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Distribution within Medical Sciences

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  • Selected Abstracts

    Update of the molecular basis of familial hypercholesterolemia in The Netherlands,

    HUMAN MUTATION, Issue 6 2005
    Sigrid W. Fouchier
    Abstract Autosomal-dominant hypercholesterolemia (ADH) has been identified as a major risk factor for coronary vascular disease (CVD) and is associated with mutations in the low-density lipoprotein receptor (LDLR) and the apolipoprotein B (APOB) gene. Since 1991 DNA samples from clinically diagnosed ADH patients have been routinely analyzed for the presence of LDLR and APOB gene mutations. As of 2001, 1,641 index patients (164 index patients per year) had been identified, while from 2001 onward a more sensitive, high-throughput system was used, resulting in the identification of 1,177 new index patients (average=294 index patients per year). Of these 1,177 index cases, 131 different causative genetic variants in the LDLR gene and six different causative mutations in the APOB gene were new for the Dutch population. Of these 131 mutations, 83 LDLR and four APOB gene mutations had not been reported before. The inclusion of all 2,818 index cases into the national screening program for familial hypercholesterolemia (FH) resulted in the identification of 7,079 relatives who carried a mutation that causes ADH. Screening of the LDLR and APOB genes in clinically diagnosed FH patients resulted in approximately 77% of the patients being identified as carriers of a causative mutation. The population of patients with ADH was divided into three genetically distinct groups: carriers of an LDLR mutation (FH), carriers of an APOB mutation (FDB), and non- LDLR/non- APOB patients (FH3). No differences were found with regard to untreated cholesterol levels, response to therapy, and onset of CVD. However, all groups were at an increased risk for CVD. Therefore, to ultimately identify all individuals with ADH, the identification of new genes and mutations in the genes that cause ADH is of crucial importance for the ongoing national program to identify patients with ADH by genetic cascade screening. Hum Mutat 26(6), 550,556, 2005. © 2005 Wiley-Liss, Inc. [source]

    Correlation between NT-pro BNP Levels and Early Mitral Annulus Velocity (E,) in Patients with Non,ST-Segment Elevation Acute Coronary Syndrome

    ECHOCARDIOGRAPHY, Issue 4 2008
    Marcia M. Barbosa M.D., Ph.D.
    Acute coronary syndromes in the absence of ST-segment elevation (NSTE-ACS) are a heterogeneous entity in which early risk stratification is essential. Diastolic dysfunction is precocious and associated with poor prognosis. BNP has been recognized as a biochemical marker of ventricular dysfunction and ischemia. Objective: To investigate if there is correlation of NT pro-BNP levels with diastolic dysfunction in patients with NSTE-ACS. Methods: Fifty-two patients with NSTE-ACS admitted to the coronary unit were included. NT-pro brain natriuretic hormone (BNP) levels and a Doppler echocardiogram were obtained in all and systolic and diastolic functions were analyzed. Their Doppler indexes were compared with those of 53 age- and sex-matched controls, without heart failure symptoms and with normal ejection fraction (EF) and normal NT-pro BNP levels. Results: Twenty-four patients (46%) with unstable angina and 28 patients (54%) with acute myocardial infarction (AMI) were included. Mean EF was 55.9 ± 10.7% and mean NT-pro BNP level was 835 ± 989 pg/ml. No mitral or pulmonary venous flow parameters of diastolic function correlated with NT-pro BNP levels. E,/A, correlated with NT-pro BNP level in univariate analysis but, in a multivariate analysis, only the EF and the E, showed negative correlation with the peptide level (r =,0.33, P = 0.024 and r =,0.29, P = 0.045, respectively). Thirteen patients presented with stage II diastolic dysfunction but the NT-pro BNP level in these patients did not differ from the level in stage I patients. Conclusion: NT-pro BNP levels are elevated in acute coronary syndromes, even in the absence of significant necrosis. Of all echocardiographic parameters investigated, only E, and the EF correlated with the levels of NT-pro BNP in this group of patients. [source]

    Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors

    L. M. Marubio
    Abstract The mesostriatal dopaminergic system influences locomotor activity and the reinforcing properties of many drugs of abuse including nicotine. Here we investigate the role of the ,4 nicotinic acetylcholine receptor (nAChR) subunit in mediating the effects of nicotine in the mesolimbic dopamine system in mice lacking the ,4 subunit. We show that there are two distinct populations of receptors in the substantia nigra and striatum by using autoradiographic labelling with 125I ,-conotoxin MII. These receptors are comprised of the ,4, ,2 and ,6 nAChR subunits and non-,4, ,2, and ,6 nAChR subunits. Non-,4 subunit-containing nAChRs are located on dopaminergic neurons, are functional and respond to nicotine as demonstrated by patch clamp recordings. In vivo microdialysis performed in awake, freely moving mice reveal that mutant mice have basal striatal dopamine levels which are twice as high as those observed in wild-type mice. Despite the fact that both wild-type and ,4 null mutant mice show a similar increase in dopamine release in response to intrastriatal KCl perfusion, a nicotine-elicited increase in dopamine levels is not observed in mutant mice. Locomotor activity experiments show that there is no difference between wild-type and mutant mice in basal activity in both habituated and non-habituated environments. Interestingly, mutant mice sustain an increase in cocaine-elicited locomotor activity longer than wild-type mice. In addition, mutant mice recover from depressant locomotor activity in response to nicotine at a faster rate. Our results indicate that ,4-containing nAChRs exert a tonic control on striatal basal dopamine release, which is mediated by a heterogeneous population of nAChRs. [source]

    Research Techniques and Their Use in Managing Non,profit Organisations , An Illustration of DEA Analysis in NPO Environments

    Jarmo Vakkuri
    This article examines nonprofit organisations from the managerial viewpoint. The objective is to study the applicability of efficiency information in managing NPOs. For this purpose important conceptual and methodological aspects are addressed. An efficiency measurement technique (DEA) is then analysed as a case in point, and its main characteristics critically reviewed. DEA applications in four NPO environments are examined. The aim is to pinpoint possibilities and limitations in using DEA,based efficiency information in the management process of NPOs. The article argues in favour of a more profound comprehension of the use of efficiency information and the application of research techniques. [source]

    Legitimacy and the Privatization of Environmental Governance: How Non,State Market,Driven (NSMD) Governance Systems Gain Rule,Making Authority

    GOVERNANCE, Issue 4 2002
    Benjamin Cashore
    In recent years, transnational and domestic nongovernmental organizations have created non,state market,driven (NSMD) governance systems whose purpose is to develop and implement environmentally and socially responsible management practices. Eschewing traditional state authority, these systems and their supporters have turned to the market's supply chain to create incentives and force companies to comply. This paper develops an analytical framework designed to understand better the emergence of NSMD governance systems and the conditions under which they may gain authority to create policy. Its theoretical roots draw on pragmatic, moral, and cognitive legitimacy granting distinctions made within organizational sociology, while its empirical focus is on the case of sustainable forestry certification, arguably the most advanced case of NSMD governance globally. The paper argues that such a framework is needed to assess whether these new private governance systems might ultimately challenge existing state,centered authority and public policy,making processes, and in so doing reshape power relations within domestic and global environmental governance. [source]

    Non- pylori Helicobacteraceae in the Upper Digestive Tract of Asymptomatic Venezuelan Subjects: Detection of Helicobacter cetorum- like and Candidatus Wolinella africanus -like DNA

    HELICOBACTER, Issue 5 2007
    M. Alexandra García-Amado
    Abstract Background: The spectrum of human non- pylori Helicobacter infections is expanding, with species such as H. heilmannii and H. felis occasionally being associated with gastritis. However, the existence of non- pylori Helicobacter colonization in asymptomatic subjects has not been evaluated. The aim of this study was to investigate whether Helicobacter species other than pylori are present in the upper digestive tract of asymptomatic human subjects. Materials and methods: A Helicobacteraceae-specific semi-nested polymerase chain reaction (PCR) assay was used to detect Helicobacter- like organisms in the upper digestive tract of 91 Venezuelan volunteers (aged 18,68 years, 41 females, 50 males). Species were identified by denaturing gradient gel electrophoresis analysis and sequencing of the PCR products. Results: We detected DNA sharing 99,100% sequence identity in over 300,400 bp with the 16S rRNA genes of H. pylori, H. cetorum, and Candidatus Wolinella africanus in 76%, 16%, and 15% of the subjects, respectively. Multiple colonization was documented in 10% of the subjects: H. cetorum and Candidatus W. africanus (4%), H. pylori and Candidatus W. africanus (4%), and H. pylori and H. cetorum (2%). Conclusions: Our results suggest that non- pylori Helicobacteraceae colonization is relatively common in the Venezuelan asymptomatic population. This is the first report documenting the presence of H. cetorum DNA in the human upper digestive tract, and the second report of the recently discovered Candidatus W. africanus. [source]

    Non,Born,Oppenheimer calculations of the ground state of H3

    Mauricio Cafiero
    Abstract We present quantum,mechanical calculations for the ground state of the H3 system performed without the Born-Oppenehimer approximation. In the calculations we use explicitly correlated Gaussian basis functions that explicitly depend on all of the interparticle distances. These basis functions allow us to achieve high accuracy while explicitly describing nucleus,nucleus, nucleus,electron, and electron,electron correlation effects. Gaussian basis sets ranging in size from 85 to 950 functions have been optimized using a gradient-based procedure. The issue of defining and extracting the H3 molecular structure based on the non-BO wave function is also discussed. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source]

    Highly Regio- and Stereoselective Iodohydroxylation of Non- Heteroatom-Substituted Allenes: An Efficient Synthesis of 4-[3,-Hydroxy-2,-iodoalk-1,(Z)-enyl]-2(5H)-furanone Derivatives

    Zhenhua Gu
    Abstract An efficient protocol for the highly regio- and stereoselective synthesis of 4-(3,-hydroxy-2,-iodoalk-1,(Z)-enyl)furan-2(5H)-one derivatives via selective iodohydroxylation of non-heteroatom-substituted allenes, i.e., 4-allenyl-2(5H)furanones, has been developed. The regio- and stereoselectivity of this reaction may be controlled by the electronic and steric effects of the furanone ring. [source]

    Non,Market Interventions in Water,Sharing:Case Studies from West Bengal, India

    Vikas Rawal
    This paper deals with two issues that are important areas of concern in the recent literature on water management in less,developed countries: forms of ownership of groundwater resources and alternatives to anarchy in the exploitation and use of groundwater. The emergence of a market for irrigation water has been argued to have the potential to provide irrigation water to large numbers of small cultivators in developing countries. The development of free markets for water, however, has also been shown to be associated with the emergence of ,water,lords' and with contracts for the purchase and sale of water that are biased against the poor. By contrast, this paper presents two examples of viable non,market interventions in water,sharing , regulation of water markets by village councils and cooperative tubewell groups , from villages in West Bengal, India. These interventions both improved the efficiency of water,use and represented relatively equitable arrangements for water,sharing. [source]

    Managerial Ownership, Information Content of Earnings, and Discretionary Accruals in a Non,US Setting

    Gorm Gabrielsen
    This study employs Danish data to examine the empirical relationship between the proportion of managerial ownership and two characteristics of accounting earnings: the information content of earnings and the magnitude of discretionary accruals. In previous research concerning American firms, Warfield et al. (1995) document a positive relationship between managerial ownership and the information content of earnings, and a negative relationship between managerial ownership and discretionary accruals. We question the generality of the Warfield et al. result, as the ownership structure found in most other countries, including Denmark, deviates from the US ownership configuration. In fact, Danish data indicate that the information content of earnings is inversely related to managerial ownership. [source]

    Non,housestaff medicine services in academic centers: Models and challenges

    Niraj L. Sehgal MD
    Abstract Non,housestaff medicine services are growing rapidly in academic medical centers (AMCs), partly driven by efforts to comply with resident duty hour restrictions. Hospitalists have emerged as a solution to providing these services given their commitment to delivering efficient and high-quality care and the field's rapid growth. However, limited evidence is available on designing these services, including the similarities and differences of existing ones. We describe non,housestaff medicine services at 5 AMCs in order to share our experiences and outline important considerations in service development. We discuss common challenges in building and sustaining these models along with local institutional factors that affect decision making. Keys to success include ensuring an equitable system for scheduling and staffing, fostering opportunities for scholarly activities and academic promotion (defining the "academic hospitalist"), and providing compensation that supports recruitment and retention of hospitalists. With further work hour restrictions expected in the future and increased requests for surgical comanagement, the relationship between AMCs and hospitalists will continue to evolve. To succeed in developing hospitalist faculty who follow long careers in hospital medicine, academic leadership must carefully plan for and evaluate the methods of providing these clinical services while expanding on our academic mission. Journal of Hospital Medicine 2008;3:247,255. © 2008 Society of Hospital Medicine. [source]

    Acute treatment of paediatric migraine: A meta-analysis of efficacy

    Shawna Silver
    Aim: To undertake a meta-analysis of all randomised controlled trials (RCTs) on the acute pharmacologic treatment of children and adolescents with migraine headache. Methods: In total, 139 abstracts of clinical trials specific to the acute treatment of paediatric migraine were appraised. Inclusion criteria required clinical trials to be randomised, blinded, placebo-controlled studies with comparable endpoints. Non- English language publications were excluded. 11 clinical trials qualified for inclusion in the final meta-analysis. Two endpoints were analysed: the proportion of patients with (1) headache relief, and (2) complete pain relief, 2 h post-treatment. Results: The following medications were included in the analysis: acetaminophen (n = 1), ibuprofen (n = 2), sumatriptan (n = 5), zolmitriptan (n = 1), rizatriptan (n = 2) and dihydroergotamine (n = 1). Results are expressed as a relative benefit (RB) conferred over placebo and the number needed to treat (NNT). Only ibuprofen and sumatriptan provided a statistically significant relative efficacy in comparison with placebo. Two hours post-treatment, ibuprofen was associated with an RB 1.50 (95% CI 1.15,1.95) in the generation of headache relief (NNT 2.4) and RB 1.92 (95% CI 1.28,2.86) in the production of complete pain relief (NNT 4.9). Sumatriptan rendered an RB 1.26 (95% CI 1.13,1.41) in headache relief (NNT 7.4) and an RB 1.56 (95% CI 1.26,1.93) in the production of complete pain relief (NNT 6.9). Conclusion: Despite the pharmacological options for the management of acute migraine, few RCTs in the paediatric population exist. Composite data demonstrate that only ibuprofen and sumatriptan are significantly more effective than placebo in the generation of headache relief in children and adolescents. [source]

    In Defence of ,Non,Expansive' Character Education

    Kristján Kristjánsson
    I first put the notion of non,expansive character education in context by locating its place within recent trends in values education and, in particular, by distinguishing it from more expansive accounts such as civic education and critical postmodernism. I argue that the essential characteristics of non,expansive character education are, on the one hand, moral cosmopolitanism and, on the other, methodological substantivism. In the second part of the essay, I defend this sort of character education against various common criticisms, with special reference to two canonical works of the movement, by Lickona and Kilpatrick. Non,expansive character education stands out, in the end, as a reasonable middle,ground proposal with neither too little nor too much meat on its bones. [source]

    Both Global Gray Matter Volume and Regional Gray Matter Volume Negatively Correlate with Lifetime Alcohol Intake in Non,Alcohol-Dependent Japanese Men: A Volumetric Analysis and a Voxel-Based Morphometry

    ALCOHOLISM, Issue 6 2006
    Yasuyuki Taki
    Background: Non,alcohol-dependent heavy drinkers, as well as alcohol-dependent individuals, show brain atrophy. The purpose of this study was to evaluate whether there are correlations between global and regional gray matter volumes and the lifetime alcohol intake using volumetric analysis and voxel-based morphometry (VBM) among Japanese non-alcohol,dependent male individuals. Methods: High-resolution three-dimensional magnetic resonance images were acquired from 405 Japanese non-alcohol,dependent male individuals. The collected images were normalized, segmented for volumetric analysis, and additionally smoothed for VBM. For volumetric analysis, the partial correlation coefficient was estimated between the gray matter ratio, which represents the percentage of gray matter volume in the intracranial volume, and the lifetime alcohol intake adjusted for the age of each subject. Multiple regression analysis was performed among regional gray matter volume, lifetime alcohol intake, and age using VBM. Results: Volumetric analysis revealed that gray matter ratio showed a negative correlation with the lifetime alcohol intake adjusted for age (p=0.059, partial correlation coefficient=,0.091). The VBM revealed that the gray matter volumes of the bilateral middle frontal gyri showed a significant negative correlation with the lifetime alcohol intake adjusted for age and systolic blood pressure (left side, p=0.006, Z=4.77; right side, p=0.023, Z=4.45, and p=0.046, Z=4.27). Conclusions: Our study suggests that non-alcohol,dependent Japanese male individuals show that both global gray matter volume and regional gray matter volume have negative correlations with the lifetime alcohol intake. Our study may contribute to clarifying the mechanism underlying the brain structural changes because of alcohol influence in healthy non-alcohol,dependent individuals. [source]

    Liver transplantation from non,heart-beating donors: Current status and future prospects

    Srikanth Reddy
    Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non,heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results. (Liver Transpl 2004;10:1223,1232.) [source]

    Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions

    ALLERGY, Issue 5 2010
    A. Vultaggio
    To cite this article: Vultaggio A, Matucci A, Nencini F, Pratesi S, Parronchi P, Rossi O, Romagnani S, Maggi E. Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy 2010; 65: 657,661. Abstract Background:, Infliximab is a chimeric monoclonal antibody against TNF-, useful in the treatment of many chronic inflammatory diseases. Severe anaphylaxis has been reported during therapy, although the exact mechanism has not been fully defined. The reactions have been related to the infliximab immunogenicity and development of specific antibodies. Aims of the study:, Evaluation of the development of IgE and non-IgE antibodies to infliximab and their relationship with infusion reaction. Methods:, Seventy-one patients (11 reactives, 11 therapeutically nonresponders, and 49 unreactive therapeutically responders) and 20 non,infliximab-exposed control subjects (ten rheumatoid arthritis, five spondyloarthropathies, five vasculitis) were evaluated for the presence of IgE (ImmunoCAP assay), IgM, and non,isotype-specific (ELISA assays) anti-infliximab antibodies. Sera were obtained at baseline and during the course of treatment, before each infliximab infusion. Results:, Eleven out of 71 patients had a hypersensitivity reaction to infliximab. Non,isotype-specific anti-infliximab antibodies were detected in eight reactive and two nonresponder patients. Three patients with severe reactions displayed anti-infliximab IgE antibodies and positive skin testing. Detectable levels of anti-infliximab IgM antibodies were shown in three additional IgE- and skin testing-negative patients. IgE and IgM antibodies to infliximab were not detectable in the two nonresponder patients. Antibodies developed before the 2nd and the 3rd infusion, and their appearance was strictly related to the timing of the reaction. Conclusions:, This report indicates that in some patients with infliximab-related severe reactions, IgE or IgM antibodies against infliximab were detectable. The majority of reactions could be predicted by the appearance of anti-infliximab antibodies. [source]

    Evolution and Free Will: A Defense of Darwinian Non,naturalism

    METAPHILOSOPHY, Issue 4 2002
    John Lemos
    In his recent book The Natural Selection of Autonomy, Bruce Waller defends a view that he calls "natural autonomy." This view holds that human beings possess a kind of autonomy that we share with nonhuman animals, a capacity to explore alternative courses of action, but an autonomy that cannot support moral responsibility. He also argues that this natural autonomy can provide support for the ethical principle of noninterference. I argue that to support the ethical principle of noninterference Waller needs either a libertarian or a compatibilist theory of autonomy. I then go on to argue that, contra Waller, the libertarian view is both compatible with Darwinism and able to make sense of how autonomous acts belong to the agents who perform them. Thus, I conclude that the libertarian position is a live option for Darwinians. If however, naturalism is taken to include a deterministic view of the universe (at least at the nonquantum level), as is often the case, then my article takes some strides in defending "Darwinian non,naturalism." [source]

    Evidence-based medical review update: Pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004

    MOVEMENT DISORDERS, Issue 5 2005
    Christopher G. Goetz MD
    Abstract The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001,January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non - Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non - efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner. © 2005 Movement Disorder Society [source]

    Attempts to Reduce and Eliminate Nuclear Weapons through the Nuclear Non -Proliferation Treaty and the Creation of Nuclear -Weapon -Free Zones

    PEACE & CHANGE, Issue 4 2008
    Paul J. Magnarella
    Nuclear weapons remain the most dangerous weapons of mass destruction threatening our lives and planet. To date, the Nuclear Non-Proliferation Treaty (NPT) is the most comprehensive international agreement aimed at limiting these weapons. In response to some of NPT's shortcomings, a large number of nonnuclear weapon states have joined together to create nuclear-weapon-free zones (NWFZs). By doing so, they emphatically rejected nuclear weapons on their soil, in their territorial waters, and in their air space. In addition, they ask nuclear weapon states to solemnly promise not to use nuclear weapons against zone members and to do nothing to promote nuclear weapons in their zones. Currently, much of the Southern Hemisphere is covered by NWFZs. An NWFZ has been newly created in Central Asia, and the League of Arab States is considering one in the Middle East. [source]

    VIII,Cognitive Expressivism, Faultless Disagreement, and Absolute but Non -Objective Truth

    Stephen Barker
    I offer a new theory of faultless disagreement, according to which truth is absolute (non-relative) but can still be non-objective. What's relative is truth-aptness: a sentence like ,Vegemite is tasty' (V) can be truth-accessible and bivalent in one context but not in another. Within a context in which V fails to be bivalent, we can affirm that there is no issue of truth or falsity about V, still disputants, affirming and denying V, were not at fault, since, in their context of assertion V was bivalent. This theory requires a theory of assertion that is a form of cognitive expressivism. [source]

    XIV,Moral Non -Cognitivism and the Grammar of Morality

    Michael Blome-Tillmann
    This paper investigates the linguistic basis for moral non-cognitivism, the view that sentences containing moral predicates do not have truth conditions. It offers a new argument against this view by pointing out that the view is incompatible with our best empirical theories about the grammatical encoding of illocutionary force potentials. Given that my arguments are based on very general assumptions about the relations between the grammar of natural languages and a sentence's illocutionary function, my arguments are broader in scope than the familiar semantic objections to non-cognitivism relating to the so-called Frege-Geach problem: even if a solution to the Frege-Geach problem has been found, my arguments still stand. [source]

    Samuel Todes's Account of Non,conceptual Perceptual Knowledge and its Relation to Thought

    RATIO, Issue 4 2002
    Hubert L. Dreyfus
    Samuel Todes's book, Body and World, makes an important contribution to the current debate among analytic philosophers concerning non,conceptual intentional content and its relation to thought. Todes's relevant theses are: (1) Our unified, active body, in moving to meet our needs, generates a unified, spatio,temporal field. (2) In that field we use our perceptual skills to make the determinable perceptual objects that show up relatively determinate. (3) Once we have made the objects of practical perception determinate, we can make ,practical perceptual judgements' about them. Such ,judgements' have conditions of satisfaction, but they are non,conceptual in that they are a way of coping with an actual object in this situation, from this point of view, in this light, in this orientation, and so forth. (4) By withholding our activity, however, we can transform our practical perception into a detached, spectatorial perception of qualities that are experienced as independent of the object they qualify. (5) Thanks to our conceptual imagination, we can then treat these qualities as reidentifiable properties of reidentifiable objects that can be entertained by thought. [source]

    Human liver-derived cells stably modified for regulated proinsulin secretion function as bioimplants in vivo

    Xiang Chen
    Abstract Background Insulin deficiency is currently treated with pharmacological insulin secretagogues, insulin injections or islet transplants. Secondary failure of pharmacological agents is common; insulin injections often fail to achieve euglycemic control; and islet transplants are rare. Non-, cells capable of regulated insulin secretion in vivo could be a functional cure for diabetes. Hepatocytes are good candidates, being naturally glucose-responsive, protein-secreting cells, while the liver is positioned to receive direct nutrient signals that regulate insulin production. Methods Human liver-derived Chang cells were modified with a plasmid construct in which a bifunctional promoter comprising carbohydrate response elements and the human metallothionein IIA promoter controlled human proinsulin cDNA expression. Secretory responses of stable cell clones were characterized in vitro and in vivo by proinsulin radioimmunoassay. Results Transfected Chang cells secreted 5,8,pmol proinsulin/106 cells per 24,h in continuous passage for at least a year in response to 5,25,mM glucose and 10,90,µM zinc in vitro. Glucose and zinc synergistically increased proinsulin production by up to 30-fold. Non-glucose secretagogues were also active. Glucose transporter 2 (GLUT2) and glucokinase cDNA co-transfection enhanced glucose responsiveness. Intraperitoneally implanted Chang cells secreted proinsulin in scid and Balb/c mice. Serum proinsulin levels were further increased 1.3-fold (p<0.05) after glucose and 1.4- to 1.6-fold (p<0.005) after zinc administration in vivo. Conclusions These results are the first to demonstrate stable proinsulin production in a human liver-derived cell line with activity in vitro and in vivo and provide a basis for engineering hepatocytes as in vivo bioimplants for future diabetes treatment. Copyright © 2002 John Wiley & Sons, Ltd. [source]

    Comparison of Economic Efficiency Estimation Methods: Parametric and Non,parametric Techniques

    Hsin Huang
    We employ a wide range of parametric and non,parametric cost frontiers' efficiency estimation methods to estimate economic efficiency and economies of scale, using the same panel data of 22 Taiwanese commercial banks over the period 1982,97. According to our empirical implementation, the two methodologies yield similar average efficiency estimates, yet they come to very dissimilar results pertaining to the efficiency rankings, the stability of measured efficiency over time, the consistency between frontier efficiency and conventional performance measures, and the estimates of scale economies. Thus, the choice of an estimation approach can result in very different conclusions and policy implications regarding cost efficiencies and cost economies. These findings suggest that making policy decisions and evaluations relies on multiple techniques and specifications. [source]

    Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

    ARTHRITIS & RHEUMATISM, Issue 8 2009
    Khalid Muhammad
    Objective Transient B cell depletion by rituximab has been used with clinical efficacy in the treatment of patients with rheumatoid arthritis (RA). Previous studies of B cell repopulation have shown long-term numerical reduction in memory B cells. Non,class-switched IgD+CD27+ memory B cells, in particular, repopulate slowly. This study was undertaken to determine whether mutational acquisition in individual B cell receptors in repopulating class-switched and non,class-switched memory B cells is affected by rituximab. Methods Cells obtained from 16 RA patients, 4 healthy donors, and 3 patients who underwent allogeneic stem cell transplantation (ASCT) were analyzed using single B cell sorting followed by nested polymerase chain reaction and Ig VH3 sequencing. Results There was a delayed acquisition of mutations in Ig receptors of IgD+ memory B cells over a period of 6 years after a single course of rituximab. One year after rituximab treatment, 84% of single repopulating IgD+CD27+ B cells were unmutated, and no highly mutated Ig receptors were found (compared with 52% before therapy). Over time, increasing numbers of mutations were detected. Even 6 years after rituximab treatment, however, mutations in IgD+ memory B cells were still significantly reduced. In contrast, class-switched memory B cells repopulated with quantitatively normal mutations. In comparison, in patients undergoing ASCT, IgD+ memory cells repopulated earlier with higher mutations in Ig receptors. Conclusion Our data suggest that IgD+ memory B cells are particularly susceptible to the effects of rituximab, with delayed acquisition of mutations in their Ig receptors still evident 6 years after a single course of rituximab. Our findings indicate that these cells have different requirements for mutational acquisition compared with class-switched memory B cells. [source]

    The (Non-)Equivalence of Input and Output Taxes Under Monopoly

    Thorsten Bay, r-Upmann
    The author argues that a government taxing a polluting monopoly by means of levies on output and inputs can implement the first-best allocation through a continuum of tax profiles. Using this degree of freedom in the tax system, the government is, in general, able to transfer income from the firm to the public sector, so that the additional tax rate acts as a non-distorting tax on profits. This transfer , and therefore public revenue , is the higher, the lower (higher) the input taxes are, and correspondingly the higher (lower) the output tax is, provided that the production function exhibits decreasing (increasing) returns to scale. [source]

    Gender Differences in the Treatment of Non,ST-Segment Elevation Myocardial Infarction

    Valeria Rac MD
    No abstract is available for this article. [source]

    Prehospital Electrocardiograms (ECGs) Do Not Improve the Process of Emergency Department Care in Hospitals with Higher Usage of ECGs in Non,ST-segment Elevation Myocardial Infarction Patients

    CLINICAL CARDIOLOGY, Issue 12 2009
    Michael T. Cudnik
    Background This article will describe the impact of prehospital electrocardiogram (ECG) use on emergency department (ED) processes of care for non,ST-segment elevation myocardial infarction (NSTEMI) patients and assess the characteristics associated with prehospital ECG use. Methods This is a retrospective, multicenter, observational analysis of NSTEMI patients captured by the National Cardiovascular Data Registry-Acute Coronary Treatment and Intervention Outcomes Network Registry,Get with the Guidelines (NCDR ACTION-GWTG) in 2007. Patient and hospital data were stratified by documentation of a prehospital ECG (pECG). Hospitals were stratified into tertiles of pECG use by higher pECG (>5.6%, n 91), lower pECG (, 5.6%, n = 83), or no pECG (n = 100). Statistical evaluation was done via Wilcoxon rank sum and ,2 tests. Results There were 21 251 patients eligible for analysis. A pECG was documented in 1609 (7.6%) patients. Of 274 hospitals, 100 (36.5%) had no pECGs recorded. Median ED length of stay (LOS) was shorter at no pECG hospitals vs lower pECG hospitals (3.97 h vs 4.12 h, P < 0.05), but not higher pECG hospitals vs no pECG hospitals (3.85 h vs 3.97 h, P = not significant [NS]). A pECG was not associated with an improvement in ED performance metrics (use of aspirin, ,-blocker, any heparin) in the higher pECG hospitals vs no pECG hospitals or the lower pECG hospitals vs no pECG hospitals. Conclusions Use of prehospital ECG in NSTEMI patients is uncommon. In contrast to its impact on reperfusion times in ST-segment elevation myocardial infarction (STEMI) patients, its use does not appear to be associated with an improvement in ED processes of care at the hospital level. Copyright © 2009 Wiley Periodicals, Inc. [source]

    The Impact of Race on the Acute Management of Chest Pain

    Arvind Venkat MD
    Abstract Objectives: African Americans with acute coronary syndromes receive cardiac catheterization less frequently than whites. The objective was to determine if such disparities extend to acute evaluation and noninterventional treatment. Methods: Data on adults with chest pain (N= 7,935) presenting to eight emergency departments (EDs) were evaluated from the Internet Tracking Registry of Acute Coronary Syndromes. Groups were selected from final ED diagnosis: 1) acute myocardial infarction (AMI), n= 400; 2) unstable angina/non,ST-elevation myocardial infarction (UA/NSTEMI), n= 1,153; and 3) nonacute coronary syndrome chest pain (non-ACS CP), n= 6,382. American College of Cardiology/American Heart Association guidelines for AMI and UA/NSTEMI were used to evaluate racial disparities with logistic regression models. Odds ratios (ORs) were adjusted for age, gender, guideline publication, and insurance status. Non-ACS CP patients were assessed by comparing electrocardiographic (ECG)/laboratory evaluation, medical treatment, admission rates, and invasive and noninvasive testing for coronary artery disease (CAD). Results: African Americans with UA/NSTEMI received glycoprotein IIb/IIIa receptor inhibitors less often than whites (OR, 0.41; 95% CI = 0.19 to 0.91). African Americans with non-ACS CP underwent ECG/laboratory evaluation, medical treatment, and invasive and noninvasive testing for CAD less often than whites (p < 0.05). Other nonwhites with non-ACS CP were admitted and received invasive testing for CAD less often than whites (p < 0.01). African Americans and other nonwhites with AMI underwent catheterization less frequently than whites (OR, 0.45; 95% CI = 0.29 to 0.71 and OR, 0.40; 95% CI = 0.17 to 0.92, respectively). A similar disparity in catheterization was noted in UA/NSTEMI therapy (OR, 0.53; 95% CI = 0.40 to 0.68 and OR, 0.68; 95% CI = 0.47 to 0.99). Conclusions: Racial disparities in acute chest pain management extend beyond cardiac catheterization. Poor compliance with recommended treatments for ACS may be an explanation. [source]

    Factors Associated with the Development of Board Sub,committees

    Elizabeth Carson
    This study examines the factors associated with the presence of board sub,committees, specifically audit, remuneration and nomination committees. Factors which are hypothesised in this study to affect sub,committee presence are Big 6 auditors, non,executive directors, non,executive chairmen, number of intercorporate relationships of the board and shareholder type. Company size, number of board members and leverage are employed as control variables as suggested by earlier research. An analysis of board sub,committees in the Australian corporate environment is relevant to other jurisdictions as there are no mandatory requirements on either board composition or board sub,committees. There is, however, a mandatory requirement to disclose corporate governance practices which allows for a study of this type to be reliably conducted. A sample of 361 Australian companies drawn from the largest 500 public companies is employed. Audit committee presence is found to be positively associated with Big 6 auditors and the number of intercorporate relationships of the directors of the board. Remuneration committees are also found to be associated with Big 6 auditors and intercorporate relationships and also higher levels of institutional investment. The presence of nomination committees is not associated with auditors, directors or investors, but is associated with board size and leverage. The study concludes that audit committees are a highly developed and mature governance mechanism, and that remuneration committees can be classed as a developing and maturing structure whilst nomination committees are relatively immature. [source]