The inevitable youthfulness of known high-redshift radio galaxies

Radio galaxies can be seen out to very high redshifts, where in principle they can serve as probes of the early evolution of the Universe. Here we show that for any model of radio-galaxy evolution in which the luminosity decreases with time after an initial rapid increase (that is, essentially all reasonable models), all observable high-redshift radio-galaxies must be seen when the lobes are less than 10^7 years old. This means that high-redshift radio galaxies can be used as a high-time-resolution probe of evolution in the early Universe. Moreover, this result helps to explain many observed trends of radio-galaxy properties with redshift [(i) the `alignment effect' of optical emission along radio-jet axes, (ii) the increased distortion in radio structure, (iii) the decrease in physical sizes, (iv) the increase in radio depolarisation, and (v) the increase in dust emission] without needing to invoke explanations based on cosmology or strong evolution of the surrounding intergalactic medium with cosmic time, thereby avoiding conflict with current theories of structure formation.Comment: To appear in Nature. 4 pages, 2 colour figures available on request. Also available at http://www-astro.physics.ox.ac.uk/~km

The epidemiology of postpartum malaria: a systematic review

Pregnant women are more susceptible to malaria than their non-pregnant counterparts. Less is known about the risk of malaria in the postpartum period. The epidemiology of postpartum malaria was systematically reviewed. Eleven articles fitted the inclusion criteria. Of the 10 studies that compared malaria data from the postpartum period with pregnancy data, nine studies suggested that the risk for malaria infection decreased after delivery. All three studies that compared postpartum data with non-pregnant non-postpartum women concluded that the risk did not return to pre-pregnancy levels immediately after delivery. The results of this review have to be carefully interpreted, as the majority of studies were not designed to study postpartum malaria, and there was large variability in study designs and reported outcomes. Current evidence suggests an effort should be made to detect and radically cure malaria during pregnancy so that women do not enter the postpartum period with residual parasites

Curcumin-Arteether Combination Therapy of Plasmodium berghei-Infected Mice Prevents Recrudescence Through Immunomodulation

Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA), a single dose of alpha,beta-arteether (ART) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE) or ART+curcumin (AC) treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2–3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFγ and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INFγ levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2−/− and IL-10−/− animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR2−/− mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naïve animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to be tested for prevention of recrudescence in falciparum and relapse in vivax malaria

Isolation and Characterization of New Leptospira Genotypes from Patients in Mayotte (Indian Ocean)

Leptospirosis has been recognized as an increasing public health problem affecting poor people from developing countries and tropical regions. However, the epidemiology of leptospirosis remains poorly understood in remote parts of the world. In this study of patients from the island of Mayotte, we isolated 22 strains from the blood of patients during the acute phase of illness. The pathogenic Leptospira strains were characterized by serology and various molecular typing methods. Based on serological data, serogroup Mini appears to be the dominant cause of leptospirosis in Mayotte. Further molecular characterization of these isolates allowed the identification of 10 pathogenic Leptospira genotypes that could correspond to previously unknown serovars. Further progress in our understanding of the epidemiology of Leptospira circulating genotypes in highly endemic regions should contribute to the development of novel strategies for the diagnosis and prevention of this neglected emerging disease

Dynamics and Control of Diseases in Networks with Community Structure

The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.) depends on the underlying host contact network. Human contact networks exhibit strong community structure. Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions. We use empirical and simulated networks to investigate the spread of disease in networks with community structure. We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals. Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network. We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention. The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure. Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health. Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics. These results have implications for the design of control strategies

Modern classification of neoplasms: reconciling differences between morphologic and molecular approaches

BACKGROUND: For over 150 years, pathologists have relied on histomorphology to classify and diagnose neoplasms. Their success has been stunning, permitting the accurate diagnosis of thousands of different types of neoplasms using only a microscope and a trained eye. In the past two decades, cancer genomics has challenged the supremacy of histomorphology by identifying genetic alterations shared by morphologically diverse tumors and by finding genetic features that distinguish subgroups of morphologically homogeneous tumors. DISCUSSION: The Developmental Lineage Classification and Taxonomy of Neoplasms groups neoplasms by their embryologic origin. The putative value of this classification is based on the expectation that tumors of a common developmental lineage will share common metabolic pathways and common responses to drugs that target these pathways. The purpose of this manuscript is to show that grouping tumors according to their developmental lineage can reconcile certain fundamental discrepancies resulting from morphologic and molecular approaches to neoplasm classification. In this study, six issues in tumor classification are described that exemplify the growing rift between morphologic and molecular approaches to tumor classification: 1) the morphologic separation between epithelial and non-epithelial tumors; 2) the grouping of tumors based on shared cellular functions; 3) the distinction between germ cell tumors and pluripotent tumors of non-germ cell origin; 4) the distinction between tumors that have lost their differentiation and tumors that arise from uncommitted stem cells; 5) the molecular properties shared by morphologically disparate tumors that have a common developmental lineage, and 6) the problem of re-classifying morphologically identical but clinically distinct subsets of tumors. The discussion of these issues in the context of describing different methods of tumor classification is intended to underscore the clinical value of a robust tumor classification. SUMMARY: A classification of neoplasms should guide the rational design and selection of a new generation of cancer medications targeted to metabolic pathways. Without a scientifically sound neoplasm classification, biological measurements on individual tumor samples cannot be generalized to class-related tumors, and constitutive properties common to a class of tumors cannot be distinguished from uninformative data in complex and chaotic biological systems. This paper discusses the importance of biological classification and examines several different approaches to the specific problem of tumor classification

Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

<p>Abstract</p> <p>Background</p> <p>Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of <it>E. coli </it>activates the expression of <it>atoDAEB </it>operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that <it>atoSC </it>is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the <it>atoDAEB </it>promoter as the single, <it>cis</it>-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the <it>E. coli </it>genome.</p> <p>Results</p> <p>Through the implementation of a computational <it>de novo </it>motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the <it>E. coli </it>genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the <it>in vivo </it>binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.</p> <p>Conclusions</p> <p>This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.</p

Patient Safety in the Cardiac Operating Room: Human Factors and Teamwork: A Scientific Study from the American Heart Association

The cardiac surgical operating room (OR) is a complex environment in which highly trained subspecialists interact with each other using sophisticated equipment to care for patients with severe cardiac disease and significant comorbidities. Thousands of patient lives have been saved or significantly improved with the advent of modern cardiac surgery. Indeed, both mortality and morbidity for coronary artery bypass surgery have decreased during the past decade. Nonetheless, the highly skilled and dedicated personnel in cardiac ORs are human and will make errors. Refined techniques, advanced technologies, and enhanced coordination of care have led to significant improvements in cardiac surgery outcomes

The plant-based immunomodulator curcumin as a potential candidate for the development of an adjunctive therapy for cerebral malaria

The clinical manifestations of cerebral malaria (CM) are well correlated with underlying major pathophysiological events occurring during an acute malaria infection, the most important of which, is the adherence of parasitized erythrocytes to endothelial cells ultimately leading to sequestration and obstruction of brain capillaries. The consequent reduction in blood flow, leads to cerebral hypoxia, localized inflammation and release of neurotoxic molecules and inflammatory cytokines by the endothelium. The pharmacological regulation of these immunopathological processes by immunomodulatory molecules may potentially benefit the management of this severe complication. Adjunctive therapy of CM patients with an appropriate immunomodulatory compound possessing even moderate anti-malarial activity with the capacity to down regulate excess production of proinflammatory cytokines and expression of adhesion molecules, could potentially reverse cytoadherence, improve survival and prevent neurological sequelae. Current major drug discovery programmes are mainly focused on novel parasite targets and mechanisms of action. However, the discovery of compounds targeting the host remains a largely unexplored but attractive area of drug discovery research for the treatment of CM. This review discusses the properties of the plant immune-modifier curcumin and its potential as an adjunctive therapy for the management of this complication