. and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen. and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs

  20. Phase II drugs currently being investigated for the treatment of hypogonadism.

    Science.gov (United States)

    Udedibia, Emeka; Kaminetsky, Jed

    2014-12-01

    Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

  1. Current antiviral drugs and their analysis in biological materials - Part II: Antivirals against hepatitis and HIV viruses.

    Science.gov (United States)

    Nováková, Lucie; Pavlík, Jakub; Chrenková, Lucia; Martinec, Ondřej; Červený, Lukáš

    2018-01-05

    This review is a Part II of the series aiming to provide comprehensive overview of currently used antiviral drugs and to show modern approaches to their analysis. While in the Part I antivirals against herpes viruses and antivirals against respiratory viruses were addressed, this part concerns antivirals against hepatitis viruses (B and C) and human immunodeficiency virus (HIV). Many novel antivirals against hepatitis C virus (HCV) and HIV have been introduced into the clinical practice over the last decade. The recent broadening portfolio of these groups of antivirals is reflected in increasing number of developed analytical methods required to meet the needs of clinical terrain. Part II summarizes the mechanisms of action of antivirals against hepatitis B virus (HBV), HCV, and HIV, their use in clinical practice, and analytical methods for individual classes. It also provides expert opinion on state of art in the field of bioanalysis of these drugs. Analytical methods reflect novelty of these chemical structures and use by far the most current approaches, such as simple and high-throughput sample preparation and fast separation, often by means of UHPLC-MS/MS. Proper method validation based on requirements of bioanalytical guidelines is an inherent part of the developed methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors.

    Science.gov (United States)

    Kolontarev, Konstantin; Govorov, Alexander; Kasyan, George; Priymak, Diana; Pushkar, Dmitry

    2016-01-01

    Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors. The authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed. Twenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected. The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.

  3. Definitions (and Current Controversies) of Diabetes and Prediabetes.

    Science.gov (United States)

    Buysschaert, Martin; Medina, Jose-Luis; Buysschaert, Benoit; Bergman, Michael

    2016-01-01

    Diagnosis of type 2 diabetes and prediabetes is mandatory. Chronic hyperglycemia in diabetes is associated with long-term micro- and macrovascular as well as with neurological complications. Prediabetes predisposes patients to develop diabetes and macrovascular disease. Diagnosis of diabetes is established on (at least) one of the following criteria: a fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/l), a casual plasma glucose ≥ 200 mg/dl (11.1 mmol/l) in the presence of symptoms, a 2-h plasma glucose during the 75-g oral glucose tolerance test (OGTT) ≥ 200 mg/dl (11.1 mmol/l) and/or an HbA1c ≥ 6.5%. Prediabetes is defined by the Position Statement of the American Diabetes Association as a fasting plasma glucose between 100 and 125 mg/dl (5.6 - 6.9 mmol/l) [a condition called Impaired Fasting Glucose] and/or by a 2-h plasma glucose during OGTT 140 - 199 mg/dl (7.8 - 11.0 mmol) [Impaired Glucose Tolerance] and/or a HbA1c level 5.7 - 6.4%, with however some potential discordance between tests. The threshold of fasting plasma glucose defining Impaired Fasting Glucose as well as the adequacy of HbA1c as a correct diagnostic tool for prediabetes is still debated.

  4. Generic immunosuppression in transplantation: current evidence and controversial issues.

    Science.gov (United States)

    El Hajj, Sandra; Kim, Miae; Phillips, Karen; Gabardi, Steven

    2015-05-01

    The overall success of organ transplantation in the 21st century has been predicated, in part, on the use of newer, more potent, and selective immunosuppressive agents. However, the high cost of lifelong immunosuppression represents a financial burden for many patients. In the past 15 years, regulatory agencies in Europe and America have approved several generic immunosuppressants. One concern is whether the conversion between innovator and generic immunosuppressants will prove to be problematic. This manuscript aims to compare and contrast the bioequivalence requirements among regulatory authorities in the USA, Europe, and Canada, evaluate published studies of generic immunosuppressants in transplant recipients, summarize consensus statements made by transplant organizations and discuss how to engage patients in discussion regarding the choice between innovator and generic immunosuppressants.

  5. Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

    Science.gov (United States)

    Jeong, Sohyun; Sohn, Minji; Kim, Jae Hyun; Ko, Minoh; Seo, Hee-Won; Song, Yun-Kyoung; Choi, Boyoon; Han, Nayoung; Na, Han-Sung; Lee, Jong Gu; Kim, In-Wha; Oh, Jung Mi; Lee, Euni

    2017-06-21

    Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

  6. Ayurveda and botanical drugs for epilepsy: Current evidence and future prospects.

    Science.gov (United States)

    Sriranjini, Sitaram Jaideep; Sandhya, Kumar; Mamta, Vernekar Sanjeeva

    2015-11-01

    The understanding of epilepsy has progressed since its earliest impression as a disease associated with paranormal and superstitious beliefs. Landmark advances have been made in deciphering the pathophysiological substrates involved in the disease process, and treatment advances have contributed significantly to ameliorating the seizures. However, disease-modifying agents are yet to be discovered. Ayurveda is a system of medicine that stresses a holistic approach to disease, and treatment is focused on disease modification and symptom management. Herbs form the core of Ayurveda medicine; though many of them have been studied for their anticonvulsant activity, very few actually mention the reference of these herbs in Ayurveda literature. Other therapeutic interventions used in Ayurveda are relatively unexplored, and future research will need to focus on this. The current manuscript briefly discusses the understanding of epilepsy as per Ayurveda and reviews herbs that have been studied for their anticonvulsant activity mentioned in Ayurveda literature. This article is part of a Special Issue entitled "Botanicals for Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

  7. African medicinal plants and their derivatives: Current efforts towards potential anti-cancer drugs.

    Science.gov (United States)

    Mbele, Mzwandile; Hull, Rodney; Dlamini, Zodwa

    2017-10-01

    Cancer is a leading cause of mortality and morbidity worldwide and second only to cardiovascular diseases. Cancer is a challenge in African countries because generally there is limited funding available to deal with the cancer epidemic and awareness and this should be prioritised and all possible resources should be utilized to prevent and treat cancer. The current review reports on the role of African medicinal plants in the treatment of cancer, and also outlines methodologies that can also be used to achieve better outcomes for cancer treatment. This review outlines African medicinal plants, isolated compounds and technologies that can be used to advance cancer research. Chemical structures of isolated compounds have an important role in anti-cancer treatments; new technologies and methods may assist to identify more properties of African medicinal plants and the treatment of cancer. In conclusion, African medicinal plants have shown their potential as enormous resources for novel cytotoxicity compounds. Finally it has been noted that the cytotoxicity depends on the chemical structural arrangements of African medicinal plants compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

    Science.gov (United States)

    Waffenschmidt, Siw; Guddat, Charlotte

    2015-01-01

    Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

  9. Cognitive styles: Controversial issues and research problems

    Directory of Open Access Journals (Sweden)

    Natalia N. Volkova

    2016-06-01

    Full Text Available The paper presents an analytical review of cognitive styles research, considering the problems of its theory, methodology, measurement and practical applications. Issues concerning the prospects, as well as theoretical and practical relevance of cognitive styles research, are discussed. We examine the main causes leading to researchers’ declining interest to study of cognitive styles, related to theory, methodology, measurement and practical applications. The main problems discussed relate to lack of clear definition and common theoretical framework. Moreover, the number of empirical studies prevails over the one aimed at theoretical generalization of empirical results and findings, and therefore the primacy of empirics appears. We analyze the possible ways of advancing the field, suggested research programs and potential perspectives for future research. We pose questions of the relationship between cognitive styles and other psychological constructs, such as abilities and cognitive strategies. We emphasize the need to develop integrative models of cognitive styles in order to systematize and organize a large number of existing cognitive styles dimensions. The main controversial issues concerning cognitive styles’ stability and value are considered. We suggest that cognitive style is a psychological mean of cognitive tasks solving, based on both situation circumstances and subject’s current cognitive resources. Issues concerning cognitive styles may answer the question on the nature of individual differences and clarify psychological mechanisms of personality-situation interaction. Furthermore, it may serve as a basis for integrated studies at the areas of personality and cognitive psychology.

  10. Lyme disease: diagnostic issues and controversies.

    Science.gov (United States)

    Aguero-Rosenfeld, Maria E; Wormser, Gary P

    2015-01-01

    The diagnosis of Lyme disease is a controversial topic. Most practitioners and scientists recognize that Lyme disease is associated with certain objective clinical manifestations supported by laboratory evidence of infection with Borrelia burgdorferi sensu lato (the etiologic agent). There are others, however, who believe that patients with Lyme disease may have a wide variety of entirely nonspecific symptoms without any objective clinical manifestation and that laboratory evidence of infection by B. burgdorferi is not required to support the diagnosis. In reality, this perspective is not evidence based and would inevitably lead to innumerable misdiagnoses, given the high frequency of medically unexplained symptoms, such as fatigue and musculoskeletal pains, in the general population. Although those espousing this viewpoint do not believe that a positive laboratory test is required, nevertheless, they often seek out and promote alternative, unapproved testing methods that frequently provide false-positive results to justify their diagnosis. Herein, we provide a brief overview of Lyme disease testing, emphasizing current usage and limitations. We also discuss the use of nonvalidated procedures and the prospects for a reduction in such testing practices in the future.

  11. Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Pierangelo eCifelli

    2013-07-01

    Full Text Available The pharmacological treatment of mesial temporal lobe epilepsy (mTLE, the most common epileptic syndrome in adults, is still unsatisfactory, as one third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown of the evoked currents (IGABA, which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam and on the neurotrophin BDNF, which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, levetiracetam did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of levetiracetam was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome.

  12. Hydroelectric power is green, although controversial

    International Nuclear Information System (INIS)

    Schulp, A.

    2003-01-01

    Hydroelectric power is worldwide the most important source of renewable energy. Still, it has some controversial aspects, which are briefly discussed in this article, focusing on Belgium and the Netherlands [nl

  13. Metastatic castration-resistant prostate cancer: a current view on drug therapy and alternative tumor cell regulation

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2018-01-01

    Full Text Available Prostate cancer (PC is one of the most common causes of death from malignant neoplasms in men in many countries around the world. Transmission of the signal in the androgenic axis of regulation is crucial for the development and progression of PC. Despite the constant dependence on androgen receptor signals in castration resistance, the use of new anti-androgenic drugs invariably leads to the stability  of the ongoing treatment. The interaction of androgen receptor and alternative (phosphoinositide-3-kinases, PI3K pathways in the regulation of cells can be one of the mechanisms of resistance to treatment. In this article, we describe current treatments for metastatic castration-resistant PC and the possible role of the PI3K pathway in the pathogenesis and progression of PC.

  14. Controversies in Persistent (Chronic) Lyme Disease

    Science.gov (United States)

    2016-01-01

    The Centers for Disease Control and Prevention estimates that more than 300 000 new cases of Lyme disease occur each year in the United States and that 10% to 20% of these patients will remain symptomatic despite receiving appropriate antibiotic therapy. Many elements of the disease are poorly understood and have generated considerable controversy. This paper discusses the medical controversies related to posttreatment manifestations and their potential impact on infusion nurses. PMID:27755213

  15. How science makes environmental controversies worse

    International Nuclear Information System (INIS)

    Sarewitz, Daniel

    2004-01-01

    I use the example of the 2000 US Presidential election to show that political controversies with technical underpinnings are not resolved by technical means. Then, drawing from examples such as climate change, genetically modified foods, and nuclear waste disposal, I explore the idea that scientific inquiry is inherently and unavoidably subject to becoming politicized in environmental controversies. I discuss three reasons for this. First, science supplies contesting parties with their own bodies of relevant, legitimated facts about nature, chosen in part because they help make sense of, and are made sensible by, particular interests and normative frameworks. Second, competing disciplinary approaches to understanding the scientific bases of an environmental controversy may be causally tied to competing value-based political or ethical positions. The necessity of looking at nature through a variety of disciplinary lenses brings with it a variety of normative lenses, as well. Third, it follows from the foregoing that scientific uncertainty, which so often occupies a central place in environmental controversies, can be understood not as a lack of scientific understanding but as the lack of coherence among competing scientific understandings, amplified by the various political, cultural, and institutional contexts within which science is carried out. In light of these observations, I briefly explore the problem of why some types of political controversies become 'scientized' and others do not, and conclude that the value bases of disputes underlying environmental controversies must be fully articulated and adjudicated through political means before science can play an effective role in resolving environmental problems

  16. Interpretation of Controversial Teratogenic Findings of Drugs Such As Phenobarbital

    OpenAIRE

    Czeizel, Andrew E.; Dudás, Istvan; Bánhidy, Ferenc

    2011-01-01

    Objective. To check the debated association between phenobarbital treatment during pregnancy and risk for congenital abnormalities (CAs) in their children. Study Design. It is a comparison of phenobarbital treatment in the mothers of cases with CA and matched controls without CAs in the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Results. Of 22,843 cases with CA, 149 (0.65%) had mothers with phenobarbital treatment, while of 38,151 control newborn infants without C...

  17. Controversies in testosterone supplementation therapy

    Directory of Open Access Journals (Sweden)

    Mohit Khera

    2015-04-01

    Full Text Available Testosterone has now become one of the most widely used medications throughout the world. The rapid growth of the testosterone market in the past 10 years is due to many factors. We currently have a worldwide aging population. In the US, the number of men 65 years old or older is increasing 2-3 times faster than the number of men younger than 65 years. In addition, poor general health and certain medical conditions such as diabetes/metabolic syndrome (MetS, cardiovascular disease (CVD, and osteoporosis have been associated with low serum testosterone levels. [1],[2],[3] There are now fewer concerns regarding the development of prostate cancer (PCa after testosterone therapy, making it a more attractive treatment option. Finally, the introduction of different forms of testosterone supplementation therapy (TST with increased promotion, marketing, and direct-to-consumer advertising is also driving market growth. As the demand for TST continues to grow, it is becoming more important for clinicians to understand how to diagnose and treat patients with low testosterone.

  18. Metabolic syndrome: definitions and controversies

    Directory of Open Access Journals (Sweden)

    Kaltsas Gregory

    2011-05-01

    Full Text Available Abstract Metabolic syndrome (MetS is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS.

  19. Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

    Science.gov (United States)

    Chaparro, María Jesús; Calderón, Félix; Castañeda, Pablo; Fernández-Alvaro, Elena; Gabarró, Raquel; Gamo, Francisco Javier; Gómez-Lorenzo, María G; Martín, Julio; Fernández, Esther

    2018-04-13

    Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits. Optimization efforts on several chemical series have been successful, and clinical candidates have been identified. In addition, recent advances in genetics and proteomics have led to the target deconvolution of phenotypic clinical candidates. New mechanisms of action will also be critical to overcome resistance and reduce attrition. Therefore, a complementary strategy focused on identifying well-validated targets to start hit identification programs is essential to reinforce the clinical pipeline. Leveraging published data, we have assessed the status quo of the current antimalarial target portfolio with a focus on the blood stage clinical disease. From an extensive list of reported Plasmodium targets, we have defined triage criteria. These criteria consider genetic, pharmacological, and chemical validation, as well as tractability/doability, and safety implications. These criteria have provided a quantitative score that has led us to prioritize those targets with the highest probability to deliver successful and differentiated new drugs.

  20. Differences in sociodemographic, drug use and health characteristics between never, former and current injecting, problematic hard-drug users in the Netherlands

    NARCIS (Netherlands)

    Havinga, Petra; van der Velden, Claudia; de Gee, Anouk; van der Poel, Agnes; Yin, Huifang

    2014-01-01

    Background: Injecting drug users are at increased risk for harmful effects compared to non-injecting drug users. Some studies have focused on differences in characteristics between these two groups (e. g., housing, overall health). However, no study has investigated the specific Dutch situation

  1. Cold dark matter: Controversies on small scales.

    Science.gov (United States)

    Weinberg, David H; Bullock, James S; Governato, Fabio; Kuzio de Naray, Rachel; Peter, Annika H G

    2015-10-06

    The cold dark matter (CDM) cosmological model has been remarkably successful in explaining cosmic structure over an enormous span of redshift, but it has faced persistent challenges from observations that probe the innermost regions of dark matter halos and the properties of the Milky Way's dwarf galaxy satellites. We review the current observational and theoretical status of these "small-scale controversies." Cosmological simulations that incorporate only gravity and collisionless CDM predict halos with abundant substructure and central densities that are too high to match constraints from galaxy dynamics. The solution could lie in baryonic physics: Recent numerical simulations and analytical models suggest that gravitational potential fluctuations tied to efficient supernova feedback can flatten the central cusps of halos in massive galaxies, and a combination of feedback and low star formation efficiency could explain why most of the dark matter subhalos orbiting the Milky Way do not host visible galaxies. However, it is not clear that this solution can work in the lowest mass galaxies, where discrepancies are observed. Alternatively, the small-scale conflicts could be evidence of more complex physics in the dark sector itself. For example, elastic scattering from strong dark matter self-interactions can alter predicted halo mass profiles, leading to good agreement with observations across a wide range of galaxy mass. Gravitational lensing and dynamical perturbations of tidal streams in the stellar halo provide evidence for an abundant population of low-mass subhalos in accord with CDM predictions. These observational approaches will get more powerful over the next few years.

  2. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

    NARCIS (Netherlands)

    Hofstra, L. Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van De Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leontios G.; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Lepej, Snjezana Zidovec; Boucher, Charles A B; Schmit, Jean Claude; Wensing, Annemarie M J; Puchhammer-Stockl, E.; Sarcletti, M.; Schmied, B.; Geit, M.; Balluch, G.; Vandamme, A. M.; Vercauteren, J.; Derdelinckx, I.; Sasse, A.; Bogaert, M.; Ceunen, H.; De Roo, A.; De Wit, S.; Echahidi, F.; Fransen, K.; Goffard, J. C.; Goubau, P.; Goudeseune, E.; Yombi, J. C.; Lacor, P.; Liesnard, C.; Moutschen, M.; Pierard, D.; Rens, R.; Schrooten, Y.; Vaira, D.; Vandekerckhove, L. P R; Van Den Heuvel, A.; Van Der Gucht, B.; Van Ranst, M.; Van Wijngaerden, E.; Vandercam, B.; Vekemans, M.; Verhofstede, C.; Clumeck, N.; Van Laethem, K.; Beshkov, D.; Alexiev, I.; Lepej, S. Zidovec; Begovac, J.; Kostrikis, Leontios G.; Demetriades, I.; Kousiappa, I.; Demetriou, V.; Hezka, J.; Linka, M.; Maly, M.; Machala, L.; Nielsen, C.; Jørgensen, L. B.; Gerstoft, J.; Mathiesen, L.; Pedersen, C.; Nielsen, H.; Laursen, A.; Kvinesdal, B.; Liitsola, K.; Ristola, M.; Suni, J.; Sutinen, J.; Descamps, D.; Assoumou, L.; Castor, G.; Grude, M.; Flandre, P.; Storto, A.; Hamouda, O.; Kücherer, C.; Berg, T.; Braun, P.; Poggensee, G.; Däumer, M.; Eberle, J.; Heiken, H.; Kaiser, R.; Knechten, H.; Korn, K.; Müller, H.; Neifer, S.; Schmidt, B.; Walter, H.; Gunsenheimer-Bartmeyer, B.; Harrer, T.; Paraskevis, D.; Hatzakis, A.; Zavitsanou, A.; Vassilakis, A.; Lazanas, M.; Chini, M.; Lioni, A.; Sakka, V.; Kourkounti, S.; Paparizos, V.; Antoniadou, A.; Papadopoulos, A.; Poulakou, G.; Katsarolis, I.; Protopapas, K.; Chryssos, G.; Drimis, S.; Gargalianos, P.; Xylomenos, G.; Lourida, G.; Psichogiou, M.; Daikos, G. L.; Sipsas, N. V.; Kontos, A.; Gamaletsou, M. N.; Koratzanis, G.; Sambatakou, E.; Mariolis, H.; Skoutelis, A.; Papastamopoulos, V.; Georgiou, O.; Panagopoulos, P.; Maltezos, E.; Coughlan, S.; De Gascun, C.; Byrne, C.; Duffy, M.; Bergin, C.; Reidy, D.; Farrell, G.; Lambert, J.; O'Connor, E.; Rochford, A.; Low, J.; Coakely, P.; O'Dea, S.; Hall, W.; Mor, O.; Levi, I.; Chemtob, D.; Grossman, Z.; Zazzi, M.; De Luca, A.; Balotta, C.; Riva, C.; Mussini, C.; Caramma, I.; Capetti, A.; Colombo, M. C.; Rossi, C.; Prati, F.; Tramuto, F.; Vitale, F.; Ciccozzi, M.; Angarano, G.; Rezza, G.; Kolupajeva, T.; Kolupajeva, T.; Vasins, O.; Griskevicius, A.; Lipnickiene, V.; Schmit, J. C.; Struck, D.; Sauvageot, N.; Hemmer, R.; Arendt, V.; Michaux, C.; Staub, T.; Sequin-Devaux, C.; Wensing, A. M J; Boucher, C. A B; Van Kessel, A.; Van Bentum, P. H M; Brinkman, K.; Connell, B. J.; Van Der Ende, M. E.; Hoepelman, I. M.; Van Kasteren, M.; Kuipers, M.; Langebeek, N.; Richter, C.; Santegoets, R. M W J; Schrijnders-Gudde, L.; Schuurman, R.; Van De Ven, B. J M; Åsjö, B.; Kran, A. M Bakken; Ormaasen, V.; Aavitsland, P.; Horban, A.; Stanczak, J. J.; Stanczak, G. P.; Firlag-Burkacka, E.; Wiercinska-Drapalo, A.; Jablonowska, E.; Maolepsza, E.; Leszczyszyn-Pynka, M.; Szata, W.; Camacho, R.; Palma, C.; Borges, F.; Paixão, T.; Duque, V.; Araújo, F.; Otelea, D.; Paraschiv, S.; Tudor, A. M.; Cernat, R.; Chiriac, C.; Dumitrescu, F.; Prisecariu, L. J.; Stanojevic, M.; Jevtovic, Dj; Salemovic, D.; Stanekova, D.; Habekova, M.; Chabadová, Z.; Drobkova, T.; Bukovinova, P.; Shunnar, A.; Truska, P.; Poljak, M.; Lunar, M.; Babic, D.; Tomazic, J.; Vidmar, L.; Vovko, T.; Karner, P.; Garcia, F.; Paredes, R.; Monge, S.; Moreno, S.; Del Amo, J.; Asensi, V.; Sirvent, J. L.; De Mendoza, C.; Delgado, R.; Gutiérrez, F.; Berenguer, J.; Garcia-Bujalance, S.; Stella, N.; De Los Santos, I.; Blanco, J. R.; Dalmau, D.; Rivero, M.; Segura, F.; Elías, M. J Pérez; Alvarez, M.; Chueca, N.; Rodríguez-Martín, C.; Vidal, C.; Palomares, J. C.; Viciana, I.; Viciana, P.; Cordoba, J.; Aguilera, A.; Domingo, P.; Galindo, M. J.; Miralles, C.; Del Pozo, M. A.; Ribera, E.; Iribarren, J. A.; Ruiz, L.; De La Torre, J.; Vidal, F.; Clotet, B.; Albert, J.; Heidarian, A.; Aperia-Peipke, K.; Axelsson, M.; Mild, M.; Karlsson, A.; Sönnerborg, A.; Thalme, A.; Navér, L.; Bratt, G.; Karlsson, A.; Blaxhult, A.; Gisslén, M.; Svennerholm, B.; Bergbrant, I.; Björkman, P.; Säll, C.; Lindholm, A.; Kuylenstierna, N.; Montelius, R.; Azimi, F.; Johansson, B.; Carlsson, M.; Johansson, E.; Ljungberg, B.; Ekvall, H.; Strand, A.; Mäkitalo, S.; Öberg, S.; Holmblad, P.; Höfer, M.; Holmberg, H.; Josefson, P.; Ryding, U.

    2016-01-01

    Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline

  3. The words of controversy about climate change

    International Nuclear Information System (INIS)

    Chetouani, Lamria

    2007-01-01

    The author analyses the rhetorical staging of controversies which occur in France about climate change, and more particularly about the greenhouse effect. In a first part, she makes a distinction between four registers of controversy: on responsibilities, on consequences and extent of the phenomenon, on solutions, and on spatio-temporal projections of the greenhouse effect. She shows that debates are structured by an opposition between optimism and pessimism. In a second part, based on a lexicological analysis, she highlights the important oppositions between scientific speeches and political speeches, independent speeches and technocratic speeches, and so on, with unexpected aspects. It appears that controversy goes largely beyond the scientific debate, and incorporates crossed interventions of economic, political and social concern

  4. On the history of the nuclear controversy

    International Nuclear Information System (INIS)

    Muench, E.

    1979-01-01

    For the past ten years or so the introduction and expansion of nuclear power in a number of industrialized countries of the Western world has been accompanied by a sometimes vehement controversy. This controversy has taken many forms and, in almost all countries, has had distinct effects on the utilization of nuclear power for energy supply purposes. It has given rise to considerable delays in the completion of nuclear installations and, in one country, has even resulted in a rejection of nuclear power altogether. The different facets of the picture, i.e. public action groups opposing nuclear power, the nuclear controversy and scientists, political activities, appeals to courts of law and actions bordering on illegality, are described chronologically and their impacts are analyzed. (orig.) [de

  5. Is there a scientific nuclear controversy

    International Nuclear Information System (INIS)

    Muench, E.; Borsch, P.

    1977-01-01

    In the present rather violent discussion about the introduction of nuclear power into the energy supply system it is often alleged that even experts disagree about many aspects, which is interpreted to prove the existence of a scientific controversy in these points. This study about the existence or in existence of such controversy critically reviews both the different collections of signatures organized by scientists and the statements published in specific areas of science. Important partial aspects are the energy requirement and the ways and means available to meet it, the safety and the risks of nuclear technology, radiation exposure and biological effects, the misuse of plutonium, and reprocessing and the ultimate storage of radioactive waste. The study concludes that there is no scientific controversy about the peaceful uses of nuclear power in the sense of the term used here. (orig.) [de

  6. 'Mysticism' in quantum mechanics: the forgotten controversy

    International Nuclear Information System (INIS)

    Marin, Juan Miguel

    2009-01-01

    This paper argues that a European controversy over a 'mystical' hypothesis, one assigning the mind a role to play at the material level of reality, shaped much of the debate over the interpretation of the quantum equations. It traces back the controversy to the past two decades, beginning in the late 1920s-birth of quantum theory-and concluding with Erwin Schroedinger's lectures published as 'Mind and Matter'. Becoming aware of the issues at stake can help us understand the historical, philosophical and cultural background from which today's physics emerged

  7. Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil.

    Science.gov (United States)

    Ma, Fangfang; Takanari, Hiroki; Masuda, Kimiko; Morishima, Masaki; Ono, Katsushige

    2016-07-01

    Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM. Bepridil also reduced I K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.

  8. A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

    Science.gov (United States)

    Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

    2018-06-30

    In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

  9. Current status and future prospects for enabling chemistry technology in the drug discovery process [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stevan W. Djuric

    2016-09-01

    Full Text Available This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

  10. Apraxia of Speech: Concepts and Controversies

    Science.gov (United States)

    Ziegler, Wolfram; Aichert, Ingrid; Staiger, Anja

    2012-01-01

    Purpose: This article was written as an editorial to a collection of original articles on apraxia of speech (AOS) in which some of the more recent advancements in the understanding of this syndrome are discussed. It covers controversial issues concerning the theoretical foundations of AOS. Our approach was motivated by a change of perspective on…

  11. The first Pico-Ficino Controversy

    DEFF Research Database (Denmark)

    Aasdalen, Unn Irene

    2011-01-01

    -scale conflict regarding how to live and die according to Platonic ideals. The themes of the controversy are firstly the interpretation of Plato’s Symposium, in particular Diotima’s speech, and secondly the practical conclusions one should draw from Plato’s fictional banquet. Ficino’s position is presented...

  12. Controversies in watermanagement : Frames and mental models

    NARCIS (Netherlands)

    Kolkman, Rien; van der Veen, A.; Geurts, Petrus A.T.M.

    2007-01-01

    Controversies in decision and policy-making processes can be analysed using frame reflection and mental model mapping techniques. The purpose of the method presented in this paper is to improve the quality of the information and interpretations available to decision makers, by surfacing and

  13. Atomic weight versus atomic mass controversy

    International Nuclear Information System (INIS)

    Holden, N.E.

    1985-01-01

    A problem for the Atomic Weights Commission for the past decade has been the controversial battle over the names ''atomic weight'' and ''atomic mass''. The Commission has considered the arguments on both sides over the years and it appears that this meeting will see more of the same discussion taking place. In this paper, I review the situation and offer some alternatives

  14. Breast cancer radiotherapy: controversies and prospectives

    Institute of Scientific and Technical Information of China (English)

    YU Jin-ming; WANG Yong-sheng

    2008-01-01

    @@ Despite consensus on breast cancer radiotherapy, there are still some controversies over post-mastectomy radiotherapy (PMRT) in patients with 1-3 positive lymph nodes, accelerated partial breast irradiation (APBI), appropriate sequence of radiotherapy, chemotherapy and hormonal treatment, and radiotherapy after preoperative systemic therapy.

  15. Controversy, Trials, and Crime--Oh My!

    Science.gov (United States)

    Rott, Kim

    2006-01-01

    Teenagers' innate interest with the justice system is one of the reasons that so many high school literary classics teem with criminals, controversial issues, and trials. Novels such as "To Kill a Mockingbird," "A Separate Peace," "The Crucible," and "Twelve Angry Men" feature high-impact trials. In the author's desire to tap into this interest,…

  16. Federal Judge Orders Showing of Controversial Film.

    Science.gov (United States)

    Flygare, Thomas J.

    1987-01-01

    Reviews a recent court decision in Nebraska regarding the cancellation of a controversial film on the University of Nebraska campus. The film was cancelled after a state senator threatened to close the theater if the movie was shown. The lawsuit alleged the university violated the First Amendment in cancelling the film; the judge ruled for the…

  17. The Saga of the HIV Controversy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 5. The Saga of the HIV Controversy - Nobel Prize in Physiology or Medicine - 2008. Udaykumar Ranga. General Article Volume 14 Issue 5 May 2009 pp 472-498. Fulltext. Click here to view fulltext PDF. Permanent link:

  18. Controversial Novels and Censorship in the Schools.

    Science.gov (United States)

    Katz, John Stuart

    The legal history of censorship in general in the United States as well as the legal context in particular of the censorship of novels from schools is discussed. This thesis deals with four novels which have aroused substantial controversy when taught in the schools. The novels are: "The Catcher in the Rye," by J. D. Salinger, "The Adventures of…

  19. Socio-scientific controversies and beginning teachers’ pedagogical practice

    Directory of Open Access Journals (Sweden)

    Pedro Reis

    2005-08-01

    Full Text Available The current investigation aimed to study the impact of recent socio-scientific controversies, made public through the media, on the concepts and practices of a group of Natural Science teachers at the start of their careers. This study is particularly relevant at a time that is heavily marked by much debate regarding the social and environmental impact of several scientific and technological innovations and by the implementation of new science curricula, that stress the importance of discussing socio-scientific controversies in the context of students’ scientific alphabetisation (namely in their understanding of the nature of science and its relation to society and culture (McComas, 2000. This investigation followed an interpretative approach of a qualitative nature. Through the construction of case studies, it sought to analyse the possible impact of socio-scientific controversies on the teachers’ concepts (about the nature, teaching and learning of science and pedagogic practice. For data collection semi-structured interviews were conducted and classes observed.The controversial issues raised by certain recent technological innovations – namely the environmental, social and cultural impact they may have – did have an impact on the teachers’ concepts about the nature, teaching and learning of science. Besides reinforcing the duality of feelings as regards science and technology, as a source of both progress and concern, they triggered in these teachers the idea of the need for a widespread scientific alphabetisation that empowers the population for understanding and deciding and acting upon these issues. However, the concept of scientific alphabetisation and the best way to achieve it vary among the teachers participating in this study.

  20. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  1. Model-based drug administration : current status of target-controlled infusion and closed-loop control

    NARCIS (Netherlands)

    Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.

    Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the

  2. 78 FR 22887 - Guidance for Industry on Non-Penicillin Beta-Lactam Drugs: A Current Good Manufacturing Practices...

    Science.gov (United States)

    2013-04-17

    ... for Preventing Cross- Contamination; Availability AGENCY: Food and Drug Administration, HHS. ACTION... require separation of manufacturing facilities to avoid cross-contamination, the only class of products... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0104...

  3. Cannabis Controversies: How genetics can inform the study of comorbidity

    Science.gov (United States)

    Agrawal, Arpana; Lynskey, Michael T.

    2014-01-01

    Aims To review three key and controversial comorbidities of cannabis use – other illicit drug use, psychosis and depression as well as suicide, from a genetically informed perspective. Design Selective review. Results Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Conclusions Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. PMID:24438181

  4. Multi-channel counter-current chromatography for high-throughput fractionation of natural products for drug discovery.

    Science.gov (United States)

    Wu, Shihua; Yang, Lu; Gao, Yuan; Liu, Xiaoyue; Liu, Feiyan

    2008-02-08

    A multi-channel counter-current chromatography (CCC) method has been designed and fabricated for the high-throughput fractionation of natural products without complications sometimes encountered with other conventional chromatographic systems, such as irreversible adsorptive constituent losses and deactivation, tailing of solute peaks and contamination. It has multiple independent CCC channels and each channel connects independent separation column(s) by parallel flow tubes, and thus the multi-channel CCC apparatus can achieve simultaneously two or more independent chromatographic processes. Furthermore, a high-throughput CCC fractionation method for natural products has been developed by a combination of a new three-channel CCC apparatus and conventional parallel chromatographic devices including pumps, sample injectors, effluent detectors and collectors, and its performance has been displayed on the fractionation of ethyl acetate extracts of three natural materials Solidago canadensis, Suillus placidus, and Trichosanthes kirilowii, which are found to be potent cytotoxic to tumor cell lines in the course of screening the antitumor candidates. By combination of biological screening programs and preparative high-performance liquid chromatography (HPLC) purification, 22.8 mg 6 beta-angeloyloxykolavenic acid and 29.4 mg 6 beta-tigloyloxykolavenic acid for S. canadensis, 25.3mg suillin for S. placidus, and 6.8 mg 23,24-dihydrocucurbitacin B for T. Kirilowii as their major cytotoxic principles were isolated from each 1000 mg crude ethyl acetate extract. Their chemical structures were characterized by electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance. The overall results indicate the multi-channel CCC is very useful for high-throughput fractionation of natural products for drug discovery in spite of the solvent balancing requirement and the lower resolution of the shorter CCC columns.

  5. Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe

    DEFF Research Database (Denmark)

    Bothamley, Graham H.; Lange, Christoph; Albrecht, Dirk

    2017-01-01

    AIM: Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. METHODS: TBNET is a pan...

  6. Controversies in the management of tongue base cancer.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2012-01-31

    BACKGROUND: Tongue base cancer is one of the most lethal head and neck cancers. There is considerable controversy in the management of this disease with wide variation of opinion within the literature. METHODS: We discuss the presentation, diagnostic and therapeutic strategies which exist in the literature. Articles were reviewed from 1970 to 2007 within the Medline, Pubmed and Cochrane libraries. CONCLUSIONS: Smokers with a history of persistent unilateral neck pain, even in the absence of clinical signs warrant MRI neck imaging. Tongue base cancer organ preservation therapeutic strategies, radiation and concomitant platinum based chemotherapy, currently optimise oncologic and quality of life outcomes.

  7. Global Banning of a Diffused Controversial Practice

    DEFF Research Database (Denmark)

    Gurses, Kerem; Giones, Ferran; Mehta, Kandarpkumar

    2017-01-01

    We study the deinstitutionalization of a controversial practice that had previously reached a level of international diffusion. We draw on international diffusion and deinstitutionalization theory to study the emergence and diffusion of the third-party ownership practice in the soccer industry. We...... use an inductive case study combining archival and interview data to study the determinants of the international diffusion of a controversial practice at a global scale, the contestation, and finally the deinstitutionalization process that resulted from the ban of the practice. We find...... that the opacity of the practice can be a diffusion driver, locally and at the international level, nevertheless the opacity also may lead to different meaning creation attempts and potential discursive battles between actors, and eventually to deinstitutionalization of the practice. This article advances our...

  8. Epistemic Authority and Genuine Ethical Controversies.

    Science.gov (United States)

    Roberts, Adam James

    2017-05-01

    In 'Professional Hubris and its Consequences', Eric Vogelstein claims that 'that there are no good arguments in favor of professional organizations taking genuinely controversial positions on issues of professional ethics'. In this response, I defend two arguments in favour of organisations taking such positions: that their stance-taking may lead to better public policy, and that it may lead to better practice by medical professionals. If either of those defences succeeds, then Vogelstein's easy path to his conclusion - that professional organisations should not take such stances - is blocked. He or others must instead look to establish that the reasons against stance-taking on genuine ethical controversies are more compelling than those for it: plausibly a more challenging task. © 2017 John Wiley & Sons Ltd.

  9. History of the Belgian nuclear power controversy

    International Nuclear Information System (INIS)

    Laes, E.

    2009-01-01

    Partly because nuclear energy technology continues to provoke profound controversy, the Flemish institute for technology assessment (viWTA) took the initiative to order a study aimed at mapping out the historical dynamics of the societal debate on nuclear energy. This study was carried out by the Belgian Nuclear Research Centre (SCK-CEN, under the research programme PISA) together with the Free university of Brussels (VUB, research group MEKO) in 2004. In 2007, the report was updated and published by Acco (Leuven) under the title Kernenergie (on)besproken. This study had three main objectives: 1) to discuss the societal debate on nuclear energy in Belgium in relation to major events (Chernobyl, TMI, etc.); 2) to elucidate the role of social actors in the controversy on both a national and international level and 3) to discuss possible alternatives for a better structuring of the debate in the future, building on existing approaches

  10. The mesh controversy [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Joshua A. Cohn

    2016-09-01

    Full Text Available Pelvic organ prolapse and stress urinary incontinence are common conditions for which approximately 11% of women will undergo surgical intervention in their lifetime. The use of vaginal mesh for pelvic organ prolapse and stress urinary incontinence rose rapidly in the early 2000s as over 100 mesh products were introduced into the clinical armamentarium with little regulatory oversight for their use. US Food and Drug Administration Public Health Notifications in 2008 and 2011, as well as reclassification of transvaginal mesh for prolapse to class III in early 2016, were a response to debilitating complications associated with transvaginal mesh placement in many women. The midurethral sling has not been subject to the same reclassification and continues to be endorsed as the “gold standard” for surgical management of stress urinary incontinence by subspecialty societies. However, litigators have not differentiated between mesh for prolapse and mesh for incontinence. As such, all mesh, including that placed for stress urinary incontinence, faces continued controversy amidst an uncertain future. In this article, we review the background of the mesh controversy, recent developments, and the anticipated role of mesh in surgery for prolapse and stress urinary incontinence going forward.

  11. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

    DEFF Research Database (Denmark)

    Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan

    2016-01-01

    BACKGROUND:  Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management......, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS:  Demographic, clinical, and virological data from 4140 antiretroviral-naive human...... immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002...

  12. Gossip in organisations: Contexts, consequences and controversies

    OpenAIRE

    Michelson, G.; van Iverson, A.; Waddington, K.

    2010-01-01

    This article examines the key themes surrounding gossip including its contexts, the various outcomes (positive and negative) of gossip as well as a selection of challenges and controversies. The challenges which are highlighted revolve around definitional issues, methodological approaches, and ethical considerations. Our analysis suggests that the characteristics and features of gossip lend itself to a process-oriented approach whereby the beginning and, particularly, end points of gossip are...

  13. Climatic change science, experience and controversies

    International Nuclear Information System (INIS)

    Le Treut, H.; Van Ypersele, J.P.; Hallegatte, St.; Hourcade, J.Ch.

    2004-01-01

    The international scientific community, gathered in the framework of the inter-governmental group for climate evolution (Giec), has confirmed the influence of human activities on climate and on the global warming. However, this diagnosis is sometimes questioned in the press. This book, published by the institute of sustainable development, gathers a series of articles written by scientists who make comments on the last Giec reports and who outline the knowledge gained, the remaining uncertainties and the controversies. (J.S.)

  14. Congenital bronchopulmonary foregut malformations: concepts and controversies

    International Nuclear Information System (INIS)

    Newman, Beverley

    2006-01-01

    This article addresses the scope, etiology, important associations and imaging features of congenital bronchopulmonary foregut malformations. Etiologic concepts, including airway obstruction and vascular anomalies, are highlighted. Technical imaging advances, especially CT and MR, have greatly enhanced our diagnostic abilities in evaluating these lesions; however, thorough and careful assessment of all aspects of the malformation is still necessary. Several specific lesions are discussed in more detail, particularly regarding controversial issues in classification, understanding, imaging and management. (orig.)

  15. Congenital bronchopulmonary foregut malformations: concepts and controversies

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Beverley [University of Pittsburgh School of Medicine and Children' s Hospital of Pittsburgh, Pittsburgh, PA (United States)

    2006-08-15

    This article addresses the scope, etiology, important associations and imaging features of congenital bronchopulmonary foregut malformations. Etiologic concepts, including airway obstruction and vascular anomalies, are highlighted. Technical imaging advances, especially CT and MR, have greatly enhanced our diagnostic abilities in evaluating these lesions; however, thorough and careful assessment of all aspects of the malformation is still necessary. Several specific lesions are discussed in more detail, particularly regarding controversial issues in classification, understanding, imaging and management. (orig.)

  16. E-cigarettes: scientific and political controversies

    OpenAIRE

    Yussuf Saloojee

    2018-01-01

    Background and challenges to implementation The e-cigarette is touted as a disruptive technology that could make combustible cigarettes obsolete. The product, its science and politics though are controversial. Intervention or response Published journal articles, reports and conference presentations on e-cigarettes were located using PubMed, plus conference, industry and other websites. These were critically reviewed. Results and lessons learnt A number of contenti...

  17. Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings.

    Science.gov (United States)

    Barker, David J; Simmons, Steven J; West, Mark O

    2015-01-01

    The present review describes ways in which ultrasonic vocalizations (USVs) have been used in studies of substance abuse. Accordingly, studies are reviewed which demonstrate roles for affective processing in response to the presentation of drug-related cues, experimenter- and self-administered drug, drug withdrawal, and during tests of relapse/reinstatement. The review focuses on data collected from studies using cocaine and amphetamine, where a large body of evidence has been collected. Data suggest that USVs capture animals' initial positive reactions to psychostimulant administration and are capable of identifying individual differences in affective responding. Moreover, USVs have been used to demonstrate that positive affect becomes sensitized to psychostimulants over acute exposure before eventually exhibiting signs of tolerance. In the drug-dependent animal, a mixture of USVs suggesting positive and negative affect is observed, illustrating mixed responses to psychostimulants. This mixture is predominantly characterized by an initial bout of positive affect followed by an opponent negative emotional state, mirroring affective responses observed in human addicts. During drug withdrawal, USVs demonstrate the presence of negative affective withdrawal symptoms. Finally, it has been shown that drug-paired cues produce a learned, positive anticipatory response during training, and that presentation of drug-paired cues following abstinence produces both positive affect and reinstatement behavior. Thus, USVs are a useful tool for obtaining an objective measurement of affective states in animal models of substance abuse and can increase the information extracted from drug administration studies. USVs enable detection of subtle differences in a behavioral response that might otherwise be missed using traditional measures.

  18. Controversies in faith and health care.

    Science.gov (United States)

    Tomkins, Andrew; Duff, Jean; Fitzgibbon, Atallah; Karam, Azza; Mills, Edward J; Munnings, Keith; Smith, Sally; Seshadri, Shreelata Rao; Steinberg, Avraham; Vitillo, Robert; Yugi, Philemon

    2015-10-31

    Differences in religious faith-based viewpoints (controversies) on the sanctity of human life, acceptable behaviour, health-care technologies and health-care services contribute to the widespread variations in health care worldwide. Faith-linked controversies include family planning, child protection (especially child marriage, female genital mutilation, and immunisation), stigma and harm reduction, violence against women, sexual and reproductive health and HIV, gender, end-of-life issues, and faith activities including prayer. Buddhism, Christianity, Hinduism, Islam, Judaism, and traditional beliefs have similarities and differences in their viewpoints. Improved understanding by health-care providers of the heterogeneity of viewpoints, both within and between faiths, and their effect on health care is important for clinical medicine, public-health programmes, and health-care policy. Increased appreciation in faith leaders of the effect of their teachings on health care is also crucial. This Series paper outlines some faith-related controversies, describes how they influence health-care provision and uptake, and identifies opportunities for research and increased interaction between faith leaders and health-care providers to improve health care. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

    Science.gov (United States)

    Cerniglia, Carl E; Pineiro, Silvia A; Kotarski, Susan F

    2016-05-01

    The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Restaurant Menu Labeling Policy: Review of Evidence and Controversies

    Science.gov (United States)

    VanEpps, Eric M.; Roberto, Christina A.; Park, Sara; Economos, Christina D.; Bleich, Sara N.

    2016-01-01

    In response to high rates of obesity in the USA, several American cities, counties, and states have passed laws requiring restaurant chains to post labels identifying the energy content of items on menus, and nationwide implementation of menu labeling is expected in late 2016. In this review, we identify and summarize the results of 16 studies that have assessed the impact of real-world numeric calorie posting. We also discuss several controversies surrounding the US Food and Drug Administration's implementation of federally mandated menu labeling. Overall, the evidence regarding menu labeling is mixed, showing that labels may reduce the energy content of food purchased in some contexts, but have little effect in other contexts. However, more data on a range of ong-term consumption habits and restaurant responses is needed to fully understand the impact menu labeling laws will have on the US population's diet. PMID:26877095

  1. Current scenario

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Current scenario. India , like other parts of the world, is also facing the problem of increase in the incidence of drug resistance in tuberculosis. Multi-drug resistance (MDR, resistance to RIF & INH) and extensively drug resistant strains (X-DR, resistance to RIF, INH, FQs ...

  2. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  3. Urine drug screening in the medical setting.

    Science.gov (United States)

    Hammett-Stabler, Catherine A; Pesce, Amadeo J; Cannon, Donald J

    2002-01-01

    The term drug screen is a misnomer since it implies screening for all drugs, which is not possible. Current practice is to limit the testing to the examination of serum for several drugs such as ethanol, acetaminophen, salicylate, and of urine for several specific drugs or classes of drugs. In the emergency setting the screen should be performed in less than one hour. Controversies continue to exist regarding the value of urine drug testing in the medical setting. The reasons for these include the drugs involved, the sample, the methods utilized to perform the tests, and the level of understanding of the physician using the data, all of which are closely related to the other. Current automated methods provide rapid results demanded in emergency situations, but are often designed for, or adapted from, workplace testing and are not necessarily optimized for clinical applications. Furthermore, the use of these methods without consideration of the frequency in which the drugs are found in a given area is not cost-effective. The laboratory must understand the limitations of the assays used and provide this information to the physician. Additionally, the laboratory and the physicians using the data must cooperate to determine which drugs are appropriate and necessary to measure for their institution and clinical setting. In doing so it should be remembered that for many drugs, the sample, urine, contains the end product(s) of drug metabolism, not the parent drug. Furthermore, it is necessary to understand the pharmacokinetic parameters of the drug of interest when interpreting data. Finally, while testing for some drugs may not appear cost-effective, the prevention or reduction of morbidity and mortality may offset any laboratory costs. While the literature is replete with studies concerning new methods and a few regarding physician understanding, there are none that we could find that thoroughly, objectively, and fully addressed the issues of utility and cost-effectiveness.

  4. Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs: current state and future perspectives

    DEFF Research Database (Denmark)

    Holmgaard, R; Nielsen, J B; Benfeldt, E

    2010-01-01

    of instrumentation, calibration and experimental procedures are discussed along with the analytical considerations necessary for successful sampling. Clinical MD studies in the skin are reviewed with emphasis on pharmacokinetic studies of topically applied drugs with or without impairment of skin barrier function...

  5. Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk.

    Science.gov (United States)

    Raschi, Emanuel; De Ponti, Fabrizio

    2015-07-08

    Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities.

  6. New Reproductive Conception Technologies: Bioethics and Controversies

    Directory of Open Access Journals (Sweden)

    Marlene Tamanini

    2004-01-01

    Full Text Available This article concerns some of the multiple ethical-bioethical and gender issues in the field of new reproductive and contraceptive technologies. The literature presented points to the plurality of possible situations and approaches in a multidimensional and controversial field. It presents some ethical-bioethical principals of biomedical action found in the study of heterosexual couples who use assisted reproduction. and of medical specialists in human reproduction in southern Brazil. It presents the ethical-bioethical presumptions that sanction medical behavior and the continuity of the so-called impregnation treatments, and analyzes the mechanisms used to raise the expectations of couples who lack confidence or success.

  7. PET in cancer screening: a controversial imaging

    International Nuclear Information System (INIS)

    Su Minggang; Tan Tianzhi

    2012-01-01

    Malignancy has been one of the most dangerous threats to human health. Early diagnosis and treatment are key factors for improving prognosis. Cancer screening is an important way to detect early stage cancer and precancerous lesion. PET has been used increasingly in cancer screening in accordance with the requirement of the public. Though a great number of data show that PET can find some subclinical malignancy, yet as a cancer screening modality, PET is still controversial in contemporary medical practice. The aim of this article is to review the application status and existing problem of PET in cancer screening, and to offer some recognition and view about cancer srceening. (authors)

  8. Dissociative identity disorder: a controversial diagnosis.

    Science.gov (United States)

    Gillig, Paulette Marie

    2009-03-01

    A brief description of the controversies surrounding the diagnosis of dissociative identity disorder is presented, followed by a discussion of the proposed similarities and differences between dissociative identity disorder and borderline personality disorder. The phenomenon of autohypnosis in the context of early childhood sexual trauma and disordered attachment is discussed, as is the meaning of alters or alternate personalities. The author describes recent neurosciences research that may relate the symptoms of dissociative identity disorder to demonstrable disordered attention and memory processes. A clinical description of a typical patient presentation is included, plus some recommendations for approaches to treatment.

  9. Fetal abuse and neglect: an emerging controversy.

    Science.gov (United States)

    Landwirth, J

    1987-04-01

    Advances in fetal medicine have expanded opportunities for protection of fetal health and intrauterine management of an increasing number of fetal disorders. The legal rights and duties of parents to provide necessary medical treatment for the child may extend to the prenatal period. Resolution of the conflict between the rights of the fetus to be born healthy and the pregnant woman's right of privacy is difficult and controversial. It is suggested that intrusion into a woman's individual fundamental rights for the potential benefit of her fetus should be permissible only in narrowly defined circumstances.

  10. Lessons learnt from the organ retention controversy

    International Nuclear Information System (INIS)

    Madden, D.

    2009-01-01

    This paper examines the lessons to be learnt from the organ retention controversy in the Republic of Ireland. The paper emphasises the importance of good communication between clinicians and families of deceased persons and a move away from a medical culture based on paternalism to a partnership approach between clinicians and patients based on mutual trust and understanding. A model of authorisation rather than consent is proposed as the way forward for dealing with the difficult and traumatic experience of asking families for permission to carry out a post mortem examination on their deceased child. (authors)

  11. Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

    Science.gov (United States)

    Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

    2017-01-01

    Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of

  12. Sponsors' and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials.

    Science.gov (United States)

    Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

    2017-06-01

    The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative-nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. The investigative site's responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors'"filtering" of reports and increased sponsor communication. Sponsors

  13. Controversial Issues in Thyroid Cancer Management.

    Science.gov (United States)

    Tuttle, R Michael

    2018-04-13

    The lack of prospective randomized clinical trials for most management topics in differentiated thyroid cancer force us to make management recommendations based on retrospective observational data which is often incomplete, subject to selection bias, and conflicting. Therefore, it is not surprising that many aspects of thyroid cancer management remain controversial and not well defined. This review will examine the controversies surrounding three important topics in thyroid cancer management: (1) the option of thyroid lobectomy as initial therapy for thyroid cancer, (2) the proper use of preoperative neck imaging to optimize the completeness of the initial surgical procedure, and (3) the selective use RAI therapy as remnant ablation, adjuvant treatment or treatment of known persistent/recurrent disease. As thyroid cancer management moves toward a much more risk adapted approach to personalized management recommendations, clinicians and patients must balance the risks and benefits of the potential management options to arrive at a management plan that is optimized based on both patient preferences/values and the philosophy/experience of the local disease management team. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Datasprints as a method for Controversy Mapping

    DEFF Research Database (Denmark)

    Jensen, Torben Elgaard; Munk, Anders Kristian; Bach, Daniel

    2017-01-01

    A datasprint is an intensive 3-5 day workshop that brings together humanistic researchers, data experts, and stakeholders from a selected field. Together, the participants visualize and analyse a collection of data sets, which have been prepared before the datasprint. In the beginning of a datasp......A datasprint is an intensive 3-5 day workshop that brings together humanistic researchers, data experts, and stakeholders from a selected field. Together, the participants visualize and analyse a collection of data sets, which have been prepared before the datasprint. In the beginning...... of a datasprint, stakeholders present their understandings and views of the field in question. Following this, the workshop participants explore how the prepared data may shed new light on the field. The final products of a datasprint are prototypes of analyses or digital products that forms the basis for future...... collaboration between the partners. Since 2015, DIGHUMLAB has sponsored a special interest group in controversy mapping. Datasprints have proved to be a very productive format for controversy making and for creating dialogue and joint projects between humanistic researchers....

  15. The Reviewing of Controversial Juvenile Books: A Study.

    Science.gov (United States)

    Crow, Sherry R.

    1986-01-01

    Describes a study which examined reviewers' treatment of controversial juvenile books in Booklist, Bulletin of Center for Children's Books, Horn Book, and School Library Journal. The total number of controversial books reviewed by each journal, promptness of reviews, and extent of discussion of controversial features are discussed. (MBR)

  16. The current status of drug development of hypoxic cell radiosensitizers and their potential role in gynecologic oncology

    International Nuclear Information System (INIS)

    Coleman, C.N.; Ballon, S.C.; Howes, A.E.; Martinez, A.; Halsey, J.; Hirst, V.K.

    1984-01-01

    Both laboratory and clinical data suggest that hypoxia contributes to the failure of radiotherapy to achieve local control of bulky gynecologic tumors. As part of a Phase I trial of hypoxic cell radiosensitizers, 19 women at Stanford University with advanced (n . 6) or recurrent (n . 13) pelvic neoplasms were treated with radiotherapy plus desmethylmisonidazole. Complete or partial response occurred in 42% of patients with some patients achieving local control for over 1 year. It is unknown if the sensitizer added to the results of radiotherapy alone. A Phase I trial of a theoretically superior sensitizer, SR-2508, is soon to begin. It is anticipated that the dose-limiting neurotoxicity seen with misonidazole and desmethylmisonidazole will either be eliminated or will occur at a much higher total dose of drug. Many patients with gynecologic tumors could potentially benefit from participation in the new drug trials

  17. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2013-01-01

    Full Text Available Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed.

  18. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Science.gov (United States)

    Saha, Shyamali; Malhotra, Meenakshi; Kahouli, Imen; Prakash, Satya

    2013-01-01

    Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed. PMID:26555963

  19. Current Challenges and Future of Lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye.

    Science.gov (United States)

    Guilherme, Viviane A; Ribeiro, Ligia N M; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Paula, Eneida; de Jesus, Marcelo Bispo

    2017-11-21

    Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin and eye. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Patients' perspective on controversial issues in total knee arthroplasty.

    Science.gov (United States)

    Kim, Tae Kyun; Choi, Jinbae; Shin, Kwang Sook; Chang, Chong Bum; Seong, Sang Cheol

    2008-03-01

    We investigated the level of patient knowledge and preferences over the currently controversial issues in TKA. One hundred patients who had decided to undergo TKA for advanced osteoarthritis were asked to complete a questionnaire inquiring their knowledge and preferences over three controversial issues: (1) computer assisted surgery (CAS), (2) minimal invasive surgery (MIS), and (3) ceramic femoral component. The patient preferences over the three issues were questioned again after they had been informed of advantages and disadvantages of each option using an explanatory document. Most (more than 75%) of the patients did not have sufficient knowledge and their knowledge was based on non-professional sources (more than 85%). Before the information was given, most (more than 80%) of the patients preferred a new option. After the information was provided, more patients preferred a standard option in the issues of CAS (60%) and MIS (88%). This study prompts health care providers to become more active in providing accurate information and to consider patients perspective in making decisions which will influence the benefits and risk of the patients.

  1. Controversies relating to the management of acromioclavicular joint dislocations.

    Science.gov (United States)

    Modi, C S; Beazley, J; Zywiel, M G; Lawrence, T M; Veillette, C J H

    2013-12-01

    The aim of this review is to address controversies in the management of dislocations of the acromioclavicular joint. Current evidence suggests that operative rather than non-operative treatment of Rockwood grade III dislocations results in better cosmetic and radiological results, similar functional outcomes and longer time off work. Early surgery results in better functional and radiological outcomes with a reduced risk of infection and loss of reduction compared with delayed surgery. Surgical options include acromioclavicular fixation, coracoclavicular fixation and coracoclavicular ligament reconstruction. Although non-controlled studies report promising results for arthroscopic coracoclavicular fixation, there are no comparative studies with open techniques to draw conclusions about the best surgical approach. Non-rigid coracoclavicular fixation with tendon graft or synthetic materials, or rigid acromioclavicular fixation with a hook plate, is preferable to fixation with coracoclavicular screws owing to significant risks of loosening and breakage. The evidence, although limited, also suggests that anatomical ligament reconstruction with autograft or certain synthetic grafts may have better outcomes than non-anatomical transfer of the coracoacromial ligament. It has been suggested that this is due to better restoration horizontal and vertical stability of the joint. Despite the large number of recently published studies, there remains a lack of high-quality evidence, making it difficult to draw firm conclusions regarding these controversial issues.

  2. Staggering successes amid controversy in California water management

    Science.gov (United States)

    Lund, J. R.

    2012-12-01

    Water in California has always been important and controversial, and it probably always will be. California has a large, growing economy and population in a semi-arid climate. But California's aridity, hydrologic variability, and water controversies have not precluded considerable economic successes. The successes of California's water system have stemmed from the decentralization of water management with historically punctuated periods of more centralized strategic decision-making. Decentralized management has allowed California's water users to efficiently explore incremental solutions to water problems, ranging from early local development of water systems (such as Hetch Hetchy, Owens Valley, and numerous local irrigation projects) to more contemporary efforts at water conservation, water markets, wastewater reuse, and conjunctive use of surface and groundwater. In the cacophony of local and stakeholder interests, strategic decisions have been more difficult, and consequently occur less frequently. California state water projects and Sacramento Valley flood control are examples where decades of effort, crises, floods and droughts were needed to mobilize local interests to agree to major strategic decisions. Currently, the state is faced with making strategic environmental and water management decisions regarding its deteriorating Sacramento-San Joaquin Delta. Not surprisingly, human uncertainties and physical and fiscal non-stationarities dominate this process.

  3. Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US.

    Science.gov (United States)

    Des Jarlais, D C; Cooper, H L F; Arasteh, K; Feelemyer, J; McKnight, C; Ross, Z

    2018-01-01

    We identified potential geographic "hotspots" for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage. We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential "hotspots" for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk-passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk-injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.

  4. [Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective].

    Science.gov (United States)

    De Lossada, A; Oteo-Álvaro, Á; Giménez, S; Oyagüez, I; Rejas, J

    2016-01-01

    To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (pcost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  5. HYDROXYCARBAMINE: FROM AN OLD DRUG USED IN MALIGNANT HEMOPATHIES TO A CURRENT STANDARD IN SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Giovanna Cannas

    2017-02-01

    Full Text Available While hydroxycarbamine (hydroxyurea, HU has less and less indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support of safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. HU has become the standard-of-care for sickle cell anemia, but remains underused. Barriers to its use should be identified and overcome.

  6. The Controversies over Bioenergy in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Andersen, Bente Hessellund

    2012-01-01

    convert coal fired power plants to biomass in order to sustain the role of these power plants. Their increasing use of imported wood pellets is criticized for increasing greenhouse gas emissions because of fast logging of years of forest growth. A Danish biotech company is developing enzymes...... a prominent role in several Danish climate and energy plans, alongside with wind and solar energy, and energy savings. There are major controversies about targets for bioenergy with respect to acceptable types, sources and amounts of biomass. Strong path dependency is identified. Energy companies in Denmark...... for processing of biomass for biofuels. The alignment with the private car regime is strong, because biofuel enables continuation of fuel-driven vehicles as dominating transportation mode. Danish farmers see manure as important source for biogas while arguing for reduction of climate impact and nuisances from...

  7. Element 74, the Wolfram Versus Tungsten Controversy

    Energy Technology Data Exchange (ETDEWEB)

    Holden,N.E.

    2008-08-11

    Two and a quarter centuries ago, a heavy mineral ore was found which was thought to contain a new chemical element called heavy stone (or tungsten in Swedish). A few years later, the metal was separated from its oxide and the new element (Z=74) was called wolfram. Over the years since that time, both the names wolfram and tungsten were attached to this element in various countries. Sixty years ago, IUPAC chose wolfram as the official name for the element. A few years later, under pressure from the press in the USA, the alternative name tungsten was also allowed by IUPAC. Now the original, official name 'wolfram' has been deleted by IUPAC as one of the two alternate names for the element. The history of this controversy is described here.

  8. [On controversies around the Oedipus Complex].

    Science.gov (United States)

    Drwiega, Marek

    2002-01-01

    In the article the author would like to draw the readers' attention to one of the central issues of psychoanalysis, i.e. Oedipus complex. In the development of the psychoanalysis the classical conception of Oedipus complex presented by Freud gave rise to a severe criticism both on the part of some psychoanalysts, especially women such as e.g. Melanie Klein, and on the part of ethnographers such as B. Malinowski. In the paper the author presents the main controversies concerning this interesting discussion. The fact of the matter is that the Oedipus complex is a hotly debated subject, not only from the cultural point of view but also within the psychoanalytical movement.

  9. Predicted supplies of oil: a controversy revisited

    International Nuclear Information System (INIS)

    Mackay, R.M.; Probert, S.D.

    1993-01-01

    This investigation had two objectives. The first was to consider future problems of the oil industry, as envisaged at the time of the impending 1973-74 unit-oil-price crisis. To this end, selected early 1970's pertinent published papers have been analysed and their conclusions now assessed in hindsight. The chosen published articles were considered then to be in part controversial, visionary and simultaneously, often predicting very different outcomes for the future supply, demand and unit cost of crude oil. The second objective was to assess pertinent recent research, and compare what we at present believe to be the status quo for the oil industry, with the perception of how the industry would have developed as portrayed by the early 1970's oil publications. (author)

  10. Status Report: Black Hole Complementarity Controversy

    International Nuclear Information System (INIS)

    Lee, Bum-Hoon; Yeom, Dong-han

    2014-01-01

    Black hole complementarity was a consensus among string theorists for the interpretation of the information loss problem. However, recently some authors find inconsistency of black hole complementarity: large N rescaling and Almheiri, Marolf, Polchinski and Sully (AMPS) argument. According to AMPS, the horizon should be a firewall so that one cannot penetrate there for consistency. There are some controversial discussions on the firewall. Apart from these papers, the authors suggest an assertion using a semi-regular black hole model and we conclude that the firewall, if it exists, should affect to asymptotic observer. In addition, if any opinion does not consider the duplication experiment and the large N rescaling, then the argument is difficult to accept

  11. Epistemological depth in a GM crops controversy.

    Science.gov (United States)

    Hicks, Daniel J

    2015-04-01

    This paper examines the scientific controversy over the yields of genetically modified [GM] crops as a case study in epistemologically deep disagreements. Appeals to "the evidence" are inadequate to resolve such disagreements; not because the interlocutors have radically different metaphysical views (as in cases of incommensurability), but instead because they assume rival epistemological frameworks and so have incompatible views about what kinds of research methods and claims count as evidence. Specifically, I show that, in the yield debate, proponents and opponents of GM crops cite two different sets of claims as evidence, which correspond to two rival epistemological frameworks, classical experimental epistemology and Nancy Cartwright's evidence for use. I go on to argue that, even if both sides of the debate accepted Cartwright's view, they might still disagree over what counts as evidence, because evidence for use ties standards of evidence to what is sometimes called the "context of application." Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The Social Life of Data (Prototyping Controversies)

    DEFF Research Database (Denmark)

    Jørgensen, Tobias Bornakke; Birkbak, Andreas; Petersen, Morten Krogh

    are out, which leaves it to the public to stumble upon the webpages and explore the results. This unspecified public, however, often seems to have more similarities to a void of non-engagement than a receptive social room. In this paper we take two related steps to counter the lack of public engagement...... that makes available a large relational data set on the Danish power elite (Ellersgaard et al. 2015) through an interactive data navigation tool. The tool allows visitors to explore a data set that is potentially controversial but difficult to navigate. Further, Google Analytics and a simple survey allows us...... to examine how visitors to the website were led to the site in the first place, how they made use of the data navigation tool and how customized maps from the webpage travelled into new and unpredictable arenas. The experiment thus explores the tension between publishing and making things public...

  13. An overview of the Hanford controversy

    International Nuclear Information System (INIS)

    Stewart, A.M.; Kneale, G.W.

    1991-01-01

    In 1964, the Atomic Energy Commission agreed to sponsor 'a study of the lifetime health and mortality experiences of all employees of AEC contractors.' The commission put in charge of this study a physician (Thomas Mancuso) who had recently shown how the U.S. Social Security system could be used to identify the dates and causes of death of all insured workers. As director of the AEC project, Mancuso was at liberty to include any or all the postwar offshoots of the Manhattan Project. His master plan included workers from Oak Ridge, Los Alamos, and Hanford, but it soon became apparent that his attempts to link radiation exposures to subsequent events were proving more successful at Hanford than elsewhere. The authors of this paper, who participated in the study, review the controversy surrounding its eventual publication.22 references

  14. Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control.

    Science.gov (United States)

    Ojanperä, Ilkka; Kolmonen, Marjo; Pelander, Anna

    2012-05-01

    Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography-mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology.

  15. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  16. Legitimacy of hospital reconfiguration: the controversial downsizing of Kidderminster hospital.

    Science.gov (United States)

    Oborn, Eivor

    2008-04-01

    This paper examines the contested organizational legitimacy of hospital reconfiguration, which continues to be a central issue in health care management. A qualitative study which focuses on the controversial downsizing of Kidderminster Hospital, a highly publicized landmark case of district general hospital closure. Rhetorical strategies are analysed to examine how legitimacy was constructed by stakeholder groups and how these strategies were used to support or resist change. Stakeholders promoting change legitimized re-organization pragmatically and morally arguing the need for centralization as a rational necessity. Stakeholders resisting change argued for cognitive and moral legitimacy in current service arrangements, contrasting local versus regionalized aspects of safety and provision. Groups managed to talk past each other, failing to establish a dialogue, which led to significant conflict and political upheaval. Stakeholders value hospitals in different ways and argue for diverse accounts of legitimacy. Broader discourses of medical science and democratic participation were drawn into rhetorical texts concerning regionalization to render them more powerful.

  17. The significance test controversy revisited the fiducial Bayesian alternative

    CERN Document Server

    Lecoutre, Bruno

    2014-01-01

    The purpose of this book is not only to revisit the “significance test controversy,”but also to provide a conceptually sounder alternative. As such, it presents a Bayesian framework for a new approach to analyzing and interpreting experimental data. It also prepares students and researchers for reporting on experimental results. Normative aspects: The main views of statistical tests are revisited and the philosophies of Fisher, Neyman-Pearson and Jeffrey are discussed in detail. Descriptive aspects: The misuses of Null Hypothesis Significance Tests are reconsidered in light of Jeffreys’ Bayesian conceptions concerning the role of statistical inference in experimental investigations. Prescriptive aspects: The current effect size and confidence interval reporting practices are presented and seriously questioned. Methodological aspects are carefully discussed and fiducial Bayesian methods are proposed as a more suitable alternative for reporting on experimental results. In closing, basic routine procedures...

  18. Unicameral bone cysts: general characteristics and management controversies.

    Science.gov (United States)

    Pretell-Mazzini, Juan; Murphy, Robert Francis; Kushare, Indranil; Dormans, John P

    2014-05-01

    Unicameral bone cysts are benign bone lesions that are often asymptomatic and commonly develop in the proximal humerus and femur of skeletally immature patients. The etiology of these lesions remains unknown. Most patients present with a pathologic fracture, but these cysts can be discovered incidentally, as well. Radiographically, a unicameral bone cyst appears as a radiolucent lesion with cortical thinning and is centrally located within the metaphysis. Although diagnosis is frequently straightforward, management remains controversial. Because the results of various management methods are heterogeneous, no single method has emerged as the standard of care. New minimally invasive techniques involve cyst decompression with bone grafting and instrumentation. These techniques have yielded promising results, with low rates of complications and recurrence reported; however, prospective clinical trials are needed to compare these techniques with current evidence-based treatments.

  19. Neural tube defects – recent advances, unsolved questions and controversies

    Science.gov (United States)

    Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E.

    2014-01-01

    Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other ‘NTD’ malformations, such as encephalocele, are likely to be post-neurulation disorders. PMID:23790957

  20. Sugars and Health Controversies: What Does the Science Say?123

    Science.gov (United States)

    Rippe, James M; Angelopoulos, Theodore J

    2015-01-01

    The consumption of sugar and its relation to various potential adverse health consequences are the subjects of considerable debate and controversy. This supplement to Advances in Nutrition provides an expanded summary of a symposium held on 26 April 2014 entitled “Sugars and Health Controversies: What Does the Science Say?” as part of the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014. The articles in the supplement discuss results of current systematic reviews and meta-analyses as well as randomized controlled trials and draw implications for public policy considerations. In addition, future research gaps are identified. Current research trials conducted with commonly consumed sugars [e.g., sucrose and high-fructose corn syrup (HFCS)] do not support a unique relation to obesity, metabolic syndrome, diabetes, risk factors for heart disease, or nonalcoholic fatty liver disease. Neurologic differences in response to studies that used pure fructose compared with pure glucose have not been confirmed using typical sugars that are consumed (i.e., sucrose and HFCS), which contain ∼50% glucose and fructose. We conclude that added sugars consumed in the normal forms in which humans consume them, at amounts typical of the human diet and for the time period studied in randomized controlled trials, do not result in adverse health consequences. Although more research trials are needed in many areas of sugar consumption and health, there is little scientific justification for recommending restricting sugar consumption below the reasonable upper limit recommended by the Dietary Guidelines for Americans, 2010 of no more than 25% of calories.

  1. Radioprotective drugs: a synopsis of current research and a proposed research plan for the Federal Emergency Management Agency. Final report

    International Nuclear Information System (INIS)

    Hickman, R.; Anspaugh, L.

    1985-04-01

    FEMA has broad roles in the management of disasters potentially involving substantial amounts of radioactive contamination. These could be either peacetime or wartime disasters. A meeting was held in March 1985 to see if there are any research contributions that FEMA might reasonably make in the area of radioprotective drugs that would substantially enhance its ability to perform its mission. The other federal agencies presently sponsoring research in the field were represented at the meeting. A few selected researchers also participated to provide complementary viewpoints. Activities of a modest scale that FEMA might undertake were identified, as were larger scale activities that might be undertaken in the event of long-term, major funding-level increases for FEMA. 2 refs

  2. General Education Today. A Critical Analysis of Controversies, Practices, and Reforms.

    Science.gov (United States)

    Gaff, Jerry G.

    The range of controversies and changes emerging from the current revival of general education are examined, and many ideas, examples, and recommendations for achieving realistic and successful curricular reform are offered. Instead of either offering an apology for general education or advocating any particular approach, the book draws on solid…

  3. The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.

    Science.gov (United States)

    Delves, Michael; Plouffe, David; Scheurer, Christian; Meister, Stephan; Wittlin, Sergio; Winzeler, Elizabeth A; Sinden, Robert E; Leroy, Didier

    2012-02-01

    Malaria remains a disease of devastating global impact, killing more than 800,000 people every year-the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance. Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and the liver stage of P. yoelii. We then compared 50 current and experimental antimalarials in these assays. We show that endoperoxides such as OZ439, a stable synthetic molecule currently in clinical phase IIa trials, are strong inhibitors of gametocyte maturation/gamete formation and impact sporogony; lumefantrine impairs development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits sporogony. These data enable objective comparisons of the strengths and weaknesses of each chemical class at targeting each stage of the lifecycle. Noting that the activities of many compounds lie within achievable blood concentrations, these results offer an invaluable guide to decisions regarding which drugs to combine in the next-generation of antimalarial drugs. This study might reveal the potential of life-cycle-wide analyses of drugs for other pathogens with complex life cycles.

  4. Impaired Inactivation of L-Type Ca2+ Current as a Potential Mechanism for Variable Arrhythmogenic Liability of HERG K+ Channel Blocking Drugs.

    Directory of Open Access Journals (Sweden)

    Jae Gon Kim

    Full Text Available The proarrhythmic effects of new drugs have been assessed by measuring rapidly activating delayed-rectifier K+ current (IKr antagonist potency. However, recent data suggest that even drugs thought to be highly specific IKr blockers can be arrhythmogenic via a separate, time-dependent pathway such as late Na+ current augmentation. Here, we report a mechanism for a quinolone antibiotic, sparfloxacin-induced action potential duration (APD prolongation that involves increase in late L-type Ca2+ current (ICaL caused by a decrease in Ca2+-dependent inactivation (CDI. Acute exposure to sparfloxacin, an IKr blocker with prolongation of QT interval and torsades de pointes (TdP produced a significant APD prolongation in rat ventricular myocytes, which lack IKr due to E4031 pretreatment. Sparfloxacin reduced peak ICaL but increased late ICaL by slowing its inactivation. In contrast, ketoconazole, an IKr blocker without prolongation of QT interval and TdP produced reduction of both peak and late ICaL, suggesting the role of increased late ICaL in arrhythmogenic effect. Further analysis showed that sparfloxacin reduced CDI. Consistently, replacement of extracellular Ca2+ with Ba2+ abolished the sparfloxacin effects on ICaL. In addition, sparfloxacin modulated ICaL in a use-dependent manner. Cardiomyocytes from adult mouse, which is lack of native IKr, demonstrated similar increase in late ICaL and afterdepolarizations. The present findings show that sparfloxacin can prolong APD by augmenting late ICaL. Thus, drugs that cause delayed ICaL inactivation and IKr blockage may have more adverse effects than those that selectively block IKr. This mechanism may explain the reason for discrepancies between clinically reported proarrhythmic effects and IKr antagonist potencies.

  5. The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites

    Science.gov (United States)

    Delves, Michael; Plouffe, David; Scheurer, Christian; Meister, Stephan; Wittlin, Sergio; Winzeler, Elizabeth A.; Sinden, Robert E.; Leroy, Didier

    2012-01-01

    Background Malaria remains a disease of devastating global impact, killing more than 800,000 people every year—the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance. Methods and Findings Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and the liver stage of P. yoelii. We then compared 50 current and experimental antimalarials in these assays. We show that endoperoxides such as OZ439, a stable synthetic molecule currently in clinical phase IIa trials, are strong inhibitors of gametocyte maturation/gamete formation and impact sporogony; lumefantrine impairs development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits sporogony. Conclusions These data enable objective comparisons of the strengths and weaknesses of each chemical class at targeting each stage of the lifecycle. Noting that the activities of many compounds lie within achievable blood concentrations, these results offer an invaluable guide to decisions regarding which drugs to combine in the next-generation of antimalarial drugs. This study might reveal the potential of life-cycle–wide analyses of drugs for other pathogens with complex life cycles. Please see later in the article for the Editors' Summary PMID

  6. Controversies in HIV-associated neurocognitive disorders

    Science.gov (United States)

    Nightingale, Sam; Winsto, Alan; Letendre, Scott; Michael, Benedict D; McArthur, Justin C; Khoo, Saye; Solomon, Tom

    2015-01-01

    Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would benefit from routine screening for cognitive difficulties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated. PMID:25316020

  7. [Foucault, Derrida, and the history of madness: notes on a controversy].

    Science.gov (United States)

    Pereira Neto, A F

    1998-01-01

    The publication of the book Folie et Déraison. Histoire de la Folie à l'Age Classique (1961), by Michel Foucault, sparked a debate between the author and philosopher Jacques Derrida during the 1960s and 70s. Derrida criticized the methodological proposal and organization of the History of Madness presented by Foucault in the foreword to the first edition. The controversy appears to have motivated the author to withdraw this same foreword from the second edition. The purpose of this article is to analyze some current points in this controversy. It also presents a research agenda for an understanding of the reasons leading Foucault to take this stance.

  8. Quantitative EEG and Current Source Density Analysis of Combined Antiepileptic Drugs and Dopaminergic Agents in Genetic Epilepsy: Two Case Studies.

    Science.gov (United States)

    Emory, Hamlin; Wells, Christopher; Mizrahi, Neptune

    2015-07-01

    Two adolescent females with absence epilepsy were classified, one as attention deficit and the other as bipolar disorder. Physical and cognitive exams identified hypotension, bradycardia, and cognitive dysfunction. Their initial electroencephalograms (EEGs) were considered slightly slow, but within normal limits. Quantitative EEG (QEEG) data included relative theta excess and low alpha mean frequencies. A combined treatment of antiepileptic drugs with a catecholamine agonist/reuptake inhibitor was sequentially used. Both patients' physical and cognitive functions improved and they have remained seizure free. The clinical outcomes were correlated with statistically significant changes in QEEG measures toward normal Z-scores in both anterior and posterior regions. In addition, low resolution electromagnetic tomography (LORETA) Z-scored source correlation analyses of the initial and treated QEEG data showed normalized patterns, supporting a neuroanatomic resolution. This study presents preliminary evidence for a neurophysiologic approach to patients with absence epilepsy and comorbid disorders and may provide a method for further research. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  9. Silica and lung cancer: a controversial issue.

    Science.gov (United States)

    Pairon, J C; Brochard, P; Jaurand, M C; Bignon, J

    1991-06-01

    The role of crystalline silica in lung cancer has long been the subject of controversy. In this article, we review the main experimental and epidemiological studies dealing with this problem. Some evidence for a genotoxic potential of crystalline silica has been obtained in the rare in vitro studies published to date. In vivo studies have shown that crystalline silica is carcinogenic in the rat; the tumour types appear to vary according to the route of administration. In addition, an association between carcinogenic and fibrogenic potency has been observed in various animal species exposed to crystalline silica. An excess of lung cancer related to occupational exposure to crystalline silica is reported in many epidemiological studies, regardless of the presence of silicosis. However, most of these studies are difficult to interpret because they do not correctly take into account associated carcinogens such as tobacco smoke and other occupational carcinogens. An excess of lung cancer is generally reported in studies based on silicosis registers. Overall, experimental and human studies suggest an association between exposure to crystalline silica and an excess of pulmonary malignancies. Although the data available are not sufficient to establish a clear-cut causal relationship in humans, an association between the onset of pneumoconiosis and pulmonary malignancies is probable. In contrast, experimental observations have given rise to a pathophysiological mechanism that might account for a putative carcinogenic potency of crystalline silica.

  10. Controversial Embodiment: Sport, Masculinity, Dis/Ability

    Directory of Open Access Journals (Sweden)

    Marilena Parlati

    2015-11-01

    Full Text Available This essay is an attempt at investigating visible forms of complex, indeed controversial embodiment, with the specific intention of concentrating on the ways they interrogate delicate issues such as disability, masculinity and prosthetic sport performance. I intend to sound the shifting boundaries between dis-ability and super-ability as manifested in iconic figures such as Stelarc and, in other fields, Oscar Pistorius, whose unsteady position as privileged/disabled bladerunner seems to require – and indeed to gather – particularly intense scrutiny. I shall introduce a few contemporary discourses on corporeality and embodiment, which focus on the ‘troubling’ nature of auxiliary organs Freud refers to in the much contended paragraph I adopt as epigraph and guiding procedural light; I shall move from Butler and Giddens to Jean-Luc Nancy’s work on transplants and/as prostheses to include theoretical debates on disintegrating embodiment and disability studies, in order to proceed towards an analysis of the short-circuiting of allegedly secure practices of (masculine embodiment in sport culture and theory.

  11. Energy controversy: the role of nuclear power

    International Nuclear Information System (INIS)

    Schmidt, F.H.; Bodansky, D.

    1975-02-01

    The objective of the paper presented is to show that nuclear fission power is the best, and maybe the only, alternative source of energy. It is written for a wide range of readers, including non-scientists and scientists who are not particularly informed on the issues involved. The first question considered concerns man's need for energy; it is concluded that conservation measures alone cannot suffice. Next, the earth's energy sources are examined, and the extent of each is estimated in the simple context of the length of time it could last at present use rates. Only nuclear fission, nuclear fusion, and solar energy can provide for future time scales commensurate with man's historic past, while avoiding the possibility of catastrophic social upheaval. Fusion and solar energy are rejected on technological grounds because the world energy problem is so pressing that one cannot gamble on hopes for future technological breakthroughs. Thus, only nuclear fission meets the twin criteria of technological feasibility and adequate resource base. Each of the controversial issues surrounding nuclear fission energy is examined in some detail. The conclusion is reached that none is serious, and that nuclear fission offers by far the best energy source from environmental, economic, longevity, and overall safety standpoints

  12. The nuclear energy controversy in Austria

    International Nuclear Information System (INIS)

    Oszuszky, F.; Szeless, A.

    1981-01-01

    The sociological aspects of the energy issue have become of overwhelming importance in the last few years. As a result, traditional considerations such as the importance of adequate and cheap energy supplies as the basis for growth, and the necessity, in a time of politically uncertain oil supplies, of energy supply security and diversity, have been equalled in importance, and sometimes replaced, by arguments about the social goals to be achieved. Nuclear energy has been selected as the vehicle for a socio-political debate on the controversial issue of the application of large-scale technology. Beyond that it has acquired a symbolic role in what is really an emotional attack on the political systems, economy and culture of present day civilization. It stands for the concentration of power, the centralization of technology and society, and man's dependence on the products of that centralization. Nuclear power is seen as one of the motors of further economic growth and thus an apparent pioneer of the further destruction of our natural and social environment. (author)

  13. Some controversy about law on private security

    Directory of Open Access Journals (Sweden)

    Stajić Ljubomir

    2014-01-01

    Full Text Available The Republic of Serbia is one of the last countries that legally regulate the private security sector, which is a new conceptual system of the national security system. Since the law is expected to solve many issues and dilemmas, and bring order to the area, which by some accounts is a very profitable branch of economy. Expectations were that by the end to regulate issues such as: 1 the need for institutionalization of partnership between the public and private sectors for mutual benefit, 2 the need of expressing mutual interest to establish the desired condition of security in the entire society and 3 the need to define the mechanisms and authority to achieve mentioned above. Based on this, legal framework of private security should explicitly provide: 1 a new role of the private sector, 2 communication and data exchange between the public and private sector, 3 mandatory notification about prepared or committed criminal acts on which there is information, 4 cooperation in the tasks of necessarily protected facilities, 4 cooperation in crisis situations including natural disasters, traffic accidents, strikes, sabotage, terrorist attacks, etc., 5 cooperate in the selection and training of staff and 6 cooperation in planning activities and project design of security. This paper presents a critical review of some theoretical and professional controversies in the solutions provided by law, for the purpose of answering whether it is achieving the purpose of passing of such a legal act.

  14. The Great Irish Head Shop Controversy

    Science.gov (United States)

    Ryall, Graham; Butler, Shane

    2011-01-01

    This research describes and analyses recent policy developments in Ireland in relation to the practice of selling psychoactive substances which, while not themselves illegal, mimic the effects of commonly used illegal drugs. These so-called "legal highs" had been sold in Ireland through an increasing number of "head shops"…

  15. Topical therapy of atopic dermatitis: controversies from Hippocrates to topical immunomodulators.

    Science.gov (United States)

    Tilles, Gérard; Wallach, Daniel; Taïeb, Alain

    2007-02-01

    Although atopic dermatitis can be treated efficiently, there is still much controversy about the risk/benefit ratio of both topical corticosteroids and topical immunomodulators. Conflicting data may be found about the usefulness of bathing, diet regulation, and other therapeutic interventions. These controversies result in part from the persistence of Hippocratic doctrines in modern medical thinking. Humoralist and diathetic doctrines, as they pertain to eczema, are reviewed. The paradoxical worsening of oozing and the deadly hazards of hospitalization before the era of antibiotics are brought to mind. We hope that this historical review will improve the understanding of current controversies and help dermatologists to manage patients with atopic dermatitis and other chronic skin diseases.

  16. Training Institutions as places of reproduction of official and scientific knowledge on ecological transition. An analysis with mapping controversies tools

    International Nuclear Information System (INIS)

    Bargues, Emilie; Landivar, Diego

    2016-01-01

    Through an exploratory approach mobilizing a 'mapping controversies methodology', this article analyses the role of training institutions in producing, distributing and criticizing knowledge related to ecological transition. The current work deals with the case of biomass production and activity, a central sector in French ecological transition. The analysis of semantic and unstructured data crawled from 3900 web sites highlights the major issues of controversy, the actors of the controversy, the points of agreement/disagreement among actors, and the particular position of training organizations in the knowledge structure. We find that these organizations are strongly correlated to official and scientific knowledge and less related to critical and marginal knowledge

  17. Mapping intravascular ultrasound controversies in interventional cardiology practice.

    Directory of Open Access Journals (Sweden)

    David Maresca

    Full Text Available Intravascular ultrasound is a catheter-based imaging modality that was developed to investigate the condition of coronary arteries and assess the vulnerability of coronary atherosclerotic plaques in particular. Since its introduction in the clinic 20 years ago, use of intravascular ultrasound innovation has been relatively limited. Intravascular ultrasound remains a niche technology; its clinical practice did not vastly expand, except in Japan, where intravascular ultrasound is an appraised tool for guiding percutaneous coronary interventions. In this qualitative research study, we follow scholarship on the sociology of innovation in exploring both the current adoption practices and perspectives on the future of intravascular ultrasound. We conducted a survey of biomedical experts with experience in the technology, the practice, and the commercialization of intravascular ultrasound. The collected information enabled us to map intravascular ultrasound controversies as well as to outline the dynamics of the international network of experts that generates intravascular ultrasound innovations and uses intravascular ultrasound technologies. While the technology is praised for its capacity to measure coronary atherosclerotic plaque morphology and is steadily used in clinical research, the lack of demonstrated benefits of intravascular ultrasound guided coronary interventions emerges as the strongest factor that prevents its expansion. Furthermore, most of the controversies identified were external to intravascular ultrasound technology itself, meaning that decision making at the industrial, financial and regulatory levels are likely to determine the future of intravascular ultrasound. In light of opinions from the responding experts', a wider adoption of intravascular ultrasound as a stand-alone imaging modality seems rather uncertain, but the appeal for this technology may be renewed by improving image quality and through combination with

  18. Management of ß-thalassemia – Consensus and controversies!

    Directory of Open Access Journals (Sweden)

    Mamta V. Manglani

    2017-12-01

    Full Text Available The mainstay of treatment of ß-Thalassemia major includes life-long regular packed red cell transfusions and iron chelation. With advances in understanding the molecular biology and its implications in the patients, newer modalities are now being explored to offer a better quality of life to transfusion dependent thalassemic patients. Improved safety of transfusions, newer chelator drugs and combination of chelators have improved outcomes in these patients. Amlodipine along with chelators may be a future option for preventing cardiac iron overload related complications. Drugs which improve HbF levels and thus ameliorate anemia such as hydroxyurea, butyrates azacytidine etc. have also been explored with little relief to transfusion dependent patients. HSCT, which is the only curative treatment available at present, has its own limitations as sibling donors may not be available to many. However, there has been extensive work done on improving outcomes with MUD and Haplo-identical HSCT in the recent times. Gene therapy using lentiviral vectors is also offering great hope to these children. Induced Pluripotent Stem Cells (iPSC is a promising advance in the treatment of thalassemia. Several newer molecules targeting different pathophysiologic aspects are being explored and have met with good success. These include luspatercept, sotatercept, macrophage inhibition, JAK2 inhibition using ruxolitinib etc. Controversies regarding use of wheat grass and ESAs are relatively less worrisome. But use of thalidomide should be done with great caution. Despite its success reported in anecdotal reports, in the absence of adequate data with larger trials, its role in routine management of thalassemia syndromes remains to be ascertained.

  19. Addressing the nuclear controversy on university campuses

    International Nuclear Information System (INIS)

    Keyes, G.B.; Poncelet, C.G.

    1977-01-01

    A strong anti-nuclear sentiment exists on many university campuses. Young minds are eager to adopt causes which purport to reflect new intellectual approaches to social, political, and economic issues. Hence, the opposition to nuclear power can be made to seem to be based on: 1) technical study of nuclear plants; 2) concern for the environment; 3) concern for public health and safety; 4) requirements for an improved economic order; and 5) demand for public decision on technical issues. All of these elements have the potential of attracting student and faculty interest and support. To contend with this problem, our company decided to attempt to achieve a dialogue with the student and faculty audiences. A small group of young nuclear engineers was chosen to undergo comprehensive training on the controversy and contemporary campus issues in the states to be visited. The selection and training emphasized the ability of the engineers to relate to the students as their peers. They were encouraged to speak candidly and for themselves. Thus, they were not burdened with the image of being viewed merely as typical corporate spokesmen. The rapport made possible by this approach is a very important element in the success of such an effort. Invitations to debate before student audiences were issued to leading opposition groups; also, to the news media to report the events. Response by the media has been outstandingly favorable: not only has the coverage been extensive, but it has carried the pro-nuclear arguments to large audiences on a scale and with a credibility not otherwise achievable. The results to date have been extremely encouraging. Other countries are invited to learn more about the ''Campus America'' program in order to evaluate whether or not such an approach, with appropriate modification, could prove effective in their own situations

  20. Child injury control: trends, themes, and controversies.

    Science.gov (United States)

    Johnston, Brian D; Ebel, Beth E

    2013-01-01

    Injury is a major cause of morbidity and mortality among US children, and an important driver of health status globally. Despite its enormous burden, injury is preventable. Over the last 10 years, significant progress has been made in the reduction of unintentional injury among US children. However, aggregate trends mask important disparities by age group, region, and injury mechanism. Basic and translation research is needed to develop and test prevention strategies to address these new or recalcitrant problems. Motor vehicle occupant injury has fallen to historic lows, but challenges remain in protecting novice drivers and managing the distraction of new technologies. Injury to pedestrians has also declined, but likely as a result of decreased exposure as fewer children walk. This calls for a broader public health perspective to promote activity while enhancing safety. Deaths due to drowning are common and illustrate the difficulty in measuring and promoting appropriate supervision. Environmental modification and use of protective products may be a more appropriate response. Concussion in sport is another challenging issue: public health laws promote identification and appropriate management of concussed athletes, but less progress has been made on primary prevention of these injuries. Unintentional poisoning is on the rise, attributable to misuse of, and overdose with, prescription opioids. Injury deaths to infants are also increasing. This trend is driven in part by better death investigation that classifies more sleep-related deaths as suffocation events. Finally, we examine a sample of cross-cutting themes and controversies in injury control that might be amenable to empiric evaluation. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  1. Addressing the nuclear controversy on university campuses

    International Nuclear Information System (INIS)

    Keyes, G.B.; Poncelet, C.G.

    1977-01-01

    A strong anti-nuclear sentiment exists on many university campuses. Young minds are eager to adopt causes which purport to reflect new intellectual approaches to social, political and economic issues. Hence, the opposition to nuclear power can be made to seem to be based on: (1) technical study of nuclear plants; (2) concern for the environment; (3) concern for public health and safety; (4) requirements for an improved economic order; and (5) demand for public decision on technical issues. All these elements could attract student and faculty interest and support. To contend with this problem in the USA, Westinghouse Electric Corporation attempted to achieve a dialogue with the student and faculty audiences. The development and results of the programme up to mid-1977 are reported in this paper. A small group of young nuclear engineers was chosen to undergo comprehensive training on the controversy and contemporary campus issues in the States to be visited. Selection and training emphasized the ability of the engineers to relate to the students as their peers. They were encouraged to speak candidly and for themselves. Thus, they did not give the impression of being merely typical corporate spokesmen. The rapport made possible by this approach is very important to the success of such an effort. Invitations to debate before student audiences were issued to leading opposition groups and to the news media. Response by the media has been outstandingly favourable: not only has the coverage been extensive, but it has carried the pro-nuclear arguments to large audiences on a scale and with a credibility not otherwise achievable. The results up to May 1977, in eight States, have been extremely encouraging. Other countries are invited to learn more about the ''Campus America'' programme in order to evaluate whether or not such an approach, with appropriate modification, could prove effective in their own situations. (author)

  2. Automated discovery systems and the inductivist controversy

    Science.gov (United States)

    Giza, Piotr

    2017-09-01

    The paper explores possible influences that some developments in the field of branches of AI, called automated discovery and machine learning systems, might have upon some aspects of the old debate between Francis Bacon's inductivism and Karl Popper's falsificationism. Donald Gillies facetiously calls this controversy 'the duel of two English knights', and claims, after some analysis of historical cases of discovery, that Baconian induction had been used in science very rarely, or not at all, although he argues that the situation has changed with the advent of machine learning systems. (Some clarification of terms machine learning and automated discovery is required here. The key idea of machine learning is that, given data with associated outcomes, software can be trained to make those associations in future cases which typically amounts to inducing some rules from individual cases classified by the experts. Automated discovery (also called machine discovery) deals with uncovering new knowledge that is valuable for human beings, and its key idea is that discovery is like other intellectual tasks and that the general idea of heuristic search in problem spaces applies also to discovery tasks. However, since machine learning systems discover (very low-level) regularities in data, throughout this paper I use the generic term automated discovery for both kinds of systems. I will elaborate on this later on). Gillies's line of argument can be generalised: thanks to automated discovery systems, philosophers of science have at their disposal a new tool for empirically testing their philosophical hypotheses. Accordingly, in the paper, I will address the question, which of the two philosophical conceptions of scientific method is better vindicated in view of the successes and failures of systems developed within three major research programmes in the field: machine learning systems in the Turing tradition, normative theory of scientific discovery formulated by Herbert Simon

  3. Lichen Planus Pigmentosus: The Controversial Consensus

    Science.gov (United States)

    Ghosh, Aparajita; Coondoo, Arijit

    2016-01-01

    A pigmented variant of lichen planus (LP) was first reported from India in 1974 by Bhutani et al. who coined the term LP pigmentosus (LPP) to give a descriptive nomenclature to it. LP has a number of variants, one of which is LPP. This disease has also later been reported from the Middle East, Latin America, Korea, and Japan, especially in people with darker skin. It has an insidious onset. Initially, small, black or brown macules appear on sun-exposed areas. They later merge to form large hyperpigmented patches. The disease principally affects the sun-exposed areas of the body such as the face, trunk, and upper extremities. The oral mucosa may rarely be involved. However, the palms, soles, and nails are not affected. Histologically, the epidermis is atrophic along with vacuolar degeneration of basal cell layer. The dermis exhibits incontinence of pigment with scattered melanophages and a sparse follicular or perivascular infiltrate. There is a considerable similarity in histopathological findings between LPP and erythema dyschromicum perstans. However, there are immunologic and clinical differences between the two. These observations have led to a controversy regarding the identity of the two entities. While some dermatologists consider them to be the same, others have opined that the two should be considered as distinctly different diseases. A number of associations such as hepatitis C virus infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic syndrome have been reported with LPP. A rare variant, LPP inversus, with similar clinical and histopathological findings was reported in 2001. As opposed to LPP, this variant occurs in covered intertriginous locations such as groins and axillae and mostly affects white-skinned persons. PMID:27688435

  4. Current-day precision oncology: from cancer prevention, screening, drug development, and treatment - have we fallen short of the promise?

    Science.gov (United States)

    Morgan, Gilberto; Aftimos, Philippe; Awada, Ahmad

    2016-09-01

    Precision oncology has been a strategy of prevention, screening, and treatment. Although much has been invested, have the results fallen so far short of the promise? The advancement of technology and research has opened new doors, yet a variety of pitfalls are present. This review presents the successes, failures, and opportunities of precision oncology in the current landscape. The use of targeted gene sequencing and the overwhelming results of superresponders have generated much excitement and support for precision oncology from the medical community. Despite notable successes, many challenges still pave the way of precision oncology: intratumoral heterogeneity, the need for serial biopsies, availability of treatments, target prioritization, ethical issues with germline incidental findings, medical education, clinical trial design, and costs. Precision oncology shows much potential through the use of next-generation sequencing and molecular advances, but does this potential warrant the investment? There are many obstacles on the way of this technology that should make us question if the investment (both monetary and man-hours) will live up to the promise. The review aims to not criticize this technology, but to give a realistic view of where we are, especially regarding cancer treatment and prevention.

  5. 16 CFR 2.3 - Policy as to private controversies.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Policy as to private controversies. 2.3 Section 2.3 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE... other action when the alleged violation of law is merely a matter of private controversy and does not...

  6. From Classroom to Controversy: Conflict in the Teaching of Religion

    Science.gov (United States)

    Neal, Lynn S.

    2013-01-01

    What happens when a class assignment becomes a source of controversy? How do we respond? What do we learn? By describing the controversy surrounding an assignment on religion and representation, this article examines conflict's productive role in teaching about New Religious Movements (NRMs) and religion. It suggests that we consider how our…

  7. Covering Conflict and Controversy: Measuring Balance, Fairness, Defamation.

    Science.gov (United States)

    Simon, Todd F.; And Others

    1989-01-01

    Measures balance, fairness, and defamation in local stories containing controversy and covering law enforcement, education, local government, and business. Finds that most stories lack balance and that the opposing side of the controversy was not contacted in 28 percent of the instances. (RS)

  8. Ego Involvement and Topic Controversiality as Related to Attitude Change.

    Science.gov (United States)

    Sledden, Elizabeth A.; Fernandez, Katherine A.

    Attitude change was measured on four different topics before and immediately after a persuasion was presented in order to compare the degree of change with the level of ego involvement as it relates to topic controversiality. Ego involvement was based on self-ratings of concern for each topic. Objective topic controversiality was based on the…

  9. Predicting Public Acceptability in Controversial Technologies

    International Nuclear Information System (INIS)

    Bruce, Donald M.

    2003-01-01

    Technology and society have a synergic relationship. New technologies are a product of the values and aspirations of the culture in which they emerge. In turn, each new technology shapes and alters these values and aspirations, to a greater or lesser degree. The acceptance by society of any particular technology depends, however, on how far the values embodied in the technology reflect those of the wider society, or only those of some privileged sector - perhaps a ruling elite, a group of academic researchers, a commercial company, or even a special interest group. As public disquiet about controversial technologies has grown, their acceptance can no longer be taken for granted. It is now becoming more important to evaluate in advance the degree of likely mismatch between the aspirations of the technologists and the values of society. This paper explores one approach to making this evaluation, based on the notion of a conditional social contract between technology and society. A given society may be prepared to embrace a new technology to deliver certain benefits, and may accept a certain degree of risk and adaptation of life styles, provided certain basic conditions are fulfilled. These conditions include the upholding of basic values, familiarity, how it compares with similar technologies, the degree of control and choice, trust in those in control, the nature of any risks, the tangible benefits, and the media profile given to the new area. If several of these factors are not fulfilled, the technology is unlikely to be accepted. This was dramatically illustrated in the UK public reaction to food products derived from imported US GM soya and maize. These failed nearly all the conditions, so that public rejection should have been seen as a foregone conclusion. In the light of this, the likely public reaction to a number of future biotechnological innovations is assessed, based on the same conditions. Some examples taken from the energy sector are also compared. The

  10. KNOW NUKES: a model for teaching controversial issues

    International Nuclear Information System (INIS)

    Thomashow, M.S.

    1986-01-01

    This dissertation articulates elements of an educational strategy derived from the experience of the KNOW NUKES program, a teacher training project designed to introduce the nuclear power controversy in the high school classroom. This strategy can be used as means of furthering the effectiveness of controversial issues education, not only in the area of nuclear power, but in teaching about any environmental issue. This is specifically achieved by (2) placing the KNOW NUKES institute in the broader context of controversial issues education; (2) describing in detail KNOW NUKES project planning; (3) reviewing the structure and content of the various teaching techniques and materials that have been developed for the KNOW NUKES institute; (4) utilizing a particular technique developed by the institute that reveals varying perspectives on controversial issues, in this case, an instrumental for decoding the controversial issues that are explicit and implicit in corporate image advertisements; and (5) qualitatively evaluating the practical implementation of the KNOW NUKES model

  11. DES the year in review: controversies.

    Science.gov (United States)

    Garg, S; Bourantas, C; Serruys, P W

    2013-04-01

    Drug-eluting stents (DES) have transformed interventional cardiology over the past decade. Whilst their efficacy has rarely been called into question, there have been concerns over the safety of the early devices, which has prompted the development of new coronary stents. Many of these new devices have entered clinical practice, however questions remain as to whether they offer the improvements in clinical outcomes that were originally anticipated. In addition, there is a debate whether the reported high efficacy of these devices enables percutaneous coronary intervention (PCI) to be performed in patient and lesion sub-groups previous entirely the domain of the cardiac surgeon. This review paper addresses these outstanding questions.

  12. Controversy around the definition of waste

    CSIR Research Space (South Africa)

    Oelofse, Suzanna HH

    2009-11-20

    Full Text Available This paper presents the information concerning the definition of waste. Discussing the importance of the clear definition, ongoing debates, broad definition of waste, problems with the broad definition, interpretation, current waste management model...

  13. Fecal microbiota transplantation: facts and controversies

    NARCIS (Netherlands)

    van Nood, Els; Speelman, Peter; Nieuwdorp, Max; Keller, Josbert

    2014-01-01

    To review the current evidence on fecal microbiota transplantations (FMTs) for recurrent Clostridium difficile infections (CDIs), metabolic syndrome and inflammatory bowel disease. Recently, a randomized trial confirmed the efficacy of this treatment strategy in patients with recurrent CDI. For

  14. Adjunctive use of the diode laser in non-surgical periodontal therapy: exploring the controversy.

    Science.gov (United States)

    Porteous, Mary Sornborger; Rowe, Dorothy J

    2014-04-01

    Despite the controversy regarding clinical efficacy, dental hygienists use the diode laser as an adjunct to non-surgical periodontal therapy. The technique to maximize successful laser therapy outcome is controversial as well. The purpose of this review is to explore the scientific foundation of the controversy surrounding the use of the diode laser as an adjunct to non-surgical periodontal therapy. Further, this paper addresses the weaknesses in study design, the heterogeneity of methodology in the published clinical studies, especially the laser parameters, and how these issues impact the collective clinical and microbial data, and thus conclusions regarding clinical efficacy. Evaluation of the literature identifies possible mechanisms that could contribute to the varied, often conflicting results among laser studies that are the foundation of the controversy surrounding clinical efficacy. These mechanisms include current paradigms of periodontal biofilm behavior, tissue response to laser therapy being dependent on tissue type and health, and that the successful therapeutic treatment window is specific to the target tissue, biofilm composition, laser wavelength, and laser energy delivered. Lastly, this paper discusses laser parameters used in the various clinical studies, and how their diversity contributes to the controversy. Although this review does not establish clinical efficacy, it does reveal the scientific foundation of the controversy and the need for standardized, well designed randomized controlled clinical trials to develop specific guidelines for using the laser as an adjunct to non-surgical periodontal therapy. Using evidence-based laser guidelines would allow dental hygienists to provide more effective non-surgical periodontal care.

  15. Cardiopulmonary resuscitation: update, controversies and new advances

    Directory of Open Access Journals (Sweden)

    Alexandre C. Zago

    1999-03-01

    Full Text Available Cardiopulmonary arrest is a medical emergency in which the lapse of time between event onset and the initiation of measures of basic and advanced support, as well as the correct care based on specific protocols for each clinical situation, constitute decisive factors for a successful therapy. Cardiopulmonary arrest care cannot be restricted to the hospital setting because of its fulminant nature. This necessitates the creation of new concepts, strategies and structures, such as the concept of life chain, cardio-pulmonary resuscitation courses for professionals who work in emergency medical services, the automated external defibrillator, the implantable cardioverter-defibrillator, and mobile intensive care units, among others. New concepts, strategies and structures motivated by new advances have also modified the treatment and improved the results of cardiopulmonary resuscitation in the hospital setting. Among them, we can cite the concept of cerebral resuscitation, the application of the life chain, the creation of the universal life support algorithm, the adjustment of drug doses, new techniques - measure of the end-tidal carbon dioxide levels and of the coronary perfusion pressure - and new drugs under research.

  16. Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-β-cyclodextrin by counter-current capillary electrophoresis.

    Science.gov (United States)

    Asensi-Bernardi, Lucía; Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Sagrado, Salvador; Medina-Hernández, María José

    2014-01-01

    The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed. Results indicate that, in general, thermodynamic enantioselectivity is the main component explaining the high resolution found, but also one case suggests that electrophoretic enantioselectivity itself is enough to obtain a satisfactory resolution. CFT results advantageous compared with conventional capillary electrophoresis (CE) and partial filling technique (PFT) for the study of the interaction between drugs and chiral selectors. It combines the use of a simple fitting model (as in CE), when the enantiomers do not exit the chiral selector plug during the separation (i.e. mobility of electroosmotic flow larger than mobility of CD), and drastic reduction of the consumption (and cost; ~99.7%) of the CD reagent (as in PFT) compared with the conventional CE. Copyright © 2013 John Wiley & Sons, Ltd.

  17. The Copyright Controversy: Issues and Opinions

    Science.gov (United States)

    Keenan, Stella, Ed.; Stillman, Mary E., Ed.

    1972-01-01

    The edited transcript of the Copyright Panel at the 9th Information Retrieval Colloquium is presented. In addition to the panel presentation and audience discussion, this issue carries, as appendix material, some of the documents which sparked much of the current copyright debate. (Author/NH)

  18. KLM senior managers forgo controversial bonuses

    NARCIS (Netherlands)

    Grünell, M.

    2004-01-01

    In April 2004, the members of the management board of KLM waived bonuses offered to them in the run-up to the Dutch airline's merger with Air France, under pressure from trade unions and the government. During the current agreed national wage freeze, increases in senior management remuneration are

  19. Controversies surrounding the clinical potential of cinnamon for the management of diabetes.

    Science.gov (United States)

    Rafehi, H; Ververis, K; Karagiannis, T C

    2012-06-01

    Obesity levels have increased significantly in the past five decades and are predicted to continue rising, resulting in important health implications. In particular, this has translated to an increase in the occurrence of type II diabetes mellitus (T2D). To alleviate associated problems, certain nutraceuticals have been considered as potential adjuncts or alternatives to conventional prescription drugs. Cinnamon, a commonly consumed spice originating from South East Asia, is currently being investigated as a potential preventative supplement and treatment for insulin resistance, metabolic syndrome and T2D. Extensive in vitro evidence has shown that cinnamon may improve insulin resistance by preventing and reversing impairments in insulin signalling in skeletal muscle. In adipose tissue, it has been shown that cinnamon increases the expression of peroxisome proliferator-activated receptors including, PPARγ. This is comparable to the action of commonly used thiazolinediones, which are PPAR agonists. Studies have also shown that cinnamon has potent anti-inflammatory properties. However, numerous human clinical trials with cinnamon have been conducted with varying findings. While some studies have showed no beneficial effect, others have indicated improvements in cholesterol levels, systolic blood pressure, insulin sensitivity and postprandial glucose levels with cinnamon. However, the only measurement consistently improved by cinnamon consumption is fasting glucose levels. While it is still premature to suggest the use of cinnamon supplementation based on the evidence, further investigation into mechanisms of action is warranted. Apart from further characterization of genetic and epigenetic changes in model systems, systematic large-scale clinical trials are required. In this study, we discuss the mechanisms of action of cinnamon in the context of T2D and we highlight some of the associated controversies. © 2011 Blackwell Publishing Ltd.

  20. The design of an enzyme: a chronology on the controversy.

    Science.gov (United States)

    Buc, Henri

    2013-05-13

    After the publication of the Monod-Wyman-Changeux model, a controversy arose between Jacques Monod, Francis Crick and Jeffries Wyman about the comparison of the regulatory performances of an oligomer undergoing a concerted transition between two states and a monomer having the same composition and subjected to a similar conformational equilibrium. The controversy took place between September 1965 and March 1966. It gave rise to several unpublished notes. Numerous misunderstandings between the participants were not fully dissipated as the controversy abruptly ended. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  2. Advance euthanasia directives: a controversial case and its ethical implications.

    Science.gov (United States)

    Miller, David Gibbes; Dresser, Rebecca; Kim, Scott Y H

    2018-03-03

    Authorising euthanasia and assisted suicide with advance euthanasia directives (AEDs) is permitted, yet debated, in the Netherlands. We focus on a recent controversial case in which a Dutch woman with Alzheimer's disease was euthanised based on her AED. A Dutch euthanasia review committee found that the physician performing the euthanasia failed to follow due care requirements for euthanasia and assisted suicide. This case is notable because it is the first case to trigger a criminal investigation since the 2002 Dutch euthanasia law was enacted. Thus far, only brief descriptions of the case have been reported in English language journals and media. We provide a detailed description of the case, review the main challenges of preparing and applying AEDs for persons with dementia and briefly assess the adequacy of the current oversight system governing AEDs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Controversies regarding decentralism, regionalism, and local governance in Serbia

    Directory of Open Access Journals (Sweden)

    Mitrović Milovan M.

    2002-01-01

    Full Text Available The article is composed from three parts. In the first part, I emphasize the importance of theoretical and sociological discussion for the design of the model of social system reforms and stress the problems that occur in Serbia with regard to this. In the second part, I discuss public controversies regarding decentralism, regionalism, and local governance in Serbia. I advocate for regionalism that is closer to local then to para-state governance and argue for the advantages of alternative model of 'functional autonomy of different tempo', that could harmonize inherited historical geopolitical, economic, and cultural differences and reconcile current political antagonisms in Serbia. In the third part I give a proposition that envisages central (Republic administration and local (municipal and city self-governance as main levels of territorial organization of governance (with original authorities, while federal and regional levels would be complementary with it, not parallel. In that sense, I propose 15 autonomous regions for Serbia, with possibility of making 4 to 6 larger regions out of them, at different pace.

  4. Streamlining antibiotic therapy with procalcitonin protocols: consensus and controversies.

    Science.gov (United States)

    Haubitz, Sebastian; Mueller, Beat; Schuetz, Philipp

    2013-04-01

    Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate biomarker for likelihood and severity of bacterial infections. In community-acquired pneumonia and other respiratory infections, PCT-guided antibiotic therapy algorithms resulted in reduced antibiotic exposure while maintaining a similar or even better level of safety compared with standard care. Reductions in antibiotic use translate into lower treatment costs, decreased risk of side effects and decreased bacterial multiresistance. This is especially important, as acute respiratory infections represent the most frequent reason for antibiotic prescriptions worldwide. Still, there is some controversy about the benefits of PCT measurement in sepsis patients in the intensive care unit and for nonrespiratory infections. Highly sensitive PCT assays are readily available in many hospitals today, and point-of-care assays with high enough sensitivity for antibiotic guidance are expected to be available soon. Herein, the authors provide an overview of recent studies evaluating PCT in different clinical situations and an outlook of currently enrolling or upcoming interventional trials.

  5. Asbestos and cancer: epidemiological and public health controversies.

    Science.gov (United States)

    Huncharek, M

    1994-01-01

    This paper discusses many of the currently controversial issues surrounding asbestos health effects and their relationship to cancer risk assessment and risk management. The major conclusions reached from this analysis are: (1) All asbestos fiber types are carcinogenic and pose a threat to human health. Therefore, all fiber types should be regulated similarly. (2) The health risks associated with indoor asbestos exposure are uncertain. Available data show that some groups, such as building maintenance personnel (among others), may contract asbestos-related diseases secondary to indoor exposure. Clearly, additional research is needed to accurately determine the extent and nature of disease risk under these conditions. (3) Controlled use has proved an elusive goal. Limited information from underdeveloped countries parallels the experience of Western industrialized nations. Efforts by the Canadian government to establish markets for asbestos in these areas should be opposed. (4) Finally, asbestos-related cancer risk is no longer confined to asbestos industry workers. Asbestos-related mesothelioma has been documented in a wide variety of occupational and nonoccupational settings, highlighting the need for continued surveillance to minimize potential health risks.

  6. Sensory processing disorders – diagnostic and therapeutic controversies

    Directory of Open Access Journals (Sweden)

    Aneta R. Borkowska

    2017-09-01

    Full Text Available This article presents the current state of knowledge regarding the controversial issue of sensory integration dysfunction/sensory processing disorder. Symptoms are defined as impairments in the accurate reception and registering of stimuli, differentiation of stimulus intensity, and adequate reactivity to stimulation. They can be of specific character and occur in isolation and can also be a nonspecific element of a clinical picture of another disease entity. Psychophysiological and neuroimaging studies confirm the existence of both a distinct group of children with symptoms of sensory processing disorder diagnosed based on descriptions of behaviours listed in questionnaires and of a specific neurobiological basis of this disorder. In clinical practice, it is of key importance to determine whether behavioural problems observed in children are caused by disorders other than sensory processing disorders. Results of meta-analyses regarding sensory integration therapy are inconclusive and do not allow this form of treatment to be considered fact-based. Future studies with high methodological standards are necessary in order to verify the effectiveness of different forms of sensory integration therapy. Parents should be informed about the existing limitations.

  7. [Methodological controversies in chronic obstructive pulmonary disease therapeutic trials].

    Science.gov (United States)

    Suissa, Samy

    2009-03-01

    Pharmacological treatment of chronic obstructive pulmonary disease (COPD) relies principally on long-acting bronchodilators. Inhaled corticosteroids (ICS) were introduced for COPD two decades ago, despite the fact that no randomized trial had yet assessed their efficacy for this indication. Since then, the numerous randomized trials and meta-analyses performed to justify their use in COPD have been contradictory and controversial. Moreover, observational studies have reported efficacy rates so exceptional that they are almost too good to be true. These studies contain important methodological flaws that produce the appearance of efficacy. The randomized trials infringe the fundamental principle of intention-to-treat analysis, an analysis necessary to prevent important biases. Two other complications are the interruption of treatment at the moment of randomization and the use of a run-in period; in both cases, the withdrawal of treatment can introduce bias. The observational studies reporting phenomenal reductions in mortality with ICS were distorted by "immortal time" bias. Finally, recent data suggest that the effect of ICS/bronchodilator combinations is due mainly to the effect of the long-acting bronchodilator. Given the absence of proof of the efficacy of inhaled corticosteroids in COPD and their associated risks, especially of ocular damage and pneumonia, and particularly among the elderly, as well as the high doses currently prescribed in COPD, it is difficult to recommend their use in this indication. They should be prescribed in COPD for at most a limited population of patients.

  8. Current drug and molecular therapies for the treatment of atrophic age-related macular degeneration: phase I to phase III clinical development.

    Science.gov (United States)

    Li, Huiling; Chintalapudi, Sumana R; Jablonski, Monica M

    2017-10-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. Atrophic AMD, including early, intermediate and geographic atrophy (GA), accounts for ~90% of all cases. It is a multifactorial degeneration characterized by chronic inflammation, oxidative stress and aging components. Although no FDA-approved treatment yet exists for the late stage of atrophic AMD, multiple pathological mechanisms are partially known and several promising therapies are in various stages of development. Areas covered: Underlying mechanisms that define atrophic AMD will help provide novel therapeutic targets that will address this largely unmet clinical need. The purpose of this paper is to review current promising drugs that are being evaluated in clinical trials. Because no pharmacological treatments are currently available for late stage of atrophic AMD, any new therapy would have extensive market potential. Expert opinion: The number of AMD patients is predicted to increase to ~30 million worldwide by 2020. In response to this enormous unmet clinical need, new promising therapies are being developed and evaluated in clinical trials. We propose that the assessment of novel interventions will also need to consider the genotypes of participants, as the benefit may be determined by polymorphisms in an individual's genetic background.

  9. Controversies in contraception for women with epilepsy

    Directory of Open Access Journals (Sweden)

    Sanjeev V Thomas

    2015-01-01

    Full Text Available Contraception is an important choice that offers autonomy to women with regard to prevention of unintended pregnancies. There is wide variation in the contraceptive practices between continents, countries, and societies. The medical eligibility for contraception for sexually active women with epilepsy (WWE is determined by the type of anti-epileptic drugs (AEDs that they use. Enzyme inducing AEDs such as phenobarbitone, phenytoin, carbamazepine, and oxcarbazepine increase the metabolism of orally administered estrogen (and progesterone to a lesser extent. Estrogen can increase the metabolism of certain AEDs, such as lamotrigine, leading to cyclical variation in its blood level with resultant adverse effect profile or seizure dyscontrol. AEDs and sex hormones can increase the risk of osteoporosis and fracture in WWE. The potential interactions between AEDs and hormonal contraception need to be discussed with all women in reproductive age-group. The alternate options of oral contraception such as intrauterine copper device, intrauterine levonorgestrel release system, and supplementary protection with barriers need to be presented to them. World Health Organization has recommended to avoid combination contraceptive pills containing estrogen and progesteron in women who desire contraception and in breastfeeding mothers. Care providers need to consider the option of non-enzyme-inducing AEDs while initiating long-term treatment in adolescent and young WWE.

  10. [The risk of direct current countershock].

    Science.gov (United States)

    Gajek, J; Zyśko, D

    2001-07-01

    Direct current cardioversion (DCC) is a procedure commonly used to restore the sinus rhythm in patients with supraventricular and ventricular arrhythmias. Its safety, regarding the use of electric current, is still a matter of controversy and debate. The patients with atrial fibrillation/flutter, supraventricular or ventricular tachycardia represent a broad spectrum of clinical conditions and it is difficult to draw the conclusions. The high success rate of DCC in restoring the sinus rhythm, may be partly responsible for enhancing and revealing proarrhythmic properties of antiarrhythmic drugs. The deaths described as a complications of DCC were mainly due to the proarrhythmia and less common to the progression of the pathologic process. The embolic, arrhythmic and anesthetic complications of DCC can be prevented if the known recommendations of performing the DCC are followed. The authors review critically the literature data about the complications of the procedure and come to the conclusion of safety of DCC.

  11. Pension Reform Act 2004 and its Controversies: Repeating or ...

    African Journals Online (AJOL)

    Pension Reform Act 2004 and its Controversies: Repeating or Learning from Past Mistakes? ... Journal of Research in National Development ... and discusses how the present pension reform will affect active employees when they retire.

  12. Electrical stimulation in dysphagia treatment: a justified controversy?

    NARCIS (Netherlands)

    Bogaardt, H. C. A.

    2008-01-01

    Electrical stimulation in dysphagia treatment: a justified controversy? Neuromuscular electrostimulation (LAMES) is a method for stimulating muscles with short electrical pulses. Neuromuscular electrostimulation is frequently used in physiotherapy to strengthen healthy muscles (as in sports

  13. Social reporting, engagements, controversies and conflict in an arena context

    NARCIS (Netherlands)

    Georgakopoulos, G.; Thomson, I.

    2008-01-01

    Purpose - To empirically investigate relationships between engagement activities and social reporting practices in a controversial and environmentally sensitive industry. The interactions investigated were not restricted to stakeholder relationships but included other communications between

  14. Family planning and the controversial contraceptives.

    Science.gov (United States)

    Dias Saxena, F

    1995-01-01

    India was one of the first countries in the world to launch a national family planning program in an apparent effort to help women gain access to birth control measures and reduce population growth. Family planning acquired a different meaning and emphasis in the 1960s, however, when a clause in the US PL480 wheat import policy demanded that India speed its implementation of birth control measures if the country wanted food aid. Women in India were therefore expected to consume contraceptives with dangerous and unknown side effects in order to quality the country for food aid. Women rejected this stipulation. By the 1980s, it was acknowledged that family planning programs in India had failed to produce a decline in the birth rate and that no sign of change was on the horizon despite the investment of substantial funds to that end, the input of expert assistance, and the establishment of appropriate infrastructure in the country. Experts and policy makers blamed women for having misused the pill and sought alternative methods which would not require user compliance. Norplant and norethisterone enanthate (Net-en) were subsequently developed. Policymakers, experts, and the press have now been clamoring for the right to conduct Norplant trials despite reported side effects. The drug's ability to prevent pregnancy is more important for family planning experts. The author notes that the emphasis has been upon contraceptive methods for women instead of men because men were not expected to take responsibility for family planning. She also notes that feminists are opposed to Norplant and Net-en, and hopes that the government withdraws them from the market.

  15. Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

    Science.gov (United States)

    Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

    2013-01-01

    Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

  16. Mapping Controversies with Social Media: The Case for Symmetry

    Directory of Open Access Journals (Sweden)

    Noortje Marres

    2015-09-01

    Full Text Available This article assesses the usefulness for social media research of controversy analysis, an approach developed in Science and Technology Studies (STS and related fields. We propose that this approach can help to address an important methodological problem in social media research, namely, the tension between social media as resource for social research and as an empirical object in its own right. Initially developed for analyzing interactions between science, technology, and society, controversy analysis has in recent decades been implemented digitally to study public debates and issues dynamics online. A key feature of controversy analysis as a digital method, we argue, is that it enables a symmetrical approach to the study of media-technological dynamics and issue dynamics. It allows us to pay equal attention to the ways in which a digital platform like Twitter mediates public issues, and to how controversies mediate “social media” as an object of public attention. To sketch the contours of such a symmetrical approach, the article discusses examples from a recent social media research project in which we mapped issues of “privacy” and “surveillance” in the wake of the National Security Agency (NSA data leak by Edward Snowden in June 2013. Through a discussion of social media research practice, we then outline a symmetrical approach to analyzing controversy with social media. We conclude that the digital implementation of such an approach requires further exchanges between social media researchers and controversy analysts.

  17. The chilling effect: how do researchers react to controversy?

    Directory of Open Access Journals (Sweden)

    Joanna Kempner

    2008-11-01

    Full Text Available BACKGROUND: Can political controversy have a "chilling effect" on the production of new science? This is a timely concern, given how often American politicians are accused of undermining science for political purposes. Yet little is known about how scientists react to these kinds of controversies. METHODS AND FINDINGS: Drawing on interview (n = 30 and survey data (n = 82, this study examines the reactions of scientists whose National Institutes of Health (NIH-funded grants were implicated in a highly publicized political controversy. Critics charged that these grants were "a waste of taxpayer money." The NIH defended each grant and no funding was rescinded. Nevertheless, this study finds that many of the scientists whose grants were criticized now engage in self-censorship. About half of the sample said that they now remove potentially controversial words from their grant and a quarter reported eliminating entire topics from their research agendas. Four researchers reportedly chose to move into more secure positions entirely, either outside academia or in jobs that guaranteed salaries. About 10% of the group reported that this controversy strengthened their commitment to complete their research and disseminate it widely. CONCLUSIONS: These findings provide evidence that political controversies can shape what scientists choose to study. Debates about the politics of science usually focus on the direct suppression, distortion, and manipulation of scientific results. This study suggests that scholars must also examine how scientists may self-censor in response to political events.

  18. The Chilling Effect: How Do Researchers React to Controversy?

    Science.gov (United States)

    Kempner, Joanna

    2008-01-01

    Background Can political controversy have a “chilling effect” on the production of new science? This is a timely concern, given how often American politicians are accused of undermining science for political purposes. Yet little is known about how scientists react to these kinds of controversies. Methods and Findings Drawing on interview (n = 30) and survey data (n = 82), this study examines the reactions of scientists whose National Institutes of Health (NIH)-funded grants were implicated in a highly publicized political controversy. Critics charged that these grants were “a waste of taxpayer money.” The NIH defended each grant and no funding was rescinded. Nevertheless, this study finds that many of the scientists whose grants were criticized now engage in self-censorship. About half of the sample said that they now remove potentially controversial words from their grant and a quarter reported eliminating entire topics from their research agendas. Four researchers reportedly chose to move into more secure positions entirely, either outside academia or in jobs that guaranteed salaries. About 10% of the group reported that this controversy strengthened their commitment to complete their research and disseminate it widely. Conclusions These findings provide evidence that political controversies can shape what scientists choose to study. Debates about the politics of science usually focus on the direct suppression, distortion, and manipulation of scientific results. This study suggests that scholars must also examine how scientists may self-censor in response to political events. PMID:19018657

  19. The prison system in the Czech Republic: Analysis of the current state of illicit drug use and prevention and treatment measures

    Czech Academy of Sciences Publication Activity Database

    Miovský, Michal; Gajdošíková, H.

    2005-01-01

    Roč. 16, č. 4 (2005), s. 262-266 ISSN 0955-3959 Institutional research plan: CEZ:AV0Z70250504 Keywords : Criminal offences * drug crime * illicit drugs * drug user * prevetntion and treatment measures Subject RIV: AN - Psychology

  20. Meningiomas in 2009: controversies and future challenges.

    Science.gov (United States)

    Campbell, Belinda A; Jhamb, Ashu; Maguire, John A; Toyota, Brian; Ma, Roy

    2009-02-01

    Meningiomas are the most common intracranial primary neoplasm in adults. Over recent years, interest in this clinically diverse group of tumors has intensified, bringing new questions and challenges to the fore, particularly in the fields of epidemiology, radiology, pathology, genetics, and treatment. Interest in modern meningioma research has been stimulated by the high tumor prevalence and the advances in technology. The incidence of meningiomas is climbing, and may indicate increased exposure to environmental risk factors or more sensitive diagnostic modalities. Technological advances have dramatically improved radiologic imaging and radiotherapy treatments, and further refinements are under investigation. Furthermore, the current era of tumor genetics and molecular biology is challenging translational researchers to discover new, targeted, therapeutic agents. This review is an update on the recent advances in the understanding of meningiomas and their management, and highlights pertinent research questions to be addressed in the future.

  1. Image diagnostic of colonic diseases - controversial questions

    International Nuclear Information System (INIS)

    Pomakov, P.; Rizov, A.; Stancheva, I.

    2013-01-01

    In the system of colonic diseases' diagnostic algorithm, fibrocolonoscopy (FCS) is defined as 'Golden Standard'. By this reason some X-ray diagnostic methods - irrigography, etc. are currently not being used in a number of health institutions. The aim of this study is a comparative analysis of FCS and irrigography diagnostic efficacy in various colonic diseases. For 10-years period, in cooperation with a gastroenterologist-gastroscopist, 2151 patients with various colonic diseases were evaluated by FCS and irrigography with pharmaco-diagnostics/when necessary. Advantage of FCS was established in diagnosing diseases with patho-morfologic changes on the inner surface of the colon - benign and malignant neoplastic processes, chronic inflammatory diseases, etc. At the same time functional changes - irritated colon syndrome, changes in defecation act, etc., are not an object of diagnosis through FCS. Correction in colonic diseases diagnostic algorithm is necessary. FCS should be mandatory. If result is negative - irrigography with pharmaco-diagnostics should be done. (authors)

  2. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

    Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

  3. Pediatric Orthogenomics: The Latest Trends and Controversies

    Directory of Open Access Journals (Sweden)

    Neha Sinha

    2017-05-01

    Full Text Available The advent of molecular biology has paved way for an era of personalized medicine. Though medical disciplines such as oncology and cardiology are advanced in their use of genomics, implementation has been slower in other specialties, such as orthopaedics. Recent advances in genomic technology have shed light on the underlying genetic basis of various pediatric orthopaedic disorders. Prior understanding of the genetic makeup of a patient may help individualize care in patients with conditions including idiopathic scoliosis, congenital talipes equinovarus and congenital limb deformities. The fastpaced growth of information in orthogenomics often makes it challenging for an orthopaedic surgeon to effectively use this information for patient care. Genetic characterization of a patient will help indicate risk of progression of a condition, recurrence and/or response to a treatment modality, and a collaborative approach between an orthopaedic surgeon and a geneticist can help tailor patient care. The following review article summarizes current understanding in molecular genomics of common pediatric orthopaedic disorders.

  4. [Genetically modified food--unnecessary controversy?].

    Science.gov (United States)

    Tchórz, Michał; Radoniewicz-Chagowska, Anna; Lewandowska-Stanek, Hanna; Szponar, Elzbieta; Szponar, Jarosław

    2012-01-01

    Fast development of genetic engineering and biotechnology allows use of genetically modified organisms (GMO) more and more in different branches of science and economy. Every year we can see an increase of food amount produced with the use of modification of genetic material. In our supermarkets we can find brand new types of plants, products including genetically modified ingredients or meat from animals fed with food containing GMO. This article presents general information about genetically modified organisms, it also explains the range of genetic manipulation, use of newly developed products and current field area for GMO in the world. Based on scientific data the article presents benefits from development of biotechnology in reference to modified food. It also presents the voice of skeptics who are extremely concerned about the impact of those organisms on human health and natural environment. Problems that appear or can appear as a result of an increase of GMO are very important not only from a toxicologist's or a doctor's point of view but first of all from the point of view of ordinary consumers--all of us.

  5. Geophysical considerations in the fifth force controversy

    International Nuclear Information System (INIS)

    Stacey, F.D.; Tuck, G.J.; Moore, G.I.

    1988-01-01

    If there are non-Newtonian components of gravity, now popularly dubbed the ''fifth force,'' as several observations indicate, then the favored representation is in terms of Yukawa potentials with ranges that make them accessible to geophysical observation. We must now consider at least two Yukawa terms of opposite signs, so that the observed effects may be subtle. Measurements in different crustal structures (continental mines and boreholes, ocean and ice sheets) could help to resolve the details, but it is possible for fortuitous cancellations to invite misleading conclusions where measurements are made in a layer that is underlain by a much denser layer. However, with currently favored parameters of a pair of Yukawa terms both ice and ocean measurements should give effects of the sign expected from mine measurements, but with amplitudes reduced by partial cancellation due to the layered structures. We also reexamine conventional interpretations of the mine gravity anomalies and reassert that uncertainties in density estimates must be discounted. A new inversion of the broad scale gravity anomalies in the area of the north Queensland mines that we have used confirms the earlier conclusion that the mine gradient anomaly is not a consequence of a regional free-air gradient anomaly, although this conclusion is not as secure as the dismissal of density error

  6. Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse.

    Science.gov (United States)

    Cazer, Casey L; Ducrot, Lucas; Volkova, Victoriya V; Gröhn, Yrjö T

    2017-01-01

    Antimicrobial use in beef cattle can increase antimicrobial resistance prevalence in their enteric bacteria, including potential pathogens such as Escherichia coli . These bacteria can contaminate animal products at slaughterhouses and cause food-borne illness, which can be difficult to treat if it is due to antimicrobial resistant bacteria. One potential intervention to reduce the dissemination of resistant bacteria from feedlot to consumer is to impose a withdrawal period after antimicrobial use, similar to the current withdrawal period designed to prevent drug residues in edible animal meat. We investigated tetracycline resistance in generic E. coli in the bovine large intestine during and after antimicrobial treatment by building a mathematical model of oral chlortetracycline pharmacokinetics-pharmacodynamics and E. coli population dynamics. We tracked three E. coli subpopulations (susceptible, intermediate, and resistant) during and after treatment with each of three United States chlortetracycline indications (liver abscess reduction, disease control, disease treatment). We compared the proportion of resistant E. coli before antimicrobial use to that at several time points after treatment and found a greater proportion of resistant enteric E. coli after the current withdrawal periods than prior to treatment. In order for the proportion of resistant E. coli in the median beef steer to return to the pre-treatment level, withdrawal periods of 15 days after liver abscess reduction dosing (70 mg daily), 31 days after disease control dosing (350 mg daily), and 36 days after disease treatment dosing (22 mg/kg bodyweight for 5 days) are required in this model. These antimicrobial resistance withdrawal periods would be substantially longer than the current U.S. withdrawals of 0-2 days or Canadian withdrawals of 5-10 days. One published field study found similar time periods necessary to reduce the proportion of resistant E. coli following chlortetracycline disease

  7. Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse

    Directory of Open Access Journals (Sweden)

    Casey L. Cazer

    2017-09-01

    Full Text Available Antimicrobial use in beef cattle can increase antimicrobial resistance prevalence in their enteric bacteria, including potential pathogens such as Escherichia coli. These bacteria can contaminate animal products at slaughterhouses and cause food-borne illness, which can be difficult to treat if it is due to antimicrobial resistant bacteria. One potential intervention to reduce the dissemination of resistant bacteria from feedlot to consumer is to impose a withdrawal period after antimicrobial use, similar to the current withdrawal period designed to prevent drug residues in edible animal meat. We investigated tetracycline resistance in generic E. coli in the bovine large intestine during and after antimicrobial treatment by building a mathematical model of oral chlortetracycline pharmacokinetics-pharmacodynamics and E. coli population dynamics. We tracked three E. coli subpopulations (susceptible, intermediate, and resistant during and after treatment with each of three United States chlortetracycline indications (liver abscess reduction, disease control, disease treatment. We compared the proportion of resistant E. coli before antimicrobial use to that at several time points after treatment and found a greater proportion of resistant enteric E. coli after the current withdrawal periods than prior to treatment. In order for the proportion of resistant E. coli in the median beef steer to return to the pre-treatment level, withdrawal periods of 15 days after liver abscess reduction dosing (70 mg daily, 31 days after disease control dosing (350 mg daily, and 36 days after disease treatment dosing (22 mg/kg bodyweight for 5 days are required in this model. These antimicrobial resistance withdrawal periods would be substantially longer than the current U.S. withdrawals of 0–2 days or Canadian withdrawals of 5–10 days. One published field study found similar time periods necessary to reduce the proportion of resistant E. coli following

  8. Neuroimaging of nonaccidental head trauma: pitfalls and controversies

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, Sujan [University of Missouri-Kansas School of Medicine, Department of Medicine, Kansas City, MO (United States); Obaldo, Ruby E. [The University of Kansas Medical Center, Department of Radiology, Kansas City, MO (United States); Walsh, Irene R. [The University of Missouri-Kansas City, Children' s Mercy Hospitals and Clinics, Department of Emergency Medicine, Kansas City, MO (United States); Lowe, Lisa H. [The University of Missouri-Kansas City, Children' s Mercy Hospitals and Clinics, Department of Radiology, Kansas City, MO (United States)

    2008-08-15

    Although certain neuroimaging appearances are highly suggestive of abuse, radiological findings are often nonspecific. The objective of this review is to discuss pitfalls, controversies, and mimics occurring in neuroimaging of nonaccidental head trauma in order to allow the reader to establish an increased level of comfort in distinguishing between nonaccidental and accidental head trauma. Specific topics discussed include risk factors, general biomechanics and imaging strategies in nonaccidental head trauma, followed by the characteristics of skull fractures, normal prominent tentorium and falx versus subdural hematoma, birth trauma versus nonaccidental head trauma, hyperacute versus acute on chronic subdural hematomas, expanded subarachnoid space versus subdural hemorrhage, controversy regarding subdural hematomas associated with benign enlarged subarachnoid spaces, controversy regarding hypoxia as a cause of subdural hematoma and/or retinal hemorrhages without trauma, controversy regarding the significance of retinal hemorrhages related to nonaccidental head trauma, controversy regarding the significance of subdural hematomas in general, and pitfalls of glutaric aciduria type 1 and hemophagocytic lymphohistiocytosis mimicking nonaccidental head trauma. (orig.)

  9. Studying a Controversy amongst Pashtuns of Torghar, Balochistan, Pakistan

    Directory of Open Access Journals (Sweden)

    Luc Bellon

    2007-10-01

    Full Text Available Much has been written about the political structures of tribal groups. The present article looks at political dynamics amongst Pashtuns of Balochistan, through the prism of a controversy. The sociological interest of studying the arguments used during a controversy has been underlined by Boltanski and Thevenot. A controversy finishes by the establishment, through consensus, of a common agreement upon accepted norms, determined limits, redefinition of social values, etc. The advantage of focusing on the argumentation itself is to avoid taking the agreement as a pre-established social truth, a reference that concerned people would reluctantly challenge. To study a controversy is to study the social realities in the making, to study the archaeology of collective consensus, to reinstate history, contingencies and individual plurality within the social dynamics and to take seriously their performative actions alongside other social determinisms. This article shows that to study controversy is a way not only to set light on political dynamics and structures, but also to discuss the impact and definition of concepts such as segmentarity, equality, rights, interests, and their relevance within the Pashtun society which was observed.

  10. COOPERATIVE CONTROVERSY TECHNIQUE TO IMPROVE STUDENTS’ MOTIVATION IN ENGLISH DEBATE

    Directory of Open Access Journals (Sweden)

    Suciati Suciati

    2016-03-01

    Full Text Available Many students do not like English debate. They argue that in the debate, they should apply four skills in English and should have appropriate matter, manner, and method. One of the reasons which make them do not like the debate is their lack of motivation. To solve this problem, teacher or lecturer should apply the appropriate technique in the teaching-learning process. Cooperative controversy technique is different with the traditional debate. In this technique, debaters change positions and try to reach a consensus at the end of the debate. By doing it before practicing the real English debate format, the students will get the basic knowledge about the debate so they do not directly practice the complicated one. Cooperative controversy increases the number of ideas, quality of ideas, feelings of stimulation, and enjoyment and originality of expression in creative problem solving. If it is compared to the group which does not use controversy, in controversy, the members get motivation and satisfaction in solving the problems.Keywords: English debate, students’ motivation, cooperative controversy

  11. Neuroimaging of nonaccidental head trauma: pitfalls and controversies

    International Nuclear Information System (INIS)

    Fernando, Sujan; Obaldo, Ruby E.; Walsh, Irene R.; Lowe, Lisa H.

    2008-01-01

    Although certain neuroimaging appearances are highly suggestive of abuse, radiological findings are often nonspecific. The objective of this review is to discuss pitfalls, controversies, and mimics occurring in neuroimaging of nonaccidental head trauma in order to allow the reader to establish an increased level of comfort in distinguishing between nonaccidental and accidental head trauma. Specific topics discussed include risk factors, general biomechanics and imaging strategies in nonaccidental head trauma, followed by the characteristics of skull fractures, normal prominent tentorium and falx versus subdural hematoma, birth trauma versus nonaccidental head trauma, hyperacute versus acute on chronic subdural hematomas, expanded subarachnoid space versus subdural hemorrhage, controversy regarding subdural hematomas associated with benign enlarged subarachnoid spaces, controversy regarding hypoxia as a cause of subdural hematoma and/or retinal hemorrhages without trauma, controversy regarding the significance of retinal hemorrhages related to nonaccidental head trauma, controversy regarding the significance of subdural hematomas in general, and pitfalls of glutaric aciduria type 1 and hemophagocytic lymphohistiocytosis mimicking nonaccidental head trauma. (orig.)

  12. Sexual orientation and gender identity: review of concepts, controversies and their relation to psychopathology classification systems.

    Science.gov (United States)

    Moleiro, Carla; Pinto, Nuno

    2015-01-01

    Numerous controversies and debates have taken place throughout the history of psychopathology (and its main classification systems) with regards to sexual orientation and gender identity. These are still reflected on present reformulations of gender dysphoria in both the Diagnostic and Statistical Manual and the International Classification of Diseases, and in more or less subtle micro-aggressions experienced by lesbian, gay, bisexual and trans patients in mental health care. The present paper critically reviews this history and current controversies. It reveals that this deeply complex field contributes (i) to the reflection on the very concept of mental illness; (ii) to the focus on subjective distress and person-centered experience of psychopathology; and (iii) to the recognition of stigma and discrimination as significant intervening variables. Finally, it argues that sexual orientation and gender identity have been viewed, in the history of the field of psychopathology, between two poles: gender transgression and gender variance/fluidity.

  13. Sexual Orientation and Gender Identity: Review of concepts, controversies and their relation to psychopathology classification systems

    Directory of Open Access Journals (Sweden)

    Carla eMoleiro

    2015-10-01

    Full Text Available Numerous controversies and debates have taken place throughout the history of psychopathology (and its main classification systems with regards to sexual orientation and gender identity. These are still reflected on present reformulations of gender dysphoria in both DSM and ICD, and in more or less subtle micro-aggressions experienced by lesbian, gay, bisexual and trans patients in mental health care. The present paper critically reviews this history and current controversies. It reveals that this deeply complex field contributes (i to the reflection on the very concept of mental illness; (ii to the focus on subjective distress and person-centered experience of psychopathology; and (iii to the recognition of stigma and discrimination as significant intervening variables. Finally, it argues that sexual orientation and gender identity have been viewed, in the history of the field of psychopathology, between two poles: gender transgression and gender variance/fluidity.

  14. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.

    Science.gov (United States)

    Maurer, Hans H; Sauer, Christoph; Theobald, Denis S

    2006-06-01

    This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed.

  15. Review of the recent carbon dioxide-climate controversy

    International Nuclear Information System (INIS)

    Luther, F.M.; Cess, R.D.

    1992-01-01

    Model calculations of the climatic impact of the increasing atmospheric carbon dioxide (CO 2 ) concentration consistently suggest that a doubling of the CO 2 concentration would lead to a warming of global average surface air temperatures by as much as several degrees Celsius. In this appendix, this controversy about the effect of CO 2 on climate is reviewed. Because the surface energy balance approach to estimating climate sensitivity has been the source of much of the controversy, a review of this approach is presented. It is shown that prior applications of this approach violate the law of conservation of energy (the first law of thermodynamics); therefore, these results are incorrect. Empirical data indicating the relationship between atmospheric emittance and surface vapor pressure and surface air temperature are shown to be consistent with climate model calculations. Consequently, it is not the experimental data that are the basis of the controversy, but rather the analysis and interpretation of these data

  16. Teaching controversial issues in the secondary school science classroom

    Science.gov (United States)

    van Rooy, Wilhelmina

    1993-12-01

    A sample of fourteen secondary school biology teachers chosen from twelve schools were interviewed. The purpose was to determine their views on how controversial issues in science might be handled in the secondary school science classroom and whether the issues of surrogacy and human embryo experimentation were suitable controversial issues for discussion in schools. In general, teachers indicated that controversial issues deserve a more prominent place in the science curriculum because they have the potential to foster thinking, learning, and interest in science. The issues of surrogacy and human embryo experimentation were seen as appropriate contexts for learning, provided that teachers were well informed and sensitive to both the students and to the school environment.

  17. Chernobylsk: a 'cloud' crosses... the facts and the controversies

    International Nuclear Information System (INIS)

    Lerouge, B.

    2008-01-01

    Twenty years after the Chernobylsk accident the effects are detailed by specialists, in radiobiology to judge the eventual sanitary injuries. It is a critical analysis that is made in this work, at the light of todays knowledge. The first part treats the question of communication, faults, late, silent. The second part is the time of controversy, the contamination in France, the radiation doses in France, thyroid cancers, the controversy of low doses effects, the controversy of sanitary consequences in USSR. The third part concerns the modernization of the nuclear world, the radiobiology, the public opinion. In annexes are: radioactivity, serious accidents, radiation doses (concepts and units), radiation protection and standards, the scientific bases of radiation protection, the figured conclusions of Chernobylsk forum, the European contamination map. (N.C.)

  18. Controversy and consensus nuclear beta decay 1911-1934

    CERN Document Server

    Jensen, Carsten

    2000-01-01

    In 1920s, a long-lasting controversy on the interpretation of nuclear beta spectrum arose between Lise Meitner and Charles Drummond Ellis. This controversy, and the reactions from the contending parties when it was settled, reflect clearly the difference between the scientific communities in Berlin and Cambridge at that time. The Meitner-Ellis controversy ended in 1929, and it left an anomaly that attracted leading theoretical physicists. A new dispute, this time between Niels Bohr and Wolfgang Pauli, broke out. It concerned the explanation of the continuity of the primary beta particles and dominated the discussions for the next five years. Pauli argued for a new particle, and Bohr for a new theory; both suggestions were radical steps, but they reflected two different ways of doing physics.

  19. The cartoon controversy as a case of multiculturalrecognition

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2007-01-01

    The paper considers what ‘recognition' might mean in theory and which policies would in practice qualify as policies of recognition in relation to multicultural conflicts such as the ‘cartoon controversy' sparked by the publication of drawings of the Prophet Mohammad in the Danish Newspaper...... Jyllands-Posten. The paper provides a general theoretical account of recognition as a strictly political concept, including distinctions between different conceptions hereof, and asks whether the cartoon controversy can be described in these terms and what the relevant meaning of recognition might then be...

  20. Current treatments for patients with Alzheimer disease.

    Science.gov (United States)

    Osborn, Gerald G; Saunders, Amanda Vaughn

    2010-09-01

    There is neither proven effective prevention for Alzheimer disease nor a cure for patients with this disorder. Nevertheless, a spectrum of biopsychosocial therapeutic measures is available for slowing progression of the illness and enhancing quality of life for patients. These measures include a range of educational, psychological, social, and behavioral interventions that remain fundamental to effective care. Also available are a number of pharmacologic treatments, including prescription medications approved by the US Food and Drug Administration for Alzheimer disease, "off-label" uses of medications to manage target symptoms, and controversial complementary therapies. Physicians must make the earliest possible diagnosis to use these treatments most effectively. Physicians' goals should be to educate patients and their caregivers, to plan long-term care options, to maximally manage concurrent illnesses, to slow and ameliorate the most disabling symptoms, and to preserve effective functioning for as long as possible. The authors review the various current treatments for patients with Alzheimer disease.

  1. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Vedantam Rajshekhar

    2016-01-01

    Full Text Available Neurocysticercosis (NCC is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues.

  2. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    Science.gov (United States)

    Rajshekhar, Vedantam

    2016-01-01

    Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530

  3. A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2005-09-01

    By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

  4. Evidence-Based Management and Controversies in Blunt Splenic Trauma

    NARCIS (Netherlands)

    Olthof, D. C.; van der Vlies, C. H.; Goslings, J. C.

    2017-01-01

    The study aims to describe the evidence-based management and controversies in blunt splenic trauma. A shift from operative management to non-operative management (NOM) has occurred over the past decades where NOM has now become the standard of care in haemodynamically stable patients with blunt

  5. Reading "Daddy's Roommate": Preservice Teachers Respond to a Controversial Text.

    Science.gov (United States)

    Williams, Shawyn

    2002-01-01

    Explores the responses of the author's 31 pre-service teachers to a controversial picture book. Begins by searching for a short text geared to elementary age children and suited for read-alouds. Notes that she believes that the majority of pre-service teachers at this stage in the program are still very impressionable and must be given multiple…

  6. [The controversy of routine articulator mounting in orthodontics].

    Science.gov (United States)

    Wang, Li; Han, Xianglong; Bai, Ding

    2013-06-01

    Articulators have been widely used by clinicians of dentistry. But routine articulator mounting is still controversial in orthodontics. Orthodontists oriented by gnathology approve routine articulator mounting while nongnathologic orthodontists disapprove it. This article reviews the thoughts of orthodontist that they agree or disagree with routine articulator mounting based on the considerations of biting, temporomandibular disorder (TMD), periodontitis, and so on.

  7. 37 CFR 351.3 - Controversy and further proceedings.

    Science.gov (United States)

    2010-07-01

    ..., the contested amount of a claim is $10,000 or less, the Copyright Royalty Judges shall decide the... CONGRESS COPYRIGHT ROYALTY JUDGES RULES AND PROCEDURES PROCEEDINGS § 351.3 Controversy and further... negotiation period, the Copyright Royalty Judges will issue an order declaring that further proceedings are...

  8. Adolescent Controversial Status Brokers: A Double-Edged Sword

    Science.gov (United States)

    Borowski, Sarah; Zeman, Janice; Carboni, Inga; Gilman, Rich; Thrash, Todd

    2017-01-01

    Using a 3-wave longitudinal, multidimensional approach, this study investigated the influence of social network position and social status on the psychosocial outcomes of 440 youth (45.1% girls; M[subscript age] = 16.1 years; 90.9% Caucasian) over 26 months, focusing on the controversial status classification (i.e., youth who are highly liked and…

  9. Allocative inefficiency and the capital-energy controversy

    International Nuclear Information System (INIS)

    Christopoulos, Dimitris K.; Tsionas, Efthymios G.

    2002-01-01

    The purpose of the paper is to estimate a system of input demands for Greek manufacturing deviating from the standard practice of assuming strict cost minimization. The study allows for the presence of price distortions and allocative inefficiency in the decision process. This assumption affects parameter estimates and estimated elasticities materially, and throws new light on the capital-energy controversy in Greek manufacturing

  10. The Future Path of Organic Farming - Values, Standards and Controversy!

    DEFF Research Database (Denmark)

    Kjærgård, Bente; Pedersen, Kirsten Bransholm; Land, Birgit

    The study focuses on the recent debate about what is, or what constitutes, organic farming and what is the right path for organic farming in the future. The study is based on a critical discourse analysis of the controversy about suspending the private standard for organic farming adopted by the ...

  11. Should We Teach Homosexuality as a Controversial Issue?

    Science.gov (United States)

    Hand, Michael

    2007-01-01

    Philosophers of education disagree on how the question of the moral status of homosexual acts should be tackled in the classroom. Some argue that the question should be taught as a controversial issue, that we should present rival moral positions as even-handedly as possible; others maintain that we should actively promote the view that homosexual…

  12. D. W. Griffith's Controversial Film, "The Birth of a Nation."

    Science.gov (United States)

    Pitcher, Conrad

    1999-01-01

    Presents a lesson plan that enables students to investigate race relations during the Progressive Era by analyzing D. W. Griffith's "The Birth of a Nation" and the controversy surrounding the release of the film. Explores the pros and cons of using motion pictures as teaching tool. Includes two student handouts. (CMK)

  13. Diversity in Information Technology Education: Issues and Controversies

    Science.gov (United States)

    Trajkovski, Goran, Ed.

    2006-01-01

    "Diversity in Information Technology Education: Issues and Controversies" sheds light on the status of diversity in the field of IT education. It identifies a wide range of problems that educators face on a daily basis, and gives practical, applicable solutions, mainly by showcasing successful and replicable examples. The chapters in "Diversity in…

  14. The Legitimizing Function of Judicial Rhetoric in the Eugenics Controversy.

    Science.gov (United States)

    Hasian, Marouf, Jr.; Croasmun, Earl

    1992-01-01

    Investigates the possibility that judicial policymaking is responsive to the situational exigencies created in part through public discourse. Investigates the elite and public perspectives regarding the eugenics controversy in the 1920s to explore the emergent relationship between the public and technical spheres of argument. (SR)

  15. Some diagnostic and therapeutic controversies in glaucoma addressed

    NARCIS (Netherlands)

    Müskens, Rogier Peter Hendrik Maria

    2008-01-01

    In the five studies contained in this thesis, several controversies on the diagnosis of and therapy for glaucoma have been addressed. The first part of this thesis consisted of three studies that aimed tot improve existing technologies for diagnosing glaucoma. The latter part consisted of two

  16. The Animal Experimentation Controversy: Ethical Views of Prospective Teachers

    Science.gov (United States)

    de Villiers, Rian

    2012-01-01

    Vivisection (live animal experimentation) is a controversial issue for many people. The purpose of this case study is to examine the attitudes of prospective teachers toward vivisection in education and research, to determine if gender has an influence on these attitudes, and to discuss the implications of these attitudes with regard to teaching…

  17. Controversial Therapies for Young Children with Developmental Disabilities.

    Science.gov (United States)

    Nickel, Robert E.

    1996-01-01

    This article examines reasons parents may choose a controversial alternative treatment for a child with developmental disabilities and reviews a few specific treatments--vitamin B-6 and magnesium, auditory integration training, megavitamins and minerals, Piracetam, intravenous immunoglobulin, and melatonin. Recommendations on talking with families…

  18. Integration of basic controversies in cross-cultural psychology

    NARCIS (Netherlands)

    Poortinga, Y.H.

    2016-01-01

    This article discusses controversies in the field of cross-cultural psychology, including cultural psychology, with a view to possible integration.1 It briefly describes the indigenisation movement as a reaction against Western scientific ethnocentrism and mentions two methodological topics, that

  19. Teaching Controversy by Seminar: An Example in Quaternary Geomorphology.

    Science.gov (United States)

    Harwood, Doug

    1987-01-01

    Describes how seminar work can be structured to help students develop skills of critical thinking and expression when discussing controversial issues in their chosen subject. Particular emphasis is given to methods of organizing instructional materials and appropriate roles for seminar leaders. The debate surrounding the existence of a prehistoric…

  20. Before We Were Us, We Were Them: Curating Controversy

    Science.gov (United States)

    Watson, Keri

    2014-01-01

    Prompted by the passage of Alabama House Bill 56, I organized the museum studies course I taught for Auburn University at Montgomery in the 2013 spring semester around an exhibition on immigration. The course offered the opportunity to engage students, faculty, and the community in discussion of an important, timely, and controversial topic.…

  1. Nuclear Deterrence in Cyber-ia: Challenges and Controversies

    Science.gov (United States)

    2016-09-01

    54 | Air & Space Power Journal Nuclear Deterrence in Cyber-ia Challenges and Controversies © Dr. Stephen J. Cimbala* Disclaimer: The views and...into here. 11. Mazanec, “International Order in Cyberspace,” 83. 12. Joel Brenner, Glass Houses: Privacy , Secrecy, and Cyber Insecurity in a Transparent

  2. Taking One's Principles Seriously: A Teacher Confronts Controversy

    Science.gov (United States)

    Hare, William

    2010-01-01

    A teacher faces hostility from certain colleagues who view his decision to attend a controversial lecture as tantamount to the repudiation of the principle of inclusive education and the rights of students with disabilities. The teacher sees the proposed boycott of the lecture as a form of censorship threatening freedom of inquiry and critical…

  3. Race and Genetics: Controversies in Biomedical, Behavioral, and Forensic Sciences

    Science.gov (United States)

    Ossorio, Pilar; Duster, Troy

    2005-01-01

    Among biomedical scientists, there is a great deal of controversy over the nature of race, the relevance of racial categories for research, and the proper methods of using racial variables. This article argues that researchers and scholars should avoid a binary-type argument, in which the question is whether to use race always or never.…

  4. Science and controversy a biography of Sir Norman Lockyer

    CERN Document Server

    Meadows, A

    2008-01-01

    Sir Norman Lockyer left Nature, the world''s leading scientific journal, as his lasting memorial. But his life, and controversial theories, are an important part of science history. His ideas were at the forefront of public debate, and ranged from brilliant to perverse. This entertaining book is a fascinating insight into his eventful life

  5. Ethical Considerations for Psychologists Taking a Public Stance on Controversial Issues: The Balance Between Personal and Professional Life.

    Science.gov (United States)

    Haeny, Angela M

    2014-07-01

    Previous literature has documented the general issues psychologists often face while balancing their personal and professional lives. The struggle stems from attempting to satisfy the need to maintain a life outside of work while having the professional obligation to follow the American Psychological Association's (APA's) Ethical Principles of Psychologists and Code of Conduct (Ethics Code) to prevent their personal lives from interfering with their professional roles and relationships. The present paper analyzes the subject of psychologists taking a public position on controversial public issues. Although the APA Ethics Code does not restrict how psychologists conduct themselves during their personal time, taking a public stance on a controversial issue could potentially strain professional relationships and inadvertently reflect negatively on the profession. The present paper examines ethical issues that a) should be taken into account before psychologists take a public position on a controversial issue, and b) are in conflict with APA's Ethics Code or current research.

  6. Ethical Considerations for Psychologists Taking a Public Stance on Controversial Issues: The Balance Between Personal and Professional Life

    Science.gov (United States)

    Haeny, Angela M.

    2014-01-01

    Previous literature has documented the general issues psychologists often face while balancing their personal and professional lives. The struggle stems from attempting to satisfy the need to maintain a life outside of work while having the professional obligation to follow the American Psychological Association’s (APA’s) Ethical Principles of Psychologists and Code of Conduct (Ethics Code) to prevent their personal lives from interfering with their professional roles and relationships. The present paper analyzes the subject of psychologists taking a public position on controversial public issues. Although the APA Ethics Code does not restrict how psychologists conduct themselves during their personal time, taking a public stance on a controversial issue could potentially strain professional relationships and inadvertently reflect negatively on the profession. The present paper examines ethical issues that a) should be taken into account before psychologists take a public position on a controversial issue, and b) are in conflict with APA’s Ethics Code or current research. PMID:25342876

  7. Risk behaviors, prevalence of HIV and hepatitis C virus infection and population size of current injection drug users in a China-Myanmar border city: results from a Respondent-Driven Sampling Survey in 2012.

    Science.gov (United States)

    Li, Lei; Assanangkornchai, Sawitri; Duo, Lin; McNeil, Edward; Li, Jianhua

    2014-01-01

    Injection drug use has been the major cause of HIV/AIDS in China in the past two decades. We measured the prevalences of HIV and hepatitis C virus (HCV) prevalence and their associated risk factors among current injection drug users (IDUs) in Ruili city, a border region connecting China with Myanmar that has been undergoing serious drug use and HIV spread problems. An estimate of the number of current IDUs is also presented. In 2012, Chinese IDUs who had injected within the past six months and aged ≥ 18 years were recruited using a respondent-driven sampling (RDS) technique. Participants underwent interviews and serological testing for HIV, HBV, HCV and syphilis. Logistic regression indentified factors associated with HIV and HCV infections. Multiplier method was used to obtain an estimate of the size of the current IDU population via combining available service data and findings from our survey. Among 370 IDUs recruited, the prevalence of HIV and HCV was 18.3% and 41.5%, respectively. 27.1% of participants had shared a needle/syringe in their lifetime. Consistent condom use rates were low among both regular (6.8%) and non-regular (30.4%) partners. Factors independently associated with being HIV positive included HCV infection, having a longer history of injection drug use and experience of needle/syringe sharing. Participants with HCV infection were more likely to be HIV positive, have injected more types of drugs, have shared other injection equipments and have unprotected sex with regular sex partners. The estimated number of current IDUs in Ruili city was 2,714 (95% CI: 1,617-5,846). IDUs may continue to be a critical subpopulation for transmission of HIV and other infections in this region because of the increasing population and persistent high risk of injection and sexual behaviours. Developing innovative strategies that can improve accessibility of current harm reduction services and incorporate more comprehensive contents is urgently needed.

  8. Removing Mill Weirs in France: The Structure and Dynamics of an Environmental Controversy

    Directory of Open Access Journals (Sweden)

    Regis Barraud

    2017-10-01

    Full Text Available In France, as in many other parts of Europe and North America, the vast increase in the number of dam removals in order to restore ecological continuity has led to a large number of local conflicts, resulting in a significant ecological controversy. Most of these hydraulic works were connected to former water mills. This article will suggest new analytical methods to help understand and interpret this controversy through the use of two complementary approaches. The first is based on a geohistorical approach. It allows us to identify the development of the meanings and values associated with mill weirs and also to trace the development, since the 19th century, of state involvement in dealing with their ecological impact. Our second method, based on political ecology, attempts to decipher the current state of the controversy. Taking this as our objective we have undertaken a qualitative analysis of the discourse produced on a national level and also of the network of actors who make up the oppositional base to dam removal. The affective and emotional dimensions of the controversy, and also the attachment to local places, both of which are often crucial in the expression of opposition on the local scale, can be identified in the discourse. Yet, the discourse we have analysed reveals argumentative poles which translate both the opposition based on rational arguments and also an alternative vision of the development of rivers (heritage status, green and local power production. The oppositional argument which has been developed notably includes a discussion of the knowledge and scientific expertise upon which the process of dam removal is based. It also includes a critique of local consultation and decision-making methods.

  9. Medical students and controversial ethical issues: results from the multicenter study SBRAME.

    Science.gov (United States)

    Lucchetti, Giancarlo; de Oliveira, Leandro Romani; Leite, José Roberto; Lucchetti, Alessandra Lamas Granero

    2014-12-15

    Medical students(MS) will face ethical issues throughout their lives as doctors. The present study aims to investigate medical students' opinions on controversial ethical issues and factors associated with these opinions. SBRAME (Spirituality and Brazilian Medical Education) is a multicenter study involving 12 Brazilian medical schools with 5950 MS. Participants completed a questionnaire that collected information on socio-demographic data, medical schools characteristics, religious beliefs and opinions on controversial ethical issues. Of all MS, 3630 participated in the survey (61.0%). The sample was 53.8% women and the mean age was 22.5 years. In general, most MS have no objections to prescription of birth control (90.8%), adult stem cell use (87.5%), embryonic stem cell use (82.0%) and abortion for genetic reasons (51.2%). Approximately half of students have no objections to human cloning (47.3%), 45.7% to withdrawal of artificial life support, 41.4% to euthanasia and 23.3% to abortion for failed contraception. Socio-demographic data such as age, gender and income had little influence on MS opinions. On the other hand, medical schools characteristics (number of medical students in the university, year of medical school foundation, location of the university and type of university) and religious aspects (religious affiliation, religious attendance, non-organizational religiousness and intrinsic religiousness) were highly correlated with their opinions. In general, MS with more supportive opinions on controversial ethical issues were less religious and from non-traditional (newer), urban, public and bigger universities. The current study reveals MS have different opinions regarding controversial ethical issues. Noteworthy, these opinions seem to be shaped more by university characteristics and religious beliefs than socio-demographic data.

  10. Science and Social Studies Teachers’ Beliefs and Practices about Teaching Controversial Issues: Certain Comparisons

    Directory of Open Access Journals (Sweden)

    Zafer Kuş

    2015-09-01

    Full Text Available The current study aims to investigate social studies and science teachers’ attitudes and classroom practices associated with controversial issues. The study is a qualitative research based on data collected through interviews and observation. Social studies and Science teachers participated in the current study which was conducted in Kirsehir, a city in the center of Turkey, during the 2012-2013 academic years. Data were collected through classroom observation and interviews with teachers. In this study, teachers' positioning during controversial issues are determined by Kelly's (1986 positioning classification: Exclusive Neutrality, Exclusive Partiality, Neutral Impartiality, and Committed Impartiality. According to results of the research, violence against women, education system, terrorism and nationalism are the leading issues among the controversial issues that both social studies and science teachers listed in Turkey. In relation to their area, social studies teachers stated that the issues such as Kemalism, democracy, military coups, and deep state, which are associated with recent history of Turkey, were among the important controversial issues. Science teachers on the other hand stated issues such as cancer and anti-toxic foods and global warming among the controversial issues in Turkey. Both social studies and science teachers stated that the most frequently encountered problem in discussions was lack of knowledge by students. Whereas social studies teachers stated that their priority goals were particularly to raise active citizens and to set up a democratic classroom environment, science teachers pointed to raising scientifically thinking students and increasing students’ knowledge as their priority goals. During in-class discussions teachers take some positions. The positions stated by the teachers and in-class observations of them conflict. Whereas the teachers stated that they prefer the 4th and 3rd positions, the in

  11. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  12. To Take or Not to Take With Meals? Unraveling Issues Related to Food Effects Labeling for Oral Antineoplastic Drugs.

    Science.gov (United States)

    Deng, Jiexin; Brar, Satjit S; Lesko, Lawrence J

    2017-12-02

    There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models. In 2000-2009, 80% (4 out of 5) of all approved oral antineoplastics with increased bioavailability in the fed state were labeled as "take on empty stomach." In contrast, we found that in 2010-2016 there is a greater diversity in food recommendations for drugs with increased bioavailability in the fed state. Currently, many oral oncology drugs are given with food to maximize their bioavailability; however, as seen from our case study of sonidegib, failure to fully adhere to label recommendations to either take with food or not could lead to adverse consequences in terms of safety and efficacy. © 2017, The American College of Clinical Pharmacology.

  13. Orphan Drug Debate: A Cheat Sheet.

    Science.gov (United States)

    Patel, Krishna R

    2017-06-01

    In some respects, the 1983 Orphan Drug Act is a success story. But high prices and allegations that some drug companies have twisted the law to their advantage have made it controversial. Here are some of the main points in the debate.

  14. New Molecules and Old Drugs as Emerging Approaches to Selectively Target Human Glioblastoma Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Roberto Würth

    2014-01-01

    Full Text Available Despite relevant progress obtained by multimodal treatment, glioblastoma (GBM, the most aggressive primary brain tumor, is still incurable. The most encouraging advancement of GBM drug research derives from the identification of cancer stem cells (CSCs, since these cells appear to represent the determinants of resistance to current standard therapies. The goal of most ongoing studies is to identify drugs able to affect CSCs biology, either inducing selective toxicity or differentiating this tumor cell population into nontumorigenic cells. Moreover, the therapeutic approach for GBM could be improved interfering with chemo- or radioresistance mechanisms, microenvironment signals, and the neoangiogenic process. During the last years, molecular targeted compounds such as sorafenib and old drugs, like metformin, displayed interesting efficacy in preclinical studies towards several tumors, including GBM, preferentially affecting CSC viability. In this review, the latest experimental results, controversies, and prospective application concerning these promising anticancer drugs will be discussed.

  15. AIDS in the workplace: current practices and possible implications.

    Science.gov (United States)

    Nykodym, N; Miners, I A; Simonetti, J L; Patel, N S

    1989-01-01

    The testing of Acquired Immune Deficiency Syndrome (AIDS) remains a political factor. Questions are being raised as to an individual's right to privacy and the public's concern for safety. Despite the controversy, the law protects contagious disease sufferers from employment discrimination. Along with AIDS testing, drug testing remains a controversial issue. Mandatory drug testing remains in both the public and private sectors. Legislative activity in California continues to the present.

  16. Advances and controversies in the management of medullary thyroid carcinoma.

    Science.gov (United States)

    Maia, Ana Luiza; Wajner, Simone Magagnin; Vargas, Carla Vaz Ferreira

    2017-01-01

    Medullary thyroid carcinoma (MTC) comprises approximately 4% of all malignant thyroid neoplasms. Although the majority of patients have a good prognosis, a subgroup of patients develops progressive disease and requires systemic therapy. Here, we focused on the current MTC therapeutic approaches and discussed the advantages and disadvantages of molecular targeted therapies. Targeted molecular therapies that inhibit RET and other tyrosine kinase receptors involved in angiogenesis have been shown to improve progression-free survival in patients with advanced MTC. Two drugs, vandetanib and cabozantinib, have been approved for the treatment of progressive or symptomatic MTC, and several others have exhibited variable efficacy. No tyrosine kinase inhibitor has been shown to improve survival. Although no definitive recommendation can currently be made, cumulative data indicate that knowledge of the tumor mutational profile may facilitate improvements in targeted therapy for MTC. Tyrosine kinase inhibitors are effective therapeutic agents for the treatment of progressive MTC. Nevertheless, it is not clear who will benefit the most from therapy, and the decision regarding when and how to initiate the treatment should be made based on the patient's medical history and tumor behavior. Hopefully, in the near future, molecular profiling of MTC can be used to determine the most effective molecular therapeutic target.

  17. The nuclear controversy as reflected in the daily newspapers

    International Nuclear Information System (INIS)

    Buire, S. van.

    1980-01-01

    The development and utilization of nuclear energy has led to conflicts of larger dimensions in our society. What has been the role of the mass communication media in this discussion. Did they fulfill their duty to inform the public, did they actively foster discussions about the facts to be considered, and did they play their part in public opinion making by publishing critical analyses. These are questions answered by this book by presenting analyses of newspaper articles on the nuclear controversy, facts and figures on the opinions and information published in the daily newspapers on the subject of nuclear energy utilization, and analyses of tendencies pro or contra nuclear energy as expressed by the various articles. By an evaluation of the history of discussions, the development and modifications of the arguments put forward and the reactions shown by the various social groups involved in the process are illustrated and commented in the light of the controversy becoming more acute. (orig./HP) [de

  18. Using deliberation to address controversial issues: Developing Holocaust education curriculum.

    Directory of Open Access Journals (Sweden)

    THOMAS MISCO

    2007-10-01

    Full Text Available This paper explores how a cross-cultural project responded to the need for new Holocaust educational materials for the Republic of Latvia through the method of curriculum deliberation. Analysis of interview, observational, and document data drawn from seven curriculum writers and numerous project members suggest that curriculum deliberation helped awaken a controversial and silenced history while attending to a wide range of needs and concerns for a variety of stakeholders. The findings highlight structural features that empowered the curriculum writers as they engaged in protracted rumination, reflected upon competing norms, and considered the nuances of the curriculum problem in relation to implementation. Understanding the process, challenges, and promises of cross-cultural curriculum deliberation holds significance for educators, curricularists, and educational researchers wishing to advance teaching and learning within silenced histories and controversial issues.

  19. Unconsciously against it. Psychological aspects of the nuclear controversy

    International Nuclear Information System (INIS)

    Wuenschmann, A.

    1980-06-01

    The book deals with the psychological aspects of the nuclear controversy. An attempt is made to describe, in psychological terms, arrange, explain and, in this sense, 'comprehend' the phenomenon of the nuclear controversy in the light of the following facts: - individual and archetypal spectra of associations arising in the minds of many people in combination with the term 'nuclear power plant', the existence of different psychological types; the suggestion and psychological regression in the group. Especially the nuclear opponents, more or less successfully, have used the individual and archetypal association spectrum as an instrument to further their own ends and have thus contributed to the erection of psychological barriers against nuclear power in the minds of many people. (orig./RW) [de

  20. Resolving the controversy over beneficial effects of ionizing radiation

    International Nuclear Information System (INIS)

    Cuttler, J.M.

    1999-01-01

    In spite of the extensive research carried out during the past century, intense controversy continues over the health effects of low-level radiation. This controversy is largely due to political, social and economic issues among scientists and analysts in a variety of disciplines. These issues cloud objectivity and strengthen paradigms. Over the past ten years, in 14 universities and two research institutes, Japanese scientists have conducted exceptional research which clearly demonstrates beneficial effects of low-level radiation and cancer cures following therapy with low doses of radiation. Assessment, replication and extension of this work in North America could lead to greater appreciation of its significance. Cancer patients would demand such treatments, leading to universal acceptance of these bio-positive effects and reducing public fear of nuclear technology. (author)

  1. Behavioural controversy concerning homo economicus: a Humean perspective

    Directory of Open Access Journals (Sweden)

    Khandakar Elahi

    2014-05-01

    Full Text Available In his monumental masterpiece, A Treatise on Human Nature, which explains the methodology of human reasoning concerning matters of fact and describes the roles that passions and morals play in it, Hume arrives at an enormously interesting maxim: An academic controversy cannot continue for long unless the disputants assign different meanings to the major terms employed in the debate. This theory has been applied in this paper to examine the behavioural criticisms about Homo Economicus (HE, the pivotal perception in the neoclassical microeconomic model.To achieve this objective, the paper discusses the origin and evolution of the concept, reviews behavioural criticisms, summarises the main tenets of Hume’s philosophy of human knowledge and finally examines the behavioural opinions from Hume’s perspective. The paper concludes that Hume’s theory convincingly explains the reason why the HE controversy is continuing for over half century- a fact that both the mainstream and behavioural economists are ignoring.

  2. The rocky flats controversy on radionuclide soil action levels

    International Nuclear Information System (INIS)

    Earle, T.C.

    2004-01-01

    This report describes the Rocky Flats radionuclide soil action level controversy as a case study for the purpose of understanding the nature and value of stakeholder involvement in the management of radiological hazards. The report consists of three main sections. The first section outlines the Rocky Flats story, including the Cold War era, the post-Cold War era, and the transition between the two. This provides the context necessary to understand the radionuclide soil action level controversy, the main events of which are described in the second section. In the final section, the Rocky Flats case is briefly discussed within the framework of a general model of stakeholder involvement and the lessons learned from the case are identified. (author)

  3. Nuclear energy: public controversies and the analysis of risks

    International Nuclear Information System (INIS)

    Sills, D.L.

    1984-01-01

    Energy is a social concept, the product of social, economic, and political processes that define certain raw materials as resources and thus convert them into usable energy. Like all social concepts, energy is controversial. Out of a wide range of controversies, three are selected for analysis here: (1) the relationship of nuclear power systems to nuclear weapons proliferation; (2) the risks of terrorism and sabotage associated with the operation of nuclear power facilities, including threats to civil liberties; and (3) the problems associated with the long-term management of radioactive wastes. The final section of the paper describes various modes of analyzing risks and the perception of risks. It is concluded that it may take many decades to learn whether nuclear energy is as natural a source of electrical power as wells are of drinking water, or whether nuclear energy is a horror that mankind in the 1980s or 1990s took a hard look at and then backed away. (author)

  4. Mercury, vaccines, and autism: one controversy, three histories.

    Science.gov (United States)

    Baker, Jeffrey P

    2008-02-01

    The controversy regarding the once widely used mercury-containing preservative thimerosal in childhood vaccines has raised many historical questions that have not been adequately explored. Why was this preservative incorporated in the first place? Was there any real evidence that it caused harm? And how did thimerosal become linked in the public mind to the "autism epidemic"? I examine the origins of the thimerosal controversy and their legacy for the debate that has followed. More specifically, I explore the parallel histories of three factors that converged to create the crisis: vaccine preservatives, mercury poisoning, and autism. An understanding of this history provides important lessons for physicians and policymakers seeking to preserve the public's trust in the nation's vaccine system.

  5. Autonomy, Respect, and Arrogance in the Danish Cartoon Controversy

    OpenAIRE

    Rostbøll, Christian F.

    2009-01-01

    Udgivelsesdato: 2009 Autonomy is increasingly rejected as a fundamental principle by liberal political theorists, because it is regarded as incompatible with respect for diversity. This article seeks, via an analysis of the Danish cartoon controversy, to show that the relationship between autonomy and diversity is more complex than often posited. Particularly, it asks whether the autonomy defense of freedom of expression encourages disrespect for religious feelings. Autonomy leads to disre...

  6. Cooperative Learning, Responsibility, Ambiguity, Controversy and Support in Motivating Students

    Directory of Open Access Journals (Sweden)

    Ronald Brecke, PhD

    2007-08-01

    Full Text Available This paper argues that student motivation is nurtured more by intrinsic rather than extrinsic rewards. Rather than relying on grades alone to stimulate students, this paper explores how engendering a natural critical learning environment can give students a sense of ownership in their own learning and lead to their commitment to that learning. We examine uses of cooperative learning, shared responsibility, ambiguity, controversy and support in student motivation.

  7. Cooperative Learning, Responsibility, Ambiguity, Controversy and Support in Motivating Students

    Directory of Open Access Journals (Sweden)

    Ronald Brecke

    2007-01-01

    Full Text Available This paper argues that student motivation is nurtured more by intrinsic rather than extrinsic rewards. Rather than relying on grades alone to stimulate students, this paper explores how engendering a natural critical learning environment can give students a sense of ownership in their own learning and lead to their commitment to that learning. We examine uses of cooperative learning, shared responsibility, ambiguity, controversy and support in student motivation.

  8. Orthopaedic traumatology: fundamental principles and current controversies for the acute care surgeon

    Science.gov (United States)

    Pharaon, Shad K; Schoch, Shawn; Marchand, Lucas; Mirza, Amer

    2018-01-01

    Multiply injured patients with fractures are co-managed by acute care surgeons and orthopaedic surgeons. In most centers, orthopaedic surgeons definitively manage fractures, but preliminary management, including washouts, splinting, reductions, and external fixations, may be performed by selected acute care surgeons. The acute care surgeon should have a working knowledge of orthopaedic terminology to communicate with colleagues effectively. They should have an understanding of the composition of bone, periosteum, and cartilage, and their reaction when there is an injury. Fractures are usually fixed urgently, but some multiply injured patients are better served with a damage control strategy. Extremity compartment syndrome should be suspected in all critically injured patients with or without fractures and a low threshold for compartment pressure measurements or empiric fasciotomy maintained. Acute care surgeons performing rib fracture fixation and other chest wall injury reconstructions should follow the principles of open fracture reduction and stabilization. PMID:29766123

  9. Orthopaedic traumatology: fundamental principles and current controversies for the acute care surgeon.

    Science.gov (United States)

    Pharaon, Shad K; Schoch, Shawn; Marchand, Lucas; Mirza, Amer; Mayberry, John

    2018-01-01

    Multiply injured patients with fractures are co-managed by acute care surgeons and orthopaedic surgeons. In most centers, orthopaedic surgeons definitively manage fractures, but preliminary management, including washouts, splinting, reductions, and external fixations, may be performed by selected acute care surgeons. The acute care surgeon should have a working knowledge of orthopaedic terminology to communicate with colleagues effectively. They should have an understanding of the composition of bone, periosteum, and cartilage, and their reaction when there is an injury. Fractures are usually fixed urgently, but some multiply injured patients are better served with a damage control strategy. Extremity compartment syndrome should be suspected in all critically injured patients with or without fractures and a low threshold for compartment pressure measurements or empiric fasciotomy maintained. Acute care surgeons performing rib fracture fixation and other chest wall injury reconstructions should follow the principles of open fracture reduction and stabilization.

  10. Current management of gender identity disorder in childhood and adolescence: guidelines, barriers and areas of controversy.

    Science.gov (United States)

    Shumer, Daniel E; Spack, Norman P

    2013-02-01

    The approach to gender identity disorder (GID) in childhood and adolescence has been rapidly evolving and is in a state of flux. In an effort to form management recommendations on the basis of the available literature, The Endocrine Society published clinical practice guidelines in 2009. The guidelines recommend against sex role change in prepubertal children, but they recommend the use of gonadotropin-releasing hormone (GnRH) agonists to suppress puberty in adolescence, and the use of cross-sex hormones starting around age 16 for eligible patients. In actual practice, the approach to GID is quite variable due to continued lack of consensus and specific barriers to treatment that are unique to GID. Recent literature has focused on the mental health approach to prepubertal children with GID and short-term outcomes using pubertal suppression and cross-sex steroids in adolescents with GID. This review will describe the literature published since the release of The Endocrine Society guidelines regarding the management of GID in both children and adolescents.

  11. Gelatin controversies in food, pharmaceuticals, and personal care products: Authentication methods, current status, and future challenges.

    Science.gov (United States)

    Ali, Eaqub; Sultana, Sharmin; Hamid, Sharifah Bee Abd; Hossain, Motalib; Yehya, Wageeh A; Kader, Abdul; Bhargava, Suresh K

    2018-06-13

    Gelatin is a highly purified animal protein of pig, cow, and fish origins and is extensively used in food, pharmaceuticals, and personal care products. However, the acceptability of gelatin products greatly depends on the animal sources of the gelatin. Porcine and bovine gelatins have attractive features but limited acceptance because of religious prohibitions and potential zoonotic threats, whereas fish gelatin is welcomed in all religions and cultures. Thus, source authentication is a must for gelatin products but it is greatly challenging due to the breakdown of both protein and DNA biomarkers in processed gelatins. Therefore, several methods have been proposed for gelatin identification, but a comprehensive and systematic document that includes all of the techniques does not exist. This up-to-date review addresses this research gap and presents, in an accessible format, the major gelatin source authentication techniques, which are primarily nucleic acid and protein based. Instead of presenting these methods in paragraph form which needs much attention in reading, the major methods are schematically depicted, and their comparative features are tabulated. Future technologies are forecasted, and challenges are outlined. Overall, this review paper has the merit to serve as a reference guide for the production and application of gelatin in academia and industry and will act as a platform for the development of improved methods for gelatin authentication.

  12. Do methodological differences account for the current controversy on tissue factor expression in platelets?

    Science.gov (United States)

    Brambilla, Marta; Rossetti, Laura; Zara, Chiara; Canzano, Paola; Giesen, Peter L A; Tremoli, Elena; Camera, Marina

    2018-06-01

    Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets. Data indicate that large-size platelets express significantly higher amount of TF compared to small-size cells, in terms of both TF protein and TF mRNA. Upon stimulation, large platelets readily expose on the cell membrane TF, which is functionally active, i.e., able to generate factor Xa (FXa) as well as thrombin. By contrast, TF activity in small platelets is almost completely quenched by tissue factor pathway inhibitor (TFPI), becoming indeed detectable only after treatment with an anti-TFPI antibody. Our data highlight that particular attention must be paid to the preparation and collection of the PRP since such preanalytical variables may influence the platelet recovery and in turn affect subsequent analysis, whether it is flow cytometry, functional activity tests, proteome, or transcriptome analysis. Indeed, the TF-positive subset of large platelets can easily be lost if centrifugation protocols are not optimized, thus erroneously leading to a false-negative result.

  13. Teaching Creativity: Current Findings, Trends, and Controversies in the Psychology of Creativity

    Science.gov (United States)

    Simonton, Dean Keith

    2012-01-01

    In the past decade, the psychological study of creativity has accelerated greatly. To facilitate the teaching of creativity, I provide an overview of the recent literature. The overview begins by discussing recent empirical results and research trends. This discussion specifically treats creativity's cognitive, differential, developmental, and…

  14. Lung carcinoma: Recent progress and current controversies in small cell limited disease

    International Nuclear Information System (INIS)

    Turrisi, Andrew T.

    1996-01-01

    Objective/Purpose: In 1996 there will be 177,000 new lung cancers and 158,000 deaths. Distant failure is the dominant cause of death for all lung cancer histologies. Radiotherapy produces local control. Local modalities have little influence on survival once resistant cells leave the primary site. A high local failure rate indicates reason to believe that improving local therapy might improve survival. If distant failure dominates, local control improvement may not increase survival. The international lung cancer staging system endorses the use of more surgical therapy in patients with positive lymph nodes. The non-surgical staging: CT, MRI and recently PET scans are not sufficiently precise. The role of systemic staging, surgical and radiographic, will be re-examined in the course. In 1996, state-of-the-art equipment is available in most communities. Important radiotherapy variables are: dose, both total physical dose and the biologic dose, time, treatment breaks, and the use of dose modifying agents (including systemic chemotherapy). Although perhaps flawed, the use of relative scales, nominal standard dose and alpha-beta ratios allow comparison of fraction schemes. The volume of irradiation warrants thoughtful examination. Reasons for margins include: uncertainty of tumor extent, set-up variations, patient motion, and physical dose build-up. It is not clear that post treating expansive nodal volumes have led to increased survival or local control. The reason to treat nodes was based on failure patterns and lymphatic anatomy. This was modeled after Halsted-like notions of 'en bloc' resection and concepts of spread by contiguity. The timing with other modalities is yet another important variable. This includes how the chemotherapy and radiotherapy is integrated: the terms sequential, concurrent and alternating will be discussed. The combined modality therapy may be used early v. delayed. Normal tissue tolerances for critical organs have been based on animal models or clinical observations of whole organ treatment. Little data exists about partial organ tolerance particularly in diseased lungs in patients that have lung cancers. Strategies to investigate partial intolerance will be discussed. Potential roles of chemotherapy will be discussed. Platinum containing chemotherapeutic regimens dominate at this time. There are new agents with novel mechanisms of action including gernatative, the taxanes, top-I inhibitors and vinorelbul. There are still unfavorable interplays with certain chemotherapeutic agents and their combined modality use is questionable. 'Neo-adjuvant chemotherapy' to radiotherapy in Stage IIIA and IIIB will be discussed, and strategies for weekly and daily concurrent platinum with radiotherapy. Prophylactic cranial irradiation, an extremely contentious issue will be outlined. The roles of continuous hyperfractionated accelerated radiotherapy, dose escalation, volume reduction will be explored. Results of randomized trials in small cell, non-small cell, and PCI will be discussed. The role of surgery in stage IIIA will be reviewed

  15. Current controversies in the interpretation of non-accidental head injury

    International Nuclear Information System (INIS)

    Jaspan, Tim

    The field of non-accidental injury (NAI) has been the subject of a number of theories and hypotheses of variable merit. Concerning injuries that occur within the intracranial compartment, much research has been undertaken to investigate the cause of SDH and parenchymal brain injury. Much, however, remains contentious, particularly regarding the medicolegal aspects of suspected child abuse. Issues that present the greatest challenges will be addressed. (orig.)

  16. Current controversies in the interpretation of non-accidental head injury

    Energy Technology Data Exchange (ETDEWEB)

    Jaspan, Tim [Imaging Centre, University Hospital, Nottingham (United Kingdom)

    2008-06-15

    The field of non-accidental injury (NAI) has been the subject of a number of theories and hypotheses of variable merit. Concerning injuries that occur within the intracranial compartment, much research has been undertaken to investigate the cause of SDH and parenchymal brain injury. Much, however, remains contentious, particularly regarding the medicolegal aspects of suspected child abuse. Issues that present the greatest challenges will be addressed. (orig.)

  17. Using International Law to Defuse Current Controversies in the South and East China Seas

    Science.gov (United States)

    2015-02-01

    the Iraq oil embargo, and engaging in human trafficking and prostitution in Europe and Asia. 16F17 Lastly, the FOC system is inherently...trade moves by container—and that trade is concentrated in a few “mega ports”—a single terrorist incident could have major impacts on the world economy ...will import 79 percent of the oil it consumes (22 percent of the world’s demand) by 2030. 58F59 Both Economy and Oystein Tunsio believe that China is

  18. Nuclear power faces up to competition. A textbook on current controversial issues

    International Nuclear Information System (INIS)

    Goering, R.W.; Oesterwind, D.

    1995-01-01

    Nuclear power plants should face up to competition in the energy sector, and nuclear power reactor technology should at last be discussed without bias. The criteria to be applied are: environmental effects, availability, economics, safety and general acceptance. For decades now nuclear power plant operation has been proving to meet the first three of the above criteria. But although the engineered safety concepts and the available operating data proved successful and reliable, the safety philosophy underlying nuclear reactor technology still could not win general acceptance among the population. There have been considerable advances in engineered nuclear safety over the last few years. Reactors have been designed on the basis of a novel safety philosophy. Such novel concepts deserve a new approach for assessment, taking into account the worldwide population explosion, increasing energy consumption, and rising environmental hazards. The book in hand reviews and explains the advanced safety concepts, so that readers can get insight into the safety qualities of novel reactor types and thus criteria for novel assessment. (orig.) [de

  19. Teaching the Evolution of the Mind: Current Findings, Trends, and Controversies in Evolutionary Psychology

    Science.gov (United States)

    Liddle, James R.; Shackelford, Todd K.

    2011-01-01

    As the burgeoning field of evolutionary psychology continues to gain exposure and acceptance throughout the psychological community, it is important to explain this field clearly and accurately to students. This article discusses some recent findings and trends in evolutionary psychological research to aid instructors in their efforts to provide…

  20. Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Charles Rupprecht

    2017-02-01

    Full Text Available Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies. Africa is the likely home to the ancestors of taxa residing within the Genus Lyssavirus, Family Rhabdoviridae. Diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. In terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species today, but for unknown reasons. All mammals are believed to be susceptible to rabies virus infection. Besides reservoirs among the Chiroptera, meso-carnivores also serve as major historical hosts and are represented among the canids, raccoons, skunks, mongooses, and ferret badgers.  Perpetuating as a disease of nature with the mammalian central nervous system as niche, host breadth alone precludes any candidacy for true eradication. Despite having the highest case fatality of any infectious disease and a burden in excess of or comparative to other major zoonoses, rabies remains neglected. Once illness appears, no treatment is proven to prevent death. Paradoxically, vaccines were developed more than a century ago, but the clear majority of human cases are unvaccinated. Tens of millions of people are exposed to suspect rabid animals and tens of thousands succumb annually, primarily children in developing countries, where canine rabies is enzootic. Rather than culling animal populations, one of the most cost-effective strategies to curbing human fatalities is the mass vaccination of dogs. Building on considerable progress to date, several complementary actions are needed in the near future, including a more harmonized approach to viral taxonomy, enhanced de-centralized laboratory-based surveillance, focal pathogen discovery and characterization, applied pathobiological research for therapeutics, improved estimates of canine populations at risk, actual production of required vaccines and related biologics, strategies to maximize prevention but minimize unnecessary human prophylaxis, and a long-term, realistic plan for sustained global program support to achieve success in disease control, prevention, and elimination.