Genetic Variation in Spatio-Temporal Confined USA300 Community-Associated MRSA Isolates: A Shift from Clonal Dispersion to Genetic Evolution?

NTRODUCTION: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA. MATERIALS AND METHODS: Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements. CONCLUSION: The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Plant Vaccines: An Immunological Perspective.

The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective

Integrating Knowledge Graphs for Analysing Academia and Industry Dynamics

Academia and industry are constantly engaged in a joint effort for producing scientific knowledge that will shape the society of the future. Analysing the knowledge flow between them and understanding how they influence each other is a critical task for researchers, governments, funding bodies, investors, and companies. However, current corpora are unfit to support large-scale analysis of the knowledge flow between academia and industry since they lack of a good characterization of research topics and industrial sectors. In this short paper, we introduce the Academia/Industry DynAmics (AIDA) Knowledge Graph, which characterizes 14M papers and 8M patents according to the research topics drawn from the Computer Science Ontology. 4M papers and 5M patents are also classified according to the type of the author's affiliations (academy, industry, or collaborative) and 66 industrial sectors (e.g., automotive, financial, energy, electronics) obtained from DBpedia. AIDA was generated by an automatic pipeline that integrates several knowledge graphs and bibliographic corpora, including Microsoft Academic Graph, Dimensions, English DBpedia, the Computer Science Ontology, and the Global Research Identifier Database

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/

Responses to gestational weight management guidance: a thematic analysis of comments made by women in online parenting forums

Background: The National Institute for Health and Clinical Excellence (NICE) published guidance on weight management in pregnancy in July 2010[1], and this received considerable press coverage across a range of media. This offered an opportunity to examine how gestational weight management guidance was received by UK women. Methods: A thematic analysis was conducted of 400 posts made in UK-based parenting internet forums in the week following the publication of the NICE guidance. This allowed us to examine the naturally occurring comments from 202 women who posted about the guidance on public forums. Results: Three main themes were identified and explored: i) Perceived control/responsibility ii) Risk perception iii) Confused messages. Conclusions: Women differed in their perceptions of the level of control that they had over being overweight with some feeling responsible and motivated to maintain a healthy lifestyle. Others felt there were multiple factors influencing their weight issues beyond their control. There were reports of feeling guilty about the impact of weight on the growing baby and experiencing significant obesity stigma from the public and health professionals. Information about the risks of overweight and obesity in pregnancy were difficult messages for women to hear, and for health professionals to deliver. Women reported being confused by the messages that they received. Health messages need to be delivered sensitively to women, and health professionals need support and training to do this. Risk information should always be accompanied with clear advice and support to help women to manage their weight in pregnancy. Keywords: internet-mediated research, gestational weight gain, parenting forums, NICE, women, views, risk perception</p

Physical comorbidities in men with mood and anxiety disorders: a population-based study

Background : The mind-body nexus has been a topic of growing interest. Further data are however required to understand the specific relationship between mood and anxiety disorders and individual physical health conditions, and to verify whether these psychiatric disorders are linked to overall medical burden. Methods : This study examined data collected from 942 men, 20 to 97 years old, participating in the Geelong Osteoporosis Study. A lifetime history of mood and anxiety disorders was identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). The presence of medical conditions (lifetime) was self-reported and confirmed by medical records, medication use or clinical data. Anthropometric measurements and socioeconomic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Logistic regression models were used to test the associations. Results : After adjustment for age, socioeconomic status, and health risk factors (body mass index, physical activity and smoking), mood disorders were associated with gastro oesophageal reflux disease (GORD), recurrent headaches, blackouts and/or epilepsy, liver disorders and pulmonary disease in older people, whilst anxiety disorders were significantly associated with thyroid, GORD and other gastrointestinal disorders, and psoriasis. Increased odds of high medical burden were associated with both mood and anxiety disorders. Conclusions : Our study provides further population-based evidence supporting the link between mental and physical illness in men. Understanding these associations is not only necessary for individual management, but also to inform the delivery of health promotion messages and health care

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications