182 research outputs found

    Redistribution and Growth for Poverty Reduction

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    Asymptotic Expansions of exp-log Functions

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    We give an algorithm to compute asymptotic expansions of exp-log functions. This algorithm automatically computes the necessary asymptotic scale and does not suffer from problems of indefinite cancellation. In particular, an asymptotic equivalent can always be computed for a given exp-log function

    Superfeminization as an effect of bisphenol A in \u3ci\u3eMarisa cornuarietis\u3c/i\u3e & Response from Forbes et al. to Oehlmann et al.

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    [Oehlmann et al.]: Recently, we had the opportunity to read two articles in volume 66 of Ecotoxicology and Environmental Safety. Forbes et al. (2007a, , 2007b) declare “to explore the reproducibility of prior work” showing that bisphenol A (BPA) induces superfeminization in the freshwater snail Marisa cornuarietis (Oehlmann et al., 2000, 2006; Schulte- Oehlmann et al., 2001). Based on the outcome of a toxicity test with the same species, the authors conclude that their results “do not support previous claims of enhanced reproduction in M. cornuarietis in response to exposure to BPA.” We take issue with the declaration of exploring the reproducibility of our challenged work and the validity of the conclusions made by Forbes et al. (2007a, 2007b). Furthermore, we feel the toxicity test is flawed because its experimental design and the selected exposure conditions result in an irresponsiveness of test animals to the tested compound. ... [Forbes et al.]:We thank the editor for giving us the opportunity to respond to Oehlmann et al.’s comments (Oehlmann et al., 2008) on our papers (Forbes et al., 2007a,b). In response to the criticisms of our studies we would first like to emphasize that it was not our aim to exactly repeat the experiments of Oehlmann and colleagues, but rather to produce robust and reproducible results that were statistically valid and that therefore could be used in the risk assessment of bisphenol A (BPA). We are disturbed by the highly speculative suggestion by Oehlmann et al. that we may have studied a different ‘cryptic’ species of Marisa cornuarietis, as there is no evidence to support such suggestion. Furthermore, the snails used in our studies were collected from a documented pristine field site and identified to species by Dr. Sharon File-Emperador from University of Puerto Rico, a recognized snail expert. They were reared for a known number of generations under tightly controlled and documented conditions. In contrast, the snails used in Oehlmann et al.’s studies (e.g., Oehlmann et al., 2006) came from the Dusseldorf Zoo (original site of field collection not indicated) and were periodically supplemented with snails from Florida (location not indicated). There is likewise very little information in the published studies about the culture and husbandry conditions of Oehlmann et al.’s snails, whereas a major portion of our research aimed to identify appropriate husbandry and culture conditions for M. cornuarietis. It is on the basis of such detailed study that our toxicity tests with BPA were conducted

    Left Ventricular Dyssynchrony Acutely After Myocardial Infarction Predicts Left Ventricular Remodeling

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    ObjectivesWe sought to identify predictors of left ventricular (LV) remodeling after acute myocardial infarction.BackgroundLeft ventricular remodeling after myocardial infarction is associated with an adverse long-term prognosis. Early identification of patients prone to LV remodeling is needed to optimize therapeutic management.MethodsA total of 178 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 h of intervention, 2-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), wall motion score index, left atrial dimension, E/E′ ratio, and severity of mitral regurgitation. Left ventricular dyssynchrony was determined using speckle-tracking radial strain analysis. At 6-month follow-up, LV volumes, LVEF, and severity of mitral regurgitation were reassessed.ResultsPatients showing LV remodeling at 6-month follow-up (20%) had comparable baseline characteristics to patients without LV remodeling (80%), except for higher peak troponin T levels (p < 0.001), peak creatine phosphokinase levels (p < 0.001), wall motion score index (p < 0.05), E/E′ ratio (p < 0.05), and a larger extent of LV dyssynchrony (p < 0.001). Multivariable analysis demonstrated that LV dyssynchrony was superior in predicting LV remodeling. Receiver-operating characteristic curve analysis demonstrated that a cutoff value of 130 ms for LV dyssynchrony yields a sensitivity of 82% and a specificity of 95% to predict LV remodeling at 6-month follow-up.ConclusionsLeft ventricular dyssynchrony immediately after acute myocardial infarction predicts LV remodeling at 6-month follow-up

    Discontinuation of anti-PD-1 monotherapy in advanced melanoma:Outcomes of daily clinical practice

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    There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation

    Healthcare costs of metastatic cutaneous melanoma in the era of immunotherapeutic and targeted drugs

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    Immunotherapeutic and targeted drugs improved survival of patients with metastatic melanoma. There is, however, a lack of evidence regarding their healthcare costs in clinical practice. The aim of our study was to provide insight into real-world healthcare costs of patients with metastatic cutaneous melanoma. Data were obtained from the Dutch Melanoma Treatment Registry for patients who were registered between July 2012 and December 2018. Mean total/monthly costs per patient were reported for all patients, patients who did not receive systemic therapy, and patients who received systemic therapy. Furthermore, mean episode/monthly costs per line of therapy and drug were reported for patients who received systemic therapy. Mean total/monthly costs were € 89,240/€ 6809: € 7988/€ 2483 for patients who did not receive systemic therapy (n = 784) and € 105,078/€ 7652 for patients who received systemic therapy (n = 4022). Mean episode/monthly costs were the highest for nivolumab plus ipilimumab (€ 79,675/€ 16,976), ipilimumab monotherapy (€ 79,110/€ 17,252), and dabrafenib plus trametinib (€ 77,053/€ 12,015). Dacarbazine yielded the lowest mean episode/monthly costs (€ 6564/€ 2027). Our study showed that immunotherapeutic and targeted drugs had a large impact on real-world healthcare costs. As new drugs continue entering the treatment landscape for (metastatic) melanoma, it remains crucial to monitor whether the benefits of these drugs outweigh their costs
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