Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

ICAR: endoscopic skull‐base surgery

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Blood lead levels in Japanese children: Effects of passive smoking

Blood lead levels (BLLs) of 188 pediatric patients were measured and their parents were queried as to the smoking style in their home. Their mean BLL was 3.16 μg/dl, which was among the lowest levels in the world, and none of them had levels of over 10 μ g/dl. Preschool children ( 1 to 6 years of age) with parents who smoked in the same room had a significantly higher BLL (mean; 4.15 μ g/dl) than those with parents who never smoked (mean; 3.06 μ g/dl) (P<0.01). However, the mean BLL of school children (6 to 15 years of age) with parents who smoked in the same room was not significantly different from that of school children with parents who never smoked. Passive smoking caused an increase of the BLL only in preschool children in Japan. This is probably because preschool infants spend much more time with their parents and have much more contact with passive smoking than school children and, additionally young infants have a limited ability to excrete lead from the body

Permo-Carboniferous granitoids with Jurassic high temperature metamorphism in Central Pontides, Northern Turkey

In the northern part of the Central Pontides (N Turkey) there are different metamorphic rocks exposed, notably the Devrekani metamorphic rocks. Here, upper amphibolite-lower granulite facies metamorphic rocks contain predominantly paragneiss, orthogneiss and metacarbonate, and to a lesser extent, amphibolite and quartzite, with cross-cutting aplite, pegmatite and granite veins. This is the first report of these rocks and includes new data on the petrochemistry, geochronology and metamorphic evolution of the Devrekani orthogneisses from the Central Pontides. The orthogneisses show five different mineral parageneses with the characteristic mineral assemblage quartz + K-feldspar + plagioclase + biotite ± hornblende ± opaque (± ilmenite and ± magnetite), and accessory minerals (zircon, sphene and apatite). These metamorphic rocks exhibit generally granoblastic, lepidogranoblastic and nematolepidogranoblastic with locally migmatitic and relic micrographic textures. They have well-developed centimeter-spaced gneissic banding and display gneissose structure with symmetric, asymmetric and irregular folds. The petrographic features, mineralogical assemblages and weak migmatization reflect high temperature conditions. Thermometric calculations in the orthogneisses indicate metamorphic temperatures reached 744 ± 33 °C. Field relations, petrography and petrochemistry suggest that the orthogneisses have predominantly granodioritic and some granitic protoliths, that show features of I-type, medium to high-potassic calc-alkaline volcanic arc granitoids. The orthogneisses have high contents of LILEs and low contents of HFSEs with negative Nb and Ti anomalies, which are typical of subduction-related magmas. The orthogneisses also show significant LREE enrichment relative to HREE with negative Eu anomalies (EuN/Eu* = 0.33–1.07) with LaN/LuN = 6.98–20.47 values. Based on U-Pb zircon dating data, the protoliths are related to Permo-Carboniferous (316–252 Ma) magmatism. It is likely that peak metamorphism took place during the Jurassic as reflected by the U-Pb zircon ages (199–158 Ma) and also 40Ar/39Ar from hornblende/biotite (163–152 Ma). The four biotite 40Ar/39Ar average ages from the rock samples are ca. 156 Ma, suggesting that the metamorphic rocks cooled to 350–400 °C at ca. 156 Ma. Conclusively, the Devrekani metamorphic rocks can be ascribed as products of Permo-Carboniferous continental arc magmatism overprinted by Jurassic metamorphism in the northern Central Pontides