MCMC Bayesian Estimation in FIEGARCH Models

Bayesian inference for fractionally integrated exponential generalized autoregressive conditional heteroskedastic (FIEGARCH) models using Markov Chain Monte Carlo (MCMC) methods is described. A simulation study is presented to access the performance of the procedure, under the presence of long-memory in the volatility. Samples from FIEGARCH processes are obtained upon considering the generalized error distribution (GED) for the innovation process. Different values for the tail-thickness parameter \nu are considered covering both scenarios, innovation processes with lighter (\nu2) tails than the Gaussian distribution (\nu=2). A sensitivity analysis is performed by considering different prior density functions and by integrating (or not) the knowledge on the true parameter values to select the hyperparameter values

Sparse precision matrix estimation in phenotypic trait evolution models

Phylogenetic trait evolution models allow for the estimation of evolutionary correlations between a set of traits observed in a sample of related organisms. By directly modeling the evolution of the traits along an estimable phylogenetic tree, the model's structure effectively controls for shared evolutionary history. In these models, relevant correlations are usually assessed through the high posterior density interval of their marginal distributions. However, the selected correlations alone may not provide the full picture regarding trait relationships. Their association structure, expressed through a graph that encodes partial correlations, can in contrast highlight sparsity patterns featuring direct associations between traits. In order to develop a model-based method to identify this association structure we explore the use of Gaussian graphical models (GGM) for covariance selection. We model the precision matrix with a G-Wishart conjugate prior, which results in sparse precision estimates. Furthermore the model naturally allows for Bayes Factor tests of association between the traits, with no additional computation required. We evaluate our approach through Monte Carlo simulations and applications that examine the association structure and evolutionary correlations of phenotypic traits in Darwin's finches and genomic and phenotypic traits in prokaryotes. Our approach provides accurate graph estimates and lower errors for the precision and correlation parameter estimates, particularly for conditionally independent traits, which are the target for sparsity in GGMs.Comment: 24 pages, 4 figure

Trends of mortality due to oral and oropharyngeal cancers in Uruguay from 1997 to 2014

To analyze the trends of oral and oropharyngeal cancer mortality in Uruguay between 1997 and 2014 according to sex and age groups and its possible association with sociodemographic factors. A time-series ecological study using secondary data was performed. The data about mortality due to oral and oropharyngeal cancers were obtained from the Statistics Vitals Department of the Public Health Ministry of Uruguay. To estimate the mortality trends of the historical series, by sex, anatomical site and age groups, linear regressions generated by the Prais-Winsten procedure were used. The analysis of mortality trends for oral cavity and oropharyngeal cancers in Uruguay indicated that the global mortality rate was stable over the studied period. The women's mortality rate increased from 0.51 per 100,000 in 1997 to 0.65 per 100,000 in 2014 while for men, rates per 100,000 went from 3.22 in 1997 to 2.20 per 100,000 in 2014. Mortality from oral cancer in men decreased between 1997 and 2014. Mortality by oropharyngeal cancer, irrespective of sex, remained stable. Analysis by cancer site revealed decreasing trends tumors situated in the base of the tongue and gum. Years of education, unemployment, smoking and Gini index were not associated with mortality trends. The overall mortality from oral and oropharyngeal cancer in Uruguay has remained constant in the period between 1997 and 2014. Oral cancer mortality decreased in men and increased in women and decreased at the base of the tongue. It?s necessary to continue monitoring the behavior of these diseases

Composition and mixing state of atmospheric aerosols determined by electron microscopy: method development and application to aged Saharan dust deposition in the Caribbean boundary layer

The microphysical properties, composition and mixing state of mineral dust, sea salt and secondary compounds were measured by active and passive aerosol sampling, followed by electron microscopy and X-ray fluorescence in the Caribbean marine boundary layer. Measurements were carried out at Ragged Point, Barbados during June–July 2013 and August 2016. Techniques are presented and evaluated, which allow for statements on atmospheric aerosol concentrations and aerosol mixing state based on collected samples. It became obvious that in the diameter range with the highest dust deposition the deposition velocity models disagree by more than 2 orders of magnitude. Aerosol at Ragged Point was dominated by dust, sea salt and soluble sulfates in varying proportions. The contribution of sea salt was dependent on local wind speed. Sulfate concentrations were linked to long-range transport from Africa and Europe, and South America and the southern Atlantic Ocean. Dust sources were located in western Africa. The dust silicate composition was not significantly varied. Pure feldspar grains were 3&thinsp;% of the silicate particles, of which about a third were K-feldspar. The average dust deposition observed was 10&thinsp;mg&thinsp;m−2&thinsp;d−1 (range of 0.5–47&thinsp;mg&thinsp;m−2&thinsp;d−1), of which 0.67&thinsp;mg&thinsp;m−2&thinsp;d−1 was iron and 0.001&thinsp;mg&thinsp;m−2&thinsp;d−1 phosphorus. Iron deposition was mainly driven by silicate particles from Africa. Dust particles were mixed internally to a minor fraction (10&thinsp;%), mostly with sea salt and less frequently with sulfate. It was estimated that the average dust deposition velocity under ambient conditions is increased by the internal mixture by 30&thinsp;%–140&thinsp;% for particles between 1 and 10&thinsp;µm dust aerodynamic diameter, with approximately 35&thinsp;% at the mass median diameter of deposition (7.0&thinsp;µm). For this size, an effective deposition velocity of 6.4&thinsp;mm&thinsp;s−1 (geometric standard deviation of 3.1 over all individual particles) was observed.</p

Treatment with the immunomodulator FTY720 does not promote spontaneous bacterial infections after experimental stroke in mice

Background: FTY720, an immunomodulator derived from a fungal metabolite which reduces circulating lymphocyte counts by increasing the homing of lymphocytes to the lymph nodes has recently gained interest in stroke research. The aim of this study was to evaluate the protective efficacy of FTY720 in cerebral ischemia in two different application paradigms and to gather first data on the effect of FTY720 on the rate of spontaneous bacterial infections in experimental stroke. Methods: Middle cerebral artery occlusion (MCAO) in C57BL/6 mice (strain J, groups of 10 animals) was performed with two different durations of ischemia (90 min and 3 h) and FTY720 was applied 2 h after vessel occlusion to study the impact of reperfusion on the protective potency of FTY720. Lesion size was determined by TTC staining. Mice treated with FTY720 or vehicle were sacrificed 48 h after 90 min MCAO to determine the bacterial burden in lung and blood. Results: FTY720 1 mg/kg significantly reduced ischemic lesion size when administered 2 h after the onset of MCAO for 3 h (45.4 +/- 22.7 mm3 vs. 84.7 +/- 23.6 mm3 in control mice, p = 0.001) and also when administered after reperfusion, 2 h after the onset of MCAO for 90 min (31.1 +/- 28.49 mm3 vs. 69.6 +/- 27.2 mm3 in control mice, p = 0.013). Bacterial burden of lung homogenates 48 h after stroke did not increase in the group treated with the immunomodulator FTY720 while there was no spontaneous bacteremia 48 h after MCAO in treated and untreated animals. Conclusions: Our results corroborate the experimental evidence of the protective effect of FTY720 seen in different rodent stroke models. Interestingly, we found no increase in bacterial lung infections even though FTY720 strongly reduces the number of circulating leukocytes

Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

BACKGROUND: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. METHODS: Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. FINDINGS: On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. INTERPRETATION: PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74386719

Characterization of a Legionella pneumophila gene encoding a lipoprotein antigen

A prominent 19kDa surface antigen of Legionella pneumophila , cloned in Escherichia coli , was found to be intimately associated with peptidoglycan. The DNA region encoding this antigen was mapped on an 11.9kb plasmid by means of deletion analysis and transposon mutagenesis. PhoA + gene fusions, generated by Tn phoA insertions into this region, confirmed the presence of a gene encoding a secreted protein. PhoA + transposon insertions were also associated with loss of the 19 kDa antigen in immunoassay s using a monoclonal antibody (mAb1E9) and the replacement of the 19kDa antigen with larger fusion proteins in immunoblots using Legionella immune serum. A 1540bp PstI fragment carrying the gene was sequenced, and the open reading frame encoding the antigen was identified. The gene encodes a polypeptide 176 amino acid residues long and 18913Da in size. The presence of a signal sequence of 22 amino acids with a consensus sequence for cleavage by signal peptidase II indicates that the antigen is a lipoprotein, and striking similarity with peptidoglycan-associated lipoproteins (PALs) from E. coli (51% amino acid homology) and Haemophilus influenzae (55% homology) is noted. We conclude that the 19kDa antigen of L. pneumophila is the structural equivalent of the PAL found in other Gram-negative species and suggest that its post-translational acylation may explain its potency as an immunogen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75712/1/j.1365-2958.1991.tb00824.x.pd