Treating Viral Respiratory Tract Infections with Antibiotics in Hospitals: No Longer a Case of Mistaken Identity

Widespread use of antibiotics in hospitalized patients contributes to the development of multidrug resistant organisms that make many infections increasingly difficult to treat. Despite calls to prescribe antibiotics judiciously, many physicians continue to order antibiotics for inpatients who do not need them. This Issue Brief investigates antibiotic use in hospitalized adults with a confirmed viral infection, a group of patients that may not benefit from such therapy. Understanding the factors that lead to inappropriate antibiotic use may help change clinical practice and limit antibiotic resistance

Bioprospecting Finds the Toughest Biological Material: Extraordinary Silk from a Giant Riverine Orb Spider

Background Combining high strength and elasticity, spider silks are exceptionally tough, i.e., able to absorb massive kinetic energy before breaking. Spider silk is therefore a model polymer for development of high performance biomimetic fibers. There are over 41.000 described species of spiders, most spinning multiple types of silk. Thus we have available some 200.000+ unique silks that may cover an amazing breadth of material properties. To date, however, silks from only a few tens of species have been characterized, most chosen haphazardly as model organisms (Nephila) or simply from researchers' backyards. Are we limited to ‘blindly fishing’ in efforts to discover extraordinary silks? Or, could scientists use ecology to predict which species are likely to spin silks exhibiting exceptional performance properties? Methodology We examined the biomechanical properties of silk produced by the remarkable Malagasy ‘Darwin's bark spider’ (Caerostris darwini), which we predicted would produce exceptional silk based upon its amazing web. The spider constructs its giant orb web (up to 2.8 m2) suspended above streams, rivers, and lakes. It attaches the web to substrates on each riverbank by anchor threads as long as 25 meters. Dragline silk from both Caerostris webs and forcibly pulled silk, exhibits an extraordinary combination of high tensile strength and elasticity previously unknown for spider silk. The toughness of forcibly silked fibers averages 350 MJ/m3, with some samples reaching 520 MJ/m3. Thus, C. darwini silk is more than twice tougher than any previously described silk, and over 10 times better than Kevlar®. Caerostris capture spiral silk is similarly exceptionally tough. Conclusions Caerostris darwini produces the toughest known biomaterial. We hypothesize that this extraordinary toughness coevolved with the unusual ecology and web architecture of these spiders, decreasing the likelihood of bridgelines breaking and collapsing the web into the river. This hypothesis predicts that rapid change in material properties of silk co-occurred with ecological shifts within the genus, and can thus be tested by combining material science, behavioral observations, and phylogenetics. Our findings highlight the potential benefits of natural history–informed bioprospecting to discover silks, as well as other materials, with novel and exceptional properties to serve as models in biomimicry.Primary funding for this work came from the Slovenian Research Agency (grant Z1-9799-0618-07 to I. Agnarsson), the National Geographic Society (grant 8655-09 to the authors), and the National Science Foundation (grants DBI-0521261, DEB-0516038 and IOS-0745379 to T. Blackledge). Additional funding came from the European Community 6th Framework Programme (a Marie Curie International Reintegration Grant MIRG-CT-2005 036536 to M. Kuntner). The 2001 field work was supported by the Sallee Charitable Trust grant to I. Agnarsson and M. Kuntner and by a United States National Science Foundation grant (DEB-9712353) to G. Hormiga and J. A. Coddington. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Heme oxygenase-1 and carbon monoxide in pulmonary medicine

Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of anti-inflammatory effects, HO-1 limits tissue damage in response to proinflammatory stimuli and prevents allograft rejection after transplantation. The transcriptional upregulation of HO-1 responds to many agents, such as hypoxia, bacterial lipopolysaccharide, and reactive oxygen/nitrogen species. HO-1 and its constitutively expressed isozyme, heme oxygenase-2, catalyze the rate-limiting step in the conversion of heme to its metabolites, bilirubin IXα, ferrous iron, and carbon monoxide (CO). The mechanisms by which HO-1 provides protection most likely involve its enzymatic reaction products. Remarkably, administration of CO at low concentrations can substitute for HO-1 with respect to anti-inflammatory and anti-apoptotic effects, suggesting a role for CO as a key mediator of HO-1 function. Chronic, low-level, exogenous exposure to CO from cigarette smoking contributes to the importance of CO in pulmonary medicine. The implications of the HO-1/CO system in pulmonary diseases will be discussed in this review, with an emphasis on inflammatory states

Seismic evidence for a lower-mantle origin of the Iceland plume

Iceland, one of the most thoroughly investigated hotspots1,2,3, is generally accepted to be the manifestation of an upwelling mantle plume4. Yet whether the plume originates from the lower mantle or from a convective instability at a thermal boundary layer between the upper and lower mantle near 660 km depth5,6 remains unconstrained. Tomographic inversions of body-wave delay times show that low seismic velocities extend to at least 400 km depth beneath central Iceland7,8, but cannot resolve structure at greater depth. Here we report lateral variations in the depths of compressional-to-shear wave conversions at the two seismic discontinuities marking the top and bottom of the mantle transition zone beneath Iceland. We find that the transition zone is 20 km thinner than in the average Earth9 beneath central and southern Iceland, but is of normal thickness beneath surrounding areas, a result indicative of a hot and narrow plume originating from the lower mantle.This work was supported by the US NSFPeer Reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Application of Head Loss Coefficient for Surcharge Straight Path Manhole to Improve the Accuracy of Urban Inundation Analysis

Currently, adopted runoff analysis models focus on the characteristic factors of watersheds and neglect the analysis of the flow in conduits. Additionally, the usually employed XP-SWMM modeling package generally underestimates the flood area because it considers manholes as nodes and does not consider local head losses according to the shape and size of the nodes. Therefore, it is a necessity to consider the loss coefficient in surcharge manholes to improve inundation and runoff analysis methods. This study aims at improving the accuracy of discharge analysis before analyzing the storage and runoff reduction effects of storage facilities. Hydraulic experiments were conducted according to the changes in discharge and manhole shapes. We show that the flood area increases as the overflow discharge at manhole increases due to the application of the head loss coefficient. We demonstrate a concordance rate &ge;95% between results and observed flood area when accurate input data (from the parameters of the target watershed) and the head loss coefficient (from hydraulic experiments) are applied. Therefore, we demonstrate that the result of our 2D inundation analysis, considering the head loss coefficient in surcharge manhole, can be used as basic data for accurately identifying urban flood risk areas

Application of Head Loss Coefficient for Surcharge Straight Path Manhole to Improve the Accuracy of Urban Inundation Analysis

Currently, adopted runoff analysis models focus on the characteristic factors of watersheds and neglect the analysis of the flow in conduits. Additionally, the usually employed XP-SWMM modeling package generally underestimates the flood area because it considers manholes as nodes and does not consider local head losses according to the shape and size of the nodes. Therefore, it is a necessity to consider the loss coefficient in surcharge manholes to improve inundation and runoff analysis methods. This study aims at improving the accuracy of discharge analysis before analyzing the storage and runoff reduction effects of storage facilities. Hydraulic experiments were conducted according to the changes in discharge and manhole shapes. We show that the flood area increases as the overflow discharge at manhole increases due to the application of the head loss coefficient. We demonstrate a concordance rate ≥95% between results and observed flood area when accurate input data (from the parameters of the target watershed) and the head loss coefficient (from hydraulic experiments) are applied. Therefore, we demonstrate that the result of our 2D inundation analysis, considering the head loss coefficient in surcharge manhole, can be used as basic data for accurately identifying urban flood risk areas