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Progressive
Kinds of Progressive Terms modified by Progressive Selected AbstractsProgressive collapse analysis through strength degradation and fracture in the Mixed Lagrangian FormulationEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 13 2009O. Lavan Abstract The dynamic analysis of progressive collapse faces a great number of obstacles that often lead to the collapse of the analysis prior to the actual analysis of collapse. Hence, the Mixed Lagrangian Formulation that has been shown to be very robust was adopted as a framework to accommodate such analysis. By modifying the loading function and the numerical scheme, the capabilities of this framework were extended to account for strength degradation and fracture, while some insight to its behavior is introduced as well. The examples presented show a very robust and stable behavior of the numerical scheme in terms of the time step size required, even in cases where a sudden fracture takes place. Copyright © 2009 John Wiley & Sons, Ltd. [source] Progressive segmented health insurance: Colombian health reform and access to health servicesHEALTH ECONOMICS, Issue 1 2007Fernando Ruiz Abstract Equal access for poor populations to health services is a comprehensive objective for any health reform. The Colombian health reform addressed this issue through a segmented progressive social health insurance approach. The strategy was to assure universal coverage expanding the population covered through payroll linked insurance, and implementing a subsidized insurance program for the poorest populations, those not affiliated through formal employment. A prospective study was performed to follow-up health service utilization and out-of-pocket expenses using a cohort design. It was representative of four Colombian cities (Cendex Health Services Use and Expenditure Study, 2001). A four part econometric model was applied. The model related medical service utilization and medication with different socioeconomic, geographic, and risk associated variables. Results showed that subsidized health insurance improves health service utilization and reduces the financial burden for the poorest, as compared to those non-insured. Other social health insurance schemes preserved high utilization with variable out-of-pocket expenditures. Family and age conditions have significant effect on medical service utilization. Geographic variables play a significant role in hospital inpatient service utilization. Both, geographic and income variables also have significant impact on out-of-pocket expenses. Projected utilization rates and a simulation favor a dual policy for two-stage income segmented insurance to progress towards the universal insurance goal. Copyright © 2006 John Wiley & Sons, Ltd. [source] Social Representations Theory: A Progressive Research Programme for Social PsychologyJOURNAL FOR THE THEORY OF SOCIAL BEHAVIOUR, Issue 4 2008MARTIN W. BAUER ABSTRACT The study "Psychoanalysis,its image and its public" intimates that common sense is increasingly informed by science. But common sense asserts its autonomy and, in turn, may affect the trajectory of science. This is a process that leads to many differentiations,in common sense, in scientific innovation and in political and regulatory structures. Bauer and Gaskell's toblerone model of triangles of mediation provided a distillation of their reading of "La Psychanalyse." Here it was argued that representations are multi-modal phenomena necessitating the use of multiple methodologies (comparative and longitudinal; qualitative and quantitative). In this paper we briefly summarise these arguments and elaborate ways in which social representation theory can be considered a progressive research programme. "Progressive" because as the theory has developed it has extended the range and depth of its conceptual basis; it provides a new synthesis for the social scientific understanding of the phenomena of common sense and of representation; it acts as an antidote to the reductionism of public opinion and, finally, it is a stimulus to depart from disciplinary silos. However, there remain unresolved issues: how to segment the relevant social milieus and how to close the feedback loop from common sense to science? [source] Making Financial Goals and Reporting Policies ServeJOURNAL OF APPLIED CORPORATE FINANCE, Issue 4 2004Corporate Strategy: The Case of Progressive Insurance The main. nancial goal of Progressive Insurance, the third largest underwriter of auto insurance in the U.S., has remained the same since the late 1960s. Expressed in three words, "96 and grow," the goal tells the company's managers to pursue all growth opportunities while maintaining a "combined ratio" no higher than 96, or what amounts to a minimum 4% spread between revenues (premiums) and costs (including expected losses). Thanks in part to the clarity of mission provided by this goal, the company has produced an average 15% rate of growth in revenues and earnings, along with a remarkably stable 15% return for its shareholders, since going public in 1971. Progressive's simplicity and clarity of mission is also partly responsible for another of the company's distinctive policies: product pricing that, while disciplined, is aggressive and highly decentralized. Having invested some $500 million per year developing statistical models for pricing individual customer risks and acquisition costs, the company was among the. rst in its industry to underwrite "non-standard" risks. And aided by sophisticated pricing models, each of Progressive's 100 or so local product managers are charged with adapting those models to come up with premiums for their own regions. To go along with its strategic and organizational innovations, Progressive also has an innovative disclosure policy. Apart from SEC reports, the company's communications seldom mention earnings or earnings per share, and the company has never provided earnings guidance. With the passage of Reg. FD in late 2000, the company brie. y considered offering guidance. But in the spring of 2001, the board decided instead to provide monthly releases of its realized combined ratio. Since adoption of this new disclosure policy, Progressive has seen a 50% drop in the volatility of its stock price. [source] Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004Qing Li Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source] Progressive circumscribed sclerosis , a novel side-effect of immunotherapy with aluminium-adsorbed allergen extractsALLERGY, Issue 6 2009El Shabrawi-Caelen In the susceptible patient aluminum may trigger an autoimmune reaction with progressive sclerosis as the key clinical feature. [source] On the Progressive and the PerfectiveNOUS, Issue 1 2004Zoltán Gendler Szabó First page of article [source] Becoming Progressive: The California Supreme Court, 1880,1910THE HISTORIAN, Issue 3-4 2002Gordon Morris Bakken [source] From Progressive to Liberal Internationalism: Carl Albert, Helen Douglas, and the Making of a Postwar ConsensusTHE JOURNAL OF THE HISTORICAL SOCIETY, Issue 4 2009Jeff BloodworthArticle first published online: 2 DEC 200 [source] A new member of the Arabidopsis WRKY transcription factor family, AtWRKY6, is associated with both senescence- and defence-related processesTHE PLANT JOURNAL, Issue 2 2001Silke Robatzek Summary WRKY proteins constitute a large family of plant-specific transcription factors whose precise functions have yet to be elucidated. Here we show that expression of one representative in Arabidopsis, AtWRKY6, is influenced by several external and internal signals often involved in triggering senescence processes and plant defence responses. Progressive 5, deletions of the AtWRKY6 promoter allowed separation of defined regions responsible for the expression in distinct organs or upon pathogen challenge. Nuclear localization of AtWRKY6 was demonstrated; protein truncations and gain-of-function studies enabled delineation of a region harbouring a novel type of functional nuclear localization signal (NLS). [source] Child abuse in South Africa: rights and wrongsCHILD ABUSE REVIEW, Issue 2 2008Linda M. Richter Abstract In a country in which human rights feature prominently in our discourse about who we are, as well as in the South African constitutional and legal framework, so many wrongs continue to be done to children. One category of wrongs is abuse, but it is not the only one. Poverty, patriarchy and gender violence, as well as the socialised obedience, dependency and silence of women and children, create conditions in which abuse can occur, often with few consequences. South Africa has extremely high rates of both physical and sexual abuse of children. Progressive, rights-based legislation exists to protect children, but it is not adequately supported or resourced by services to fulfil their provisions. Child abuse and neglect will not be significantly reduced in South Africa, without simultaneous improvements in the social and economic conditions in which very large numbers of children live. Copyright © 2008 John Wiley & Sons, Ltd. [source] Making Financial Goals and Reporting Policies ServeJOURNAL OF APPLIED CORPORATE FINANCE, Issue 4 2004Corporate Strategy: The Case of Progressive Insurance The main. nancial goal of Progressive Insurance, the third largest underwriter of auto insurance in the U.S., has remained the same since the late 1960s. Expressed in three words, "96 and grow," the goal tells the company's managers to pursue all growth opportunities while maintaining a "combined ratio" no higher than 96, or what amounts to a minimum 4% spread between revenues (premiums) and costs (including expected losses). Thanks in part to the clarity of mission provided by this goal, the company has produced an average 15% rate of growth in revenues and earnings, along with a remarkably stable 15% return for its shareholders, since going public in 1971. Progressive's simplicity and clarity of mission is also partly responsible for another of the company's distinctive policies: product pricing that, while disciplined, is aggressive and highly decentralized. Having invested some $500 million per year developing statistical models for pricing individual customer risks and acquisition costs, the company was among the. rst in its industry to underwrite "non-standard" risks. And aided by sophisticated pricing models, each of Progressive's 100 or so local product managers are charged with adapting those models to come up with premiums for their own regions. To go along with its strategic and organizational innovations, Progressive also has an innovative disclosure policy. Apart from SEC reports, the company's communications seldom mention earnings or earnings per share, and the company has never provided earnings guidance. With the passage of Reg. FD in late 2000, the company brie. y considered offering guidance. But in the spring of 2001, the board decided instead to provide monthly releases of its realized combined ratio. Since adoption of this new disclosure policy, Progressive has seen a 50% drop in the volatility of its stock price. [source] The Illusion of Relevance: Southern Progressives and American Higher EducationTHE JOURNAL OF THE HISTORICAL SOCIETY, Issue 2 2008Michael Dennis [source] Urban Ethnography's "Saloon Problem" and Its Challenge to Public SociologyCITY & COMMUNITY, Issue 2 2007Greggor Mattson This essay assesses the legacy of urban ethnography's (UE) early engagement with the "saloon problem." Early sociologists (1880,1915) intervened in the national debate on alcohol on the basis of their long-term, in-depth understanding of the urban poor. Ethnographers highlighted the role of the saloon as a haven for maintaining social ties while socializing immigrants to American norms. Instead of prohibition or temperance, sociologists advocated replacing the saloon's positive functions with more democratic institutions, especially an egalitarian domestic sphere. This position was shared by both academic and settlement house sociologists whose saloon investigations offer a coherent sociological research paradigm that antedates the Chicago School. The activism of early sociologists exemplifies the characteristics of Michael Burawoy's recent call for public sociology. Yet the early sociologists failed to redeem the saloon amongst Progressives, who increasingly rallied around the National Anti-Saloon League and constitutional Prohibition. By only investigating alcohol in its public manifestations, sociologists failed to challenge the way the social problem was framed and may even have contributed to the stigmatization of the saloon. This voyeuristic opportunism has plagued the American tradition of urban ethnography, the ineffective legacy of which poses a challenge to a contemporary revival of public sociology. [source] Creating Research Questions from Strategies and Perspectives of Contemporary ArtCURRICULUM INQUIRY, Issue 1 2001G. Thomas Fox This essay considers how strategies and perspectives from contemporary art can suggest new questions for educational research. Although arts-based research has become more prominent lately, the concern of this paper is that the arts have become used primarily as decorative features to educational research (to further illuminate, depict, and explain the ambiguities and complexities of educational practices, see Donmoyer 1997), rather than deeply moving or disorientating perspectives on education. Another stimulant for looking into contemporary art is the concern that education must focus more on the edges of what is understood, rather than on the centers (see, for example, Fox 1995). The essay uses examples to demonstrate how a number of themes from contemporary art can be interpreted to redirect our curiosity about educational practices, policies, and theories. The paper concludes that further consideration of contemporary art can move researchers to ask more varied questions, especially about the wisdom of our progressive, critical, or humanistic views of students and learning that we have built over this century. [source] A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a dyskinetic movement disorderDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2010MICHAEL ABSOUD ARX mutations are associated with variable clinical phenotypes. We report a new neurodegenerative phenotype associated with a known ARX mutation and causing early abnormal neurodevelopment, a complex movement disorder, and early infantile epileptic encephalopathy with a suppression-burst pattern (Ohtahara syndrome). A male infant presented at age 5 months with a dyskinetic movement disorder, which was initially diagnosed as infantile spasms. Clinical deterioration was accompanied by progressive cortical atrophy with a reduction in white matter volume and resulting in death in the first year of life; such a rapidly progressive and severe phenotype has not previously been described. ARX mutation testing should be undertaken in children aged less than 1 year with Ohtahara syndrome and a movement disorder, and in infants with unexplained neurodegeneration, progressive white matter loss, and cortical atrophy. [source] Ganglion cell regeneration following whole-retina destruction in zebrafishDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2008Tshering Sherpa Abstract The retinas of adult teleost fish can regenerate neurons following injury. The current study provides the first documentation of functional whole retina regeneration in the zebrafish, Danio rerio, following intraocular injection of the cytotoxin, ouabain. Loss and replacement of laminated retinal tissue was monitored by analysis of cell death and cell proliferation, and by analysis of retina-specific gene expression patterns. The spatiotemporal process of retinal ganglion cell (RGC) regeneration was followed through the use of selective markers, and was found to largely recapitulate the spatiotemporal process of embryonic ganglion cell neurogenesis, over a more protracted time frame. However, the re-expression of some ganglion cell markers was not observed. The growth and pathfinding of ganglion cell axons was evaluated by measurement of the optic nerve head (ONH), and the restoration of normal ONH size was found to correspond to the time of recovery of two visually-mediated behaviors. However, some abnormalities were noted, including overproduction of RGCs, and progressive and excessive growth of the ONH at longer recovery times. This model system for whole-retina regeneration has provided an informative view of the regenerative process. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Thiazolidinediones and the preservation of ,-cell function, cellular proliferation and apoptosisDIABETES OBESITY & METABOLISM, Issue 8 2008Michael Decker The thiazolidinediones (TZDs) or glitazones are pharmaceutical agents that have profound effects on energy expenditure and conservation. They also exert significant anti-inflammatory effects and influence cell proliferation and cell death. The drugs are primarily used in clinical practice in the treatment of patients with type 2 diabetes mellitus, a disorder of insulin resistance that occurs when the pancreatic ,-cells are unable to produce adequate amounts of insulin to maintain euglycaemia. Loss of pancreatic ,-cell function in type 2 diabetes is progressive and often precedes overt diabetes by 10 years or more, as was shown by the United Kingdom Prospective Diabetes Study. Any therapeutic or preventive approach that would limit or reverse loss of ,-cell function in diabetes would have profound effects on the morbidity associated with this widespread disease. Evidence suggesting a potential role of TZDs in preserving ,-cell function in type 2 diabetes as well as the ability of these agents to exert anti-inflammatory and proapoptotic anticancer effects, and their ability to promote cellular proliferation in various organs is reviewed. [source] New potential treatments for protection of pancreatic B-cell function in Type 1 diabetesDIABETIC MEDICINE, Issue 11 2008S. Cernea Abstract Type 1 diabetes mellitus results from the progressive and specific autoimmune destruction of insulin-secreting pancreatic B-cells, which develops over a period of years and continues after the initial clinical presentation. The ultimate goal of therapeutic intervention is prevention or reversal of the disease by the arrest of autoimmunity and by preservation/restoration of B-cell mass and function. Recent clinical trials of antigen-specific or non-specific immune therapies have proved that modulation of islet specific autoimmunity in humans and prevention of insulin secretion loss in the short term after the onset of disease is achievable. The identification of suitable candidates for therapy, appropriate dosage and timing, specificity of intervention and the side-effect profile are crucial for the success of any approach. Considering the complexity of the disease, it is likely that a rationally designed approach of combined immune-based therapies that target suppression of B-cell specific autoreactivity and maintenance of immune tolerance, coupled with islet regeneration or replacement of the destroyed B-cell mass, will prove to be most effective in causing remission/reversal of disease in a durable fashion. [source] Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5-fluorouracil resistanceELECTROPHORESIS, Issue 12 2009Young-Kyoung Shin Abstract 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, resistance to this drug is a major obstacle in CRC chemotherapy. Accurate prediction of response to 5-FU would avoid unnecessary chemotherapy and allow the selection of other effective drugs. To identify a candidate predictor of 5-FU resistance, we isolated secreted proteins that were up- or downregulated in a 5-FU-resistant cancer cell line, compared with the parent cell line (SNU-C4), using a stable isotope-coded labeling protocol. For validating the clinical applicability of this method, levels of the identified proteins were determined in the sera of 46 patients treated with 5-FU. In total, 238 proteins with molecular weights ranging from 50 to 75,kDa were identified. Among these, 45 and 35 secreted proteins were up- and downregulated in the 5-FU-resistant cell line, respectively. We observed significant upregulation of glycolytic enzymes, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase M2 (PK-M2), transketolase, and NADP(+)-dependent malic enzyme 1. In particular, the level of PK-M2, a key enzyme in the glycolytic pathway, showed an increasing tendency in both sera and tissues from CRC patients displaying no response to 5-FU-based chemotherapy (progressive and stable disease cases), compared with that in complete or partial responders to 5-FU-based chemotherapy; however, it did not reach the statistical significance. In conclusion, increasing pattern of PK-M2 observed with 5-FU resistance induced in vitro and in sera and tissues from CRC patients displaying poor response to 5-FU-based chemotherapy suggest the relevance of dysregulated glycolysis and 5-FU-resistant CRC. [source] Aroclor 1254 alters morphology, survival, and gene expression in Xenopus laevis tadpolesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2002Anna M. Jelaso Abstract PCBs are persistent environmental contaminants that cause a variety of adverse health effects in wildlife and humans. This article describes the use of signature gene expression patterns that link increased PCB exposure with progressive, adverse biological effects. Developing Xenopus laevis tadpoles of two age classes were exposed to the PCB mixture Aroclor 1254 for 2 days. Real-time PCR was used to quantitate mRNA expression for 11 physiologically relevant, potential bioindicator genes. Younger tadpoles (5 days postfertilization) were resistant to Aroclor 1254 and showed few changes in gross morphology, swimming behavior, survival, or gene expression. Older tadpoles (11 days postfertilization) were more susceptible to Aroclor 1254. Exposure to 25 and 50 ppm Aroclor 1254 caused alterations in gross morphology and swimming behavior and statistically significant decreases in survival. These tadpoles showed statistically significant decreases in gene expression for 9 out of the 11 genes measured. Tadpoles exposed to 10 ppm showed incipient health changes but had gene expression profiles similar to the tadpoles treated with higher doses of Aroclor 1254. Tadpoles exposed to 1 ppm did not exhibit any observable adverse health effects, yet statistically significant decreases in gene expression occurred in these tadpoles (4 out of 11 genes). After prolonged exposure, tadpoles exposed to 1 and 10 ppm Aroclor 1254 exhibited health effects similar to those exposed to higher concentrations. Therefore, changes in expression of specific genes may serve not only as molecular bioindicators of Aroclor 1254 exposure but also as predictors of impending adverse health effects. Environ. Mol. Mutagen. 40:24,35, 2002. © 2002 Wiley-Liss, Inc. [source] rTMS Reveals Premotor Cortex Dysfunction in Frontal Lobe EpilepsyEPILEPSIA, Issue 2 2007Wolfgang N. Löscher Summary:,Purpose: Studies of motor cortex excitability provided evidence that focal epilepsies may alter the excitability of cortical areas distant from the epileptogenic zone. In order to explore this hypothesis we studied the functional connectivity between premotor and motor cortex in seven patients with frontal lobe epilepsy and seizure onset zone outside the premotor or motor cortex. Methods: Low-frequency subthreshold repetitive transcranial magnetic stimulation was applied to the premotor cortex and its impact on motor cortex excitability was measured by the amplitude of motor-evoked potentials in response to direct suprathreshold stimulation of the motor cortex. Results: Stimulation of the premotor cortex of the non-epileptogenic hemisphere resulted in a progressive and significant inhibition of the motor cortex as evidenced by a reduction of motor evoked potential amplitude. On the other hand, stimulation of the premotor cortex of the epileptogenic hemisphere failed to inhibit the motor cortex. The reduced inhibition of the motor cortex by remote areas was additionally supported by the significantly shorter cortical silent periods obtained after stimulation of the motor cortex of the epileptogenic hemisphere. Conclusion: These results show that the functional connectivity between premotor and motor cortex or motor cortex interneuronal excitability is impaired in the epileptogenic hemisphere in frontal lobe epilepsy while it is normal in the nonepileptogenic hemisphere. [source] Adult-Onset Rasmussen's Encephalitis: Anatomical-Electrographic-Clinical Features of 7 Italian CasesEPILEPSIA, Issue 2006Flavio Villani Summary:,Purpose: A limited number of cases of adult-onset Rasmussen's encephalitis (A-RE) have been reported, but the features of the syndrome are still unclear. The aim of this study was to verify the clinical features of A-RE, and outline a noninvasive approach that may allow its early diagnosis and treatment. Methods: Retrospective evaluation of extensive noninvasive work-up of seven patients with A-RE, including repeat clinical, neurophysiological, and neuroimaging investigations. Results: The study identified two distinct patterns of disease presentation, one characterized by focal motor epilepsy (the "epileptic" phenotype), and the other by focal cortical myoclonus (the "myoclonic" phenotype). Unilateral neurological deficits and brain atrophy were progressive in both phenotypes, but they were more prominent and were detected earlier in the "epileptic" phenotype. Conclusions: The anatomo-electroclinical features of these patients allowed a noninvasive diagnosis of A-RE and identification of two distinct disease phenotypes. Early noninvasive diagnosis can allow faster initiation of treatment. [source] Qualifications Frameworks: some conceptual issuesEUROPEAN JOURNAL OF EDUCATION, Issue 4 2007MICHAEL YOUNG The aim of this article is to contribute to realising the progressive and democratic opportunities that National Qualifications Frameworks (NQFs) can offer. In doing so it will be critical of many of the ways that NQFs have been interpreted to date and the claims that have been made for them. The article has six sections. Section 1 considers some of the reasons for the recent growth of interest in NQFs. Section 2 is concerned with the widely shared goals of NQFs and some of the contradictions and problems that they involve. Section 3 discusses the very different forms that NQFs can take. Section 4 examines a number of issues that underlie all approaches to qualifications but are made more explicit by qualification frameworks and concludes by questioning the much lauded claim that NQFs can promote and accredit informal learning. The concluding section considers the longer term implications for the future of NQFs of the earlier analysis. [source] Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shuntEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Elena Mishchenko Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source] PRECLINICAL STUDY: FULL ARTICLE: The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-accessADDICTION BIOLOGY, Issue 3 2010Laura Orio ABSTRACT Previous work suggests a role for dopamine D3-like receptors in psychostimulant reinforcement. The development of new compounds acting selectively at dopamine D3 receptors has opened new possibilities to explore the role of these receptors in animal models of psychostimulant dependence. Here we investigated whether the dopamine D3 partial agonist CJB090 (1,10 mg/kg, i.v) and the D3 antagonist PG01037 (8,32 mg/kg, s.c.) modified methamphetamine (0.05 mg/kg/injection) intravenous self-administration under fixed- (FR) and progressive- (PR) ratio schedules in rats allowed limited (short access, ShA; 1-hour sessions 3 days/week) or extended access (long access, LgA; 6 hour sessions 6 days/week). Under a FR1 schedule, the highest dose of the D3 partial agonist CJB090 selectively reduced methamphetamine self-administration in LgA but not in ShA rats, whereas the full D3 antagonist PG01037 produced no effect in either group. Under a PR schedule of reinforcement, the D3 partial agonist CJB090 reduced the maximum number of responses performed (,breakpoint') for methamphetamine in LgA rats at the doses of 5 and 10 mg/kg, and also it produced a significant reduction in the ShA group at the highest dose. However, the D3 full antagonist PG01037 only reduced PR methamphetamine self-administration in LgA rats at the highest dose of 32 mg/kg with no effect in the ShA group. The results suggest that rats might be more sensitive to pharmacological modulation of dopamine D3 receptors following extended access to methamphetamine self-administration, opening the possibility that D3 receptors play a role in excessive methamphetamine intake. [source] An exploration of anger phenomenology in multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2009U. Nocentini Background and purpose:, Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics. Patients and methods:, About 195 cognitively unimpaired MS patients (150 relapsing,remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients' anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance. Results:, Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients. Conclusions:, The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex. [source] Repeat intrathecal triamcinolone acetonide application is beneficial in progressive MS patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2006V. Hoffmann Available immunomodulatory and conventional steroid treatment regimens provide a limited symptomatic benefit for patients with progressive multiple sclerosis (MS). We performed an open trial on the short-term efficacy of repeated intrathecal application of the sustained release steroid triamcinolone acetonide (TCA) in 27 progressive MS patients. Six TCA administrations, performed every third day, reduced the Expanded Disability Status Scale (EDSS) score [initial: 5.4 ± 1.3, 3,7.5 (mean ± SD, range); end: 4.9 ± 1.1; 2.5,6.5; P < 0.001] and significantly increased the walking distance and speed in particular after the fourth TCA injection. Concomitantly serially determined cerebrospinal fluid (CSF) markers of cell injury, neuron-specific enolase, total , -protein, S-100, and , -amyloid did not significantly change within the interval of TCA treatment. No serious side effects appeared. We conclude that repeat intrathecal injection of 40 mg TCA provides a substantial benefit in progressive MS patients with predominant spinal symptoms and does not alter CSF markers of neuronal cell injury. [source] EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapsesEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2005F. Sellebjerg Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing-remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High-dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence-based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short-term, high-dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS. [source] Fate of airborne metal pollution in soils as related to agricultural management.EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 3 2007Summary The fate of airborne metal pollutants in soils is still relatively unknown. We studied the incorporation of such airborne metal pollution in two soils under long-term permanent pasture (PP) and conventional arable land (CA). Both soils were located at an almost equal distance from a former zinc smelter complex and developed under comparable pedogenetic conditions. Profiles of total concentrations of Zn, chosen as a mobile, and Pb as a little- or non-mobile element, were examined and compared with macro- and micromorphological soil characteristics (soil colour, biological activity). The two soils showed different profiles of total Zn and Pb concentrations, with a marked decrease of concentrations of both elements under the plough layer in CA, whereas the decrease was more progressive in PP. However, the stocks of Zn and Pb for the 1-m soil profiles of CA and PP were comparable. Correlation of Zn and Pb concentration at different depths with total Fe contents and comparison with estimated data for the local geochemical background (LGCB), suggests transport of Zn from the surface to depth in CA and PP, and Pb movement in PP. In CA, 53% of Zn and 92.5% of Pb stocks derived from airborne metal pollution were located at depths < 26 cm. In PP, only 40% of Zn and 82% of Pb, derived from airborne pollution, were found in the A11 and A12 horizons (< 26 cm), the remaining 18% of the Pb stock being incorporated until 50 cm depth; one-third of total Zn stock ascribed to airborne pollution was found at depths > 50 cm. Studies of the composition of gravitational water collected in soils from the same study area suggest two mechanisms for metal movement. First, mobile metal ions (Zn2+) move in the soil solution and are intercepted by iron-clay complexes in deeper soil horizons. Second, observed only in PP, simultaneous movement of Zn and Pb is ascribed to bioturbation by earthworms. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||