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Sample records for evolving treatment paradigm

  1. Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders.

    Science.gov (United States)

    Mesa, Ruben A

    2007-01-01

    The diagnosis and management of the BCR-ABL-negative myeloproliferative disorders (MPDs) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are at an explosive crossroads of scientific investigation and evolving paradigms since the discovery of the tyrosine kinase-activating JAK2V617F mutation in 2005. Additional discovery of relevant molecular lesions (JAK2 exon 12 mutations and c-MplW515L/K) have only further enriched our understanding of MPD pathogenesis. The improved diagnostic certainty these molecular markers provide have resulted in the modification, and simplification, of the World Health Organization (WHO) diagnostic algorithms for MPDs. Despite these scientific advances, however, the initial management of MPDs continues to rely upon a risk-based strategy to minimize the risk of vascular events with control of erythrocytosis, targeted antiplatelet therapy, and risk-based myelosuppressive therapy. No current medical therapy has altered the natural trend of the MPDs to lead to overt severe myelofibrosis or acute leukemia. Investigations into targeted therapies for MPDs are proceeding at a brisk pace with agents aimed at immunomodulation, decreasing marrow stromal reaction to the aberrant clone, DNA hypomethylation, or the inhibition of tyrosine kinases. Specific inhibition of JAK2 itself appears promising by in vitro investigations, and clinical trials with multiple agents are planned to commence enrollment in 2007. The potential impact of JAK2 inhibitors on the manifestations of the MPDs is unclear, but is awaited with great interest.

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

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

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

  3. Evolving paradigms in the treatment of opioid-induced bowel dysfunction.

    Science.gov (United States)

    Poulsen, Jakob Lykke; Brock, Christina; Olesen, Anne Estrup; Nilsson, Matias; Drewes, Asbjørn Mohr

    2015-11-01

    In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

  4. Diverticular Disease: Traditional and Evolving Paradigms.

    Science.gov (United States)

    Lamanna, Lenore; Moran, Patricia E

    Diverticular disease includes diverticulosis, which are sac protrusions of the intestinal mucosa, and diverticulitis, inflammation of the diverticula. Diverticular disease is listed as one of the top 10 leading physician diagnoses for gastrointestinal disorders in outpatient clinic visits in the United States. There are several classifications of diverticular disease ranging from asymptomatic diverticulosis to diverticulitis with complications. Several theories are linked to the development of diverticula which includes the physiology of the colon itself, collagen cross-linking, and recently challenged, low-fiber intake. The differential diagnoses of lower abdominal pain in addition to diverticular disease have overlapping signs and symptoms, which can make a diagnosis challenging. Identification of the distinct signs and symptoms of each classification will assist the practitioner in making the correct diagnosis and lead to appropriate management. The findings from recent studies have changed the paradigm of diverticular disease. The purpose of this article is to discuss traditional dogma and evolving concepts in the pathophysiology, prevention, and management of diverticular disease. Practitioners must be knowledgeable about diverticular disease for improved outcomes.

  5. Pulmonary Sporotrichosis: An Evolving Clinical Paradigm.

    Science.gov (United States)

    Aung, Ar K; Spelman, Denis W; Thompson, Philip J

    2015-10-01

    In recent decades, sporotrichosis, caused by thermally dimorphic fungi Sporothrix schenckii complex, has become an emerging infection in many parts of the world. Pulmonary infection with S. schenckii still remains relatively uncommon, possibly due to underrecognition. Pulmonary sporotrichosis presents with distinct clinical and radiological patterns in both immunocompetent and immunocompromised hosts and can often result in significant morbidity and mortality despite treatment. Current understanding regarding S. schenckii biology, epidemiology, immunopathology, clinical diagnostics, and treatment options has been evolving in the recent years with increased availability of molecular sequencing techniques. However, this changing knowledge has not yet been fully translated into a better understanding of the clinical aspects of pulmonary sporotrichosis, as such current management guidelines remain unsupported by high-level clinical evidence. This article examines recent advances in the knowledge of sporotrichosis and its application to the difficult challenges of managing pulmonary sporotrichosis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Nonalcoholic fatty liver disease: Evolving paradigms

    Science.gov (United States)

    Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

    2017-01-01

    In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

  7. Evolving conservation paradigms for the Anthropocene

    Science.gov (United States)

    Ariel E. Lugo

    2014-01-01

    The Anthropocene will have fundamental effects on the species composition, function, and structure of the ecosystems of the world. Land management agencies such as the USDA Forest Service will need to adapt their policies and conservation activities to avoid engaging in continuous conflict with natural processes and unfamiliar biotic assemblages. Conservation paradigms...

  8. Evolvable mathematical models: A new artificial Intelligence paradigm

    Science.gov (United States)

    Grouchy, Paul

    We develop a novel Artificial Intelligence paradigm to generate autonomously artificial agents as mathematical models of behaviour. Agent/environment inputs are mapped to agent outputs via equation trees which are evolved in a manner similar to Symbolic Regression in Genetic Programming. Equations are comprised of only the four basic mathematical operators, addition, subtraction, multiplication and division, as well as input and output variables and constants. From these operations, equations can be constructed that approximate any analytic function. These Evolvable Mathematical Models (EMMs) are tested and compared to their Artificial Neural Network (ANN) counterparts on two benchmarking tasks: the double-pole balancing without velocity information benchmark and the challenging discrete Double-T Maze experiments with homing. The results from these experiments show that EMMs are capable of solving tasks typically solved by ANNs, and that they have the ability to produce agents that demonstrate learning behaviours. To further explore the capabilities of EMMs, as well as to investigate the evolutionary origins of communication, we develop NoiseWorld, an Artificial Life simulation in which interagent communication emerges and evolves from initially noncommunicating EMM-based agents. Agents develop the capability to transmit their x and y position information over a one-dimensional channel via a complex, dialogue-based communication scheme. These evolved communication schemes are analyzed and their evolutionary trajectories examined, yielding significant insight into the emergence and subsequent evolution of cooperative communication. Evolved agents from NoiseWorld are successfully transferred onto physical robots, demonstrating the transferability of EMM-based AIs from simulation into physical reality.

  9. Evolving regulatory paradigm for proarrhythmic risk assessment for new drugs.

    Science.gov (United States)

    Vicente, Jose; Stockbridge, Norman; Strauss, David G

    Fourteen drugs were removed from the market worldwide because their potential to cause torsade de pointes (torsade), a potentially fatal ventricular arrhythmia. The observation that most drugs that cause torsade block the potassium channel encoded by the human ether-à-go-go related gene (hERG) and prolong the heart rate corrected QT interval (QTc) on the ECG, led to a focus on screening new drugs for their potential to block the hERG potassium channel and prolong QTc. This has been a successful strategy keeping torsadogenic drugs off the market, but has resulted in drugs being dropped from development, sometimes inappropriately. This is because not all drugs that block the hERG potassium channel and prolong QTc cause torsade, sometimes because they block other channels. The regulatory paradigm is evolving to improve proarrhythmic risk prediction. ECG studies can now use exposure-response modeling for assessing the effect of a drug on the QTc in small sample size first-in-human studies. Furthermore, the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new in vitro paradigm for cardiac safety evaluation of new drugs that provides a more accurate and comprehensive mechanistic-based assessment of proarrhythmic potential. Under CiPA, the prediction of proarrhythmic potential will come from in vitro ion channel assessments coupled with an in silico model of the human ventricular myocyte. The preclinical assessment will be checked with an assessment of human phase 1 ECG data to determine if there are unexpected ion channel effects in humans compared to preclinical ion channel data. While there is ongoing validation work, the heart rate corrected J-T peak interval is likely to be assessed under CiPA to detect inward current block in presence of hERG potassium channel block. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Childhood vitiligo: Treatment paradigms

    Directory of Open Access Journals (Sweden)

    Amrinder Jit Kanwar

    2012-01-01

    Full Text Available Childhood vitiligo differs from the adults by showing a higher incidence in females, segmental vitiligo being more common and less frequent association with other systemic autoimmune and endocrine disorders.Childhood vitiligo is often associated with a marked psychosocial and long lasting effect on the self-esteem of the affected children and their parents, hence an adequate treatment is very essential. Treatment of vitiligo is indeed a tough challenge for the dermatologists′ more so in the background of childhood vitiligo. Although multiple therapeutic modalities are available in the therapeutic armamentarium, not all can be used in children. This brief report updates regarding various therapies available in the treatment of childhood vitiligo.

  11. Osteosarcoma: Evolution of Treatment Paradigms

    Directory of Open Access Journals (Sweden)

    Norman Jaffe

    2013-01-01

    Full Text Available This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success.

  12. Understanding emerging treatment paradigms in rheumatoid arthritis.

    Science.gov (United States)

    Breedveld, Ferdinand C; Combe, Bernard

    2011-05-25

    Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice.

  13. Understanding emerging treatment paradigms in rheumatoid arthritis

    OpenAIRE

    Breedveld, Ferdinand C; Combe, Bernard

    2011-01-01

    Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early ...

  14. Evolving paradigm of illnesses presented to medical Intensive Care Unit in body builders: Cases from tertiary care center.

    Science.gov (United States)

    Garg, Sunil Kumar

    2015-04-01

    Bodybuilding is the use of progressive resistance exercise to control and develop one's musculature. With the rise in number of persons adopting this activity, there is evolving paradigm of illnesses presented to intensive care in this population subset. Strict adherence to details of bodybuilding and avoidance of unsupervised medications are essential to prevent untoward effects.

  15. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly & Cushing Disease Paradigms

    Directory of Open Access Journals (Sweden)

    Michael Anthony Mooney

    2016-07-01

    Full Text Available The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  16. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    Science.gov (United States)

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  17. Current treatment paradigms in rheumatoid arthritis.

    Science.gov (United States)

    Fries, J F

    2000-06-01

    Rheumatoid arthritis (RA) has traditionally been treated using the pyramid approach, in which non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and disease-modifying anti-rheumatic drugs (DMARDs) are introduced relatively late in the disease. This approach is no longer valid. Previously regarded as a benign disease, RA is now recognized as causing substantial morbidity and mortality, as do the NSAIDs used in treatment. DMARDs are more effective in controlling the pain and disability of RA than NSAIDs, and are often no more toxic. The current treatment paradigm emphasizes early, consistent use of DMARDs. A 'sawtooth' strategy of DMARD use has been proposed, in which a rising but low level of disability triggers a change in therapy. Determining the most clinically useful DMARD combinations and the optimal sequence of DMARD use requires effectiveness studies, Bayesian approaches and analyses of long-term outcomes. Such approaches will allow optimization of multiple drug therapies in RA, and should substantially improve the long-term outcome for many patients.

  18. Pediatric facial fractures: evolving patterns of treatment.

    Science.gov (United States)

    Posnick, J C; Wells, M; Pron, G E

    1993-08-01

    This study reviews the treatment of facial trauma between October 1986 and December 1990 at a major pediatric referral center. The mechanism of injury, location and pattern of facial fractures, pattern of facial injury, soft tissue injuries, and any associated injuries to other organ systems were recorded, and fracture management and perioperative complications reviewed. The study population consisted of 137 patients who sustained 318 facial fractures. Eighty-one patients (171 fractures) were seen in the acute stage, and 56 patients (147 fractures) were seen for reconstruction of a secondary deformity. Injuries in boys were more prevalent than in girls (63% versus 37%), and the 6- to 12-year cohort made up the largest group (42%). Most fractures resulted from traffic-related accidents (50%), falls (23%), or sports-related injuries (15%). Mandibular (34%) and orbital fractures (23%) predominated; fewer midfacial fractures (7%) were sustained than would be expected in a similar adult population. Three quarters of the patients with acute fractures required operative intervention. Closed reduction techniques with maxillomandibular fixation were frequently chosen for mandibular condyle fractures and open reduction techniques (35%) for other regions of the facial skeleton. When open reduction was indicated, plate-and-screw fixation was the preferred method of stabilization (65%). The long-term effects of the injuries and the treatment given on facial growth remain undetermined. Perioperative complication rates directly related to the surgery were low.

  19. Evolving understanding and treatment of labour dystocia.

    Science.gov (United States)

    Karaçam, Zekiye; Walsh, Denis; Bugg, George John

    2014-11-01

    The objective of the review is to critically review the diagnosis and management of dystocia in the first stage of labour. We conducted a narrative review of research since 1998. Eight studies were identified, four about the onset and duration of active phase of the first stage of labour, one on the diagnosis of dystocia, and three focused on the treatment of dystocia. The review demonstrates that current understandings of dystocia rest on outdated definitions of active first stage of labour, its progress and on treatments with an equivocal evidence base. These include the cervical dilatation threshold for active first stage, uncertainty over whether a reduced rate of dilatation and reduced strength of uterine contractions always represent pathology and the effectiveness of amniotomy/oxytocin for treating dystocia. Prospective studies should evaluate the impact of defining the active phase of the first stage of labour as commencing at 6 cm dilated and should test this definition in combination with Zhang's revised partogram. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. EVOLVE

    CERN Document Server

    Deutz, André; Schütze, Oliver; Legrand, Pierrick; Tantar, Emilia; Tantar, Alexandru-Adrian

    2017-01-01

    This book comprises nine selected works on numerical and computational methods for solving multiobjective optimization, game theory, and machine learning problems. It provides extended versions of selected papers from various fields of science such as computer science, mathematics and engineering that were presented at EVOLVE 2013 held in July 2013 at Leiden University in the Netherlands. The internationally peer-reviewed papers include original work on important topics in both theory and applications, such as the role of diversity in optimization, statistical approaches to combinatorial optimization, computational game theory, and cell mapping techniques for numerical landscape exploration. Applications focus on aspects including robustness, handling multiple objectives, and complex search spaces in engineering design and computational biology.

  1. Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future DirectionsSummary

    Directory of Open Access Journals (Sweden)

    Luai R. Zarour

    2017-03-01

    Full Text Available In patients with colorectal cancer (CRC that metastasizes to the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. Although new therapeutic regimens developed over the past decade have increased survival, there is substantial room for improvement in selecting targeted treatment regimens for the patients who will derive the most benefit. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem of detecting and treating the metastatic spread of CRC to the liver. Our multidisciplinary group held a state-of-the-science symposium this past year to review advances in this rapidly evolving field. Herein, we present a discussion around the issues facing treatment of patients with CRC liver metastases, including the relationship of discrete gene signatures with prognosis. We also discuss the latest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. As we continue to advance clinically and technologically in the field of colorectal tumor biology, our goal should be continued refinement of predictive and prognostic studies to decrease recurrence after curative resection and minimize treatment toxicity to patients through a tailored multidisciplinary approach to cancer care. Keywords: Colorectal Cancer Liver Metastasis, Biomarkers, Hepatic Arterial Infusion, High-Risk Colorectal

  2. Paradigm shifts in orthodontic treatment with mini-implant anchorage

    Directory of Open Access Journals (Sweden)

    Johnny Joung-Lin Liaw

    2015-01-01

    Full Text Available After the applications of mini-implant anchorage, the envelope of orthodontic treatment was expanded and some treatment modes were changed because of more predictable tooth movement with empowered anchorage. The author tried to share his experience of TADs applications for clarifying the paradigm shifts of orthodontic treatment assisted with the mini-implant anchorage.

  3. Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women.

    Science.gov (United States)

    Rossi, Lorenzo; Pagani, Olivia

    2017-05-01

    In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

  4. [Chronic prostatitis: a new paradigm of treatment].

    Science.gov (United States)

    Bozhedomov, V A

    2016-08-01

    This paper proposes health care recommendations for men with chronic prostatitis (CP) taking into account etiopathogenesis and the clinical presentation of the disease. The proposal is based on the experience of federal and regional clinics of urology and gynecology, respective departments for postgraduate education and on the analysis of scientific literature. It is shown that managing patients with CP requires consideration of factors beyond the traditional practice of urology. The author validates the need to use the modern prostatitis classification UPOINT instead of the traditional NIH NIDDK (1995) to increase the effectiveness of treatment. It is demonstrated that the concurrent use of medications and non-pharmacological treatments aimed at different aspects of the state improve the treatment effectiveness. Indications are refined for medical and non-pharmacological treatments: antibiotics, alpha-blockers, anticholinergic agents, analgesics, antidepressants, herbal remedies, pelvic floor physiotherapy, psychotherapy. The shortcomings and mistakes of existing guidelines/standards are analyzed.

  5. Evolving techniques of diagnosis. Toward establishment of new paradigm for human machine cooperation

    International Nuclear Information System (INIS)

    Kitamura, Masaharu; Takahashi, Makoto; Kanamoto, Shigeru; Saeki, Akira; Washio, Takashi; Ohga, Yukiharu; Furuta, Kazuo; Yoshikawa, Shinji

    1998-01-01

    By monitoring equipments of a plant and state of a process, the diagnostic technique to detect a sign of abnormality properly to identify its reason has often been advanced on a lot of researches in various industrial fields containing atomic force. Some fundamental studies expected for such diagnostic technique to play an important role to keep and improve operational safety of a nuclear plant have been conducted since early period of the nuclear reaction development, but their contents are evolved and changed rapidly, in recent. The technique on the diagnosis was related closely to a statistical analysis method on signal fluctuation component, so-called reactor noise analysis method in early 1980s, but technical innovation step of their recent advancement were remarkable by introduction of new techniques such as chaos theory, wavelet analysis, model base application of expert system, artificial intelligence, and so on at middle of 1980s. And, when diagnosing in the field of atomic force, owing to be required for much high ability, studies on a multi method integration system considered complementary application of a plurality of technical methods and a cooperative method between human and mechanical intelligences, are also forwarded actively faster than those in other industrial areas. In this paper, in each important item, its technical nature and present state of its application to diagnosis are described with their future technical view. (G.K.)

  6. Oropharyngeal cancer and human papilloma virus: evolving diagnostic and management paradigms.

    Science.gov (United States)

    Buckley, Lisa; Gupta, Ruta; Ashford, Bruce; Jabbour, Joe; Clark, Jonathan R

    2016-06-01

    The significant increase in human papilloma virus (HPV)-associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV-associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de-escalation to reduce long-term treatment-associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV-associated OPC; hence, alternative risk stratification and staging classifications are being proposed. © 2015 Royal Australasian College of Surgeons.

  7. Nanotechnology, a new paradigm in atherosclerosis treatment.

    Science.gov (United States)

    Martín Giménez, Virna M; Ruiz-Roso, María Belén; Camargo, Alejandra Beatriz; Kassuha, Diego; Manucha, Walter

    Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Exploring open innovation with a patient focus in drug discovery: an evolving paradigm of patient engagement.

    Science.gov (United States)

    Allarakhia, Minna

    2015-06-01

    It is suggested in this article that patient engagement should occur further upstream during the drug discovery stage. 'Lead patients', namely those patients who are proactive with respect to their health, possess knowledge of their disease and resulting symptoms. They are also well informed about the conventional as well as non-conventional treatments for disease management; and so can provide a nuanced perspective to drug design. Understanding how patients view the management of their diseases and how they view the use of conventional versus non-conventional interventions is of imperative importance to researchers. Indeed, this can provide insight into how conventional treatments might be designed from the outset to encourage compliance and positive health outcomes. Consequently, a continuum of lead patient engagement is employed that focuses on drug discovery processes ranging from participative, informative to collaborative engagement. This article looks at a variety of open innovation models that are currently employed across this engagement spectrum. It is no longer sufficient for industry stakeholders to consider conventional therapies as the only mechanisms being sought after by patients. Without patient engagement, the industry risks being re-prioritized in terms of its role in the patient journey towards not only recovery of health, but also sustained health and wellness before disease onset.

  9. Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm.

    Science.gov (United States)

    Josephy-Hernandez, Sylvia; Jmaeff, Sean; Pirvulescu, Iulia; Aboulkassim, Tahar; Saragovi, H Uri

    2017-01-01

    Neurodegenerative disorders are prevalent, complex and devastating conditions, with very limited treatment options currently available. While they manifest in many forms, there are commonalities that link them together. In this review, we will focus on neurotrophins - a family of related factors involved in neuronal development and maintenance. Neurodegenerative diseases often present with a neurotrophin imbalance, in which there may be decreases in trophic signaling through Trk receptors for example, and/or increases in pro-apoptotic activity through p75. Clinical trials with neurotrophins have continuously failed due to their poor pharmacological properties as well as the unavoidable activation of p75. Thus, there is a need for drugs without such setbacks. Small molecule neurotrophin mimetics are favorable options since they can selectively activate Trks or inactivate p75. In this review, we will initially present a brief outline of how these molecules are synthesized and their mechanisms of action; followed by an update in the current state of neurotrophins and small molecules in major neurodegenerative diseases. Although there has been significant progress in the development of potential therapeutics, more studies are needed to establish clear mechanisms of action and target specificity in order to transition from animal models to the assessment of safety and use in humans. Copyright © 2016. Published by Elsevier Inc.

  10. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

    Science.gov (United States)

    Giovannoni, Gavin

    2018-06-01

    The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

  11. Medically unexplained physical symptoms: toward an alternative paradigm for diagnosis and treatment.

    Science.gov (United States)

    Ballas, Christos A; Staab, Jeffrey P

    2003-12-01

    The treatment of patients with unexplained medical symptoms is difficult because there is neither a clear etiology for the symptoms, nor a useful paradigm with which to understand and treat them. Patients with such symptoms are often referred to psychiatry with vague diagnoses of "somatization" or "hypochondriasis." Rather than considering somatoform diagnoses based on the number or diversity of physical symptoms, evolving research suggests an emphasis on the type of physical symptom as an indicator of Axis I pathology. This article links specific symptomatic complaints, such as chronic pain, chest pain, and dizziness, to the respective Axis I disorders associated with them, such as depression, panic disorder, and anxiety disorders.

  12. Management of the Regional Lymph Nodes Following Breast-Conservation Therapy for Early-Stage Breast Cancer: An Evolving Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Laura E.G. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Punglia, Rinaa S.; Wong, Julia S. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Bellon, Jennifer R., E-mail: jbellon@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2014-11-15

    Radiation therapy to the breast following breast conservation surgery has been the standard of care since randomized trials demonstrated equivalent survival compared to mastectomy and improved local control and survival compared to breast conservation surgery alone. Recent controversies regarding adjuvant radiation therapy have included the potential role of additional radiation to the regional lymph nodes. This review summarizes the evolution of regional nodal management focusing on 2 topics: first, the changing paradigm with regard to surgical evaluation of the axilla; second, the role for regional lymph node irradiation and optimal design of treatment fields. Contemporary data reaffirm prior studies showing that complete axillary dissection may not provide additional benefit relative to sentinel lymph node biopsy in select patient populations. Preliminary data also suggest that directed nodal radiation therapy to the supraclavicular and internal mammary lymph nodes may prove beneficial; publication of several studies are awaited to confirm these results and to help define subgroups with the greatest likelihood of benefit.

  13. Towards new paradigms for the treatment of hypobaric decompression sickness.

    Science.gov (United States)

    Dart, T S; Butler, W

    1998-04-01

    Altitude induced (hypobaric) decompression sickness (DCS) has long been treated with ground level oxygen and U.S. Navy Treatment Tables 5 and 6. These treatment tables originate from surface excursion diving and, when implemented, require significant resource allocation. Although they are effective treatment regimens, these tables were not developed for treating hypobaric DCS which has an etiology similar to saturation diving DCS. In this review, different treatment options for hypobaric DCS are presented. These options include more aggressive use of ground level oxygen and treatment tables using a maximum pressure of 2 atmospheres (ATA). Specific attention is given to USAF Table VIII, an experimental hypobaric DCS treatment-table, and space suit overpressurization treatment. This paradigm shift for DCS treatment is based on a projected increase in hypobaric DCS treatment from exposure to low pressure during several operational conditions: cruise flight in the next generation aircraft (e.g., F-22); high altitude, unpressurized flight by special operations forces; and the extraordinary amount of extravehicular activity (EVA) required to construct the international space station. Anticipating the need to treat DCS encountered during these and other activities, it is proposed that 2 ATA or less hyperbaric oxygen (HBO) treatment conjoined with new collapsible chamber technology can be used to address these issues in a safe and cost effective fashion.

  14. Positive communication paradigm decreases early recurrence in clubfoot treatment.

    Science.gov (United States)

    Morin, Matthew L; Hoopes, Daniel M; Szalay, Elizabeth A

    2014-03-01

    The Ponseti method has become the treatment standard for idiopathic clubfoot. Deformity recurrence is most commonly attributed to premature abandonment of the requisite abduction orthosis. A study in 2009 from our center revealed a high rate of deformity recurrence in our patient population. It was surmised that the importance of bracing to maintain correction had not been adequately communicated to some families, especially Native Americans. As a result, the principal investigator developed a different communication protocol for parents of infants. All children treated for clubfoot at the University of New Mexico Carrie Tingley Hospital, Albuquerque, NM, from 2008 to 2010 were reviewed. They were compared with a historical control group from this institution, the subjects of the 2009 study, and were analyzed for the rate of recurrence and Pirani score improvement. Our study cohort comprised 69 infants (104 clubfeet), all of whom were treated with the new communication style. The recurrence rate for the new communication paradigm was 2.88% compared with 18.2% in the control group (Pgroup compared with 3.5 in the control group (P=0.001). Native American recurrence was zero in the treatment group and 41% in the control group (P=0.011). A positive, rather than a negative communication style, emphasis on the brace as the most important aspect of treatment, and a more culturally sensitive family education paradigm, resulted in a lower rate of deformity recurrence when treating children with clubfeet using the Ponseti method. Level III.

  15. Research Review: Gender identity in youth: treatment paradigms and controversies.

    Science.gov (United States)

    Turban, Jack L; Ehrensaft, Diane

    2017-10-26

    Pediatric gender identity has gained increased attention over the past several years in the popular media, political arena, and medical literature. This article reviews terminology in this evolving field, traditional models of gender identity development and their limitations, epidemiology and natural history of cross-gender identification among children and adolescents, co-occurring conditions and behaviors, research into the biological and psychosocial determinants of cross-gender identification, and research into the options regarding and benefits of clinical approaches to gender incongruent youth. Based on a critical review of the extant literature, both theoretical and empirical, that addresses the issue of pediatric gender identity, the authors synthesized what is presently known and what is in need of further research in order to elucidate the developmental trajectory and clinical needs of gender diverse youth. The field of pediatric gender identity has evolved substantially over the past several years. New research suggests that cross-gender identification is prevalent (approximately 1% of youth). These youth suffer disproportionately high rates of anxiety, depression, and suicidality. Although research into the etiology of cross-gender identification is limited, emerging data have shown that affirmative treatment protocols may improve the high rates of mental health difficulties seen among these patients. The field of pediatric gender identity has evolved dramatically. Emerging data suggest that these patients' high rates of anxiety, depression, and suicidality appear to be improved with affirmative protocols, although future longitudinal data are needed. © 2017 Association for Child and Adolescent Mental Health.

  16. Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

    Science.gov (United States)

    Sirish, Padmini; Li, Ning; Timofeyev, Valeriy; Zhang, Xiao-Dong; Wang, Lianguo; Yang, Jun; Lee, Kin Sing Stephen; Bettaieb, Ahmed; Ma, Sin Mei; Lee, Jeong Han; Su, Demetria; Lau, Victor C; Myers, Richard E; Lieu, Deborah K; López, Javier E; Young, J Nilas; Yamoah, Ebenezer N; Haj, Fawaz; Ripplinger, Crystal M; Hammock, Bruce D; Chiamvimonvat, Nipavan

    2016-05-01

    Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β. This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation. © 2016 American Heart Association, Inc.

  17. Evolving concepts in the treatment of relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Comi, Giancarlo; Radaelli, Marta; Soelberg Sørensen, Per

    2017-01-01

    In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical...... or MRI activity. The choice for therapy is increasingly complex and should be driven by an appropriate knowledge of the mechanisms of action of the different drugs and of their risk-benefit profile. Because the relapsing phase of the disease is characterised by inflammation, treatment should be started...... as early as possible and aim to re-establish the normal complex interactions in the immune system. Before starting a treatment, neurologists should carefully consider the state of the disease, its prognostic factors and comorbidities, the patient's response to previous treatments, and whether the patient...

  18. New guidelines for topical NSAIDs in the osteoarthritis treatment paradigm.

    Science.gov (United States)

    Altman, Roy D

    2010-12-01

    Osteoarthritis (OA), the most common form of arthritis, often affects hands, hips, and knees and involves an estimated 26.9 million US adults. Women have a higher prevalence of OA, and the risk of developing OA increases with age, obesity, and joint malalignment. OA typically presents with pain and reduced function. Therapeutic programs are often multimodal and must take into account pharmaceutical toxicities and patient comorbidities. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with cardiovascular, gastrointestinal, and renal adverse events. Topical NSAIDs offer efficacy with reduced systemic drug exposure. This is a review of current guideline recommendations regarding the use of topical NSAIDs in OA of the hand and knee. Articles were identified by PubMed search (January 1, 2000 to May 21, 2010). Several current guidelines for management of OA recommend topical NSAIDs, indicating them as a safe and effective treatment. One guideline recommends that topical NSAIDs be considered as first-line pharmacologic therapy. A US guideline for knee OA recommends topical NSAIDs in older patients and in patients with increased gastrointestinal risk. The consensus across US and European OA guidelines is that topical NSAIDs are a safe and effective treatment for OA. Because the research base on topical NSAIDs for OA is small, guidelines will continue to evolve.

  19. Evolving role of cetuximab in the treatment of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gunter Schuch

    2009-07-01

    Full Text Available Gunter Schuch, Sebastian Kobold, Carsten BokemeyerDepartment of Oncology, Hematology, and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyAbstract: In recent years, the monoclonal epidermal growth factor receptor (EGFR-targeting antibody cetuximab was introduced into systemic therapy of colorectal cancer and gained an established role in the treatment of this disease. Cetuximab was shown to be active as a single agent in chemorefractory metastatic disease as well as in combination with varying chemotherapies. Recently, randomized trials demonstrated the activity of cetuximab combinations in the first-line setting of metastatic colorectal cancer. Interestingly, the activity of cetuximab was restricted to patients with KRAS wildtype tumors, as was seen with panitumumab, another EGFR antibody. While 60%–70% of tumors harbor KRAS wildtype genes, 30%–40% of tumors express oncogenic KRAS with mutations in codons 12 and 13 causing constitutive activation of signaling cascades downstream of EGFR and resistance to EGFR blockade. Since proof of KRAS wildtype status became a prerequisite for cetuximab treatment, KRAS testing is being established throughout the world. Future trials will address the question which part of the KRAS wildtype cohort will benefit from EGFR inhibition and how to identify those patients. Additionally, new strategies for treatment of KRAS mutated tumors are strongly needed. Recent developments and future strategies will be summarized.Keywords: cetuximab, colorectal cancer, KRAS

  20. Evolving role of cetuximab in the treatment of colorectal cancer

    International Nuclear Information System (INIS)

    Schuch, Gunter; Kobold, Sebastian; Bokemeyer, Carsten

    2009-01-01

    In recent years, the monoclonal epidermal growth factor receptor (EGFR)-targeting antibody cetuximab was introduced into systemic therapy of colorectal cancer and gained an established role in the treatment of this disease. Cetuximab was shown to be active as a single agent in chemorefractory metastatic disease as well as in combination with varying chemotherapies. Recently, randomized trials demonstrated the activity of cetuximab combinations in the first-line setting of metastatic colorectal cancer. Interestingly, the activity of cetuximab was restricted to patients with KRAS wildtype tumors, as was seen with panitumumab, another EGFR antibody. While 60%–70% of tumors harbor KRAS wildtype genes, 30%–40% of tumors express oncogenic KRAS with mutations in codons 12 and 13 causing constitutive activation of signaling cascades downstream of EGFR and resistance to EGFR blockade. Since proof of KRAS wildtype status became a prerequisite for cetuximab treatment, KRAS testing is being established throughout the world. Future trials will address the question which part of the KRAS wildtype cohort will benefit from EGFR inhibition and how to identify those patients. Additionally, new strategies for treatment of KRAS mutated tumors are strongly needed. Recent developments and future strategies will be summarized

  1. Evolving strategies in the treatment of childhood rhabdomyosarcoma. Slovenian experience

    International Nuclear Information System (INIS)

    Pohar-Marinsek, Z.; Anzic, J.; Jereb, B.

    2001-01-01

    Background. Neoadjuvant chemotherapy (Cht) has changed the treatment of rhabdomyosarcoma (RMS) in children. The purpose of our study was to review the children treated for RMS between 1974 and 1996. Patients and methods. Fifty-one children, 1-15 years old, were included. Primary sites of tumour were: head and neck 15, orbit 6, genitourinary 12, extremity 9, torso 5 and paratesticular 4. Twelve patients were in stage I, 10 in stage II, 26 in stage III and 3 in stage IV. Of 43 histologically confirmed RMS 25 were embryonal, 13 alveolar, 1 botryoid, 1 spindle cell and 3 sarcoma NOS. In 8 patients, only fine needle aspiration biopsy (FNAB) was available. All patients had Cht, 29 neoadjuvant, 20 had surgery first, 40 had irradiation (RT), 2 stage IV patients had bone marrow transplant (ABMT). Multidrug Cht varied: VCR, AMD, and cyclophosphamide (VAC) were used in the 1970s, with Adriablastine (T2), methotrexat (MTX) and/or other drugs (T6, T11) in the 1980s, and in the 1990s, cyclophosphamide was replaced by ifosfamide (VAIA). The treatment was started with Cht in orbital and head and neck tumours and in the majority of genitourinary tumours, but surgery was first in paratesticular and in the majority of extremity tumours. Results. The 3 patients with stage IV disease died. Of those with localised tumour, 34 (70%) were alive and well 5 years after treatment, 80% stage I, 75% stage II and 61% stage III. One patient died of heart failure, 3 of Cht toxicity and 1 of intercurrent disease. Conclusions. The survival of our patients has improved during the last 2 decades and increased from 57 % to 70 % for patients treated after 1985. It is now comparable to that in other centres. With the introduction of neoadjuvant Cht, surgery and RT have become more conservative and could sometimes even be abandoned, thereby reducing considerably the risk of late sequels. Orbital, genitourinary and paratesticular embryonal RMS of low stages have very good prognosis. Primary tumours of the

  2. Changing treatment paradigms for the management of inflammatory bowel disease.

    Science.gov (United States)

    Im, Jong Pil; Ye, Byong Duk; Kim, You Sun; Kim, Joo Sung

    2018-01-01

    Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory condition of the gastrointestinal tract causing bowel damage, hospitalizations, surgeries, and disability. Although there has been much progress in the management of IBD with established and evolving therapies, most current approaches have failed to change the natural course. Therefore, the treatment approach and follow-up of patients with IBD have undergone a significant change. Usage of immunosuppressants and/or biologics early during the course of the disease, known as top-down or accelerated step-up approach, was shown to be superior to conventional management in patients who had been recently diagnosed with IBD. This approach can be applied to selected groups based on prognostic factors to control disease activity and prevent progressive disease. Therapeutic targets have been shifted from clinical remission mainly based on symptoms to objective parameters such as endoscopic healing due to the discrepancies observed between symptoms, objectively evaluated inf lammatory activity, and intestinal damage. The concept of treat-to-target in IBD has been supported by population-based cohort studies, post hoc analysis of clinical trials, and meta-analysis, but more evidence is needed to support this concept to be applied to the clinical practice. In addition, individualized approach with tight monitoring of non-invasive biomarker such as C-reactive protein and fecal calprotectin and drug concentration has shown to improve clinical and endoscopic outcomes. An appropriate de-escalation strategy is considered based on patient demographics, disease features, current disease status, and patients' preferences.

  3. Treatment of Children with Speech Oral Placement Disorders (OPDs): A Paradigm Emerges

    Science.gov (United States)

    Bahr, Diane; Rosenfeld-Johnson, Sara

    2010-01-01

    Epidemiological research was used to develop the Speech Disorders Classification System (SDCS). The SDCS is an important speech diagnostic paradigm in the field of speech-language pathology. This paradigm could be expanded and refined to also address treatment while meeting the standards of evidence-based practice. The article assists that process…

  4. 78 FR 56719 - Challenging Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of...

    Science.gov (United States)

    2013-09-13

    ...] Challenging Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Metabolic Diseases... announcing a public workshop entitled ``Changing Regulatory and Reimbursement Paradigms for Medical Devices... registration information on the AGA Web site. If you need special accommodations due to a disability, please...

  5. 78 FR 69694 - Changing Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Obesity...

    Science.gov (United States)

    2013-11-20

    ...] Changing Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Obesity and... Administration (FDA) is announcing a public workshop entitled ``Changing Regulatory and Reimbursement Paradigms... information on the AGA Web site. If you need special accommodations due to a disability, please contact...

  6. Moving towards precision orthodontics: An evolving paradigm shift in the planning and delivery of customized orthodontic therapy.

    Science.gov (United States)

    Jheon, A H; Oberoi, S; Solem, R C; Kapila, S

    2017-06-01

    Advances in precision medicine portend similar progress in orthodontics and will be increasingly harnessed to achieve customized treatment approaches and enhance treatment efficiencies. Our goal is to provide a background on emerging advances in computer technologies and biomedicine and highlight their current and likely future applications to precision orthodontics. A review of orthodontically relevant technologies and advances in pertinent biological research was undertaken. Innovations in computer hardware and software, and 3D imaging technologies offer the ability for customized treatment and biomechanical planning that will be more fully realized within the next few decades. These technologies combined with 3D printing are already being applied to customized appliance fabrication such as aligners and retainers. The future prospects for custom fabrication of orthodontic brackets of appropriate material properties and smart devices are highly desirable and compelling goals. Within biomedicine, the fundamental understanding of cartilage growth and bone biology is currently being tested in animal models to modify mandibular growth and modulate tooth movement, respectively. Some of these discoveries will ultimately have clinical applications in orthodontics including for growth modification, accelerating orthodontic tooth movement, and enhancing anchorage or retention of teeth. Additional genomic and proteomic information will add to further customization of orthodontic diagnosis and treatments. Over the coming decades, precision orthodontics will continue to benefit from advances in many fields and will require the integration of advances in technology, and biomedical and clinical research to deliver optimal, efficient, safe, and reproducible personalized orthodontic treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Realizing a new paradigm in radiation therapy treatment planning

    International Nuclear Information System (INIS)

    Ziegenhein, Peter

    2013-01-01

    This thesis investigates the feasibility of a new IMRT planning paradigm called Interactive Dose Shaping (IDS). The IDS paradigm enables the therapist to directly impose local dose features into the therapy plan. In contrast to the conventional IMRT planning approach, IDS does not employ an objective function to drive an iterative optimization procedure. In the first part of this work, the conventional IMRT plan optimization method is investigated. Concepts for a near-optimal implementation of the planning problem are provided. The second part of this work introduces the IDS concept. It is designed to overcome clinical drawbacks of the conventional method on the one hand and to provide interactive planning strategies which exploit the full potential of modern high-performance computer hardware on the other hand. The realization of the IDS concept consists of three main parts. (1)A two-step Dose Variation and Recovery (DVR) strategy which imposes localized plan features and recovers for unintentional plan modifications elsewhere. (2)A new dose calculation method (3)The design of an IDS planning framework which provides a powerful graphical user interface. It could be shown that the IDS paradigm is able to reproduce conventionally optimized therapy plans and that the IDS concepts can be realized in real-time.

  8. Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy.

    Science.gov (United States)

    Ali, Mohamed A M

    2016-08-01

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the unrestrained expansion of pluripotent hematopoietic stem cells. CML was the first malignancy in which a unique chromosomal abnormality was identified and a pathophysiologic association was suggested. The hallmark of CML is a reciprocal chromosomal translocation between the long arms of chromosomes 9 and 22, t(9; 22)(q34; q11), creating a derivative 9q+ and a shortened 22q-. The latter, known as the Philadelphia (Ph) chromosome, harbors the breakpoint cluster region-abelson (BCR-ABL) fusion gene, encoding the constitutively active BCR-ABL tyrosine kinase that is necessary and sufficient for initiating CML. The successful implementation of tyrosine kinase inhibitors (TKIs) for the treatment of CML remains a flagship for molecularly targeted therapy in cancer. TKIs have changed the clinical course of CML; however, some patients nonetheless demonstrate primary or secondary resistance to such therapy and require an alternative therapeutic strategy. Therefore, the assessment of early response to treatment with TKIs has become an important tool in the clinical monitoring of CML patients. Although mutations in the BCR-ABL have proven to be the most prominent mechanism of resistance to TKIs, other mechanisms-either rendering the leukemic cells still dependent on BCR-ABL activity or supporting oncogenic properties of the leukemic cells independent of BCR-ABL signaling-have been identified. This article provides an overview of the current understanding of CML pathogenesis; recommendations for diagnostic tools, treatment strategies, and management guidelines; and highlights the BCR-ABL-dependent and -independent mechanisms that contribute to the development of resistance to TKIs.

  9. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    DEFF Research Database (Denmark)

    Bygum, Anette

    2014-01-01

    stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...

  10. Organizational issues in stroke treatment: The Swiss paradigm - Stroke units

    Directory of Open Access Journals (Sweden)

    Georgios K Matis

    2013-01-01

    Full Text Available Stroke represents the leading cause of acquired disability in adults and poses a tremendous socioeconomic burden both on patients and the society. In this sense, prompt diagnosis and urgent treatment are needed in order to radically reduce the devastating consequences of this disease. Herein the authors present the new guidelines recently adopted by the Swiss Stroke Society concerning the establishment of stroke units. Standardized treatment and allocation protocols along with an acute rehabilitation concept seem to be the core of the Swiss stroke management system. Coordinated multidisciplinary care provided by specialized medical, nursing and therapy staff is of utmost importance for achieving a significant dependency and death reduction. It is believed that the implementation of these guidelines in the stroke care system would be beneficial not only for the stroke patients, but also for the health system.

  11. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria.

    Science.gov (United States)

    Nicolle, Lindsay E

    2016-04-19

    Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

  12. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria

    Directory of Open Access Journals (Sweden)

    Lindsay E. Nicolle

    2016-04-01

    Full Text Available Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

  13. A new paradigm for heat treatment of alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ustinovshikov, Y., E-mail: ust@ftiudm.ru

    2014-11-25

    Highlights: • The sign of the ordering energy in alloys varies with the temperature. • Each temperature of heating leads to formation of its characteristic microstructure. • Quenching of alloys is a totally unnecessary and useless operation. - Abstract: The article considers the consequences in the field of heat treatment of alloys that could follow the introduction of the concept of phase transition ordering-phase separation into common use. By example of the Fe{sub 50}Cr{sub 50} alloy, industrial carbon tool steel and Ni{sub 88}Al{sub 12} alloy, it is shown that this transition occurs at a temperature, which is definite for each system, that the change of the sign of the chemical interaction between component atoms reverses the direction of diffusion fluxes in alloys, which affects changes in the type of microstructures. The discovery of this phase transition dramatically changes our understanding of the solid solution, changes the ideology of alloy heat treatment. It inevitably leads to the conclusion about the necessity of carrying out structural studies with the help of TEM in order to adjust the phase diagrams of the systems where this phase transition has been discovered. Conclusions have been made that quenching of alloys from the so-called region of the solid solution, which is usually performed before tempering (aging) is a completely unnecessary and useless operation, that the final structure of the alloy is formed during tempering (aging) no matter what the structure was before this heat treatment.

  14. Glioblastoma: background, standard treatment paradigms, and supportive care considerations.

    Science.gov (United States)

    Ellor, Susan V; Pagano-Young, Teri Ann; Avgeropoulos, Nicholas G

    2014-01-01

    Glioblastoma is a brain tumor condition marked by rapid neurological and clinical demise, resulting in disproportionate disability for those affected. Caring for this group of patients is complex, intense, multidisciplinary in nature, and fraught with the need for expensive treatments, surveillance imaging, physician follow-up, and rehabilitative, psychological, and social support interventions. Few of these patients return to the workforce for any meaningful time frame, and because of the enormity of the financial burden that patients, their caregivers, and society face, utilization reviews become the focus of ethical scrutiny. © 2014 American Society of Law, Medicine & Ethics, Inc.

  15. Quest for biomarkers of treatment-resistant depression: shifting the paradigm toward risk

    DEFF Research Database (Denmark)

    Smith, Donald F.

    2013-01-01

    have, however, used a post hoc experimental design that failed to determine the association between biomarkers and the initial risk ofTRD. Particular ttention in future studies should be on shifting the experimental paradigm oward procedures that can determine the risk for developing treatment...

  16. Treatment of off-gas evolved from thermal decomposition of sludge waste

    International Nuclear Information System (INIS)

    Doo-Seong Hwang; Yun-Dong Choi; Gyeong-Hwan Jeong; Jei-Kwon Moon

    2013-01-01

    Korea Atomic Energy Research Institute (KAERI) started a decommissioning program of a uranium conversion plant. The treatment of the sludge waste, which was generated during the operation of the plant, is one of the most important tasks in the decommissioning program of the plant. The major compounds of sludge waste are nitrate salts and uranium. The sludge waste is denitrated by thermal decomposition. The treatment of off-gas evolved from the thermal decomposition of nitrate salts in the sludge waste is investigated. The nitrate salts in the sludge were decomposed in two steps: the first decomposition is due to the ammonium nitrate, and the second is due to the sodium and calcium nitrate and calcium carbonate. The components of off-gas from the decomposition of ammonium nitrate at low temperature are NH 3 , N 2 O, NO 2 , and NO. In addition, the components from the decomposition of sodium and calcium nitrate at high temperature are NO 2 and NO. Off-gas from the thermal decomposition is treated by the catalytic oxidation of ammonia and selective catalytic reduction (SCR). Ammonia is converted into nitrogen oxides through the oxidation catalyst and all nitrogen oxides are removed by SCR treatment besides nitrous oxide, which is greenhouse gas. An additional process is needed to remove nitrous oxide, and the feeding rate of ammonia in SCR should be controlled properly for evolved nitrogen oxides. (author)

  17. Clinical outcomes associated with evolving treatment modalities and radiation techniques for base-of-tongue carcinoma: thirty years of institutional experience

    International Nuclear Information System (INIS)

    Chen, Leechuan Andy; Anker, Christopher J; Hunt, Jason P; Buchmann, Luke O; Grossmann, Kenneth F; Boucher, Kenneth; Fang, Li-Ming Christine; Shrieve, Dennis C; Hitchcock, Ying J

    2015-01-01

    Curative treatment for base-of-tongue squamous cell carcinoma (BOT SCC) has evolved over time; however, comparative outcomes analysis for various treatment strategies is lacking. The authors reviewed the evolution of treatment modality and radiotherapy (RT) technique for 231 consecutive BOT SCC patients at our institution between 1981 and 2011. Treatment modalities included definitive chemoradiotherapy (chemoRT) (42%), definitive RT (33%), surgery followed by RT (20%), and surgery alone (5%). RT techniques included external beam plus interstitial brachytherapy (EBRT + IB) (37%), conventional EBRT (29%), intensity-modulated radiation therapy ± simultaneous integrated boost (IMRT ± SIB) (34%). Clinical characteristics and outcomes were stratified by modality or RT technique. Treatment modality evolved from definitive RT (1980s–1990s) to definitive chemoRT (1990s–2000s). RT technique evolved from EBRT + IB (1980s–1990s) to conventional EBRT (1990s–2000s) to IMRT + SIB (2000s). With median alive follow-up of 6 years (0.3–28 years), the 5-year LC, LRC, and OS rates were 80%, 73%, and 51%. There was no difference in distribution of gender, age, stage among treatment modalities. Definitive chemoRT had improved LRC (HR 1.6) and OS (HR 1.7) compared to definitive RT. IMRT + SIB had improved LRC (HR 3.2), DFS (HR 3.4), and OS (HR 3.0) compared to conventional EBRT. Over the past 30 years, BOT SCC treatment has undergone major paradigm shifts that incorporate nonsurgical functional preservation, concurrent chemotherapy, and advanced RT techniques. Excellent locoregional control and survival outcomes are associated with accelerated IMRT with chemotherapy

  18. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    OpenAIRE

    Tiku, Moti L.; Sabaawy, Hatem E.

    2015-01-01

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates c...

  19. High Risk Aortic Valve Replacement - The Challenges of Multiple Treatment Strategies with an Evolving Technology.

    Science.gov (United States)

    Booth, K; Beattie, R; McBride, M; Manoharan, G; Spence, M; Jones, J M

    2016-01-01

    Deciding on the optimal treatment strategy for high risk aortic valve replacement is challenging. Transcatheter Aortic Valve implantation (TAVI) has been available in our centre as an alternative treatment modality for patients since 2008. We present our early experience of TAVI and SAVR (surgical Aortic Valve Replacement) in high risk patients who required SAVR because TAVI could not be performed. The database for Surgical aortic valve and Transcatheter aortic valve replacement referrals was interrogated to identify relevant patients. Survival to hospital discharge was 95.5% in the forty five patients who had SAVR when TAVI was deemed technically unsuitable. One year survival was 86%. Defining who is appropriate for TAVI or high risk SAVR is challenging and multidisciplinary team discussion has never been more prudent in this field of evolving technology with ever decreasing risks of surgery. The introduction of TAVI at our institution has seen a rise in our surgical caseload by approximately by 25%. Overall, the option of aortic valve intervention is being offered to more patients in general which is a substantial benefit in the treatment of aortic valve disease.

  20. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm

    DEFF Research Database (Denmark)

    Razavi, H; Waked, I; Sarrazin, C

    2014-01-01

    The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total...... number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries...

  1. [Paradigm shift in dentistry for children: from restorative to preventive treatment of caries].

    Science.gov (United States)

    van Amerongen, J P; van Palenstein Helderman, W H

    2010-03-01

    First, the development of dental health care for children in the Netherlands is discussed. Caries prevalence among children has declined sharply. The present situation, however, makes clear that the majority of carious cavities in the temporary dentition remain untreated. This has led to the conclusion that the level of restorative care has to increase. On the basis of new insights in cariology gained in recent decades, the authors of this article argue for abandoning the old paradigm of restorative treatment in favour of prevention in the treatment of caries.

  2. Interstitial laser coagulation in the treatment of benign prostatic hyperplasia using a diode laser system: results of an evolving technology

    NARCIS (Netherlands)

    Mårtenson, A. C.; de la Rosette, J. J. M. C. H.

    1999-01-01

    Interstitial laser coagulation (ILC) treatment is a recent technique in the treatment of BPH that is evolving rapidly. The results of a prospective randomised study vs transurethral resection of the prostate (TURP) is presented as well as results of patients treated with a temperature sensing laser

  3. Naloxegol in opioid-induced constipation: a new paradigm in the treatment of a common problem.

    Science.gov (United States)

    Yoon, Stephanie C; Bruner, Heather C

    2017-01-01

    Opioid-induced constipation (OIC) imposes a significant burden for patients taking pain medications, often resulting in decreased quality of life. Treatment of OIC with traditional medications for functional constipation can be incompletely effective, leading to nonadherence with opioid treatment and undertreated pain. An emerging class of medications that counteract the adverse effects of opioids in the gastrointestinal tract while preserving central nervous system-based pain relief may represent a paradigm shift in the prevention and treatment of OIC. One of these medications, naloxegol, is a once-daily, oral opioid antagonist that is effective, well-tolerated, and approved for treatment of OIC in patients with noncancer pain. More studies are needed to demonstrate this same utility in patients with cancer-related pain.

  4. Changing the Paradigm for the Treatment and Development of New Therapies for FSGS

    Directory of Open Access Journals (Sweden)

    Cathie eSpino

    2016-03-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is a renal pathology finding that represents a constellation of rare kidney diseases which manifest as proteinuria, edema nephrotic syndrome, hypertension and increased risk for kidney failure. Therapeutic options for FSGS are reviewed displaying the expected efficacy from 25 to 69% depending on specific therapy, patient characteristics, cost, and common side effects. This variability in treatment response is likely caused, in part, by the heterogeneity in the etiology and active molecular mechanisms of FSGS. Clinical trials in FSGS have been scant in number and slow to recruit, which may stem, in part, from reliance on classic clinical trial design paradigms. Traditional clinical trial designs based on the learn and confirm paradigm may not be appropriate for rare diseases such as FSGS. Future drug development and testing will require novel approaches to trial designs that have the capacity to enrich study populations as well as adapt the trial in a planned way to gain efficiencies in trial completion timelines. A clinical trial simulation is provided that compares a classical and more modern design to determine the maximum tolerated dose in FSGS.

  5. Membrane paradigm

    International Nuclear Information System (INIS)

    Price, R.H.; Thorne, K.S.

    1986-01-01

    The membrane paradigm is a modified frozen star approach to modeling black holes, with particles and fields assuming a complex, static, boundary-layer type structure (membrane) near the event horizon. The membrane has no effects on the present or future evolution of particles and fields above itself. The mathematical representation is a combination of a formalism containing terms for the shear and bulk viscosity, surface pressure, momentum, temperature, entropy, etc., of the horizon and the 3+1 formalism. The latter model considers a family of three-dimensional spacelike hypersurfaces in one-dimensional time. The membrane model considers a magnetic field threading the hole and undergoing torque from the hole rotation. The field is cleaned by the horizon and distributed over the horizon so that ohmic dissipation is minimized. The membrane paradigm is invalid inside the horizon, but is useful for theoretically probing the properties of slowly evolving black holes

  6. Dextromethorphan in the treatment of early myoclonic encephalopathy evolving into migrating partial seizures in infancy

    Directory of Open Access Journals (Sweden)

    Yin-Hsuan Chien

    2012-05-01

    Full Text Available Epileptic encephalopathy with suppression-burst in electroencephalography (EEG can evolve into a few types of epileptic syndromes. We present here an unusual case of early myoclonic encephalopathy that evolved into migrating partial seizures in infancy. A female neonate initially had erratic myoclonus movements, hiccups, and a suppression-burst pattern in EEG that was compatible with early myoclonic encephalopathy. The seizures were controlled with dextromethorphan (20 mg/kg, and a suppression-burst pattern in EEG was reverted to relatively normal background activity. However, at 72 days of age, alternating focal tonic seizures, compatible with migrating partial seizures in infancy, were demonstrated by the 24-hour EEG recording. The seizures responded poorly to dextromethorphan. To our knowledge, this is the first reported case of early myoclonic encephalopathy evolving into migrating partial seizure in infancy. Whether it represents another age-dependent epilepsy evolution needs more clinical observation.

  7. Naloxegol in opioid-induced constipation: a new paradigm in the treatment of a common problem

    Directory of Open Access Journals (Sweden)

    Yoon SC

    2017-07-01

    Full Text Available Stephanie C Yoon,1 Heather C Bruner2 1Scripps Health and University of California San Diego, Joint Hospice and Palliative Medicine Fellowship, San Diego, 2Department of Medicine, University of California San Diego, Doris A. Howell Palliative Care Service, La Jolla, CA, USA Abstract: Opioid-induced constipation (OIC imposes a significant burden for patients taking pain medications, often resulting in decreased quality of life. Treatment of OIC with traditional medications for functional constipation can be incompletely effective, leading to nonadherence with opioid treatment and undertreated pain. An emerging class of medications that counteract the adverse effects of opioids in the gastrointestinal tract while preserving central nervous system-based pain relief may represent a paradigm shift in the prevention and treatment of OIC. One of these medications, naloxegol, is a once-daily, oral opioid antagonist that is effective, well-tolerated, and approved for treatment of OIC in patients with noncancer pain. More studies are needed to demonstrate this same utility in patients with cancer-related pain. Keywords: opioid-induced constipation, chronic pain, bowel care, peripherally acting mu-opioid-receptor antagonist, OIBD

  8. Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation

    NARCIS (Netherlands)

    Camm, A.J.; Accetta, G.; Ambrosio, G.; Atar, D.; Bassand, J.P.; Berge, E. van de; Cools, F.; Fitzmaurice, D.A.; Goldhaber, S.Z.; Goto, S.; Haas, S.; Kayani, G.; Koretsune, Y.; Mantovani, L.G.; Misselwitz, F.; Oh, S.; Turpie, A.G.G.; Verheugt, F.W.A.; Kakkar, A.K.

    2017-01-01

    OBJECTIVE: We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and >/=1 additional stroke risk factor between 2010 and 2015. METHODS: 39 670 patients were prospectively enrolled in four sequential cohorts in the Global

  9. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    Science.gov (United States)

    Sabaawy, Hatem E.

    2015-01-01

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints. PMID:26029269

  10. Foreign correspondence from Sub-Saharan Africa: An evolving communicational paradigm shift / Corresponsales extranjeros en África Subsahariana: Un paradigma comunicativo en evolución

    Directory of Open Access Journals (Sweden)

    Paulo Nuno Vicente

    2013-11-01

    Full Text Available A sizable portion of our everyday knowledge about Sub-Saharan Africa comes from the work of international news reporters. Even though these news actors play a critical role in the communication of the distant Other, frequently criticized for its representational deficits, scholar empirical research on the work of foreign correspondents has been considerably neglected: it is now decades old, it lacks a systematic examination of the on the ground realities of journalism in Africa and of the evolving work of professionals and Pro-Ams supported by networked digital media. This article analyses the evolving professional cultures and newswork of those individuals (micro. It inspects long-term trajectories in international journalism combined with short-term developments based on transformations on microelectronics and digitization. We conduct the first recorded Pan-African online survey on the work of international news reporters, collecting answers from 124 participants in 41 countries. These findings are complemented by semi-structured interviews with 43 professionals based in Nairobi, Dakar and Johannesburg. Our findings challenge the narrative of international news reporting as a dying breed. Instead, they support a nuanced view towards localized continuities and localized ruptures in contemporary post-industrial mediascape: its socio-demographics express a considerably precarious new economy of foreign correspondence –particularly, in the case of freelance workers– while the use of network-based digital media is driving the field towards the rising of a multilayered confederacy of distinct correspondences.Una parte importante de nuestro conocimiento cotidiano de África al sur del Sahara proviene de la labor de los periodistas internacionales. A pesar de que estos actores desempeñan un papel fundamental en la comunicación sobre los Otros distantes, frecuentemente criticados por su déficit de representación, el trabajo académico de

  11. Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

    Science.gov (United States)

    Hoermann, Rudolf; Midgley, John E. M.; Larisch, Rolf; Dietrich, Johannes W.

    2017-01-01

    In thyroid health, the pituitary hormone thyroid-stimulating hormone (TSH) raises glandular thyroid hormone production to a physiological level and enhances formation and conversion of T4 to the biologically more active T3. Overstimulation is limited by negative feedback control. In equilibrium defining the euthyroid state, the relationship between TSH and FT4 expresses clusters of genetically determined, interlocked TSH–FT4 pairs, which invalidates their statistical correlation within the euthyroid range. Appropriate reactions to internal or external challenges are defined by unique solutions and homeostatic equilibria. Permissible variations in an individual are much more closely constrained than over a population. Current diagnostic definitions of subclinical thyroid dysfunction are laboratory based, and do not concur with treatment recommendations. An appropriate TSH level is a homeostatic concept that cannot be reduced to a fixed range consideration. The control mode may shift from feedback to tracking where TSH becomes positively, rather than inversely related with FT4. This is obvious in pituitary disease and severe non-thyroid illness, but extends to other prevalent conditions including aging, obesity, and levothyroxine (LT4) treatment. Treatment targets must both be individualized and respect altered equilibria on LT4. To avoid amalgamation bias, clinically meaningful stratification is required in epidemiological studies. In conclusion, pituitary TSH cannot be readily interpreted as a sensitive mirror image of thyroid function because the negative TSH–FT4 correlation is frequently broken, even inverted, by common conditions. The interrelationships between TSH and thyroid hormones and the interlocking elements of the control system are individual, dynamic, and adaptive. This demands a paradigm shift of its diagnostic use. PMID:29375474

  12. Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Rudolf Hoermann

    2017-12-01

    Full Text Available In thyroid health, the pituitary hormone thyroid-stimulating hormone (TSH raises glandular thyroid hormone production to a physiological level and enhances formation and conversion of T4 to the biologically more active T3. Overstimulation is limited by negative feedback control. In equilibrium defining the euthyroid state, the relationship between TSH and FT4 expresses clusters of genetically determined, interlocked TSH–FT4 pairs, which invalidates their statistical correlation within the euthyroid range. Appropriate reactions to internal or external challenges are defined by unique solutions and homeostatic equilibria. Permissible variations in an individual are much more closely constrained than over a population. Current diagnostic definitions of subclinical thyroid dysfunction are laboratory based, and do not concur with treatment recommendations. An appropriate TSH level is a homeostatic concept that cannot be reduced to a fixed range consideration. The control mode may shift from feedback to tracking where TSH becomes positively, rather than inversely related with FT4. This is obvious in pituitary disease and severe non-thyroid illness, but extends to other prevalent conditions including aging, obesity, and levothyroxine (LT4 treatment. Treatment targets must both be individualized and respect altered equilibria on LT4. To avoid amalgamation bias, clinically meaningful stratification is required in epidemiological studies. In conclusion, pituitary TSH cannot be readily interpreted as a sensitive mirror image of thyroid function because the negative TSH–FT4 correlation is frequently broken, even inverted, by common conditions. The interrelationships between TSH and thyroid hormones and the interlocking elements of the control system are individual, dynamic, and adaptive. This demands a paradigm shift of its diagnostic use.

  13. POTENTIAL PLACE OF SGLT2 INHIBITORS IN TREATMENT PARADIGMS FOR TYPE 2 DIABETES MELLITUS.

    Science.gov (United States)

    Handelsman, Yehuda

    2015-09-01

    Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms. The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin. Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time. The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.

  14. Same-day {sup 90}Y radioembolization: implementing a new treatment paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Gabr, Ahmed; Kallini, Joseph Ralph; Gates, Vanessa L.; Hickey, Ryan; Desai, Kush; Thornburg, Bartley; Marshall, Karen; Salzig, Krystina; Williams, Melissa; Del Castillo, Carlene; Hohlastos, Elias; Lewandowski, Robert J. [Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Kulik, Laura; Ganger, Daniel [Northwestern University, Department of Medicine, Division of Hepatology, Chicago, IL (United States); Baker, Talia [Northwestern University, Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Chicago, IL (United States); Salem, Riad [Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Northwestern University, Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Chicago, IL (United States); Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Department of Medicine, Division of Hematology and Oncology, Chicago, IL (United States)

    2016-12-15

    To assess the feasibility of conducting pretreatment mesenteric angiography, coil embolization, {sup 99m}Tc macroaggregated albumin ({sup 99m}Tc-MAA) scintigraphy, and {sup 90}Y radioembolization treatment in a single, same-day, combined outpatient encounter. This was a retrospective study of 78 patients treated during the period 2008 - 2015 who were managed in a single outpatient encounter under the guidance of the Interventional Radiology Department and The Nuclear Medicine Department. Pretreatment planning was performed by reviewing baseline imaging and estimated perfused liver volume bearing the tumor. The region of interest was estimated using 3-D software; this value was used for dosimetry planning. Maximum lung shunting fractions of 10 % for hepatocellular carcinoma and 5 % for liver metastases were assumed. Subsequently, hepatic angiography and {sup 99m}Tc-MAA scintigraphy were performed followed by {sup 90}Y treatment in one outpatient encounter. Total in-room procedure time was recorded. All patients underwent same-day angiography, {sup 99m}Tc-MAA scintigraphy and {sup 90}Y radioembolization. Of the 78 patients, 16 received multiple segmental treatments to both lobes, 44 received treatment to the right lobe, and 18 received treatment to the left lobe. The median dose was 106 Gy. The median number of {sup 90}Y vials needed was two (range one to six). The median in-room time was 160 min (75 - 250 min). The residential status of the patients was as follows, 18 % (14/78) were local residents, 55 % (43/78) traveled from outside the city limits, 18 % (14/78) were from out-of-state, and 9 % (7/78) were resident abroad. Of the 78 patients, 61 (77 %) had hepatocellular carcinoma, and 17 (22 %) had liver metastases. The median lung dose was 3.5 Gy. This study demonstrated the feasibility of same-day {sup 90}Y evaluation and treatment while maintaining the principles of safe and effective {sup 90}Y infusion including tumoricidal dosimetry (lobar, segmentectomy

  15. Limited-stage small cell lung cancer: current chemoradiotherapy treatment paradigms.

    Science.gov (United States)

    Stinchcombe, Thomas E; Gore, Elizabeth M

    2010-01-01

    In the U.S., the prevalence of small cell lung cancer (SCLC) is declining, probably reflecting the decreasing prevalence of tobacco use. However, a significant number of patients will receive a diagnosis of SCLC, and approximately 40% of patients with SCLC will have limited-stage (LS) disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for LS-SCLC is concurrent chemoradiotherapy, and the 5-year survival rate observed in clinical trials is approximately 25%. The standard chemotherapy remains cisplatin and etoposide, but carboplatin is frequently used in patients who cannot tolerate or have a contraindication to cisplatin. Substantial improvements in survival have been made through improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred therapy for patients who are appropriate candidates. The optimal timing of concurrent chemoradiotherapy is during the first or second cycle, based on data from meta-analyses. The optimal radiation schedule and dose remain topics of debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8-2.0 Gy daily to a total dose of 60-70 Gy are commonly used treatments. For patients who obtain a near complete or complete response, prophylactic cranial radiation reduces the incidence of brain metastases and improves overall survival. The ongoing Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European and Canadian phase III trials will investigate different radiation treatment paradigms for patients with LS-SCLC, and completion of these trials is critical.

  16. Four evolving strategies in the emergent treatment of acute ischemic stroke.

    Science.gov (United States)

    Thurman, R Jason; Jauch, Edward C; Panagos, Peter D; Reynolds, Matthew R; Mocco, J

    2012-07-01

    Stroke is the leading cause of long-term disability in the United States and is the fourth leading cause of death, affecting nearly 800,000 patients each year. The physical, emotional, and financial toll stroke inflicts on patients and their families cannot be overstated. At the forefront of acute stroke care, emergency clinicians are positioned to have a major impact on the quality of care that stroke patients receive. This issue outlines and reviews the literature on 4 evolving strategies reflecting developing advancements in the care of acute ischemic stroke and their potential to impact patients in the emergency department setting: (1) the expanding window for intravenous rt-PA, (2) the use of multimodal computed tomographic scanning in emergent diagnostic imaging, (3) endovascular therapies for stroke, and (4) stroke systems of care. Whether practicing in a tertiary care environment or in a remote emergency department, emergency clinicians will benefit from familiarizing themselves with these advancements and should consider how these new approaches might influence their management of patients with acute ischemic stroke.

  17. The Protection of Civilians: An Evolving Paradigm?

    Directory of Open Access Journals (Sweden)

    Stuart Gordon

    2013-08-01

    Full Text Available Whilst the protection of civilians (POC in conflict has been a recurring feature of the humanitarian discourse the same has not been true in military doctrines, where the protection of civilians has long been cast in terms of arms bearers upholding their responsibilities under international humanitarian law (IHL. However, opportunities for and pressures on military actors to develop more specific capacities and approaches in this field have grown: partly as a response to the changing nature, location and scope of conflict, particularly the increasing proportion of internal conflicts fought by irregular armed groups in urban environments. It is also a response to the scale and complexity of protection challenges in the Balkans, Rwanda, Darfur and Libya - each of which has clearly demonstrated that threats to civilians are complex and dynamic and that no single international actor is capable of mitigating them without significant support from other institutions (O’Callaghan and Pantuliano, 2007. Despite the enormous growth in opportunities for interaction between militaries and humanitarians there is only a very limited literature on their interaction over protection issues and evaluations of the emerging doctrines. Consequently this article charts the growth in military policies towards POC in the UN, UK, NATO and a range of other states as well as drawing attention to the challenges that still remain in operationalising responses.

  18. Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics.

    Science.gov (United States)

    Robinson, Leslie C; Santagata, Sandro; Hankinson, Todd C

    2016-12-01

    The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors. Dysregulation of epidermal growth factor receptor (EGFR) and of sonic hedgehog (SHH) signaling in ACP suggest that paracrine oncogenic mechanisms may underlie ACP growth and implicate these signaling pathways as potential targets for therapeutic intervention using directed therapies. Recent work shows that ACP cells have primary cilia, further supporting the potential importance of SHH signaling in the pathogenesis of these tumors. While further preclinical data are needed, directed therapies could defer, or replace, the need for radiation therapy and/or allow for less aggressive surgical interventions. Furthermore, the prospect for reliable control of cystic disease without the need for surgery now exists. Studies of papillary craniopharyngioma (PCP) are more clinically advanced than those for ACP. The vast majority of PCPs harbor the BRAF v600e mutation. There are now 2 reports of patients with PCP that had dramatic therapeutic responses to targeted agents. Ongoing clinical and research studies promise to not only advance our understanding of these challenging tumors but to offer new approaches for patient management.

  19. HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Rüveyda Dok

    2016-03-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a highly heterogeneous disease that is the result of tobacco and/or alcohol abuse or infection with high-risk Human papillomaviruses. Despite the fact that HPV positive HNSCC cancers form a distinct clinical entity with better treatment outcome, all HNSCC are currently treated uniformly with the same treatment modality. At present, biologic basis of these different outcomes and their therapeutic influence are areas of intense investigation. In this review, we will summarize the molecular basis for this different outcome, novel treatment opportunities and possible biomarkers for HPV positive HNSCC. In particular, the focus will be on several molecular targeted strategies that can improve the chemoradiation response by influencing DNA repair mechanisms.

  20. An evolving scientific basis for the prevention and treatment of pediatric obesity.

    Science.gov (United States)

    Katzmarzyk, P T; Barlow, S; Bouchard, C; Catalano, P M; Hsia, D S; Inge, T H; Lovelady, C; Raynor, H; Redman, L M; Staiano, A E; Spruijt-Metz, D; Symonds, M E; Vickers, M; Wilfley, D; Yanovski, J A

    2014-07-01

    The 2013 Pennington Biomedical Research Center's Scientific Symposium focused on the treatment and management of pediatric obesity and was designed to (i) review recent scientific advances in the prevention, clinical treatment and management of pediatric obesity, (ii) integrate the latest published and unpublished findings and (iii) explore how these advances can be integrated into clinical and public health approaches. The symposium provided an overview of important new advances in the field, which led to several recommendations for incorporating the scientific evidence into practice. The science presented covered a range of topics related to pediatric obesity, including the role of genetic differences, epigenetic events influenced by in utero development, pre-pregnancy maternal obesity status, maternal nutrition and maternal weight gain on developmental programming of adiposity in offspring. Finally, the relative merits of a range of various behavioral approaches targeted at pediatric obesity were covered, together with the specific roles of pharmacotherapy and bariatric surgery in pediatric populations. In summary, pediatric obesity is a very challenging problem that is unprecedented in evolutionary terms; one which has the capacity to negate many of the health benefits that have contributed to the increased longevity observed in the developed world.

  1. Evolving Knowledge in Pharmacologic Treatments of Age-Related Macular Degeneration.

    Science.gov (United States)

    Soubrane Daguet, Gisèle; Risard-Gasiorowski, Sarah; Massamba, Nathalie

    2016-01-01

    Modern retinal drug therapy is a result of the recent challenges and breakthroughs in chemistry, physics, genetics, cell biology and biotechnologies. Specific pharmaceutical and pharmacokinetic characteristics of a drug are of major importance and contribute to its ability to penetrate targeted ocular tissues in order to result in effective therapeutic concentrations. In addition, the drugs should maintain a prolonged time of activity and be safe with minimal local and systemic toxicity. The transporter vehicle or drug delivery system is crucial in order to enhance ocular tissue penetration and establish controlled drug release. Administration methods should be local, thereby reducing systemic side effects, and, ideally, treatment should be noninvasive. Within the group of so-called classic therapies, the use of pharmacologic treatments has become widespread for most severe retinal diseases. Thereby, ocular therapy of diseases like exudative age-related macular degeneration has improved markedly. Moreover, new metabolic pathways have been identified, new molecules have emerged, new synthesis technologies have been discovered, and new formulae conceived. These developments have opened new avenues for limiting disease progression. © 2016 S. Karger AG, Basel.

  2. Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and Treatment.

    Science.gov (United States)

    Iweala, Onyinye I; Burks, A Wesley

    2016-05-01

    Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.

  3. Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

    Science.gov (United States)

    Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila

    2017-08-01

    Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.

  4. Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars.

    Science.gov (United States)

    Jackisch, Christian; Lammers, Philip; Jacobs, Ira

    2017-04-01

    Human epidermal growth factor receptor 2-positive (HER2+) breast cancer comprises approximately 15%-20% of all breast cancers and is associated with a poor prognosis. The introduction of anti-HER2 therapy has significantly improved clinical outcomes for patients with HER2+ breast cancer, and multiple HER2-directed agents (ie, trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine [T-DM1]) are approved for clinical use in various settings. The treatment landscape for patients with HER2+ breast cancer is continuing to evolve. While novel agents and therapeutic strategies are emerging, biologic therapies, particularly trastuzumab, are likely to remain a mainstay of treatment. However, access issues create barriers to the use of biologics, and there is evidence for underuse of trastuzumab worldwide. A biosimilar is a biologic product that is highly similar to a licensed biologic in terms of product safety and effectiveness. Biosimilars of trastuzumab are in development and may soon become available. The introduction of biosimilars may improve access to anti-HER2 therapies by providing additional treatment options and lower-cost alternatives. Because HER2-targeted drugs may be administered for extended periods of time and in combination with other systemic therapies, biosimilars have the potential to result in significant savings for healthcare systems. Herein we review current and emerging treatment options for, and discuss the possible role of biosimilars in, treating patients with HER2+ breast cancer. Copyright © 2017 Authors, Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.

  5. Paradigm of Unity as a Prospect for Research and Treatment in Psychology

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    Biela Adam

    2014-07-01

    Full Text Available The purpose of this paper is to show the methodological power and potentiality of the concept paradigm of unity introduced originally in the ceremony on the occasion of honoring Chiara Lubich with the doctor honoris causa title by the Catholic University of Lublin in 1996. Originally this conception was used to suggest the societal activity of Chiara Lubich in building, via the Focolari movement, psychosocial infrastructures for unity in various social domains, (for example in the economy of communion, in politics (politicians for unity project, in public media (journalists for unity, in ecumenism and inter-religious contacts (ecumenical and inter-religion Focolari Centers This conception is a kind of a great inspiration (a kind of Copernican revolution in the social sciences which would motivate the social sciences to build their own research paradigm of a type of mental and methodological power and potentiality which could give a new vision of social world (as Copernicus did in natural sciences (Biela, 1996, 2006. Thomas Kuhn (1962 regarded the Copernician revolution as the one which, in the history of science, best illustrates the nature of scientific revolution. The essence of paradigm in a Kuhnian sense is a mentality change in its nature. Copernicus had to change the well-established geocentric system which functioned not only in the science of his day but also in culture, tradition, social perception, and even in the mentality of religious and political authorities. And he did it in a well prepared empirical, methodological and psychological way.

  6. Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies

    Energy Technology Data Exchange (ETDEWEB)

    Muggia, F.M. (NYU Medical Center, New York); Blum, R.H.; Foreman, J.D.

    1984-01-01

    Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages.

  7. Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies

    International Nuclear Information System (INIS)

    Muggia, F.M.; Blum, R.H.; Foreman, J.D.

    1984-01-01

    Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages

  8. Dental Infection and Pregnancy: the Lack of Treatment by the Dental Professional Evolving to a Complex Maxillofacial Infection.

    Science.gov (United States)

    Pereira, Rodrigo Dos Santos; Gomes-Ferreira, Pedro Henrique Silva; Bonardi, João Paulo; Silva, Jonathan Ribeiro da; Latini, Gustavo Lima; Hochuli-Vieira, Eduardo

    2017-11-01

    Infections of the maxillofacial complex caused by caries disease are common in dental practice. The professionals have to have technical knowledge to treat it at the onset of the condition and avoid the spread to deep anatomical spaces of face and neck, which can implicate in a risk of patients' life.In Brazil, current dental professionals usually denied oral surgical treatments in patients with some clinical conditions, not because of fear to resolve it but for lack of knowledge to treat it. An example of these conditionals is pregnancy. It is well known that during the pregnancy period, the patient can be treated in the correct period of gestation. Early diagnosis is crucial for effective therapy in serious infections. The treatment has to be crucial during pregnancy because of the potentially fatal situation that the disease can create to the pregnant woman and the fetus.The aim of this article is to demonstrate a case of dental caries in a pregnant patient, which was evaluated by other professionals and had the treatment denied, evolving to a serious maxillofacial infection.

  9. Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial.

    Science.gov (United States)

    Kubo, Yumi; Sterling, Lulu Ren; Parfrey, Patrick S; Gill, Karminder; Mahaffey, Kenneth W; Gioni, Ioanna; Trotman, Marie-Louise; Dehmel, Bastian; Chertow, Glenn M

    2015-01-01

    Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations.

    Science.gov (United States)

    Ramirez-Zamora, Adolfo; Smith, Heather; Kumar, Vignessh; Prusik, Julia; Phookan, Sujoy; Pilitsis, Julie G

    2016-01-01

    Although thalamic deep brain stimulation (DBS) has been established as an effective therapy for refractory tremor in Parkinson's disease and essential tremor, reports investigating the efficacy of posterior subthalamic area (PSA) DBS for severe, debilitating tremors continue to emerge. However, questions regarding the optimal anatomical target, surgical approach, programming paradigms and effectiveness compared to other targets remain. In this report, we aimed to review the current literature to assess different stereotactic techniques, anatomical considerations, adverse effects and stimulation settings in PSA DBS. A comprehensive literature review was performed searching for articles discussing tremors and PSA stimulation. We performed a quantitative analysis comparing different DBS tremor targets. Tremor improvement is consistently documented in most reports with an average reduction in tremor of 79% depending on the specific tremor syndrome. Tremor benefit in patients with multiple sclerosis (MS) tremor was significantly higher than for other stimulation targets. Transient paresthesias, imbalance, dizziness and dysarthria are the most common side effects with PSA DBS. PSA DBS is an effective and safe treatment for tremor control and should be considered in patients with refractory tremors with associated cerebellar or dystonic features, proximal tremors and MS tremor. © 2016 S. Karger AG, Basel.

  11. Down syndrome and personalized medicine: changing paradigms from genotype to phenotype to treatment.

    Science.gov (United States)

    McCabe, Linda L; McCabe, Edward R B

    2013-03-01

    Personalized Medicine represents a paradigm shift in the conceptual framework of research and clinical care. This shift argues that Down syndrome is a treatable condition, and therefore we must invest in research to improve outcomes. Individuals with Down syndrome have varying levels of increased risk for a number of co-morbidities, including infantile spasms and early onset Alzheimer's disease. We will review research in these associated conditions to show how investigators are attempting to identify biomarkers, including genomic, epigenomic, proteomic and metabolomic "signatures" that will predict who may be at risk to develop a specific co-morbidity prior to onset and will provide novel targets for therapeutic development. This Personalized Medicine approach will permit predictive and preventive approaches for individuals at increased risk for co-morbidities. The support for clinical trials among individuals with Down syndrome is beginning to overcome the "culture of intractability" that has surrounded this disorder. © 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.

  12. WSC-07: Evolving the Web Services Challenge

    NARCIS (Netherlands)

    Blake, M. Brian; Cheung, William K.W.; Jaeger, Michael C.; Wombacher, Andreas

    Service-oriented architecture (SOA) is an evolving architectural paradigm where businesses can expose their capabilities as modular, network-accessible software services. By decomposing capabilities into modular services, organizations can share their offerings at multiple levels of granularity

  13. Has the Introduction of Laparoscopic Heller Myotomy Altered the Treatment Paradigm of Achalasia?

    Directory of Open Access Journals (Sweden)

    Lorenzo E Ferri

    2005-01-01

    Full Text Available Although surgical myotomy is well established as the most effective and durable treatment for achalasia, wide acceptance of this procedure as a first-line treatment has been hampered by perceived invasiveness and morbidity. Laparoscopic myotomy has significantly reduced surgical trauma and morbidity while maintaining effectiveness. The effect of laparoscopic myotomy on the treatment pattern for achalasia is not currently known. All patients undergoing surgical myotomy in Quebec from 1997 to 2002 were identified from the Régie de l'assurance maladie du Québec billing database; previous endoscopic treatment was documented from 1990 to the time of surgery. Patients were divided into two groups (prelaparoscopy and postlaparoscopy defined by the approximate date when laparoscopic myotomy became generally available in Quebec. A questionnaire examining treatment preference for achalasia was sent to all Quebec gastroenterologists. The number of myotomies performed in Quebec remained stable (prelaparoscopy = 28.7/year; postlaparoscopy = 33/year, but were performed on an older population. The rate of preoperative endoscopic treatment did not differ from prelaparoscopy (29.2% to postlaparoscopy (23.3%. However, the time interval between the last endoscopy and myotomy diminished significantly. Questionnaire response rate was 41% (60 of 147. Although myotomy was recognized as the most effective treatment (54 of 60, only 22 of 60 gastroenterologists would refer a healthy patient for myotomy as initial treatment. Other choices included dilation (33 of 60, Botulinum toxin (two of 60 or calcium channel blockade (three of 60. Despite a decrease in time interval between endoscopic treatment and surgery, no decrease in the rate of existing endoscopic therapies occurred after laparoscopic myotomy became widely available. The benefits and minimal risks associated with laparoscopic myotomy need to be more effectively communicated by referring physicians.

  14. Maintaining evolvability.

    Science.gov (United States)

    Crow, James F

    2008-12-01

    Although molecular methods, such as QTL mapping, have revealed a number of loci with large effects, it is still likely that the bulk of quantitative variability is due to multiple factors, each with small effect. Typically, these have a large additive component. Conventional wisdom argues that selection, natural or artificial, uses up additive variance and thus depletes its supply. Over time, the variance should be reduced, and at equilibrium be near zero. This is especially expected for fitness and traits highly correlated with it. Yet, populations typically have a great deal of additive variance, and do not seem to run out of genetic variability even after many generations of directional selection. Long-term selection experiments show that populations continue to retain seemingly undiminished additive variance despite large changes in the mean value. I propose that there are several reasons for this. (i) The environment is continually changing so that what was formerly most fit no longer is. (ii) There is an input of genetic variance from mutation, and sometimes from migration. (iii) As intermediate-frequency alleles increase in frequency towards one, producing less variance (as p --> 1, p(1 - p) --> 0), others that were originally near zero become more common and increase the variance. Thus, a roughly constant variance is maintained. (iv) There is always selection for fitness and for characters closely related to it. To the extent that the trait is heritable, later generations inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these reasons a selected population retains its ability to evolve. Of course, genes with large effect are also important. Conspicuous examples are the small number of loci that changed teosinte to maize, and major phylogenetic changes in the animal kingdom. The relative importance of these along with duplications, chromosome rearrangements, horizontal transmission and polyploidy

  15. The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms.

    Science.gov (United States)

    Willemse, S B; Razavi-Shearer, D; Zuure, F R; Veldhuijzen, I K; Croes, E A; van der Meer, A J; van Santen, D K; de Vree, J M; de Knegt, R J; Zaaijer, H L; Reesink, H W; Prins, M; Razavi, H

    2015-11-01

    Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands.

  16. Transoral incision free fundoplication (TIF – A new paradigm in the surgical treatment of GERD

    Directory of Open Access Journals (Sweden)

    Elliot Goodman

    2010-07-01

    Full Text Available An estimated 10 billion dollars is spent treating gastro-oesophageal reflux disease (GERD in the USA every year. The present article reports a case of the safe and successful use of transoral incisionless fundoplication (TIF using the EsophyX™ device in the surgical treatment of GERD.

  17. Totality of outcomes: A different paradigm in assessing interventions for treatment of tuberculosis

    Directory of Open Access Journals (Sweden)

    Grace Montepiedra

    2016-08-01

    Full Text Available Conventional analytic methods used for tuberculosis (TB outcomes research use standardized outcomes definitions and assess safety and efficacy separately. These methods are subject to important limitations. Conventionally utilized outcome definitions fail to capture important aspects of patients' treatment experience and obscure meaningful differences between patients.Assessing safety and efficacy separately fails to yield an objective risk–benefit comparison to guide clinical practice. We propose to address these issues through an analytic approach based on prioritized outcomes. This approach enables a more comprehensive and integrated assessment of TB interventions. It simultaneously considers a “totality of outcomes”, including clinical benefit, adverse events, and quality of life. These composite outcomes are ranked terms of overall desirability and compared using statistical methods for ordinal outcomes. Here we discuss the application of this approach to TB research, the considerations involved with prioritizing TB treatment outcomes, and the statistical methods involved in comparing prioritized outcomes. Keywords: Tuberculosis, Treatment outcome, Risk–benefit assessment

  18. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

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    Luis Fernando Hernández-Zimbrón

    2018-01-01

    Full Text Available Age-related macular degeneration (AMD is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the “dry” and the “wet” form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1 advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2 this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

  19. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD.

    Science.gov (United States)

    Hernández-Zimbrón, Luis Fernando; Zamora-Alvarado, Ruben; Ochoa-De la Paz, Lenin; Velez-Montoya, Raul; Zenteno, Edgar; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo; Gonzalez-Salinas, Roberto

    2018-01-01

    Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the "dry" and the "wet" form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1) advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2) this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

  20. THE KETOGENIC DIET AS A TREATMENT PARADIGM FOR DIVERSE NEUROLOGICAL DISORDERS

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    Jong Min Rho

    2012-04-01

    Full Text Available Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more natural treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

  1. [Personalized molecular medicine: new paradigms in the treatment of cochlear implant and cancer patients].

    Science.gov (United States)

    Zenner, H P; Pfister, M; Friese, N; Zrenner, E; Röcken, M

    2014-07-01

    To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.

  2. Biomechanical paradigm and interpretation of female pelvic floor conditions before a treatment

    Directory of Open Access Journals (Sweden)

    Lucente V

    2017-08-01

    Full Text Available Vincent Lucente,1 Heather van Raalte,2 Miles Murphy,1 Vladimir Egorov3 1The Institute for Female Pelvic Medicine and Reconstructive Surgery, Allentown, PA, USA; 2Princeton Urogynecology, Princeton, NJ, USA; 3Artann Laboratories, Trenton, NJ, USA Background: Further progress in restoring a woman’s health may be possible if a patient with a damaged pelvic floor could undergo medical imaging and biomechanical diagnostic tests. The results of such tests could contribute to the analysis of multiple treatment options and suggest the optimal one for that patient.Aim: To develop a new approach for the biomechanical characterization of vaginal conditions, muscles, and connective tissues in the female pelvic floor.Methods: Vaginal tactile imaging (VTI allows biomechanical assessment of the soft tissue along the entire length of the anterior, posterior, and lateral vaginal walls at rest, with manually applied deflection pressures and with muscle contraction, muscle relaxation, and Valsalva maneuver. VTI allows a large body of measurements to evaluate individual variations in tissue elasticity, support defects, as well as pelvic muscle function. Presuming that 1 the female pelvic floor organs are suspended by ligaments against which muscles contract to open or close the outlets and 2 damaged ligaments weaken the support and may reduce the force of muscle contraction, we made an attempt to characterize multiple pelvic floor structures from VTI data.Results: All of the 138 women enrolled in the study were successfully examined with the VTI. The study subjects have had normal pelvic support or pelvic organ prolapse (stages I–IV. The average age of this group of subjects was 60±15 years. We transposed a set of 31 VTI parameters into a quantitative characterization of pelvic muscles and ligamentous structures. Interpretation of the acquired VTI data for normal pelvic floor support and prolapse conditions is proposed based on biomechanical assessment of the

  3. Recent Advances in Fractional Laser Resurfacing: New Paradigm in Optimal Parameters and Post-Treatment Wound Care

    Science.gov (United States)

    Hsiao, Francis C.; Bock, Gerald N.; Eisen, Daniel B.

    2012-01-01

    Background Laser plays an increasingly prominent role in skin rejuvenation. The advent of fractional photothermolysis revolutionizes its application. Microcolumns of skin are focally injured, leaving intervening normal skin to facilitate rapid wound healing and orderly tissue remodeling. The Problem Even with the popularity of fractional laser devices, we still have limited knowledge about the ideal treatment parameters and postlaser wound care. Basic/Clinical Science Advances Many clinicians believe that higher microbream energy in fractional laser devices results in better clinical outcome. Two recent studies argue against this assumption. One article demonstrates that lower fluence can induce comparable molecular changes with fewer side effects. Another study corroborates this by showing that lower-density settings produce similar clinical outcome in scar remodeling as higher-density ones, but with fewer side effects. To shed light on the optimal post-treatment wound care regimen from fractional ablative resurfacing, another paper shows that platelet-rich plasma (PRP) can reduce transepidermal water loss and skin color changes within 1 month after treatment. Clinical Care Relevance For fractional nonablative resurfacing, lower settings in fluence or density may produce similar dermal remodeling as higher settings and with a better side-effect profile. Moreover, autologous PRP appears to expedite wound healing after fractional ablative resurfacing. Conclusion Lower microbeam energy in fractional laser resurfacing produces similar molecular changes and clinical outcome with fewer side effects. The findings might portend a shift in the paradigm of treatment parameters. Autologous PRP can facilitate better wound healing, albeit modestly. Long-term follow-ups and larger studies are necessary to confirm these findings. PMID:24527307

  4. Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

    International Nuclear Information System (INIS)

    Scheithauer, Heike R; Schulz, Diana S; Belka, Claus

    2011-01-01

    Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: 'Endometrial cancer', 'Endometrial Neoplasms', 'Endometrial Neoplasms/radiotherapy', 'External beam radiation therapy', 'Brachytherapy' and adequate combinations. Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer

  5. Paradigm shift in cancer treatment: Cancer treatment as a metabolic disease – fusion of Eastern and Western medicine

    Directory of Open Access Journals (Sweden)

    Reo Hamaguchi

    2017-10-01

    Full Text Available Current standard therapies for cancer, including surgery, anti-cancer drugs, and radiotherapy, are thought to contribute to the improvement in the survival rates of cancer patients. However, such standard therapies have 3 major problems: in advanced cancers, it is unlikely that standard cancer treatments will cure the disease; adverse side effects that accompany standard cancer treatments put many patients in distress; and a large amount of medical expenditure is required for new and expensive anti-cancer drugs. These problems may be viewed as a result of establishing treatments without any consideration regarding the root cause of the cancer. Otto Warburg suggested that particular changes in the energy metabolism of cells, which are associated with a shortage of oxygen, are the root cause of cancer. Cancer cells have unique metabolic characteristics, and thus we believe that it is important to treat cancer as a metabolic disease. More specifically, not only is it important to suppress cancer cell metabolism, but it is also important to improve the chronic inflammation that is associated with the development and progression of cancer, and to support the functions of immune cells. This type of view of cancer treatment coincides with the principles of Chinese medicine, which has a history of 4000 years, such as “fuzheng quxie” and “zhibing qiuben”, which can assist in the establishment of cancer treatments for patients. In this article, we discuss cancer treatments from the view of cancer as a metabolic disease and their association with Chinese medicine, and introduce some clinical cases along with a review of the literature.

  6. Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.

    Science.gov (United States)

    Papadia, Andrea; Bellati, Filippo; Ditto, Antonino; Bogani, Giorgio; Gasparri, Maria Luisa; Di Donato, Violante; Martinelli, Fabio; Lorusso, Domenica; Benedetti-Panici, Pierluigi; Raspagliesi, Francesco

    2015-12-01

    Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

  7. A Multiplan Treatment-Planning Framework: A Paradigm Shift for Intensity-Modulated Radiotherapy

    International Nuclear Information System (INIS)

    Meyer, Robert R.; Zhang, Hao H.; Goadrich, Laura; Nazareth, Daryl P.; Shi Leyuan; D'Souza, Warren D.

    2007-01-01

    Purpose: To describe a multiplan intensity-modulated radiotherapy (IMRT) planning framework, and to describe a decision support system (DSS) for ranking multiple plans and modeling the planning surface. Methods and Materials: One hundred twenty-five plans were generated sequentially for a head-and-neck case and a pelvic case by varying the dose-volume constraints on each of the organs at risk (OARs). A DSS was used to rank plans according to dose-volume histogram (DVH) values, as well as equivalent uniform dose (EUD) values. Two methods for ranking treatment plans were evaluated: composite criteria and pre-emptive selection. The planning surface determined by the results was modeled using quadratic functions. Results: The DSS provided an easy-to-use interface for the comparison of multiple plan features. Plan ranking resulted in the identification of one to three 'optimal' plans. The planning surface models had good predictive capability with respect to both DVH values and EUD values and generally, errors of <6%. Models generated by minimizing the maximum relative error had significantly lower relative errors than models obtained by minimizing the sum of squared errors. Using the quadratic model, plan properties for one OAR were determined as a function of the other OAR constraint settings. The modeled plan surface can then be used to understand the interdependence of competing planning objectives. Conclusion: The DSS can be used to aid the planner in the selection of the most desirable plan. The collection of quadratic models constructed from the plan data to predict DVH and EUD values generally showed excellent agreement with the actual plan values

  8. Is It Time to Change the Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain the Foundation Therapy for Type 2 Diabetes.

    Science.gov (United States)

    Inzucchi, Silvio E

    2017-08-01

    Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U.S. However, based on the release of newer agents over the recent past, some have suggested that the modern approach to disease management should be based upon identification of its etiology and correcting the underlying biological disturbances. That is, we should use interventions that normalize or at least ameliorate the recognized derangements in physiology that drive the clinical manifestation of disease, in this circumstance, hyperglycemia. Thus, it is argued that therapeutic interventions that target glycemia but do not correct the underlying pathogenic disturbances are unlikely to result in a sustained benefit on the disease process. In our field, there is an evolving debate regarding the suggested first step in diabetes management and a call for a new paradigm. Given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative that precedes the counterpoint narrative below, Drs. Abdul-Ghani and DeFronzo provide their argument that a treatment approach for type 2 diabetes based upon correcting the underlying pathophysiological abnormalities responsible for the development of hyperglycemia provides the best therapeutic strategy. Such an approach requires a change in the recommendation for first-line therapy from metformin to a GLP-1 receptor agonist. In the counterpoint narrative below, Dr. Inzucchi argues that based on the medical community's extensive experience and the drug

  9. [Change of paradigms in the surgical treatment of complex thoracic aortic disease].

    Science.gov (United States)

    Herold, Ulf; Tsagakis, Konstantinos; Kamler, Markus; Massoudy, Parwis; Assenmacher, Eva; Eggebrecht, Holger; Buck, Thomas; Jakob, Heinz

    2006-08-01

    group. The experience gained with these devices revealed the limitations of the devices designed for pure retrograde aortic delivery. This required a complete redesign and new construction of the stent graft itself as well as the introducer system. In a preliminary series of 14 patients the required stent-graft properties were presented in detail and resulted in the first industrially manufactured standardized and CE-marked Hybrid stent graft (Essen 1 prosthesis, E-vita Open, Jotec), especially made for antegrade open stent grafting of the descending aorta. This device consists of a stent graft with an integrated Dacron vascular prosthesis, enabling for direct and continuous aortic arch replacement after stent grafting of the descending aorta. From 01/2005 to 03/2006, this hybrid prosthesis was implanted in 16 patients (one aneurysm and 15 aortic dissections). In all cases, the underlying pathology within the thoracic aspect of the aorta could be excluded in a one-stage approach. In case of aortic dissection, thrombosis of the false lumen was detectable by transesophageal echocardiography already at the end of surgery. Though long-term results using this new method are not yet available, the initial promising results postoperatively are encouraging toward true one-stage repair by combining classic aortic surgery with open antegrade stent grafting utilizing the newly designed hybrid prosthesis. While surgical trauma is markedly reduced, this treatment option can be offered to elderly patients as well.

  10. A STRATEGY FOR DEVELOPING NEW TREATMENT PARADIGMS FOR NEUROPSYCHIATRIC AND NEUROCOGNITIVE SYMPTOMS IN ALZHEIMER’S DISEASE

    Directory of Open Access Journals (Sweden)

    Hugo eGeerts

    2013-04-01

    Full Text Available Successful disease-modifying drug development for Alzheimer’s disease has hit a roadblock with the recent failures of amyloid-based therapies, highlighting the translational disconnect between preclinical animal models and clinical outcome. Although disease-modifying therapies are the Holy Grail to pursue, symptomatic therapies addressing cognitive and neuropsychiatric aspects of the disease are also extremely important for the quality of life of patients and caregivers. Despite the fact that neuropsychiatric problems in Alzheimer patients are the major driver for costs associated with institutionalization, no good preclinical animal models with predictive validity have been documented. We propose a combination of quantitative systems pharmacology (QSP, phenotypic screening and preclinical animal models as a novel strategy for addressing the bottleneck in both cognitive and neuropsychiatric drug discovery and development for Alzheimer’s disease. Preclinical animal models such as transgene rats documenting changes in neurotransmitters with tau and amyloid pathology will provide key information that together with human imaging, pathology and clinical data will inform the virtual patient model. In this way QSP modeling can partially overcome the translational disconnect and reduce the attrition of drug programs in the clinical setting. This approach is different from target driven drug discovery as it aims to restore emergent properties of the networks and therefore likely will identify multitarget drugs. We review examples on how this hybrid humanized QSP approach has been helpful in predicting clinical outcomes in schizophrenia treatment and cognitive impairment in Alzheimer’s disease and expand on how this strategy could be applied to neuropsychiatric symptoms in dementia. We believe such an innovative approach when used carefully could change the R&D paradigm for symptomatic treatment in Alzheimer’s disease.

  11. Treatment paradigms for advanced stage non-small cell lung cancer in the era of multiple lines of therapy.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2009-02-01

    The duration of first-line and the timing of second-line therapy for advanced non-small cell lung cancer has been an area of recent investigation. Five trials have been performed that have investigated shorter (3-4 cycles) versus longer duration of platinum-based therapy; four trials revealed an equivalent overall survival with the shorter duration of therapy, and one trial revealed superior survival with the longer duration of therapy. The toxicity and quality of life data has either been equivalent or favored the shorter duration of therapy. Two trials have investigated the timing of a second-line therapy after completion of four cycles of platinum-based therapy versus the standard treatment paradigm of initiating second-line therapy upon disease progression. Both of these trials have revealed a statistically significant improvement in the progression-free survival, and a trend towards improved survival for the earlier use of second-line therapy. Only 50 to 60% of patients on the standard treatment arm initiated second-line therapy, and the promising results observed are most likely related to the fact that a higher percentage of patients received second-line therapy on the experimental arm. Several trials have investigated maintenance chemotherapy, and these trials have not revealed a survival benefit probably due to the fact that many patients experience disease progression or unacceptable toxicity during the initial or maintenance therapy. The addition of a targeted agent (bevacizumab or cetuximab) to the initial chemotherapy and the continuation of the targeted agent after completion of the chemotherapy have yielded superior overall survival in comparison to chemotherapy alone. The incremental benefit of the maintenance therapy with the targeted agent is unknown.

  12. Evolving guidelines in the use of topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

    Science.gov (United States)

    Balmaceda, Casilda M

    2014-01-21

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs.

  13. Ovarian cancer survivors' acceptance of treatment side effects evolves as goals of care change over the cancer continuum.

    Science.gov (United States)

    Frey, Melissa K; Ellis, Annie E; Koontz, Laura M; Shyne, Savannah; Klingenberg, Bernhard; Fields, Jessica C; Chern, Jing-Yi; Blank, Stephanie V

    2017-08-01

    Women with ovarian cancer can have long overall survival and goals of treatment change over time from cure to remission to stable disease. We sought to determine whether survivors' acceptance of treatment side effects also changes over the disease continuum. Women with ovarian cancer completed an online survey focusing on survivors' goals and priorities. The survey was distributed through survivor networks and social media. Four hundred and thirty-four women visited the survey website and 328 (76%) completed the survey. Among participants, 141 (43%) identified themselves as having ever recurred, 119 (36%) were undergoing treatment at the time of survey completion and 86 (26%) had received four or more chemotherapy regimens. Respondents' goals of care were cure for 115 women (35%), remission for 156 (48%) and stable disease for 56 (17%). When asked what was most meaningful, 148 women (45%) reported overall survival, 135 (41%) reported quality of life and 40 (12%) reported progression-free survival. >50% of survivors were willing to tolerate the following symptoms for the goal of cure: fatigue (283, 86%), alopecia (281, 86%), diarrhea (232, 71%), constipation (227, 69%), neuropathy (218, 66%), arthralgia (210, 64%), sexual side effects (201, 61%), reflux symptoms (188, 57%), memory loss (180, 55%), nausea/vomiting (180, 55%), hospitalization for treatment side effects (179, 55%) and pain (169, 52%). The rates of tolerance for most symptoms decreased significantly as the goal of treatment changed from cure to remission to stable disease. Women with ovarian cancer willingly accept many treatment side effects when the goal of treatment is cure, however become less accepting when the goal is remission and even less so when the goal is stable disease. Physicians and survivors must carefully consider treatment toxicities and quality of life effects when selecting drugs for patients with incurable disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A New Paradigm for the Treatment of Ovarian Cancer: The Use of Epigenetic Therapy to Sensitize Patients to Immunotherapy and Chemotherapy

    Science.gov (United States)

    2017-10-01

    information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...potently stimulates tumor immune attraction of T-cells to the tumor microenvironment. The treatment paradigm involves a newly regimen we first...Actual or anticipated problems or delays and actions or plans to resolve them None anticipated at this time . We have been moving at a rapid pace during

  15. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF).

    Science.gov (United States)

    McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jianjian; Lefkowitz, Martin; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

    2014-07-01

    To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin-angiotensin-aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction. Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction. The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886-3221 pg/mL). PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction. © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  16. Novel and evolving therapies in the treatment of malignant phaeochromocytoma: experience with the mTOR inhibitor everolimus (RAD001).

    Science.gov (United States)

    Druce, M R; Kaltsas, G A; Fraenkel, M; Gross, D J; Grossman, A B

    2009-09-01

    Phaeochromocytoma and paraganglioma are rare neuroendocrine tumours (NETS). They may be benign or malignant but the pathological distinction is mainly made when metastases are present. Available treatments in the form of surgery, chemotherapy, and radionuclide therapy may improve symptoms and biochemical markers, but the results for the control of tumour bulk are less favourable. Furthermore, responses to treatment are frequently short-lived. This short review outlines the main molecular and histological features of malignant phaeochromocytoma and the difficulties in differentiating between benign and malignant disease. We list current therapies used for malignant pheochromocytoma; however, these generally achieve relatively low success rates. Hence, there is a need for new and more effective therapies. In vitro studies have implicated the PI3/Akt/mTOR pathway in the pathogenesis of malignant NETS, including phaeochromocytoma. Everolimus (RAD001, Novartis UK) is a compound that inhibits mTOR (mammalian Target Of Rapamycin) signalling. We have used RAD001 in four patients with progressive malignant paraganglioma/phaeochromocytoma in addition to other therapies (with institutional approval for compassionate use), and evaluated the effects of this treatment. We outline these four cases and review the theoretical background for this therapy, although the outcomes were relatively disappointing.

  17. Designing Garments to Evolve Over Time

    DEFF Research Database (Denmark)

    Riisberg, Vibeke; Grose, Lynda

    2017-01-01

    This paper proposes a REDO of the current fashion paradigm by investigating how garments might be designed to evolve over time. The purpose is to discuss ways of expanding the traditional role of the designer to include temporal dimensions of creating, producing and using clothes and to suggest...... to a REDO of design education, to further research and the future fashion and textile industry....

  18. Evolving Role of Endoscopic Retrograde Cholangiopancreatography in Management of Extrahepatic Hepatic Ductal Injuries due to Blunt Trauma: Diagnostic and Treatment Algorithms

    Directory of Open Access Journals (Sweden)

    Nikhil P. Jaik

    2008-01-01

    Full Text Available Extrahepatic hepatic ductal injuries (EHDIs due to blunt abdominal trauma are rare. Given the rarity of these injuries and the insidious onset of symptoms, EHDI are commonly missed during the initial trauma evaluation, making their diagnosis difficult and frequently delayed. Diagnostic modalities useful in the setting of EHDI include computed tomography (CT, abdominal ultrasonography (AUS, nuclear imaging (HIDA scan, and cholangiography. Traditional options in management of EHDI include primary ductal repair with or without a T-tube, biliary-enteric anastomosis, ductal ligation, stenting, and drainage. Simple drainage and biliary decompression is often the most appropriate treatment in unstable patients. More recently, endoscopic retrograde cholangiopancreatography (ERCP allowed for diagnosis and potential treatment of these injuries via stenting and/or papillotomy. Our review of 53 cases of EHDI reported in the English-language literature has focused on the evolving role of ERCP in diagnosis and treatment of these injuries. Diagnostic and treatment algorithms incorporating ERCP have been designed to help systematize and simplify the management of EHDI. An illustrative case is reported of blunt traumatic injury involving both the extrahepatic portion of the left hepatic duct and its confluence with the right hepatic duct. This injury was successfully diagnosed and treated using ERCP.

  19. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  20. Three paradigms of horror

    Directory of Open Access Journals (Sweden)

    Dejan Ognjanović

    2016-07-01

    Full Text Available Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the individual psyche, in the split, deceived, or in some other way unreliable self which is, consciously or unconsciously, harmful to others, and ultimately to itself. Paradigm 2 deals with the “Fear of others”: the root of fear is outside and is concerned with other people and other creatures which have an urge to occupy a certain human microcosm. Paradigm 3 is concerned with the “Fear of the numinous”: the root of the fear is mostly situated on the outside; however its shape is amorphous, ambivalent and unknowable. The “monster” is faceless; it touches on primary forces of the divine/demonic, and as such is situated on the very border between inside/outside. All three paradigms, with their main approaches and constitutive elements, are modulated through two basic possible treatments: the conservative and the progressive (liberal, which affords a total of six basic variations of horror. Starting from definitions given by John Carpenter, Robin Wood and his own, the author analyzes representative examples from horror literature and film for each paradigm and its variation, with a special accent on the image of Otherness and its connection to the norm, its intrusion into the status quo, anthropocentrism and the presence or absence of a happy ending. The paper demonstrates the richness of connotative potential within the horror genre and provides a basis for its taxonomy.

  1. Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments

    Science.gov (United States)

    Bosch, Jaume; Groszmann, Roberto J.; Shah, Vijay H.

    2015-01-01

    Summary Among the common complication of cirrhosis portal hypertension witnessed a major improvement of prognosis during the past decades. Principally due to the introduction of rational treatments based on new pathophysiological paradigms (concepts of thought) developed in the 1980s. The best example being the use of non-selective beta-blockers and of vasopressin analogs, somatostatin, and its analogs. Further refinement in the knowledge of the molecular mechanisms involved in the regulation of both the splanchnic and hepatic circulation has led to the emergence of new treatments, which are based on evidence that show not only structural but also vasoactive components increase the hepatic vascular resistance, as well as of angiogenesis. This knowledge and future improvements will most likely result in more effective treatment of portal hypertension and effective prevention of its complications in early stages. PMID:25920081

  2. A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health

    Directory of Open Access Journals (Sweden)

    Kendall-Tackett Kathleen

    2007-03-01

    Full Text Available Abstract Background Research in the field of psychoneuroimmunology (PNI has revealed that depression is associated with inflammation manifested by increased levels of proinflammatory cytokines. Discussion The old paradigm described inflammation as simply one of many risk factors for depression. The new paradigm is based on more recent research that has indicated that physical and psychological stressors increase inflammation. These recent studies constitute an important shift in the depression paradigm: inflammation is not simply a risk factor; it is the risk factor that underlies all the others. Moreover, inflammation explains why psychosocial, behavioral and physical risk factors increase the risk of depression. This is true for depression in general and for postpartum depression in particular. Puerperal women are especially vulnerable to these effects because their levels of proinflammatory cytokines significantly increase during the last trimester of pregnancy – a time when they are also at high risk for depression. Moreover, common experiences of new motherhood, such as sleep disturbance, postpartum pain, and past or current psychological trauma, act as stressors that cause proinflammatory cytokine levels to rise. Breastfeeding has a protective effect on maternal mental health because it attenuates stress and modulates the inflammatory response. However, breastfeeding difficulties, such as nipple pain, can increase the risk of depression and must be addressed promptly. Conclusion PNI research suggests two goals for the prevention and treatment of postpartum depression: reducing maternal stress and reducing inflammation. Breastfeeding and exercise reduce maternal stress and are protective of maternal mood. In addition, most current treatments for depression are anti-inflammatory. These include long-chain omega-3 fatty acids, cognitive therapy, St. John's wort, and conventional antidepressants.

  3. PARADIGMS IN CONSUMER BEHAVIOR

    OpenAIRE

    Sabrina Oktoria Sihombing

    2011-01-01

    A paradigm influences what we see and conceive about certain facts. Paradigm can also influence what we accept as a truth. Yet, the debate over which paradigm and methodology is best suit for marketing and consumer behavior has begun since 1980s. Many researchers criticized the domination of logical empiricism paradigm and offered alternative paradigm to understand marketing and consumer behavior. This article discusses several paradigms and methodology, which are part of qualitative paradigm...

  4. PARADIGMS IN CONSUMER BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Sabrina Oktoria Sihombing

    2011-05-01

    Full Text Available A paradigm influences what we see and conceive about certain facts. Paradigm can also influence what we accept as a truth. Yet, the debate over which paradigm and methodology is best suit for marketing and consumer behavior has begun since 1980s. Many researchers criticized the domination of logical empiricism paradigm and offered alternative paradigm to understand marketing and consumer behavior. This article discusses several paradigms and methodology, which are part of qualitative paradigm, and compares them with positivism paradigm. This article will also point to the importance of reconciliation between qualitative and quantitative paradigm in order to improve marketing and consumer behavior studies.

  5. Gynecomastia: evolving paradigm of management and comparison of techniques.

    Science.gov (United States)

    Petty, Paul M; Solomon, Matthias; Buchel, Edward W; Tran, Nho V

    2010-05-01

    Since 1997, the authors have used a minimally invasive technique for the management of gynecomastia using ultrasound-assisted liposuction and the arthroscopic shaver to remove breast tissue through a remote incision. This technique has allowed for a consistent, refined, "unoperated" postoperative appearance in this patient population. This study analyzes the outcomes of this procedure and compares the procedure against established techniques. A retrospective study was performed on all patients who underwent surgery for gynecomastia at the authors' institution between January of 1988 and October of 2007. A total of 227 patients were divided into four groups: group 1, open excision only (n = 45); group 2, open excision plus liposuction (n = 56); group 3, liposuction only (n = 50); and group 4, liposuction plus arthroscopic shaver (n = 76). Medical records and photographs were used to compare groups for complications and results. Complications using the liposuction plus arthroscopic shaver technique included seroma (n = 2), hematoma (n = 1), scar revision (n = 1), and skin buttonhole from the arthroscopic shaver (n = 1). There was no difference between groups in the overall incidence of complications (p liposuction plus arthroscopic shaver) had the overall highest mean score, with statistical significance between group 2 (open excision plus liposuction) and group 4 (p gynecomastia is a safe and effective technique, with excellent cosmetic results and an acceptable complication rate.

  6. Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

    Science.gov (United States)

    Willis, Rudolph E.

    2016-01-01

    It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

  7. The evolving war on cancer.

    Science.gov (United States)

    Haber, Daniel A; Gray, Nathanael S; Baselga, Jose

    2011-04-01

    Building on years of basic scientific discovery, recent advances in the fields of cancer genetics and medicinal chemistry are now converging to revolutionize the treatment of cancer. Starting with serendipitous observations in rare subsets of cancer, a paradigm shift in clinical research is poised to ensure that new molecular insights are rapidly applied to shape emerging cancer therapies. Could this mark a turning point in the "War on Cancer"? Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Long-term prognosis of young breast cancer patients (≤40 years) who did not receive adjuvant systemic treatment: protocol for the PARADIGM initiative cohort study.

    Science.gov (United States)

    Dackus, Gwen Mhe; Ter Hoeve, Natalie D; Opdam, Mark; Vreuls, Willem; Varga, Zsuzsanna; Koop, Esther; Willems, Stefan M; Van Deurzen, Carolien Hm; Groen, Emilie J; Cordoba, Alicia; Bart, Jos; Mooyaart, Antien L; van den Tweel, Jan G; Zolota, Vicky; Wesseling, Jelle; Sapino, Anna; Chmielik, Ewa; Ryska, Ales; Amant, Frederic; Broeks, Annegien; Kerkhoven, Ron; Stathonikos, Nikolas; Veta, Mitko; Voogd, Adri; Jozwiak, Katarzyna; Hauptmann, Michael; Hoogstraat, Marlous; Schmidt, Marjanka K; Sonke, Gabe; van der Wall, Elsken; Siesling, Sabine; van Diest, Paul J; Linn, Sabine C

    2017-11-14

    Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative. Our aim is to reduce overtreatment of women diagnosed with breast cancer aged ≤ 40 years. All young, adjuvant systemic treatment naive breast cancer patients, who had no prior malignancy and were diagnosed between 1989 and 2000, were identified using the population based Netherlands Cancer Registry (n=3525). Archival tumour tissues were retrieved through linkage with the Dutch nationwide pathology registry. Tissue slides will be digitalised and placed on an online image database platform for clinicopathological revision by an international team of breast pathologists. Immunohistochemical subtype will be assessed using tissue microarrays. Tumour RNA will be isolated and subjected to next-generation sequencing. Differences in gene expression found between patients with a favourable and those with a less favourable prognosis will be used to establish a prognostic classifier, using the triple negative patients as proof of principle. Observational data from the Netherlands Cancer Registry and left over archival patient material are used. Therefore, the Dutch law on Research Involving Human Subjects Act (WMO) is not applicable. The PARADIGM study received a 'non-WMO' declaration from the Medical Ethics Committee of the Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, waiving individual patient

  9. Chronic subordinate colony housing paradigm: A mouse model for mechanisms of PTSD vulnerability, targeted prevention, and treatment-2016 Curt Richter Award Paper.

    Science.gov (United States)

    Reber, Stefan O; Langgartner, Dominik; Foertsch, Sandra; Postolache, Teodor T; Brenner, Lisa A; Guendel, Harald; Lowry, Christopher A

    2016-12-01

    There is considerable individual variability in vulnerability for developing posttraumatic stress disorder (PTSD); evidence suggests that this variability is related in part to genetic and environmental factors, including adverse early life experience. Interestingly, recent studies indicate that induction of chronic low-grade inflammation may be a common mechanism underlying gene and environment interactions that increase the risk for development of PTSD symptoms, and, therefore, may be a target for novel interventions for prevention or treatment of PTSD. Development of murine models with face, construct, and predictive validity would provide opportunities to investigate in detail complex genetic, environmental, endocrine, and immunologic factors that determine vulnerability to PTSD-like syndromes, and furthermore may provide mechanistic insight leading to development of novel interventions for both prevention and treatment of PTSD symptoms. Here we describe the potential use of the chronic subordinate colony housing (CSC) paradigm in mice as an adequate animal model for development of a PTSD-like syndrome and describe recent studies that suggest novel interventions for the prevention and treatment of PTSD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Evolving Concepts of Asthma

    Science.gov (United States)

    Ray, Anuradha; Wenzel, Sally E.

    2015-01-01

    Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapies treated most patients with asthma similarly, with bronchodilators and corticosteroids, but these therapies had varying degrees of success. Similarly, despite initial studies that identified an underlying type 2 inflammation in the airways of patients with asthma, biologic therapies targeted toward these type 2 pathways were unsuccessful in all patients. These observations led to increased interest in phenotyping asthma. Clinical approaches, both biased and later unbiased/statistical approaches to large asthma patient cohorts, identified a variety of patient characteristics, but they also consistently identified the importance of age of onset of disease and the presence of eosinophils in determining clinically relevant phenotypes. These paralleled molecular approaches to phenotyping that developed an understanding that not all patients share a type 2 inflammatory pattern. Using biomarkers to select patients with type 2 inflammation, repeated trials of biologics directed toward type 2 cytokine pathways saw newfound success, confirming the importance of phenotyping in asthma. Further research is needed to clarify additional clinical and molecular phenotypes, validate predictive biomarkers, and identify new areas for possible interventions. PMID:26161792

  11. A Direct Synergistic Effect of Immunotherapy and Chemotherapy as a New Paradigm in Treatment of Breast Cancer

    Science.gov (United States)

    2010-04-01

    mouse macrophage nucleofector kit (Program-Y-01) was used. For EL4 cells mouse cell transfection kit (Program-C-09) was used. As controls...direct synergy between immunotherapy and chemotherapy in vitro. We found that pre-treatment of tumor target cells with doxorubicin or paclitaxel...significantly increased cytotoxic effect of T-lymphocytes. Importantly, that effect was antigen-specific, since it was observed only in tumor cells loaded

  12. Real-Life Treatment Paradigms Show Adalimumab Is Cost-Effective for the Management of Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Candace L. Beilman

    2016-01-01

    Full Text Available Background. Adalimumab is effective for the maintenance of remission in patients with moderate-to-severe ulcerative colitis (UC. Currently, biologic therapies are used in cases where patients fail conventional medical therapies. If biologic therapies are not available, patients often choose to remain in an unwell state rather than undergo colectomy. Objective. The aim of the study was to evaluate the cost-effectiveness of adalimumab in patients with UC where adalimumab was readily available compared to not available. Methods. A previously validated Markov model was used to simulate disease progression of patients with UC who are corticosteroid-dependent and/or did not respond to thiopurine therapy. Utility scores and transition probabilities between health states were determined by using data from randomized controlled trials and real-life observational studies. Costs were obtained from the Ontario Case Costing Initiative and the Alberta Health Schedule of Medical Benefits. Results. The incremental cost-effectiveness ratios for readily available adalimumab treatment of UC were $40,000 and $59,000 per quality-adjusted life year, compared with ongoing medical therapy in an unwell state, at 5-year and 10-year treatment time horizons, respectively. Conclusion. Considering real-life patient preferences to avoid colectomy, adalimumab is cost-effective according to a willingness-to-pay threshold of $80,000 for treatment of UC.

  13. Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.

    Science.gov (United States)

    Brand, Sarel Jacobus; Harvey, Brian Herbert

    2017-08-01

    Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

  14. Echoes of old HIV paradigms: reassessing the problem of engaging men in HIV testing and treatment through women's perspectives.

    Science.gov (United States)

    Katirayi, Leila; Chadambuka, Addmore; Muchedzi, Auxilia; Ahimbisibwe, Allan; Musarandega, Reuben; Woelk, Godfrey; Tylleskar, Thorkild; Moland, Karen Marie

    2017-10-05

    With the introduction of 2016 World Health Organization guidelines recommending universal antiretroviral therapy (ART), there has been increased recognition of the lack of men engaging in HIV testing and treatment. Studies in sub-Saharan Africa indicate there have been challenges engaging men in HIV testing and HIV-positive men into treatment. This qualitative study explored women's perspective of their male partner's attitudes towards HIV and ART and how it shapes woman's experience with ART. Data were collected through in-depth interviews and focus group discussions with HIV-positive pregnant and postpartum women on Option B+ and health care workers in Malawi and Zimbabwe. In Malawi, 19 in-depth interviews and 12 focus group discussions were conducted from September-December 2013. In Zimbabwe, 15 in-depth interviews and 21 focus-group discussions were conducted from July 2014-March 2014. The findings highlighted that many men discourage their partners from initiating or adhering to ART. One of the main findings indicated that despite the many advancements in HIV care and ART regimens, there are still many lingering negative beliefs about HIV and ART from the earlier days of the epidemic. In addition to existing theories explaining men's resistance to/absence in HIV testing and treatment as a threat to their masculinity or because of female-focused health facilities, this paper argues that men's aversion to HIV may be a result of old beliefs about HIV and ART which have not been addressed. Due to lack of accurate and up to date information about HIV and ART, many men discourage their female partners from initiating and adhering to ART. The effect of lingering and outdated beliefs about HIV and ART needs to be addressed through strengthened communication about developments in HIV care and treatment. Universal ART offers a unique opportunity to curb the epidemic, but successful implementation of these new guidelines is dependent on ART initiation and adherence by

  15. An Obesity Dietary Quality Index Predicts Abdominal Obesity in Women: Potential Opportunity for New Prevention and Treatment Paradigms

    Directory of Open Access Journals (Sweden)

    Dolores M. Wolongevicz

    2010-01-01

    Full Text Available Background. Links between dietary quality and abdominal obesity are poorly understood. Objective. To examine the association between an obesity-specific dietary quality index and abdominal obesity risk in women. Methods. Over 12 years, we followed 288 Framingham Offspring/Spouse Study women, aged 30–69 years, without metabolic syndrome risk factors, cardiovascular disease, cancer, or diabetes at baseline. An 11-nutrient obesity-specific dietary quality index was derived using mean ranks of nutrient intakes from 3-day dietary records. Abdominal obesity (waist circumference >88 cm was assessed during follow-up. Results. Using multiple logistic regression, women with poorer dietary quality were more likely to develop abdominal obesity compared to those with higher dietary quality (OR 1.87; 95% CI, 1.01, 3.47; P for trend =.048 independent of age, physical activity, smoking, and menopausal status. Conclusions. An obesity-specific dietary quality index predicted abdominal obesity in women, suggesting targets for dietary quality assessment, intervention, and treatment to address abdominal adiposity.

  16. Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms.

    Science.gov (United States)

    Wheler, Jennifer J; Parker, Barbara A; Lee, Jack J; Atkins, Johnique T; Janku, Filip; Tsimberidou, Apostolia M; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Schwab, Richard; Moulder, Stacy; Valero, Vicente; Schwaederle, Maria; Yelensky, Roman; Miller, Vincent A; Stephens, M Philip J; Meric-Bernstam, Funda; Kurzrock, Razelle

    2014-05-15

    Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient's tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via 'crosstalk'). The 'molecular individuality' of these tumors suggests that a customized strategy, using an "N-of-One" model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors.

  17. Metastatic squamous cell non-small-cell lung cancer (NSCLC: disrupting the drug treatment paradigm with immunotherapies

    Directory of Open Access Journals (Sweden)

    Sarah L Scarpace

    2015-10-01

    Full Text Available Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR and anaplastic lymphoma kinase (ALK mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. Immunotherapies directed at the programmed cell death-1 receptor (PD-1 or its ligand (PD-L1 (nivolumab and pembrolizumab have demonstrated efficacy in both nonsquamous and squamous cell NSCLC. Because of their similar mechanism of action against the PD-L1/PD-1 pathway, both drugs have similar toxicity profiles related to immune-mediated adverse reactions that can generally be monitored and managed with oral corticosteroids. This paper provides an overview of drug therapy options for squamous cell NSCLC with a focus on the evidence and clinical application of the anti-PD1 therapies. A comparison of the dosing, administration, indications, and differences in the measurement of PD-L1 expression in the clinical trials of nivolumab and pembrolizumab is also provided.

  18. A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

    International Nuclear Information System (INIS)

    Asher, Anthony L.; Burri, Stuart H.; Wiggins, Walter F.; Kelly, Renee P.; Boltes, Margaret O.; Mehrlich, Melissa; Norton, H. James; Fraser, Robert W.

    2014-01-01

    Purpose: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong

  19. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence.

    Science.gov (United States)

    Asher, Anthony L; Burri, Stuart H; Wiggins, Walter F; Kelly, Renee P; Boltes, Margaret O; Mehrlich, Melissa; Norton, H James; Fraser, Robert W

    2014-03-15

    Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits

  20. A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Asher, Anthony L., E-mail: asher@cnsa.com [Department of Neurosurgery, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States); Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (United States); Burri, Stuart H. [Department of Radiation Oncology, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States); Wiggins, Walter F. [Wake Forest School of Medicine MD/PhD Program, Winston-Salem, North Carolina (United States); Kelly, Renee P. [Brain Tumor Fund for the Carolinas, Charlotte, North Carolina (United States); Boltes, Margaret O.; Mehrlich, Melissa [Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (United States); Norton, H. James [Department of Biostatistics, Carolinas Medical Center, Charlotte, North Carolina (United States); Fraser, Robert W. [Department of Radiation Oncology, Levine Cancer Institute and Carolinas Medical Center, Charlotte, North Carolina (United States)

    2014-03-15

    Purpose: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong

  1. Integrative Mental Health (IMH): paradigm, research, and clinical practice.

    Science.gov (United States)

    Lake, James; Helgason, Chanel; Sarris, Jerome

    2012-01-01

    This paper provides an overview of the rapidly evolving paradigm of "Integrative Mental Health (IMH)." The paradigm of contemporary biomedical psychiatry and its contrast to non-allopathic systems of medicine is initially reviewed, followed by an exploration of the emerging paradigm of IMH, which aims to reconcile the bio-psycho-socio-spiritual model with evidence-based methods from traditional healing practices. IMH is rapidly transforming conventional understandings of mental illness and has significant positive implications for the day-to-day practice of mental health care. IMH incorporates mainstream interventions such as pharmacologic treatments, psychotherapy, and psychosocial interventions, as well as alternative therapies such as acupuncture, herbal and nutritional medicine, dietary modification, meditation, etc. Two recent international conferences in Europe and the United States show that interest in integrative mental health care is growing rapidly. In response, the International Network of Integrative Mental Health (INIMH: www.INIMH.org) was established in 2010 with the objective of creating an international network of clinicians, researchers, and public health advocates to advance a global agenda for research, education, and clinical practice of evidence-based integrative mental health care. The paper concludes with a discussion of emerging opportunities for research in IMH, and an exploration of potential clinical applications of integrative mental health care. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. New energy paradigm?

    International Nuclear Information System (INIS)

    Goldoni, Giovanni

    2007-01-01

    The rise of oil prices, the difficulties in markets liberalization, and the poor results of competition have convinced many that a new energy paradigm is necessary. Taking the original definition of scientific paradigm, it doesn't seem that a practical solution could be found outside the present paradigm of energy policy, made of privatisation, liberalisation and competition [it

  3. Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.

    Science.gov (United States)

    Fujiwara, Keiichi; McAlpine, Jessica N; Lheureux, Stephanie; Matsumura, Noriomi; Oza, Amit M

    2016-01-01

    The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

  4. Mentoring: An Evolving Relationship.

    Science.gov (United States)

    Block, Michelle; Florczak, Kristine L

    2017-04-01

    The column concerns itself with mentoring as an evolving relationship between mentor and mentee. The collegiate mentoring model, the transformational transcendence model, and the humanbecoming mentoring model are considered in light of a dialogue with mentors at a Midwest university and conclusions are drawn.

  5. Methods Evolved by Observation

    Science.gov (United States)

    Montessori, Maria

    2016-01-01

    Montessori's idea of the child's nature and the teacher's perceptiveness begins with amazing simplicity, and when she speaks of "methods evolved," she is unveiling a methodological system for observation. She begins with the early childhood explosion into writing, which is a familiar child phenomenon that Montessori has written about…

  6. EVOLVE 2014 International Conference

    CERN Document Server

    Tantar, Emilia; Sun, Jian-Qiao; Zhang, Wei; Ding, Qian; Schütze, Oliver; Emmerich, Michael; Legrand, Pierrick; Moral, Pierre; Coello, Carlos

    2014-01-01

    This volume encloses research articles that were presented at the EVOLVE 2014 International Conference in Beijing, China, July 1–4, 2014.The book gathers contributions that emerged from the conference tracks, ranging from probability to set oriented numerics and evolutionary computation; all complemented by the bridging purpose of the conference, e.g. Complex Networks and Landscape Analysis, or by the more application oriented perspective. The novelty of the volume, when considering the EVOLVE series, comes from targeting also the practitioner’s view. This is supported by the Machine Learning Applied to Networks and Practical Aspects of Evolutionary Algorithms tracks, providing surveys on new application areas, as in the networking area and useful insights in the development of evolutionary techniques, from a practitioner’s perspective. Complementary to these directions, the conference tracks supporting the volume, follow on the individual advancements of the subareas constituting the scope of the confe...

  7. Evolving Procurement Organizations

    DEFF Research Database (Denmark)

    Bals, Lydia; Laine, Jari; Mugurusi, Godfrey

    Procurement has to find further levers and advance its contribution to corporate goals continuously. This places pressure on its organization in order to facilitate its performance. Therefore, procurement organizations constantly have to evolve in order to match these demands. A conceptual model...... and external contingency factors and having a more detailed look at the structural dimensions chosen, beyond the well-known characteristics of centralization, formalization, participation, specialization, standardization and size. From a theoretical perspective, it opens up insights that can be leveraged...

  8. Symbiotic Composition and Evolvability

    OpenAIRE

    Watson, Richard A.; Pollack, Jordan B.

    2001-01-01

    Several of the Major Transitions in natural evolution, such as the symbiogenic origin of eukaryotes from prokaryotes, share the feature that existing entities became the components of composite entities at a higher level of organisation. This composition of pre-adapted extant entities into a new whole is a fundamentally different source of variation from the gradual accumulation of small random variations, and it has some interesting consequences for issues of evolvability. In this paper we p...

  9. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  10. The Next Paradigm

    Directory of Open Access Journals (Sweden)

    Bernardo Kastrup

    2018-04-01

    Full Text Available In order to perceive the world, we need more than just raw sensory input: a subliminal paradigm of thought is required to interpret raw sensory data and, thereby, create the objects and events we perceive around ourselves. As such, the world we see reflects our own unexamined, culture-bound assumptions and expectations, which explains why every generation in history has believed that it more or less understood the world. Today, we perceive a world of objects and events outside and independent of mind, which merely reflects our current paradigm of thought. Anomalies that contradict this paradigm have been accumulated by physicists over the past couple of decades, which will eventually force our culture to move to a new paradigm. Under this new paradigm, a form of universal mind will be viewed as nature’s sole fundamental entity. In this paper, I offer a sketch of what the new paradigm may look like.

  11. Evolved H II regions

    International Nuclear Information System (INIS)

    Churchwell, E.

    1975-01-01

    A probable evolutionary sequence of H II regions based on six distinct types of observed objects is suggested. Two examples which may deviate from this idealized sequence, are discussed. Even though a size-mean density relation of H II regions can be used as a rough indication of whether a nebula is very young or evolved, it is argued that such a relation is not likely to be useful for the quantitative assignment of ages to H II regions. Evolved H II regions appear to fit into one of four structural types: rings, core-halos, smooth structures, and irregular or filamentary structures. Examples of each type are given with their derived physical parameters. The energy balance in these nebulae is considered. The mass of ionized gas in evolved H II regions is in general too large to trace the nebula back to single compact H II regions. Finally, the morphological type of the Galaxy is considered from its H II region content. 2 tables, 2 figs., 29 refs

  12. Didaktiske paradigmer og refleksion

    DEFF Research Database (Denmark)

    Christensen, Torben Spanget

    2014-01-01

    analysis of subject didactics by Sigmund Ongstad. The two positions offer fundamentally different insights into didactics. Nielsen’s position establishes didactics as a knowledge domain and Ongstad’s position points to the dynamics of subject didactics by analyzing communication as a basic aspect. Krogh...... this article. A possible utilitarian didactical paradigm, already indicated by Krogh as a historical paradigm prominent in our time, is also discussed. It is suggested that reflection could be seen as a normative response to the utilitarian paradigm, and not as a paradigm in its own right. It is concluded...

  13. Dynamic paradigm of turbulence

    International Nuclear Information System (INIS)

    Mukhamedov, Alfred M.

    2006-01-01

    In this paper a dynamic paradigm of turbulence is proposed. The basic idea consists in the novel definition of chaotic structure given with the help of Pfaff system of PDE associated with the turbulent dynamics. A methodological analysis of the new and the former paradigm is produced

  14. An Integrative Paradigm

    Science.gov (United States)

    Hammack, Phillip L.

    2005-01-01

    Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

  15. Evolving treatment implementation among HIV-infected pregnant women and their partners: results from a national surveillance study in Italy, 2001-2015.

    Science.gov (United States)

    Floridia, Marco; Frisina, Valentina; Ravizza, Marina; Marconi, Anna Maria; Pinnetti, Carmela; Cetin, Irene; Sansone, Matilde; Molinari, Atim; Cervi, Francesca; Meloni, Alessandra; Luzi, Kety; Masuelli, Giulia; Tamburrini, Enrica

    2017-06-01

    The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV-negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P  HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P  = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV

  16. Evolving Procurement Organizations

    DEFF Research Database (Denmark)

    Bals, Lydia; Laiho, Aki; Laine, Jari

    Procurement has to find further levers and advance its contribution to corporate goals continuously. This places pressure on its organization in order to facilitate its performance. Therefore, Procurement organizations constantly have to evolve in order to match these demands. A conceptual model...... is presented and results of a first case study discussed. The findings highlight the importance of taking a contingency perspective on Procurement organization, understanding the internal and internal contingency factors. From a theoretical perspective, it opens up insights that can be furthermore leveraged...... in future studies in the fields of hybrid procurement organizations, global sourcing organizations as well as international procurement offices (IPOs). From a practical standpoint, an assessment of external and internal contingencies provides the opportunity to consciously match organization to its...

  17. Diffusion between evolving interfaces

    International Nuclear Information System (INIS)

    Juntunen, Janne; Merikoski, Juha

    2010-01-01

    Diffusion in an evolving environment is studied by continuous-time Monte Carlo simulations. Diffusion is modeled by continuous-time random walkers on a lattice, in a dynamic environment provided by bubbles between two one-dimensional interfaces driven symmetrically towards each other. For one-dimensional random walkers constrained by the interfaces, the bubble size distribution dominates diffusion. For two-dimensional random walkers, it is also controlled by the topography and dynamics of the interfaces. The results of the one-dimensional case are recovered in the limit where the interfaces are strongly driven. Even with simple hard-core repulsion between the interfaces and the particles, diffusion is found to depend strongly on the details of the dynamical rules of particles close to the interfaces.

  18. The Evolving Treatment Patterns of NCAA Division I Football Players by Orthopaedic Team Physicians Over the Past Decade, 2008-2016.

    Science.gov (United States)

    Carver, Trevor J; Schrock, John B; Kraeutler, Matthew J; McCarty, Eric C

    Previous studies have analyzed the treatment patterns used to manage injuries in National Collegiate Athletic Association (NCAA) Division I football players. Treatment patterns used to manage injuries in NCAA Division I football players will have changed over the study period. Descriptive epidemiology study. Level 5. The head orthopaedic team physicians for all 128 NCAA Division I football teams were asked to complete a survey containing questions regarding experience as team physician, medical coverage of the team, reimbursement issues, and treatment preferences for some of the most common injuries occurring in football players. Responses from the current survey were compared with responses from the same survey sent to NCAA Division I team physicians in 2008. Responses were received from 111 (111/119, 93%) NCAA Division I orthopaedic team physicians in 2008 and 115 (115/128, 90%) orthopaedic team physicians between April 2016 and April 2017. The proportion of team physicians who prefer a patellar tendon autograft for primary anterior cruciate ligament reconstruction (ACLR) increased from 67% in 2008 to 83% in 2016 ( P football players over the study period. In particular, physicians have changed their preferred techniques for ACLR, anterior shoulder stabilization, and PCL reconstruction. Physicians have also become more conservative with pregame Toradol injections. These opinions may help guide treatment decisions and lead to better care of all athletes.

  19. Of Paradigms and Power

    DEFF Research Database (Denmark)

    Carstensen, Martin B.; Matthijs, Matthias

    in the study of policy paradigms. To demonstrate the general applicability of our framework, the paper examines the evolution of British macroeconomic policy making since 1990. We show that various Prime Ministers and their Chancellors were able to reinterpret and redefine the dominant neoliberal understanding......? Despite the profound impact of Peter Hall’s approach to policy paradigms and social learning, there is a burgeoning consensus that transposing a rudimentary ‘Kuhnian’ understanding of paradigms into the context of public policy making leads to a notion of punctuated equilibrium style shifts as the only...

  20. Virtual reality jogging as a novel exposure paradigm for the acute urge to be physically active in patients with eating disorders: Implications for treatment.

    Science.gov (United States)

    Paslakis, Georgios; Fauck, Vanessa; Röder, Kathrin; Rauh, Elisabeth; Rauh, Manfred; Erim, Yesim

    2017-11-01

    The acute urge to be physically active is a relevant clinical phenomenon in patients suffering from eating disorders. In this study with n = 20 female patients with anorexia nervosa and n = 10 female patients with bulimia nervosa, a virtual reality (VR) jogging paradigm was applied as a novel highly immersive 3D exposure paradigm. Patients were asked to rate their acute urge to be physically active during the exposure procedure. A 10-item self-report questionnaire (smQ) was developed to capture the cognitive, emotional, and behavioral aspects of the acute urge to move. We hypothesized that exposure would lead to habituation of the urge to be physically active. We also hypothesized that leptin levels would be associated with the degree of the subjective urge to be physically active, while habituation would be associated with a decrease in stress hormones (α-amylase, cortisol, and cortisone in saliva). A statistically significant change in subjective scores in the smQ from baseline to postexposure was seen. Our novel VR paradigm may serve as a therapeutic tool for exposure and habituation of the urge of acutely engaging in physical activity in patients with eating disorders. © 2017 Wiley Periodicals, Inc.

  1. A New Paradigm for Evaluating Avoidance/Escape Motivation.

    Science.gov (United States)

    Tsutsui-Kimura, Iku; Bouchekioua, Youcef; Mimura, Masaru; Tanaka, Kenji F

    2017-07-01

    Organisms have evolved to approach pleasurable opportunities and to avoid or escape from aversive experiences. These 2 distinct motivations are referred to as approach and avoidance/escape motivations and are both considered vital for survival. Despite several recent advances in understanding the neurobiology of motivation, most studies addressed approach but not avoidance/escape motivation. Here we develop a new experimental paradigm to quantify avoidance/escape motivation and examine the pharmacological validity. We set up an avoidance variable ratio 5 task in which mice were required to press a lever for variable times to avoid an upcoming aversive stimulus (foot shock) or to escape the ongoing aversive event if they failed to avoid it. We i.p. injected ketamine (0, 1, or 5 mg/kg) or buspirone (0, 5, or 10 mg/kg) 20 or 30 minutes before the behavioral task to see if ketamine enhanced avoidance/escape behavior and buspirone diminished it as previously reported. We found that the performance on the avoidance variable ratio 5 task was sensitive to the intensity of the aversive stimulus. Treatment with ketamine increased while that with buspirone decreased the probability of avoidance from an aversive stimulus in the variable ratio 5 task, being consistent with previous reports. Our new paradigm will prove useful for quantifying avoidance/escape motivation and will contribute to a more comprehensive understanding of motivation. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  2. Programming Language Paradigms

    OpenAIRE

    Felician ALECU

    2013-01-01

    This paper's goal is to briefly explain the basic theory behind programming languages and their history while taking a close look at different programming paradigms that are used today as well as describing their differences, benefits, and drawbacks

  3. Why did heterospory evolve?

    Science.gov (United States)

    Petersen, Kurt B; Burd, Martin

    2017-08-01

    The primitive land plant life cycle featured the production of spores of unimodal size, a condition called homospory. The evolution of bimodal size distributions with small male spores and large female spores, known as heterospory, was an innovation that occurred repeatedly in the history of land plants. The importance of desiccation-resistant spores for colonization of the land is well known, but the adaptive value of heterospory has never been well established. It was an addition to a sexual life cycle that already involved male and female gametes. Its role as a precursor to the evolution of seeds has received much attention, but this is an evolutionary consequence of heterospory that cannot explain the transition from homospory to heterospory (and the lack of evolutionary reversal from heterospory to homospory). Enforced outcrossing of gametophytes has often been mentioned in connection to heterospory, but we review the shortcomings of this argument as an explanation of the selective advantage of heterospory. Few alternative arguments concerning the selective forces favouring heterospory have been proposed, a paucity of attention that is surprising given the importance of this innovation in land plant evolution. In this review we highlight two ideas that may lead us to a better understanding of why heterospory evolved. First, models of optimal resource allocation - an approach that has been used for decades in evolutionary ecology to help understand parental investment and other life-history patterns - suggest that an evolutionary increase in spore size could reach a threshold at which small spores yielding small, sperm-producing gametophytes would return greater fitness per unit of resource investment than would large spores and bisexual gametophytes. With the advent of such microspores, megaspores would evolve under frequency-dependent selection. This argument can account for the appearance of heterospory in the Devonian, when increasingly tall and complex

  4. Evolving a photosynthetic organelle

    Directory of Open Access Journals (Sweden)

    Nakayama Takuro

    2012-04-01

    Full Text Available Abstract The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles. The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis - the conversion of solar energy into chemical energy - and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  5. Fat: an evolving issue

    Directory of Open Access Journals (Sweden)

    John R. Speakman

    2012-09-01

    Work on obesity is evolving, and obesity is a consequence of our evolutionary history. In the space of 50 years, we have become an obese species. The reasons why can be addressed at a number of different levels. These include separating between whether the primary cause lies on the food intake or energy expenditure side of the energy balance equation, and determining how genetic and environmental effects contribute to weight variation between individuals. Opinion on whether increased food intake or decreased energy expenditure drives the obesity epidemic is still divided, but recent evidence favours the idea that food intake, rather than altered expenditure, is most important. There is more of a consensus that genetics explains most (probably around 65% of weight variation between individuals. Recent advances in genome-wide association studies have identified many polymorphisms that are linked to obesity, yet much of the genetic variance remains unexplained. Finding the causes of this unexplained variation will be an impetus of genetic and epigenetic research on obesity over the next decade. Many environmental factors – including gut microbiota, stress and endocrine disruptors – have been linked to the risk of developing obesity. A better understanding of gene-by-environment interactions will also be key to understanding obesity in the years to come.

  6. Evolving a photosynthetic organelle.

    Science.gov (United States)

    Nakayama, Takuro; Archibald, John M

    2012-04-24

    The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles.The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis--the conversion of solar energy into chemical energy--and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  7. Communicability across evolving networks.

    Science.gov (United States)

    Grindrod, Peter; Parsons, Mark C; Higham, Desmond J; Estrada, Ernesto

    2011-04-01

    Many natural and technological applications generate time-ordered sequences of networks, defined over a fixed set of nodes; for example, time-stamped information about "who phoned who" or "who came into contact with who" arise naturally in studies of communication and the spread of disease. Concepts and algorithms for static networks do not immediately carry through to this dynamic setting. For example, suppose A and B interact in the morning, and then B and C interact in the afternoon. Information, or disease, may then pass from A to C, but not vice versa. This subtlety is lost if we simply summarize using the daily aggregate network given by the chain A-B-C. However, using a natural definition of a walk on an evolving network, we show that classic centrality measures from the static setting can be extended in a computationally convenient manner. In particular, communicability indices can be computed to summarize the ability of each node to broadcast and receive information. The computations involve basic operations in linear algebra, and the asymmetry caused by time's arrow is captured naturally through the noncommutativity of matrix-matrix multiplication. Illustrative examples are given for both synthetic and real-world communication data sets. We also discuss the use of the new centrality measures for real-time monitoring and prediction.

  8. UKAEA'S evolving contract philosophy

    International Nuclear Information System (INIS)

    Nicol, R. D.

    2003-01-01

    The United Kingdom Atomic Energy Authority (UKAEA) has gone through fundamental change over the last ten years. At the heart of this change has been UKAEA's relationship with the contracting and supply market. This paper describes the way in which UKAEA actively developed the market to support the decommissioning programme, and how the approach to contracting has evolved as external pressures and demands have changed. UKAEA's pro-active approach to industry has greatly assisted the development of a healthy, competitive market for services supporting decommissioning in the UK. There have been difficult changes and many challenges along the way, and some retrenchment was necessary to meet regulatory requirements. Nevertheless, UKAEA has sustained a high level of competition - now measured in terms of competed spend as a proportion of competable spend - with annual out-turns consistently over 80%. The prime responsibility for market development will pass to the new Nuclear Decommissioning Authority (NDA) in 2005, as the owner, on behalf of the Government, of the UK's civil nuclear liabilities. The preparatory work for the NDA indicates that the principles established by UKAEA will be carried forward. (author)

  9. Evolving spiking networks with variable resistive memories.

    Science.gov (United States)

    Howard, Gerard; Bull, Larry; de Lacy Costello, Ben; Gale, Ella; Adamatzky, Andrew

    2014-01-01

    Neuromorphic computing is a brainlike information processing paradigm that requires adaptive learning mechanisms. A spiking neuro-evolutionary system is used for this purpose; plastic resistive memories are implemented as synapses in spiking neural networks. The evolutionary design process exploits parameter self-adaptation and allows the topology and synaptic weights to be evolved for each network in an autonomous manner. Variable resistive memories are the focus of this research; each synapse has its own conductance profile which modifies the plastic behaviour of the device and may be altered during evolution. These variable resistive networks are evaluated on a noisy robotic dynamic-reward scenario against two static resistive memories and a system containing standard connections only. The results indicate that the extra behavioural degrees of freedom available to the networks incorporating variable resistive memories enable them to outperform the comparative synapse types.

  10. Evolving trade policy and the Trans-Pacific Partnership Agreement: does it threaten Vietnam's access to medicine and its progress towards scaling up HIV prevention, treatment and care?

    Science.gov (United States)

    Linh, Nguyen Nhat; Huong, Nguyen Thanh; Thuy, Hua Thanh

    2015-01-01

    The Trans-Pacific Partnership Agreement (TPP) has undergone 18 rounds of secretive negotiation between the USA and 11 Asia-Pacific countries. Aiming at a free trade area, this multilateral trade proposal covers all aspects of commercial relations among the countries involved. Despite some anticipated positive impacts in trade, specific articles in this proposal's intellectual property and transparency chapters might negatively impact access to medicine, in general, and to antiretroviral (ARV) drugs, in particular, in Vietnam. Drawing on a desk review and qualitative in-depth interviews with 20 key informants from government, academia, hospitals and civil society, we analyse various provisions of the proposal being negotiated leaked after the 14th round of negotiations in September 2012. Findings suggest that the TPP could lead to increased monopoly protection and could limit technological advancements within the local pharmaceutical manufacturing industry, resulting in higher medicine prices in Vietnam. This outcome would have a significant impact on Vietnam's ability to achieve goals for HIV prevention, treatment and care, and create barriers to universal health-care coverage. This research provides unique evidence for Vietnam to advocate for more equitable pharmaceutical provisions in and to raise awareness of the implications of the TPP among the pharmaceutical stakeholder community in Vietnam.

  11. Winnicott's paradigm outlined

    Directory of Open Access Journals (Sweden)

    Zeljko Loparic

    Full Text Available The main objective of this paper is to present a unified view of Winnicott’s contribution to psychoanalysis. Part I (Sections 1-4 starts off by recalling that, according to some important commentators, Winnicott introduced a change in paradigms in psychoanalysis. In order to show that this change can be viewed as an overall “switch in paradigms”, in the sense given by T. S. Kuhn, this paper presents an account of the Kuhn’s view of science and offers a reconstruction of Freud’s Oedipal, Triangular or “Toddler-in-the-Mother’s-Bed” Paradigm. Part II (Sections 5-13 shows that as early as the 1920’s Winnicott encountered insurmountable anomalies in the Oedipal paradigm and, for that reason, started what can be called revolutionary research for a new framework of psychoanalysis. This research led Winnicott, especially during the last period of his life, to produce an alternative dual or “Baby-on-the-Mother’s-Lap” Paradigm. This new paradigm is described in some detail, especially the paradigmatic dual mother-baby relation and Winnicott’s dominant theory of maturation. Final remarks are made regarding Winnicott’s heritage and the future of psychoanalysis.

  12. Consumers and Makers: Exploring Opposing Paradigms of Millennial College Readiness

    Science.gov (United States)

    Jackson, Matthew

    2017-01-01

    The political and technological circumstances of the past two decades have culminated in opposing epistemic paradigms of college readiness, where millennial students' conceptual understanding of "learning" is both narrowed to meet the demands of school systems bound to accountability and amplified by a rapidly evolving digital world. The…

  13. Three paradigms of horror

    OpenAIRE

    Dejan Ognjanović

    2016-01-01

    Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the indivi...

  14. Evolving NASA's Earth Science Data Systems

    Science.gov (United States)

    Walter, J.; Behnke, J.; Murphy, K. J.; Lowe, D. R.

    2013-12-01

    NASA's Earth Science Data and Information System Project (ESDIS) is charged with managing, maintaining, and evolving NASA's Earth Observing System Data and Information System (EOSDIS) and is responsible for processing, archiving, and distributing NASA Earth science data. The system supports a multitude of missions and serves diverse science research and other user communities. Keeping up with ever-changing information technology and figuring out how to leverage those changes across such a large system in order to continuously improve and meet the needs of a diverse user community is a significant challenge. Maintaining and evolving the system architecture and infrastructure is a continuous and multi-layered effort. It requires a balance between a "top down" management paradigm that provides a coherent system view and maintaining the managerial, technological, and functional independence of the individual system elements. This presentation will describe some of the key elements of the current system architecture, some of the strategies and processes we employ to meet these challenges, current and future challenges, and some ideas for meeting those challenges.

  15. Disgust: Evolved function and structure

    NARCIS (Netherlands)

    Tybur, J.M.; Lieberman, D.; Kurzban, R.; DeScioli, P.

    2013-01-01

    Interest in and research on disgust has surged over the past few decades. The field, however, still lacks a coherent theoretical framework for understanding the evolved function or functions of disgust. Here we present such a framework, emphasizing 2 levels of analysis: that of evolved function and

  16. Natural selection promotes antigenic evolvability

    NARCIS (Netherlands)

    Graves, C.J.; Ros, V.I.D.; Stevenson, B.; Sniegowski, P.D.; Brisson, D.

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide

  17. Paradigms in object recognition

    International Nuclear Information System (INIS)

    Mutihac, R.; Mutihac, R.C.

    1999-09-01

    A broad range of approaches has been proposed and applied for the complex and rather difficult task of object recognition that involves the determination of object characteristics and object classification into one of many a priori object types. Our paper revises briefly the three main different paradigms in pattern recognition, namely Bayesian statistics, neural networks, and expert systems. (author)

  18. Programming Language Paradigms

    Directory of Open Access Journals (Sweden)

    Bartoníček Jan

    2014-01-01

    Full Text Available This paper's goal is to briefly explain the basic theory behind programming languages and their history while taking a close look at different programming paradigms that are used today as well as describing their differences, benefits, and drawbacks

  19. Shifting the paradigm

    DEFF Research Database (Denmark)

    Kiss, Katalin; Brozik, Anna; Kucsma, Nora

    2012-01-01

    ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticuloc...... paradigm linking the expression and function of ABCB6 to mitochondria....

  20. Deconstructing Research: Paradigms Lost

    Science.gov (United States)

    Trifonas, Peter Pericles

    2009-01-01

    In recent decades, proponents of naturalistic and/or critical modes of inquiry advocating the use of ethnographic techniques for the narrative-based study of phenomena within pedagogical contexts have challenged the central methodological paradigm of educational research: that is, the tendency among its practitioners to adhere to quantitative…

  1. About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

    Science.gov (United States)

    Kaellis, Eugene

    2006-01-01

    Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

  2. Computational Genetic Regulatory Networks Evolvable, Self-organizing Systems

    CERN Document Server

    Knabe, Johannes F

    2013-01-01

    Genetic Regulatory Networks (GRNs) in biological organisms are primary engines for cells to enact their engagements with environments, via incessant, continually active coupling. In differentiated multicellular organisms, tremendous complexity has arisen in the course of evolution of life on earth. Engineering and science have so far achieved no working system that can compare with this complexity, depth and scope of organization. Abstracting the dynamics of genetic regulatory control to a computational framework in which artificial GRNs in artificial simulated cells differentiate while connected in a changing topology, it is possible to apply Darwinian evolution in silico to study the capacity of such developmental/differentiated GRNs to evolve. In this volume an evolutionary GRN paradigm is investigated for its evolvability and robustness in models of biological clocks, in simple differentiated multicellularity, and in evolving artificial developing 'organisms' which grow and express an ontogeny starting fr...

  3. Revisiting System Paradigms from the Viewpoint of Manufacturing Sustainability

    Directory of Open Access Journals (Sweden)

    Zhuming Bi

    2011-08-01

    Full Text Available A system paradigm is an abstract representation of system; it includes system architecture used to determine the types and numbers of components and their relations in the system. The design of system paradigm relies on customers’ requirements and the characteristics of the manufacturing environment. Many system paradigms and design guidelines have been proposed for a variety of customers’ needs including functions, cost, quality, personalization, and lead time of products. However, the consideration of sustainability becomes essential to today’s manufacturing systems; a new challenge is how to evolve existing paradigms to accommodate the requirements of sustainability. In contrast to ample research activities on system paradigms in past decades, recent studies on system paradigms have been restricted, partially due to unclear research directions. Limited works can be found on conceiving new manufacturing system paradigms from the perspective of sustainability; most of the related literature concerns the new requirements of sustainability. The objectives of this work are (i to examine the requirements of manufacturing systems in a wider scope; (ii to revisit existing paradigms to clarify their limitations and bottlenecks; and eventually (iii to identify some research directions, which will lead to a solution of sustainable manufacturing. To achieve these objectives, firstly, a brief description of today’s manufacturing environment is provided. Secondly, the requirements of sustainability are discussed, and the relevant researches on system sustainability are surveyed. Thirdly, the reconfigurable system paradigm is focused, and the gaps between a reconfigurable manufacturing system and a sustainable manufacturing system are discussed. Finally, the future endeavors towards to the next-generation manufacturing system paradigms are discussed.

  4. End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R: A paradigm shift in clinical decision making.

    Science.gov (United States)

    Melani, Christopher; Advani, Ranjana; Roschewski, Mark; Walters, Kelsey M; Chen, Clara C; Baratto, Lucia; Ahlman, Mark A; Miljkovic, Milos D; Steinberg, Seth M; Lam, Jessica; Shovlin, Margaret; Dunleavy, Kieron; Pittaluga, Stefania; Jaffe, Elaine S; Wilson, Wyndham H

    2018-05-10

    Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow-up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3) and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R (NCT00001337). Copyright © 2018, Ferrata Storti Foundation.

  5. The resilience of paradigm mixes

    DEFF Research Database (Denmark)

    Daugbjerg, Carsten; Farsund, Arild Aurvåg; Langhelle, Oluf

    2017-01-01

    This paper argues that a policy regime based on a paradigm mix may be resilient when challenged by changing power balances and new agendas. Controversies between the actors can be contained within the paradigm mix as it enables them to legitimize different ideational positions. Rather than engaging...... context changed. The paradigm mix proved sufficiently flexible to accommodate food security concerns and at the same time continue to take steps toward further liberalization. Indeed, the main players have not challenged the paradigm mix....

  6. CHANGE OF ENERGY PARADIGM

    Directory of Open Access Journals (Sweden)

    Ionut PURICA

    2013-05-01

    Full Text Available We are at the beginning of a change of paradigm in the energy systems of the whole World. Both new resources being found and exploited and the new technologies for energy conversion, transport and distribution, along with the associated artificial intelligence systems, are starting to create new futures, with different living values, for the greatest machine created by men: the energy system. Some relevant elements are presented in the paper along with the position and the perspectives of Romania.

  7. Spacetimes containing slowly evolving horizons

    International Nuclear Information System (INIS)

    Kavanagh, William; Booth, Ivan

    2006-01-01

    Slowly evolving horizons are trapping horizons that are ''almost'' isolated horizons. This paper reviews their definition and discusses several spacetimes containing such structures. These include certain Vaidya and Tolman-Bondi solutions as well as (perturbatively) tidally distorted black holes. Taking into account the mass scales and orders of magnitude that arise in these calculations, we conjecture that slowly evolving horizons are the norm rather than the exception in astrophysical processes that involve stellar-scale black holes

  8. Natural selection promotes antigenic evolvability.

    Science.gov (United States)

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  9. Natural selection promotes antigenic evolvability.

    Directory of Open Access Journals (Sweden)

    Christopher J Graves

    Full Text Available The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish

  10. Robustness to Faults Promotes Evolvability: Insights from Evolving Digital Circuits.

    Science.gov (United States)

    Milano, Nicola; Nolfi, Stefano

    2016-01-01

    We demonstrate how the need to cope with operational faults enables evolving circuits to find more fit solutions. The analysis of the results obtained in different experimental conditions indicates that, in absence of faults, evolution tends to select circuits that are small and have low phenotypic variability and evolvability. The need to face operation faults, instead, drives evolution toward the selection of larger circuits that are truly robust with respect to genetic variations and that have a greater level of phenotypic variability and evolvability. Overall our results indicate that the need to cope with operation faults leads to the selection of circuits that have a greater probability to generate better circuits as a result of genetic variation with respect to a control condition in which circuits are not subjected to faults.

  11. Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria.

    Science.gov (United States)

    Frenoy, Antoine; Bonhoeffer, Sebastian

    2018-05-01

    The stress-induced mutagenesis hypothesis postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to better withstand the stress. This has implications for antibiotic treatment: exposure to subinhibitory doses of antibiotics has been reported to increase bacterial mutation rates and thus probably the rate at which resistance mutations appear and lead to treatment failure. More generally, the hypothesis posits that stress increases evolvability (the ability of a population to generate adaptive genetic diversity) and thus accelerates evolution. Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet subinhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus providing more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress. We developed a system based on plasmid segregation that allows us to measure death and division rates simultaneously in bacterial populations. Using this system, we found that a substantial death rate occurs at the tested subinhibitory concentrations previously reported to increase mutation rate. Taking this death rate into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover, even when antibiotics increase mutation rate, we show that subinhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics. We conclude that antibiotic-induced mutagenesis is overestimated because of death and that understanding evolvability under stress requires accounting for the effects of stress on population dynamics as much as on mutation rate. Our goal here is dual: we show that population dynamics and, in particular, the

  12. The peopleware paradigm.

    Science.gov (United States)

    Andrew, C G

    1996-08-01

    Manufacturing managements and practitioners alike are at long last realizing that the heartbeat of competitive advantage springs from peopleware, not hardware and software. But despite this heightened awareness the problem persists even among manufacturing professionals--they may talk a good game about priortizing people and quality, but all too many have precious little idea of how to go about it with constancy of purpose. This article bridges the gap and addresses the key issues in adopting the powerful new peopleware paradigm that provides the positive motivational climate for the improvement-change journey toward world-class performance through teamwork, innovation, and continuous improvement.

  13. Competitiveness: new economic paradigm?

    Directory of Open Access Journals (Sweden)

    Marlene Peñaloza

    2005-10-01

    Full Text Available Nowadays competitiveness is made up of “the new” paradigm that allows to prevail in the global World. Thus, it is inevitable to ask, was it required to be competitive to be successful in the international trade arena? Recognizing the discussion about it and its theoretical-conceptual density, the present paper studies this old notion whose meaning, in essence, is always the same one. This applies even though new realities in the present world-wide atmosphere confer to it a distinguishing character and new and old players are forced to organize actions and bring efforts together to obtain the competitive supremacy.

  14. A neighbourhood evolving network model

    International Nuclear Information System (INIS)

    Cao, Y.J.; Wang, G.Z.; Jiang, Q.Y.; Han, Z.X.

    2006-01-01

    Many social, technological, biological and economical systems are best described by evolved network models. In this short Letter, we propose and study a new evolving network model. The model is based on the new concept of neighbourhood connectivity, which exists in many physical complex networks. The statistical properties and dynamics of the proposed model is analytically studied and compared with those of Barabasi-Albert scale-free model. Numerical simulations indicate that this network model yields a transition between power-law and exponential scaling, while the Barabasi-Albert scale-free model is only one of its special (limiting) cases. Particularly, this model can be used to enhance the evolving mechanism of complex networks in the real world, such as some social networks development

  15. Long-term prognosis of young breast cancer patients (≤40 years) who did not receive adjuvant systemic treatment: protocol for the PARADIGM initiative cohort study

    NARCIS (Netherlands)

    Dackus, Gwen M. H. E.; ter Hoeve, Natalie D.; Opdam, Mark; Vreuls, Willem; Varga, Zsuzsanna; Koop, Esther; Willems, Stefan M.; van Deurzen, Carolien H. M.; Groen, Emilie J.; Cordoba, Alicia; Bart, Jos; Mooyaart, Antien L.; van den Tweel, Jan G.; Zolota, Vicky; Wesseling, Jelle; Sapino, Anna; Chmielik, Ewa; Ryska, Ales; Amant, Frederic; Broeks, Annegien; Kerkhoven, Ron; Stathonikos, Nikolas; Veta, Mitko; Voogd, Adri; Jozwiak, Katarzyna; Hauptmann, Michael; Hoogstraat, Marlous; Schmidt, Marjanka K.; Sonke, Gabe; van der Wall, Elsken; Siesling, Sabine; van Diest, Paul J.; Linn, Sabine C.

    2017-01-01

    Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically

  16. Long-term prognosis of young breast cancer patients (≤40 years) who did not receive adjuvant systemic treatment: protocol for the PARADIGM initiative cohort study

    NARCIS (Netherlands)

    Dackus, Gwen M.H.E.; ter Hoeve, Natalie.D.; Opdam, Mark; Vreuls, Willem; Varga, Zsuzanna; Koop, Esther; Willems, Stefan M.; van Deurzen, Carolien H.M.; Groen, Emilie J.; Cordoba, Alicia; Bart, Jos; Mooyaart, Antien L.; van den Tweel, Jan G.; Zolota, Vicky; Wesseling, Jelle; Sapino, Anna; Chmielik, Ewa; Ryska, Ales; Amant, Frederic; Broeks, Annegien; Kerkhoven, Ron; Stathonikos, Nikolas; Veta, Mitko; Voogd, Adri C.; Jozwiak, Katarzyna; Hauptmann, Michael; Hoogstraat, Marlous; Schmidt, Marjanka K.; Sonke, Gabe S.; van der Wall, E.; Siesling, Sabine; van Diest, Paul J.; Linn, Sabine C.

    2017-01-01

    Introduction Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient’s prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered

  17. Long-term prognosis of young breast cancer patients (≤40 years) who did not receive adjuvant systemic treatment : protocol for the PARADIGM initiative cohort study

    NARCIS (Netherlands)

    Dackus, Gwen Mhe; ter Hoeve, Natalie D.; Opdam, Mark; Vreuls, Willem; Varga, Zsuzsanna; Koop, Esther; Willems, Stefan M; van Deurzen, Carolien Hm; Groen, Emilie J; Cordoba, Alicia; Bart, Jos; Mooyaart, Antien L; van den Tweel, Jan G; Zolota, Vicky; Wesseling, Jelle; Sapino, Anna; Chmielik, Ewa; Ryska, Ales; Amant, Frederic; Broeks, Annegien; Kerkhoven, Ron; Stathonikos, Nikolas; Veta, Mitko; Voogd, Adri C.; Jozwiak, Katarzyna; Hauptmann, Michael; Hoogstraat, Marlous; Schmidt, Marjanka K.; Sonke, Gabe S; van der Wall, Elsken; Siesling, Sabine; van Diest, Paul J; Linn, Sabine C

    2017-01-01

    INTRODUCTION: Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered

  18. Long-term prognosis of young breast cancer patients (≤40 years) who did not receive adjuvant systemic treatment : Protocol for the PARADIGM initiative cohort study

    NARCIS (Netherlands)

    Dackus, Gwen Mhe; Ter Hoeve, Natalie D; Opdam, Mark; Vreuls, Willem; Varga, Zsuzsanna; Koop, Esther; Willems, Stefan M; Van Deurzen, Carolien Hm; Groen, Emilie J; Cordoba, Alicia; Bart, Jos; Mooyaart, Antien L; van den Tweel, Jan G; Zolota, Vicky; Wesseling, Jelle; Sapino, Anna; Chmielik, Ewa; Ryska, Ales; Amant, Frederic; Broeks, Annegien; Kerkhoven, Ron; Stathonikos, Nikolas; Veta, Mitko; Voogd, Adri; Jozwiak, Katarzyna; Hauptmann, Michael; Hoogstraat, Marlous; Schmidt, Marjanka K; Sonke, Gabe; van der Wall, Elsken; Siesling, Sabine; van Diest, Paul J; Linn, Sabine C

    2017-01-01

    INTRODUCTION: Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered

  19. Microgrids in the Evolving Electricity Generation and DeliveryInfrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Marnay, Chris; Venkataramanan, Giri

    2006-02-01

    The legacy paradigm for electricity service in most of the electrified world today is based on the centralized generation-transmission-distribution infrastructure that evolved under a regulated environment. More recently, a quest for effective economic investments, responsive markets, and sensitivity to the availability of resources, has led to various degrees of deregulation and unbundling of services. In this context, a new paradigm is emerging wherein electricity generation is intimately embedded with the load in microgrids. Development and decay of the familiar macrogrid is discussed. Three salient features of microgrids are examined to suggest that cohabitation of micro and macro grids is desirable, and that overall energy efficiency can be increased, while power is delivered to loads at appropriate levels of quality.

  20. Vascular access surveillance: case study of a false paradigm.

    Science.gov (United States)

    Paulson, William D; Moist, Louise; Lok, Charmaine E

    2013-01-01

    The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm for a new test or treatment can lead to adoption of a false paradigm. Paradigms are the beliefs and assumptions shared by those in a field of knowledge, and are commonly included in clinical practice guidelines. The guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend that arteriovenous vascular accesses undergo routine surveillance for detection and correction of stenosis. This recommendation is based on the paradigm that surveillance of access blood flow or dialysis venous pressure combined with correction of stenosis improves access outcomes. However, the quality of evidence that supports this paradigm has been widely criticized. We tested the validity of the surveillance paradigm by applying World Health Organization (WHO) criteria for evaluating screening tests to a literature review of published vascular access studies. These criteria include four components: undesired condition, screening test, intervention, and desired outcome. The WHO criteria show that surveillance as currently practiced fails all four components and provides little or no significant benefit, suggesting that surveillance is a false paradigm. Once a paradigm is established, however, challenges to its validity are usually resisted even as new evidence indicates the paradigm is not valid. Thus, it is paramount to apply rigorous criteria when developing guidelines. Regulators may help promote needed changes in paradigms when cost and safety considerations coincide. © 2013 Wiley Periodicals, Inc.

  1. Geographic Object-Based Image Analysis - Towards a new paradigm.

    Science.gov (United States)

    Blaschke, Thomas; Hay, Geoffrey J; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

    2014-01-01

    The amount of scientific literature on (Geographic) Object-based Image Analysis - GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ' per-pixel paradigm ' and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm.

  2. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  3. The WIMP Paradigm: Current Status

    International Nuclear Information System (INIS)

    Feng, Jonathan

    2011-01-01

    The WIMP paradigm is the glue that joins together much of the high energy and cosmic frontiers. It postulates that most of the matter in the Universe is made of weakly-interacting massive particles, with implications for a broad range of experiments and observations. I will review the WIMP paradigm's underlying motivations, its current status in view of rapid experimental progress on several fronts, and recent theoretical variations on the WIMP paradigm theme.

  4. Changing environments or shifting paradigms? Strategic decision making toward water protection in Helsinki, 1850-2000.

    Science.gov (United States)

    Laakkonen, Simo; Laurila, Sari

    2007-04-01

    The study examines the history of strategic decision-making concerning water protection in Helsinki, 1850-2000. We identified five major strategic decisions that occurred during the study period. The results indicate that strategic decision-making evolves in long-term policy cycles that last on average 20-30 years. New policy cycles are caused by paradigm shifts. Paradigms are shared and predominant ways of understanding reality that help when groups must act to solve common and complex environmental problems. However the internal structure and external dynamics of paradigms are contradictory. Although paradigms serve initially as means to redefine problems and find creative solutions, as time goes by each paradigm seems to become also a barrier that restricts the introduction of new ways of thinking and acting. The power of paradigms lies in the fact that they can be defined as scientific but also social, political, or cultural agreements depending on the context.

  5. PARADIGM OF ACCOUNTING CHANGE

    Directory of Open Access Journals (Sweden)

    Constanta Iacob

    2016-12-01

    Full Text Available The words and phrases swop with each other and the apparent stability of a word’s meaning sometimes change in time. This explains why the generic term of accounting is used when referring to the qualities attributed to accounting,but also when it comes to organizing financial accounting function within the entity, and when referring concretely to keeping a double record with its specific means, methods and tools specific, respectively seen as a technical accounting.Speaking about the qualities of accounting, but also about the organizational form it takes, we note that there is a manifold meaning of the word accounting, which is why the purpose of this article is to demonstrate that the paradigm shift aimed at a new set of rules and if the rules changes, then we can change the very purpose of accounting.

  6. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  7. Fasting plasma triglycerides predict the glycaemic response to treatment of Type 2 diabetes by gastric electrical stimulation. A novel lipotoxicity paradigm

    Science.gov (United States)

    Lebovitz, H E; Ludvik, B; Yaniv, I; Haddad, W; Schwartz, T; Aviv, R

    2013-01-01

    Background Non-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level. Method An analysis of 40 patients who had had detailed longitudinal studies for 12 months. Results Twenty-two patients with fasting plasma triglycerides ≤ 1.7 mmol/l had mean decreases in HbA1c after 3, 6 and 12 months of gastric contraction modulation treatment of −15 ± 2.1 mmol/mol (−1.39 ± 0.20%), −16 ± 2.2 mmol/mol (−1.48 ± 0.20%) and −14 ± 3.0 mmol/mol (−1.31 ± 0.26%), respectively. In contrast, 18 patients with fasting plasma triglyceride > 1.7 mmol/l had mean decreases in HbA1c of −7 ± 1.7 mmol/mol (−0.66 ± 0.16%), −5 ± 1.6 mmol/mol (−0.44 ± 0.18%) and −5 ± 1.7 mmol/mol (−0.42 ± 0.16%), respectively. Pearson's correlation coefficient between fasting plasma triglyceride and decreases in HbA1c at 12 months of treatment was 0.34 (P triglycerides, while it progressively improved in patients with low fasting plasma triglycerides. Patients with low fasting plasma triglycerides had a tendency to lose more weight than those with high fasting plasma triglycerides, but this did not achieve statistical significance. Conclusions The data presented suggest the existance of a triglyceride lipotoxic mechanism that interferes with gastric/neural mediated pathways that can regulate glycaemic control in patients with type 2 diabetes. The data suggest the existence of a triglyceride lipotoxic pathway that interferes with gastric/neural mediated pathways that can regulate glycaemic control

  8. Management Trends and Outcomes for Stage I to II Mantle Cell Lymphoma Using the National Cancer Data Base: Ascertaining the Ideal Treatment Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Beant S.; Vargo, John A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Pai, Sarah S. [Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Balasubramani, Goundappa K. [Department of Epidemiology, Epidemiology Data Center, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania (United States); Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States)

    2015-11-01

    Purpose: Mantle cell lymphoma (MCL) is a rare, albeit aggressive subset of non-Hodgkin lymphoma, resulting in varied treatment approaches. Given the paucity of data defining the optimal management for early-stage MCL, we conducted an analysis using the National Cancer Data Base (NCDB) to identify practice patterns and outcomes. Methods and Materials: The NCDB was queried for patients with stage I to II MCL diagnosed from 1998 to 2012 receiving chemotherapy (CT) or radiation therapy (RT), or both (CT+RT). Univariate and multivariable analyses for factors associated with treatment selection were completed using logistic regression. Propensity scores with inverse probability treatment weighting (IPTW) were calculated based on the conditional probability of receiving CT+RT. The log-rank test and Cox proportional hazards modeling with IPTW adjustment were conducted for the survival analyses. Results: In total, 2539 patients were identified. The key characteristics were as follows: 69% were male, 71% were aged ≥60 years, 28% had extranodal involvement, and 51% had stage I disease. Of the 2539 patients, 70% underwent CT, 11% underwent RT, and 19% underwent CT+RT. The use of CT+RT decreased from 23.1% to 14.1% in 1998 to 2002 and 2010 to 2012 (P<.001). CT+RT usage was lower for patients with the following characteristics: age ≥60 years, female sex, stage II disease, and the presence of B symptoms. With a median follow-up period of 42.8 months, the unadjusted 3-year overall survival estimates for patients receiving CT, RT, or CT+RT were 67.8%, 72.4%, and 79.8%, respectively (P<.001). After correcting for indication bias through IPTW-adjusted modeling, CT+RT reduced the risk of overall mortality compared with monotherapy (hazard ratio 0.65, P=.029). Conclusions: Although uncommon, patients with stage I-II MCL can have favorable outcomes. Despite a continued decline in the usage of consolidative RT, combined modality therapy improves survival in this cohort compared

  9. Management Trends and Outcomes for Stage I to II Mantle Cell Lymphoma Using the National Cancer Data Base: Ascertaining the Ideal Treatment Paradigm

    International Nuclear Information System (INIS)

    Gill, Beant S.; Vargo, John A.; Pai, Sarah S.; Balasubramani, Goundappa K.; Beriwal, Sushil

    2015-01-01

    Purpose: Mantle cell lymphoma (MCL) is a rare, albeit aggressive subset of non-Hodgkin lymphoma, resulting in varied treatment approaches. Given the paucity of data defining the optimal management for early-stage MCL, we conducted an analysis using the National Cancer Data Base (NCDB) to identify practice patterns and outcomes. Methods and Materials: The NCDB was queried for patients with stage I to II MCL diagnosed from 1998 to 2012 receiving chemotherapy (CT) or radiation therapy (RT), or both (CT+RT). Univariate and multivariable analyses for factors associated with treatment selection were completed using logistic regression. Propensity scores with inverse probability treatment weighting (IPTW) were calculated based on the conditional probability of receiving CT+RT. The log-rank test and Cox proportional hazards modeling with IPTW adjustment were conducted for the survival analyses. Results: In total, 2539 patients were identified. The key characteristics were as follows: 69% were male, 71% were aged ≥60 years, 28% had extranodal involvement, and 51% had stage I disease. Of the 2539 patients, 70% underwent CT, 11% underwent RT, and 19% underwent CT+RT. The use of CT+RT decreased from 23.1% to 14.1% in 1998 to 2002 and 2010 to 2012 (P<.001). CT+RT usage was lower for patients with the following characteristics: age ≥60 years, female sex, stage II disease, and the presence of B symptoms. With a median follow-up period of 42.8 months, the unadjusted 3-year overall survival estimates for patients receiving CT, RT, or CT+RT were 67.8%, 72.4%, and 79.8%, respectively (P<.001). After correcting for indication bias through IPTW-adjusted modeling, CT+RT reduced the risk of overall mortality compared with monotherapy (hazard ratio 0.65, P=.029). Conclusions: Although uncommon, patients with stage I-II MCL can have favorable outcomes. Despite a continued decline in the usage of consolidative RT, combined modality therapy improves survival in this cohort compared

  10. Romanian spa tourism: a communist paradigm in a post communist era

    Directory of Open Access Journals (Sweden)

    George Erdeli

    2011-11-01

    Full Text Available Spa tourism is one of the oldest forms of tourism which continuously evolved in time as the leisure industry paradigm and the consumers’ behavior changed. Similar to other countries in Central and Eastern Europe, spa tourism is an old phenomenon in Romania which expanded to the dimensions of a well defined tourism industry during the mass tourism period which also corresponded to the communism epoch. Although severely affected by the major political and socio-economic changes which occurred after the Revolution in 1989, this industry coexists with new emergent forms of tourism orienting, itself towards new dimensions embraced by the contemporary leisure consumerism (e.g. medical tourism, cosmetic treatments. Lying on considerable balneal and climate resources and displaying an important communist heritage both in physical terms (large and massive tourism structures and in virtual and psychological terms (social supportive ticket granting system, Romanian spa tourism faces various challenges in the attempt to adapt in a new tourism era.

  11. Black holes: the membrane paradigm

    International Nuclear Information System (INIS)

    Thorne, K.S.; Price, R.H.; Macdonald, D.A.

    1986-01-01

    The physics of black holes is explored in terms of a membrane paradigm which treats the event horizon as a two-dimensional membrane embedded in three-dimensional space. A 3+1 formalism is used to split Schwarzschild space-time and the laws of physics outside a nonrotating hole, which permits treatment of the atmosphere in terms of the physical properties of thin slices. The model is applied to perturbed slowly or rapidly rotating and nonrotating holes, and to quantify the electric and magnetic fields and eddy currents passing through a membrane surface which represents a stretched horizon. Features of tidal gravitational fields in the vicinity of the horizon, quasars and active galalctic nuclei, the alignment of jets perpendicular to accretion disks, and the effects of black holes at the center of ellipsoidal star clusters are investigated. Attention is also given to a black hole in a binary system and the interactions of black holes with matter that is either near or very far from the event horizon. Finally, a statistical mechanics treatment is used to derive a second law of thermodynamics for a perfectly thermal atmosphere of a black hole

  12. The Rational Relevance of the Diffuse Paradigms

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-01-01

    Full Text Available Processes like the globalization consistency and learning about society are screened by diffuse concepts such as those taking the last steps of the industrial civilization and hierarchically ordered world through hegemony. This is why the meaning of globalization is given by deviant trends, like globalism, and the knowledge society is taken for the tools promoted by itself, such as the internet. This does not imply only approximations of meaning but rather the vanity of change, preserving the status quo represented by the pre-global world or the adversity principle. Historicism of paradigm cannot be avoided. Evolvement towards something else, announced by globalization is implacable, and the new ordinating principle, the one of competition, opens the opportunity horizon to global world.

  13. The Rational Relevance of the Diffuse Paradigms

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-03-01

    Full Text Available Processes like the globalization consistency and learning about society are screened by diffuse concepts such as those taking the last steps of the industrial civilization and hierarchically ordered world through hegemony. This is why the meaning of globalization is given by deviant trends, like globalism, and the knowledge society is taken for the tools promoted by itself, such as the internet. This does not imply only approximations of meaning but rather the vanity of change, preserving the status quo represented by the pre-global world or the adversity principle. Historicism of paradigm cannot be avoided. Evolvement towards something else, announced by globalization is implacable, and the new ordinating principle, the one of competition, opens the opportunity horizon to global world

  14. Systems healthcare: a holistic paradigm for tomorrow.

    Science.gov (United States)

    Fiandaca, Massimo S; Mapstone, Mark; Connors, Elenora; Jacobson, Mireille; Monuki, Edwin S; Malik, Shaista; Macciardi, Fabio; Federoff, Howard J

    2017-12-19

    Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer's and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.

  15. Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

    Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

  16. Evolving phenotypic networks in silico.

    Science.gov (United States)

    François, Paul

    2014-11-01

    Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  17. Ranking in evolving complex networks

    Science.gov (United States)

    Liao, Hao; Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng; Zhou, Ming-Yang

    2017-05-01

    Complex networks have emerged as a simple yet powerful framework to represent and analyze a wide range of complex systems. The problem of ranking the nodes and the edges in complex networks is critical for a broad range of real-world problems because it affects how we access online information and products, how success and talent are evaluated in human activities, and how scarce resources are allocated by companies and policymakers, among others. This calls for a deep understanding of how existing ranking algorithms perform, and which are their possible biases that may impair their effectiveness. Many popular ranking algorithms (such as Google's PageRank) are static in nature and, as a consequence, they exhibit important shortcomings when applied to real networks that rapidly evolve in time. At the same time, recent advances in the understanding and modeling of evolving networks have enabled the development of a wide and diverse range of ranking algorithms that take the temporal dimension into account. The aim of this review is to survey the existing ranking algorithms, both static and time-aware, and their applications to evolving networks. We emphasize both the impact of network evolution on well-established static algorithms and the benefits from including the temporal dimension for tasks such as prediction of network traffic, prediction of future links, and identification of significant nodes.

  18. Intraoperative detection of subtle endometriosis: a novel paradigm for detection and treatment of pelvic pain associated with the loss of peritoneal integrity.

    Science.gov (United States)

    Lessey, Bruce A; Higdon, H Lee; Miller, Sara E; Price, Thomas A

    2012-12-21

    Endometriosis is a common disease affecting 40 to 70% of reproductive-aged women with chronic pelvic pain (CPP) and/or infertility. The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surfaces during laparoscopy (L/S) to detect the loss of peritoneal integrity in patients with pelvic pain and suspected endometriosis. Forty women with CPP and 5 women without pain were evaluated in this pilot study. During L/S, concentrated dye was sprayed onto peritoneal surfaces, then aspirated and rinsed with Lactated Ringers solution. Areas of localized dye uptake were evaluated for the presence of visible endometriotic lesions. Areas of intense peritoneal staining were resected and some fixed in 2.5% buffered gluteraldehyde and examined by scanning (SEM) electron microscopy. Blue dye uptake was more common in women with endometriosis and chronic pelvic pain than controls (85% vs. 40%). Resection of the blue stained areas revealed endometriosis by SEM and loss of peritoneal cell-cell contact compared to normal, non-staining peritoneum. Affected peritoneum was associated with visible endometriotic implants in most but not all patients. Subjective pain relief was reported in 80% of subjects. Based on scanning electron microscopy, we conclude that endometrial cells extend well beyond visible implants of endometriosis and appear to disrupt the underlying mesothelium. Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity, allowing menstrual or ovulatory blood and associated pain factors access to underlying sensory nerves. Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP. This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at L/S and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy.

  19. EVOLVE : a Bridge between Probability, Set Oriented Numerics, and Evolutionary Computation II

    CERN Document Server

    Coello, Carlos; Tantar, Alexandru-Adrian; Tantar, Emilia; Bouvry, Pascal; Moral, Pierre; Legrand, Pierrick; EVOLVE 2012

    2013-01-01

    This book comprises a selection of papers from the EVOLVE 2012 held in Mexico City, Mexico. The aim of the EVOLVE is to build a bridge between probability, set oriented numerics and evolutionary computing, as to identify new common and challenging research aspects. The conference is also intended to foster a growing interest for robust and efficient methods with a sound theoretical background. EVOLVE is intended to unify theory-inspired methods and cutting-edge techniques ensuring performance guarantee factors. By gathering researchers with different backgrounds, a unified view and vocabulary can emerge where the theoretical advancements may echo in different domains. Summarizing, the EVOLVE focuses on challenging aspects arising at the passage from theory to new paradigms and aims to provide a unified view while raising questions related to reliability,  performance guarantees and modeling. The papers of the EVOLVE 2012 make a contribution to this goal. 

  20. The 'E' factor -- evolving endodontics.

    Science.gov (United States)

    Hunter, M J

    2013-03-01

    Endodontics is a constantly developing field, with new instruments, preparation techniques and sealants competing with trusted and traditional approaches to tooth restoration. Thus general dental practitioners must question and understand the significance of these developments before adopting new practices. In view of this, the aim of this article, and the associated presentation at the 2013 British Dental Conference & Exhibition, is to provide an overview of endodontic methods and constantly evolving best practice. The presentation will review current preparation techniques, comparing rotary versus reciprocation, and question current trends in restoration of the endodontically treated tooth.

  1. Historical ESWT Paradigms Are Overcome: A Narrative Review

    OpenAIRE

    Lohrer, Heinz; Nauck, Tanja; Korakakis, Vasileios; Malliaropoulos, Nikos

    2016-01-01

    Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a hi...

  2. A nomenclature paradigm for benign midmembranous vocal fold lesions.

    Science.gov (United States)

    Rosen, Clark A; Gartner-Schmidt, Jackie; Hathaway, Bridget; Simpson, C Blake; Postma, Gregory N; Courey, Mark; Sataloff, Robert T

    2012-06-01

    There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature. Clinical consensus conferences were held to develop an initial BVFL nomenclature paradigm. Perceptual video analysis was performed to validate the stroboscopy component of the paradigm. The culmination of the consensus conferences and the video-perceptual analysis was used to evaluate the BVFL nomenclature paradigm using a retrospective review of patients with BVFL. An initial BVFL nomenclature paradigm was proposed utilizing detailed definitions relating to vocal fold lesion morphology, stroboscopy, response to voice therapy and intraoperative findings. Video-perceptual analysis of stroboscopy demonstrated that the proposed binary stroboscopy system used in the BVFL nomenclature paradigm was valid and widely applicable. Retrospective review of 45 patients with BVFL followed to the conclusion of treatment demonstrated that slight modifications of the initial BVFL nomenclature paradigm were required. With the modified BVFL nomenclature paradigm, 96% of the patients fit into the predicted pattern and definitions of the BVFL nomenclature system. This study has validated a multidimensional BVFL nomenclature paradigm. This vocal fold nomenclature paradigm includes nine distinct vocal fold lesions: vocal fold nodules, vocal fold polyp, pseudocyst, vocal fold cyst (subepithelial or ligament), nonspecific vocal fold lesion, vocal fold fibrous mass (subepithelial or ligament), and reactive lesion. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  3. Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving cardiac safety testing paradigm.

    Science.gov (United States)

    Wiśniowska, Barbara; Tylutki, Zofia; Polak, Sebastian

    2017-10-01

    Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.

    Science.gov (United States)

    Reinsmoen, Nancy L; Lai, Chi-Hung; Vo, Ashley; Jordan, Stanley C

    2012-04-01

    The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. More recent advances have occurred through implementation of a national allocation system requiring the entering of unacceptable antigens that reduces the rate of crossmatch positivity. Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.

  5. Negative pressure darwinism: survival of the fittest paradigm.

    Science.gov (United States)

    Miller, Michael; Bybordi, Farhad

    2009-07-01

    The use of negative pressure for wound healing has been based on a set of parameters and devices that until recently were combined into a single paradigm. Despite historical and more recent evidence providing viable alternative considerations, it is only recently that this paradigm and its tenets have come into question. As the understanding of the limits of the current paradigm and specific instances of its benefits and drawbacks are identified, shifts in the paradigm must take place if the therapy is to evolve, develop, and continue to be efficacious. The pertinence of the concept of survival of the fittest is used to explore the need for a paradigm shift in negative pressure wound therapy.

  6. The Consumption Paradigm in Marketing

    Directory of Open Access Journals (Sweden)

    Eka Ardianto

    2003-08-01

    Full Text Available This article elaborates consumption paradigm in marketing. In background, this paper reviews different perspectives of consumption: economic perspective and marketing perspective. In ontology, this work describes various issues regarding consumption view. In epistemology, this article demonstrates how marketers especially researches explore the consumption phenomena. In methodology, the article describes experiential marketing –one of applied consumption paradigm in marketing, which could be an alternative choice of marketing practices.

  7. Peripartum hysterectomy: an evolving picture.

    LENUS (Irish Health Repository)

    Turner, Michael J

    2012-02-01

    Peripartum hysterectomy (PH) is one of the obstetric catastrophes. Evidence is emerging that the role of PH in modern obstetrics is evolving. Improving management of postpartum hemorrhage and newer surgical techniques should decrease PH for uterine atony. Rising levels of repeat elective cesarean deliveries should decrease PH following uterine scar rupture in labor. Increasing cesarean rates, however, have led to an increase in the number of PHs for morbidly adherent placenta. In the case of uterine atony or rupture where PH is required, a subtotal PH is often sufficient. In the case of pathological placental localization involving the cervix, however, a total hysterectomy is required. Furthermore, the involvement of other pelvic structures may prospectively make the diagnosis difficult and the surgery challenging. If resources permit, PH for pathological placental localization merits a multidisciplinary approach. Despite advances in clinical practice, it is likely that peripartum hysterectomy will be more challenging for obstetricians in the future.

  8. Infrared spectroscopy of evolved objects

    International Nuclear Information System (INIS)

    Aitken, D.K.; Roche, P.F.

    1984-01-01

    In this review, the authors are concerned with spectroscopic observations of evolved objects made in the wavelength range 1-300μm. Spectroscopic observations can conveniently be divided into studies of narrow lines, bands and broader continua. The vibrational frequencies of molecular groups fall mainly in this spectral region and appear as vibration-rotation bands from the gas phase, and as less structured, but often broader, features from the solid state. Many ionic lines, including recombination lines of abundant species and fine structure lines of astrophysically important ions also appear in this region. The continuum can arise from a number of mechanisms - photospheric emission, radiation from dust, free-free transitions in ionized gas and non-thermal processes. (Auth.)

  9. CERN internal communication is evolving

    CERN Multimedia

    2016-01-01

    CERN news will now be regularly updated on the CERN People page (see here).      Dear readers, All over the world, communication is becoming increasingly instantaneous, with news published in real time on websites and social networks. In order to keep pace with these changes, CERN's internal communication is evolving too. From now on, you will be informed of what’s happening at CERN more often via the “CERN people” page, which will frequently be updated with news. The Bulletin is following this trend too: twice a month, we will compile the most important articles published on the CERN site, with a brand-new layout. You will receive an e-mail every two weeks as soon as this new form of the Bulletin is available. If you have interesting news or stories to share, tell us about them through the form at: https://communications.web.cern.ch/got-story-cern-website​. You can also find out about news from CERN in real time...

  10. Economies Evolve by Energy Dispersal

    Directory of Open Access Journals (Sweden)

    Stanley Salthe

    2009-10-01

    Full Text Available Economic activity can be regarded as an evolutionary process governed by the 2nd law of thermodynamics. The universal law, when formulated locally as an equation of motion, reveals that a growing economy develops functional machinery and organizes hierarchically in such a way as to tend to equalize energy density differences within the economy and in respect to the surroundings it is open to. Diverse economic activities result in flows of energy that will preferentially channel along the most steeply descending paths, leveling a non-Euclidean free energy landscape. This principle of 'maximal energy dispersal‘, equivalent to the maximal rate of entropy production, gives rise to economic laws and regularities. The law of diminishing returns follows from the diminishing free energy while the relation between supply and demand displays a quest for a balance among interdependent energy densities. Economic evolution is dissipative motion where the driving forces and energy flows are inseparable from each other. When there are multiple degrees of freedom, economic growth and decline are inherently impossible to forecast in detail. Namely, trajectories of an evolving economy are non-integrable, i.e. unpredictable in detail because a decision by a player will affect also future decisions of other players. We propose that decision making is ultimately about choosing from various actions those that would reduce most effectively subjectively perceived energy gradients.

  11. Recommendation in evolving online networks

    Science.gov (United States)

    Hu, Xiao; Zeng, An; Shang, Ming-Sheng

    2016-02-01

    Recommender system is an effective tool to find the most relevant information for online users. By analyzing the historical selection records of users, recommender system predicts the most likely future links in the user-item network and accordingly constructs a personalized recommendation list for each user. So far, the recommendation process is mostly investigated in static user-item networks. In this paper, we propose a model which allows us to examine the performance of the state-of-the-art recommendation algorithms in evolving networks. We find that the recommendation accuracy in general decreases with time if the evolution of the online network fully depends on the recommendation. Interestingly, some randomness in users' choice can significantly improve the long-term accuracy of the recommendation algorithm. When a hybrid recommendation algorithm is applied, we find that the optimal parameter gradually shifts towards the diversity-favoring recommendation algorithm, indicating that recommendation diversity is essential to keep a high long-term recommendation accuracy. Finally, we confirm our conclusions by studying the recommendation on networks with the real evolution data.

  12. Evolving Capabilities for Virtual Globes

    Science.gov (United States)

    Glennon, A.

    2006-12-01

    Though thin-client spatial visualization software like Google Earth and NASA World Wind enjoy widespread popularity, a common criticism is their general lack of analytical functionality. This concern, however, is rapidly being addressed; standard and advanced geographic information system (GIS) capabilities are being developed for virtual globes--though not centralized into a single implementation or software package. The innovation is mostly originating from the user community. Three such capabilities relevant to the earth science, education, and emergency management communities are modeling dynamic spatial phenomena, real-time data collection and visualization, and multi-input collaborative databases. Modeling dynamic spatial phenomena has been facilitated through joining virtual globe geometry definitions--like KML--to relational databases. Real-time data collection uses short scripts to transform user-contributed data into a format usable by virtual globe software. Similarly, collaborative data collection for virtual globes has become possible by dynamically referencing online, multi-person spreadsheets. Examples of these functions include mapping flows within a karst watershed, real-time disaster assessment and visualization, and a collaborative geyser eruption spatial decision support system. Virtual globe applications will continue to evolve further analytical capabilities, more temporal data handling, and from nano to intergalactic scales. This progression opens education and research avenues in all scientific disciplines.

  13. The maturing of the quality improvement paradigm in the SEL

    Science.gov (United States)

    Basili, Victor R.

    1993-01-01

    The Software Engineering Laboratory uses a paradigm for improving the software process and product, called the quality improvement paradigm. This paradigm has evolved over the past 18 years, along with our software development processes and product. Since 1976, when we first began the SEL, we have learned a great deal about improving the software process and product, making a great many mistakes along the way. Quality improvement paradigm, as it is currently defined, can be broken up into six steps: characterize the current project and its environment with respect to the appropriate models and metrics; set the quantifiable goals for successful project performance and improvement; choose the appropriate process model and supporting methods and tools for this project; execute the processes, construct the products, and collect, validate, and analyze the data to provide real-time feedback for corrective action; analyze the data to evaluate the current practices, determine problems, record findings, and make recommendations for future project improvements; and package the experience gained in the form of updated and refined models and other forms of structured knowledge gained from this and prior projects and save it in an experience base to be reused on future projects.

  14. The evolving integrated vascular surgery residency curriculum.

    Science.gov (United States)

    Smith, Brigitte K; Greenberg, Jacob A; Mitchell, Erica L

    2014-10-01

    PDs voiced concern over the lack of standardization among the differing programs and most of the PDs agree that some degree of programmatic standardization is critical for the continued success of the 0 + 5 training paradigm. Qualitative evaluation of PD experiences with the development of 0 + 5 vascular surgery residency programs reveals the key factors that commonly influence program design. Programs continue to evolve in both structure and content as PDs respond to these influences. Learning from the collective experience of PDs and some standardization of the curricula may help current and future programs avoid common pitfalls in curricular development. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Hormonal evaluation of the infertile male: has it evolved?

    Science.gov (United States)

    Sussman, Ernest M; Chudnovsky, Aleksander; Niederberger, Craig S

    2008-05-01

    An endocrinologic evaluation of patients who have male-factor infertility has clearly evolved and leads to specific diagnoses and treatment strategies in a large population of infertile men. A well-considered endocrine evaluation is especially essential with the ever-growing popularity of assisted reproductive techniques and continued refinements with intracytoplasmic sperm injection.

  16. Nonlinear attractor dynamics in the fundamental and extended prism adaptation paradigm

    International Nuclear Information System (INIS)

    Frank, T.D.; Blau, Julia J.C.; Turvey, M.T.

    2009-01-01

    Adaptation and re-adaptation processes are studied in terms of dynamic attractors that evolve and devolve. In doing so, a theoretical account is given for the fundamental observation that adaptation and re-adaptation processes do not exhibit one-trial learning. Moreover, the emergence of the latent aftereffect in the extended prism paradigm is addressed

  17. Paradigm Shifts in Ophthalmic Diagnostics.

    Science.gov (United States)

    Sebag, J; Sadun, Alfredo A; Pierce, Eric A

    2016-08-01

    Future advances in ophthalmology will see a paradigm shift in diagnostics from a focus on dysfunction and disease to better measures of psychophysical function and health. Practical methods to define genotypes will be increasingly important and non-invasive nanotechnologies are needed to detect molecular changes that predate histopathology. This is not a review nor meant to be comprehensive. Specific topics have been selected to illustrate the principles of important paradigm shifts that will influence the future of ophthalmic diagnostics. It is our impression that future evaluation of vision will go beyond visual acuity to assess ocular health in terms of psychophysical function. The definition of disease will incorporate genotype into what has historically been a phenotype-centric discipline. Non-invasive nanotechnologies will enable a paradigm shift from disease detection on a cellular level to a sub-cellular molecular level. Vision can be evaluated beyond visual acuity by measuring contrast sensitivity, color vision, and macular function, as these provide better insights into the impact of aging and disease. Distortions can be quantified and the psychophysical basis of vision can be better evaluated than in the past by designing tests that assess particular macular cell function(s). Advances in our understanding of the genetic basis of eye diseases will enable better characterization of ocular health and disease. Non-invasive nanotechnologies can assess molecular changes in the lens, vitreous, and macula that predate visible pathology. Oxygen metabolism and circulatory physiology are measurable indices of ocular health that can detect variations of physiology and early disease. This overview of paradigm shifts in ophthalmology suggests that the future will see significant improvements in ophthalmic diagnostics. The selected topics illustrate the principles of these paradigm shifts and should serve as a guide to further research and development. Indeed

  18. The evolved athlete a guide for elite sport enhancement

    CERN Document Server

    Ivancevic, Tijana; Gojkovic, Zoran; Greenberg, Ronald; Greenberg, Helen; Jovanovic, Bojan; Lukman, Aleksandar

    2017-01-01

    This handbook provides insights into becoming a better and more evolved athlete. It offers aspiring athletes, regardless of skill level, a better understanding of their bodies and how to unlock the unlimited potential of muscles without injury. It focuses on the “superhero” muscle: the iliopsoas, and also sheds light on Diamond-Corporation’s new technology and elite athleticism, and how these can contribute to a healthier life. Lastly, the authors explore the mindset of success and provide exercises for remaining calm under pressure. This stand-alone book is the sequel to Paradigm Shift for Future Tennis and Enhancing Performance and Reducing Stress in Sport (2014, Springer). This book is written by scientists, whose expertise collectively spans the fields of biomechanics, clinical surgery, current and former elite athleticism, engineering and naturopath doctoral work. Together, they aim to inspire and educate athletes on how to improve their sports performance by using new technologies, world class bio...

  19. The synthesis paradigm in genetics.

    Science.gov (United States)

    Rice, William R

    2014-02-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics--and other fields of biology--are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous "-omics" data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.

  20. Transmission pricing: paradigms and methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)

    1994-12-31

    In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

  1. CNN a paradigm for complexity

    CERN Document Server

    Chua, Leon O

    1998-01-01

    Revolutionary and original, this treatise presents a new paradigm of EMERGENCE and COMPLEXITY, with applications drawn from numerous disciplines, including artificial life, biology, chemistry, computation, physics, image processing, information science, etc.CNN is an acronym for Cellular Neural Networks when used in the context of brain science, or Cellular Nonlinear Networks, when used in the context of emergence and complexity. A CNN is modeled by cells and interactions: cells are defined as dynamical systems and interactions are defined via coupling laws. The CNN paradigm is a universal Tur

  2. Idiopathic pulmonary fibrosis: evolving concepts.

    Science.gov (United States)

    Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

    2014-08-01

    Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  3. Tibiotalar torsion: bioengineering paradigm.

    Science.gov (United States)

    Michele, A A; Nielsen, P M

    1976-10-01

    1. Medial tibiotalar torsion is the most common disorder peculiar to mankind. 2. The pathogonomic findings are (a) an axial medially rotated and adducted distal third of the shaft of the tibia, (b) the plafond of the tibia with its mortise containing the "track-bound" talus, which is deflected strongly toward the tibial side, (c) an exaggerated midtarsal equinus, (d) ostensible restriction of dorsiflexion of the hindfoot against the tibia, (e) mild separation of the distal tibiofibular articulation, and (f) forward displacement of the gravitational axis to the naviculocunei-form joint. 3. Faulty leg crossing in utero resulting in an abnormal pelvofemoral-tibial design is discussed and its important consequences in the vulnerable 40 per cent of the population are emphasized. 4. The kinesiomechanics of the leg, ankle and foot is reviewed. 5. The radiographic parameters of medial tibiotalar torsion are presented, as well as the multiple facets of the clinical examination. 6. Methods of treatment depending on age and severity of the disorder are recommended. Surgery, detortional casts, and corrective footwear are discussed. Shoes presently available are inadequate for tibiotalar torsion and therefore engineering principles must be applied in the design and construction of all footwear, including sneakers and sportswear. This can be done only if the pathological biomechanics of this group of disorders is recognized. Biplane proximal tibial osteotomy is recommended in refractory cases, especially when tibiotalar torsion is demonstrated. 7. After 30 years of experience, the author finds that results with these patients have been uniformly good to excellent, depending on age and mode of treatment. 8. In medial tibiotalar torsion, the consequent adaptive changes are readily observed, but rarely are they recognized as the inevitable sequelae of medial tibiotalar torsion. 9. Adaptive compensating disorders are identified and their mechanism described. 10. The management of

  4. Evolving expectations from international organisations

    International Nuclear Information System (INIS)

    Ruiz Lopez, C.

    2008-01-01

    The author stated that implementation of the geological disposal concept requires a strategy that provides national decision makers with sufficient confidence in the level of long-term safety and protection ultimately achieved. The concept of protection against harm has a broader meaning than radiological protection in terms of risk and dose. It includes the protection of the environment and socio-economic interests of communities. She recognised that a number of countries have established regulatory criteria already, and others are now discussing what constitutes a proper regulatory test and suitable time frame for judging the safety of long-term disposal. Each regulatory programme seeks to define reasonable tests of repository performance, using protection criteria and safety approaches consistent with the culture, values and expectations of the citizens of the country concerned. This means that there are differences in how protection and safety are addressed in national approaches to regulation and in the bases used for that. However, as was recognised in the Cordoba Workshop, it would be important to reach a minimum level of consistency and be able to explain the differences. C. Ruiz-Lopez presented an overview of the development of international guidance from ICRP, IAEA and NEA from the Cordoba workshop up to now, and positions of independent National Advisory Bodies. The evolution of these guidelines over time demonstrates an evolving understanding of long-term implications, with the recognition that dose and risk constraints should not be seen as measures of detriment beyond a few hundred years, the emphasis on sound engineering practices, and the introduction of new concepts and approaches which take into account social and economical aspects (e.g. constrained optimisation, BAT, managerial principles). In its new recommendations, ICRP (draft 2006) recognizes. in particular, that decision making processes may depend on other societal concerns and considers

  5. Programming Language: Concepts and Paradigms

    OpenAIRE

    Ruiz Lizama, Edgar

    2014-01-01

    The article presents the concepts that govern around the programming languages and the paradigms of the programming and the influence in the development of the software. El artículo presenta los conceptos que rigen a los lenguajes de programación y los paradigmas de la programación y como estos influyen en el desarrollo del software.

  6. Understanding the land management paradigm

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration...

  7. Artificial life, the new paradigm

    International Nuclear Information System (INIS)

    Martinez Paez, Jose Jesus

    1998-01-01

    A chronological synthesis of the most important facts is presented in the theoretical development and computational simulation that they have taken to the formation of a new paradigm that is known as artificial life; their characteristics and their main investigation lines are analyzed. Finally, a description of its work is made in the National University of Colombia

  8. Biofabrication: a 21st century manufacturing paradigm

    International Nuclear Information System (INIS)

    Mironov, V; Trusk, T; Markwald, R; Kasyanov, V; Little, S; Swaja, R

    2009-01-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry. (topical review)

  9. Biofabrication: a 21st century manufacturing paradigm.

    Science.gov (United States)

    Mironov, V; Trusk, T; Kasyanov, V; Little, S; Swaja, R; Markwald, R

    2009-06-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry.

  10. Ubiquitous health in practice: the interreality paradigm.

    Science.gov (United States)

    Gaggioli, Andrea; Raspelli, Simona; Grassi, Alessandra; Pallavicini, Federica; Cipresso, Pietro; Wiederhold, Brenda K; Riva, Giuseppe

    2011-01-01

    In this paper we introduce a new ubiquitous computing paradigm for behavioral health care: "Interreality". Interreality integrates assessment and treatment within a hybrid environment, that creates a bridge between the physical and virtual worlds. Our claim is that bridging virtual experiences (fully controlled by the therapist, used to learn coping skills and emotional regulation) with real experiences (allowing both the identification of any critical stressors and the assessment of what has been learned) using advanced technologies (virtual worlds, advanced sensors and PDA/mobile phones) may improve existing psychological treatment. To illustrate the proposed concept, a clinical scenario is also presented and discussed: Daniela, a 40 years old teacher, with a mother affected by Alzheimer's disease.

  11. [Meta-legal paradigms of nanomedicine].

    Science.gov (United States)

    Pérez Alvarez, Salvador

    2012-01-01

    Nanomedicine is the Nanotechnology applied in the field of Medicine. Nanomedicine includes a wide range of technologies applied to devices, materials, medical procedures and treatment modalities are being developed, in some cases, through the convergence of living and nonliving materials. The developments in this scientific field are the prelude of a new era in health where Nanotechnology will provide, in a short period of time, substantial benefits for the general welfare and health of people with serious and incurable diseases using other more traditional medical treatments. This is, in brief, the object of this research that has been focused in the study of the ethical-legal paradigms that should inform the developments and expectations generated by medical applications of Nanotechnology.

  12. Evolving Technologies: A View to Tomorrow

    Science.gov (United States)

    Tamarkin, Molly; Rodrigo, Shelley

    2011-01-01

    Technology leaders must participate in strategy creation as well as operational delivery within higher education institutions. The future of higher education--the view to tomorrow--is irrevocably integrated and intertwined with evolving technologies. This article focuses on two specific evolving technologies: (1) alternative IT sourcing; and (2)…

  13. Japanese experience of evolving nurses' roles in changing social contexts.

    Science.gov (United States)

    Kanbara, S; Yamamoto, Y; Sugishita, T; Nakasa, T; Moriguchi, I

    2017-06-01

    To discuss the evolving roles of Japanese nurses in meeting the goals and concerns of ongoing global sustainable development. Japanese nurses' roles have evolved as the needs of the country and the communities they served, changed over time. The comprehensive public healthcare services in Japan were provided by the cooperation of hospitals and public health nurses. The nursing profession is exploring ways to identify and systemize nursing skills and competencies that address global health initiatives for sustainable development goals. This paper is based on the summary of a symposium, (part of the 2015 annual meeting of the Japan Association for International Health) with panel members including experts from Japan's Official Development Assistance. The evolving role of nurses in response to national and international needs is illustrated by nursing practices from Japan. Japanese public health nurses have also assisted overseas healthcare plans. In recent catastrophes, Japanese nurses assumed the roles of community health coordinators for restoration and maintenance of public health. The Japanese experience shows that nursing professionals are best placed to work with community health issues, high-risk situations and vulnerable communities. Their cooperation can address current social needs and help global communities to transform our world. Nurses have tremendous potential to make transformative changes in health and bring about the necessary paradigm shift. They must be involved in global sustainable development goals, health policies and disaster risk management. A mutual understanding of global citizen and nurses will help to renew and strengthen their capacities. Nursing professionals can contribute effectively to achieve national and global health goals and make transformative changes. © 2017 International Council of Nurses.

  14. Policy paradigms, transnationalism, and domestic politics

    National Research Council Canada - National Science Library

    Skogstad, Grace Darlene

    2011-01-01

    Policy Paradigms, Transnationalism, and Domestic Politics offers a variety of perspectives on the development of policy paradigms -- the ideas that structure thinking about what can and should be done in a policy domain...

  15. Evolvability Search: Directly Selecting for Evolvability in order to Study and Produce It

    DEFF Research Database (Denmark)

    Mengistu, Henok; Lehman, Joel Anthony; Clune, Jeff

    2016-01-01

    of evolvable digital phenotypes. Although some types of selection in evolutionary computation indirectly encourage evolvability, one unexplored possibility is to directly select for evolvability. To do so, we estimate an individual's future potential for diversity by calculating the behavioral diversity of its...... immediate offspring, and select organisms with increased offspring variation. While the technique is computationally expensive, we hypothesized that direct selection would better encourage evolvability than indirect methods. Experiments in two evolutionary robotics domains confirm this hypothesis: in both...... domains, such Evolvability Search produces solutions with higher evolvability than those produced with Novelty Search or traditional objective-based search algorithms. Further experiments demonstrate that the higher evolvability produced by Evolvability Search in a training environment also generalizes...

  16. The Evolving Classification of Pulmonary Hypertension.

    Science.gov (United States)

    Foshat, Michelle; Boroumand, Nahal

    2017-05-01

    - An explosion of information on pulmonary hypertension has occurred during the past few decades. The perception of this disease has shifted from purely clinical to incorporate new knowledge of the underlying pathology. This transfer has occurred in light of advancements in pathophysiology, histology, and molecular medical diagnostics. - To update readers about the evolving understanding of the etiology and pathogenesis of pulmonary hypertension and to demonstrate how pathology has shaped the current classification. - Information presented at the 5 World Symposia on pulmonary hypertension held since 1973, with the last meeting occurring in 2013, was used in this review. - Pulmonary hypertension represents a heterogeneous group of disorders that are differentiated based on differences in clinical, hemodynamic, and histopathologic features. Early concepts of pulmonary hypertension were largely influenced by pharmacotherapy, hemodynamic function, and clinical presentation of the disease. The initial nomenclature for pulmonary hypertension segregated the clinical classifications from pathologic subtypes. Major restructuring of this disease classification occurred between the first and second symposia, which was the first to unite clinical and pathologic information in the categorization scheme. Additional changes were introduced in subsequent meetings, particularly between the third and fourth World Symposia meetings, when additional pathophysiologic information was gained. Discoveries in molecular diagnostics significantly progressed the understanding of idiopathic pulmonary arterial hypertension. Continued advancements in imaging modalities, mechanistic pathogenicity, and molecular biomarkers will enable physicians to define pulmonary hypertension phenotypes based on the pathobiology and allow for treatment customization.

  17. Black hole evaporation: a paradigm

    International Nuclear Information System (INIS)

    Ashtekar, Abhay; Bojowald, Martin

    2005-01-01

    A paradigm describing black hole evaporation in non-perturbative quantum gravity is developed by combining two sets of detailed results: (i) resolution of the Schwarzschild singularity using quantum geometry methods and (ii) time evolution of black holes in the trapping and dynamical horizon frameworks. Quantum geometry effects introduce a major modification in the traditional spacetime diagram of black hole evaporation, providing a possible mechanism for recovery of information that is classically lost in the process of black hole formation. The paradigm is developed directly in the Lorentzian regime and necessary conditions for its viability are discussed. If these conditions are met, much of the tension between expectations based on spacetime geometry and structure of quantum theory would be resolved

  18. Three Paradigms of Social Assistance

    Directory of Open Access Journals (Sweden)

    Pierre-Marc Daigneault

    2014-11-01

    Full Text Available “Ideas,” which are defined as the normative and cognitive beliefs of actors, are fundamental to a full understanding of the welfare state and, in particular, of social assistance. However, policy ideas have been neglected in most typologies of social assistance regimes. Based on a selective review of the literature, this article proposes a brief but systematic analysis of policy paradigms in the field of social assistance. Three ideal types that emphasize the ideational dimension of social assistance are analyzed, namely, the entitlement, workfare, and activation paradigms. The value of the typology lies in its utility for characterizing the ideational orientation of social assistance regimes. Specifically, the typology provides a yardstick for measuring the ideas of policy actors with respect to social assistance and can facilitate the conduct of case studies, comparative research, and causal analyses on this policy sector.

  19. Parity and the medicalization of addiction treatment.

    Science.gov (United States)

    Roy, Ken; Miller, Michael

    2010-06-01

    Parity, the idea that insurance coverage for the treatment of addiction should be on a par with insurance coverage for the treatment of other medical illnesses, is not a new idea, but the path to achieving "real parity" has been a long, hard and complex journey. Action by Congress to pass major parity legislation in 2008 was a huge step forward, but does not mean that parity has been achieved. Parity has required a paradigm shift in the understanding of addiction as a biological illness: many developments of science and policy changes by professional organizations and governmental entities have contributed to that paradigm shift. Access to adequate treatment for patients must acknowledge the paradigm shift reflected in parity as it has evolved to the current point: that this biological illness is widespread, that it is important that it be treated effectively, that appropriate third party payment for physician-provided or physician-supervised addiction treatment is critical for addiction medicine to become a part of the mainstream of our nation's healthcare delivery system, and that medical specialty care provides the most effective and cost effective benefit to patients and therefore to our society.

  20. Exploring Paradigms of Crime Reduction

    DEFF Research Database (Denmark)

    Soothill, Keith; Christoffersen, Mogens N.; Hussain, Azhar

    2010-01-01

    Using Danish registers for a 1980 birth cohort of 29,944 males with parental information and following up these cases for 25 years, the study considers four paradigms of crime reduction (parental child rearing, structural factors around adolescence, locality and individual resources). Focusing on...... have more widespread benefits, but the assumed causal links need to be further explored. The use of population registers, under controlled conditions, provides an important window on criminal careers....

  1. Storytelling, advertising and paradigm fusion

    OpenAIRE

    Anderson, David

    2012-01-01

    'The art of storytelling in the modern age is fundamentally important. So, how we create stories for a screen-based culture is vitally important to master' (Hegarty, 2011, p.96-97). This paper explores the potential benefit of fusing aspects of creative writing with the curriculum of the BA Creative Advertising programme (BACAP) at Leeds College of Art (LCA) in order to address Sir John Hegarty's assertion. In particular it will focus on the characteristics of the 'classical paradigms' us...

  2. Mandarin functional MRI Language paradigms

    OpenAIRE

    Ci, He; van Graan, Andre; Gonz?lvez, Gloria; Thompson, Pamela; Hill, Andrea; Duncan, John S.

    2016-01-01

    Abstract Objective The objective of this study was to implement convenient, fast, and accurate Mandarin task paradigms for functional MRI, and to locate the Chinese language functional areas in frontal and temporal lobes. Materials and Methods Nineteen healthy Chinese volunteers participated in this study, which utilized a block design with four language tasks: auditory naming (AN), picture naming (PN), verbal fluency?character (VFC), and verbal fluency?letter (VFL). All functional images wer...

  3. Cancer research in need of a scientific revolution: Using 'paradigm shift' as a method of investigation.

    Science.gov (United States)

    Wion, Didier; Appaix, Florence; Burruss, Meriwether; Berger, Francois; van der Sanden, Boudewijn

    2015-09-01

    Despite important human and financial resources and considerable accumulation of scientific publications, patents, and clinical trials, cancer research has been slow in achieving a therapeutic revolution similar to the one that occurred in the last century for infectious diseases. It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of 'paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the 'paradigm shift' method in cancer research requires identifying its founding paradigms. In this review, two of these founding paradigms will be discussed: (i) the reification of cancer as a tumour mass and (ii) the translation of the concepts issued from infectious disease in cancer research. We show how these founding paradigms can generate biases that lead to over-diagnosis and over-treatment and also hamper the development of curative cancer therapies. We apply the 'paradigm shift' method to produce perspective reversals consistent with current experimental evidence. The 'paradigm shift' method enlightens the existence of a tumour physiologic-prophylactic-pathologic continuum. It integrates the target/antitarget concept and that cancer is also an extracellular disease. The 'paradigm shift' method has immediate implications for cancer prevention and therapy. It could be a general method of investigation for other diseases awaiting therapy.

  4. A Self-Control Versus a Counterconditioning Paradigm for Systematic Desensitization: An Experimental Comparison

    Science.gov (United States)

    Spiegler, Michael D.; And Others

    1976-01-01

    A comparison was made between the traditional counterconditioning paradigm and a self-control paradigm of systematic desensitization. College students reporting high test anxiety and indicating interest in receiving treatment were assigned to counterconditioning, self-control, or wait-list control conditions. As predicted, self-control procedures…

  5. Emergence of life: Physical chemistry changes the paradigm.

    Science.gov (United States)

    Spitzer, Jan; Pielak, Gary J; Poolman, Bert

    2015-06-10

    Origin of life research has been slow to advance not only because of its complex evolutionary nature (Franklin Harold: In Search of Cell History, 2014) but also because of the lack of agreement on fundamental concepts, including the question of 'what is life?'. To re-energize the research and define a new experimental paradigm, we advance four premises to better understand the physicochemical complexities of life's emergence: (1) Chemical and Darwinian (biological) evolutions are distinct, but become continuous with the appearance of heredity. (2) Earth's chemical evolution is driven by energies of cycling (diurnal) disequilibria and by energies of hydrothermal vents. (3) Earth's overall chemical complexity must be high at the origin of life for a subset of (complex) chemicals to phase separate and evolve into living states. (4) Macromolecular crowding in aqueous electrolytes under confined conditions enables evolution of molecular recognition and cellular self-organization. We discuss these premises in relation to current 'constructive' (non-evolutionary) paradigm of origins research - the process of complexification of chemical matter 'from the simple to the complex'. This paradigm artificially avoids planetary chemical complexity and the natural tendency of molecular compositions toward maximum disorder embodied in the second law of thermodynamics. Our four premises suggest an empirical program of experiments involving complex chemical compositions under cycling gradients of temperature, water activity and electromagnetic radiation.

  6. Nonalcoholic Steatohepatitis: An Evolving Diagnosis

    Directory of Open Access Journals (Sweden)

    Brent A Neuschwander-Tetri

    2000-01-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is a histological diagnosis applied to a constellation of liver biopsy findings that develop in the absence of alcohol abuse. Steatosis, a mixed cellular inflammatory infiltrate across the lobule, evidence of hepatocyte injury and fibrosis are the findings that can be seen. This entity is often identified during evaluation of elevated aminotransferases after exclusion of viral, metabolic and other causes of liver disease. Obesity is a major risk factor for NASH. The role of diabetes is less certain, although evidence is accumulating that hyperinsulinism may play an important pathophysiological role. Patients sometimes suffer from right upper quadrant abdominal pain and fatigue; examination may reveal centripetal obesity and hepatomegaly. Although patients are often discovered because of persistent aminotransferase elevations, these enzymes can be normal in NASH. When they are elevated, the alanine aminotransferase level is typically significantly greater than the aspartate aminotransferase level. This can be particularly helpful for excluding occult alcohol abuse. Imaging studies identify hepatic steatosis when the amount of fat in the liver is significant; however, imaging does not distinguish benign steatosis from NASH. Ultimately a liver biopsy is needed to diagnose NASH. The biopsy may be useful for establishing prognosis based on the presence or absence of fibrosis and for excluding other unexpected causes of liver enzyme elevations. Weight loss is the mainstay of treatment for obese patients. About 15% to 40% of NASH patients develop fibrosis; how many of these cases progress to cirrhosis is unknown, but about 1% of liver transplants are performed with a pretransplant diagnosis of NASH.

  7. Connecting traditional sciences with the OLAP and data mining paradigms

    Science.gov (United States)

    Guergachi, Aziz A.

    2003-03-01

    The paradigms of OLAP, multidimensional modeling and data mining have first emerged in the areas of market analysis and finance to address various needs of people working in these areas. Does this mean that they are useful and applicable in these areas only? Or, can they also be applicable in the other more traditional areas of science and engineering? What characterize the systems for which these paradigms are suitable? What are the goals of these paradigms? How do they relate to the traditional body of knowledge that has been developed throughout the centuries in the areas of mathematics, statistics, systems science and engineering? Where, how and to what extent can we leverage the conventional wisdom that has been accumulated in the aforementioned disciplines to develop a foundational basis for the above paradigms? The goal of this paper is to address these questions at the foundational level. We argue that the paradigms of OLAP, multidimensional modeling and data mining can also be applied successfully to complex engineering systems, such as membrane-based water/wastewater treatment plants, for example. We develop mathematically-based axiomatic definition of the concepts of 'dimension,' 'dimension level,' 'dimension hierarchy' and 'measure' using set theory and equivalence relations.

  8. Sex determination: ways to evolve a hermaphrodite.

    OpenAIRE

    Braendle , Christian; Félix , Marie-Anne

    2006-01-01

    Most species of the nematode genus Caenorhabditis reproduce through males and females; C. elegans and C. briggsae, however, produce self-fertile hermaphrodites instead of females. These transitions to hermaphroditism evolved convergently through distinct modifications of germline sex determination mechanisms.

  9. Marshal: Maintaining Evolving Models, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SIFT proposes to design and develop the Marshal system, a mixed-initiative tool for maintaining task models over the course of evolving missions. Marshal-enabled...

  10. Satcom access in the Evolved Packet Core

    NARCIS (Netherlands)

    Cano Soveri, M.D.; Norp, A.H.J.; Popova, M.P.

    2011-01-01

    Satellite communications (Satcom) networks are increasingly integrating with terrestrial communications networks, namely Next Generation Networks (NGN). In the area of NGN the Evolved Packet Core (EPC) is a new network architecture that can support multiple access technologies. When Satcom is

  11. Satcom access in the evolved packet core

    NARCIS (Netherlands)

    Cano, M.D.; Norp, A.H.J.; Popova, M.P.

    2012-01-01

    Satellite communications (Satcom) networks are increasingly integrating with terrestrial communications networks, namely Next Generation Networks (NGN). In the area of NGN the Evolved Packet Core (EPC) is a new network architecture that can support multiple access technologies. When Satcom is

  12. Introduction: Science, Sexuality, and Psychotherapy: Shifting Paradigms.

    Science.gov (United States)

    Cerbone, Armand R

    2017-08-01

    This introduction presents an overview of the current issue (73, 8) of Journal of Clinical Psychology: In Session. This issue features a series of articles, with clinical cases, each presented to illustrate the challenges faced by individuals and couples whose sexual and gender identities and expressions do not comport with traditional and cultural norms. These articles also document the challenges to the therapists who treat them. Considered individually, each article underscores the need to recognize the importance of evidence in guiding psychotherapy in cases involving sexuality. The discussions in each article offer recommendations meant to help and guide psychotherapists. Considered collectively, they raise important questions and considerations about shifting paradigms of human sexuality. Implications for assessment and treatment of cases involving sexuality and gender identity are discussed and recommended. © 2017 Wiley Periodicals, Inc.

  13. Evolving effective incremental SAT solvers with GP

    OpenAIRE

    Bader, Mohamed; Poli, R.

    2008-01-01

    Hyper-Heuristics could simply be defined as heuristics to choose other heuristics, and it is a way of combining existing heuristics to generate new ones. In a Hyper-Heuristic framework, the framework is used for evolving effective incremental (Inc*) solvers for SAT. We test the evolved heuristics (IncHH) against other known local search heuristics on a variety of benchmark SAT problems.

  14. Paradigm for new scientific technology; Shinkagaku gijutsu paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Shindo, Y [National Chemical Lab. for Industry, Tokyo (Japan)

    1995-01-05

    This paper reviews the current status from the standpoint of chemical engineers facing the coming of the 21st century, and surveys the paradigm for new scientific technologies. The criticism is mixed with unique opinions everywhere, such as `departure of students from scientific and engineering faculties is none other than the result of a market principle`, `national burden of trillions of yens should not be spent only under a justice of advancement of the science`, and `the global civilization itself has no other way but to change from the conventional expansive development type of the western country style to the internal development type of the oriental country style`. Values that define the paradigm for new scientific technologies may include such keywords as saturation in technology, baseless expansion of research projects, criticism on science, market principle, and centering human being. It should be looked at seriously that profit from research and development should exceed the cast invested therein in the future, and scientific technologies that serve truly the society should be aimed at. These efforts will result in one of the large pillars that support the future in which creation of new functions is aimed at as a result of structuring the new systems. Trying to overcome the environmental problems is one of them.

  15. GRB 110731A within the IGC paradigm

    Directory of Open Access Journals (Sweden)

    Primorac Daria

    2018-01-01

    Full Text Available Bright gamma-ray burst (GRB 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV emission. We analyze these data within the induced gravitational collapse (IGC paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep–GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ ~ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n ~ 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = –1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

  16. GRB 110731A within the IGC paradigm

    Science.gov (United States)

    Primorac, Daria; Ruffini, Remo; Pisani, Giovanni Battista; Aimuratov, Yerlan; Biancol, Carlo Luciano; Karlica, Mile; Melon Fuksman, Julio David; Moradi, Rahim; Muccino, Marco; Penacchioni, Ana Virginia; Rueda, Jorge Armando; Wang, Yu

    2018-01-01

    Bright gamma-ray burst (GRB) 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV) emission. We analyze these data within the induced gravitational collapse (IGC) paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN) assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep-GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = -1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

  17. The Paradigm of Distributed Creativity

    DEFF Research Database (Denmark)

    Glaveanu, Vlad Petre

    This presentation aims to focus on and develop the notion of distributed creativity from a cultural psychological perspective. It will start by outlining the need for a cultural psychological paradigm of creative expression and argue that this perspective is primarily concerned with what can...... be called ‘distributed creativity’. Drawing on related literature on distributed cognition (Hutchins, 2000), I will consider here the three inter-related ways in which creative action is distributed: across people, across people and objects, and across time. This particular understanding of creativity...

  18. Psychiatry beyond the current paradigm.

    LENUS (Irish Health Repository)

    Bracken, Pat

    2012-12-01

    A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry\\'s identity as essentially \\'applied neuroscience\\'. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.

  19. Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.

    Science.gov (United States)

    Bujarski, Spencer; Ray, Lara A

    2016-11-01

    In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The portrayal of natural environment in the evolution of the ecological public health paradigm.

    Science.gov (United States)

    Coutts, Christopher; Forkink, Annet; Weiner, Jocelyn

    2014-01-10

    This paper explores the conceptualization of the natural environment in an evolving ecological public health paradigm. The natural environment has long been recognized as essential to supporting life, health, and wellbeing. Our understanding of the relationship between the natural environment and health has steadily evolved from one of an undynamic environment to a more sophisticated understanding of ecological interactions.  This evolution is reflected in a number of ecological public health models which demonstrate the many external and overlapping determinants of human health. Six models are presented here to demonstrate this evolution, each model reflecting an increasingly ecological appreciation for the fundamental role of the natural environment in supporting human health. We conclude that after decades of public health's acceptance of the ecological paradigm, we are only now beginning to assemble knowledge of sophisticated ecological interdependencies and apply this knowledge to the conceptualization and study of the relationship between the natural environment and the determinants of human health.

  1. The detour paradigm in animal cognition.

    Science.gov (United States)

    Kabadayi, Can; Bobrowicz, Katarzyna; Osvath, Mathias

    2018-01-01

    In this paper, we review one of the oldest paradigms used in animal cognition: the detour paradigm. The paradigm presents the subject with a situation where a direct route to the goal is blocked and a detour must be made to reach it. Often being an ecologically valid and a versatile tool, the detour paradigm has been used to study diverse cognitive skills like insight, social learning, inhibitory control and route planning. Due to the relative ease of administrating detour tasks, the paradigm has lately been used in large-scale comparative studies in order to investigate the evolution of inhibitory control. Here we review the detour paradigm and some of its cognitive requirements, we identify various ecological and contextual factors that might affect detour performance, we also discuss developmental and neurological underpinnings of detour behaviors, and we suggest some methodological approaches to make species comparisons more robust.

  2. Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy.

    Science.gov (United States)

    Hoos, Axel; Ibrahim, Ramy; Korman, Alan; Abdallah, Kald; Berman, David; Shahabi, Vafa; Chin, Kevin; Canetta, Renzo; Humphrey, Rachel

    2010-10-01

    Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative regulator of T-cell activity led to development of the fully human, monoclonal antibody ipilimumab to block CTLA-4 and potentiate antitumor T-cell responses. Animal studies first provided insight into the ability of an anti-CTLA-4 antibody to cause tumor regression, particularly in combination regimens. Early clinical studies defined ipilimumab pharmacokinetics and possibilities for combinability. Phase II trials of ipilimumab in advanced melanoma showed objective responses, but a greater number of patients had disease stabilization. In a phase III trial, ipilimumab was the first agent to demonstrate an improvement in overall survival in patients with previously treated, advanced melanoma. The adverse event profile associated with ipilimumab was primarily immune-related. Adverse events can be severe and life-threatening, but most were reversible using treatment guidelines. Ipilimumab monotherapy exhibits conventional and new patterns of activity in advanced melanoma, with a delayed separation of Kaplan-Meier survival curves. The observation of some new response patterns with ipilimumab, which are not captured by standard response criteria, led to novel criteria for the evaluation of immunotherapy in solid tumors. Overall, lessons from the development of ipilimumab contributed to a new clinical paradigm for cancer immunotherapy evolved by the Cancer Immunotherapy Consortium. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    OpenAIRE

    D. D. Miniaeva

    2014-01-01

    This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism) into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism). The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, ta...

  4. Romanian spa tourism: a communist paradigm in a post communist era

    OpenAIRE

    George Erdeli; Ana Irina Dincă; Aurel Gheorghilas; Camelia Surugiu

    2011-01-01

    Spa tourism is one of the oldest forms of tourism which continuously evolved in time as the leisure industry paradigm and the consumers’ behavior changed. Similar to other countries in Central and Eastern Europe, spa tourism is an old phenomenon in Romania which expanded to the dimensions of a well defined tourism industry during the mass tourism period which also corresponded to the communism epoch. Although severely affected by the major political and socio-economic changes which occurred a...

  5. The Oral Paradigm and Snapchat

    Directory of Open Access Journals (Sweden)

    Oren Soffer

    2016-09-01

    Full Text Available In this short essay, I argue that the ephemeral nature of emerging instant-messaging applications, such as Snapchat, applies an oral paradigm. While online discourse of computer-mediated communication shares many qualities with oral communication, the case of ephemeral applications is unique, as the oral features are already integrated in the application technology design and as orality is often implemented on highly visual products. Snapchat applies technology that fades visual contents as if they were spoken words fading in the air after utterance. Moreover, Snapchat’s promise to delete all messages from its database after they are viewed echoes a key characteristic of primary oral culture: that is, the inability (and in our case, the obligation not to store knowledge. In this, Snapchat demonstrates counter-logic to the contemporary grammar of new media, which is based on information aggregation.

  6. Toward a New Energy Paradigm

    International Nuclear Information System (INIS)

    Farhad Mahmud

    2006-01-01

    More than 50% of the developing world does not have access to electricity. It is our belief that it is as much a problem of distribution as of production. The traditional approach of power distribution through a national grid system is remarkably slow. Alternate methods are not sought because of an implicit assumption that it is an area that would necessarily involve large infra-structural undertaking. However, the traditional distribution paradigm can be challenged by new developments in fuel cell technology that can open up the possibility of involvement of small private initiatives in the distribution of power in remote areas where grid penetration has not taken place. This would require distribution re-engineering in an innovative and practical way based on advancement in new technology (fuel cells in our case). Our business approach would require a shift in focus away from production to distribution in addressing the issue. (authors)

  7. Shield calculations, optimization vs. paradigm

    International Nuclear Information System (INIS)

    Cornejo D, N.; Hernandez S, A.; Martinez G, A.

    2006-01-01

    Many shieldings have been designed under the criteria of 'Maximum dose rates of project'. It has created the paradigm of those 'low dose rates', for the one which not few specialists would consider unacceptable levels of dose rate superior to the units of μSv.h -1 , independently of the exposure times. At the present time numerous shieldings are being designed considering dose restrictions in real times of exposure. After these new shieldings, the dose rates could be notably superior to those after traditional shieldings, without it implies inadequate designs or constructive errors. In the work significant differences in levels of dose rates and thickness of shieldings estimated by both methods for some typical facilities. It was concluded that the use of real times of exposure is more adequate for the optimization of the Radiological Protection, although this method demands bigger care in its application. (Author)

  8. Shielding calculations. Optimization vs. Paradigms

    International Nuclear Information System (INIS)

    Cornejo Diaz, Nestor; Hernandez Saiz, Alejandro; Martinez Gonzalez, Alina

    2005-01-01

    Many radiation shielding barriers in Cuba have been designed according to the criterion of Maxi-mum Projected Dose Rates. This fact has created the paradigm of low dose rates. Because of this, dose rate levels greater than units of Sv.h-1 would be considered unacceptable by many specialists, regardless of the real exposure times. Nowadays many shielding barriers are being designed using dose constraints in real exposure times. Behind the new barriers, dose rates could be notably greater than those behind the traditional ones, and it does not imply inadequate designs or constructive errors. In this work were obtained significant differences in dose rate levels and shield-ing thicknesses calculated by both methods for some typical installations. The work concludes that real exposure time approach is more adequate in order to optimise Radiation Protection, although this method should be carefully applied

  9. Emerging Paradigms in Machine Learning

    CERN Document Server

    Jain, Lakhmi; Howlett, Robert

    2013-01-01

    This  book presents fundamental topics and algorithms that form the core of machine learning (ML) research, as well as emerging paradigms in intelligent system design. The  multidisciplinary nature of machine learning makes it a very fascinating and popular area for research.  The book is aiming at students, practitioners and researchers and captures the diversity and richness of the field of machine learning and intelligent systems.  Several chapters are devoted to computational learning models such as granular computing, rough sets and fuzzy sets An account of applications of well-known learning methods in biometrics, computational stylistics, multi-agent systems, spam classification including an extremely well-written survey on Bayesian networks shed light on the strengths and weaknesses of the methods. Practical studies yielding insight into challenging problems such as learning from incomplete and imbalanced data, pattern recognition of stochastic episodic events and on-line mining of non-stationary ...

  10. Evolving Intelligent Systems Methodology and Applications

    CERN Document Server

    Angelov, Plamen; Kasabov, Nik

    2010-01-01

    From theory to techniques, the first all-in-one resource for EIS. There is a clear demand in advanced process industries, defense, and Internet and communication (VoIP) applications for intelligent yet adaptive/evolving systems. Evolving Intelligent Systems is the first self- contained volume that covers this newly established concept in its entirety, from a systematic methodology to case studies to industrial applications. Featuring chapters written by leading world experts, it addresses the progress, trends, and major achievements in this emerging research field, with a strong emphasis on th

  11. Interactively Evolving Compositional Sound Synthesis Networks

    DEFF Research Database (Denmark)

    Jónsson, Björn Þór; Hoover, Amy K.; Risi, Sebastian

    2015-01-01

    the space of potential sounds that can be generated through such compositional sound synthesis networks (CSSNs). To study the effect of evolution on subjective appreciation, participants in a listener study ranked evolved timbres by personal preference, resulting in preferences skewed toward the first......While the success of electronic music often relies on the uniqueness and quality of selected timbres, many musicians struggle with complicated and expensive equipment and techniques to create their desired sounds. Instead, this paper presents a technique for producing novel timbres that are evolved...

  12. On the Benefits of Divergent Search for Evolved Representations

    DEFF Research Database (Denmark)

    Lehman, Joel; Risi, Sebastian; Stanley, Kenneth O

    2012-01-01

    Evolved representations in evolutionary computation are often fragile, which can impede representation-dependent mechanisms such as self-adaptation. In contrast, evolved representations in nature are robust, evolvable, and creatively exploit available representational features. This paper provide...

  13. Preface: evolving rotifers, evolving science: Proceedings of the XIV International Rotifer Symposium

    Czech Academy of Sciences Publication Activity Database

    Devetter, Miloslav; Fontaneto, D.; Jersabek, Ch.D.; Welch, D.B.M.; May, L.; Walsh, E.J.

    2017-01-01

    Roč. 796, č. 1 (2017), s. 1-6 ISSN 0018-8158 Institutional support: RVO:60077344 Keywords : evolving rotifers * 14th International Rotifer Symposium * evolving science Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 2.056, year: 2016

  14. Parallel dispatch: a new paradigm of electrical power system dispatch

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jun Jason; Wang, Fei-Yue; Wang, Qiang; Hao, Dazhi; Yang, Xiaojing; Gao, David Wenzhong; Zhao, Xiangyang; Zhang, Yingchen

    2018-01-01

    Modern power systems are evolving into sociotechnical systems with massive complexity, whose real-time operation and dispatch go beyond human capability. Thus, the need for developing and applying new intelligent power system dispatch tools are of great practical significance. In this paper, we introduce the overall business model of power system dispatch, the top level design approach of an intelligent dispatch system, and the parallel intelligent technology with its dispatch applications. We expect that a new dispatch paradigm, namely the parallel dispatch, can be established by incorporating various intelligent technologies, especially the parallel intelligent technology, to enable secure operation of complex power grids, extend system operators U+02BC capabilities, suggest optimal dispatch strategies, and to provide decision-making recommendations according to power system operational goals.

  15. Views on Evolvability of Embedded Systems

    NARCIS (Netherlands)

    Laar, P. van de; Punter, T.

    2011-01-01

    Evolvability, the ability to respond effectively to change, represents a major challenge to today's high-end embedded systems, such as those developed in the medical domain by Philips Healthcare. These systems are typically developed by multi-disciplinary teams, located around the world, and are in

  16. Views on evolvability of embedded systems

    NARCIS (Netherlands)

    Laar, van de P.J.L.J.; Punter, H.T.

    2011-01-01

    Evolvability, the ability to respond effectively to change, represents a major challenge to today's high-end embedded systems, such as those developed in the medical domain by Philips Healthcare. These systems are typically developed by multi-disciplinary teams, located around the world, and are in

  17. EVOLVING AN EMPIRICAL METHODOLOGY DOR DETERMINING ...

    African Journals Online (AJOL)

    The uniqueness of this approach, is that it can be applied to any forest or dynamic feature on the earth, and can enjoy universal application as well. KEY WORDS: Evolving empirical methodology, innovative mathematical model, appropriate interval, remote sensing, forest environment planning and management. Global Jnl ...

  18. Continual Learning through Evolvable Neural Turing Machines

    DEFF Research Database (Denmark)

    Lüders, Benno; Schläger, Mikkel; Risi, Sebastian

    2016-01-01

    Continual learning, i.e. the ability to sequentially learn tasks without catastrophic forgetting of previously learned ones, is an important open challenge in machine learning. In this paper we take a step in this direction by showing that the recently proposed Evolving Neural Turing Machine (ENTM...

  19. Did Language Evolve Like the Vertebrate Eye?

    Science.gov (United States)

    Botha, Rudolf P.

    2002-01-01

    Offers a critical appraisal of the way in which the idea that human language or some of its features evolved like the vertebrate eye by natural selection is articulated in Pinker and Bloom's (1990) selectionist account of language evolution. Argues that this account is less than insightful because it fails to draw some of the conceptual…

  20. Is This the Paradigm Shift We Need?

    Science.gov (United States)

    Mirvis, Jonathan

    2012-01-01

    Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

  1. Testing the membrane paradigm with holography

    NARCIS (Netherlands)

    de Boer, J.; Heller, M.P.; Pinzani-Fokeeva, N.

    2015-01-01

    One version of the membrane paradigm states that, as far as outside observers are concerned, black holes can be replaced by a dissipative membrane with simple physical properties located at the stretched horizon. We demonstrate that such a membrane paradigm is incomplete in several aspects. We argue

  2. Programming Paradigms in Computer Science Education

    OpenAIRE

    Bolshakova, Elena

    2005-01-01

    Main styles, or paradigms of programming – imperative, functional, logic, and object-oriented – are shortly described and compared, and corresponding programming techniques are outlined. Programming languages are classified in accordance with the main style and techniques supported. It is argued that profound education in computer science should include learning base programming techniques of all main programming paradigms.

  3. Towards a New Paradigm of Moral Personhood

    Science.gov (United States)

    Frimer, Jeremy A.; Walker, Lawrence J.

    2008-01-01

    Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

  4. Evolving concepts in staging and treatment of colorectal cancer

    NARCIS (Netherlands)

    Sloothaak, D.A.M.

    2015-01-01

    For localized colorectal cancer (CRC), lymph node metastases are the most powerful prognostic factor for disease specific and overall survival. In the first part of the thesis, we explore the prognostic role of lymph nodes in patients with stage I/II colon cancer. In these patients, nodal metastases

  5. Understanding paradigms used for nursing research.

    Science.gov (United States)

    Weaver, Kathryn; Olson, Joanne K

    2006-02-01

    The aims of this paper are to add clarity to the discussion about paradigms for nursing research and to consider integrative strategies for the development of nursing knowledge. Paradigms are sets of beliefs and practices, shared by communities of researchers, which regulate inquiry within disciplines. The various paradigms are characterized by ontological, epistemological and methodological differences in their approaches to conceptualizing and conducting research, and in their contribution towards disciplinary knowledge construction. Researchers may consider these differences so vast that one paradigm is incommensurable with another. Alternatively, researchers may ignore these differences and either unknowingly combine paradigms inappropriately or neglect to conduct needed research. To accomplish the task of developing nursing knowledge for use in practice, there is a need for a critical, integrated understanding of the paradigms used for nursing inquiry. We describe the evolution and influence of positivist, postpositivist, interpretive and critical theory research paradigms. Using integrative review, we compare and contrast the paradigms in terms of their philosophical underpinnings and scientific contribution. A pragmatic approach to theory development through synthesis of cumulative knowledge relevant to nursing practice is suggested. This requires that inquiry start with assessment of existing knowledge from disparate studies to identify key substantive content and gaps. Knowledge development in under-researched areas could be accomplished through integrative strategies that preserve theoretical integrity and strengthen research approaches associated with various philosophical perspectives. These strategies may include parallel studies within the same substantive domain using different paradigms; theoretical triangulation to combine findings from paradigmatically diverse studies; integrative reviews; and mixed method studies. Nurse scholars are urged to

  6. Self-organized criticality paradigm

    International Nuclear Information System (INIS)

    Duran, I.; Stoeckel, J.; Hron, M.; Horacek, J.; Jakubka, K.; Kryska, L.

    2000-01-01

    According to the paradigm of the Self-Organized Criticality (SOC), the anomalous transport in tokamaks is caused by fast transient processes - avalanches. One of the manifestations of these phenomena should be 1/f decay of electrostatic fluctuations power spectra in a certain frequency range. In this paper, the frequency spectra of floating potential, density and fluctuation-induced flux, measured by poloidal and radial arrays of Langmuir probes on the CASTOR tokamak, are presented. The floating potential and the fluctuation-induced flux decay from 30 kHz up to 100 kHz as f -1 . The plasma density decays as f -1 in a more narrow band, 20 to 40 kHz. The possible limitation of SOC behavior for frequencies higher than 100 kHz due to intermittency is stressed. For this reason the Probability Distribution Functions (PDFs) of floating potential fluctuations were computed at different time scales using wavelet transform. A clear departure of the computed PDFs from Gaussianity, which is a classical signature of intermittency, is observed at time scales under 10 μs (100 kHz). (author)

  7. MDMA and the "ecstasy paradigm".

    Science.gov (United States)

    Cole, Jon C

    2014-01-01

    For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

  8. Cancer: shift of the paradigm.

    Science.gov (United States)

    Lichtenstein, Anatoly V

    2008-12-01

    Cancer is usually considered to be a by-product of design limitations of a multicellular organism and its intrinsic fallibility. However, recent data prompt a revision of some established notions about carcinogenesis and form a new paradigm of carcinogenesis as a highly conserved biological phenomenon - a programmed death of an organism. This altruistic program, which is unleashed when mutagenesis surpasses a certain critical threshold, gives a population the important benefit acting as a guardian of the gene pool against the spread of certain mutant genes. A growing body of evidence supports this point of view: (i) epigenetic changes leading to cancer arise early, simultaneously in many cells and look like deterministic regulation; (ii) concept of cancer stem cell suggests a view of carcinogenesis not as vague transformation but as well known differentiation; (iii) tumor/host relations usually perceived as antagonistic are, in reality, synergistic; (iv) death of an individual from cancer is predetermined and results apparently from a specific activity (killer function) of cancer cell and (v) evolutionary conservation indicates that cancer comes with a general advantage that explains its evolutionary success. A holistic approach to carcinogenesis suggests new avenues of research and new therapeutic strategy.

  9. When Darwin meets Lorenz: Evolving new chaotic attractors through genetic programming

    International Nuclear Information System (INIS)

    Pan, Indranil; Das, Saptarshi

    2015-01-01

    Highlights: •New 3D continuous time chaotic systems with analytical expressions are obtained. •The multi-gene genetic programming (MGGP) paradigm is employed to achieve this. •Extends earlier works for evolving generalised family of Lorenz attractors. •Over one hundred of new chaotic attractors along with their parameters are reported. •The MGGP method have the potential for finding other similar chaotic attractors. -- Abstract: In this paper, we propose a novel methodology for automatically finding new chaotic attractors through a computational intelligence technique known as multi-gene genetic programming (MGGP). We apply this technique to the case of the Lorenz attractor and evolve several new chaotic attractors based on the basic Lorenz template. The MGGP algorithm automatically finds new nonlinear expressions for the different state variables starting from the original Lorenz system. The Lyapunov exponents of each of the attractors are calculated numerically based on the time series of the state variables using time delay embedding techniques. The MGGP algorithm tries to search the functional space of the attractors by aiming to maximise the largest Lyapunov exponent (LLE) of the evolved attractors. To demonstrate the potential of the proposed methodology, we report over one hundred new chaotic attractor structures along with their parameters, which are evolved from just the Lorenz system alone

  10. Health Paradigm Shifts in the 20th Century

    Directory of Open Access Journals (Sweden)

    Jose Miguel DeAngulo

    2015-01-01

    Full Text Available The application of systems theory and the study of complexity to medicine and human health allows for a more comprehensive understanding and a more holistic view of what it means to be human. Such application overcomes the limitations of the traditional, fragmented understanding of phenomena and problems based on the mechanistic or Newtonian worldview. It recognizes that phenomena are interrelated, and that individual parts cannot be understood by only focusing on the analysis of their individual qualities. Rather, the individual parts can only be understood in relation to the whole and by being analyzed in the context of their interaction with the whole. The door is opened to previously unimagined models of thinking.In the 20th Century there have been shifts in the paradigms that have governed medicine and human health in the modern western world. There has been a shift from the focus on specific biological analysis and pathological diagnostics to complex human interactions with the environment and with sociopolitical and economic processes. There are complex models of systems in immunology, in neuroscience, and in genetics, as well as complex ways of understanding interactions as in epidemic modeling, in social media technologies, socioeconomic factors, and artificial intelligence.In this paper we describe three paradigms of the health-disease process that in some degree correspond to the historical development of modern medicine and healthcare over the previous century. The oldest paradigm focused on specific disease mechanisms and treatment. This gave way to paradigms that historically were broader and more inclusive, such as “international health”. The international health paradigm focused primarily on the control of epidemics across national borders and considered government as the only health actor. However, this perspective has come to be seen as excessively reductionist and excluded many critical components essential to a robust

  11. Moving alcohol prevention research forward-Part I: introducing a complex systems paradigm.

    Science.gov (United States)

    Apostolopoulos, Yorghos; Lemke, Michael K; Barry, Adam E; Lich, Kristen Hassmiller

    2018-02-01

    The drinking environment is a complex system consisting of a number of heterogeneous, evolving and interacting components, which exhibit circular causality and emergent properties. These characteristics reduce the efficacy of commonly used research approaches, which typically do not account for the underlying dynamic complexity of alcohol consumption and the interdependent nature of diverse factors influencing misuse over time. We use alcohol misuse among college students in the United States as an example for framing our argument for a complex systems paradigm. A complex systems paradigm, grounded in socio-ecological and complex systems theories and computational modeling and simulation, is introduced. Theoretical, conceptual, methodological and analytical underpinnings of this paradigm are described in the context of college drinking prevention research. The proposed complex systems paradigm can transcend limitations of traditional approaches, thereby fostering new directions in alcohol prevention research. By conceptualizing student alcohol misuse as a complex adaptive system, computational modeling and simulation methodologies and analytical techniques can be used. Moreover, use of participatory model-building approaches to generate simulation models can further increase stakeholder buy-in, understanding and policymaking. A complex systems paradigm for research into alcohol misuse can provide a holistic understanding of the underlying drinking environment and its long-term trajectory, which can elucidate high-leverage preventive interventions. © 2017 Society for the Study of Addiction.

  12. Geographic Object-Based Image Analysis – Towards a new paradigm

    Science.gov (United States)

    Blaschke, Thomas; Hay, Geoffrey J.; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

    2014-01-01

    The amount of scientific literature on (Geographic) Object-based Image Analysis – GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ‘per-pixel paradigm’ and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm. PMID:24623958

  13. The evolving definition of systemic arterial hypertension.

    Science.gov (United States)

    Ram, C Venkata S; Giles, Thomas D

    2010-05-01

    Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

  14. The evolving epidemiology of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, Fergus

    2009-07-01

    Epidemiologic studies in inflammatory bowel disease (IBD) include assessments of disease burden and evolving patterns of disease presentation. Although it is hoped that sound epidemiologic studies provide aetiological clues, traditional risk factor-based epidemiology has provided limited insights into either Crohn\\'s disease or ulcerative colitis etiopathogenesis. In this update, we will summarize how the changing epidemiology of IBD associated with modernization can be reconciled with current concepts of disease mechanisms and will discuss studies of clinically significant comorbidity in IBD.

  15. Development and the evolvability of human limbs

    OpenAIRE

    Young, Nathan M.; Wagner, Günter P.; Hallgrímsson, Benedikt

    2010-01-01

    The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primate...

  16. Quantum games on evolving random networks

    OpenAIRE

    Pawela, Łukasz

    2015-01-01

    We study the advantages of quantum strategies in evolutionary social dilemmas on evolving random networks. We focus our study on the two-player games: prisoner's dilemma, snowdrift and stag-hunt games. The obtained result show the benefits of quantum strategies for the prisoner's dilemma game. For the other two games, we obtain regions of parameters where the quantum strategies dominate, as well as regions where the classical strategies coexist.

  17. The Evolving Leadership Path of Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Kluse, Michael; Peurrung, Anthony J.; Gracio, Deborah K.

    2012-01-02

    This is a requested book chapter for an internationally authored book on visual analytics and related fields, coordianted by a UK university and to be published by Springer in 2012. This chapter is an overview of the leadship strategies that PNNL's Jim Thomas and other stakeholders used to establish visual analytics as a field, and how those strategies may evolve in the future.

  18. Evolving artificial metalloenzymes via random mutagenesis

    Science.gov (United States)

    Yang, Hao; Swartz, Alan M.; Park, Hyun June; Srivastava, Poonam; Ellis-Guardiola, Ken; Upp, David M.; Lee, Gihoon; Belsare, Ketaki; Gu, Yifan; Zhang, Chen; Moellering, Raymond E.; Lewis, Jared C.

    2018-03-01

    Random mutagenesis has the potential to optimize the efficiency and selectivity of protein catalysts without requiring detailed knowledge of protein structure; however, introducing synthetic metal cofactors complicates the expression and screening of enzyme libraries, and activity arising from free cofactor must be eliminated. Here we report an efficient platform to create and screen libraries of artificial metalloenzymes (ArMs) via random mutagenesis, which we use to evolve highly selective dirhodium cyclopropanases. Error-prone PCR and combinatorial codon mutagenesis enabled multiplexed analysis of random mutations, including at sites distal to the putative ArM active site that are difficult to identify using targeted mutagenesis approaches. Variants that exhibited significantly improved selectivity for each of the cyclopropane product enantiomers were identified, and higher activity than previously reported ArM cyclopropanases obtained via targeted mutagenesis was also observed. This improved selectivity carried over to other dirhodium-catalysed transformations, including N-H, S-H and Si-H insertion, demonstrating that ArMs evolved for one reaction can serve as starting points to evolve catalysts for others.

  19. CMIP6 Data Citation of Evolving Data

    Directory of Open Access Journals (Sweden)

    Martina Stockhause

    2017-06-01

    Full Text Available Data citations have become widely accepted. Technical infrastructures as well as principles and recommendations for data citation are in place but best practices or guidelines for their implementation are not yet available. On the other hand, the scientific climate community requests early citations on evolving data for credit, e.g. for CMIP6 (Coupled Model Intercomparison Project Phase 6. The data citation concept for CMIP6 is presented. The main challenges lie in limited resources, a strict project timeline and the dependency on changes of the data dissemination infrastructure ESGF (Earth System Grid Federation to meet the data citation requirements. Therefore a pragmatic, flexible and extendible approach for the CMIP6 data citation service was developed, consisting of a citation for the full evolving data superset and a data cart approach for citing the concrete used data subset. This two citation approach can be implemented according to the RDA recommendations for evolving data. Because of resource constraints and missing project policies, the implementation of the second part of the citation concept is postponed to CMIP7.

  20. Ostracism Online: A social media ostracism paradigm.

    Science.gov (United States)

    Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

    2015-06-01

    We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism.

  1. Evolution of the radiological protection paradigms

    International Nuclear Information System (INIS)

    Sordi, Gian Maria A.A.

    2009-01-01

    We consider as initial radiological protection paradigms those in vigour after the release of the atomic energy for pacific usages in 1955. In that occasion, only one paradigm was introduced, presently named dose limitation system. After arguing about the basis that raised the paradigm, we introduced the guidance, that is, the measurements to be implemented to comply with the paradigm. In that occasion, they were two, i.e., the radiation dose monitoring and the workplace classification. Afterwards, the reasons that caused the radiological protection paradigms changes in force until 1995 are discussed. The initial paradigm was modified introducing the justification and the optimization principles, adding that the radiological protection should be economical and effective. The guidance also increased to four: personal monitoring, workplace classification, reference level and workers classification. Afterwards, we give the main justifications for the present paradigms that besides the formers were added the dose constraints, the potential exposure and the annual risk limits. Due to these modifications, the workers classifications were eliminated from the guidance, but the potential exposure and the search for the dose constraints were added. Eventually, we discuss the tendencies for the next future and the main changes introduced by the ICRP in the Publication 103, 2007. (author)

  2. The Cognitive Paradigm Ontology: Design and Application

    Science.gov (United States)

    Laird, Angela R.

    2013-01-01

    We present the basic structure of the Cognitive Paradigm Ontology (CogPO) for human behavioral experiments. While the experimental psychology and cognitive neuroscience literature may refer to certain behavioral tasks by name (e.g., the Stroop paradigm or the Sternberg paradigm) or by function (a working memory task, a visual attention task), these paradigms can vary tremendously in the stimuli that are presented to the subject, the response expected from the subject, and the instructions given to the subject. Drawing from the taxonomy developed and used by the BrainMap project (www.brainmap.org) for almost two decades to describe key components of published functional imaging results, we have developed an ontology capable of representing certain characteristics of the cognitive paradigms used in the fMRI and PET literature. The Cognitive Paradigm Ontology is being developed to be compliant with the Basic Formal Ontology (BFO), and to harmonize where possible with larger ontologies such as RadLex, NeuroLex, or the Ontology of Biomedical Investigations (OBI). The key components of CogPO include the representation of experimental conditions focused on the stimuli presented, the instructions given, and the responses requested. The use of alternate and even competitive terminologies can often impede scientific discoveries. Categorization of paradigms according to stimulus, response, and instruction has been shown to allow advanced data retrieval techniques by searching for similarities and contrasts across multiple paradigm levels. The goal of CogPO is to develop, evaluate, and distribute a domain ontology of cognitive paradigms for application and use in the functional neuroimaging community. PMID:21643732

  3. Gas transmission : a paradigm shift

    International Nuclear Information System (INIS)

    Cornelson, D.W.

    1997-01-01

    The evolution of energy markets in North America was discussed. The investment opportunities that are possible in a deregulated energy market, be it in production or in the generation of energy commodities, in the development of midstream infrastructure, or in the provision of energy services, were outlined. Deregulation of crude oil, natural gas and electricity has resulted in significant changes in the structure of energy markets and the way in which customers are served. One of the advantages of competition regarding power generation is that it has turned energy into a commodity which has resulted in greater customer choice and efficiency. As one example of midstream infrastructure development, the Alliance Pipeline project was described. This project was conceived as a means to enhance the value of western Canadian natural gas. The 1,900 mile pipeline will run from British Columbia, through Alberta into Chicago where it will interconnect with the North American gas transmission grid. The pipeline is an efficient means of transporting energy from Western Canada to North American markets, and Alliance, as a lowest cost transporter, will continue to put pressure on the traditional infrastructure to become even more competitive at the margin. As such, Alliance represents a paradigm shift in energy transportation, and serves as an excellent example of the type of investment opportunity that a deregulated market can provide. It was suggested that innovation and competition in a deregulated North American energy market will continue to increase. As electricity is deregulated, the energy market will respond more quickly to changes in supply and demand than it did in the past, in an effort to satisfy the needs of investors and customers. This will provide increased opportunities for restructuring and further competition

  4. Stroke mimics under the drip-and-ship paradigm.

    Science.gov (United States)

    Mehta, Sonal; Vora, Nirav; Edgell, Randall C; Allam, Hesham; Alawi, Aws; Koehne, Jennifer; Kumar, Abhay; Feen, Eliahu; Cruz-Flores, Salvador; Alshekhlee, Amer

    2014-01-01

    Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). The drip-and-ship paradigm and any psychiatric history predict the diagnosis of

  5. PARADIGM OF EDUCATION FOR THE INFORMATION SOCIETY

    Directory of Open Access Journals (Sweden)

    Yuriy M. Bogachkov

    2015-10-01

    Full Text Available Considering total crisis in education in Informational Age, we suggest that to overcome the crisis, it is necessary to promote pedagogical science up from "pre-paradigm stage” to the "paradigm stage". For this purpose it is necessary to separate the "educational science" from "education." “Educational paradigm” in such study will be the subject of the science. The key concepts for the "pedagogical paradigm" should be the concepts of "educational practice", "class of problems" and "educational text". We offer some axioms around these concepts.

  6. The Prerequisites for a Degrowth Paradigm Shift

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2018-01-01

    What would it take for a degrowth paradigm shift to take place? Drawing on contemporary critical political economy scholarship, this article identifies four prerequisites for socio-economic paradigm shifts: deep crisis, an alternative political project, a comprehensive coalition of social forces...... currently facing humanity. On the other hand, the prospects for a degrowth paradigm shift remain bleak: unlike political projects that became hegemonic in the past, degrowth has neither support from a comprehensive coalition of social forces nor any consent to its agenda among the broader population....

  7. Mathematical modeling of bone marrow--peripheral blood dynamics in the disease state based on current emerging paradigms, part I.

    Science.gov (United States)

    Afenya, Evans K; Ouifki, Rachid; Camara, Baba I; Mundle, Suneel D

    2016-04-01

    Stemming from current emerging paradigms related to the cancer stem cell hypothesis, an existing mathematical model is expanded and used to study cell interaction dynamics in the bone marrow and peripheral blood. The proposed mathematical model is described by a system of nonlinear differential equations with delay, to quantify the dynamics in abnormal hematopoiesis. The steady states of the model are analytically and numerically obtained. Some conditions for the local asymptotic stability of such states are investigated. Model analyses suggest that malignancy may be irreversible once it evolves from a nonmalignant state into a malignant one and no intervention takes place. This leads to the proposition that a great deal of emphasis be placed on cancer prevention. Nevertheless, should malignancy arise, treatment programs for its containment or curtailment may have to include a maximum and extensive level of effort to protect normal cells from eventual destruction. Further model analyses and simulations predict that in the untreated disease state, there is an evolution towards a situation in which malignant cells dominate the entire bone marrow - peripheral blood system. Arguments are then advanced regarding requirements for quantitatively understanding cancer stem cell behavior. Among the suggested requirements are, mathematical frameworks for describing the dynamics of cancer initiation and progression, the response to treatment, the evolution of resistance, and malignancy prevention dynamics within the bone marrow - peripheral blood architecture. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kısım Aslı

    2010-07-01

    Full Text Available Abstract Background Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR, myeloid cell leukemia-1 (MCL-1, tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A, TNFRSF1A-associated death domain protein (TRADD. Results We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF, TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions These are the preliminary molecular results of a novel combination treatment of

  9. Evolving molecular era of childhood medulloblastoma: time to revisit therapy.

    Science.gov (United States)

    Khatua, Soumen

    2016-01-01

    Currently medulloblastoma is treated with a uniform therapeutic approach based on histopathology and clinico-radiological risk stratification, resulting in unpredictable treatment failure and relapses. Improved understanding of the biological, molecular and genetic make-up of these tumors now clearly identifies it as a compendium of four distinct subtypes (WNT, SHH, group 3 and 4). Advances in utilization of the genomic and epigenomic machinery have now delineated genetic aberrations and epigenetic perturbations in each subgroup as potential druggable targets. This has resulted in endeavors to profile targeted therapy. The challenge and future of medulloblastoma therapeutics will be to keep pace with the evolving novel biological insights and translating them into optimal targeted treatment regimens.

  10. Beyond desertification: New paradigms for dryland landscapes

    Science.gov (United States)

    The dryland desertification paradigm focuses on losses of ecosystem services accompanying transitions from grasslands to systems dominated by bare ground or woody plants unpalatable for domestic livestock. However, recent studies reveal complex transitions across a range of environmental conditions ...

  11. The safety implications of emerging software paradigms

    International Nuclear Information System (INIS)

    Suski, G.J.; Persons, W.L.; Johnson, G.L.

    1994-10-01

    This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants

  12. Major Development Communication Paradigms and Practices ...

    African Journals Online (AJOL)

    info

    major paradigms of development and communication practices on graphic ... mobilize, educate and persuade target audience to support human development ... facilitates the understanding of the themes, issues and facts of a campaign.

  13. Paradigms and pragmatism: approaches to medical statistics.

    Science.gov (United States)

    Healy, M J

    2000-01-01

    Until recently, the dominant philosophy of science was that due to Karl Popper, with its doctrine that the proper task of science was the formulation of hypotheses followed by attempts at refuting them. In spite of the close analogy with significance testing, these ideas do not fit well with the practice of medical statistics. The same can be said of the later philosophy of Thomas Kuhn, who maintains that science proceeds by way of revolutionary upheavals separated by periods of relatively pedestrian research which are governed by what Kuhn refers to as paradigms. Through there have been paradigm shifts in the history of statistics, a degree of continuity can also be discerned. A current paradigm shift is embodied in the spread of Bayesian ideas. It may be that a future paradigm will emphasise the pragmatic approach to statistics that is associated with the name of Daniel Schwartz.

  14. New Indivisible Planetary Science Paradigm: Consequence of Questioning Popular Paradigms

    Science.gov (United States)

    Marvin Herndon, J.

    2014-05-01

    Progress in science involves replacing less precise understanding with more precise understanding. In science and in science education one should always question popular ideas; ask "What's wrong with this picture?" Finding limitations, conflicts or circumstances that require special ad hoc consideration sometimes is the key to making important discoveries. For example, from thermodynamic considerations, I found that the 'standard model of solar system formation' leads to insufficiently massive planetary cores. That understanding led me to discover a new indivisible planetary science paradigm. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures, accumulating heterogeneously on the basis of volatility with liquid core-formation preceding mantle-formation; the interior states of oxidation resemble that of the Abee enstatite chondrite. Core-composition was established during condensation based upon the relative solubilities of elements, including uranium, in liquid iron in equilibrium with an atmosphere of solar composition at high pressures and high temperatures. Uranium settled to the central region and formed planetary nuclear fission reactors, producing heat and planetary magnetic fields. Earth's complete condensation included a ~300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions, associated with the thermonuclear ignition of the Sun, stripped the gases away from the Earth and the inner planets. The T-Tauri outbursts stripped a portion of Mercury's incompletely condensed protoplanet and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System, forming the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. With its massive gas/ice shell

  15. Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of Natural Selection.

    Science.gov (United States)

    Janković, Srdja; Ćirković, Milan M

    2016-03-01

    Physical processes that characterize living matter are qualitatively distinct in that they involve encoding and transfer of specific types of information. Such information plays an active part in the control of events that are ultimately linked to the capacity of the system to persist and multiply. This algorithmicity of life is a key prerequisite for its Darwinian evolution, driven by natural selection acting upon stochastically arising variations of the encoded information. The concept of evolvability attempts to define the total capacity of a system to evolve new encoded traits under appropriate conditions, i.e., the accessible section of total morphological space. Since this is dependent on previously evolved regulatory networks that govern information flow in the system, evolvability itself may be regarded as an evolved ability. The way information is physically written, read and modified in living cells (the "coding concept") has not changed substantially during the whole history of the Earth's biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a product of natural selection, since the overall evolvability conferred by its coding concept (nucleic acids as information carriers with the "rulebook of meanings" provided by codons, as well as all the subsystems that regulate various conditional information-reading modes) certainly played a key role in enabling this biosphere to survive up to the present, through alterations of planetary conditions, including at least five catastrophic events linked to major mass extinctions. We submit that, whatever the actual prebiotic physical and chemical processes may have been on our home planet, or may, in principle, occur at some time and place in the Universe, a particular coding concept, with its respective potential to give rise to a biosphere, or class of biospheres, of a certain evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural selection.

  16. A Viable Paradigm for Quantum Reality

    Science.gov (United States)

    Srivastava, Jagdish

    2010-10-01

    After a brief discussion of the EPR paradox, Bell's inequality, and Aspect's experiment, arguments will be presented in favor of the following statements: ``As it stands, Quantum mechanics is incomplete. There is further hidden structure, which would involve variables. No influence can move faster than light. The wave function is one whole thing and any change in its structure instantly influences its outcomes. Bell's theorem has not been applied correctly. There is a better paradigm.'' The said paradigm will be presented.

  17. International business and the eclectic paradigm

    DEFF Research Database (Denmark)

    The eclectic paradigm has become the dominant theoretical basis in the study of international business, multinational corporations and internationalization since 1980. However, developments such as economic globalization and the subsequent growth of global and alliance capitalism have fundamentally......, finance, evolutionary economics, resource-based theory or strategic management? Can it be utilized to explain new developments in international business and economics? Do these require new ideas and concepts to be integrated within the eclectic paradigm? What are the new challenges to which international...

  18. Revealing evolved massive stars with Spitzer

    Science.gov (United States)

    Gvaramadze, V. V.; Kniazev, A. Y.; Fabrika, S.

    2010-06-01

    Massive evolved stars lose a large fraction of their mass via copious stellar wind or instant outbursts. During certain evolutionary phases, they can be identified by the presence of their circumstellar nebulae. In this paper, we present the results of a search for compact nebulae (reminiscent of circumstellar nebulae around evolved massive stars) using archival 24-μm data obtained with the Multiband Imaging Photometer for Spitzer. We have discovered 115 nebulae, most of which bear a striking resemblance to the circumstellar nebulae associated with luminous blue variables (LBVs) and late WN-type (WNL) Wolf-Rayet (WR) stars in the Milky Way and the Large Magellanic Cloud (LMC). We interpret this similarity as an indication that the central stars of detected nebulae are either LBVs or related evolved massive stars. Our interpretation is supported by follow-up spectroscopy of two dozen of these central stars, most of which turn out to be either candidate LBVs (cLBVs), blue supergiants or WNL stars. We expect that the forthcoming spectroscopy of the remaining objects from our list, accompanied by the spectrophotometric monitoring of the already discovered cLBVs, will further increase the known population of Galactic LBVs. This, in turn, will have profound consequences for better understanding the LBV phenomenon and its role in the transition between hydrogen-burning O stars and helium-burning WR stars. We also report on the detection of an arc-like structure attached to the cLBV HD 326823 and an arc associated with the LBV R99 (HD 269445) in the LMC. Partially based on observations collected at the German-Spanish Astronomical Centre, Calar Alto, jointly operated by the Max-Planck-Institut für Astronomie Heidelberg and the Instituto de Astrofísica de Andalucía (CSIC). E-mail: vgvaram@mx.iki.rssi.ru (VVG); akniazev@saao.ac.za (AYK); fabrika@sao.ru (SF)

  19. Evolving Random Forest for Preference Learning

    DEFF Research Database (Denmark)

    Abou-Zleikha, Mohamed; Shaker, Noor

    2015-01-01

    This paper introduces a novel approach for pairwise preference learning through a combination of an evolutionary method and random forest. Grammatical evolution is used to describe the structure of the trees in the Random Forest (RF) and to handle the process of evolution. Evolved random forests ...... obtained for predicting pairwise self-reports of users for the three emotional states engagement, frustration and challenge show very promising results that are comparable and in some cases superior to those obtained from state-of-the-art methods....

  20. An evolving network model with community structure

    International Nuclear Information System (INIS)

    Li Chunguang; Maini, Philip K

    2005-01-01

    Many social and biological networks consist of communities-groups of nodes within which connections are dense, but between which connections are sparser. Recently, there has been considerable interest in designing algorithms for detecting community structures in real-world complex networks. In this paper, we propose an evolving network model which exhibits community structure. The network model is based on the inner-community preferential attachment and inter-community preferential attachment mechanisms. The degree distributions of this network model are analysed based on a mean-field method. Theoretical results and numerical simulations indicate that this network model has community structure and scale-free properties

  1. Radio Imaging of Envelopes of Evolved Stars

    Science.gov (United States)

    Cotton, Bill

    2018-04-01

    This talk will cover imaging of stellar envelopes using radio VLBI techniques; special attention will be paid to the technical differences between radio and optical/IR interferomery. Radio heterodyne receivers allow a straightforward way to derive spectral cubes and full polarization observations. Milliarcsecond resolution of very bright, i.e. non thermal, emission of molecular masers in the envelopes of evolved stars can be achieved using VLBI techniques with baselines of thousands of km. Emission from SiO, H2O and OH masers are commonly seen at increasing distance from the photosphere. The very narrow maser lines allow accurate measurements of the velocity field within the emitting region.

  2. Mobile computing acceptance grows as applications evolve.

    Science.gov (United States)

    Porn, Louis M; Patrick, Kelly

    2002-01-01

    Handheld devices are becoming more cost-effective to own, and their use in healthcare environments is increasing. Handheld devices currently are being used for e-prescribing, charge capture, and accessing daily schedules and reference tools. Future applications may include education on medications, dictation, order entry, and test-results reporting. Selecting the right handheld device requires careful analysis of current and future applications, as well as vendor expertise. It is important to recognize the technology will continue to evolve over the next three years.

  3. Evolved Minimal Frustration in Multifunctional Biomolecules.

    Science.gov (United States)

    Röder, Konstantin; Wales, David J

    2018-05-25

    Protein folding is often viewed in terms of a funnelled potential or free energy landscape. A variety of experiments now indicate the existence of multifunnel landscapes, associated with multifunctional biomolecules. Here, we present evidence that these systems have evolved to exhibit the minimal number of funnels required to fulfil their cellular functions, suggesting an extension to the principle of minimum frustration. We find that minimal disruptive mutations result in additional funnels, and the associated structural ensembles become more diverse. The same trends are observed in an atomic cluster. These observations suggest guidelines for rational design of engineered multifunctional biomolecules.

  4. SALT Spectroscopy of Evolved Massive Stars

    Science.gov (United States)

    Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

    2017-06-01

    Long-slit spectroscopy with the Southern African Large Telescope (SALT) of central stars of mid-infrared nebulae detected with the Spitzer Space Telescope and Wide-Field Infrared Survey Explorer (WISE) led to the discovery of numerous candidate luminous blue variables (cLBVs) and other rare evolved massive stars. With the recent advent of the SALT fiber-fed high-resolution echelle spectrograph (HRS), a new perspective for the study of these interesting objects is appeared. Using the HRS we obtained spectra of a dozen newly identified massive stars. Some results on the recently identified cLBV Hen 3-729 are presented.

  5. Project management: a new service delivery paradigm

    Directory of Open Access Journals (Sweden)

    G. van der Walt

    2007-07-01

    Full Text Available In line with international trends in governance, the South African Government’s initial focus on the development of policy frameworks, structures and systems in order to give effect to the values and principles of the Constitution, shifted to the most critical issue, namely service delivery. The Government became increasingly aware that a significant expansion in the scope and quality of service provision was not possible with traditional delivery settings and approaches. There is growing evidence that there is a need for a significant departure from conventional approaches and that a leap into a new service delivery paradigm is necessary. Increasingly this new paradigm highlights the need to further develop the government’s project management skills and applications with a view to achieving improved delivery capability. In this article the focus will be placed on the changing service delivery paradigm – from an “old” traditional model through the transition to a “new” paradigm. This paradigm is shaped by international and national trends and events in government. The contribution and advantages of project management applications for effective governance are highlighted and the article concludes with an explanation of project management organisational arrangements necessary to support the new paradigm.

  6. The Underlying Social Dynamics of Paradigm Shifts.

    Science.gov (United States)

    Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  7. The Underlying Social Dynamics of Paradigm Shifts.

    Directory of Open Access Journals (Sweden)

    Carlos Rodriguez-Sickert

    Full Text Available We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm; and ii radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  8. InSpire to Promote Lung Assessment in Youth: Evolving the Self-Management Paradigms of Young People With Asthma.

    Science.gov (United States)

    Elias, Pierre; Rajan, Nithin O; McArthur, Kara; Dacso, Clifford C

    2013-01-01

    Asthma is the most common chronic disease in childhood, disproportionately affecting urban, minority, and disadvantaged children. Individualized care plans supported by daily lung-function monitoring can reduce morbidity and mortality. However, despite 20 years of interventions to increase adherence, only 50% of US youth accurately follow their care plans, which leads to millions of preventable hospitalizations, emergency room visits, and sick days every year. We present a feasibility study of a novel, user-centered approach to increasing young people's lung-function monitoring and asthma self-care. Promoting Lung Assessment in Youth (PLAY) helps young people become active managers of their asthma through the Web 2.0 principles of participation, cocreation, and information sharing. Specifically, PLAY combines an inexpensive, portable spirometer with the motivational power and convenience of mobile phones and virtual-community gaming. The objective of this study was to develop and pilot test InSpire, a fully functional interface between a handheld spirometer and an interactive game and individualized asthma-care instant-messaging system housed on a mobile phone. InSpire is an application for mobile smartphones that creates a compelling world in which youth collaborate with their physicians on managing their asthma. Drawing from design-theory on global timer mechanics and role playing, we incentivized completing spirometry maneuvers by making them an engaging part of a game young people would want to play. The data can be sent wirelessly to health specialists and return care recommendations to patients in real-time. By making it portable and similar to applications normally desired by the target demographic, InSpire is able to seamlessly incorporate asthma management into their lifestyle. We describe the development process of building and testing the InSpire prototype. To our knowledge, the prototype is a first-of-its kind mobile one-stop shop for asthma management. Feasibility testing in children aged 7 to 14 with asthma assessed likability of the graphical user interface as well as young people's interest in our incentivizing system. Nearly 100% of children surveyed said they would play games like those in PLAY if they involved breathing into a spirometer. Two-thirds said they would prefer PLAY over the spirometer alone, whereas 1/3 would prefer having both. No children said they would prefer the spirometer over PLAY. Previous efforts at home-monitoring of asthma in children have experienced rapid decline in adherence. An inexpensive monitoring technology combined with the computation, interactive communication, and display ability of a mobile phone is a promising approach to sustainable adherence to lung-function monitoring and care plans. An exciting game that redefines the way youth conduct health management by inviting them to collaborate in their health better can be an incentive and a catalyst for more far-reaching goals.

  9. Endeavor research into evolving paradigms around ophiolites: the case of the oceanic igneous complexes of Costa Rica

    International Nuclear Information System (INIS)

    Alvarado, Guillermo E.; Denyer, Perci; Gazel, Esteban

    2009-01-01

    Studies on the radiolarite igneous (ophiolitic) complexes were done for more than one century in Costa Rica that range from Jurassic to Eocene. These studies can be grouped in four stages of knowledge: 1) from 1904 to 1957 were recognized the cherts, and the mafic and ultramafic igneous complexes, the first regional maps were done, and the first time were recognized ellipsoidal basalts, now widely known as pillow lavas. 2) From 1958 to 1978 the complexes were seen under the concept of the association of ophiolites (serpentine, gabbro, diabase, basalts, and related rocks) and interpreted the radiolarites as deep-sea sediments. The stage is characterized by the seminal work of Gabriel Dengo and by the first geochemical analyses in the framework of the plate tectonics. 3) A huge amount of geochemical data, paleontological and K/Ar ages were published from 1979 to 1994 and it was the stage of more controversial papers, their interpretation varied for the same locality (i.e. (Nicoya Peninsula) from relative simple stratigraphic model to a very complex nappe slices, and from a simple tectonic evolution (in situ and formed by a mid oceanic ridge volcanism) to a multistage evolution (terrains, and mid oceanic ridge, aseismic ridge, intraplate and island arc volcanism). The situation was similar in the other Costa Rican oceanic complexes. 4) The outlook for 1995 to the present it has been clarified and mutual agreement between the different groups. The stage is characterized by joint collaboration, the use of modern laboratory techniques as Sr, Nd, and Pb isotopes, major, trace and complete rare earth elements. 40A r/ 39 Ar dating, and volcanological criteria, together with detailed field mapping. The main new result of these studies was that the radiolarites (164-84 Ma) in the Nicoya Peninsula were significatively older than the basic igneous rocks (140-84 Ma), indicating a complex magmatic event intruding and erupting into the thick sedimentary sequence. For other areas, like Santa Elena Peninsula, Tortugal, Herradura and Quepos, the picture on these oceanic complexes are more or less clear. In the case of Osa-Golfito-Burica area, more studies are necessary. In general, the detailed field mapping is a powerful tool in combination with the modern techniques. The similarity in age, petrology, geochemistry and tectonic context for other oceanic complexes in Guatemala, Antilles and the northern part of South America, is more than a coincidence, they have a similar evolution. Therefore, a multidisciplinary study of the chrono- and bio-stratigraphic relations, together with modern petrology, geochemical and micropaleontology approach is necessary to provide a solid base for a robust plate tectonic reconstruction and geologic history. (author)

  10. Evolving Learning Paradigms: Re-Setting Baselines and Collection Methods of Information and Communication Technology in Education Statistics

    Science.gov (United States)

    Gibson, David; Broadley, Tania; Downie, Jill; Wallet, Peter

    2018-01-01

    The UNESCO Institute for Statistics (UIS) has been measuring ICT in education since 2009, but with such rapid change in technology and its use in education, it is important now to revise the collection mechanisms to focus on how technology is being used to enhance learning and teaching. Sustainable development goal (SDG) 4, for example, moves…

  11. InSpire to Promote Lung Assessment in Youth: Evolving the Self-Management Paradigms of Young People With Asthma

    OpenAIRE

    Elias, Pierre; Rajan, Nithin O; McArthur, Kara; Dacso, Clifford C

    2013-01-01

    Background Asthma is the most common chronic disease in childhood, disproportionately affecting urban, minority, and disadvantaged children. Individualized care plans supported by daily lung-function monitoring can reduce morbidity and mortality. However, despite 20 years of interventions to increase adherence, only 50% of US youth accurately follow their care plans, which leads to millions of preventable hospitalizations, emergency room visits, and sick days every year. We present a feasibil...

  12. BOOK REVIEW: OPENING SCIENCE, THE EVOLVING GUIDE ...

    Science.gov (United States)

    The way we get our funding, collaborate, do our research, and get the word out has evolved over hundreds of years but we can imagine a more open science world, largely facilitated by the internet. The movement towards this more open way of doing and presenting science is coming, and it is not taking hundreds of years. If you are interested in these trends, and would like to find out more about where this is all headed and what it means to you, consider downloding Opening Science, edited by Sönke Bartling and Sascha Friesike, subtitled The Evolving Guide on How the Internet is Changing Research, Collaboration, and Scholarly Publishing. In 26 chapters by various authors from a range of disciplines the book explores the developing world of open science, starting from the first scientific revolution and bringing us to the next scientific revolution, sometimes referred to as “Science 2.0”. Some of the articles deal with the impact of the changing landscape of how science is done, looking at the impact of open science on Academia, or journal publishing, or medical research. Many of the articles look at the uses, pitfalls, and impact of specific tools, like microblogging (think Twitter), social networking, and reference management. There is lots of discussion and definition of terms you might use or misuse like “altmetrics” and “impact factor”. Science will probably never be completely open, and Twitter will probably never replace the journal article,

  13. The Comet Cometh: Evolving Developmental Systems.

    Science.gov (United States)

    Jaeger, Johannes; Laubichler, Manfred; Callebaut, Werner

    In a recent opinion piece, Denis Duboule has claimed that the increasing shift towards systems biology is driving evolutionary and developmental biology apart, and that a true reunification of these two disciplines within the framework of evolutionary developmental biology (EvoDevo) may easily take another 100 years. He identifies methodological, epistemological, and social differences as causes for this supposed separation. Our article provides a contrasting view. We argue that Duboule's prediction is based on a one-sided understanding of systems biology as a science that is only interested in functional, not evolutionary, aspects of biological processes. Instead, we propose a research program for an evolutionary systems biology, which is based on local exploration of the configuration space in evolving developmental systems. We call this approach-which is based on reverse engineering, simulation, and mathematical analysis-the natural history of configuration space. We discuss a number of illustrative examples that demonstrate the past success of local exploration, as opposed to global mapping, in different biological contexts. We argue that this pragmatic mode of inquiry can be extended and applied to the mathematical analysis of the developmental repertoire and evolutionary potential of evolving developmental mechanisms and that evolutionary systems biology so conceived provides a pragmatic epistemological framework for the EvoDevo synthesis.

  14. Active training paradigm for motor imagery BCI.

    Science.gov (United States)

    Li, Junhua; Zhang, Liqing

    2012-06-01

    Brain-computer interface (BCI) allows the use of brain activities for people to directly communicate with the external world or to control external devices without participation of any peripheral nerves and muscles. Motor imagery is one of the most popular modes in the research field of brain-computer interface. Although motor imagery BCI has some advantages compared with other modes of BCI, such as asynchronization, it is necessary to require training sessions before using it. The performance of trained BCI system depends on the quality of training samples or the subject engagement. In order to improve training effect and decrease training time, we proposed a new paradigm where subjects participated in training more actively than in the traditional paradigm. In the traditional paradigm, a cue (to indicate what kind of motor imagery should be imagined during the current trial) is given to the subject at the beginning of a trial or during a trial, and this cue is also used as a label for this trial. It is usually assumed that labels for trials are accurate in the traditional paradigm, although subjects may not have performed the required or correct kind of motor imagery, and trials may thus be mislabeled. And then those mislabeled trials give rise to interference during model training. In our proposed paradigm, the subject is required to reconfirm the label and can correct the label when necessary. This active training paradigm may generate better training samples with fewer inconsistent labels because it overcomes mistakes when subject's motor imagination does not match the given cues. The experiments confirm that our proposed paradigm achieves better performance; the improvement is significant according to statistical analysis.

  15. Evolvability as a Quality Attribute of Software Architectures

    NARCIS (Netherlands)

    Ciraci, S.; van den Broek, P.M.; Duchien, Laurence; D'Hondt, Maja; Mens, Tom

    We review the definition of evolvability as it appears on the literature. In particular, the concept of software evolvability is compared with other system quality attributes, such as adaptability, maintainability and modifiability.

  16. Cancer research in need of a scientific revolution: Using `paradigm ...

    Indian Academy of Sciences (India)

    It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of `paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the `paradigm shift' method in cancer research ...

  17. Evolving colon injury management: a review.

    Science.gov (United States)

    Greer, Lauren T; Gillern, Suzanne M; Vertrees, Amy E

    2013-02-01

    The colon is the second most commonly injured intra-abdominal organ in penetrating trauma. Management of traumatic colon injuries has evolved significantly over the past 200 years. Traumatic colon injuries can have a wide spectrum of severity, presentation, and management options. There is strong evidence that most non-destructive colon injuries can be successfully managed with primary repair or primary anastomosis. The management of destructive colon injuries remains controversial with most favoring resection with primary anastomosis and others favor colonic diversion in specific circumstances. The historical management of traumatic colon injuries, common mechanisms of injury, demographics, presentation, assessment, diagnosis, management, and complications of traumatic colon injuries both in civilian and military practice are reviewed. The damage control revolution has added another layer of complexity to management with continued controversy.

  18. Resiliently evolving supply-demand networks

    Science.gov (United States)

    Rubido, Nicolás; Grebogi, Celso; Baptista, Murilo S.

    2014-01-01

    The ability to design a transport network such that commodities are brought from suppliers to consumers in a steady, optimal, and stable way is of great importance for distribution systems nowadays. In this work, by using the circuit laws of Kirchhoff and Ohm, we provide the exact capacities of the edges that an optimal supply-demand network should have to operate stably under perturbations, i.e., without overloading. The perturbations we consider are the evolution of the connecting topology, the decentralization of hub sources or sinks, and the intermittence of supplier and consumer characteristics. We analyze these conditions and the impact of our results, both on the current United Kingdom power-grid structure and on numerically generated evolving archetypal network topologies.

  19. Development and the evolvability of human limbs.

    Science.gov (United States)

    Young, Nathan M; Wagner, Günter P; Hallgrímsson, Benedikt

    2010-02-23

    The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change.

  20. Life cycle planning: An evolving concept

    International Nuclear Information System (INIS)

    Moore, P.J.R.; Gorman, I.G.

    1994-01-01

    Life-cycle planning is an evolving concept in the management of oil and gas projects. BHP Petroleum now interprets this idea to include all development planning from discovery and field appraisal to final abandonment and includes safety, environmental, technical, plant, regulatory, and staffing issues. This article describes in the context of the Timor Sea, how despite initial successes and continuing facilities upgrades, BHPP came to perceive that current operations could be the victim of early development successes, particularly in the areas of corrosion and maintenance. The search for analogies elsewhere lead to the UK North Sea, including the experiences of Britoil and BP, both of which performed detailed Life of Field studies in the later eighties. These materials have been used to construct a format and content for total Life-cycle plans in general and the social changes required to ensure their successful application in Timor Sea operations and deployment throughout Australia

  1. Argentina and Brazil: an evolving nuclear relationship

    International Nuclear Information System (INIS)

    Redick, J.R.

    1990-01-01

    Argentina and Brazil have Latin America's most advanced nuclear research and power programs. Both nations reject the Non-Proliferation Treaty (NPT), and have not formally embraced the Tlatelolco Treaty creating a regional nuclear-weapon-free zone. Disturbing ambiguities persist regarding certain indigenous nuclear facilities and growing nuclear submarine and missile capabilities. For these, and other reasons, the two nations are widely considered potential nuclear weapon states. However both nations have been active supporters of the International Atomic Energy Agency (IAEA) and have, in recent years, assumed a generally responsible position in regard to their own nuclear export activities (requiring IAEA safeguards). Most important, however, has been the advent of bilateral nuclear cooperation. This paper considers the evolving nuclear relationship in the context of recent and dramatic political change in Argentina and Brazil. It discusses current political and nuclear developments and the prospects for maintaining and expanding present bilateral cooperation into an effective non-proliferation arrangement. (author)

  2. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    Directory of Open Access Journals (Sweden)

    D. D. Miniaeva

    2014-06-01

    Full Text Available This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism. The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, targets, tools, processes. Results of research show that the beginning of the XXI century is distinguished by the development of new types of political concepts that explain interaction of elements in modern international relations in the area of environmental protection. The reason of these changes lies in the phenomena of environmentalism integration into Three paradigms of international relations. However, we cannot say that any of the examined paradigms accumulated all features of environmentalism without their modification. Better to say, it's rather similar to adaptation of environmental ideas. Therefore, to understand modern international relations processes, it is necessary to take into account their environmental element. Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-4

  3. The genotype-phenotype map of an evolving digital organism

    OpenAIRE

    Fortuna, Miguel A.; Zaman, Luis; Ofria, Charles; Wagner, Andreas

    2017-01-01

    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms fr...

  4. Understanding Mixed Emotions: Paradigms and Measures

    Science.gov (United States)

    Kreibig, Sylvia D.; Gross, James J.

    2017-01-01

    In this review, we examine the paradigms and measures available for experimentally studying mixed emotions in the laboratory. For eliciting mixed emotions, we describe a mixed emotions film library that allows for the repeated elicitation of a specific homogeneous mixed emotional state and appropriately matched pure positive, pure negative, and neutral emotional states. For assessing mixed emotions, we consider subjective and objective measures that fall into univariate, bivariate, and multivariate measurement categories. As paradigms and measures for objectively studying mixed emotions are still in their early stages, we conclude by outlining future directions that focus on the reliability, temporal dynamics, and response coherence of mixed emotions paradigms and measures. This research will build a strong foundation for future studies and significantly advance our understanding of mixed emotions. PMID:28804752

  5. A New Paradigm for Chemical Engineering?

    DEFF Research Database (Denmark)

    Gani, Rafiqul

    evidence of this change comes from the jobs taken by graduating chemical engineering professionals in North America, Europe, and some of the Asian countries. In terms of where the graduating chemical engineers are going to work, a clear shift from the commodity chemical industry to the product oriented...... businesses has been observed. There is an increasing trend within the chemical industry to focus on products and the sustainable processes that can make them. Do these changes point to a paradigm shift in chemical engineering as a discipline? Historically, two previous paradigm shifts in chemical engineering...... corresponded to major shifts in chemical engineering as a discipline, which affected not only the education of chemical engineers, but also the development of chemical engineering as a discipline. Has the time come for a new paradigm shift that will prepare the current and future chemical engineering graduates...

  6. RFID security a lightweight paradigm

    CERN Document Server

    Khattab, Ahmed; Amini, Esmaeil; Bayoumi, Magdy

    2017-01-01

    This book provides a comprehensive treatment of security in the widely adopted, Radio Frequency Identification (RFID) technology. The authors present the fundamental principles of RFID cryptography in a manner accessible to a broad range of readers, enabling them to improve their RFID security design. This book also offers the reader a range of interesting topics portraying the current state-of-the-art in RFID technology and how it can be integrated with today’s Internet of Things (IoT) vision. The authors describe a first-of-its-kind, lightweight symmetric authenticated encryption cipher called Redundant Bit Security (RBS), which enables significant, multi-faceted performance improvements compared to existing cryptosystems. This book is a must-read for anyone aiming to overcome the constraints of practical implementation in RFID security technologies.

  7. A new paradigm of cardiovascular risk factor modification

    Directory of Open Access Journals (Sweden)

    Muhammad Firdaus

    2005-07-01

    Full Text Available Muhammad Firdaus1, Jeffery M Asbury2, Dwight W Reynolds21Donald W Reynolds Department of Geriatric Medicine, University of Oklahoma, Oklahoma City, OK, USA; 2Department of Medicine, Cardiovascular Section, University of Oklahoma, Oklahoma City, OK, USAAbstract: Atherosclerotic cardiovascular diseases (CVDs are the leading cause of death and disability in the United States. While multiple studies have demonstrated that modification of atherosclerotic cardiovascular risk factors (CVRFs significantly reduces morbidity and mortality rates, clinical control of CVDs and CVRFs remains poor. By 2010, the American Heart Association seeks to reduce coronary heart disease, stroke, and risk by 25%. To meet this goal, clinical practitioners must establish new treatment paradigms for CVDs and CVRFs. This paper discusses one such treatment model – a comprehensive atherosclerosis program run by physician extenders (under physician supervision, which incorporates evidence-based CVD and CVRF interventions to achieve treatment goals.Keywords: atherosclerosis, cardiovascular risk factors, prevention, modification

  8. Cryptic species as a window into the paradigm shift of the species concept.

    Science.gov (United States)

    Fišer, Cene; Robinson, Christopher T; Malard, Florian

    2018-02-01

    The species concept is the cornerstone of biodiversity science, and any paradigm shift in the delimitation of species affects many research fields. Many biologists now are embracing a new "species" paradigm as separately evolving populations using different delimitation criteria. Individual criteria can emerge during different periods of speciation; some may never evolve. As such, a paradigm shift in the species concept relates to this inherent heterogeneity in the speciation process and species category-which is fundamentally overlooked in biodiversity research. Cryptic species fall within this paradigm shift: they are continuously being reported from diverse animal phyla but are poorly considered in current tests of ecological and evolutionary theory. The aim of this review is to integrate cryptic species in biodiversity science. In the first section, we address that the absence of morphological diversification is an evolutionary phenomenon, a "process" counterpart to the long-studied mechanisms of morphological diversification. In the next section regarding taxonomy, we show that molecular delimitation of cryptic species is heavily biased towards distance-based methods. We also stress the importance of formally naming of cryptic species for better integration into research fields that use species as units of analysis. Finally, we show that incorporating cryptic species leads to novel insights regarding biodiversity patterns and processes, including large-scale biodiversity assessments, geographic variation in species distribution and species coexistence. It is time for incorporating multicriteria species approaches aiming to understand speciation across space and taxa, thus allowing integration into biodiversity conservation while accommodating for species uncertainty. © 2018 John Wiley & Sons Ltd.

  9. The evolving energy budget of accretionary wedges

    Science.gov (United States)

    McBeck, Jessica; Cooke, Michele; Maillot, Bertrand; Souloumiac, Pauline

    2017-04-01

    The energy budget of evolving accretionary systems reveals how deformational processes partition energy as faults slip, topography uplifts, and layer-parallel shortening produces distributed off-fault deformation. The energy budget provides a quantitative framework for evaluating the energetic contribution or consumption of diverse deformation mechanisms. We investigate energy partitioning in evolving accretionary prisms by synthesizing data from physical sand accretion experiments and numerical accretion simulations. We incorporate incremental strain fields and cumulative force measurements from two suites of experiments to design numerical simulations that represent accretionary wedges with stronger and weaker detachment faults. One suite of the physical experiments includes a basal glass bead layer and the other does not. Two physical experiments within each suite implement different boundary conditions (stable base versus moving base configuration). Synthesizing observations from the differing base configurations reduces the influence of sidewall friction because the force vector produced by sidewall friction points in opposite directions depending on whether the base is fixed or moving. With the numerical simulations, we calculate the energy budget at two stages of accretion: at the maximum force preceding the development of the first thrust pair, and at the minimum force following the development of the pair. To identify the appropriate combination of material and fault properties to apply in the simulations, we systematically vary the Young's modulus and the fault static and dynamic friction coefficients in numerical accretion simulations, and identify the set of parameters that minimizes the misfit between the normal force measured on the physical backwall and the numerically simulated force. Following this derivation of the appropriate material and fault properties, we calculate the components of the work budget in the numerical simulations and in the

  10. Ethics in dermatology: toward a new paradigm.

    Science.gov (United States)

    López-Martín, S; Galera-Martin, C; Guerra-Tapia, A

    2013-01-01

    Medical ethics have evolved over time, and ethical responsibilities have often been shared by priests, the governing classes, and physicians. The emergence of scientific medicine led to the separation of functions, yet physicians have nonetheless continued to enjoy an extraordinary degree of moral authority and great social privilege. From this starting point, professional medical ethics developed as a specific moral system based on special rights and duties (paternalism and medical confidentiality). Various historical events brought this longstanding situation to a point of crisis toward the middle of the 20th century, and for several decades since, medical ethics have been based on freedom of choice for the patient with regard to decisions about his or her own body and health. Recent developments have created a new, still poorly defined model that takes into consideration such matters as euthanasia, abortion, provision of information on the benefits and harm of treatments, the sharing of therapeutic decision-making with the patient and/or family members, the choice of public or private medical providers, therapeutic guidelines, and the extension of the scope of practice to include preventive measures and cosmetic procedures. What is needed now is a new ethical system for plural societies that harbor different religions, beliefs and lifestyles, but that is also rational, universal and subject to ongoing revision-a system always striving for scientific, technical and moral excellence. Such an ethical system would have to be taught in medical schools, as it would need to bear fruit beyond mere good intentions. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  11. Closed loop deep brain stimulation: an evolving technology.

    Science.gov (United States)

    Hosain, Md Kamal; Kouzani, Abbas; Tye, Susannah

    2014-12-01

    Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

  12. On the Critical Role of Divergent Selection in Evolvability

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    2016-08-01

    Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

  13. Approximating centrality in evolving graphs: toward sublinearity

    Science.gov (United States)

    Priest, Benjamin W.; Cybenko, George

    2017-05-01

    The identification of important nodes is a ubiquitous problem in the analysis of social networks. Centrality indices (such as degree centrality, closeness centrality, betweenness centrality, PageRank, and others) are used across many domains to accomplish this task. However, the computation of such indices is expensive on large graphs. Moreover, evolving graphs are becoming increasingly important in many applications. It is therefore desirable to develop on-line algorithms that can approximate centrality measures using memory sublinear in the size of the graph. We discuss the challenges facing the semi-streaming computation of many centrality indices. In particular, we apply recent advances in the streaming and sketching literature to provide a preliminary streaming approximation algorithm for degree centrality utilizing CountSketch and a multi-pass semi-streaming approximation algorithm for closeness centrality leveraging a spanner obtained through iteratively sketching the vertex-edge adjacency matrix. We also discuss possible ways forward for approximating betweenness centrality, as well as spectral measures of centrality. We provide a preliminary result using sketched low-rank approximations to approximate the output of the HITS algorithm.

  14. Functional Topology of Evolving Urban Drainage Networks

    Science.gov (United States)

    Yang, Soohyun; Paik, Kyungrock; McGrath, Gavan S.; Urich, Christian; Krueger, Elisabeth; Kumar, Praveen; Rao, P. Suresh C.

    2017-11-01

    We investigated the scaling and topology of engineered urban drainage networks (UDNs) in two cities, and further examined UDN evolution over decades. UDN scaling was analyzed using two power law scaling characteristics widely employed for river networks: (1) Hack's law of length (L)-area (A) [L∝Ah] and (2) exceedance probability distribution of upstream contributing area (δ) [P>(A≥δ>)˜aδ-ɛ]. For the smallest UDNs ((A≥δ>) plots for river networks are abruptly truncated, those for UDNs display exponential tempering [P>(A≥δ>)=aδ-ɛexp⁡>(-cδ>)]. The tempering parameter c decreases as the UDNs grow, implying that the distribution evolves in time to resemble those for river networks. However, the power law exponent ɛ for large UDNs tends to be greater than the range reported for river networks. Differences in generative processes and engineering design constraints contribute to observed differences in the evolution of UDNs and river networks, including subnet heterogeneity and nonrandom branching.

  15. An Evolving Worldview: Making Open Source Easy

    Science.gov (United States)

    Rice, Z.

    2017-12-01

    NASA Worldview is an interactive interface for browsing full-resolution, global satellite imagery. Worldview supports an open data policy so that academia, private industries and the general public can use NASA's satellite data to address Earth science related issues. Worldview was open sourced in 2014. By shifting to an open source approach, the Worldview application has evolved to better serve end-users. Project developers are able to have discussions with end-users and community developers to understand issues and develop new features. Community developers are able to track upcoming features, collaborate on them and make their own contributions. Developers who discover issues are able to address those issues and submit a fix. This reduces the time it takes for a project developer to reproduce an issue or develop a new feature. Getting new developers to contribute to the project has been one of the most important and difficult aspects of open sourcing Worldview. After witnessing potential outside contributors struggle, a focus has been made on making the installation of Worldview simple to reduce the initial learning curve and make contributing code easy. One way we have addressed this is through a simplified setup process. Our setup documentation includes a set of prerequisites and a set of straightforward commands to clone, configure, install and run. This presentation will emphasize our focus to simplify and standardize Worldview's open source code so that more people are able to contribute. The more people who contribute, the better the application will become over time.

  16. Extreme insular dwarfism evolved in a mammoth.

    Science.gov (United States)

    Herridge, Victoria L; Lister, Adrian M

    2012-08-22

    The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan 'Palaeoloxodon' creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of 'P'. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages.

  17. How does cognition evolve? Phylogenetic comparative psychology.

    Science.gov (United States)

    MacLean, Evan L; Matthews, Luke J; Hare, Brian A; Nunn, Charles L; Anderson, Rindy C; Aureli, Filippo; Brannon, Elizabeth M; Call, Josep; Drea, Christine M; Emery, Nathan J; Haun, Daniel B M; Herrmann, Esther; Jacobs, Lucia F; Platt, Michael L; Rosati, Alexandra G; Sandel, Aaron A; Schroepfer, Kara K; Seed, Amanda M; Tan, Jingzhi; van Schaik, Carel P; Wobber, Victoria

    2012-03-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution.

  18. An evolving network model with modular growth

    International Nuclear Information System (INIS)

    Zou Zhi-Yun; Liu Peng; Lei Li; Gao Jian-Zhi

    2012-01-01

    In this paper, we propose an evolving network model growing fast in units of module, according to the analysis of the evolution characteristics in real complex networks. Each module is a small-world network containing several interconnected nodes and the nodes between the modules are linked by preferential attachment on degree of nodes. We study the modularity measure of the proposed model, which can be adjusted by changing the ratio of the number of inner-module edges and the number of inter-module edges. In view of the mean-field theory, we develop an analytical function of the degree distribution, which is verified by a numerical example and indicates that the degree distribution shows characteristics of the small-world network and the scale-free network distinctly at different segments. The clustering coefficient and the average path length of the network are simulated numerically, indicating that the network shows the small-world property and is affected little by the randomness of the new module. (interdisciplinary physics and related areas of science and technology)

  19. How does cognition evolve? Phylogenetic comparative psychology

    Science.gov (United States)

    Matthews, Luke J.; Hare, Brian A.; Nunn, Charles L.; Anderson, Rindy C.; Aureli, Filippo; Brannon, Elizabeth M.; Call, Josep; Drea, Christine M.; Emery, Nathan J.; Haun, Daniel B. M.; Herrmann, Esther; Jacobs, Lucia F.; Platt, Michael L.; Rosati, Alexandra G.; Sandel, Aaron A.; Schroepfer, Kara K.; Seed, Amanda M.; Tan, Jingzhi; van Schaik, Carel P.; Wobber, Victoria

    2014-01-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution. PMID:21927850

  20. A local-world evolving hypernetwork model

    International Nuclear Information System (INIS)

    Yang Guang-Yong; Liu Jian-Guo

    2014-01-01

    Complex hypernetworks are ubiquitous in the real system. It is very important to investigate the evolution mechanisms. In this paper, we present a local-world evolving hypernetwork model by taking into account the hyperedge growth and local-world hyperedge preferential attachment mechanisms. At each time step, a newly added hyperedge encircles a new coming node and a number of nodes from a randomly selected local world. The number of the selected nodes from the local world obeys the uniform distribution and its mean value is m. The analytical and simulation results show that the hyperdegree approximately obeys the power-law form and the exponent of hyperdegree distribution is γ = 2 + 1/m. Furthermore, we numerically investigate the node degree, hyperedge degree, clustering coefficient, as well as the average distance, and find that the hypernetwork model shares the scale-free and small-world properties, which shed some light for deeply understanding the evolution mechanism of the real systems. (interdisciplinary physics and related areas of science and technology)

  1. Evolving autonomous learning in cognitive networks.

    Science.gov (United States)

    Sheneman, Leigh; Hintze, Arend

    2017-12-01

    There are two common approaches for optimizing the performance of a machine: genetic algorithms and machine learning. A genetic algorithm is applied over many generations whereas machine learning works by applying feedback until the system meets a performance threshold. These methods have been previously combined, particularly in artificial neural networks using an external objective feedback mechanism. We adapt this approach to Markov Brains, which are evolvable networks of probabilistic and deterministic logic gates. Prior to this work MB could only adapt from one generation to the other, so we introduce feedback gates which augment their ability to learn during their lifetime. We show that Markov Brains can incorporate these feedback gates in such a way that they do not rely on an external objective feedback signal, but instead can generate internal feedback that is then used to learn. This results in a more biologically accurate model of the evolution of learning, which will enable us to study the interplay between evolution and learning and could be another step towards autonomously learning machines.

  2. Orbital Decay in Binaries with Evolved Stars

    Science.gov (United States)

    Sun, Meng; Arras, Phil; Weinberg, Nevin N.; Troup, Nicholas; Majewski, Steven R.

    2018-01-01

    Two mechanisms are often invoked to explain tidal friction in binary systems. The ``dynamical tide” is the resonant excitation of internal gravity waves by the tide, and their subsequent damping by nonlinear fluid processes or thermal diffusion. The ``equilibrium tide” refers to non-resonant excitation of fluid motion in the star’s convection zone, with damping by interaction with the turbulent eddies. There have been numerous studies of these processes in main sequence stars, but less so on the subgiant and red giant branches. Motivated by the newly discovered close binary systems in the Apache Point Observatory Galactic Evolution Experiment (APOGEE-1), we have performed calculations of both the dynamical and equilibrium tide processes for stars over a range of mass as the star’s cease core hydrogen burning and evolve to shell burning. Even for stars which had a radiative core on the main sequence, the dynamical tide may have very large amplitude in the newly radiative core in post-main sequence, giving rise to wave breaking. The resulting large dynamical tide dissipation rate is compared to the equilibrium tide, and the range of secondary masses and orbital periods over which rapid orbital decay may occur will be discussed, as well as applications to close APOGEE binaries.

  3. Minority games, evolving capitals and replicator dynamics

    International Nuclear Information System (INIS)

    Galla, Tobias; Zhang, Yi-Cheng

    2009-01-01

    We discuss a simple version of the minority game (MG) in which agents hold only one strategy each, but in which their capitals evolve dynamically according to their success and in which the total trading volume varies in time accordingly. This feature is known to be crucial for MGs to reproduce stylized facts of real market data. The stationary states and phase diagram of the model can be computed, and we show that the ergodicity breaking phase transition common for MGs, and marked by a divergence of the integrated response, is present also in this simplified model. An analogous majority game turns out to be relatively void of interesting features, and the total capital is found to diverge in time. Introducing a restraining force leads to a model akin to the replicator dynamics of evolutionary game theory, and we demonstrate that here a different type of phase transition is observed. Finally we briefly discuss the relation of this model with one strategy per player to more sophisticated minority games with dynamical capitals and several trading strategies per agent

  4. An evolving model of online bipartite networks

    Science.gov (United States)

    Zhang, Chu-Xu; Zhang, Zi-Ke; Liu, Chuang

    2013-12-01

    Understanding the structure and evolution of online bipartite networks is a significant task since they play a crucial role in various e-commerce services nowadays. Recently, various attempts have been tried to propose different models, resulting in either power-law or exponential degree distributions. However, many empirical results show that the user degree distribution actually follows a shifted power-law distribution, the so-called Mandelbrot’s law, which cannot be fully described by previous models. In this paper, we propose an evolving model, considering two different user behaviors: random and preferential attachment. Extensive empirical results on two real bipartite networks, Delicious and CiteULike, show that the theoretical model can well characterize the structure of real networks for both user and object degree distributions. In addition, we introduce a structural parameter p, to demonstrate that the hybrid user behavior leads to the shifted power-law degree distribution, and the region of power-law tail will increase with the increment of p. The proposed model might shed some lights in understanding the underlying laws governing the structure of real online bipartite networks.

  5. Evolving application of biomimetic nanostructured hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Norberto Roveri

    2010-11-01

    Full Text Available Norberto Roveri, Michele IafiscoLaboratory of Environmental and Biological Structural Chemistry (LEBSC, Dipartimento di Chimica ‘G. Ciamician’, Alma Mater Studiorum, Università di Bologna, Bologna, ItalyAbstract: By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical–physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical–physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical–physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.Keywords: hydroxyapatite, nanocrystals, biomimetism, biomaterials, drug delivery, remineralization

  6. School on Cloud: Towards a Paradigm Shift

    Science.gov (United States)

    Koutsopoulos, Kostis C.; Kotsanis, Yannis C.

    2014-01-01

    This paper presents the basic concept of the EU Network School on Cloud: Namely, that present conditions require a new teaching and learning paradigm based on the integrated dimension of education, when considering the use of cloud computing. In other words, it is suggested that there is a need for an integrated approach which is simultaneously…

  7. Den postmoderna stadens två paradigm

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2005-01-01

    the attention of politicians, planners and architects today is focused on the individual, not the collective. But the policy of the third way has no counterpart in an urbanism torn between two paradigms. Tom Nielsen paints the picture of what has to urban development since the welfare state...

  8. Redesigning Higher Education: Embracing a New Paradigm

    Science.gov (United States)

    Watson, William R.; Watson, Sunnie Lee

    2014-01-01

    Higher education is under enormous pressure to transform itself and embrace a new paradigm. Operating under an outdated model that no longer aligns with the realities of modern society, institutions of higher education are recognizing the need to drastically remake themselves or possibly cease to exist. This article explores the current landscape…

  9. A postfoundationalist research paradigm of practical theology

    Directory of Open Access Journals (Sweden)

    Sung Kyu Park

    2010-10-01

    This article examines and argues for postfoundationalism – transversal reason, interdisciplinarity and interpreted experience – as a viable theological option against rigid foundationalism and relativistic nonfoundationalism. Also discussed are the process and the interdisciplinary nature of practical theology. It is suggested that narrative research and social constructionism should be part of the research paradigm of postfoundational practical theology.

  10. New Paradigms for Computer Aids to Invention.

    Science.gov (United States)

    Langston, M. Diane

    Many people are interested in computer aids to rhetorical invention and want to know how to evaluate an invention aid, what the criteria are for a good one, and how to assess the trade-offs involved in buying one product or another. The frame of reference for this evaluation is an "old paradigm," which treats the computer as if it were…

  11. Diet and Cancer: The Fourth Paradigm

    Science.gov (United States)

    Walter C. Willett, MD, DrPH, an international expert in diet and nutrition, with posts as a Professor of Epidemiology and Nutrition and Chairman of the Department of Nutrition at Harvard School of Public Health and as Professor of Medicine at Harvard Medical School, presented "Diet and Cancer: The Fourth Paradigm".

  12. Challenging paradigms in estuarine ecology and management

    Science.gov (United States)

    Elliott, M.; Whitfield, A. K.

    2011-10-01

    For many years, estuarine science has been the 'poor relation' in aquatic research - freshwater scientists ignored estuaries as they tended to get confused by salt and tides, and marine scientists were more preoccupied by large open systems. Estuaries were merely regarded by each group as either river mouths or sea inlets respectively. For the past four decades, however, estuaries (and other transitional waters) have been regarded as being ecosystems in their own right. Although often not termed as such, this has led to paradigms being generated to summarise estuarine structure and functioning and which relate to both the natural science and management of these systems. This paper defines, details and affirms these paradigms that can be grouped into those covering firstly the science (definitions, scales, linkages, productivity, tolerances and variability) and secondly the management (pressures, valuation, health and services) of estuaries. The more 'science' orientated paradigms incorporate the development and types of ecotones, the nature of stressed and variable systems (with specific reference to resilience and redundancy), the relationship between generalists and specialists produced by environmental tolerance, the relevance of scale in relation to functioning and connectivity, the sources of production and degree of productivity, the biodiversity-ecosystem functioning and the stress-subsidy debates. The more 'management' targeted paradigms include the development and effects of exogenic unmanaged pressures and endogenic managed pressures, the perception of health and the ability to manage estuaries (related to internal and external influences), and the influence of all of these on the production of ecosystem services and societal benefits.

  13. THE NEW PUBLIC ADMINISTRATION PARADIGM DIRECTIONS

    OpenAIRE

    CHERVYAKOVA OLHA VOLODYMYRIVNA

    2017-01-01

    This article presents aspects of public administration paradigm of using disciplinary matrix, a public management model based on a feedback mechanism in the subject-subject interaction, which is the basis of theoretical and methodological establishment in public administration science (Public administration) in Ukraine.

  14. Trace elements as paradigms of developmental neurotoxicants

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Herz, Katherine T

    2015-01-01

    Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available...

  15. 06472 Abstracts Collection - XQuery Implementation Paradigms

    NARCIS (Netherlands)

    Boncz, Peter A.; Grust, Torsten; Siméon, Jerome; Boncz, P.A.; Grust, T.; Siméon, J.; van Keulen, Maurice

    From 19.11.2006 to 22.11.2006, the Dagstuhl Seminar 06472 ``XQuery Implementation Paradigms'' was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were

  16. Answer Set Programming and Other Computing Paradigms

    Science.gov (United States)

    Meng, Yunsong

    2013-01-01

    Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to…

  17. Toward an Ecological Paradigm in Adventure Programming

    Science.gov (United States)

    Beringer, Almut

    2004-01-01

    Many forms of adventure therapy, in particular wilderness therapy, rely on challenges in the outdoors to achieve objectives of client change. While nature is drawn on as a medium for therapy and healing, some adventure therapists give nature little if any mention when it comes to explaining therapeutic success. The dominant paradigm in psychology…

  18. ACCOUNTING PARADIGMS WHICH FAVOR HISTORICAL COST

    Directory of Open Access Journals (Sweden)

    Valentin Gabriel CRISTEA

    2014-05-01

    Full Text Available Henning Kirkegaard shows that the evolution of accounting is to shift from one paradigm to another . Business continuity perspective should guide the company into the future , without confine it exclusively in the past. Accounting in its classical form , however, can not be dissociated from the historical cost evaluation .

  19. On the solitary wave paradigm for tsunamis

    DEFF Research Database (Denmark)

    Madsen, Per A.; Fuhrman, David R.; Schäffer, Hemming Andreas

    2008-01-01

    Since the 1970s, solitary waves have commonly been used to model tsunamis especially in experimental and mathematical studies. Unfortunately, the link to geophysical scales is not well established, and in this work we question the geophysical relevance of this paradigm. In part 1, we simulate...

  20. A new paradigm for doing Reformed dogmatics

    Directory of Open Access Journals (Sweden)

    G. J. Spykman

    1992-06-01

    Full Text Available When discussing Reformational Theology: A New Paradigm for Doing Dogmatics some people may call it my opus magnum. Perhaps time 'will tell. The book has only recently - early 1992 - entered the marketplace of theological ideas. How critic readers and reviewers respond will go a long way toward settling the case.

  1. Moral Developmental Science between Changing Paradigms

    Science.gov (United States)

    Keller, Monika

    2012-01-01

    This review encompasses a time-span of about 50 years of research on morality and moral development. It discusses Kohlberg's (1984) work as a milestone that constituted the cognitive developmental viewpoint of morality and that dominated research for about three decades. In this paradigm the role of reasoning and deliberation was emphasized as the…

  2. Paradigms of Interaction Between Culture and Politics

    Directory of Open Access Journals (Sweden)

    Morteza Bahrani

    2012-12-01

    Full Text Available Political thought as a normative knowledge seeks a good society and the means for its realization. Accordingly, every intellectual paradigm introduces us a social and individual situation which is the best. This model, itself requires a dramatic change in the culture and flourishes it. In another words, there is a necessary relationship between the elements of political thought and the culture in every society. This relationship is twofold, so it is impossible to indicate whether which aspect is the first. So every paradigm feeds some special elements into the current culture of society, while there is it feedback. It is important that political thought goes in search of condition for cultural flourishing which is according whit the criteria of good society. This paper focuses on most important paradigm in political thought history and shows the trend in which indicates the relationships between political thought and culture. This trend looks at human beings as "citizen", then "the individual"; and in the modem era, paradigms of "critical modem", "postmodern", and "communitarian" has a key role in prospering the realm of culture.

  3. Fourth Generation War: Paradigm for Change

    Science.gov (United States)

    2005-06-01

    PARADIGM FOR CHANGE by Ghanshyam Singh Katoch June 2005 Thesis Advisor : Kalev Sepp Second Reader...Approved by: Kalev Sepp Thesis Advisor Douglas Borer Second Reader Gordon McCormick Chairman, Department of Defense...combination of all the resources of the government, not just the army. d. Economy of Effort A Robo -Soldier is a small, tracked, electrically powered vehicle

  4. Operationalizing Social Justice Counseling: Paradigm to Practice

    Science.gov (United States)

    Lewis, Judith A.

    2011-01-01

    Social justice counseling, like all humanistic models, recognizes the dignity of each human being, affirms the right of all people to choose and work toward their own goals, and asserts the importance of service to community. The social justice paradigm brings a special emphasis on the role of the environment. (Contains 1 figure and 1 table.)

  5. Historical ESWT Paradigms Are Overcome: A Narrative Review

    Science.gov (United States)

    Nauck, Tanja; Korakakis, Vasileios; Malliaropoulos, Nikos

    2016-01-01

    Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a historical consensus meeting in 1995 are to be revised. First, modern musculoskeletal ESWT is divided into focused and radial technology and the physical differences are about 100-fold with respect to the applied energy. Most lesions to be treated are easy to reach and clinical focusing plays a major role today. Lesion size is no longer a matter of concern. With the exception of nonunion fractures full, regional, or even local anesthesia is not helpful in musculoskeletal indications. Juvenile patients can also effectively be treated without risk of epiphyseal damage. Further research is needed to answer the question about if and which acute injuries can be managed effectively. Treatment parameters like the number of sessions are still relying on empirical data and have to be further elucidated. PMID:27493955

  6. Historical ESWT Paradigms Are Overcome: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Heinz Lohrer

    2016-01-01

    Full Text Available Extracorporeal Shock Wave Therapy (ESWT is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a historical consensus meeting in 1995 are to be revised. First, modern musculoskeletal ESWT is divided into focused and radial technology and the physical differences are about 100-fold with respect to the applied energy. Most lesions to be treated are easy to reach and clinical focusing plays a major role today. Lesion size is no longer a matter of concern. With the exception of nonunion fractures full, regional, or even local anesthesia is not helpful in musculoskeletal indications. Juvenile patients can also effectively be treated without risk of epiphyseal damage. Further research is needed to answer the question about if and which acute injuries can be managed effectively. Treatment parameters like the number of sessions are still relying on empirical data and have to be further elucidated.

  7. Streptococcus mutans: a new Gram-positive paradigm?

    Science.gov (United States)

    Quivey, Robert G.; Koo, Hyun; Abranches, Jacqueline

    2013-01-01

    Despite the enormous contributions of the bacterial paradigms Escherichia coli and Bacillus subtilis to basic and applied research, it is well known that no single organism can be a perfect representative of all other species. However, given that some bacteria are difficult, or virtually impossible, to cultivate in the laboratory, that some are recalcitrant to genetic and molecular manipulation, and that others can be extremely dangerous to manipulate, the use of model organisms will continue to play an important role in the development of basic research. In particular, model organisms are very useful for providing a better understanding of the biology of closely related species. Here, we discuss how the lifestyle, the availability of suitable in vitro and in vivo systems, and a thorough understanding of the genetics, biochemistry and physiology of the dental pathogen Streptococcus mutans have greatly advanced our understanding of important areas in the field of bacteriology such as interspecies biofilms, competence development and stress responses. In this article, we provide an argument that places S. mutans, an organism that evolved in close association with the human host, as a novel Gram-positive model organism. PMID:23393147

  8. Universities in the global knowledge economy: the eclectic paradigm

    Directory of Open Access Journals (Sweden)

    Denys Ilnytskyy

    2015-06-01

    Full Text Available As institutions of knowledge generation and diffusion, in the course of their activities universities should take into account not only the level of an organization or a country but also that of individual knowledge transformation, whereby creating favorable conditions for developing creativity of both graduates and academic staff who form the basis of the intellectual capital of the university and the country. While functioning in the global competitive climate, the national intellectual capital is a factor of socio-economic development and international competitive status of individual countries. During decades the concept of university has been evolving toward determining the operation mode of a university as that of an institution providing mass education, carrying out fundamental and applied researches as well as largely participating in local, national and global development. However, the university operation paradigm remains eclectic. Equal relationships between universities, government and industry in a knowledge-based society are well-defined by the concept of triple helix innovation systems engaging NGOs. World-class universities tend ever more to incorporate the feature of an entrepreneurial university actively competing in the global academic domain.

  9. Quantum mechanics in an evolving Hilbert space

    Science.gov (United States)

    Artacho, Emilio; O'Regan, David D.

    2017-03-01

    Many basis sets for electronic structure calculations evolve with varying external parameters, such as moving atoms in dynamic simulations, giving rise to extra derivative terms in the dynamical equations. Here we revisit these derivatives in the context of differential geometry, thereby obtaining a more transparent formalization, and a geometrical perspective for better understanding the resulting equations. The effect of the evolution of the basis set within the spanned Hilbert space separates explicitly from the effect of the turning of the space itself when moving in parameter space, as the tangent space turns when moving in a curved space. New insights are obtained using familiar concepts in that context such as the Riemann curvature. The differential geometry is not strictly that for curved spaces as in general relativity, a more adequate mathematical framework being provided by fiber bundles. The language used here, however, will be restricted to tensors and basic quantum mechanics. The local gauge implied by a smoothly varying basis set readily connects with Berry's formalism for geometric phases. Generalized expressions for the Berry connection and curvature are obtained for a parameter-dependent occupied Hilbert space spanned by nonorthogonal Wannier functions. The formalism is applicable to basis sets made of atomic-like orbitals and also more adaptative moving basis functions (such as in methods using Wannier functions as intermediate or support bases), but should also apply to other situations in which nonorthogonal functions or related projectors should arise. The formalism is applied to the time-dependent quantum evolution of electrons for moving atoms. The geometric insights provided here allow us to propose new finite-difference time integrators, and also better understand those already proposed.

  10. Public participation at Fernald: FERMCO's evolving role

    International Nuclear Information System (INIS)

    Williams, J.B.; Fellman, R.W.; Brettschneider, D.J.

    1995-01-01

    In an effort to improve public involvement in the site restoration decision making process, the DOE has established site specific advisory boards, of which the Fernald Citizens Task Force is one. The Fernald Task Force is focused on making recommendations in four areas: (1) What should be the future use of the site? (2) Determinations of cleanup levels (how clean is clean?) (3) Where should the wastes be disposed of? (4) What should be the cleanup priorities? Because these questions are being asked very early in the decision-making process, the answers are necessarily qualified, and are based on a combination of preliminary data, assumptions, and professional judgment. The requirement to make progress in the absence of accurate data has necessitated FERMCO and the Task Force to employ an approach similar to sensitivity analysis, in which a range of possible data values are evaluated and the relative importance of the various factors is assessed. Because of its charter to provide recommendations of future site use, the Task Force has developed a sitewide perspective, compared to the more common operable unit specific focus of public participation under CERCLA. The relationship between FERMCO and the Task Force is evolving toward one of partnership with DOE in managing the obstacles and hidden opportunities for success. The Task Force likely will continue to participate in the Fernald project long after its initial recommendations have been made. DOE already has made the commitment that the process of public participation will extend into the Remedial Design phase. There is substantial reason for optimism that continuing the Task Force process through the design phase will assist in developing the appropriate balance of cost and engineered protectiveness

  11. Changing paradigms of anti-VEGF in the Indian scenario

    Directory of Open Access Journals (Sweden)

    P Mahesh Shanmugam

    2014-01-01

    Full Text Available Anti-vascular endothelial growth factors (VEGF agents have revolutionized the treatment of retinal diseases. Use of anti-VEGF agents in the Indian Scenario present some unique challenges considering the absence of compounding pharmacies, poor penetrance of health insurance and limited affordability of the citizens of a developing economy. To study the changing paradigms of anti-VEGF use in the Indian scenario, all articles published by Indian authors, data from web-based surveys amongst Indian vitreo-retinal specialists were reviewed. In the paucity of compounding pharmacies in India, fractionation and injection techniques differ from those of developed countries. Frequent anti-VEGF monotherapy offers the best anatomical and visual results, but economics of scale do not allow the same in the Indian scenario, resulting in PRN dosing and combination of anti-VEGF with laser photocoagulation, being the commonly employed treatment protocols.

  12. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria

    OpenAIRE

    Nicolle, Lindsay E.

    2016-01-01

    Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequenc...

  13. New treatment paradigm of combined raloxifene and conjugated ...

    African Journals Online (AJOL)

    Marwa N. Emam

    2016-07-25

    Jul 25, 2016 ... partnering a selective estrogen receptor modulator (SERM) with one or more estrogens. Aim: Our ... in which there is a gradual rather than abrupt decline of sex ..... responsive organ, it has received little attention compared to.

  14. Logistic paradigm for industrial solid waste treatment processes

    Directory of Open Access Journals (Sweden)

    Janusz Grabara

    2014-12-01

    Full Text Available Due to the fact that industrial waste are a growing problem, both economic and environmental as their number is increasing every year, it is important to take measures to correctly dealing wi th industrial waste. This article presents the descriptive model of logistics processes concerning the management of industrial waste. In this model the flow of waste begins in the place of production and ends at their disposal. The article presents the concept of logistics model in graphical form together with an analysis of individual processes and their linkages, and opportunities to improve flow of industrial waste streams. Furthermore, the model allows for justification of the relevance of use logistics and its processes for waste management

  15. Logistic paradigm for industrial solid waste treatment processes

    OpenAIRE

    Janusz Grabara; Ioan Constantin Dima

    2014-01-01

    Due to the fact that industrial waste are a growing problem, both economic and environmental as their number is increasing every year, it is important to take measures to correctly dealing wi th industrial waste. This article presents the descriptive model of logistics processes concerning the management of industrial waste. In this model the flow of waste begins in the place of production and ends at their disposal. The article presents the concept of logistics model in graphical form...

  16. New treatment paradigm of combined raloxifene and conjugated ...

    African Journals Online (AJOL)

    estradiol (E2), vehicle treated groups used as positive and negative controls, respectively. The bone turnover markers (BTM) were measured. The uterotropic activity was assessed by the uterine index and peroxidase assay. Vaginal wet weight ...

  17. A new paradigm for HIV care: ethical and clinical considerations.

    Science.gov (United States)

    Noring, S; Dubler, N N; Birkhead, G; Agins, B

    2001-05-01

    Although dramatic advances in clinical treatment have greatly improved the lives of many people with HIV/AIDS, many other patients do not have information about or access to these treatments because of health care providers' presumptive judgments about patients' ability to adhere to medical regimens. The authors contend that with sufficient support and education most patients, even those with difficult social and medical problems, can be helped to initiate and maintain HIV treatment in accordance with current clinical standards. This commentary delineates a new paradigm for HIV care in which patients and providers collaborate on individualized plans to establish patients' readiness for treatment, ensure maintenance of treatment, and make use of the social services necessary to accomplish these goals. Providers have an ethical responsibility to do everything possible to see that patients who might benefit from new HIV treatments have a fair opportunity to do so, and health systems have a responsibility to facilitate this process. Substantial progress toward meeting these responsibilities can be made within the current health care environment.

  18. Evolving R Coronae Borealis Stars with MESA

    Science.gov (United States)

    Clayton, Geoffrey C.; Lauer, Amber; Chatzopoulos, Emmanouil; Frank, Juhan

    2018-01-01

    being a WD. Solving the mystery of how the RCB stars evolve will lead to a better understanding of other important types of stellar merger events such as Type Ia SNe.

  19. Mechanics of evolving thin film structures

    Science.gov (United States)

    Liang, Jim

    In the Stranski-Krastanov system, the lattice mismatch between the film and the substrate causes the film to break into islands. During annealing, both the surface energy and the elastic energy drive the islands to coarsen. Motivated by several related studies, we suggest that stable islands should form when a stiff ceiling is placed at a small gap above the film. We show that the role of elasticity is reversed: with the ceiling, the total elastic energy stored in the system increases as the islands coarsen laterally. Consequently, the islands select an equilibrium size to minimize the combined elastic energy and surface energy. In lithographically-induced self-assembly, when a two-phase fluid confined between parallel substrates is subjected to an electric field, one phase can self-assemble into a triangular lattice of islands in another phase. We describe a theory of the stability of the island lattice. The islands select the equilibrium diameter to minimize the combined interface energy and electrostatic energy. Furthermore, we study compressed SiGe thin film islands fabricated on a glass layer, which itself lies on a silicon wafer. Upon annealing, the glass flows, and the islands relax. A small island relaxes by in-plane expansion. A large island, however, wrinkles at the center before the in-plane relaxation arrives. The wrinkles may cause significant tensile stress in the island, leading to fracture. We model the island by the von Karman plate theory and the glass layer by the Reynolds lubrication theory. Numerical simulations evolve the in-plane expansion and the wrinkles simultaneously. We determine the critical island size, below which in-plane expansion prevails over wrinkling. Finally, in devices that integrate dissimilar materials in small dimensions, crack extension in one material often accompanies inelastic deformation in another. We analyze a channel crack advancing in an elastic film under tension, while an underlayer creeps. We use a two

  20. Discrimination in Public Employment: The Evolving Law.

    Science.gov (United States)

    McCarthy, Martha M.

    This monograph reviews the current status of constitutional, statutory, and case law governing public employers' obligations to assure equal employment opportunities and employees' rights to nondiscriminatory treatment. An initial overview of the legal framework discusses federal equal protection mandates including the guarantee of equal…

  1. The membrane paradigm for black holes

    International Nuclear Information System (INIS)

    Price, R.H.; Thorne, K.S.

    1988-01-01

    It is now widely accepted that black holes exist and have an astrophysical role, in particular as the likely power source of quasars. To understand this role with ease, the authors and their colleagues have developed a new paradigm for black holes - a new way to picture, think about and describe them. As far as possible it treats black holes as ordinary astrophysical objects, made of real material. A black hole in this description is a spherical or oblate surface made of a thin, electrically conducting membrane. It was the author's quest to understand the Blandford-Znajek process intuitively that led them to create the membrane paradigm. Their strategy was to translate the general-relativistic mathematics of black holes into the same language of three-dimensional space that is used for magnetized plasmas and to create a new set of black-hole diagrams and pictures to go along with the language. 9 figs

  2. Changing the Dominant Paradigm in Economics

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Mollo

    2015-10-01

    Full Text Available This article addresses the discussion proposed by the World Academy of Art & Science (WAAS about the need to build a new paradigm to confront the challenges of the global society and to move across to a New Society discussing specific problems related to economic globalization and proposing changes. The ways in which economic orthodoxy and heterodoxy analyze the role of the State and the question of sustainability of development and the problems of environmental sustainability depend on their different views or theoretical arguments about the role of the market. The article contrasts the mainstream economics arguments to support the free market context of globalization with Post-Keynesian and Marxist’s skeptical or critical views. Finally, it proposes some strategies to face the critical aspects analyzed making suggestions to move to another dominant economic paradigm.

  3. [Assistance to the climacteric woman: new paradigms].

    Science.gov (United States)

    Lorenzi, Dino Roberto Soares De; Catan, Lenita Binelli; Moreira, Karen; Artico, Graziela Rech

    2009-01-01

    Population aging is a demographic reality for Brazil. Consequently, in the next years it is expected a progressive increase in seeking health care services in the country by women with complaints related to climacterium. Parallel to it, assistance at this part of woman's life has been going through a paradigm shift which has imposed to health professionals a change of attitude in relation to this stage of woman's life. Today it is acknowledged that the climacterium is influenced by biological, psychosocial and cultural factors, whose knowledge is fundamental for planning a more qualified and humanized care. This article proposes a reflection on the paradigm shifts in assistance at climacterium, highlighting important aspects as multidisciplinarity and interdisciplinarity, so as to serve better this portion of population, and provide it with more integrated and individualized care, bringing together knowledge and sensitivity, and always aiming at a better quality of life.

  4. Inhabiting compassion: A pastoral theological paradigm

    Directory of Open Access Journals (Sweden)

    Phil C. Zylla

    2017-08-01

    Full Text Available Inspired by the vision of care in Vincent van Gogh’s depiction of the parable of the Good Samaritan, this article offers a paradigm for inhabiting compassion. Compassion is understood in this article as a moral emotion that is also a pathocentric virtue. This definition creates a dynamic view of compassion as a desire to alleviate the suffering of others, the capacity to act on behalf of others and a commitment to sustain engagement with the suffering other. To weave this vision of compassion as a habitus rather than a theoretical construct, the article develops three phases of compassion: seeing, companioning and sighing. This framework deepens and augments a pastoral theological paradigm of compassion with the aim of inculcating an inhabited compassion in caregivers and the communities in which they participate.

  5. BMS invariance and the membrane paradigm

    International Nuclear Information System (INIS)

    Penna, Robert F.

    2016-01-01

    The Bondi-van der Burg-Metzner-Sachs (BMS) group is the asymptotic symmetry group of asymptotically flat spacetime. It is infinite dimensional and entails an infinite number of conservation laws. According to the black hole membrane paradigm, null infinity (in asymptotically flat spacetime) and black hole event horizons behave like fluid membranes. The fluid dynamics of the membrane is governed by an infinite set of symmetries and conservation laws. Our main result is to point out that the infinite set of symmetries and conserved charges of the BMS group and the membrane paradigm are the same. This relationship has several consequences. First, it sheds light on the physical interpretation of BMS conservation laws. Second, it generalizes the BMS conservation laws to arbitrary subregions of arbitrary null surfaces. Third, it clarifies the identification of the superrotation subgroup of the BMS group. We briefly comment on the black hole information problem.

  6. Radiation a new paradigm... Societal impacts

    International Nuclear Information System (INIS)

    Sutcliffe, Jill

    2010-01-01

    Latency is associated with the time lag it takes for the health effects resulting from exposure to ionising radiation to show up. However, the term latency can also be applied to the time it takes for a policy to be implemented. This length of time has been suggested as broadly 40-year process. Given that radioactivity was identified and named in 1896, three paradigms are identified and examined from 1896 to 2016 and the criteria for a 4th paradigm suggested for the period 2017-2056. The review examines the changes that have taken place in scientific understanding and in public trust, a few key developments and the associated establishment of the related organisational infrastructure designed to collate and assess the evidence.

  7. Brachytherapy in the treatment of cervical cancer: a review

    Directory of Open Access Journals (Sweden)

    Banerjee R

    2014-05-01

    Full Text Available Robyn Banerjee,1 Mitchell Kamrava21Department of Radiation Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada; 2Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USAAbstract: Dramatic advances have been made in brachytherapy for cervical cancer. Radiation treatment planning has evolved from two-dimensional to three-dimensional, incorporating magnetic resonance imaging and/or computed tomography into the treatment paradigm. This allows for better delineation and coverage of the tumor, as well as improved avoidance of surrounding organs. Consequently, advanced brachytherapy can achieve very high rates of local control with a reduction in morbidity, compared with historic approaches. This review provides an overview of state-of-the-art gynecologic brachytherapy, with a focus on recent advances and their implications for women with cervical cancer.Keywords: cervical cancer, brachytherapy, image-guided brachytherapy

  8. Paradigms of modern radio-biology

    International Nuclear Information System (INIS)

    Grodzins'kij, D.M.

    2005-01-01

    The basic paradigms of modern radio-biology are considered as models of pictures of essence of radio-biology problems and methods of their decision. It is marked on absolute heuristics of these ascending conceptual assertions and their assistance to subsequent development of experimental science. That has the concrete display in the decision of actual tasks of protection of people from action of ionizing radiation

  9. The Knowledge Society: A Sustainability Paradigm

    Directory of Open Access Journals (Sweden)

    Naim Hamdija Afgan

    2010-10-01

    Full Text Available This paper defines the knowledge society as a human structured organisation based on contemporary developed knowledge and representing new quality of life support systems. It implies the need for a full understanding of distribution of knowledge, access to information and the capability to transfer information into a knowledge. The understanding of knowledge is the central challenge when defining a knowledge society. From our present perception of knowledge society, it is of interest to emphasize the role of the knowledge society in future development of human society. The life support systems are essential pillars of human society development. In this respect knowledge society represents a new paradigm for future development and it is strongly correlated to sustainable development. For this reason the sustainability paradigm of knowledge society is a potential frame for human society development leading to social cohesion, economic competitiveness and stability, use of resources and economic development, safeguarding biodiversity and the ecosystem.In order to verify the mutual relation between knowledge society and sustainability, we have to introduce the difference between these two terms. The knowledge society is based on the agglomeration of eco-knowledge, env-knowledge and soc-knowledge, it may be evaluated as the complex knowledge of quality of life support systems. We have to introduce metrics which will allow us to present knowledge as the paradigm of the number of indicators for verifying progress made.Sustainability metrics are designed to consolidate measures of economic, environmental and social performance of any system. It can be understood as a pattern for evaluation of the available knowledge about systems and their performance. In particular the decision-making process for the selection of the system under consideration must be based on the available knowledge. The link between knowledge and sustainability makes it possible for

  10. Agricultural Economics and Qualitative Research: Incompatible Paradigms?

    OpenAIRE

    Vera Bitsch

    2000-01-01

    The disciplinary paradigm of agricultural economics emphasizes rational behavior in a world constrained by scarce resources. The research practice focuses on the quantitative modeling of optimization behavior. These models, though, only offer limited support to practitioners in solving real-world problems. Qualitative research approaches contribute to this task, particularly with research in developing countries. Participatory action research was introduced in the seventies; case studies have...

  11. Doing smooth pursuit paradigms in Windows 7

    DEFF Research Database (Denmark)

    Wilms, Inge Linda

    predict strengths or deficits in perception and attention. However, smooth pursuit movements have been difficult to study and very little normative data is available for smooth pursuit performance in children and adults. This poster describes the challenges in setting up a smooth pursuit paradigm...... in Windows 7 with live capturing of eye movements using a Tobii TX300 eye tracker. In particular, the poster describes the challenges and limitations created by the hardware and the software...

  12. What Do Ecological Paradigms Offer to Conservation?

    International Nuclear Information System (INIS)

    Ale, S.B.; Howe, H.F.; Ale, S.B.; Howe, H.F.

    2010-01-01

    Ecological theory provides applications to biodiversity management but often falls short of expectations. One possibility is that heuristic theories of a young science are too immature. Logistic growth predicts a carrying capacity, but fisheries managed with the Lotka-Volterra paradigm continue to collapse. A second issue is that general predictions may not be useful. The theory of island biogeography predicts species richness but does not predict community composition. A third possibility is that the theory itself may not have much to do with nature, or that empirical parameterization is too difficult to know. The meta population paradigm is relevant to conservation, but meta populations might not be common in nature. For instance, empirical parameterization within the meta population paradigm is usually infeasible. A challenge is to determine why ecology fails to match needs of managers sometimes but helps at other. Managers may expect too much of paradigmatic blueprints, while ecologists believe them too much. Those who implement biodiversity conservation plans need simple, pragmatic guidelines based on science. Is this possible. What is possible An eclectic review of theory and practice demonstrate the power and weaknesses of the ideas that guide conservation and attempt to identify reasons for prevailing disappointment.

  13. Toward a Metatheoretical Integration of Developmental Paradigms

    Directory of Open Access Journals (Sweden)

    Mark W. Antley

    2010-07-01

    Full Text Available This paper shows how a partial consilience might be achieved in the field of human development by means of principles from general systems theory. The author concurs with Sameroff (1989 that it is possible to interpret the mechanistic, organisimic, and contextualist paradigms/worldviews (Goldhaber, 2000; Pepper, 1970 in terms of general systems theory. The author selects a major developmentalist from each paradigm and interprets that scholar’s work in terms of systems principles. The following developmentalists were selected: Arnold Sameroff (contextualism, Erik Erickson (organicism, and Albert Bandura (mechanism. The systems principles employed are wholeness and order, self-stabilization, self-reorganization, hierarchical interaction, and dialectical contradiction (Sameroff, 1989. The author addresses the conflicting presuppositions of the major paradigms in order to provide for their theoretical subsuming under systems theory. Finally, the author notes areas of inconsistency that will need to be resolved in the future and calls for further scholarship to translate developmental theory in terms of general systems theory for the benefit of students, scholars, consultants and other practitioners familiar with systems theory.

  14. Marketing communications: Qualitative and quantitative paradigm

    Directory of Open Access Journals (Sweden)

    Uzelac Nikola

    2005-01-01

    Full Text Available This paper focuses on key issues in relation to the choice of basic language of communication of marketing as a practical and academic field. Principally, marketing managers prefer descriptive way of expression, but they should use the advantages of language of numbers much more. By doing so, they will advance decision-making process - and the communication with finance and top management. In this regard, models offered by academic community could be helpful. This especially pertains to those positive or normative verbal approaches and models in which mathematics and statistical solutions have been embedded, as well as to those which emphasize financial criteria in decision-making. Concerning the process of creation and verification of scientific knowledge, the choice between languages of words and numbers is the part of much wider dimension, because it is inseparable from the decision on basic research orientation. Quantitative paradigm is more appropriate for hypotheses testing, while qualitative paradigm gives greater contribution in their generation. Competition factor could become the key driver of changes by which existing "parallel worlds" of main paradigms would be integrating, for the sake of disciplinary knowledge advancement.

  15. Paradigm Adherence and Personality Correlates across Mental Health Professions

    Science.gov (United States)

    Rauscher, Laura Anne

    2012-01-01

    Paradigm adherence has been developed as a meta-theoretical approach to organize and to classify the multitude of different theories of counseling and psychotherapy. Four paradigms have been identified in the literature: The Organic-Medical, The Psychological, The Systemic-Relational, and the Social Constructivist paradigms. Only one other study…

  16. Linking aims, paradigm and method in nursing research.

    Science.gov (United States)

    Houghton, Catherine; Hunter, Andrew; Meskell, Pauline

    2012-01-01

    To explore the use of paradigms as ontological and philosophical guides for conducting PhD research. A paradigm can help to bridge the aims of a study and the methods to achieve them. However, choosing a paradigm can be challenging for doctoral researchers: there can be ambiguity about which paradigm is suitable for a particular research question and there is a lack of guidance on how to shape the research process for a chosen paradigm. The authors discuss three paradigms used in PhD nursing research: post-positivism, interpretivism and pragmatism. They compare each paradigm in relation to its ontology, epistemology and methodology, and present three examples of PhD nursing research studies to illustrate how research can be conducted using these paradigms in the context of the research aims and methods. The commonalities and differences between the paradigms and their uses are highlighted. Creativity and flexibility are important when deciding on a paradigm. However, consistency and transparency are also needed to ensure the quality and rigour necessary for conducting nursing research. When choosing a suitable paradigm, the researcher should ensure that the ontology, epistemology and methodology of the paradigm are manifest in the methods and research strategies employed.

  17. The Imperative Paradigm of Korowai, a language of West Papua

    NARCIS (Netherlands)

    de Vries, Lourens; Aikhenvald, Alexandra; Dixon, R.M.W

    2017-01-01

    The imperative paradigm of Korowai, a Papuan language of West Papua, is the richest independent verb paradigm of Korowai: it makes more tense, aspect, mood, person and number distinctions than all other verb paradigms. This formal richness is matched by functional richness: imperatives are used in a

  18. A New Control Paradigm for Stochastic Differential Equations

    Science.gov (United States)

    Schmid, Matthias J. A.

    to scalar systems subject to state-dependent noise and to systems of higher order. The suggested control paradigm is further advanced when a sequential application of MLD control is considered. This technique yields a nominal path corresponding to the minimum total deviation probability on the entire time domain. It is demonstrated that this sequential optimization concept can be unified in a single objective function which is revealed to be the Jacobi field performance index on the entire domain subject to an endpoint deviation. The emerging closed-form term replaces the previously required nested optimization and, thus, results in a highly efficient application-ready control design. This effectively substantiates Minimum Path Deviation (MPD) control. The proposed control paradigm allows the specific problem of stochastic cost control to be addressed as a special case. This new technique is employed within this study for the stochastic cost problem giving rise to Cost Constrained MPD (CCMPD) as well as to Minimum Quadratic Cost Deviation (MQCD) control. An exemplary treatment of a generic scalar nonlinear system subject to quadratic costs is performed for MQCD control to demonstrate the elementary expandability of the new control paradigm. This work concludes with a numerical evaluation of both MPD and CCMPD control for three exemplary benchmark problems. Numerical issues associated with the simulation of SDEs are briefly discussed and illustrated. The numerical examples furnish proof of the successful design. This study is complemented by a thorough review of statistical control methods, stochastic processes, Large Deviations techniques and the Freidlin-Wentzell theory, providing a comprehensive, self-contained account. The presentation of the mathematical tools and concepts is of a unique character, specifically addressing an engineering audience.

  19. Rationalizing virtual reality based on manufacturing paradigms

    NARCIS (Netherlands)

    Damgrave, Roy Gerhardus Johannes; Lutters, Diederick; Drukker, J. W.

    2014-01-01

    Comparing the evolvement of the manufacturing industry of the last century to the way virtual reality is used nowadays some remarkable similarities come to light. Current virtual reality equipment requires a high level of craftsmanship to achieve the maximum results, and often equipment is specially

  20. Truck shipment risks for assessing hazardous materials - a new paradigm incorporating safety and security

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, A.; McSweeney, T.; Allen, J.; Lepofsky, M. [Battelle Memorial Inst., Columbus, OH (United States); Abkowitz, M. [Dept. of Civil Engineering, Vanderbilt Univ., Nashville, TN (United States)

    2004-07-01

    Recent terrorist events, most notably September 11, 2001, have taught us that transportation risk management must be performed with a different lens to accommodate terrorism scenarios that would have previously been considered unlikely to warrant serious attention. Given these circumstances, a new paradigm is needed for managing the risks associated with highway transport of hazardous materials. In particular, this paradigm must: 1) more explicitly consider security threat and vulnerability, and 2) integrate security considerations into an overall framework for addressing natural and man-made disasters, be they accidental or planned. This paper summarizes the results of a study sponsored by the U.S. Department of Transportation, Federal Motor Carrier Safety Administration for the purpose of exploring how a paradigm might evolve in which both safety and security risks can be evaluated as a systematic, integrated process. The work was directed at developing a methodology for assessing the impacts of hazardous materials safety and security incident consequences when transported by highway. This included consideration of the manner in which these materials could be involved in initiating events as well as potential outcomes under a variety of release conditions. The methodology is subsequently applied to various classes of hazardous materials to establish an economic profile of the impacts that might be expected if a major release were to occur. The paper concludes with a discussion of the findings and implications associated with this effort.

  1. Truck shipment risks for assessing hazardous materials - a new paradigm incorporating safety and security

    International Nuclear Information System (INIS)

    Greenberg, A.; McSweeney, T.; Allen, J.; Lepofsky, M.; Abkowitz, M.

    2004-01-01

    Recent terrorist events, most notably September 11, 2001, have taught us that transportation risk management must be performed with a different lens to accommodate terrorism scenarios that would have previously been considered unlikely to warrant serious attention. Given these circumstances, a new paradigm is needed for managing the risks associated with highway transport of hazardous materials. In particular, this paradigm must: 1) more explicitly consider security threat and vulnerability, and 2) integrate security considerations into an overall framework for addressing natural and man-made disasters, be they accidental or planned. This paper summarizes the results of a study sponsored by the U.S. Department of Transportation, Federal Motor Carrier Safety Administration for the purpose of exploring how a paradigm might evolve in which both safety and security risks can be evaluated as a systematic, integrated process. The work was directed at developing a methodology for assessing the impacts of hazardous materials safety and security incident consequences when transported by highway. This included consideration of the manner in which these materials could be involved in initiating events as well as potential outcomes under a variety of release conditions. The methodology is subsequently applied to various classes of hazardous materials to establish an economic profile of the impacts that might be expected if a major release were to occur. The paper concludes with a discussion of the findings and implications associated with this effort

  2. The genotype-phenotype map of an evolving digital organism.

    Directory of Open Access Journals (Sweden)

    Miguel A Fortuna

    2017-02-01

    Full Text Available To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences, which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

  3. The genotype-phenotype map of an evolving digital organism.

    Science.gov (United States)

    Fortuna, Miguel A; Zaman, Luis; Ofria, Charles; Wagner, Andreas

    2017-02-01

    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

  4. An Evolving Asymmetric Game for Modeling Interdictor-Smuggler Problems

    Science.gov (United States)

    2016-06-01

    ASYMMETRIC GAME FOR MODELING INTERDICTOR-SMUGGLER PROBLEMS by Richard J. Allain June 2016 Thesis Advisor: David L. Alderson Second Reader: W...DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE AN EVOLVING ASYMMETRIC GAME FOR MODELING INTERDICTOR- SMUGGLER PROBLEMS 5. FUNDING NUMBERS 6...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited AN EVOLVING

  5. Adaptation of Escherichia coli to glucose promotes evolvability in lactose.

    Science.gov (United States)

    Phillips, Kelly N; Castillo, Gerardo; Wünsche, Andrea; Cooper, Tim F

    2016-02-01

    The selective history of a population can influence its subsequent evolution, an effect known as historical contingency. We previously observed that five of six replicate populations that were evolved in a glucose-limited environment for 2000 generations, then switched to lactose for 1000 generations, had higher fitness increases in lactose than populations started directly from the ancestor. To test if selection in glucose systematically increased lactose evolvability, we started 12 replay populations--six from a population subsample and six from a single randomly selected clone--from each of the six glucose-evolved founder populations. These replay populations and 18 ancestral populations were evolved for 1000 generations in a lactose-limited environment. We found that replay populations were initially slightly less fit in lactose than the ancestor, but were more evolvable, in that they increased in fitness at a faster rate and to higher levels. This result indicates that evolution in the glucose environment resulted in genetic changes that increased the potential of genotypes to adapt to lactose. Genome sequencing identified four genes--iclR, nadR, spoT, and rbs--that were mutated in most glucose-evolved clones and are candidates for mediating increased evolvability. Our results demonstrate that short-term selective costs during selection in one environment can lead to changes in evolvability that confer longer term benefits. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  6. PCBA demand forecasting using an evolving Takagi-Sugeno system

    NARCIS (Netherlands)

    van Rooijen, M.; Almeida, R.J.; Kaymak, U.

    2016-01-01

    This paper investigates the use of using an evolving fuzzy system for printed circuit board (PCBA) demand forecasting. The algorithm is based on the evolving Takagi-Sugeno (eTS) fuzzy system, which has the ability to incorporate new patterns by changing its internal structure in an on-line fashion.

  7. Laplacian Estrada and normalized Laplacian Estrada indices of evolving graphs.

    Directory of Open Access Journals (Sweden)

    Yilun Shang

    Full Text Available Large-scale time-evolving networks have been generated by many natural and technological applications, posing challenges for computation and modeling. Thus, it is of theoretical and practical significance to probe mathematical tools tailored for evolving networks. In this paper, on top of the dynamic Estrada index, we study the dynamic Laplacian Estrada index and the dynamic normalized Laplacian Estrada index of evolving graphs. Using linear algebra techniques, we established general upper and lower bounds for these graph-spectrum-based invariants through a couple of intuitive graph-theoretic measures, including the number of vertices or edges. Synthetic random evolving small-world networks are employed to show the relevance of the proposed dynamic Estrada indices. It is found that neither the static snapshot graphs nor the aggregated graph can approximate the evolving graph itself, indicating the fundamental difference between the static and dynamic Estrada indices.

  8. Laplacian Estrada and normalized Laplacian Estrada indices of evolving graphs.

    Science.gov (United States)

    Shang, Yilun

    2015-01-01

    Large-scale time-evolving networks have been generated by many natural and technological applications, posing challenges for computation and modeling. Thus, it is of theoretical and practical significance to probe mathematical tools tailored for evolving networks. In this paper, on top of the dynamic Estrada index, we study the dynamic Laplacian Estrada index and the dynamic normalized Laplacian Estrada index of evolving graphs. Using linear algebra techniques, we established general upper and lower bounds for these graph-spectrum-based invariants through a couple of intuitive graph-theoretic measures, including the number of vertices or edges. Synthetic random evolving small-world networks are employed to show the relevance of the proposed dynamic Estrada indices. It is found that neither the static snapshot graphs nor the aggregated graph can approximate the evolving graph itself, indicating the fundamental difference between the static and dynamic Estrada indices.

  9. Animal to human translational paradigms relevant for approach avoidance conflict decision making.

    Science.gov (United States)

    Kirlic, Namik; Young, Jared; Aupperle, Robin L

    2017-09-01

    Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Paradigm Shift in Language Teaching and Language Teacher Education

    Directory of Open Access Journals (Sweden)

    Elaine Ferreira do Vale Borges

    2014-11-01

    Full Text Available In this article, I intend to conduct a short literature review and discussion about paradigm shift in language teaching and language teacher education from Cartesian to the complexity paradigm. For that, I use the Kuhnian notion of scientific revolution to present a short compilation of works related to paradigm shift in different sciences, including psychology, linguistics and, more emphatically, applied linguistics. The main proposal is to show the evolutions of paradigm shift in language and social sciences and its impact on the emergence of the complexity paradigm in language teaching and language teacher education fields.

  11. Revisiting Robustness and Evolvability: Evolution in Weighted Genotype Spaces

    Science.gov (United States)

    Partha, Raghavendran; Raman, Karthik

    2014-01-01

    Robustness and evolvability are highly intertwined properties of biological systems. The relationship between these properties determines how biological systems are able to withstand mutations and show variation in response to them. Computational studies have explored the relationship between these two properties using neutral networks of RNA sequences (genotype) and their secondary structures (phenotype) as a model system. However, these studies have assumed every mutation to a sequence to be equally likely; the differences in the likelihood of the occurrence of various mutations, and the consequence of probabilistic nature of the mutations in such a system have previously been ignored. Associating probabilities to mutations essentially results in the weighting of genotype space. We here perform a comparative analysis of weighted and unweighted neutral networks of RNA sequences, and subsequently explore the relationship between robustness and evolvability. We show that assuming an equal likelihood for all mutations (as in an unweighted network), underestimates robustness and overestimates evolvability of a system. In spite of discarding this assumption, we observe that a negative correlation between sequence (genotype) robustness and sequence evolvability persists, and also that structure (phenotype) robustness promotes structure evolvability, as observed in earlier studies using unweighted networks. We also study the effects of base composition bias on robustness and evolvability. Particularly, we explore the association between robustness and evolvability in a sequence space that is AU-rich – sequences with an AU content of 80% or higher, compared to a normal (unbiased) sequence space. We find that evolvability of both sequences and structures in an AU-rich space is lesser compared to the normal space, and robustness higher. We also observe that AU-rich populations evolving on neutral networks of phenotypes, can access less phenotypic variation compared to

  12. Psychiatric disorders revealing multiple sclerosis after 20 years of evolvement

    Directory of Open Access Journals (Sweden)

    Aicha Slassi Sennou

    2014-01-01

    Full Text Available Previous research indicates that the onset of psychiatric disorders is sometimes associated with multiple sclerosis (MS evolving several years later. However, information on why this might occur, and on the outcomes of such patients, is still lacking. We aim to discuss these limitations with the current paper. We describe a 51-year-old female who demonstrated severe anxiety disorder and depression years before developing MS neurological symptoms. The patient was treated for these psychiatric disorders over 20 years. In the last 3 years of her treatment, the patient demonstrated a choreic-type of movement disorder in all her limbs. This disorder is consistent with relapsing-remitting MS. Clinical and magnetic resonance imaging (MRI examinations demonstrated aspects of MS, without MS being diagnosed conclusively. The visual evoked potential indicated a diagnosis of conduction abnormalities. The established diagnosis was slow relapsing MS. The patient underwent methylprednisolone bolus (1 g/day. This case-study suggests that health professionals should conduct a full neurological assessment when they find atypical psychiatric symptoms in a patient. This would make sure that patients receive a better standard of care, and thus experience a better quality of life.

  13. Evolving Spiking Neural Networks for Recognition of Aged Voices.

    Science.gov (United States)

    Silva, Marco; Vellasco, Marley M B R; Cataldo, Edson

    2017-01-01

    The aging of the voice, known as presbyphonia, is a natural process that can cause great change in vocal quality of the individual. This is a relevant problem to those people who use their voices professionally, and its early identification can help determine a suitable treatment to avoid its progress or even to eliminate the problem. This work focuses on the development of a new model for the identification of aging voices (independently of their chronological age), using as input attributes parameters extracted from the voice and glottal signals. The proposed model, named Quantum binary-real evolving Spiking Neural Network (QbrSNN), is based on spiking neural networks (SNNs), with an unsupervised training algorithm, and a Quantum-Inspired Evolutionary Algorithm that automatically determines the most relevant attributes and the optimal parameters that configure the SNN. The QbrSNN model was evaluated in a database composed of 120 records, containing samples from three groups of speakers. The results obtained indicate that the proposed model provides better accuracy than other approaches, with fewer input attributes. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  14. Intracellular metabolite profiling of Saccharomyces cerevisiae evolved under furfural.

    Science.gov (United States)

    Jung, Young Hoon; Kim, Sooah; Yang, Jungwoo; Seo, Jin-Ho; Kim, Kyoung Heon

    2017-03-01

    Furfural, one of the most common inhibitors in pre-treatment hydrolysates, reduces the cell growth and ethanol production of yeast. Evolutionary engineering has been used as a selection scheme to obtain yeast strains that exhibit furfural tolerance. However, the response of Saccharomyces cerevisiae to furfural at the metabolite level during evolution remains unknown. In this study, evolutionary engineering and metabolomic analyses were applied to determine the effects of furfural on yeasts and their metabolic response to continuous exposure to furfural. After 50 serial transfers of cultures in the presence of furfural, the evolved strains acquired the ability to stably manage its physiological status under the furfural stress. A total of 98 metabolites were identified, and their abundance profiles implied that yeast metabolism was globally regulated. Under the furfural stress, stress-protective molecules and cofactor-related mechanisms were mainly induced in the parental strain. However, during evolution under the furfural stress, S. cerevisiae underwent global metabolic allocations to quickly overcome the stress, particularly by maintaining higher levels of metabolites related to energy generation, cofactor regeneration and recovery from cellular damage. Mapping the mechanisms of furfural tolerance conferred by evolutionary engineering in the present study will be led to rational design of metabolically engineered yeasts. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  15. Treatment

    Directory of Open Access Journals (Sweden)

    Safaa M. Raghab

    2013-08-01

    The main goal of this study is to utilize a natural low cost material “as an accelerator additive to enhance the chemical treatment process using Alum coagulant and the accelerator substances were Perlite and Bentonite. The performance of the chemical treatment was enhanced using the accelerator substances with 90 mg/l Alum as a constant dose. Perlite gave better performance than the Bentonite effluent. The removal ratio for conductivity, turbidity, BOD and COD for Perlite was 86.7%, 87.4%, 89.9% and 92.8% respectively, and for Bentonite was 83.5%, 85.0%, 86.5% and 85.0% respectively at the same concentration of 40 mg/l for each.

  16. The implications of the new paradigm of dental caries.

    Science.gov (United States)

    Kidd, Edwina

    2011-12-01

    The caries process is the ubiquitous, natural metabolism in the biofilm that causes numerous fluctuations in pH. The interaction of this biofilm with the dental tissues may result in a caries lesion. However, lesion formation and progression can be controlled, particularly by disturbing plaque regularly with a fluoride containing toothpaste. This paradigm implies that everyone with teeth is at risk to lesion development. Treatment of caries is principally non-operative, involving plaque control, fluoride and a sensible diet. Operative dentistry repairs un-cleansable cavities and is part of plaque control. A diagnosis is a mental resting place on the way to a treatment decision. The relevant diagnostic features with respect to caries are lesion activity (active lesions require active management) and un-cleansable cavities. When teaching undergraduates, it is important that they are credited for the non-operative treatment of caries as well as for operative dentistry. This is equally important in dental practice where an appropriate skills mix of the dental team is required to deliver dental health cost-effectively. Training more dentists may be an expensive mistake as far as disease control is concerned. It is ironic that dentists make most money from operative care and specialist treatment when disease control could be delivered relatively cheaply. The key to dental health is regular and effective plaque control with a fluoride containing toothpaste, from cradle to grave. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. SCHOOL ECONOMY IN THE INVENTING EDUCATION PARADIGM

    Directory of Open Access Journals (Sweden)

    Anatoliy Alexandrovich Lepeshev

    2018-01-01

    Full Text Available Requirements applied to specialists for working in the sixth wave of innovation, i.e. Industry 4.0, determines the necessity of education system improvement concerning training solution and, as a result, creation of inventive ideas. Today in our country this process is stimulated by various competitions, including financing for the implementation of results. In training programs knowledge approach still prevails. The corresponding methods, along with stimulation, are included into educational programs in leading foreign educational institutions, mostly at universities. If in previous decades mostly divergent methods were studied (morphological analysis, the focal objects method, synectics, etc., then now the leading place is taken by theory of inventive problem solving – TRIZ created in the former USSR by G.S. Altshuller in connection with the increasing leading corporations requirement for specialists in TRIZ. This fact gives Russia essential competitive advantages in the innovative way of development. For effective use of this advantage it is important to form the TRIZ-based innovative thinking beginning from school days. For this purpose authors developed new methods in TRIZ-pedagogics, uniting metasubject results (in higher education institutions – competences into the system of innovative thinking. As a result, both educational and economic effects are achieved: the intellectual property created in educational process. For schools it is the possibility of significant improvement of financing causing importance of new mechanisms of intellectual property fixation, protection and implementation. Recommendations about creation of such system are provided in the article. Purpose Defining the opportunities and ways of improving economic effectiveness of educational activities in the paradigm of inventive education. Tasks: – analysis of school education institutions experience in implementation of approaches preceding the inventing education

  18. Urgency of changing paradigms in radiation hygiene

    International Nuclear Information System (INIS)

    Kudritskij, Yu.K.; Karpov, V.I.; Georgievskij, A.B.

    1991-01-01

    A problem has been raised on the necessity to substitute the linear-nonthreshold hypothesis as a paradigm of radiation hygiene for the hypothesis of the biological effectiveness of ionizing irradiations. A comparison of the methodological substantiation for both hypotheses and a conception of 'acceptable risk' has been carried out. It is suggested that the possibility of theoretical substantiation of safety standards for the radiational factor on the basis of adatational hypothesis be acknowledged instead of the linear - nonthreshold conception which has lost its historic significance

  19. Causal hydrodynamics and the membrane paradigm

    International Nuclear Information System (INIS)

    Natsuume, Makoto

    2008-01-01

    We obtain the relaxation time for the shear viscous stress for various geometries using the 'membrane paradigm' formula proposed recently. We consider the generic Schwarzschild-anti-de Sitter black holes (SAdS), the generic Dp-brane, the Klebanov-Tseytlin (KT) geometry, and the N=2* theory. The formula is the 'shear mode' result and is not fully trustable, but it may be helpful to learn some generic behaviors about the relaxation time. For example, a simple formula summarizes all known results for SAdS, and a single expression summarizes the results for the Dp-brane and the KT geometry.

  20. In search of a new paradigm

    DEFF Research Database (Denmark)

    Poulsen, Lars K.

    2005-01-01

    In this review of research priorities, presented for the European Commission, food allergy is established as a disease with a considerable impact on modern society. Research paradigms have changed from establishing basic symptomatology and diagnostic methods over allergen characterization to a risk...... mechanisms in the cross-field between immunology and gastroenterology. Research priorities should include the molecular basis of cross-reactivity, the digestion and maintenance of antigenicity, the genetics of food allergy, and the immune response to food antigens and effects on the gastrointestinal immune...

  1. Three paradigms for the analysis of corruption

    Directory of Open Access Journals (Sweden)

    Alberto Vannucci

    2015-10-01

    Full Text Available In the last decades a growing awareness emerged of the relevance of corruption as an hidden factor which may negatively affect political and economic decision-making processes. In spite of a lively scientific debate there is no general consensus on a commonly accepted definition of what corruption is.The A. distinguishes three main paradigms, focusing on different (though not irreconcilable variables.The first is the economic paradigm, which usually takes the principal-agent model of corruption as its founding pillar. In this paradigm corruption is considered the outcome of rational individual choices, and its spread within a certain organization is influenced by the factors defining the structure of expected costs and rewards.A second approach – the cultural paradigm – looks at the differences in cultural traditions, social norms and interiorized values which shape individuals’ moral preferences and consideration of his social and institutional role. These are a leading forces that can push a corrupt public or private agent (not to violate legal norms.A third neo-institutional approach considers also mechanisms which allow the internal regulation of social interactions within corrupt networks, and their effects on individuals’ beliefs and preferences. Though the corrupt agreements cannot be enforced with legal sanctions, several informal, non-written rules, contractual provisos and conventions may regulate the corrupt exchange between agent and corruptor.The A. underlines that corruption is the outcome of a multitude of individual and collective choices which change public opinion towards corruption and its diffusion throughout the state, markets and civil society. There is no univocal recipe to deal with anti-bribery measures, since corruption is a complex and multifaceted phenomenon.Reforms aimed at dismantling systemic corruption have to be finely tuned against its hidden governance structures, i.e. its internal regulation of

  2. Chua's circuit a paradigm for chaos

    CERN Document Server

    1993-01-01

    For uninitiated researchers, engineers, and scientists interested in a quick entry into the subject of chaos, this book offers a timely collection of 55 carefully selected papers covering almost every aspect of this subject. Because Chua's circuit is endowed with virtually every bifurcation phenomena reported in the extensive literature on chaos, and because it is the only chaotic system which can be easily built by a novice, simulated in a personal computer, and tractable mathematically, it has become a paradigm for chaos, and a vehicle for illustrating this ubiquitous phenomenon. Its supreme

  3. Behavioral fluency: Evolution of a new paradigm

    OpenAIRE

    Binder, Carl

    1996-01-01

    Behavioral fluency is that combination of accuracy plus speed of responding that enables competent individuals to function efficiently and effectively in their natural environments. Evolving from the methodology of free-operant conditioning, the practice of precision teaching set the stage for discoveries about relations between behavior frequency and specific outcomes, notably retention and maintenance of performance, endurance or resistance to distraction, and application or transfer of tra...

  4. A changed name with an evolving function.

    Science.gov (United States)

    Xie, Z

    1995-12-01

    Changes in family planning, which took place in 1994, are described for the Mianzhu County Family Planning Committee and other townships in Sichuan Province. The Committee changed its name to Population Committee. The administrative structure changed at the town and township level. The Secretary of the Chinese Communist Party assigned the former Director of the township Family Planning Office to serve as Director of the General Office of township Population Committee. This administrative change did not take place in the county office. Reforms at the county level were expected to be more gradual, since there was no other model elsewhere in China to follow. The name change reflected a change in function and not a decline in family planning. The function will include implementation, management, and coordination instead of just fertility control. The Committee joined with the Women's Federation in offering premarital education to young people and in establishing a kindergarten for 3-5 year old children. In Qifu there were 18 township businesses, which hired surplus labor. In Qifu preferential treatment in hiring was given to single-child and two-daughter families. Wage labor has resulted in higher income and less time in the fields. The average Qifu township income in 1994 was 1250 yuan. 3200 of the 6100 single-child households were given elderly insurance by the Population Committee. In Dongbei town 4173 households had single children (56.4% of total households). In 1994 average household yearly income was 1400 yuan. 3350 households (80.2% of total single-child households) had an average yearly income of 1500-3000 yuan. 307 households (7.5%) had a yearly income of 3000-5000 yuan. 100 households (2.5%) had income greater than 5000 yuan.

  5. Diabetes benefit management: evolving strategies for payers.

    Science.gov (United States)

    Tzeel, Albert L

    2011-11-01

    Over the next quarter century, the burden of type 2 diabetes mellitus (T2DM) is expected to at least double. Currently, 1 in every 10 healthcare dollars is spent on diabetes management; by 2050, it has been projected that the annual costs of managing T2DM will rise to $336 billion. Without substantial, systemic changes, T2DM management costs will lead to a potentially untenable strain on the healthcare system. However, the appropriate management of diabetes can reduce associated mortality and delay comorbidities. In addition, adequate glycemic control can improve patient outcomes and significantly reduce diabetes-related complications. This article provides an overview of key concepts associated with a value-based insurance design (VBID) approach to T2DM coverage. By promoting the use of services or treatments that provide high benefits relative to cost, and by alternatively discouraging patients from utilizing services whose benefits do not justify their cost, VBID improves the quality of healthcare while simultaneously reining in spending. VBID initiatives tend to focus on chronic disease management and generally target prescription drug use. However, some programs have expanded their scope by incorporating services traditionally offered by wellness and disease management programs. The concept of VBID is growing, and it is increasingly being implemented by a diverse and growing number of public and private entities, including pharmacy benefit managers, health plans, and employers. This article provides key background on VBID strategies, with a focus on T2DM management. It also provides a road map for health plans seeking to implement VBID as part of their programs.

  6. Liver Transplantation: Evolving Patient Selection Criteria

    Directory of Open Access Journals (Sweden)

    Andy S Yu

    2001-01-01

    Full Text Available The widespread recognition of the success of liver transplantation as a treatment for most types of acute and chronic liver failure has led to increased referrals for transplantation in the setting of a relatively fixed supply of cadaver donor organs. These events have led to a marked lengthening of the waiting time for liver transplantation, resulting in increased deaths of those on the waiting list and sicker patients undergoing transplantation. Nearly 5000 liver transplantations were performed in the United States in 2000, while the waiting list grew to over 17,000 patients. The mounting disparity between the number of liver transplant candidates and the limited supply of donor organs has led to reassessment of the selection and listing criteria for liver transplantation, as well as revision of organ allocation and distribution policies for cadaver livers. The development of minimal listing criteria for patients with chronic liver disease based on a specific definition for decompensation of cirrhosis has facilitated the more uniform listing of patients at individual centres across the United States. The United Network for Organ Sharing, under pressure from transplant professionals, patient advocacy groups and the federal government, has continuously revised allocation and distribution policies based on the ethical principles of justice for the individual patient versus optimal utility of the limited organ supply available annually. Beginning in 2002, it is likely that the Model for End-stage Liver Disease (MELD score will be implemented to determine disease severity and direct donor organs to the sickest patients rather than to those with the longest waiting times.

  7. Changing the paradigm: the potential for targeted therapy in laryngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Ludwig, Megan L.; Birkeland, Andrew C.; Hoesli, Rebecca; Swiecicki, Paul; Spector, Matthew E.; Brenner, J. Chad

    2016-01-01

    Laryngeal squamous cell carcinoma (LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21 st century

  8. RENEGOTIATION MINING CONTRACT: LEGAL PARADIGM RECONSTRUCTION EFFORTS

    Directory of Open Access Journals (Sweden)

    Marilang -

    2014-07-01

    Full Text Available Renegotiation contract mining is not a priori notion that was born but is driven by the fact that empirical Work Contract (KK and coal mining concessions of the Works Agreement (Cca that are valid for this resulted in profits which are not comparable between countries with investors (domestic and foreign. In addition, Law No. 4 of 2009 about Mineral and Coal Mining (minerba through article 169 have been injected that though the mining contracts during the validity of this, still respected until the end, however, if the implementation of these contracts give rise to distortions for the national interest, then the Government must encourage the investors to do Renegotiation against existing contracts to comply with legislation minerba forever within a period of one year since the enactment of the legislation this minerba. Renegotiation mining contracts that have been approved on the fact of the matter is simply an attempt to reconstruct the ruling paradigm, so with that paradigm shift, both parties can reach the intersection for the benefit of both parties, i.e. the parties proportionately Indonesia suffered no losses on the one hand, and the benefit of the domestic and foreign investors remain in reasonable limits on the other. 

  9. Consumers’ Empowerement for a New Marketing Paradigm

    Directory of Open Access Journals (Sweden)

    Victor Danciu

    2013-09-01

    Full Text Available The marketing practices of the companies show that not all of them are observing ethical and moral standards and they manipulate the consumers. This paper has as main goal to examine the most usual unethical techniques, the present status of consumers’ power and how more power could work for a new marketing paradigm. There are many unethical marketing techniques which could be found in deceptive product recipes, packaging, promotion, prices and in other areas. Most consumers have no appropriate powers and tools to counteract the manipulation techniques and feel they have fewer rights than the marketers. The current state of empowerment of the consumer show that the European consumers are not in the best position in the market as the Consumer Empowerment Index proves. This matter of facts emphasizes a strong need for a better empowerment of the consumers. The consumer which has more power and wisely use it could improve the balance of power in the market. But the consumers should have a proactive buying behavior in order to get such results. These revolutionary consumers attack the structural roots of the social, economic and political problems which produces a new market ideology as a part of the new tier of transnational institutional ideology. This consumer behavior may have a strong influence toward a new marketing paradigm.

  10. Osteoporosis: Modern Paradigms for Last Century's Bones.

    Science.gov (United States)

    Kruger, Marlena C; Wolber, Frances M

    2016-06-17

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

  11. Imaging deductive reasoning and the new paradigm

    Science.gov (United States)

    Oaksford, Mike

    2015-01-01

    There has been a great expansion of research into human reasoning at all of Marr’s explanatory levels. There is a tendency for this work to progress within a level largely ignoring the others which can lead to slippage between levels (Chater et al., 2003). It is argued that recent brain imaging research on deductive reasoning—implementational level—has largely ignored the new paradigm in reasoning—computational level (Over, 2009). Consequently, recent imaging results are reviewed with the focus on how they relate to the new paradigm. The imaging results are drawn primarily from a recent meta-analysis by Prado et al. (2011) but further imaging results are also reviewed where relevant. Three main observations are made. First, the main function of the core brain region identified is most likely elaborative, defeasible reasoning not deductive reasoning. Second, the subtraction methodology and the meta-analytic approach may remove all traces of content specific System 1 processes thought to underpin much human reasoning. Third, interpreting the function of the brain regions activated by a task depends on theories of the function that a task engages. When there are multiple interpretations of that function, interpreting what an active brain region is doing is not clear cut. It is concluded that there is a need to more tightly connect brain activation to function, which could be achieved using formalized computational level models and a parametric variation approach. PMID:25774130

  12. The Institutional Paradigm of Human Capital Development

    Directory of Open Access Journals (Sweden)

    Kolomiiets Viktoriia М.

    2018-03-01

    Full Text Available The formation of the modern conception of human capital is connected with the development of post-industrial information society, knowledge economy and digital economy. The main role in analyzing of the content and role of human capital can play a new institutional economic theory. It is determined that the methodology of research of paradigm change in economic science remains the subject of discussion. The conception of institutional paradigm of human capital development can be attributed to the new economy, the development of which is carried out on the condition that the employee is not always alienated from the relationships of ownership: he himself becomes the owner of the «new» economic resources. The factors of education along with the factors of health care which are determining in the development of human capital are researched. Special attention is paid to education, as it acts as an intellectual capital of the new economy, where knowledge and skills become the «intellectual 5D printer», producing the modern human capital. The transition to a new, post-industrial economy is characterized by a major long-term tendency: the progress of knowledge and the increasing complexity of the socio-economic life; created by powerful factors of information and computer technologies and leading to expansion of global economic space.

  13. Passage of American shad: paradigms and realities

    Science.gov (United States)

    Haro, Alex; Castro-Santos, Theodore

    2012-01-01

    Despite more than 250 years of development, the passage of American shad Alosa sapidissima at dams and other barriers frequently remains problematic. Few improvements in design based on knowledge of the swimming, schooling, and migratory behaviors of American shad have been incorporated into passage structures. Large-scale technical fishways designed for the passage of adult salmonids on the Columbia River have been presumed to have good performance for American shad but have never been rigorously evaluated for this species. Similar but smaller fishway designs on the East Coast frequently have poor performance. Provision of effective downstream passage for both juvenile and postspawning adult American shad has been given little consideration in most passage projects. Ways to attract and guide American shad to both fishway entrances and downstream bypasses remain marginally understood. The historical development of passage structures for American shad has resulted in assumptions and paradigms about American shad behavior and passage that are frequently unsubstantiated by supporting data or appropriate experimentation. We propose that many of these assumptions and paradigms are either unfounded or invalid and that significant improvements to American shad upstream and downstream passage can be made via a sequential program of behavioral experimentation, application of experimental results to the physical and hydraulic design of new structures, and controlled tests of large-scale prototype structures in the laboratory and field.

  14. New paradigms of Game Theory from globalization

    Directory of Open Access Journals (Sweden)

    Francisco Javier Esquivel

    2015-06-01

    Full Text Available Games Theory constitutes a model by means every player tries to predict what they will make the other players in reply to his own actions, and to optimize the result of the above mentioned actions in his benefit knowing that the others are thinking to about the same form. The development of the theory supposed a boom after the World War II, which happened of analyzing exclusively competitive behaviors to considering situations with competitive and cooperative characteristics. Nevertheless, the advance of the humanity and the disappearance of both geopolitical blocks have eliminated the balance of power and have produced the emergence of a world the most based on the exclusive conquest of the power. This has originated the model change and dilemmas, happening from the most cooperative models (Prisoner’s Dilemma or from the models of the Cold War (Dilemma of the Gallina up to reaching the dilemmas of the Leader or of the Hero. This change of paradigm owes to the extension of the globalization, which originates an immeasurable loss of economic, social, political power, of human rights, which they have affected negatively to the poor people. In this paper is studied the change of paradigm caused by the consequences of the globalization and the geopolitical transformations in a monopolar world, analyzing the consequences on the basis of the Theory of Games.

  15. Tolerance of sexual harassment: a laboratory paradigm.

    Science.gov (United States)

    Angelone, David J; Mitchell, Damon; Carola, Kara

    2009-12-01

    The present study attempted to develop a laboratory analogue for the study of tolerance for sexual harassment by using an online speed-dating paradigm. In that context, the relation between participants' sexual harassment attitudes, perpetrator attractiveness, perpetrator status, and perceived dating potential of the perpetrator were examined as factors influencing participants' tolerance of sexually harassing behavior. Participants were 128 female college students from a small northeastern public university. Results indicated that attractiveness, high social status, and attitudinal beliefs about sexual harassment were all predictive of tolerance for sexual harassment, providing preliminary support for the validity of this paradigm. In addition, participants' self reported likelihood to date a bogus male dating candidate was also predictive of tolerance for sexual harassment, over and above the aforementioned variables, suggesting that dating potential can play a role in perceptions of sexual harassment. Further, this experiment demonstrated that perceptions of sexual harassment can be assessed using the in vivo measurement of behavior. In addition, using an online environment not only provides a contemporary spin and adds a greater degree of external validity compared to other sexual harassment analogues, it also reduces any risk of potential physical sexual contact for participants.

  16. Colloidal paradigm in supercapattery electrode systems

    Science.gov (United States)

    Chen, Kunfeng; Xue, Dongfeng

    2018-01-01

    Among decades of development, electrochemical energy storage systems are now sorely in need of a new design paradigm at the nano size and ion level to satisfy the higher energy and power demands. In this review paper, we introduce a new colloidal electrode paradigm for supercapattery that integrates multiple-scale forms of matter, i.e. ion clusters, colloidal ions, and nanosized materials, into one colloid system, coupled with multiple interactions, i.e. electrostatic, van der Waals forces, and chemical bonding, thus leading to the formation of many redox reactive centers. This colloidal electrode not only keeps the original ionic nature in colloidal materials, but also creates a new attribute of high electroactivity. Colloidal supercapattery is a perfect application example of the novel colloidal electrode, leading to higher specific capacitance than traditional electrode materials. The high electroactivity of the colloidal electrode mainly comes from the contribution of exposed reactive centers, owing to the confinement effect of carbon and a binder matrix. Systematic and thorough research on the colloidal system will significantly promote the development of fundamental science and the progress of advanced energy storage technology.

  17. A new guiding paradigm for waste disposal

    International Nuclear Information System (INIS)

    Suter, Peter

    2003-01-01

    New situations call for a revision of strategies in the waste recycling and recovery sector. The guiding paradigm is that the evaluation and optimization of strategies ought to be integral, i.e. it ought to incorporate all steps from cradle to grave, all cost components and also to take into account all environmental aspects, as well as resource depletion. Furthermore, all variants of a comparison must have the same output and the same boundaries in space and time. Total cost (comprising also environmental damage and resource depletion) is proposed here as the evaluation function; environmental damage can be made operational by the DALY concept (Hofstetter P. Perspectives in life cycle impact assessment. Boston: Kluwer Academic, 1998) ('disability adjusted loss of life years') accounting for the years of life lost due to premature death, to illness or annoyance. The search for optimal strategies in the waste sector evidently requires the solution of a system with an enormous number of parameters; the method of genetic algorithms may represent a suitable solution paradigm, leading to the result in a reasonable computing time

  18. Tourism development and the degrowth paradigm

    Directory of Open Access Journals (Sweden)

    Andriotis Konstantinos

    2014-01-01

    Full Text Available This paper aims to look at alternatives to the classic models of development by exploring the paradigm of degrowth in a tourism context. Degrowth touted as an alternative to mainstream paradigms of development, aims to ensure a high quality of life for people in a society where work, production and consumption are reduced. As a weapon to the problems accrued by capitalism, degrowth reorients the current unsustainable and inequitable path through the transition to a smaller economy with less production and consumption. By arguing that natural limits to growth of many destinations have already been surpassed and their carrying capacity levels have been reached, degrowth proposes the abandonment of growth which promotes nothing other than a quest for profits on part of the owners of capital and results in disastrous implications for the environment and the humanity. As a philosophical concept and movement, degrowth is revolutionary and anticapitalist directed to sustainable change which results from an interest in locality and place, small and medium-sized enterprises, employment generation and reduction in working hours, ecology and quality of life, decommodification of tourism activity, carbon reduction in transport, changed pattern of production and consumption, and high priority in the travel experience.

  19. Special Feature: Epistemological Paradigms in Evaluation: Implications for Practice. Section 3: "Paradigm Complementarity" Case Studies.

    Science.gov (United States)

    Kamis-Gould, Edna; And Others

    1991-01-01

    Three studies are presented, which illustrate situations in which researchers and funders agreed on the primacy of either the experimental or pragmatic paradigms but acknowledged a role for the other. The studies involved evaluations of mental health care, information systems, and a curriculum for behavioral and academic dysfunction. (SLD)

  20. Waste treatment

    International Nuclear Information System (INIS)

    Hutson, G.V.

    1996-01-01

    Numerous types of waste are produced by the nuclear industry ranging from high-level radioactive and heat-generating, HLW, to very low-level, LLW and usually very bulky wastes. These may be in solid, liquid or gaseous phases and require different treatments. Waste management practices have evolved within commercial and environmental constraints resulting in considerable reduction in discharges. (UK)

  1. Project Seahorse evolves into major marine protector | IDRC ...

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

    2012-10-29

    Oct 29, 2012 ... Project Seahorse evolves into major marine protector ... local people, have greatly improved the prospects of survival for threatened species. ... “We tackle issues on any political level or geographical scale, according to what ...

  2. Incremental Frequent Subgraph Mining on Large Evolving Graphs

    KAUST Repository

    Abdelhamid, Ehab; Canim, Mustafa; Sadoghi, Mohammad; Bhatta, Bishwaranjan; Chang, Yuan-Chi; Kalnis, Panos

    2017-01-01

    , such as social networks, utilize large evolving graphs. Mining these graphs using existing techniques is infeasible, due to the high computational cost. In this paper, we propose IncGM+, a fast incremental approach for continuous frequent subgraph mining problem

  3. Genetic Algorithms Evolve Optimized Transforms for Signal Processing Applications

    National Research Council Canada - National Science Library

    Moore, Frank; Babb, Brendan; Becke, Steven; Koyuk, Heather; Lamson, Earl, III; Wedge, Christopher

    2005-01-01

    .... The primary goal of the research described in this final report was to establish a methodology for using genetic algorithms to evolve coefficient sets describing inverse transforms and matched...

  4. Biofabrication : reappraising the definition of an evolving field

    NARCIS (Netherlands)

    Groll, Jürgen; Boland, Thomas; Blunk, Torsten; Burdick, Jason A; Cho, Dong-Woo; Dalton, Paul D; Derby, Brian; Forgacs, Gabor; Li, Qing; Mironov, Vladimir A; Moroni, Lorenzo; Nakamura, Makoto; Shu, Wenmiao; Takeuchi, Shoji; Vozzi, Giovanni; Woodfield, Tim B F; Xu, Tao; Yoo, James J; Malda, Jos|info:eu-repo/dai/nl/412461099

    2016-01-01

    Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in

  5. Biofabrication : Reappraising the definition of an evolving field

    NARCIS (Netherlands)

    Groll, Jürgen; Boland, Thomas; Blunk, Torsten; Burdick, Jason A.; Cho, Dong Woo; Dalton, Paul D.; Derby, Brian; Forgacs, Gabor; Li, Qing; Mironov, Vladimir A.; Moroni, Lorenzo; Nakamura, Makoto; Shu, Wenmiao; Takeuchi, Shoji; Vozzi, Giovanni; Woodfield, Tim B.F.; Xu, Tao; Yoo, James J.; Malda, Jos

    2016-01-01

    Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in

  6. Orthogonally Evolved AI to Improve Difficulty Adjustment in Video Games

    DEFF Research Database (Denmark)

    Hintze, Arend; Olson, Randal; Lehman, Joel Anthony

    2016-01-01

    Computer games are most engaging when their difficulty is well matched to the player's ability, thereby providing an experience in which the player is neither overwhelmed nor bored. In games where the player interacts with computer-controlled opponents, the difficulty of the game can be adjusted...... not only by changing the distribution of opponents or game resources, but also through modifying the skill of the opponents. Applying evolutionary algorithms to evolve the artificial intelligence that controls opponent agents is one established method for adjusting opponent difficulty. Less-evolved agents...... (i.e. agents subject to fewer generations of evolution) make for easier opponents, while highly-evolved agents are more challenging to overcome. In this publication we test a new approach for difficulty adjustment in games: orthogonally evolved AI, where the player receives support from collaborating...

  7. Evolving the Evolving: Territory, Place and Rewilding in the California Delta

    Directory of Open Access Journals (Sweden)

    Brett Milligan

    2017-10-01

    Full Text Available Current planning and legislation in California’s Sacramento-San Joaquin Delta call for the large-scale ecological restoration of aquatic and terrestrial habitats. These ecological mandates have emerged in response to the region’s infrastructural transformation and the Delta’s predominant use as the central logistical hub in the state’s vast water conveyance network. Restoration is an attempt to recover what was externalized by the logic and abstractions of this logistical infrastructure. However, based on findings from our research, which examined how people are using restored and naturalized landscapes in the Delta and how these landscapes are currently planned for, we argue that as mitigatory response, restoration planning continues some of the same spatial abstractions and inequities by failing to account for the Delta as an urbanized, cultural and unique place. In interpreting how these conditions have come to be, we give attention to a pluralistic landscape approach and a coevolutionary reading of planning, policy, science and landscapes to discuss the conservation challenges presented by “Delta as an Evolving Place”. We suggest that for rewilding efforts to be successful in the Delta, a range of proactive, opportunistic, grounded and participatory tactics will be required to shift towards a more socio-ecological approach.

  8. Unifying the field: developing an integrative paradigm for behavior therapy.

    Science.gov (United States)

    Eifert, G H; Forsyth, J P; Schauss, S L

    1993-06-01

    The limitations of early conditioning models and treatments have led many behavior therapists to abandon conditioning principles and replace them with loosely defined cognitive theories and treatments. Systematic theory extensions to human behavior, using new concepts and processes derived from and built upon the basic principles, could have prevented the divisive debates over whether psychological dysfunctions are the results of conditioning or cognition and whether they should be treated with conditioning or cognitive techniques. Behavior therapy could also benefit from recent advances in experimental cognitive psychology that provide objective behavioral methods of studying dysfunctional processes. We suggest a unifying paradigm for explaining abnormal behavior that links and integrates different fields of study and processes that are frequently believed to be incompatible or antithetical such as biological vulnerability variables, learned behavioral repertoires, and that also links historical and current antecedents of the problem. An integrative paradigmatic behavioral approach may serve a unifying function in behavior therapy (a) by promoting an understanding of the dysfunctional processes involved in different disorders and (b) by helping clinicians conduct functional analyses that lead to theory-based, individualized, and effective treatments.

  9. Matrotrophy and placentation in invertebrates: a new paradigm.

    Science.gov (United States)

    Ostrovsky, Andrew N; Lidgard, Scott; Gordon, Dennis P; Schwaha, Thomas; Genikhovich, Grigory; Ereskovsky, Alexander V

    2016-08-01

    Matrotrophy, the continuous extra-vitelline supply of nutrients from the parent to the progeny during gestation, is one of the masterpieces of nature, contributing to offspring fitness and often correlated with evolutionary diversification. The most elaborate form of matrotrophy-placentotrophy-is well known for its broad occurrence among vertebrates, but the comparative distribution and structural diversity of matrotrophic expression among invertebrates is wanting. In the first comprehensive analysis of matrotrophy across the animal kingdom, we report that regardless of the degree of expression, it is established or inferred in at least 21 of 34 animal phyla, significantly exceeding previous accounts and changing the old paradigm that these phenomena are infrequent among invertebrates. In 10 phyla, matrotrophy is represented by only one or a few species, whereas in 11 it is either not uncommon or widespread and even pervasive. Among invertebrate phyla, Platyhelminthes, Arthropoda and Bryozoa dominate, with 162, 83 and 53 partly or wholly matrotrophic families, respectively. In comparison, Chordata has more than 220 families that include or consist entirely of matrotrophic species. We analysed the distribution of reproductive patterns among and within invertebrate phyla using recently published molecular phylogenies: matrotrophy has seemingly evolved at least 140 times in all major superclades: Parazoa and Eumetazoa, Radiata and Bilateria, Protostomia and Deuterostomia, Lophotrochozoa and Ecdysozoa. In Cycliophora and some Digenea, it may have evolved twice in the same life cycle. The provisioning of developing young is associated with almost all known types of incubation chambers, with matrotrophic viviparity more widespread (20 phyla) than brooding (10 phyla). In nine phyla, both matrotrophic incubation types are present. Matrotrophy is expressed in five nutritive modes, of which histotrophy and placentotrophy are most prevalent. Oophagy, embryophagy and

  10. (N+1)-dimensional Lorentzian evolving wormholes supported by polytropic matter

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Mauricio [Universidad del Bio-Bio, Departamento de Fisica, Facultad de Ciencias, Concepcion (Chile); Arostica, Fernanda; Bahamonde, Sebastian [Universidad de Concepcion, Departamento de Fisica, Concepcion (Chile)

    2013-08-15

    In this paper we study (N+1)-dimensional evolving wormholes supported by energy satisfying a polytropic equation of state. The considered evolving wormhole models are described by a constant redshift function and generalizes the standard flat Friedmann-Robertson-Walker spacetime. The polytropic equation of state allows us to consider in (3+1)-dimensions generalizations of the phantom energy and the generalized Chaplygin gas sources. (orig.)

  11. A new evolutionary system for evolving artificial neural networks.

    Science.gov (United States)

    Yao, X; Liu, Y

    1997-01-01

    This paper presents a new evolutionary system, i.e., EPNet, for evolving artificial neural networks (ANNs). The evolutionary algorithm used in EPNet is based on Fogel's evolutionary programming (EP). Unlike most previous studies on evolving ANN's, this paper puts its emphasis on evolving ANN's behaviors. Five mutation operators proposed in EPNet reflect such an emphasis on evolving behaviors. Close behavioral links between parents and their offspring are maintained by various mutations, such as partial training and node splitting. EPNet evolves ANN's architectures and connection weights (including biases) simultaneously in order to reduce the noise in fitness evaluation. The parsimony of evolved ANN's is encouraged by preferring node/connection deletion to addition. EPNet has been tested on a number of benchmark problems in machine learning and ANNs, such as the parity problem, the medical diagnosis problems, the Australian credit card assessment problem, and the Mackey-Glass time series prediction problem. The experimental results show that EPNet can produce very compact ANNs with good generalization ability in comparison with other algorithms.

  12. Quantitative analysis of distributed control paradigms of robot swarms

    DEFF Research Database (Denmark)

    Ngo, Trung Dung

    2010-01-01

    describe the physical and simulated robots, experiment scenario, and experiment setup. Third, we present our robot controllers based on behaviour based and neural network based paradigms. Fourth, we graphically show their experiment results and quantitatively analyse the results in comparison of the two......Given a task of designing controller for mobile robots in swarms, one might wonder which distributed control paradigms should be selected. Until now, paradigms of robot controllers have been within either behaviour based control or neural network based control, which have been recognized as two...... mainstreams of controller design for mobile robots. However, in swarm robotics, it is not clear how to determine control paradigms. In this paper we study the two control paradigms with various experiments of swarm aggregation. First, we introduce the two control paradigms for mobile robots. Second, we...

  13. Information processing as a paradigm for decision making.

    Science.gov (United States)

    Oppenheimer, Daniel M; Kelso, Evan

    2015-01-03

    For decades, the dominant paradigm for studying decision making--the expected utility framework--has been burdened by an increasing number of empirical findings that question its validity as a model of human cognition and behavior. However, as Kuhn (1962) argued in his seminal discussion of paradigm shifts, an old paradigm cannot be abandoned until a new paradigm emerges to replace it. In this article, we argue that the recent shift in researcher attention toward basic cognitive processes that give rise to decision phenomena constitutes the beginning of that replacement paradigm. Models grounded in basic perceptual, attentional, memory, and aggregation processes have begun to proliferate. The development of this new approach closely aligns with Kuhn's notion of paradigm shift, suggesting that this is a particularly generative and revolutionary time to be studying decision science.

  14. Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

    Directory of Open Access Journals (Sweden)

    Niczyporuk Aneta

    2016-12-01

    Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

  15. Evolving herbal formulations in management of dengue fever.

    Science.gov (United States)

    Singh, Pawan Kumar; Rawat, Pooja

    Dengue is endemic in more than 100 countries and it is estimated that annually above 390 million infections occur globally. During the period between 1996-2015, a massive increase of more than 500 per cent has been recorded in number of dengue cases reported in India. Till date, there are no specific globally accepted treatments for dengue fever in any system of medicine. Dengue does not cause very high mortality if properly handled and is currently being managed by clinicians through various adjuvant and alternative therapeutic options. Various plant based preparations have been used in different parts of India for combating dengue and are simultaneously also being scientifically validated by researchers. However, number of such scientific validation studies on phytomedicines are very less in India. Out of twenty-two plants reported against dengue, only four have been studied scientifically. Azadirachta indica, Carica papaya, Hippophae rhamnoides and Cissampelos pareira extracts were found effective and demonstrated improvement in clinical symptoms and direct inhibitory effect on dengue virus. C. papaya clinical trial showed increase in platelet count and faster recovery. These plants may be explored further as probable candidates for drug discovery against dengue. There is a need to search more such herbal formulations, which are being practiced at local level, document properly and validate them scientifically to confirm efficacy, mechanistic action and safety, before use. The herbal formulations being used by communities are the low hanging fruits which may provide alternative or adjuvant therapy if proper validation, value addition and product development steps are followed. This paper aims to review the recent status of dengue cases, deaths and evolving curative herbal solutions adapted and reported from India to combat the disease. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights

  16. Fluid flow and sediment transport in evolving sedimentary basins

    Science.gov (United States)

    Swenson, John Bradley

    This thesis consists of three studies that focus on groundwater flow and sediment transport in evolving sedimentary basins. The first study considers the subsurface hydrodynamic response to basin-scale transgression and regression and its implications for stratiform ore genesis. I demonstrate that the transgressive sequence focuses marginward-directed, compaction-driven discharge within a basal aquifer during progradation and deposition of the overlying regressive sequence, isolates the basal aquifer from overlying flow systems, and serves as a chemical sink for metal-bearing brines. In the second study, I develop a new theory for the shoreline response to subsidence, sediment supply, and sea level. In this theory, sediment transport in a fluvio-deltaic basin is formally equivalent to heat transfer in a two-phase (liquid and isothermal solid) system: the fluvial system is analogous to a conduction-dominated liquid phase, the shoreline is the melting front, and the water depth at the delta toe is equivalent to the latent heat of fusion. A natural consequence of this theory is that sediment-starved basins do not possess an equilibrium state. In contrast to existing theories, I do not observe either strong phase shifting or attenuation of the shoreline response to low-frequency eustatic forcing; rather, shoreline tracks sea level over a spectrum of forcing frequencies, and its response to low-frequency forcing is amplified relative to the high-frequency response. For the third study, I use a set of dimensionless numbers from the previous study as a mathematical framework for providing a unified treatment of existing stratigraphic theories. In the limit of low-amplitude eustatic forcing, my study suggests that strong phase shifting between shoreline and sea level is a consequence of specifying the sedimentation rate at the shoreline; basins free of this constraint do not develop strong phase shifts.

  17. Death: a foe to be conquered? Questioning the paradigm.

    Science.gov (United States)

    Gellie, Anthea; Mills, Amber; Levinson, Michele; Stephenson, Gemma; Flynn, Eleanor

    2015-01-01

    There are few certainties in life-death is one of them. Yet death is often thought of today as the 'loss of the battle' against illness, where in traditional societies it was the natural, meaningful, end to life. Medical knowledge and technologies have extended the possibilities of medical care and increased our life span. People living in most developed countries today can expect to survive to an advanced age and die in hospital rather than at home as in the past. Owing to these and other historical, cultural and social factors, our views on death have been skewed. Medical technology provides an arsenal of weapons to launch against death and the 'war against disease' has entrenched itself in medical philosophy. We now primarily experience death through the lens of a camera. Representations of 'death as spectacle' distort our perceptions and leave us ill-prepared for the reality. Additionally, death as a natural consequence of life has become much less visible than it was in the past due to our longer life expectancies and lack of infectious disease. The continued thrust for treatment, wedded with a failure to recognise the dying process, can rob individuals of a peaceful, dignified death. Progress being made in Advance Care Planning and palliative care is limited by the existing paradigm of death as a 'foe to be conquered'. It is time for a shift in this paradigm. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Learning Paradigms in e-Society

    Directory of Open Access Journals (Sweden)

    Gabriel ZAMFIR

    2013-01-01

    Full Text Available Learning, defined both as the cognitive process of acquiring knowledge, and as the knowledge received by instruction, depends on the environment. Our world, analyzed as an educational environment, evolved from a natural native stage to a scientific technological based phase. Educative system, developed as a public service, including formal, non-formal and informal education, originated its foundations on the textbook, and at present, teacher preparation is based on the same technique. This article is designed as a conceptual basis analyze of learning in a scientific environment, in order to synthesize the interdependencies between the cognitive process of acquiring knowledge and the methods applied in knowledge conversion.

  19. canEvolve: a web portal for integrative oncogenomics.

    Directory of Open Access Journals (Sweden)

    Mehmet Kemal Samur

    Full Text Available BACKGROUND & OBJECTIVE: Genome-wide profiles of tumors obtained using functional genomics platforms are being deposited to the public repositories at an astronomical scale, as a result of focused efforts by individual laboratories and large projects such as the Cancer Genome Atlas (TCGA and the International Cancer Genome Consortium. Consequently, there is an urgent need for reliable tools that integrate and interpret these data in light of current knowledge and disseminate results to biomedical researchers in a user-friendly manner. We have built the canEvolve web portal to meet this need. RESULTS: canEvolve query functionalities are designed to fulfill most frequent analysis needs of cancer researchers with a view to generate novel hypotheses. canEvolve stores gene, microRNA (miRNA and protein expression profiles, copy number alterations for multiple cancer types, and protein-protein interaction information. canEvolve allows querying of results of primary analysis, integrative analysis and network analysis of oncogenomics data. The querying for primary analysis includes differential gene and miRNA expression as well as changes in gene copy number measured with SNP microarrays. canEvolve provides results of integrative analysis of gene expression profiles with copy number alterations and with miRNA profiles as well as generalized integrative analysis using gene set enrichment analysis. The network analysis capability includes storage and visualization of gene co-expression, inferred gene regulatory networks and protein-protein interaction information. Finally, canEvolve provides correlations between gene expression and clinical outcomes in terms of univariate survival analysis. CONCLUSION: At present canEvolve provides different types of information extracted from 90 cancer genomics studies comprising of more than 10,000 patients. The presence of multiple data types, novel integrative analysis for identifying regulators of oncogenesis, network

  20. [The template principle: paradigm of modern genetics].

    Science.gov (United States)

    Inge-Vechtomov, S G

    2013-01-01

    The idea of continuity in living systems, which was initially developed in mid-19th century, reached its peak in 1928 thanks to N.K. Koltsov, who proposed the template principle in chromosome reproduction. The determination of genetic functions of nucleic acids and the advent of molecular genetics led to F. Crick's statement of the central dogma of molecular biology in 1958. This dogma became a contemporary version of the template principle (templates of the first order). The discovery of "protein inheritance" underlay the notion of steric or conformational templates (second order) for reproducing conformation in a number of proteins. The template principle supplemented by this notion claims to be the main paradigm of modern genetics.