Penalized Likelihood Methods for Estimation of Sparse High Dimensional Directed Acyclic Graphs

Directed acyclic graphs (DAGs) are commonly used to represent causal relationships among random variables in graphical models. Applications of these models arise in the study of physical, as well as biological systems, where directed edges between nodes represent the influence of components of the system on each other. The general problem of estimating DAGs from observed data is computationally NP-hard, Moreover two directed graphs may be observationally equivalent. When the nodes exhibit a natural ordering, the problem of estimating directed graphs reduces to the problem of estimating the structure of the network. In this paper, we propose a penalized likelihood approach that directly estimates the adjacency matrix of DAGs. Both lasso and adaptive lasso penalties are considered and an efficient algorithm is proposed for estimation of high dimensional DAGs. We study variable selection consistency of the two penalties when the number of variables grows to infinity with the sample size. We show that although lasso can only consistently estimate the true network under stringent assumptions, adaptive lasso achieves this task under mild regularity conditions. The performance of the proposed methods is compared to alternative methods in simulated, as well as real, data examples.Comment: 19 pages, 8 figure

Phenotypic and molecular characterization of plasmid mediated AmpC among clinical isolates of Klebsiella pneumoniae isolated from different hospitals in Tehran

Introduction: Klebsiella pneumoniae is one of the main opportunistic pathogens which can cause different types of infections. Production of beta-lactamases like AmpC and ESBL mostly lead to beta-lactam resistance in these Gram-Negative bacteria. The aim of this study was the detection of AmpC-producing K. pneumoniae in clinical isolates. Materials and Methods: Three hundred and three isolates of K. pneumoniae were identified. Double disc method including cefoxitin with cefepime and using boronic acid with cloxacillin were performed as two phenotypic methods for detection of AmpC. Amplification of AmpC gene was performed by PCR. Results: Eight and three isolates showed positive results in double disc method and by using boronic acid with cloxacillin, respectively. Five isolates had specific band for AmpC gene after electrophoresis. Conclusion: Our results were indicated the low prevalence of AmpC-producer-K. pnemoniae in Iran. On the other hand these two tested phenotypic methods showed low sensitivity for detection of AmpC. © 2015 Journal of Clinical and Diagnostic Research. All Rights Reserved

THINK Back: KNowledge-based Interpretation of High Throughput data

Results of high throughput experiments can be challenging to interpret. Current approaches have relied on bulk processing the set of expression levels, in conjunction with easily obtained external evidence, such as co-occurrence. While such techniques can be used to reason probabilistically, they are not designed to shed light on what any individual gene, or a network of genes acting together, may be doing. Our belief is that today we have the information extraction ability and the computational power to perform more sophisticated analyses that consider the individual situation of each gene. The use of such techniques should lead to qualitatively superior results

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants

Background: Conflicting data suggest that statins could cause chronic liver disease in certain group of patients, while improving prognosis in those with chronic viral hepatitis (CVH). Purpose: To quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on CVH patients.Data Sources: The search strategy was explored by a medical librarian using bibliographic databases, from January 2015 to April 2020.Data synthesis: The results showed no significant difference in the risk of mortality between statin users and non-users in the overall analysis. However, the risk of mortality significantly reduced by 39% in statin users who were followed for more than three years. Moreover, the risk of HCC, fibrosis, and cirrhosis in those on statins decreased by 53%, 45% and 41%, respectively. Although ALT and AST reduced slightly following statin therapy, this reduction was not statistically significant. Limitations: A significant heterogeneity among studies was observed, resulting from differences in clinical characteristics between statin users and non-users, study designs, population samples, diseases stage, comorbidities, and confounding covariates. Conclusion: Not only long-term treatment with statins seems to be safe in patients affected by hepatitis, but also it significantly improves their prognosis

Single left coronary artery with origin of right coronary artery from left circumflex: a case report

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: A 40-years-old female presented with intermittent chest pain and dyspnea on exertion. Case Presentation: Electrocardiography showed sinus rhythm with ST-depression in inferior and lateral leads. Subsequent exercise treadmill testing revealed significant ST-depression in V4–V5 and V6 leads. Coronary angiography later showed a single left coronary artery with right coronary artery arising from left circumflex artery, a rare anomaly of coronary arteries. No atheromatous lesion was seen during angiography. Conclusion: The dignosis of this anomaly is importsnt because the symptoms cannot be differentiated from atherosclerotic coronary artery disease. Case presentation A 40-years-old female was admitted to the hospital with intermittent substernal chest pain and dyspnea. She visited our outpatient clinic because of exacerbation o

Antimicrobial susceptibility patterns of the gram-negative bacteria isolated from septicemia in Children?s Medical Center, Tehran, Iran

Introduction. The choice of antimicrobial treatment for septicemia is often empirical and based on the knowledge of local antimicrobial activity patterns of the most common bacteria causing such bloodstream infections. The current study aimed to study the prevalence of bacterial pathogens causing septicemia and their antimicrobial resistant profiles in hospital admitted patients. Methods. This cross sectional study done at Children?s Medical Center, Tehran, Iran. We examined 168 bacterial strains isolated from 186 clinically diagnosed septicemia cases refereed at Children?s Medical Center, Tehran, Iran Over a period of twelve months from July 2010 to 2011 July. 11446 blood samples from patients of clinically suggestive septicemia were evaluated. Results. Bacterial strains were isolated from 910 (7.95%) of blood cultures. Gram-negative bacteria identified were Pseudomonas species (20.5%), Pseudomonas aeruginosa (1.86%), Salmonella spp (1.09%), Acinetobacter naumannii (8.13%), Escherichia coli (4.06%), Klebsiella spp (5.16%). Gram-negative pathogens were more than gram positive in bloodstream infections. Antimicrobial susceptibility testing was done according to Clinical and Labo- ratory Standards Institute (CLSI, USA) guidelines against: amikacin ampicillin, amoxicillin, amoxiclav, cefuroxime, cefotaxime, ceftazidime, cefoperazone tetracycline, chloramphenicol, ciprofloxacin, gentamicin. Resistanc to different antibiotics in the most important isolated bacteria were: 32.1 %, 10.8%, 87.8%, 96%, 39.1%, 35.2, 49.4%, 69%, 80.02%, 22%, 59%, 30.1% respectively, for Pseudomonas spp, 32%, 3.7%, 84.2 %, 83.2%, 80.1%, 75.4%, 44.8%, 45.2%, 33.3%, 19%, 34.1, 11.5% respectively for Acinetobacter species. Discussion. Resistant to majority of the antimicrobial agents for several pathogens implicated in bloodstream infections, particularly in Gram-negative bacteria, can make complication in treatment of infection cause by them

Chameleonic Generalized Brans--Dicke model and late-time acceleration

In this paper we consider Chameleonic Generalized Brans--Dicke Cosmology in the framework of FRW universes. The bouncing solution and phantom crossing is investigated for the model. Two independent cosmological tests: Cosmological Redshift Drift (CRD) and distance modulus are applied to test the model with the observation.Comment: 20 pages, 15 figures, to be published in Astrophys. Space Sci. (2011

FRW Cosmology From Five Dimensional Vacuum Brans-Dicke Theory

We follow approach of induced matter theory for 5D vacuum BD, introduce induced matter and potential in 4D hypersurfaces, and employ generalized FRW type solution. We confine ourselves to scalar field and scale factors be functions of the time. This makes the induced potential, by its definition, vanishes. When the scale factor of fifth dimension and scalar field are not constants, 5D eqs for any geometry admit a power law relation between scalar field and scale factor of fifth dimension. Hence the procedure exhibits that 5D vacuum FRW like eqs are equivalent, in general, to corresponding 4D vacuum ones with the same spatial scale factor but new scalar field and coupling constant. We show that 5D vacuum FRW like eqs or its equivalent 4D vacuum ones admit accelerated solutions. For constant scalar field, eqs reduce to usual FRW eqs with typical radiation dominated universe. For this situation we obtain dynamics of scale factors for any geometry without any priori assumption. For nonconstant scalar fields and spatially flat geometries, solutions are found to be power law and exponential ones. We also employ weak energy condition for induced matter, that allows negative/positive pressures. All types of solutions fulfill WEC in different ranges. The power law solutions with negative/positive pressures admit both decelerating and accelerating ones. Some solutions accept shrinking extra dimension. By considering nonghost scalar fields and recent observational measurements, solutions are more restricted. We illustrate that accelerating power law solutions, which satisfy WEC and have nonghost fields, are compatible with recent observations in ranges -4/3 < \omega </- -1.3151 and 1.5208 </- n < 1.9583 for dependence of fifth dimension scale factor with usual scale factor. These ranges also fulfill condition nonghost fields in the equivalent 4D vacuum BD eqs.Comment: 18 pages, 16 figures, 11 table

Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila.

In most organisms, dietary restriction (DR) increases lifespan. However, several studies have found that genotypes within the same species vary widely in how they respond to DR. To explore the mechanisms underlying this variation, we exposed 178 inbred Drosophila melanogaster lines to a DR or ad libitum (AL) diet, and measured a panel of 105 metabolites under both diets. Twenty four out of 105 metabolites were associated with the magnitude of the lifespan response. These included proteinogenic amino acids and metabolites involved in α-ketoglutarate (α-KG)/glutamine metabolism. We confirm the role of α-KG/glutamine synthesis pathways in the DR response through genetic manipulations. We used covariance network analysis to investigate diet-dependent interactions between metabolites, identifying the essential amino acids threonine and arginine as hub metabolites in the DR response. Finally, we employ a novel metabolic and genetic bipartite network analysis to reveal multiple genes that influence DR lifespan response, some of which have not previously been implicated in DR regulation. One of these is CCHa2R, a gene that encodes a neuropeptide receptor that influences satiety response and insulin signaling. Across the lines, variation in an intronic single nucleotide variant of CCHa2R correlated with variation in levels of five metabolites, all of which in turn were correlated with DR lifespan response. Inhibition of adult CCHa2R expression extended DR lifespan of flies, confirming the role of CCHa2R in lifespan response. These results provide support for the power of combined genomic and metabolomic analysis to identify key pathways underlying variation in this complex quantitative trait