Use of Wishart Prior and Simple Extensions for Sparse Precision Matrix Estimation

A conjugate Wishart prior is used to present a simple and rapid procedure for computing the analytic posterior (mode and uncertainty) of the precision matrix elements of a Gaussian distribution. An interpretation of covariance estimates in terms of eigenvalues is presented, along with a simple decision-rule step to improve the performance of the estimation of sparse precision matrices and associated graphs. In this, elements of the estimated precision matrix that are zero or near zero can be detected and shrunk to zero. Simulated data sets are used to compare posterior estimation with decision-rule with two other Wishart-based approaches and with graphical lasso. Furthermore, an empirical Bayes procedure is used to select prior hyperparameters in high dimensional cases with extension to sparsity.     

Distribution of sulphate and iduronic acid residues in heparin and heparan sulphate

1. A method was developed for determination of the uronic acid composition of heparin-like glycosaminoglycans. Polymers or oligosaccharides are degraded to monosaccharides by a combination of acid hydrolysis and deamination with HNO₂. The resulting uronic acid monosaccharides (accounting for about 70% of the uronic acid contents of the starting materials) are isolated and converted into the corresponding aldono-1,4-lactones, which are separated by g.l.c. The calculated ratios of glucuronic acid/iduronic acid are reproducible within 5%. 2. Samples of heparin from pig intestinal mucosa (molar ratio of sulphate/disaccharide unit, 2.40) and heparan sulphate from human aorta (sulphate/disaccharide ratio, 0.46) were subjected to uronic acid analysis. l-Iduronic acid constituted 77% and 19% respectively of the total uronic acid contents. 3. The correlation between the contents of sulphate and iduronic acid indicated by this finding also applied to the fractionated deamination products of the two polymers. The sulphated fragments varied in size from disaccharide to octasaccharide (or larger) and showed sulphate/disaccharide molar ratios in the range of 0.05–2.0. The proportion of iduronic acid increased with increasing ester sulphate contents of the oligosaccharides. 4. Previous studies on the biosynthesis of heparin in a cell-free system have shown that l-iduronic acid residues are formed by C-5 epimerization of d-glucuronic acid units at the polymer level; the process requires concomitant sulphation of the polymer. The results obtained in the present structural study conform to these findings, and suggest further that similar mechanisms may operate in the biosynthesis of heparan sulphate. The epimerization reaction appears to be linked to the sulphation of hydroxyl groups but does not seem to require sulphation of the target uronic acid residues. The significance of sulphamino groups in relation to the formation of iduronic acid is unknown.     

Incidence of peptic ulcer disease in Gothenburg, 1985.

OBJECTIVE--To determine the incidence and age distribution of peptic ulcer disease in adults in Gothenburg. DESIGN--Retrospective study of patients with symptoms over one year. SETTING--All gastroenterology and x ray departments. PATIENTS--Any patient found to have an active ulcer crater during 1985. MAIN OUTCOME MEASURES--Sex, age, past history of gastrointestinal ulcers, and smoking habit. RESULTS--In 1985, 1402 peptic ulcers were diagnosed in 1137 adults. Over half (403; 54%) of the ulcers in men and 393 (60%) ulcers in women were in patients aged over 60. All types of ulcer showed increasing incidence with age. The sex ratio of patients aged 40-50 with peptic ulcers was 1:1. Nearly half (109; 48%) of ulcers diagnosed for the first time in men and 129 (57%) of such ulcers in women were in patients aged over 60. Elderly men and women were also more likely to develop haemorrhage. CONCLUSIONS--In Gothenburg there is a surprisingly high incidence of peptic ulcer disease, which increases considerably with age, possibly explained by the availability of modern diagnostic techniques as 1121 (80%) ulcers had been diagnosed by gastroscopy. Compared with earlier studies there was no difference in the incidence between men and women aged 40-50.     

Correction or transfer of immunodeficiency due to TNF-LT alpha deletion by bone marrow transplantation.

BACKGROUND: Mice with inactivated tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) genes have profound abnormalities of the immune system including lymphocytosis, lack of lymph nodes, undifferentiated spleen, hypoimmunoglobulinaemia, and defective Ig class switch. Here, we asked whether this phenotype is due to incompetent lymphohemopoietic progenitors or to a defective environment. MATERIALS AND METHODS: Lethally irradiated TNF-LT alpha-deficient and wild-type mice received bone marrow cells from either TNF-LT alpha-deficient or wild-type mice. The reconstitution and transfer of the phenotype was followed by morphological and functional analyses. RESULTS: Bone marrow cells from wild-type mice restored the synthesis of TNF and LT alpha, corrected the splenic microarchitecture, normalized the lymphocyte counts in the circulation, and repopulated the lamina propria with IgA-producing plasma cells of TNF-LT alpha-deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch in response to a T-cell dependent antigen was corrected, while no lymph nodes were formed. Conversely, the TNF-LT alpha phenotype could be transferred to wild-type mice by bone marrow transplantation after lethal irradiation. CONCLUSIONS: These data demonstrate that most TNF- and LT alpha-producing cells are bone marrow derived and radiosensitive, and that the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow cell transplantation. The genotype of the donor bone marrow cells determines the functional and structural phenotype of the TNF-LT alpha-deficient adult murine host, with the exception of lymph node formation. These findings may have therapeutic implications for the restoration of genetically defined immunodeficiencies in humans.     

Evaluation of Antioxidant,Antibacterial and Enhancement of Antibiotic Action by Punica granatum Leaves Crude Extract and Enriched Fraction against Multidrug-Resistant Bacteria

The aim of this study was to evaluate the phytochemical composition, antioxidant, and antimicrobial potential of crude extract and fractions of Punica granatum leaves. The extract was produced by turbo extraction, after which hexanic, ethyl acetate, and aqueous fractions were obtained by partitioning. The chemical analyses were performed by thin layer chromatography and high-performance liquid chromatography, and the antioxidant activities were assayed by DPPH^. and ABTS^.+. Minimal inhibitory and bactericidal concentrations (MIC/MBC) were applied to twenty-two bacteria. Most strains susceptible to extract/fractions and resistant to antibiotics were selected, and ampicillin, azithromycin, ciprofloxacin, and gentamicin were associated with the ethyl acetate fraction (EAF) against multidrug-resistant strains in modulatory and checkboard models. The data from chromatographic analyses showed flavonoids and tannins in the extract, as well as the enrichment of EAF in phenols, mainly flavonoids. The flavonoids were connected to the electron transfer activity demonstrated in the DPPH^. and ABTS^.+ assays. Gram-positive strains are more susceptible to EAF. The subinhibitory concentrations of P. granatum enhanced the antimicrobial activity of the agents and reduced the EAF individual MIC, and the combination of EAF and antibiotics demonstrated a synergistic effect. These results present a promising approach for developing a therapy in which antioxidant extracts and fractions can be used in combination with antibiotics.     

Morphological and immunohistochemical study of the midgut and fat body of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: noctuidae) treated with essential oils of the genus Piper

ABSTRACT

Essential oils are a promising alternative to insecticides. We investigated the LD₅₀ of oils extracted from Piper corcovadensis, P. marginatum, and P. arboreum after 48 h topical contact with Spodoptera frugiperda larvae using morphometry, histochemistry and immunohistochemistry of the midgut and fat body. Chromatography revealed that E-caryophyllene was the principal compound common to the Piper species. The essential oils of P. corcovadensis, P. marginatum and P. arboreum caused deleterious changes in the midgut of S. frugiperda larvae. P. corcovadensis oil produced the lowest LD₅₀ and significant histopathological alterations including elongation of the columnar cells, formation of cytoplasmic protrusions, reduction in carbohydrate, increased apoptotic index and decreased cell proliferation. P. arboreum oil caused histopathological alterations similar to P. corcovadensis, but caused the highest rate of cell proliferation and increased regenerative cells, which indicated rapid regeneration of the epithelium. Our findings demonstrated the insecticidal potential of P. corcovadensis for control of S. frugiperda owing to the significant damage it inflicted on S. frugiperda midgut.     

Mode of Death on Chagas Heart Disease: Comparison with Other Etiologies. A Subanalysis of the REMADHE Prospective Trial

Background

Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy.

Methods and results

We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34–5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04–1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97–0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47–6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01–1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34–0.94; p = 0.014) were independently associated with sudden death mortality.

Conclusions

In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death.

Trial Registration

ClinicalTrails.gov {"type":"clinical-trial","attrs":{"text":"NCT00505050","term_id":"NCT00505050"}}NCT00505050 (REMADHE)     

Occurrence of Nontuberculous Mycobacterial Pulmonary Infection in an Endemic Area of Tuberculosis

The majority of investigations of the epidemiology of nontuberculous mycobacteria (NTM) have focused on highly developed nations with a low prevalence of tuberculosis. In contrast, the Para state of north Brazil represents an area of high tuberculosis prevalence and increasing NTM incidence. Toward the goal of understanding the dynamics of infection by all Mycobacterium species, we report patient characteristics and the identification of NTM strains isolated from sputum samples from patients that were residents of Para, a state in the Amazon region, Northern of Brazil, over the period January 2010 through December 2011 (2 years). The 29 NTM patients comprised 13.5% of positive mycobacterial cultures over the 2-year period. A major risk factor for NTM pulmonary disease was previous tuberculosis (76%). Further, the average age of NTM patients (52 years) was significantly higher than that of tuberculosis patients (39 years) and more were female (72.4% vs. 37.4%). Unlike other Brazilian states, NTM pulmonary patients in Para were infected with a different spectrum of mycobacteria; primarily the rapidly growing Mycobacterium massiliense and Mycobacterium simiae complex.     

Using Information Interaction to Discover Epistatic Effects in Complex Diseases

It is widely agreed that complex diseases are typically caused by the joint effects of multiple instead of a single genetic variation. These genetic variations may show stronger effects when considered together than when considered individually, a phenomenon known as epistasis or multilocus interaction. In this work, we explore the applicability of information interaction to discover pairwise epistatic effects related with complex diseases. We start by showing that traditional approaches such as classification methods or greedy feature selection methods (such as the Fleuret method) do not perform well on this problem. We then compare our information interaction method with BEAM and SNPHarvester in artificial datasets simulating epistatic interactions and show that our method is more powerful to detect pairwise epistatic interactions than its competitors. We show results of the application of information interaction method to the WTCCC breast cancer dataset. Our results are validated using permutation tests. We were able to find 89 statistically significant pairwise interactions with a p-value lower than . Even though many recent algorithms have been designed to find epistasis with low marginals, we observed that all (except one) of the SNPs involved in statistically significant interactions have moderate or high marginals. We also report that the interactions found in this work were not present in gene-gene interaction network STRING.