Comparative effectiveness of diversion of cerebrospinal fluid for children with severe traumatic brain injury

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies. Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome Score-Extended for Pediatrics (GOS-EP) and decreased intracranial pressure (ICP) in children with severe TBI. Design, Setting, and Participants: This observational comparative effectiveness study was performed at 51 clinical centers that routinely care for children with severe TBI in 8 countries (US, United Kingdom, Spain, the Netherlands, Australia, New Zealand, South Africa, and India) from February 2014 to September 2017, with follow-up at 6 months after injury (final follow-up, October 22, 2021). Children with severe TBI were included if they had Glasgow Coma Scale (GCS) scores of 8 or lower, had intracranial pressure (ICP) monitor placed on-site, and were aged younger than 18 years. Children were excluded if they were pregnant or an ICP monitor was not placed at the study site. Consecutive children were screened and enrolled, data regarding treatments were collected, and at discharge, consent was obtained for outcomes testing. Propensity matching for pretreatment characteristics was performed to develop matched pairs for primary analysis. Data analyses were completed on April 18, 2022. Exposures: Clinical care followed local standards, including the use of CSF diversion (or not), with patients stratified at the time of ICP monitor placement (CSF group vs no CSF group). Main Outcomes and Measures: The primary outcome was GOS-EP at 6 months, while ICP was considered as a secondary outcome. CSF vs no CSF was treated as an intention-to-treat analysis, and a sensitivity analysis was performed for children who received delayed CSF diversion. Results: A total of 1000 children with TBI were enrolled, including 314 who received CSF diversion (mean [SD] age, 7.18 [5.45] years; 208 [66.2%] boys) and 686 who did not (mean [SD] age, 7.79 [5.33] years; 437 [63.7%] boys). The propensity-matched analysis included 98 pairs. In propensity score-matched analyses, there was no difference between groups in GOS-EP (median [IQR] difference, 0 [-3 to 1]; P = .08), but there was a decrease in overall ICP in the CSF group (mean [SD] difference, 3.97 [0.12] mm Hg; P \u3c .001). Conclusions and Relevance: In this comparative effectiveness study, CSF diversion was not associated with improved outcome at 6 months after TBI, but a decrease in ICP was observed. Given the higher quality of evidence generated by this study, current evidence-based guidelines related to CSF diversion should be reconsidered

Evaluating the use of rCBV as a tumor grade and treatment response classifier across NCI Quantitative Imaging Network sites: Part II of the DSC-MRI digital reference object (DRO) challenge

We have previously characterized the reproducibility of brain tumor relative cerebral blood volume (rCBV) using a dynamic susceptibility contrast magnetic resonance imaging digital reference object across 12 sites using a range of imaging protocols and software platforms. As expected, reproducibility was highest when imaging protocols and software were consistent, but decreased when they were variable. Our goal in this study was to determine the impact of rCBV reproducibility for tumor grade and treatment response classification. We found that varying imaging protocols and software platforms produced a range of optimal thresholds for both tumor grading and treatment response, but the performance of these thresholds was similar. These findings further underscore the importance of standardizing acquisition and analysis protocols across sites and software benchmarking

Fundamental Aspects of the ISM Fractality

The ubiquitous clumpy state of the ISM raises a fundamental and open problem of physics, which is the correct statistical treatment of systems dominated by long range interactions. A simple solvable hierarchical model is presented which explains why systems dominated by gravity prefer to adopt a fractal dimension around 2 or less, like the cold ISM and large scale structures. This has direct relation with the general transparency, or blackness, of the Universe.Comment: 6 pages, LaTeX2e, crckapb macro, no figure, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

Structural insights on TRPV5 gating by endogenous modulators.

TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery

History-sensitive versus future-sensitive approaches to security in distributed systems

We consider the use of aspect-oriented techniques as a flexible way to deal with security policies in distributed systems. Recent work suggests to use aspects for analysing the future behaviour of programs and to make access control decisions based on this; this gives the flavour of dealing with information flow rather than mere access control. We show in this paper that it is beneficial to augment this approach with history-based components as is the traditional approach in reference monitor-based approaches to mandatory access control. Our developments are performed in an aspect-oriented coordination language aiming to describe the Bell-LaPadula policy as elegantly as possible. Furthermore, the resulting language has the capability of combining both history- and future-sensitive policies, providing even more flexibility and power.Comment: In Proceedings ICE 2010, arXiv:1010.530

Overview of the Initial NSTX Experimental Results

The main aim of the National Spherical Torus Experiment (NSTX) is to establish the fusion physics principles of the spherical torus (ST) concept. The NSTX device began plasma operations in February 1999 and the plasma current Ip was successfully brought up to the design value of 1 million amperes on December 14, 1999. The planned plasma shaping parameters, k = 1.6 {+-} 2.2 and d = 0.2 {+-} 0.4, were achieved in inner limited, single null and double null configurations. The CHI (Coaxial Helicity Injection) and HHFW (High Harmonic Fast Wave) experiments were also initiated. A CHI injected current of 27 kA produced up to 260 kA of toroidal current without using an ohmic solenoid. With an injection of 2.3 MW of HHFW power, using twelve antennas connected to six transmitters, electrons were heated from a central temperature of 400 eV to 900 eV at a centraldensity of 3.5 x 1013 cm-3 increasing the plasma energy to 59 kJ and the toroidal beta, bT to 10 %. Finally, the NBI system commenced operatio n in Sept. 2000. The initial results with two ion sources (PNBI = 2.8 MW) shows good heating, producing a total plasma stored energy of 90 kJ corresponding to bT = 18 % at a plasma current of 1.1 M