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Kinds of Might Selected AbstractsRapid and easy semi-quantitative evaluation method for diacylglycerol and inositol-1,4,5-trisphosphate generation in orexin receptor signallingACTA PHYSIOLOGICA, Issue 3 2010M. E. Ekholm Abstract Aim:, Fluorescent protein-based indicators have enabled measurement of intracellular signals previously nearly inaccessible for studies. However, indicators showing intracellular translocation upon response suffer from serious limitations, especially the very time-consuming data collection. We therefore set out in this study to evaluate whether fixing and counting cells showing translocation could mend this issue. Methods:, Altogether three different genetically encoded indicators for diacylglycerol and inositol-1,4,5-trisphosphate were transiently expressed in Chinese hamster ovary cells stably expressing human OX1 orexin receptors. Upon stimulation with orexin-A, the cells were fixed with six different protocols. Results:, Different protocols showed clear differences in their ability to preserve the indicator's localization (i.e. translocation after stimulus) and its fluorescence, and the best results for each indicator were obtained with a different protocol. The concentration,response data obtained with cell counting are mostly comparable to the real-time translocation and biochemical data. Conclusion:, The counting method, as used here, works at single time point and looses the single-cell-quantitative aspect. However, it also has some useful properties. First, it easily allows processing of a 100- to 1000-fold higher cell numbers than real-time imaging producing statistically consistent population-quantitative data much faster. Secondly, it does not require expensive real-time imaging equipment. Fluorescence in fixed cells can also be quantitated, though this analysis would be more time-consuming than cell counting. Thirdly, in addition to the quantitative data collection, the method could be applied for identifying responsive cells. This might be very useful in identification of e.g. orexin-responding neurones in a large population of non-responsive cells in primary cultures. [source] Contamination by nickel, copper and zinc during the handling of euro coinsCONTACT DERMATITIS, Issue 4 2003Paul-Guy Fournier The introduction of the euro has revived interest in the risk of nickel allergy due to the handling of coins. In the present work, the transfer of metallic contamination during the manipulation of coins is examined by means of leaching experiments and manipulation tests. It is shown that pre-existing metallic species present on the surface of the coins are the major source of contamination during manipulation, and that friction inherent to everyday usage contributes predominantly to their transfer to the hands. The comparison of coins as to their relative risks of metal contamination should therefore rely on tests that simulate the friction inherent in everyday human handling. Carrying out such tests with the newly issued 1, and 2, pieces, we find, contrary to long-term leaching measurements, that the euros release less nickel than previously circulated pure-nickel coins, but that this decrease is less pronounced than might have been hoped for on the basis of their surface composition. When the coins are rubbed to a shiny polish before manipulation, contamination of the fingers is reduced by more than a factor of 10. A comparison of coins used in France indicates that the introduction of the common currency has led to a fourfold reduction in contamination by nickel, while causing a 45% increase in contamination by copper. [source] The Coming Transformation of Shareholder ValueCORPORATE GOVERNANCE, Issue 1 2005Simon Deakin This essay challenges the primacy of shareholder value. Shareholder primacy originates not in company law, but rather in the norms and practices surrounding the rise of the hostile takeover movement in Britain and America in the 1970s and 1980s. It is less strongly institutionalised than might be supposed, because it is essentially a cultural rather than a legal point of reference. Moreover, in the course of the past decade, a shift in the content of shareholder value has occurred which reflects the stakeholder critique of that period: this reflects the idea that shareholders should exercise their power not as representatives of the market, but as agents of society as a whole. The corporate governance of the future will be centrally concerned with how this idea is worked out in practice. [source] Corporate Governance and Capital Structure Decisions of the Chinese Listed FirmsCORPORATE GOVERNANCE, Issue 2 2002Yu Wen This paper studies the relationship between some characteristics of the corporate board and the firm's capital structure in Chinese listed firms. The findings provide some preliminary empirical evidence and seem to suggest that managers tend to pursue lower financial leverage when they face stronger corporate governance from the board. However, the empirical results of the relationships are statistically significant only in the case of the board composition and the CEO tenure. The results are statistically insignificant in the case of the board size and fixed CEO compensation. This may in general suggest that, up to the time period of our investigation, the corporate board structures and processes in Chinese listed firms might not as yet be fully working in the manner, or as well, as might have been so far assumed on the basis of Western theoretical finance literature. [source] Can services lead to radical eco-efficiency improvements?CORPORATE SOCIAL RESPONSIBILITY AND ENVIRONMENTAL MANAGEMENT, Issue 4 2003a review of the debate, evidence Eco-efficient services, or sustainable product,service systems, are a popular topic in discussions on sustainability and eco-efficiency. In these discussions, ,service' actually refers to many different things. It may refer to the role of the service sector in the economy, or to a new business strategy, or to the service (utility) provided by a product. Furthermore, the discussion on eco-efficient services has been linked to concepts such as the ,new', ,experience' or ,customized' economy. The article analyses the central arguments and evidence put forth in the discussion on eco-efficient services. The findings address questions occupying policy-makers, managers and researchers: how relevant are eco-efficient services in environmental management, and what might be the next steps in exploring their potential? Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment. [source] QTc-interval abnormalities in a forensic populationCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 2 2007Sobhi Girgis Background,Antipsychotic drugs have been linked to sudden death among psychiatric patients, with a suggestion that prolongation of the QT-interval detectable on a standard electrocardiogram may be linked to fatal cardiac arrhythmias in these circumstances. Patients in secure forensic psychiatric facilities may be particularly likely to be on high-dose antipsychotic medication, and yet, as far as the authors are aware, no study of QT-intervals among such patients has been reported. Aim,To investigate the prevalence of QT-interval abnormalities and associated known risk factors for fatal cardiac arrhythmias in a sample of forensic patients. Method,Participants had a 12-lead electrocardiogram taken at 50 mm/s. Information was collected on their age, gender, psychiatric diagnosis, history of cardiovascular, liver and kidney diseases, and smoking, on all medications and on history of seclusion over the previous 12 months. Analysis was carried out using binary logistic regression. Results,Lower rates of QT-interval abnormalities than might be expected for this population were found. It was also found that a high dose of antipsychotics was associated with QTc prolongation (Adjusted OR = 9.5, 95% CI 2.6,34.2), a result consistent with previous literature. Conclusion,Forensic patients need not be at increased risk of QTc abnormality provided risk factors are properly managed. A high dose of antipsychotic medication increases the risk of QTc prolongation. Copyright © 2007 John Wiley & Sons, Ltd. [source] Resistin increases islet blood flow and decreases subcutaneous adipose tissue blood flow in anaesthetized ratsACTA PHYSIOLOGICA, Issue 2 2009T. Danielsson Abstract Aim:, Resistin is an adipokine which has been suggested to participate in the induction of insulin resistance associated with type 2 diabetes. The aim of the present study was to investigate whether acute administration of resistin influences tissue blood perfusion in rats. Methods:, Resistin was administered as an intravenous infusion of 7.5 ,g h,1 (1.5 mL h,1) for 30 min to rats anaesthetized with thiobutabarbital. A microsphere technique was used to estimate the blood flow to six different depots of white adipose tissue (WAT), brown adipose tissue (BAT), as well as to the pancreas, islets, duodenum, colon, kidneys, adrenal glands and liver. Results:, Resistin administration led to an increased blood flow to the pancreas and islets and a decrease in subcutaneous WAT and BAT. Intra-abdominal white adipose tissue blood flow and that to other organs were not affected. Conclusion:, Acute administration of resistin markedly affects the blood perfusion of both the pancreas and subcutaneous white adipose tissue depots. At present it is unknown whether resistin exerts a direct effect on the vasculature, or works through local or systemic activation of endothelial cells and/or macrophages. The extent to which this might contribute to the insulin resistance caused by resistin is yet unknown. [source] To Laputa and back: a missing chapter of Gulliver's Travels To the memory of Edward Said, citizen-scholarCRITICAL QUARTERLY, Issue 1-2 2005Darko Suvin The article is divided into three parts. Part 1, 'Entering Laputa in the winter of our discontent', deals with general presuppositions, including those on intellectuals in Post-Fordism and as members of de facto English departments. Part 2, 'Visiting the word-machine', deals with some aporias of literary and English studies. Part 3, 'How to leave Laputa', asks what might be some components of our agenda today. It includes a plea for English studies as an independent, international field of inquiry and teaching, and discusses some possible orientations for us. [source] Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidantsACTA PHYSIOLOGICA, Issue 4 2007M. P. Koeners Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source] How Is Education Possible When There's a Body in the Middle of the Room?CURRICULUM INQUIRY, Issue 1 2004Freema Elbaz-Luwisch ABSTRACT This article explores the possibility of education for multiculturalism and diversity in a situation of violent conflict. It tells the story of my attempt to figure out what might be learned from the situation of living with violence, threats to personal safety, and death as part of the everyday. I draw on recent experiences of dialogue between Jewish and Arab/Palestinian Israelis in preservice and in-service settings at the University of Haifa to suggest that attention to feelings, to the expression of fear, vulnerability, and anger, and to the body that carries these feelings and experiences, are needed in order to make such dialogue possible. [source] Engaging Science Education Within Diverse CulturesCURRICULUM INQUIRY, Issue 3 2003James Gaskell At the heart of discussions about an appropriate school science in a diverse world are questions about the status of modern science versus other schemes for understanding the natural world. Does modern science occupy a privileged epistemological position with respect to alternative beliefs? There has been a movement from an emphasis on replacing students' ideas based on traditional cultures to one of respecting those ideas and adding to them an understanding of modern science ideas and an exploration of when each might be useful. Respecting both sets of explanations need not deny discussions about credibility in particular contexts. School science, however, is always located within wider educational and political structures. Broad elements of the community must be engaged in dialogue concerning what knowledge about the natural world is important, to whom, and for what purposes. [source] Reverse Auctions with Multiple Reinforcement Learning Agents,DECISION SCIENCES, Issue 1 2008Subhajyoti Bandyopadhyay ABSTRACT Reverse auctions in business-to-business (B2B) exchanges provide numerous benefits to participants. Arguably the most notable benefit is that of lowered prices driven by increased competition in such auctions. The competition between sellers in reverse auctions has been analyzed using a game-theoretic framework and equilibria have been established for several scenarios. One finding of note is that, in a setting in which sellers can meet total demand with the highest-bidding seller being able to sell only a fraction of the total capacity, the sellers resort to a mixed-strategy equilibrium. Although price randomization in industrial bidding is an accepted norm, one might argue that in reality managers do not utilize advanced game theory calculations in placing bids. More likely, managers adopt simple learning strategies. In this situation, it remains an open question as to whether the bid prices converge to the theoretical equilibrium over time. To address this question, we model reverse-auction bidding behavior by artificial agents as both two-player and n -player games in a simulation environment. The agents begin the game with a minimal understanding of the environment but over time analyze wins and losses for use in determining future bids. To test for convergence, the agents explore the price space and exploit prices where profits are higher, given varying cost and capacity scenarios. In the two-player case, the agents do indeed converge toward the theoretical equilibrium. The n -player case provides results that reinforce our understanding of the theoretical equilibria. These results are promising enough to further consider the use of artificial learning mechanisms in reverse auctions and other electronic market transactions, especially as more sophisticated mechanisms are developed to tackle real-life complexities. We also develop the analytical results when one agent does not behave strategically while the other agent does and show that our simulations for this environment also result in convergence toward the theoretical equilibrium. Because the nature of the best response in the new setting is very different (pure strategy as opposed to mixed), it indicates the robustness of the devised algorithm. The use of artificial agents can also overcome the limitations in rationality demonstrated by human managers. The results thus have interesting implications for designing artificial agents in automating bid responses for large numbers of bids where human intervention might not always be possible. [source] Crescent Versus Rectangle: Is It a True Negative Margin in Second and Subsequent Stages of Mohs Surgery?DERMATOLOGIC SURGERY, Issue 2 2010YUE YU MD BACKGROUND The hallmark of Mohs micrographic surgery is using tangential tissue sections that theoretically allow 100% of the tissue margin to be examined, but when taking additional layers for second and subsequent Mohs stages, no detailed methods have been described to ensure that 100% of the tissue margins are analyzed. METHOD A rectangular or a crescent-shaped layer is often used to take second and subsequent stages. Here we compare the two techniques for their theoretic advantages and disadvantages. SUMMARY The advantage of the rectangular shape has been ease of processing, as well as built in vertical "nicks" that automatically mark the border of the tissue removed, but the rectangular layer may not provide 100% evaluation of the tumor margin because the vertical edges of the rectangular layer are not always completely analyzed, and thus tumor cells cannot be visualized in the vertical margins of these layers. This might result in a false-negative margin reading, which can be avoided by using the crescent layer. CONCLUSION We propose taking second and subsequent Mohs layers with only a crescent shape, which allows true 100% tissue margin assessment. The authors have indicated no significant interest with commercial supporters. [source] Intricacies of the Single-Scar Technique for Donor Harvesting in Hair Transplantation SurgeryDERMATOLOGIC SURGERY, Issue 6 2004Dominic A. Brandy MD Background. Although single-scar techniques have been published and are used by approximately half of all surgeons, this approach is not as common as one might suspect. Objective. The objective is to demonstrate several surgical gems that make the single-scar donor technique a viable method that can be performed by the vast majority of hair restoration surgeons. Methods. The author presents various techniques such as postauricular skin elevation, subcutaneous undermining of the nape scalp, debulking of underlying scar tissue, temporary staple closure, and permanent double-layered closure using magnification (preferably 2.5 × or greater). All of these contribute to a loose closure with an aesthetically pleasing single donor scar after multiple surgeries. Results. Utilizing the various techniques described in this article, the author has been able to achieve a cosmetically attractive single scar after multiple surgeries in the vast majority of patients. Conclusion. An aesthetically pleasing single, thin donor scar is preferable to multiple scars or a thick single scar at the donor area after multiple hair restoration surgical procedures. The author presents several methods that help hair restoration surgeons conquer some of the obstacles that have deterred them from performing a single-scar technique with consistently excellent results. [source] Post-conflict Statebuilding and State Legitimacy: From Negative to Positive Peace?DEVELOPMENT AND CHANGE, Issue 4 2008David Roberts ABSTRACT This article is concerned with the potential that statebuilding interventions have to institutionalize social justice, in addition to their more immediate ,negative' peace mandates, and the impact this might have, both on local state legitimacy and the character of the ,peace' that might follow. Much recent scholarship has stressed the legitimacy of a state's behaviour in relation to conformity to global governance norms or democratic ,best practice'. Less evident is a discussion of the extent to which post-conflict polities are able to engender the societal legitimacy central to political stability. As long as this level of legitimacy is absent (and it is hard to generate), civil society is likely to remain distant from the state, and peace and stability may remain elusive. A solution to this may be to apply existing international legislation centred in the UN and the ILO to compel international organizations and national states to deliver basic needs security through their institutions. This has the effect of stimulating local-level state legitimacy while simultaneously formalizing social justice and positive peacebuilding. [source] Patterns of motor disability in very preterm childrenDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2002Melanie Bracewell Abstract Motor development in very preterm children differs in several important ways from that of children born at full term. Variability is common, although the anatomic and physiologic bases for that variability are often poorly understood. Motor patterns over the first postnatal year may depend on behaviours learned during often long periods of neonatal intensive care. The normal pattern of development may be modified by disturbances of brain function caused both by the interruption of normal brain maturation ex-utero and the superimposition of focal brain injuries following very preterm birth. Abnormal patterns of development over the first year may evolve into clear neuromotor patterns of cerebral palsy or resolve, as "transient dystonias." Cerebral palsy is associated with identified patterns of brain injury secondary to ischaemic or haemorrhagic lesions, perhaps modified by activation of inflammatory cytokines. Cerebral palsy rates have not fallen as might be expected over the past 10 years as survival has improved, perhaps because of increasing survival at low gestations, which is associated with the highest prevalence of cerebral palsy. Children who escape cerebral palsy are also at risk of motor impairments during the school years. The relationship of these impairments to perinatal factors or to neurological progress over the first postnatal year is debated. Neuromotor abnormalities are the most frequent of the "hidden disabilities" among ex-preterm children and are thus frequently associated with poorer cognitive ability and attention deficit disorders. Interventions to prevent cerebral palsy or to reduce these late disabilities in very preterm children are needed. MRDD Research Reviews 2002;8:241,248. © 2002 Wiley-Liss, Inc. [source] Head regeneration in HydraDEVELOPMENTAL DYNAMICS, Issue 2 2003Hans R. Bode Abstract Hydra, a primitive metazoan, has a simple structure consisting of a head, body column, and foot aligned along a single oral,aboral axis. The body column has a high capacity for regeneration of both the head and foot. Because of the tissue dynamics that take place in adult Hydra, the processes governing axial patterning are continuously active to maintain the form of the animal. Regeneration in hydra is morphallactic and closely related to these axial patterning processes. As might be expected, analysis at the molecular level indicates that the same set of genes are involved in head regeneration and the maintenance of the head in the context of the tissue dynamics of the adult. The genes analyzed so far play roles in axial patterning processes in bilaterians. Developmental Dynamics 226:225,236, 2003. © 2003 Wiley-Liss, Inc. [source] Does antipsychotic withdrawal provoke psychosis?ACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2006Review of the literature on rapid onset psychosis (supersensitivity psychosis), withdrawal-related relapse Objective:, To examine the evidence that discontinuation of long-term antipsychotic medication, including clozapine, may provoke a psychotic episode. Method:, Databases were searched and citations scrutinised. Results:, Evidence for a rapid onset psychosis (supersensitivity psychosis) following clozapine withdrawal was found and weaker evidence that this might occur with some other antipsychotic drugs. Some cases were reported in people without a psychiatric history. It appears that the psychosis may be a feature of drug withdrawal rather than the re-emergence of an underlying illness, at least in some patients. Meta-analyses of withdrawal studies have suggested that antipsychotic discontinuation may also increase the risk of relapse over and above the risk because of the underlying disorder, but not all individual studies show this effect. Mechanisms may relate to brain adaptations to long-term drug use but data are sparse. Conclusion:, These effects require further urgent research. Interventions to reduce morbidity after drug withdrawal need to be developed. [source] The pharmacology of cilostazolDIABETES OBESITY & METABOLISM, Issue 2002Karsten Schrör Cilostazol (6-[4-(1-cyclohexyl- 1H -tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone; OPC-13013) is a 2-oxo-quinoline derivative with antithrombotic, vasodilator, antimitogenic and cardiotonic properties. The compound is a potent inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the cardiovascular system (IC50: 0.2 µm). In addition, there is inhibition of adenosine uptake, eventually resulting in changes in cAMP levels, dependent on the type of adenosine receptors (A1 or A2). Cilostazol inhibits platelet aggregation and has considerable antithrombotic effects in vivo. The compound relaxes vascular smooth muscle and inhibits mitogenesis and migration of vascular smooth muscle cells. In the heart, cilostazol causes positive inotropic and chronotropic effects. Most, if not all, of these actions are cAMP-mediated, including the modification of cAMP-controlled gene expression. Cilostazol decreases levels of serum triglycerides and causes some increase in HDL-cholesterol levels. The compound has a number of additional effects which might contribute to its overall clinical efficacy. Cilostazol undergoes intensive and finally complete hepatic metabolism via the cytochrome P450 systems. This might result in some drug interaction, i.e. with erythromycin and omeprazole. The half-life is approximately 10 h, resulting in about 2-fold accumulation of the drug during repeated administration. [source] What predicts the occurrence of the metabolic syndrome in a population-based cohort of adult healthy subjects?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2009S. Bo Abstract Background Metabolic syndrome (MS), the concurrence of hyperglycaemia, dyslipidaemia, hypertension and visceral obesity, increases cardiovascular risk and mortality. Predictors of MS were previously evaluated in patients without the full syndrome, but with some of its traits. This might confound the resulting associations. Methods The relationship between baseline variables and MS development was evaluated in healthy middle-aged subjects without any MS component at baseline, over a 4.5-year follow-up. Results From a population-based cohort of 1658 subjects, 241 individuals showed no MS components and 201 (83.4%) of them participated in a follow-up screening. At baseline, patients who developed the MS (n = 28/201; 13.9%) showed significantly higher Homeostasis Model Assessment-Insulin Resistance score (HOMA-IR) and C-reactive protein (CRP) values, and lower exercise level than subjects who did not. In a multiple logistic regression analysis, after multiple adjustments, the only baseline variable significantly (p < 0.01) associated with the MS was CRP (OR = 4.05; 95% CI 2.23,7.38; p < 0.001). Results did not change after adjusting for weight gain. The area under the receiver-operating curve was 0.83 for CRP after multiple adjustments. The optimal cut-off point of baseline CRP values was 2.1 mg/L, with 86% (95% CI 81,90) sensitivity and 75% (69,81) specificity in predicting the MS. Baseline CRP resulted associated with after-study glucose values in a multiple regression model (, = 0.14; 0.08,0.20; p < 0.001). Conclusions Higher baseline CRP values confer a significant increased risk of developing the MS in healthy subjects, independently of weight gain. Copyright © 2009 John Wiley & Sons, Ltd. [source] Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2005Jonas Burén Abstract The importance of understanding insulin action is emphasized by the increasing prevalence of insulin resistance in various populations and by the fact that it plays an important pathophysiological role in many common disorders, for example, diabetes, obesity, hypertension and dyslipidemia. The primary factors responsible for the development of insulin resistance are so far unknown, although both genetic and environmental factors are involved. The genetic defects responsible for the common forms of insulin resistance, for example, in type 2 diabetes, are largely unidentified. Some studies from our group as well as by other investigators suggest that cellular insulin resistance is reversible and that it may be secondary to factors in the in vivo environment. These may include insulin-antagonistic action of hormones like catecholamines, glucocorticoids, sex steroids and adipokines as well as dysregulation of autonomic nervous activity and they could contribute to the early development of insulin resistance. Some of these factors can directly impair glucose uptake capacity and this might be due to alterations in key proteins involved in insulin's intracellular signaling pathways. This article briefly summarizes proposed mechanisms behind cellular and whole-body insulin resistance. In particular, we question the role of intrinsic defects in insulin's target cells as primary mechanisms in the development of insulin resistance in type 2 diabetes and we suggest that metabolic and neurohormonal factors instead are the main culprits. Copyright © 2005 John Wiley & Sons, Ltd. [source] Continuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectivenessDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2004Régis Pierre Radermecker Abstract Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or insulin aspart, may offer an advantage over regular human insulin for insulin pumps. Several open-label randomised crossover trials demonstrated that continuous subcutaneous insulin infusion (CSII) with insulin lispro provided a better control of postprandial hyperglycaemia and a slightly but significantly lower glycated haemoglobin level, with lower daily insulin requirement and similar or even less hypoglycaemic episodes. A CSII study comparing insulin lispro and insulin aspart demonstrated similar results with the two analogues, and better results than those with regular insulin. Because these analogues have a quicker onset and a shorter duration of action than regular insulin, one might expect an earlier and greater metabolic deterioration in case of CSII interruption, but a more rapid correction of metabolic abnormalities after insulin boluses when reactivating the pump. These expectations were confirmed in randomised protocols comparing the metabolic changes occurring during and after CSII interruption of various durations when the pump infused either insulin lispro or regular insulin. The extra cost resulting from the use of CSII and insulin analogues in diabetes management should be compensated for by better metabolic control and quality of life. In conclusion, CSII delivering fast-acting insulin analogues may be considered as one of the best methods to replace insulin in a physiological manner by mimicking meal and basal insulin requirements, without higher risk of hypoglycaemia or ketoacidosis in well-educated diabetic patients. Copyright © 2004 John Wiley & Sons, Ltd. [source] Insulin treatment and cardiovascular disease; friend or foe?DIABETIC MEDICINE, Issue 2 2005A point of view Abstract Background Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. Summary of comment Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. Conclusion Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area. [source] Quine, Davidson, and the Naturalization of MetaethicsDIALECTICA, Issue 2 2001Robert Feleppa Quine's ethical views typify what might seem to be natural sympathies between empiricism and ethical noncognitivism. LikeAyer, he sees a case for noncognitivism rooted in an epistemic discontinuity between ethics and science. Quine argues that the absence of genuine moral observation sentences, and thus the absence of empirical checkpoints for the resolution of theoretical disputes, renders ethics, as he terms it, "methodologically infirm" However, recent papers in this journal make clear that Quine appears to be voicing mutually incompatible commitments to both noncognitivism and cognitivism. Here I argue that Davidson's theory of interpretation offers promising ways to resolve these tensions. His constructive program fleshes out the implications of Quine's largely destructive critique of intensional semantics and contains a fairly well-articulated account of evaluative semantics, one which seems to combine cognitivist and noncognitivist elements harmoniously. Moreover, it is argued that Davidson's long-standing differences with Quine over the epistemological status Quine accords observation sentences with do not undermine Quine's metaethical critique. [source] Hippocampal structure and the action of cholinomimetic drugsDRUG DEVELOPMENT RESEARCH, Issue 3 2002John G. Csernansky Abstract Cholinomimetic drugs have become the clinical standard for the treatment of patients with dementia of the Alzheimer type (DAT). However, uncertainty remains as to the proportion of patients that respond to such drugs, and how one might predict the capacity for response before treatment is begun. The thesis of the present review is that the neuroanatomical integrity of the hippocampus determines, at least in part, the capacity of DAT patients to respond to cholinomimetic drugs. Neuroimaging studies suggest that volume losses and other neuroanatomical deformities of the hippocampus are common in patients with even mild DAT. Moreover, more severe neuroanatomical deformities of the hippocampus are associated with more severe dementia symptoms and more rapid clinical decline. Animal research, including studies of cholinergic antagonists, glutamatergic antagonists, hippocampal lesions, and animals with mutant amyloid precursor protein genes, demonstrate that behavioral abnormalities similar to those found in DAT patients, especially those related to memory, are associated with hippocampal pathology. Cholinomimetic drugs, in particular, the cholinesterase inhibitors, have been shown to reverse some but not all of these behavioral abnormalities. More research is needed in DAT patients to determine whether an analysis of hippocampal structure or function can reliably predict the outcome of treatment with cholinomimetic drugs. Further work in animals is also needed to determine the limitations of cholinomimetic drugs for reversing various types of cognitive deficits, and to develop and test other pharmacological strategies for the treatment of DAT. Drug Dev. Res. 56:531,540, 2002. © 2002 Wiley-Liss, Inc. [source] Phonological and orthographic spelling in high-functioning adult dyslexicsDYSLEXIA, Issue 2 2009Nenagh Kemp Abstract Despite a history of reading or spelling difficulties, some adults attain age-appropriate spelling skills and succeed at university. We compared the spelling of 29 such high-functioning dyslexics with that of 28 typical students, matched on general spelling ability, and controlling for vocabulary and non-verbal intelligence. Participants wrote derived real and pseudo words, whose spelling relationship to their base forms was categorized as phonologically simple (apt-aptly), orthographically simple (deceit-deceitful), phonologically complex (ash-ashen), or orthographically complex (plenty-plentiful). Dyslexic participants spelled all word and pseudoword categories more poorly than controls. Both groups spelled simple phonological words best. Dyslexics were particularly poor at spelling simple orthographic words, whose letter patterns and rules must likely be memorized. In contrast, dyslexics wrote more plausible spellings of orthographic than phonological pseudowords, but this might be an artefact of their more variable spelling attempts. These results suggest that high-functioning dyslexics make some use of phonological skills to spell familiar words, but they have difficulty in memorizing orthographic patterns, which makes it difficult to spell unfamiliar words consistently in the absence of sufficient phonological cues or orthographic rules. Copyright © 2008 John Wiley & Sons, Ltd. [source] A pictographic method for teaching spelling to Greek dyslexic childrenDYSLEXIA, Issue 2 2002Th.D. Mavrommati Abstract In the Greek orthography every letter consistently represents the same sound, but the same sound can be represented by different letters or pairs of letters. This makes spelling more difficult than reading. Two methods of teaching spelling to Greek dyslexic children are compared. The first involved pictograms (specially drawn pictures) for use when alternative spellings are possible. This is referred to as the ,PICTO' method. The second was in effect a combination of two traditional methods: the first involved the teaching of letter-sound correspondences in a multisensory way; the second involved the use of concepts derived from linguistics, the children being taught the derivations of words and shown how the same root morphemes, derivative morphemes, etc., were cosistently represented by the same spelling pattern. This combination of methods is referred to as ,TRAD', signifying ,traditional'. There were 72 subjects in the study, aged between 9 and 11 years. Four different teachers, each using both PICTO and TRAD, took part in the teaching sessions. The PICTO method proved considerably more effective; and possible reasons are suggested as to why this might be so. Copyright © 2002 John Wiley & Sons, Ltd. [source] Science, systems and geomorphologies: why LESS may be moreEARTH SURFACE PROCESSES AND LANDFORMS, Issue 9 2008Keith Richards Abstract This paper has been stimulated by a debate triggered by the then British Geomorphological Research Group (now the British Society for Geomorphology) about the connections between geomorphology and Earth system science (ESS). Its purpose is to expand on some arguments we have already made about these connections, amongst other things drawing attention to neglected historical antecedents, and to the questionable status of the science implied by ESS. A premise of this further paper is that such a debate cannot be assumed to mirror conventional assessments of the content of a science, since it is about scientific institutional structures, names, boundaries and relationships. This implies that the terms of reference go well beyond critical scientific appraisal, extending to matters of evaluating a social organization, and to politics, policies, purposes and practices. We therefore begin by considering the sociology of science, scientific knowledge and technology, before moving to a consideration of the historical relationship amongst geomorphology, geology and physical geography; and to some perspectives this might offer for the current debate. Epistemological issues, arising both from the use of systems theory over multiple spatial and temporal scales, and from the demands of contemporary environmental science, are then introduced, and these lead to a conclusion that geomorphology might more appropriately be assessed against (or seen as part of) a more locally orientated ESS, which we term LESS. Copyright © 2008 John Wiley & Sons, Ltd. [source] Reciprocal specialization in ecological networksECOLOGY LETTERS, Issue 9 2009Lucas N. Joppa Abstract Theories suggest that food webs might consist of groups of species forming ,blocks', ,compartments' or ,guilds'. We consider ecological networks , subsets of complete food webs , involving species at adjacent trophic levels. Reciprocal specializations occur when (say) a pollinator (or group of pollinators) specializes on a particular flower species (or group of such species) and vice versa. Such specializations tend to group species into guilds. We characterize the level of reciprocal specialization for both antagonistic interactions , particularly parasitoids and their hosts , and mutualistic ones , such as insects and the flowers that they pollinate. We also examine whether trophic patterns might be ,palimpsests', that is, there might be reciprocal specialization within taxonomically related species within a network, but these might be obscured when these relationships are combined. Reciprocal specializations are rare in all these systems when tested against the most conservative null model. [source] Virulence evolution via host exploitation and toxin production in spore-producing pathogensECOLOGY LETTERS, Issue 4 2002Troy Day Many pathogens produce resilient free-living propagules that allow their dissemination in the absence of direct contact between susceptible and infected hosts. One might expect pathogens capable of producing such long-lived propagules to evolve high levels of virulence because their reproductive success is de-coupled from the survival of their host. Despite some comparative data supporting this prediction, theory has questioned its general validity. I present theoretical results that incorporate two transmission routes neglected by previous theory: death-mediated propagule production and direct host-host transmission. This theory predicts that spore-producing pathogens should evolve high levels of virulence under quite broad conditions. Moreover, a novel prediction of this theory is that the production of propagules can generate selection for the evolution of pathogen characteristics such as toxins whose sole function is to kill the host. This latter result reveals an unanticipated mechanism through which virulence is expected to evolve in spore-producing pathogens. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||