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.

Between writing and type: the stencil letter

An exhibition of stencil letters from the 18th century to the present day. Co-curated by Eric Kindel and Fred Smeijers, the exhibition featured a wide selection of stencil letters in the context of historical artefacts, documents and ephemera, including stencil plates and stencilling devices, specimens and catalogues and patent inventions. The exhibition also introduced a series of new stencil fonts designed by Maurice Göldner, Pierre Pané-Farré and Fred Smeijers. The design of each font made reference to and was informed by the historical material.

Typography papers, 9

This latest issue of the series of Typography papers opens with a beautifully illustrated article by the type designer Gerard Unger on ‘Romanesque’ letters. A further installment of Eric Kindel’s pathbreaking history of stencil letters is published in contributions by him, Fred Smeijers, and James Mosley. Maurice Göldner writes the first history of an early twentieth-century German typefounder, Brüder Butter. William Berkson and Peter Enneson recover the notion of ‘readability’ through a history of the collaboration between Matthew Luckiesh and the Linotype Company. Paul Luna discusses the role of pictures in dictionaries. Titus Nemeth describes a new form of Arabic type for metal composition. The whole gathering shows the remarkable variety and vitality of typography now.

Scattered power from non-thermal, F-region plasma observed by EISCAT—evidence for coherent echoes?

Three rapid, poleward bursts of plasma flow, observed by the U.K.-POLAR EISCAT experiment, are studied in detail. In all three cases the large ion velocities (> 1 kms−1) are shown to drive the ion velocity distribution into a non-Maxwellian form, identified by the characteristic shape of the observed spectra and the fact that analysis of the spectra with the assumption of a Maxwellian distribution leads to excessive rises in apparent ion temperature, and an anticorrelation of apparent electron and ion temperatures. For all three periods the total scattered power is shown to rise with apparent ion temperature by up to 6 dB more than is expected for an isotropic Maxwellian plasma of constant density and by an even larger factor than that expected for non-thermal plasma. The anomalous increases in power are only observed at the lower altitudes (< 300 km). At greater altitudes the rise in power is roughly consistent with that simulated numerically for homogeneous, anisotropic, non-Maxwellian plasma of constant density, viewed using the U.K.-POLAR aspect angle. The spectra at times of anomalously high power are found to be asymmetric, showing an enhancement near the downward Doppler-shifted ion-acoustic frequency. Although it is not possible to eliminate completely rapid plasma density fluctuations as a cause of these power increases, such effects cannot explain the observed spectra and the correlation of power and apparent ion temperature without an unlikely set of coincidences. The observations are made along a beam direction which is as much as 16.5° from orthogonality with the geomagnetic field. Nevertheless, some form of coherent-like echo contamination of the incoherent scatter spectrum is the most satisfactory explanation of these data.

Non-Maxwellian ion velocity distributions observed using EISCAT

Recent observations from the EISCAT incoherent scatter radar have revealed bursts of poleward ion flow in the dayside auroral ionosphere which are consistent with the ionospheric signature of flux transfer events at the magnetopause. These bursts frequently contain ion drifts which exceed the neutral thermal speed and, because the neutral thermospheric wind is incapable of responding sufficiently rapidly, toroidal, non-Maxwellian ion velocity distributions are expected. The EISCAT observations are made with high time resolution (15 seconds) and at a large angle to the geomagnetic field (73.5°), allowing the non-Maxwellian nature of the distribution to be observed remotely for the first time. The observed features are also strongly suggestive of a toroidal distribution: characteristic spectral shape, increased scattered power (both consistent with reduced Landau damping and enhanced electric field fluctuations) and excessively high line-of-sight ion temperatures deduced if a Maxwellian distribution is assumed. These remote sensing observations allow the evolution of the distributions to be observed. They are found to be non-Maxwellian whenever the ion drift exceeds the neutral thermal speed, indicating that such distributions can exist over the time scale of the flow burst events (several minutes).

Comparison of bioactivities, binding properties and intra-follicular levels of bovine follistatins

Five isoforms of follistatin (FST) (Mr 31, 33, 35, 37, 41kDa) were purified from bovine follicular fluid (bFF). Comparison of their activin- and heparan sulphate proteoglycan (HSP)-binding properties and bio-potencies in neutralization of activin-A action in vitro revealed that all five isoforms bound activin-A, but with different affinities. Only the 31kDa isoform (FST-288) bound to HSP. FST-288 also showed the greatest biopotency with 35 and 41kDa isoforms being least potent. To determine whether bovine follicle development is associated with changing intrafollicular FST and activin profiles, we analyzed bFF from dominant (DF) and subordinate (SF) follicles collected at strategic times during a synchronized estrous cycle. Total FST, activin-A and activin-AB were measured by immunoassay while individual FST isoforms were quantified by immunoblotting. Follicle diameter was positively correlated with estrogen:progesterone ratio (r=0.56) in bFF but negatively correlated with activin-A (r=-0.34), activin-AB (r=-0.80) and ‘total’ FST (r=-0.70) levels. Follicle diameter was positively correlated with abundance of the 41 kDa isoform (r=0.59) but negatively correlated with abundance of 33 and 31 kDa isoforms (r=-0.56, -0.41). Both follicle status (DF vs SF) and cycle stage affected total FST, activin-A, activin-B levels while follicle status, but not cycle stage, affected abundance of 41, 37, 33 and 31kDa FST isoforms. Collectively, these findings indicate that intrafollicular FST isoforms that differ in their ability to bind and neutralise activins and associate with cell-surface proteoglycans, show divergent changes during follicle development. Enhanced FST production may have an important negative role, either directly or via inhibition of the positive effects of activins, on follicle growth and function during follicular waves.

The application of social marketing in reducing road traffic accidents amoung young male drivers: an investigation using physical fear threat appeals

There were 338 road fatalities on Irish roads in 2007. Research in 2007 by the Road Safety Authority in Ireland states that young male drivers (17 – 25 years) are seven times more likely to be killed on Irish roads than other road users. The car driver fatality rate was found to be approximately 10 times higher for young male drivers than for female drivers in 2000. Young male drivers in particular demonstrate a high proclivity for risky driving behaviours. These risky behaviours include drink driving, speeding, rug-driving and engaging in aggressive driving. Speed is the single largest contributing factor to road deaths in Ireland. Approximately 40% of fatal accidents are caused by excessive or inappropriate speed. This study focuses on how dangerous driving behaviours may be addressed through social marketing. This study analyses the appropriate level of fear that needs to be induced in order to change young male driving behaviour.

Change in the archive: Blanchot's 'L'Entretien infini'

Today we are faced with the problem of how to relate the archives of deconstructionist thinkers to their thought, which seems opposed to historically-oriented or genetic criticism. This article is the first to look comprehensively at the gestation of Maurice Blanchot's L'Entretien infini, including the work's page-proofs which were made available in 2009. I thus address the multiple processes of change at work throughout Blanchot's writing, with change being a process whose importance goes beyond any single new form of writing resulting from it. My presentation of the archival material is contextualized via a discussion of the notion of L'Absence de livre (the project's working title). Rather than being a straightfoward incompleteness or fragmentation, this notion establishes a fraught relationship between such ideas and what it calls ‘le Livre’.

Since we have been a dialogue: Blanchot's 'Entretiens'

At the turn of the 1960s, Maurice Blanchot began publishing texts that he named entretiens, this change in his writing responding to what deconstruction sees as the closure of logocentric or continuous discourse. Paradoxically, this closure does not prevent such discourse, in which philosophical enquiry and technological change are intertwined, from dominating the modern world. By changing his writing, and by reiterating the dialogical form so central to metaphysical tradition since Plato, Blanchot gives voice to the tensions between continuity and its ‘outside’, between philosophy and literature. This is one sense in which his entretiens do not engage in a representation of difference, but instead open themselves to the inflections of what Jean-Luc Nancy calls le partage des voix.

The ancient Britons: groundwater fauna survived extreme climate change over tens of millions of years across NW Europe

Global climate changes during the Cenozoic (65.5–0 Ma) caused major biological range shifts and extinctions. In northern Europe, for example, a pattern of few endemics and the dominance of wide-ranging species is thought to have been determined by the Pleistocene (2.59–0.01 Ma) glaciations. This study, in contrast, reveals an ancient subsurface fauna endemic to Britain and Ireland. Using a Bayesian phylogenetic approach, we found that two species of stygobitic invertebrates (genus Niphargus) have not only survived the entire Pleistocene in refugia but have persisted for at least 19.5 million years. Other Niphargus species form distinct cryptic taxa that diverged from their nearest continental relative between 5.6 and 1.0 Ma. The study also reveals an unusual biogeographical pattern in the Niphargus genus. It originated in north-west Europe approximately 87 Ma and underwent a gradual range expansion. Phylogenetic diversity and species age are highest in north-west Europe, suggesting resilience to extreme climate change and strongly contrasting the patterns seen in surface fauna. However, species diversity is highest in south-east Europe, indicating that once the genus spread to these areas (approximately 25 Ma), geomorphological and climatic conditions enabled much higher diversification. Our study highlights that groundwater ecosystems provide an important contribution to biodiversity and offers insight into the interactions between biological and climatic processes.