Intestinal injury and endotoxemia in children undergoing surgery for congenital heart disease

RATIONALE: Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively. OBJECTIVES: To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease. METHODS: We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease. MEASUREMENTS AND MAIN RESULTS: Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells. CONCLUSIONS: Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.

The Climate-G testbed: towards large scale distributed data management for climate change

Climate-G is a large scale distributed testbed devoted to climate change research. It is an unfunded effort started in 2008 and involving a wide community both in Europe and US. The testbed is an interdisciplinary effort involving partners from several institutions and joining expertise in the field of climate change and computational science. Its main goal is to allow scientists carrying out geographical and cross-institutional data discovery, access, analysis, visualization and sharing of climate data. It represents an attempt to address, in a real environment, challenging data and metadata management issues. This paper presents a complete overview about the Climate-G testbed highlighting the most important results that have been achieved since the beginning of this project.

Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method

We report the investigation of the mechanical properties of different types of amyloid fibrils by the peak force quantitative nanomechanical (PF-QNM) technique. We demonstrate that this technique correctly measures the Young’s modulus independent of the polymorphic state and the cross-sectional structural details of the fibrils, and we show that values for amyloid fibrils assembled from heptapeptides, a-synuclein, Ab(1–42), insulin, b-lactoglobulin,lysozyme, ovalbumin, Tau protein and bovine serum albumin all fall in the range of 2–4 GPa.

Numerical simulation of tephra transport and deposition of the 1982 El Chichón eruption and implications for hazard assessment

El Chichón volcano, Chiapas, Mexico, erupted explosively on March 29th, 1982, after a repose period of about 550 years. Amongst ten eruptive episodes documented between March 29th and April 4th, only the three that occurred on March 29th and April 4th produced significant pyroclastic tephra deposits. Here we use analytical (HAZMAP) and numerical (FALL3D) tephra transport models to reconstruct the deposits and the atmospheric plume dispersal associated with the three main fallout units of the 1982 eruption. On the basis of such a reconstruction, we produce hazard maps of tephra fallout associated to a Plinian eruption and discuss the implications of such a severe eruption scenario.

Change detection evokes a Simon-like effect

A change detection paradigm was used to estimate the role of explicit change detection in the generation of the irrelevant spatial stimulus coding underlying the Simon effect. In one condition, no blank was interposed between two successive displays, which produced efficient change detection. In another condition, the presence of a blank frame produced a robust change blindness effect, which is crucially assumed to occur as the consequence of impaired attentional orienting to the change location. The results showed a strong Simon-like effect under conditions of efficient change detection. By contrast, no Simon-like effect was observed under conditions of change blindness, namely when attention shifting towards the change location was hampered. Experiment 2 supported this pattern by showing that a Simon-like effect could be observed when the blank was present, but only when participants detected the change by means of a cue that was informative as to change location. Overall, our findings show that a Simon-like effect can only be observed under conditions of explicit change detection, likely because a shift of attention towards the change location has occurred.

Ozone and climate: a review of interconnections

Stratospheric ozone has been depleted over the last 25 years following anthropogenic emissions of a number of chlorine- and bromine-containing compounds (ozone-depleting substances, ODSs), which are now regulated under the Montreal Protocol. The Protocol has been effective in controlling the net growth of these compounds in the atmosphere. As chlorine and bromine slowly decrease in the future, ozone levels are expected to increase in the coming decades, although the evolution will also depend on the changing climate system.

Medieval foreign exchange: a time series analysis

This chapter applies rigorous statistical analysis to existing datasets of medieval exchange rates quoted in merchants’ letters sent from Barcelona, Bruges and Venice between 1380 and 1310, which survive in the archive of Francesco di Marco Datini of Prato. First, it tests the exchange rates for stationarity. Second, it uses regression analysis to examine the seasonality of exchange rates at the three financial centres and compares them against contemporary descriptions by the merchant Giovanni di Antonio da Uzzano. Third, it tests for structural breaks in the exchange rate series.

Cigarette smoke-induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents

Cigarette smoke (CS) inhalation causes an early inflammatory response in rodent airways by stimulating capsaicin-sensitive sensory neurons that express transient receptor potential cation channel, subfamily V, member 1 (TRPV1) through an unknown mechanism that does not involve TRPV1. We hypothesized that 2 alpha,beta-unsaturated aldehydes present in CS, crotonaldehyde and acrolein, induce neurogenic inflammation by stimulating TRPA1, an excitatory ion channel coexpressed with TRPV1 on capsaicin-sensitive nociceptors. We found that CS aqueous extract (CSE), crotonaldehyde, and acrolein mobilized Ca2+ in cultured guinea pig jugular ganglia neurons and promoted contraction of isolated guinea pig bronchi. These responses were abolished by a TRPA1-selective antagonist and by the aldehyde scavenger glutathione but not by the TRPV1 antagonist capsazepine or by ROS scavengers. Treatment with CSE or aldehydes increased Ca2+ influx in TRPA1-transfected cells, but not in control HEK293 cells, and promoted neuropeptide release from isolated guinea pig airway tissue. Furthermore, the effect of CSE and aldehydes on Ca2+ influx in dorsal root ganglion neurons was abolished in TRPA1-deficient mice. These data identify alpha,beta-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases.

A spatial view of ensemble spread in convection permitting ensembles

With movement toward kilometer-scale ensembles, new techniques are needed for their characterization. A new methodology is presented for detailed spatial ensemble characterization using the fractions skill score (FSS). To evaluate spatial forecast differences, the average and standard deviation are taken of the FSS calculated over all ensemble member–member pairs at different scales and lead times. These methods were found to give important information about the ensemble behavior allowing the identification of useful spatial scales, spinup times for the model, and upscale growth of errors and forecast differences. The ensemble spread was found to be highly dependent on the spatial scales considered and the threshold applied to the field. High thresholds picked out localized and intense values that gave large temporal variability in ensemble spread: local processes and undersampling dominate for these thresholds. For lower thresholds the ensemble spread increases with time as differences between the ensemble members upscale. Two convective cases were investigated based on the Met Office United Model run at 2.2-km resolution. Different ensemble types were considered: ensembles produced using the Met Office Global and Regional Ensemble Prediction System (MOGREPS) and an ensemble produced using different model physics configurations. Comparison of the MOGREPS and multiphysics ensembles demonstrated the utility of spatial ensemble evaluation techniques for assessing the impact of different perturbation strategies and the need for assessing spread at different, believable, spatial scales.

Gender and the business cycle: an analysis of labour markets in the US and UK

Starting from an improved understanding of the relationship between gender labour market stocks and the business cycle, we analyse the contributing role of flows in the US and UK. Focusing on the post 2008 recession period, the subsequent greater rise in male unemployment can mostly be explained by a less cyclical response of flows between employment and unemployment for women, especially the entry into unemployment. Across gender and country, the inactivity rate is generally not sensitive to the state of the economy. However, a flows based analysis reveals a greater importance of the participation margin over the cycle. Changes in the rates of flow between unemployment and inactivity can each account for around 0.8-1.1 percentage points of the rise in US male and female unemployment rates during the latest downturn. For the UK, although the participation flow to unemployment similarly contributed to the increase of the female unemployment rate, this was not the case for men. The countercyclical flow rate from inactivity to employment was also more significant for women, especially in the US, where it accounted for approximately all of the fall in employment, compared with only 40% for men.