Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes

Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 x 10(-10). Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (r(g) = 0.39, P = 1.68 x 10(-4)). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.Peer reviewe

Experimental Correlation of Combined Heat and Mass Transfer for NH 3 -H 2 0 falling film absorption

vection. The main conclusion from this study is that the negative concentration gradient of the surface tension is a trigger for inducement of Marangoni convection before the additive solubility, while the imbalance of the surface tension and the interfacial tension is a trigger after the solubility limit. Acknowledgment The authors thank Mr. K. Iizuka, Tokyo University of Agriculture and Technology, for his experimental assistance. The authors acknowledge that this work has been partially funded by the Japan Science and Technology Corporation (JST). References Beutler, A., Greiter, I., Wagner, A., Hohhmann, L., Schreier, S., and Alefeld, G., 1996, &quot;Surfactants and Fluid Properties,&quot; Int. J. Refrigeration, Vol. 19, No. 5, pp. 342-346. Chavepeyer, G&quot; Salajan, M., Platten, J. K., and Smet, P., 1995, &quot;InterfacialTension and Surface Adsorption in j-Heptanol/Water Systems,&quot; Journal of Colloid and Interface Science, Vol. 174, Daiguji, H,, Hihara, E., and Saito, T., 1997, &quot;Mechanism of Absorption Enhancement by Surfactant,&quot; Int. J. Heat and Mass Transfer, Vol. 40, No. 8, pp. 1743-1752. Fujita, T., 1993, &quot;Falling Liquid Films in Absorption Machines,&quot; Int. J. Refrigeration, Vol. 16, No. 4, pp. 282-294. Hihara, E&quot; and Saito, T., 1993 Journal of Heat Transfer TL = temperature of the fluid far away from the plate t&apos; = time t R = reference time u = velocity of the fluid UD = reference velocity at&apos; = frequency X,, = distance of the transition point from the leading edge |3 = coefficient of volume expansion p = density e = amplitude (constant) 9 = nondimensional temperature u = nondimensional velocity i = y-i Introduction Transient laminar-free convection flow past an infinite vertical plate under different plate conditions was studied by many researchers. The first closed-form solutions for Prandtl number Pr = 1.0 in case of a step change in wall temperature with time was derived by Illingworth (1950) and for Pr # 1.0, he derived the solution in integral form. Siegel (1958) studied the unsteady freeconvection flow past a semi-infinite vertical plate under stepchange in wall temperature or surface heat flux by employing the momentum integral method. Experimental evidence for such a situation was presented by Goldstein and Eckert (1960). For a semi-infinite vertical plate, unsteady free-convection flow was studied analytically b

Properties of Rubble-Pile Asteroid (101955) Bennu from OSIRIS-REx Imaging and Thermal Analysis

Establishing the abundance and physical properties of regolith and boulders on asteroids is crucial for understanding the formation and degradation mechanisms at work on their surfaces. Using images and thermal data from NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft, we show that asteroid (101955) Bennu's surface is globally rough, dense with boulders, and low in albedo. The number of boulders is surprising given Bennu's moderate thermal inertia, suggesting that simple models linking thermal inertia to particle size do not adequately capture the complexity relating these properties. At the same time, we find evidence for a wide range of particle sizes with distinct albedo characteristics. Our findings imply that ages of Bennu's surface particles span from the disruption of the asteroid's parent body (boulders) to recent in situ production (micrometre-scale particles)

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

A Prototype Four-Inch Short Hydride (FISH) Bed as a Replacement Tritium Storage Bed

The Savannah River Site (SRS) tritium facilities have used 1st generation (Gen1) metal hydride storage bed assemblies with process vessels (PVs) fabricated from 3 inch nominal pipe size (NPS) pipe to hold up to 12.6 kg of LaNi{sub 4.25}Al{sub 0.75} metal hydride for tritium gas absorption, storage, and desorption for over 15 years. The 2nd generation (Gen2) of the bed design used the same NPS for the PV, but the added internal components produced a bed nominally 1.2 m long, and presented a significant challenge for heater cartridge replacement in a footprint limited glove-box. A prototype 3rd generation (Gen3) metal hydride storage bed has been designed and fabricated as a replacement candidate for the Gen2 storage bed. The prototype Gen3 bed uses a PV pipe diameter of 4 inch NPS so the bed length can be reduced below 0.7 m to facilitate heater cartridge replacement. For the Gen3 prototype bed, modeling results show increased absorption rates when using hydrides with lower absorption pressures. To improve absorption performance compared to the Gen2 beds, a LaNi{sub 4.15}Al{sub 0.85} material was procured and processed to obtain the desired pressure-composition-temperature (PCT) properties. Other bed design improvements are also presented