1,316 research outputs found

    Mortality Contingent Claims, Health Care, and Social Insurance

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    This paper analyzes the savings and health care impacts of mortality contingent claims, defined here as income measures, such as annuities and life-insurance, under which earned income is contingent on the length of one's life. The postwar increase in mandatory annuity and life-insurance programs, as well as the rapid increase in life-expectancy, motivates a better understanding of the effects that mortality contingent claims have on resources devoted to life-extension. We analyze the incentives that such claims imply for life-extension when resources may affect mortality endogenously and argue that these incentives dramatically alter the standard conclusions obtained when mortality is treated exogenously.

    Complete atrial-specific knockout of sodium-calcium exchange eliminates sinoatrial node pacemaker activity.

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    The origin of sinoatrial node (SAN) pacemaker activity in the heart is controversial. The leading candidates are diastolic depolarization by "funny" current (If) through HCN4 channels (the "Membrane Clock" hypothesis), depolarization by cardiac Na-Ca exchange (NCX1) in response to intracellular Ca cycling (the "Calcium Clock" hypothesis), and a combination of the two ("Coupled Clock"). To address this controversy, we used Cre/loxP technology to generate atrial-specific NCX1 KO mice. NCX1 protein was undetectable in KO atrial tissue, including the SAN. Surface ECG and intracardiac electrograms showed no atrial depolarization and a slow junctional escape rhythm in KO that responded appropriately to Ī²-adrenergic and muscarinic stimulation. Although KO atria were quiescent they could be stimulated by external pacing suggesting that electrical coupling between cells remained intact. Despite normal electrophysiological properties of If in isolated patch clamped KO SAN cells, pacemaker activity was absent. Recurring Ca sparks were present in all KO SAN cells, suggesting that Ca cycling persists but is uncoupled from the sarcolemma. We conclude that NCX1 is required for normal pacemaker activity in murine SAN

    MAES Service Case: Wetland ecosystem condition mapping (v.1.0)

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    SWOS Technical publicationThe MAES working group is preparing the workshop on ā€œecosystem condition mappingā€ to streamline the efforts done so far with regards to the mapping and assessment of the condition of Europeā€™s ecosystems. The MAES WG has requested directly to SWOS partners a specific document to support the mapping and assessing wetland ecosystem condition for this workshop. This document shall highlight the different elements to take into account for the mapping and assessment of wetland ecosystems with the aim of supporting Member States and the European Commission in their efforts to better describe the situation of wetland ecosystems in Europe. This document represents the major output of the MAES Service case that shall show how SWOS outputs are useful to support the MAES WG with regards to wetland ecosystem mapping and assessment

    Tooth Discoloration in Patients With Neonatal Diabetes After Transfer Onto Glibenclamide: A previously unreported side effect

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    PublishedJournal ArticleMulticenter StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tOBJECTIVE To assess if tooth discoloration is a novel side effect of sulfonylurea therapy in patients with permanent neonatal diabetes due to mutations in KCNJ11. RESEARCH DESIGN AND METHODS A total of 67 patients with a known KCNJ11 mutation who had been successfully transferred from insulin injections onto oral sulfonylureas were contacted and asked about the development of tooth discoloration after transfer. RESULTS Altered tooth appearance was identified in 5 of the 67 patients. This was variable in severity, ranging from mild discoloration/staining (n = 4) to loss of enamel (n = 1) and was only seen in patients taking glibenclamide (glyburide). CONCLUSIONS These previously unreported side effects may relate to the developing tooth and/or to the high local concentrations in the children who frequently chewed glibenclamide tablets or took it as a concentrated solution. Given the multiple benefits of sulfonylurea treatment for patients with activating KCNJ11 mutations, this association warrants further investigation but should not preclude such treatment.This work was funded by the Welcome Trust (grant 067463/Z/2/Z), National Institutes of Health Grants DK-44752 and DK-20595, and a gift from the Kovler Family Foundation. S.E.F. is the Sir Graham Wilkins, Peninsula Medical School Research Fellow. A.T.H. is a Welcome Trust Research Leave Fellow. O.R.-C. was supported by an ā€œAyuda para contratos post-FormacioĀ“n Sanitaria Especializadaā€ from the ā€œInstituto de Salud Carlos IIIā€ (FIS CM06/00013

    Three decades of post-logging tree community recovery in naturally regenerating and actively restored dipterocarp forest in Borneo

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    Selective logging has affected large areas of tropical forests and there is increasing interest in how to manage selectively logged forests to enhance recovery. However, the impacts of logging and active restoration, by liberation cutting and enrichment planting, on tree community composition are poorly understood compared to trajectories of biomass recovery. Here, we assess the long-term impacts of selective logging and active restoration for biomass recovery on tree species diversity, community composition, and forest structure. We censused all stems ā‰„2 cm diameter at breast height (DBH) on 46 permanent plots in unlogged, primary forest in the Danum Valley Conservation Area (DVCA; 12 plots, totalling 0.6 ha) and in sites logged 23ā€“35 years prior to the census in the Ulu Segama Forest Reserve adjacent to DVCA (34 plots, totalling 1.7 ha) in Sabah, Malaysian Borneo. Active restoration treatments, including enrichment planting and climber cutting, were implemented on 17 of the logged forest plots 12ā€“24 years prior to the census. Total plot-level basal area and pole (5ā€“10 cm DBH) stem density were lower in logged than unlogged forests, however no difference was found in stem density amongst saplings (2ā€“5 cm DBH) or established trees (ā‰„10 cm DBH). Neither basal area, nor plot-level stem density varied with time since logging at any size class, although sapling and pole stem densities were lower in actively restored than naturally regenerating logged forest. Sapling species diversity was lower in logged than unlogged forest, however there were no other significant effects of logging on tree species richness or diversity indices. Tree species composition, however, differed between logged and unlogged forests across all stem size classes (PERMANOVA), reflected by 23 significant indicator species that were only present in unlogged forest. PERMANOVA tests revealed no evidence that overall species composition changed with time since logging or with active restoration treatments at any size class. However, when naturally regenerating and actively restored communities were compared, two indicator species were identified in naturally regenerating forest and three in actively restored forests. Together our results suggest that selective logging has a lasting effect on tree community composition regardless of active restoration treatments and, even when species richness and diversity are stable, species composition remains distinct from unlogged forest for more than two decades post-harvest. Active restoration efforts should be targeted, monitored, and refined to try to ensure positive outcomes for multiple metrics of forest recovery

    Exenatide extended release in patients with type 1 diabetes with and without residual insulin production

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    AimsTo test whether a long- acting GLP- 1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.MethodsWe performed a randomized placebo- controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C- peptide. Seventy- nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C- peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24- weeks. Participants were followed for another 6 months off study drug.ResultsAt week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C- peptide. Those treated with exenatide ER lost weight at 12 and 24- weeks compared to those treated with placebo (P- <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.ConclusionTreatment with exenatide ER may have short- term benefits in some individuals with T1D who are overweight or who have detectable levels of C- peptide, but short- term improvements were not sustained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/1/dom14121_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/2/dom14121.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/3/dom14121-sup-0001-Supinfo.pd

    Seed dispersal increases local species richness and reduces spatial turnover of tropical tree seedlings

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    Dispersal is thought to be a key process underlying the high spatial diversity of tropical forests. Just how important dispersal is in structuring plant communities is nevertheless an open question because it is very difficult to isolate dispersal from other processes, and thereby measure its effect. Using a unique situation, the loss of vertebrate seed dispersers on the island of Guam and their presence on the neighboring islands of Saipan and Rota, we quantify the contribution of vertebrate seed dispersal to spatial patterns of diversity of tree seedlings in treefall gaps. The presence of vertebrate seed dispersers approximately doubled seedling species richness within canopy gaps and halved species turnover among gaps. Our study demonstrates that dispersal plays a key role in maintaining local and regional patterns of diversity, and highlights the potential for ongoing declines in vertebrate seed dispersers to profoundly alter tropical forest composition

    Drugā€“drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

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    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drugā€“drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD ā€“POD. Gliclazide (Ā½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution
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