Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures

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An extraterrestrial trigger for the Early Cretaceous massive volcanism? Evidence from the paleo-Tethys Ocean

The Early Cretaceous Greater Ontong Java Event in the Pacific Ocean may have covered ca. 1% of the Earth's surface with volcanism. It has puzzled scientists trying to explain its origin by several mechanisms possible on Earth, leading others to propose an extraterrestrial trigger to explain this event. A large oceanic extraterrestrial impact causing such voluminous volcanism may have traces of its distal ejecta in sedimentary rocks around the basin, including the paleo-Tethys Ocean which was then contiguous with the Pacific Ocean. The contemporaneous marine sequence at central Italy, containing the sedimentary expression of a global oceanic anoxic event (OAE1a), may have recorded such ocurrence as indicated by two stratigraphic intervals with 187Os/188Os indicative of meteoritic influence. Here we show, for the first time, that platinum group element abundances and inter-element ratios in this paleo-Tethyan marine sequence provide no evidence for an extraterrestrial trigger for the Early Cretaceous massive volcanism

The trade-off between taxi time and fuel consumption in airport ground movement

Environmental impact is a very important agenda item in many sectors nowadays, which the air transportation sector is also trying to reduce as much as possible. One area which has remained relatively unexplored in this context is the ground movement problem for aircraft on the airport’s surface. Aircraft have to be routed from a gate to a runway and vice versa and it is still unknown whether fuel burn and environmental impact reductions will best result from purely minimising the taxi times or whether it is also important to avoid multiple acceleration phases. This paper presents a newly developed multi-objective approach for analysing the trade-off between taxi time and fuel consumption during taxiing. The approach consists of a combination of a graph-based routing algorithm and a population adaptive immune algorithm to discover different speed profiles of aircraft. Analysis with data from a European hub airport has highlighted the impressive performance of the new approach. Furthermore, it is shown that the trade-off between taxi time and fuel consumption is very sensitive to the fuel-related objective function which is used

The role of inflammation in epilepsy.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Sport in a youth prison: male young offenders' experiences of a sporting intervention

The numbers of children under the age of 18 being incarcerated in England and Wales has decreased of late, with official figures indicating that the current population of just over 1500 has halved during the last decade. But levels of reoffending among children released from prison remain the highest, with three out of four young people being reconvicted within one year of release from juvenile custody. Despite the fact that the overwhelming majority of community-based sports projects target children and young people, when it comes to incarcerated populations, sporting initiatives are less prevalent. Where sport has become well established as a useful social cohesion/inclusion strategy in community settings, some of these approaches have been translated into custodial settings. Resulting research has often proclaimed sporting pursuits as a modern-day panacea in terms of their social, psychological and emotional benefits, yet few studies have explored the nuances of sports-based interventions within secure settings. This paper comprises a small-scale, qualitative study of one such intervention in a Young Offender Institution in the South of England. Placing respondent accounts at the centre of the analysis, the paper sheds light on the practicalities of programme delivery by uncovering the motivating factors behind participant engagement whilst exploring broader notions of personal development. The paper concludes by highlighting that sport/physical activity can confer significant psychosocial benefits and promote the rehabilitation of young people leaving custody, particularly when integrated into wider programmes of support and provision

On impact and volcanism across the Cretaceous-Paleogene boundary

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism

Mental Addition in Bilinguals: An fMRI Study of Task-Related and Performance-Related Activation

Behavioral studies show that bilinguals are slower and less accurate when performing mental calculation in their nondominant (second; L2) language than in their dominant (first; L1) language. However, little is known about the neural correlates associated with the performance differences observed between bilinguals' 2 languages during arithmetic processing. To address the cortical activation differences between languages, the current study examined task-related and performance-related brain activation during mental addition when problems were presented auditorily in participants' L1 and L2. Eleven Chinese–English bilinguals heard 2-digit addition problems that required exact or approximate calculations. Functional magnetic resonance imaging results showed that auditorily presented multidigit addition in bilinguals activates bilateral inferior parietal and inferior frontal regions in both L1 and L2. Language differences were observed in the form of greater activation for L2 exact addition in the left inferior frontal area. A negative correlation between brain activation and behavioral performance during mental addition in L2 was observed in the left inferior parietal area. Current results provide further evidence for the effects of language-specific experience on arithmetic processing in bilinguals at the cortical level

Task-Specific Effects of tDCS-Induced Cortical Excitability Changes on Cognitive and Motor Sequence Set Shifting Performance

In this study, we tested the effects of transcranial Direct Current Stimulation (tDCS) on two set shifting tasks. Set shifting ability is defined as the capacity to switch between mental sets or actions and requires the activation of a distributed neural network. Thirty healthy subjects (fifteen per site) received anodal, cathodal and sham stimulation of the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). We measured set shifting in both cognitive and motor tasks. The results show that both anodal and cathodal single session tDCS can modulate cognitive and motor tasks. However, an interaction was found between task and type of stimulation as anodal tDCS of DLPFC and M1 was found to increase performance in the cognitive task, while cathodal tDCS of DLPFC and M1 had the opposite effect on the motor task. Additionally, tDCS effects seem to be most evident on the speed of changing sets, rather than on reducing the number of errors or increasing the efficacy of irrelevant set filtering

Biocompatibility, Inflammatory Response, and Recannalization Characteristics of Nonradioactive Resin Microspheres: Histological Findings

Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10–30 microspheres (15–30 μm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15–30 μm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization