BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

Abstract Background B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. Methods Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). Results Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes ( p \u2009<\u20090.01), lower values of BAFF Index (11.9\u2009\ub1\u20096.1 vs 17.5\u2009\ub1\u20095.2, p \u2009<\u20090.01), and higher CSF CXCL13 levels (27.7\u2009\ub1\u200933.5 vs 0.9\u2009\ub1\u20091.5, p \u2009<\u20090.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis ( r \u2009>\u20090.5 and p \u2009<\u20090.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB\u2212 ( p \u2009<\u20090.05) and HC ( p \u2009<\u20090.01), and correlated to CSF CXCL13 concentrations ( r 0.77, p \u2009<\u20090.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41\u2009\ub1\u20090.1 vs 2.49\u2009\ub1\u20090.1\ua0mm, p \u2009<\u20090.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB\u2212. Conclusions The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by ..

Liquid filled canyons on Titan

In May 2013 the Cassini RADAR altimeter observed channels in Vid Flumina, a drainage network connected to Titan’s second largest hydrocarbon sea, Ligeia Mare. Analysis of these altimeter echoes shows that the channels are located in deep (up to ~570 m), steep-sided, canyons and have strong specular surface reflections that indicate they are currently liquid filled. Elevations of the liquid in these channels are at the same level as Ligeia Mare to within a vertical precision of about 0.7 m, consistent with the interpretation of drowned river valleys. Specular reflections are also observed in lower order tributaries elevated above the level of Ligeia Mare, consistent with drainage feeding into the main channel system

Vibrações em estruturas no Brasil: uma revisão bibliográfica da literatura

O presente artigo trata-se de uma revisão da literatura referente às ações dinâmicas em estruturas no Brasil. Esse trabalho objetiva determinar os principais aspectos referentes à vibrações em estruturas, apontar as causas e as consequências dessas ações dinâmicas. Trata-se da caracterização dos fenômenos dinâmicos e das principais fontes geradoras de vibrações. O artigo também apresenta uma breve contextualização das normativas brasileiras e por último aborda as principais consequências desse tipo de carregamento nas estruturas e alguns casos que aconteceram no Brasil, devido aos efeitos dinâmicos do meio. Pelos aspectos analisados, verificou-se a necessidade da realização de estudos na área de ações dinâmicas em estruturas, principalmente se tratando de sismos e a falta de conhecimento da norma que rege projetos sujeitos a ações sísmicas, por parte dos engenheiros. Outro fator de extrema necessidade é a realização de fiscalizações das edificações que são implantadas próximas à meios de grande geração de vibrações decorrentes dos modais de transporte

Early red nucleus atrophy in relapse-onset multiple sclerosis

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18–56) years and mean disease duration of 1.1 ± 1.5 (0–5) years, and 36 age- and sex-matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T-MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm3 vs. 99.37 ± 11.53 mm3, p =.019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3, p =.020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = −.333, p =.004 and r = −.298, p =.010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = −.147, p =.216; left RN: r = −.153, p =.196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = −.310, p =.008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = −.164, p =.164; left RN: r = −.64, p =.588). Finally, left RN volume correlated with vermis VIIb (r =.297, p =.011) and right interposed nucleus (r =.249, p =.034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS

Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening: The Application of a Second-Tier Test

Abstract The isodecyl neopentanoate is an ingredient used in the cosmetic industry to prepare a nipple fissure balm. We report on 12 newborns that showed elevated C5-acylcarnitine levels upon newborn screening following treatment with balm. The first 3 neonates were immediately recalled for confirmatory tests and resulted negative for both isovaleric acidemia and short/branched chain acyl-CoA dehydrogenase deficiency. In the other 9 cases, the immediate recall was avoided by applying a new second-tier test able to confirm the presence of pivaloylcarnitine. The concentration of C5-acylcarnitine was measured in the days following the suspension of balm application. Abnormal concentrations of C5-acylcarnitine did not seem to be associated with free carnitine deficiency, probably due to the short time of exposure. A direct correlation between balm ingestion and the elevation in pivaloylcarnitine has been demonstrated in 10 adult volunteers. The commercial balm containing a pivalic acid derivative is causal of false-positive results during newborn screening, and it could have the potential to cause secondary carnitine deficiency when used chronically

Light yield non-proportionality of inorganic crystals and its effect on cosmic-ray measurements

The multi-TeV energy region of the cosmic-ray spectra has been recently explored by direct detection experiments that used calorimetric techniques to measure the energy of the cosmic particles. Interesting spectral features have been observed in both all-electron and nuclei spectra. However, the interpretation of the results is compromised by the disagreements between the data obtained from the various experiments, that are not reconcilable with the quoted experimental uncertainties. Understanding the reason for the discrepancy among the measurements is of fundamental importance in view of the forthcoming high-energy cosmic-ray experiments planned for space, as well as for the correct interpretation of the available results. The purpose of this work is to investigate the possibility that a systematic effect may derive from the non-proportionality of the light response of inorganic crystals, typically used in high-energy calorimetry due to their excellent energy-resolution performance. The main reason for the non-proportionality of the crystals is that scintillation light yield depends on ionisation density. Experimental data obtained with ion beams were used to characterize the light response of various scintillator materials. The obtained luminous efficiencies were used as input of a Monte Carlo simulation to perform a comparative study of the effect of the light-yield non-proportionality on the detection of high-energy electromagnetic and hadronic showers. The result of this study indicates that, if the calorimeter response is calibrated by using the energy deposit of minimum ionizing particles, the measured shower energy might be affected by a significant systematic shift, at the level of few percent, whose sign and magnitude depend specifically on the type of scintillator material used. © 2022 IOP Publishing Ltd and Sissa Medialab

DART Impact Ejecta Plume Evolution: Implications for Dimorphos

The NASA Double Asteroid Redirection Test (DART) spacecraft impacted the moon Dimorphos of the [65803] Didymos binary system and changed the binary orbit period, demonstrating asteroid deflection by a kinetic impact and indicating that more momentum was transferred to Dimorphos by escaping impact ejecta than was incident with DART. Images of the DART impact ejecta plume were obtained by the Light Italian cubesat for Imaging of Asteroids (LICIACube) in the first few minutes after the DART impact. The ejecta plume imaged by LICIACube 158 s after the DART impact prior to closest approach shows no evidence for plume clearing at low altitude. The ejecta plume imaged 175 s after the DART impact is optically thick up to projected altitudes of 200 m above the surface of Dimorphos. These observations are compared with models of the impact ejecta plume optical depth, structure, and evolution, which are developed from point-source scaling models fitted to numerical simulations of the DART impact into a rubble pile Dimorphos with different material strengths. The observations of the impact plume optical depth and the high momentum transfer from the DART impact are not consistent with impact and ejecta plume models assuming the Dimorphos cohesive strength to be as high as 5000 Pa. Models with 5 and 50 Pa Dimorphos cohesive strength provide the overall best consistency with plume opacity observations and high momentum transfer

DART Impact Ejecta Plume Evolution: Implications for Dimorphos

The NASA Double Asteroid Redirection Test (DART) spacecraft impacted the moon Dimorphos of the [65803] Didymos binary system and changed the binary orbit period, demonstrating asteroid deflection by a kinetic impact and indicating that more momentum was transferred to Dimorphos by escaping impact ejecta than was incident with DART. Images of the DART impact ejecta plume were obtained by the Light Italian cubesat for Imaging of Asteroids (LICIACube) in the first few minutes after the DART impact. The ejecta plume imaged by LICIACube 158 s after the DART impact prior to closest approach shows no evidence for plume clearing at low altitude. The ejecta plume imaged 175 s after the DART impact is optically thick up to projected altitudes of 200 m above the surface of Dimorphos. These observations are compared with models of the impact ejecta plume optical depth, structure, and evolution, which are developed from point-source scaling models fitted to numerical simulations of the DART impact into a rubble pile Dimorphos with different material strengths. The observations of the impact plume optical depth and the high momentum transfer from the DART impact are not consistent with impact and ejecta plume models assuming the Dimorphos cohesive strength to be as high as 5000 Pa. Models with 5 and 50 Pa Dimorphos cohesive strength provide the overall best consistency with plume opacity observations and high momentum transfer

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos’s along-track orbital velocity component of 2.70 ± 0.10 mm s−1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m−3, we find that the expected value of the momentum enhancement factor, β, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m−3, β=3.61−0.25+0.19(1σ). These β values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos