149 research outputs found
Inequality amongst the wealthiest and its link with economic growth
In this paper we correlate the key features of the distribution of wealth of the 500 wealthiest individuals in the Netherlands with economic growth and stock market returns for 1998 to 2009. We show that each year the distribution obeys a power law and that the key parameter measures the degree of inequality. Our main finding is that more inequality amongst the wealthiest is associated with higher economic growth
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We investigate closed copies of~ in powers of~ with
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Automated detection of wedge-shaped defects in polarimetric images of the retinal nerve fibre layer
Purpose: Automated glaucoma detection in images obtained by scanning laser polarimetry is currently insensitive to local abnormalities, impairing its performance. The purpose of this investigation was to tes
Bayesian hierarchical modeling of longitudinal glaucomatous visual fields using a two-stage approach
The Bayesian approach has become increasingly popular because it allows to fit quite complex models to data via Markov chain Monte Carlo sampling. However, it is also recognized nowadays that Markov chain Monte Carlo sampling can become computationally prohibitive when applied to a large data set. We encountered serious computational difficulties when fitting an hierarchical model to longitudinal glaucoma data of patients who participate in an ongoing Dutch study. To overcome this problem, we applied and extended a recently proposed two-stage approach to model these data. Glaucoma is one of the leading causes of blindness in the world. In order to detect deterioration at an early stage, a model for predicting visual fields (VFs) in time is needed. Hence, the true underlying VF progression can be determined, and treatment strategies can then be optimized to prevent further VF loss. Because we were unable to fit these data with the classical one-stage approach upon which the current popular Bayesian software is based, we made use of the two-stage Bayesian approach. The considered hierarchical longitudinal model involves estimating a large number of random effects and deals with censoring and high measurement variability. In addition, we extended the approach with tools for model evaluation. Copyrigh
Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers
Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a \u201cdouble hit score\u201d upon positivity for BCL2 and MYC. PCDLBCL-NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B-cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a \u201cnon-germinal B-cell\u201d profile, whereas \u201cgerminal center\u201d cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC-LT, which often coexpressed MYC and BCL2. The impact of single factors on 5-year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group\u2014PCDLBCL-NOS\u2014exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information
Selenium and outcome in heart failure
Aims:
Severe deficiency of the essential trace element selenium can cause myocardial dysfunction although the mechanism at cellular level is uncertain. Whether, in clinical practice, moderate selenium deficiency is associated with worse symptoms and outcome in patients with heart failure is unknown.
Methods and results:
BIOSTATâCHF is a multinational, prospective, observational cohort study that enrolled patients with worsening heart failure. Serum concentrations of selenium were measured by inductively coupled plasma mass spectrometry. Primary endpoint was a composite of allâcause mortality and hospitalization for heart failure; secondary endpoint was allâcause mortality. To investigate potential mechanisms by which selenium deficiency might affect prognosis, human cardiomyocytes were cultured in absence of selenium, and mitochondrial function and oxidative stress were assessed. Serum selenium concentration (deficiency) was <70âÎŒg/L in 485 (20.4%) patients, who were older, more often women, had worse New York Heart Association class, more severe signs and symptoms of heart failure and poorer exercise capacity (6âmin walking test) and quality of life (Kansas City Cardiomyopathy Questionnaire). Selenium deficiency was associated with higher rates of the primary endpoint [hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.06â1.42] and allâcause mortality (HR 1.52; 95% CI 1.26â1.86). In cultured human cardiomyocytes, selenium deprivation impaired mitochondrial function and oxidative phosphorylation, and increased intracellular reactive oxygen species levels.
Conclusions:
Selenium deficiency in heart failure patients is independently associated with impaired exercise tolerance and a 50% higher mortality rate, and impaired mitochondrial function in vitro, in human cardiomyocytes. Clinical trials are needed to investigate the effect of selenium supplements in patients with heart failure, especially if they have low plasma concentrations of selenium
Novel mutations in the VKORC1 gene of wild rats and mice â a response to 50 years of selection pressure by warfarin?
<p>Abstract</p> <p>Background</p> <p>Coumarin derivatives have been in world-wide use for rodent pest control for more than 50 years. Due to their retarded action as inhibitors of blood coagulation by repression of the vitamin K reductase (VKOR) activity, they are the rodenticides of choice against several species. Resistance to these compounds has been reported for rodent populations from many countries around the world and poses a considerable problem for efficacy of pest control.</p> <p>Results</p> <p>In the present study, we have sequenced the <it>VKORC1 </it>genes of more than 250 rats and mice trapped in anticoagulant-exposed areas from four continents, and identified 18 novel and five published missense mutations, as well as eight neutral sequence variants, in a total of 178 animals. Mutagenesis in <it>VKORC1 </it>cDNA constructs and their recombinant expression revealed that these mutations reduced VKOR activities as compared to the wild-type protein. However, the <it>in vitro </it>enzyme assay used was not suited to convincingly demonstrate the warfarin resistance of all mutant proteins</p> <p>Conclusion</p> <p>Our results corroborate the <it>VKORC1 </it>gene as the main target for spontaneous mutations conferring warfarin resistance. The mechanism(s) of how mutations in the <it>VKORC1 </it>gene mediate insensitivity to coumarins <it>in vivo </it>has still to be elucidated.</p
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