Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Recent

  • many recent

  • Terms modified by Recent

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  • Selected Abstracts


    Research Summary: Following reforms of the federal firearms licensing system, nearly 70% of the nation's retail gun dealers active in 1994 dropped out of business by 1998. Dropout dealers supplied one-third of guns recovered and traced by police but were linked to fewer crime guns than were other dealers, most likely because dropouts tended to be lower volume dealers. It is not clear if guns sold by dropouts had a higher probability of being used in crime, but guns supplied by dropouts did not move into criminal channels more quickly. Policy Implications: If federal reforms have reduced the availability of guns to criminals, the effect has probably been more modest than suggested by the overall reduction in dealers. Producing further reductions in the flow of guns to criminals through oversight of gun dealers will require refinement in the identification of problematic gun dealers. [source]


    Henk J. Ter Bogt
    Dutch municipalities and provinces have recently introduced many changes relating to management control. This paper explores the role of economic and social rationality in the introduction of reforms, and the nature of possible future reforms. Based on interviews with politicians and professional managers and on documents, the paper examines experiences with recent management changes. In addition, it discusses ,change initiating factors'. Budget cuts and trends seem to be such change initiating factors. However, particularly more demanding citizens, increases in voters' volatility and politicians' uncertainty seemed to initiate changes. The paper speculates that in the near future, too, it could be a rational survival strategy for politicians and managers to focus on initiatives that are intended to enhance performance and efficiency. [source]

    Etiology, pathogenesis and prevention of neural tube defects

    Rengasamy Padmanabhan
    ABSTRACT Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene,environment interactions in the pathogenesis of NTD. [source]

    Drifters and the Dancing Mad: The Public School Music Curriculum and the Fabrication of Boundaries for Participation

    CURRICULUM INQUIRY, Issue 3 2008
    ABSTRACT Recent reforms in the general music curriculum have, for the most part, failed to lessen the attrition rates of African Americans from public school music programs. In this article I assert that an embodied ideal of cultural nobility, exemplified by Auguste Rodin's famous statue, The Thinker, has unconsciously operated as a template for participation. As a model comportment in the Western musical tradition, The Thinker has a broader relevance insofar as other school subjects emerged from similar cultural ideals. Beginning with the early period of public music instruction up to the present, I examine the construction of racial boundaries by linking a specific body comportment hailed as worthy by the music curriculum to historically constructed notions of Whiteness. This issue has been underexplored in research in both music and general education. For that reason, this article examines overlapping systems of reasoning about music, comportment, class, religion, language, nationality, and race in professional and popular texts from the early 1800s to the present. This positions public music instruction as authored, not by pedagogical insight alone, but through changes in musical taste, social practices, strategies of governing populations, and definitions of worthy citizenship. There are three levels of analysis. The first is a personal account of the early manifestations of attrition of African Americans from school music programs. The second level of analysis brings the problem of equity into proximity with the tradition of genteel comportment that permeated the training of the good ear or listener and the fabrication of the bona fide citizen. These, I argue are congruent with the historical construction of Whiteness as a standard mark of worthiness. At the third level of analysis, I take up present-day curriculum designs. This section discusses how the language of the music curriculum continues to draw boundaries for participation through protocols that regulate musical response. Here, I argue that the exclusion of popular genres such as hip-hop should be rethought in light of the evidence that shifting historical definitions for music fabricated an overly restrictive template for comportment, recognizing the prototype of Whiteness as the sole embodiment of merit. [source]

    Anti-Politics as Political Strategy: Neoliberalism and Transfrontier Conservation in Southern Africa

    Bram Büscher
    ABSTRACT Studies on conservation and development often point out that interventions rely on anti-political manoeuvring to acquire legitimacy and support. Recent ,aidnography', in particular, has done much to expand and add nuance to our understanding of the complex, micro- (anti-)politics at work in conservation and development interventions. In doing this, however, aidnography seems to have led the focus away from two crucial, broader issues related to conservation and development interventions: how they are regulated through the wider, neoliberal political economy, and how this fuels and obscures (global) inequality. Drawing on empirical research on a transfrontier conservation and development intervention in Southern Africa, this article argues that the differential workings of anti-politics in practice warrant a renewed appreciation and a more explicit political operationalization of the concept. This is done by re-emphasizing anti-politics as an essential political strategy within conservation and development interventions and as an intrinsic element of the wider political economy of neoliberalism. [source]

    Fossils provide better estimates of ancestral body size than do extant taxa in fishes

    ACTA ZOOLOGICA, Issue 2009
    James S. Albert
    Abstract The use of fossils in studies of character evolution is an active area of research. Characters from fossils have been viewed as less informative or more subjective than comparable information from extant taxa. However, fossils are often the only known representatives of many higher taxa, including some of the earliest forms, and have been important in determining character polarity and filling morphological gaps. Here we evaluate the influence of fossils on the interpretation of character evolution by comparing estimates of ancestral body size in fishes (non-tetrapod craniates) from two large and previously unpublished datasets; a palaeontological dataset representing all principal clades from throughout the Phanerozoic, and a macroecological dataset for all 515 families of living (Recent) fishes. Ancestral size was estimated from phylogenetically based (i.e. parsimony) optimization methods. Ancestral size estimates obtained from analysis of extant fish families are five to eight times larger than estimates using fossil members of the same higher taxa. These disparities arise from differential survival of large-bodied members of early branching lineages, and are not statistical or taphonomic artefacts. Estimates of ancestral size obtained from a limited but judicious selection of fossil fish taxa are more accurate than estimates from a complete dataset of extant fishes. [source]

    Understanding the costs of an environmentally ,friendly' common agricultural policy for the European Union1,

    Pamela M. Barnes
    Part of the bedrock of the European Union's (EU's) Environmental Policy is the principle that those who pollute the environment should pay for the cost of remedying the damage they cause (the polluter pays principle) (Article 174 para. 2 TEC ex Article 130r TEC). In addition environmental objectives must be integrated into all the sectoral policies of the European Union (Article 6 TEC ex Article 3c TEC). The Common Agricultural Policy's (CAP's) role at the centre of the EU's sectoral policies would appear to make it an ideal focus for implementing Article 6 of the Treaty establishing the European Community (TEC). If integration of environmental protection can be achieved in this central area of the EU's activities then a major source of environmental degradation could be overcome. However, if these requirements are applied to European agriculture the sector will face a budgetary and financial crisis of even greater magnitude than at the present time. Recent reforms of the CAP have been designed with the objective of achieving an agricultural sector that is moving towards sustainability. As this article argues the political, social and economic significance of the agriculture sector is such that national governments of the EU have repeatedly shied away from adopting the measures, which could significantly reduce the pollution from the sector. The proposals for reform made by the Agricultural Commissioner, Franz Fischler, were amended by the meeting of the European Council that took place in Berlin on 24/25 March 1999. These amendments substantially weakened the ambitions of the strategy for development of the EU, the ,Agenda 2000' adopted in 1997, for a number of reasons (CEC, 1997). This article examines the reasons for the disappointments with the amended reforms and speculates on the possible future path that may be taken to improve matters. Copyright © 2001 John Wiley & Sons, Ltd and ERP Environment. [source]

    A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet function

    De Miguel
    Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source]

    The European Judicial Organisation in a New Paradigm: The Influence of Principles of ,New Public Management' on the Organisation of the European Courts

    EUROPEAN LAW JOURNAL, Issue 6 2008
    Elaine Mak
    Recent reforms regarding the European Courts raise the question in which way do ,new public management' principles influence the European judicial organisation and how is a balance struck between these principles and classic ,rule of law' principles? The article first presents a classification of these types of principles in the framework for discussion regarding the European judicial organisation. Starting out from two paradigms, an inquiry is made into the status of the two sets of principles in the present-day European ,constitutional' framework. Second, the interaction of principles is investigated with regard to a number of current dilemmas, including the demarcation of the judicial domain, the management of the Courts and the distribution of judicial competences. [source]

    Ancient hydrocarbon seeps from the Mesozoic convergent margin of California: carbonate geochemistry, fluids and palaeoenvironments

    GEOFLUIDS (ELECTRONIC), Issue 2 2002
    K. A. Campbell
    Abstract More than a dozen hydrocarbon seep-carbonate occurrences in late Jurassic to late Cretaceous forearc and accretionary prism strata, western California, accumulated in turbidite/fault-hosted or serpentine diapir-related settings. Three sites, Paskenta, Cold Fork of Cottonwood Creek and Wilbur Springs, were analyzed for their petrographic, geochemical and palaeoecological attributes, and each showed a three-stage development that recorded the evolution of fluids through reducing,oxidizing,reducing conditions. The first stage constituted diffusive, reduced fluid seepage (CH4, H2S) through seafloor sediments, as indicated by Fe-rich detrital micrite, corroded surfaces encrusted with framboidal pyrite, anhedral yellow calcite and negative cement stable isotopic signatures (,13C as low as ,35.5, PDB; ,18O as low as ,10.8, PDB). Mega-invertebrates, adapted to reduced conditions and/or bacterial chemosymbiosis, colonized the sites during this earliest period of fluid seepage. A second, early stage of centralized venting at the seafloor followed, which was coincident with hydrocarbon migration, as evidenced by nonluminescent fibrous cements with ,13C values as low as ,43.7, PDB, elevated ,18O (up to +2.3, PDB), petroleum inclusions, marine borings and lack of pyrite. Throughout these early phases of hydrocarbon seepage, microbial sediments were preserved as layered and clotted, nondetrital micrites. A final late-stage of development marked a return to reducing conditions during burial diagenesis, as implied by pore-associated Mn-rich cement phases with bright cathodoluminescent patterns, and negative ,18O signatures (as low as ,14, PDB). These recurring patterns among sites highlight similarities in the hydrogeological evolution of the Mesozoic convergent margin of California, which influenced local geochemical conditions and organism responses. A comparison of stable carbon and oxygen isotopic data for 33 globally distributed seep-carbonates, ranging in age from Devonian to Recent, delineated three groupings that reflect variable fluid input, different tectono-sedimentary regimes and time,temperature-dependent burial diagenesis. [source]

    Fish and ostracod remains from the Santos Basin (Cretaceous to Recent), Brazil

    GEOLOGICAL JOURNAL, Issue 4 2002
    C. Giles Miller
    Abstract For the first time, ichthyoliths are described from the Santos sedimentary basin, offshore southern Brazil. Isolated teeth, dermal scales and the first documented otoliths from Cretaceous (Albian) to Recent cuttings from five wells are described. The following groups are represented: Chondrichthyans: Triakidae, Carcharhinidae; Ginglymostomatidae: ?Ginglymostoma sp., Lamnidae indet., Scyliorhinidae; Osteichthyans: Teleostei; Myctophiidae: Diaphus aff. splendidus sp. complex, Diaphus spp., Diaphus cf. garmani, Ceratoscopelus aff. warmingii; Sternoptychidae: Valenciennellus tripunctulatus, teeth of indeterminate Teleostei. The majority of these ichthyofossils represent extant forms, known to occur in the Atlantic Ocean, and are of potential value for stratigraphical correlations between oil-yielding basins in the region. Ostracods are not well preserved but can be identified to generic level indicating marine environments. The ostracod faunas offer potential for intrabasinal correlation in the Eocene and Oligocene. Copyright © 2002 John Wiley & Sons, Ltd. [source]

    Role for glia in synaptogenesis

    GLIA, Issue 3 2004
    Erik M. Ullian
    Abstract Nearly one-half of the cells in a human brain are astrocytes, but the function of these little cells remains a great mystery. Astrocytes form an intimate association with synapses throughout the adult CNS, where they help regulate ion and neurotransmitter concentrations. Recent in vitro studies, however, have found that astrocytes also exert powerful control over the number of CNS synapses that form, are essential for postsynaptic function, and are required for synaptic stability and maintenance. Moreover, recent studies increasingly implicate astrocytes in vivo as participants in activity-dependent structural and functional synaptic changes throughout the nervous system. Taken together, these data force us to rethink the role of glia. We propose that astrocytes should not be viewed primarily as support cells, but rather as cells that actively control the structural and functional plasticity of synapses in developing and adult organisms. © 2004 Wiley-Liss, Inc. [source]

    Shame and the Future of Feminism

    HYPATIA, Issue 4 2007
    Recent works have recovered the ethical and political value of shame, suggesting that if shame is felt for the right reasons, toxic forms of shame may be alleviated. Rereading Hannah Arendt's biography of the "conscious pariah," Rahel Varnhagen, Locke concludes that a politics of shame does not have the radical potential its proponents seek. Access to a public world, not shaming those who shame us, catapults the shamed pariah into the practices of democratic citizenship. [source]

    Discontinuing Medications: A Novel Approach for Revising the Prescribing Stage of the Medication-Use Process

    Kevin T. Bain PharmD
    Thousands of Americans are injured or die each year from adverse drug reactions, many of which are preventable. The burden of harm conveyed by the use of medications is a significant public health problem, and therefore, improving the medication-use process is a priority. Recent and ongoing efforts to improve the medication-use process have focused primarily on improving medication prescribing, and not much emphasis has been put on improving medication discontinuation. A formalized approach for rationally discontinuing medications is a necessary antecedent to improving medication safety and improving the nation's quality of care. This article proposes a conceptual framework for revising the prescribing stage of the medication-use process to include discontinuing medications. This framework has substantial practice and research implications, especially for the clinical care of older persons, who are particularly susceptible to the adverse effects of medications. [source]

    Endogenous TNF, Lowers Maximum Peak Bone Mass and Inhibits Osteoblastic Smad Activation Through NF-,B,,

    Yan Li
    Abstract Endogenous TNF, prevents the attainment of maximum achievable peak bone mass in vivo. In vitro, TNF, suppresses BMP-2, and TGF,-mediated Smad activation through induction of NF-,B. Consistently, pharmacological suppression of NF-,B augments osteoblast differentiation and mineralization in vitro. Introduction: Osteoporosis is a major health threat. Traditional therapeutic strategies have centered on anti-catabolic drugs that block bone resorption. Recently focus has shifted to anabolic agents that actively rebuild lost bone mass. Future strategies may involve elevating peak bone mass to delay osteoporosis development. Recent in vitro studies show that TNF, represses osteoblast differentiation and mineralization; however, the mechanisms are poorly understood and the impact of basal TNF, concentrations on the acquisition of peak bone mass in vivo is unknown. Materials and Methods: We examined peak BMD, bone volume, and bone turnover makers in mice deficient in TNF, or its receptors. We further examined the effect of TNF, on Smad-induced signaling by TGF, and BMP-2 in vitro using a Smad responsive reporter. The effect of TNF,-induced NF-,B signaling on Smad signaling and on in vitro osteoblast mineralization was examined using specific NF-,B inhibitors and activators, and effects of TNF,-induced NF-,B signaling on BMP-2,induced Runx2 mRNA were examined using RT-PCR. Results: Mice null for TNF, or its p55 receptor had significantly increased peak bone mass, resulting exclusively from elevated bone formation. In vitro, TNF, potently suppressed Smad signaling induced by TGF, and BMP-2, downregulated BMP-2,mediated Runx2 expression, and inhibited mineralization of osteoblasts. These effects were mimicked by overexpression of NF-,B and prevented by pharmacological NF-,B suppression. Conclusions: Our data suggest that TNF, and NF-,B antagonists may represent novel anabolic agents for the maximization of peak basal bone mass and/or the amelioration of pathological bone loss. [source]

    Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational science

    Bruce J. Dezube
    Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source]

    Egg jelly influences sperm motility in the externally fertilizing frog, Crinia georgiana

    Abstract Recent in vitro fertilization studies have revealed female and male × female interaction effects on the probability of fertilization. These findings suggest a mechanism of cryptic female choice via sperm,egg interactions. The egg jelly of anuran amphibians contains proteins that facilitate the chemoattraction and binding of sperm for fertilization. Here we show that egg jelly also influences the onset of motility and swimming velocity of motile sperm in the frog Crinia georgiana. Moreover, we found significant among female variation in the effects of egg jelly on sperm motility. We discuss this finding with respect to male and female effects on nonrandom fertilization observed in this species. [source]

    Insulin-like growth factor-binding protein-1: an evolutionarily conserved fine tuner of insulin-like growth factor action under catabolic and stressful conditions

    S. Kajimura
    The insulin-like growth factor-binding proteins (IGFBPs) are evolutionarily conserved components of the insulin-like growth factor (IGF) system. The six forms of IGFBPs (IGFBP-1,6) bind the IGF ligands (IGF-1 and -2) with high affinity and regulate the IGFs available to their receptors, therefore providing additional flexibilities in regulating IGF signalling. IGFBP-1, the first identified member of the IGFBP family is highly inducible under a variety of catabolic conditions, such as food deprivation, malnutrition, stress, injury and hypoxia. Recent in vivo studies have indicated that the induced IGFBP-1 serves as a molecular switch by restricting IGF signalling and diverts the limited energy resources away from growth and development towards those metabolic processes essential for survival. This article reviews the recent understandings of the molecular basis of IGFBP-1 regulation and its biological functions, as revealed through research in mammalian and fish models. [source]

    Fluid evolution and thermal structure in the rapidly exhuming gneiss complex of Namche Barwa,Gyala Peri, eastern Himalayan syntaxis

    D. CRAW
    Abstract High-grade gneisses (amphibolite,granulite facies) of the Namche Barwa and Gyala Peri massifs, in the eastern Himalayan syntaxis, have been unroofed from metamorphic depths in the late Tertiary,Recent. Rapid exhumation (2,5 mm year,1) has resulted in a pronounced shallow conductive thermal anomaly beneath the massifs and the intervening Tsangpo gorge. The position of the 300 °C isotherm has been estimated from fluid inclusions using CO2,H2O immiscibility phase equilibria to be between 2.5 and 6.2 km depth below surface. Hence, the near-surface average thermal gradient exceeds 50 °C km,1 beneath valleys, although the thermal gradient is relatively lower beneath the high mountains. The original metamorphic fluid in the gneisses was >90% CO2. This fluid was displaced by incursion of brines from overlying marine sedimentary rocks that have since been largely removed by erosion. Brines can exceed 60 wt% dissolved salts, and include Ca, Na, K and Fe chlorides. These brines were remobilized during the earliest stages of uplift at >500 °C. During exhumation, incursion of abundant topography-driven surface waters resulted in widespread fracture-controlled hydrothermal activity and brine dilution down to the brittle,ductile transition. Boiling water was particularly common at shallow levels (<2.5 km) beneath the Yarlung Tsangpo valley, and numerous hot springs occur at the surface in this valley. Dry steam is not a major feature of the hydrothermal system in the eastern syntaxis (in contrast to the western syntaxis at Nanga Parbat), but some dry steam fluids may have developed locally. [source]

    Detecting local convexity on the pareto surface

    Georges Fadel
    Abstract Recent regain in interest in multi-criteria optimization approaches to provide a designer with multiple solutions to select from and support decisions has led to various methodologies to generate such solutions and possibly approximate the Pareto set. This paper introduces the notions of H - and w -convexities, and develops a simple method to identify local convexity of Pareto hyper-surfaces since their shape can dictate the choice of the method to use to obtain Pareto solutions and possibly to build an approximation of that set. The method is based on comparing the results from the weighting method to those of the Tchebycheff method at any point on the Pareto hyper-surface. If, under some conditions, the points obtained from the two methods are identical or not, a local convexity or its lack can be assumed at that location and in its immediate neighbourhood. A numerical example is included. Copyright © 2002 John Wiley & Sons, Ltd. [source]

    Chronic exposure to nicotine and saquinavir decreases endothelial Notch-4 expression and disrupts blood-brain barrier integrity

    Vamshi K. Manda
    J. Neurochem. (2010) 115, 515,525. Abstract Since the advent of HAART, there have been substantial improvements in HIV patient survival; however, the prevalence of HIV associated dementia has increased. Importantly, HIV positive individuals who smoke progress to HIV associated neurological conditions faster than those who do not. Recent in vitro data have shown that pharmacological levels of saquinavir causes endothelial oxidative stress and significantly decreases Notch-4 expression, a primary protein involved in maintaining stability of blood-brain barrier (BBB) endothelium. This is concerning as nicotine can also generate reactive oxygen species in endothelium. It is largely unknown if pharmacological doses of these drugs can cause a similar in vivo down-regulation of Notch-4 and if there is a concurrent destabilization of the integrity of the BBB. The data herein show: (i) nicotine and protease inhibitors cause an additive oxidative stress burden in endothelium; (ii) that the integrity of the BBB is disrupted after concurrent chronic nicotine and protease inhibitor administration; and (iii) that BBB endothelial dysfunction is correlated with a decrease in Notch-4 and ZO-1 expression. Considering the high prevalence of smoking in the HIV infected population (3- to 4-fold higher than in the general population) this data must be followed up to determine if all protease inhibitors cause a similar BBB disruption or if there is a safer alternative. In addition, this data may suggest that the induced BBB disruption may allow foreign molecules to gain access to brain and be a contributing factor to the slow progression of HIV associated dementia. [source]

    Novel targets for valproic acid: up-regulation of melatonin receptors and neurotrophic factors in C6 glioma cells

    Lyda M. Rincón Castro
    Abstract Valproic acid (VPA) is a potent anti-epileptic and effective mood stabilizer. It is known that VPA enhances central GABAergic activity and activates the mitogen-activated protein kinase,extracellular signal-regulated kinase (MAPK,ERK) pathway. It can also inhibit various isoforms of the enzyme, histone deacetylase (HDAC), which is associated with modulation of gene transcription. Recent in vivo studies indicate a neuroprotective role for VPA, which has been found to up-regulate the expression of brain-derived neurotrophic factor (BDNF) in the rat brain. Given the interaction between the pineal hormone, melatonin, and GABAergic systems in the central nervous system, the effects of VPA on the expression of the mammalian melatonin receptor subtypes, MT1 and MT2, were examined in rat C6 glioma cells. The effects of VPA on the expression of glial cell line-derived neurotrophic factor (GDNF) and BDNF were also examined. RT-PCR studies revealed a significant induction of melatonin MT1 receptor mRNA in C6 cells following treatment with 3 or 5 mm VPA for 24 h or 5 mm VPA for 48 h. Western analysis and immunocytochemical detection confirmed that the VPA-induced increase in MT1 mRNA results in up-regulation of MT1 protein expression. Blockade of the MAPK,ERK pathway by PD98059 enhanced the effect of VPA on MT1 expression, suggesting a negative role for this pathway in MT1 receptor regulation. In addition, significant increases in BDNF, GDNF and HDAC mRNA expression were observed after treatment with VPA for 24 or 48 h. Taken together, the present findings suggest that the neuroprotective properties of VPA involve modulation of neurotrophic factors and receptors for melatonin, which is also thought to play a role in neuroprotection. Moreover, the foregoing suggests that combinations of VPA and melatonin could provide novel therapeutic strategies in neurological and psychiatric disorders. [source]

    Screening for Hazardous Drinking Using the Michigan Alcohol Screening Test,Geriatric Version (MAST-G) in Elderly Persons With Acute Cerebrovascular Accidents

    ALCOHOLISM, Issue 9 2009
    Doug Johnson-Greene
    Background:, Effective and valid screening methods are needed to identify hazardous drinking in elderly persons with new onset acute medical illness. The goal of the current study was to examine the effectiveness of the Michigan Alcohol Screening Test,Geriatric Version (MAST-G) in identifying hazardous drinking among elderly patients with acute cerebrovascular accidents (CVA) and to compare the effectiveness of 2 shorter versions of the MAST-G with the full instrument. Methods:, The study sample included 100 men and women who averaged 12 days posthemorrhagic or ischemic CVA admitted to a rehabilitation unit and who were at least 50 years of age and free of substance use other than alcohol. This cross-sectional validation study compared the 24-item full MAST-G, the 10-item Short MAST-G (SMAST-G), and a 2-item regression analysis derived Mini MAST-G (MMAST-G) to the reference standard of hazardous drinking during the past 3 months. Alcohol use was collected using the Timeline Followback (TLFB). Recent and lifetime alcohol-related consequences were collected using the Short Inventory of Problems (SIP). Results:, Nearly one-third (28%) of the study sample met the World Health Organization (WHO) criteria for hazardous drinking. Moderately strong associations were found for the MAST-G, SMAST-G, and MMAST-G with alcohol quantity and frequency and recent and lifetime alcohol consequences. All 3 MAST-G versions could differentiate hazardous from nonhazardous drinkers and had nearly identical area under the curve characteristics. Comparable sensitivity was found across the 3 MAST-G measures. The optimal screening threshold for hazardous drinking was 5 for the MAST-G, 2 for the SMAST-G, and 1 for the MMAST-G. Conclusions:, The 10-item SMAST-G and 2-item MMAST-G are brief screening tests that show comparable effectiveness in detecting hazardous drinking in elderly patients with acute CVA compared with the full 24-item MAST-G. Implications for research and clinical practice are discussed. [source]

    Considering the care of the suicidal client and the case for ,engagement and inspiring hope' or ,observations'

    J. R. Cutcliffe rmn rgn bsc (hons) phd
    Psychiatric/mental health (P/MH) nursing has rightly been described as a ,broad church', and one that contains many contested matters and areas of differing opinion. One such contested matter is that of the appropriate care for the person who is at risk of suicide. Recent, albeit limited, debate of this issue has taken place, and the literature, such as it is, indicates two principal (though linked) positions. These can be summarized as the ,engagement and hope inspiration' position and the ,observations' position. Given the P/MH nurse's unique position in providing 24-hour, day-to-day care to suicidal clients and the growing problem of suicide within people who suffer from mental health problems, it is both necessary and perhaps timely to consider this debate in more detail. Accordingly, this paper considers the debate regarding care for suicidal mental health care clients. First, the paper briefly describes the historical policy context of care for the suicidal client. Next, it focuses on ,observations' and concludes that there is a range of well-established, empirically based problems or drawbacks to this approach. Following this, it focuses on ,engagement, inspiring hope' and points out the key processes of engagement: forming a relationship, a human,human connection, conveying acceptance and tolerance, and hearing and understanding. The value and importance of these most fundamental of interpersonal processes is described and alluded to throughout the limited research into care of the suicidal client. The paper then describes the range of criticisms that have been levelled at the engagement,inspiring hope approach and considers these criticisms in more detail. As a result of this detailed examination, the paper then reiterates the need to replace ,observations' with ,engagement,hope inspiration' as the principal approach to caring for suicidal mental health clients. [source]

    Multiprofessional clinical supervision: challenges for mental health nurses

    K. Mullarkey ma bsc(hons) rn cpncert rnt
    Recent reform and developments in mental health care provision have increasingly espoused the value of multiprofessional teamwork in order to ensure that clients are offered co-ordinated packages of care that draw on the full range of appropriate services available (DoH 1999a; DoH 2000). Supervision in some form is seen as a key part of all professional practice to provide support to practitioners, enhance ongoing learning, and, to a greater or lesser degree, offer some protection to the public (Brown & Bourne 1996, UKCC 1996). Clinical supervision has gained increasing momentum within the nursing profession, but to a large extent this has been within a uni-professional framework , nurses supervising other nurses. This paper seeks to explore the ways in which multiprofessional working and clinical supervision interlink, and whether supervision across professional boundaries might be desirable, possible, and/or justifiable. Whilst our own view is that multiprofessional supervision is both possible and desirable, we seek to open up a debate, from our perspective as mental health nurses, about some of the issues related to the concept. Our motivation to explore this topic area emanates from our experiences as supervisors to colleagues within multiprofessional teams, as well as the experiences of those attending supervisor training courses. Following a brief overview of the development of clinical supervision in mental health care and recent policy guidelines, some models of clinical supervision are reviewed in terms of their suitability and applicability for multiprofessional working. [source]

    Seasonal records of climatic change in annually laminated tufas: short review and future prospects,

    J. E. Andrews
    Abstract Many Recent and fossil freshwater tufa stromatolites contain millimetre-scale, alternating laminae of dense micrite and more porous or sparry crystalline calcites. These alternating laminae have been interpreted to represent seasonally controlled differences in the biotic activity of microbes, and/or seasonally controlled changes in the rate of calcification. Either way, couplets of these microbially mediated alternating calcified laminae are generally agreed to represent annual seasonality. Combined stable isotope (,18O and ,13C) and trace element (Mg, Sr, Ba) geochemistry from Recent tufa stromatolites show that seasonal climatic information is available from these calcites. Variability in ,18O (and in one case Mg concentration) has been shown to be controlled primarily by stream temperature change, usually driven by solar insolation. In arid climates, seasonal evaporation can also cause ,18O enrichment by at least 1,. Variability in ,13C results potentially from: (1) seasonal change in plant uptake of 12C-enriched CO2; (2) seasonal change in degassing of 12C-enriched CO2 in the aquifer system; and (3) precipitation of calcite along the aquifer or river flow path, a process that increases ,13C of dissolved inorganic carbon (DIC) in the remaining water. Mechanisms 2 and 3 are linked because calcite precipitates in aquifers where degassing occurs, e.g. air pockets. The latter mechanism for ,13C enrichment has also been shown to cause sympathetic variation between trace element/Ca ratios and ,13C because trace elements with partition coefficients much greater than 1 (e.g. Sr, Ba) remain preferentially in solution. Since degassing in air pockets will be enhanced during decreased recharge when water saturation of the aquifer is lowest, sympathetic variation in trace element/Ca ratios and ,13C is a possible index of recharge and therefore precipitation intensity. High-resolution geochemical data from well-dated tufa stromatolites have great potential for Quaternary palaeoclimate reconstructions, possibly allowing recovery of annual seasonal climatic information including water temperature variation and change in rainfall intensity. However, careful consideration of diagenetic effects, particularly aggrading neomorphism, needs to be the next step. Copyright © 2005 John Wiley & Sons, Ltd. [source]

    Capability as Opportunity: How Amartya Sen Revises Equal Opportunity

    Harlan Beckley
    Although the concept of equal opportunity has received scant attention from theological ethics, it attracts widespread approval in the U.S. popular culture and has been examined extensively by contemporary moral philosophy. Amartya Sen's conception of capabilities as "freedom" or "real opportunity" corrects deficiencies in both popular and philosophical conceptions of equal opportunity that ignore interpersonal variations in mental, physical, and psychological abilities beyond agents' control. Recent theologically informed conceptions of love and common grace affirm and revise Sen's conception of equal capability as equal opportunity. The resulting understanding of equal opportunity is quite different from some uses of this concept and could be an important criterion for a just society. [source]

    Particle Rearrangement and Pore Space Coarsening During Solid-State Sintering

    Hans Eckart Exner
    Coarsening of porosity during sintering has been observed in powder compacts of metallic, ceramic, and amorphous materials. Monitoring and modelling of the growth of individual (closed) pores in the late sintering stages are well established. Porosity is interconnected up to very high densities. Coarsening of the continuous pore space takes place during the initial and intermediate sintering stages. This coarsening is caused by localized transport of atoms or molecules (diffusion or viscous flow) as well as by bulk particle movement (rearrangement). Its quantitative exploration poses problems both experimentally and theoretically. Ways to characterize the geometry of the interconnected pore space and of closed pores are discussed with emphasis on stereological parameters. Recent and classical approaches, experimental findings with 2D model arrangements (as the formation and opening up of particle contacts, pore coarsening, and particle rearrangement) and some advances of computer simulations are discussed together with open questions. [source]

    Review article: gene therapy, recent developments and future prospects in gastrointestinal oncology

    Y. Touchefeu
    Aliment Pharmacol Ther 2010; 32: 953,968 Summary Background, Gene therapy consists of the introduction of genetic material into cells for a therapeutic purpose. A wide range of gene therapy vectors have been developed and used for applications in gastrointestinal oncology. Aim, To review recent developments and published clinical trials concerning the application of gene therapy in the treatment of liver, colon and pancreatic cancers. Methods, Search of the literature published in English using the PubMed database. Results, A large variety of therapeutic genes are under investigation, such as tumour suppressor, suicide, antiangiogenesis, inflammatory cytokine and micro-RNA genes. Recent progress concerns new vectors, such as oncolytic viruses, and the synergy between viral gene therapy, chemotherapy and radiation therapy. As evidence of these basic developments, recently published phase I and II clinical trials, using both single agents and combination strategies, in adjuvant or advanced disease settings, have shown encouraging results and good safety records. Conclusions, Cancer gene therapy is not yet indicated in clinical practice. However, basic and clinical advances have been reported and gene therapy is a promising, new therapeutic approach for the treatment of gastrointestinal tumours. [source]

    Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel

    C. S. KWOK
    Summary Background, Recent studies have suggested an adverse interaction between proton pump inhibitors (PPI) and clopidogrel. Aim, To perform a meta-analysis of cardiovascular outcomes and mortality in patients taking clopidogrel, with and without concomitant PPI. Methods, We searched MEDLINE, EMBASE, Cochrane Controlled Trials Register in October 2009, and checked conference abstracts for randomized and nonrandomized studies that reported the risk of cardiovascular events and mortality with PPI exposure in patients taking clopidogrel. We performed random effects meta-analysis, stratified by study design and assessed heterogeneity using the I2 statistic. Results, Our review included 23 studies covering 93 278 patients. There was substantial heterogeneity in the meta-analyses of major cardiovascular events (19 studies, I2 = 79%) or myocardial infarction (12 studies, I2 = 77%). Analysis of propensity-matched or randomized trial participants showed no associated cardiovascular risk with PPIs, whereas other observational studies generally showed a significant association. Meta-analysis of 13 studies showed no significant association between PPI use and overall mortality (RR 1.09, 95% CI: 0.94,1.26, P = 0.23, I2 = 60%). Conclusion, As there are conflicting and inconsistent data regarding the adverse clopidogrel,PPI interaction, clinicians should focus on potential harm from ulcers/haemorrhage before deciding to omit PPIs in patients taking clopidogrel. [source]