Randomized controlled trials in adult traumatic brain injury: A systematic review on the use and reporting of clinical outcome assessments

As part of efforts to improve study design, the use of outcome measures in randomized controlled trials (RCTs) in traumatic brain injury (TBI) is receiving increasing attention. This review aimed to assess how clinical outcome assessments (COAs) have been used and reported in RCTs in adult TBI. Systematic literature searches were conducted to identify medium to large (n ≥ 100) acute and post-acute TBI trials published since 2000. Data were extracted independently by two reviewers using a set of structured templates. Items from the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement and CONSORT patient-reported outcomes (PRO) extension were used to evaluate reporting quality of COAs. Glasgow Outcome Scale/Extended (GOS/GOSE) data were extracted using a checklist developed specifically for the review. A total of 126 separate COAs were identified in 58 studies. The findings demonstrate heterogeneity in the use of TBI outcomes, limiting comparisons and meta-analyses of RCT findings. The GOS/GOSE was included in 39 studies, but implemented in a variety of ways, which may not be equivalent. Multidimensional outcomes were used in 30 studies, and these were relatively more common in rehabilitation settings. The use of PROs was limited, especially in acute study settings. Quality of reporting was variable, and key information concerning COAs was often omitted, making it difficult to know how precisely outcomes were assessed. Consistency across studies would be increased and future meta-analyses facilitated by (a) using common data elements recommendations for TBI outcomes and (b) following CONSORT guidelines when publishing RCTs

Expansion of W 3(OH)

A direct measurement of the expansion of W 3(OH) is made by comparing Very Large Array images taken about 10 yr apart. The expansion is anisotropic with a typical speed of 3 to 5 km/s, indicating a dynamical age of only 2300 yr. These observations are inconsistent with either the freely expanding shell model or a simple bow shock model. The most favored model is a slowly expanding shell-like HII region, with either a fast rarefied flow or another less massive diffuse ionized region moving towards the observer. There is also a rapidly evolving source near the projected center of emission, perhaps related to the central star.Comment: LaTeX file, 28 pages, includes 8 figures. To appear in ApJ in December 10 (1998) issue. Also available at http://www.submm.caltech.edu/~kawamura/w3oh_pp.p

Comparative study of the dynamics of laser and acoustically generated bubbles in viscoelastic media

Experimental observations of the growth and collapse of acoustically and laser-nucleated single bubbles in water and agarose gels of varying stiffness are presented. The maximum radii of generated bubbles decreased as the stiffness of the media increased for both nucleation modalities, but the maximum radii of laser-nucleated bubbles decreased more rapidly than acoustically nucleated bubbles as the gel stiffness increased. For water and low stiffness gels, the collapse times were well predicted by a Rayleigh cavity, but bubbles collapsed faster than predicted in the higher stiffness gels. The growth and collapse phases occurred symmetrically (in time) about the maximum radius in water but not in gels, where the duration of the growth phase decreased more than the collapse phase as gel stiffness increased. Numerical simulations of the bubble dynamics in viscoelastic media showed varying degrees of success in accurately predicting the observations

Light and depth dependency of nitrogen fixation by the non‐photosynthetic, symbiotic cyanobacterium UCYN‐A

The symbiotic cyanobacterium UCYN-A is one of the most globally abundant marine dinitrogen (N2)-fixers, but cultures have not been available and its biology and ecology are poorly understood. We used cultivation-independent approaches to investigate how UCYN-A single-cell N2 fixation rates (NFRs) and nifH gene expression vary as a function of depth and photoperiod. Twelve-hour day/night incubations showed that UCYN-A only fixed N2 during the day. Experiments conducted using in situ arrays showed a light-dependence of NFRs by the UCYN-A symbiosis, with the highest rates in surface waters (5–45 m) and lower rates at depth (≥ 75 m). Analysis of NFRs versus in situ light intensity yielded a light saturation parameter (Ik) for UCYN-A of 44 μmol quanta m−2 s−1. This is low compared with other marine diazotrophs, suggesting an ecological advantage for the UCYN-A symbiosis under low-light conditions. In contrast to cell-specific NFRs, nifH gene-specific expression levels did not vary with depth, indicating that light regulates N2 fixation by UCYN-A through processes other than transcription, likely including host–symbiont interactions. These results offer new insights into the physiology of the UCYN-A symbiosis in the subtropical North Pacific Ocean and provide clues to the environmental drivers of its global distributions.En prens

Heterogeneity in the histidine-brace copper coordination sphere in auxiliary activity family 10 (AA10) lytic polysaccharide monooxygenases

Copper-dependent lytic polysaccharide monooxygenases (LPMOs) are enzymes that oxidatively deconstruct polysaccharides. The active site copper in LPMOs is coordinated by a histidine-brace. This utilizes the amino group and side chain of the N-terminal His residue with the side chain of a second His residue to create a T-shaped arrangement of nitrogen ligands. We report a structural, kinetic, and thermodynamic appraisal of copper binding to the histidine-brace in an auxiliary activity family 10 (AA10) LPMO from Streptomyces lividans (SliLPMO10E). Unexpectedly, we discovered the existence of two apo-SliLPMO10E species in solution that can each bind copper at a single site with distinct kinetic and thermodynamic (exothermic and endothermic) properties. The experimental EPR spectrum of copper-bound SliLPMO10E requires the simulation of two different line shapes, implying two different copper-bound species, indicative of three and two nitrogen ligands coordinating the copper. Amino group coordination was probed through the creation of an N-terminal extension variant (SliLPMO10E- Ext). The kinetics and thermodynamics of copper binding to SliLPMO10E-Ext are in accord with copper binding to one of the apo-forms in the wild-type protein, suggesting that amino group coordination is absent in the two-nitrogen coordinate form of SliLPMO10E. Copper binding to SliLPMO10B was also investigated, and again it revealed the presence of two apo-forms with kinetics and stoichiometry of copper binding identical to that of SliLPMO10E. Our findings highlight that heterogeneity exists in the active site copper coordination sphere of LPMOs that may have implications for the mechanism of loading copper in the cell

Metabolic rate throughout the annual cycle reveals the demands of an Arctic existence in Great Cormorants

Aquatic endotherms living in polar regions are faced with a multitude of challenges, including low air and water temperatures and low illumination, especially in winter. Like other endotherms from cold environments, Great Cormorants (Phalacrocorax carbo) living in Arctic waters were hypothesized to respond to these challenges through combination of high daily rate of energy expenditure (DEE) and high food requirements, which are met by a high rate of catch per unit effort (CPUE). CPUE has previously been shown in Great Cormorants to be the highest of any diving bird. In the present study, we tested this hypothesis by making the first measurements of DEE and foraging activity of Arctic-dwelling Great Cormorants throughout the annual cycle. We demonstrate that, in fact, Great Cormorants have surprisingly low rates of DEE. This low DEE is attributed primarily to very low levels of foraging activity, particularly during winter, when the cormorants spent only 2% of their day submerged. Such a low level of foraging activity can only be sustained through consistently high foraging performance. We demonstrate that Great Cormorants have one of the highest recorded CPUEs for a diving predator; 18.6 g per minute submerged (95% prediction interval 13.0-24.2 g/min) during winter. Temporal variation in CPUE was investigated, and highest CPUE was associated with long days and shallow diving depths. The effect of day length is attributed to seasonal variation in prey abundance. Shallow diving leads to high CPUE because less time is spent swimming between the surface and the benthic zone where foraging occurs. Our study demonstrates the importance of obtaining accurate measurements of physiology and behavior from free-living animals when attempting to understand their ecology

NGC 7582: The Prototype Narrow-Line X-ray Galaxy

NGC 7582 is a candidate prototype of the Narrow Line X-ray Galaxies (NLXGs) found in deep X-ray surveys. An ASCA observation shows the hard (> 3 keV) X-ray continuum of NGC 7582 drops 40% in ~6 ks, implying an AGN, while the soft band (< 3 keV) does not drop in concert with the hard continuum, requiring a separate component. The X-ray spectrum of NGC 7582 also shows a clear 0.5-2 keV soft (kT = 0.8 (+0.9,-0.3) keV or Gamma = 2.4 +/- 0.6; L(X) = 6 x 10**40 ergs s**-1) low--energy component, in addition to a heavily absorbed [N(H) = (6 +/- 2)\times 10**22 cm**-2 ] and variable 2-10 keV power law [Gamma = 0.7 (+0.3,-0.4); L(X) = (1.7-2.3) x 10**42 ergs s**-1]. This is one of the flattest 2-10 keV slopes in any AGN observed with ASCA. (The ROSAT HRI image of NGC 7582 further suggests extent to the SE.) These observations make it clear that the hard X-ray emission of NGC 7582, the most "narrow-line" of the NLXGs, is associated with an AGN. The strong suggestion is that all NLXGs are obscured AGNs, as hypothesized to explain the X-ray background spectral paradox. The separate soft X-ray component makes NGC 7582 (and by extension other NLXGs) detectable as a ROSAT source.Comment: text: Latex2e 10 pages, including 1 table, and 2 postscript figures via psfi

Right ventricular outflow tract velocity time integral-to-pulmonary artery systolic pressure ratio: a non-invasive metric of pulmonary arterial compliance differs across the spectrum of pulmonary hypertension.

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG \u3c 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P \u3c 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P \u3c 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010-0.25] vs. Cpc-PH: 0.20 [0.12-0.25] vs. Ipc-PH: 0.35 [0.22-0.44]; P \u3c 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63-0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68-0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized β-coefficient = 27.7, 95% CI = 9.2-46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity

Control-focused, nonlinear and time-varying modelling of dielectric elastomer actuators with frequency response analysis

Current models of dielectric elastomer actuators (DEAs) are mostly constrained to first principal descriptions that are not well suited to the application of control design due to their computational complexity. In this work we describe an integrated framework for the identification of control focused, data driven and time-varying DEA models that allow advanced analysis of nonlinear system dynamics in the frequency-domain. Experimentally generated input–output data (voltage-displacement) was used to identify control-focused, nonlinear and time-varying dynamic models of a set of film-type DEAs. The model description used was the nonlinear autoregressive with exogenous input structure. Frequency response analysis of the DEA dynamics was performed using generalized frequency response functions, providing insight and a comparison into the time-varying dynamics across a set of DEA actuators. The results demonstrated that models identified within the presented framework provide a compact and accurate description of the system dynamics. The frequency response analysis revealed variation in the time-varying dynamic behaviour of DEAs fabricated to the same specifications. These results suggest that the modelling and analysis framework presented here is a potentially useful tool for future work in guiding DEA actuator design and fabrication for application domains such as soft robotics

Naturally Occurring Disease-Related Mutations in the 40–57 Ω-Loop of Human Cytochrome c Control Triggering of the Alkaline Isomerization

American Chemical Society. Naturally occurring mutations found in one of the two ω-loop substructures in human cytochrome c are associated with low blood platelet count (thrombocytopenia). Both ω-loops participate in the formation of conformers associated with cytochrome c peroxidase activity and apoptotic function. At alkaline pH values, the Met80 ligand to the ferric heme iron dissociates, and a lysine residue in the 71-85 ω-loop coordinates to the iron. The alkaline isomerization has been the focus of extensive kinetic studies, and it is established that a deprotonation triggers the release of the Met80 ligand (pKtrigger). A second deprotonation stabilizes a pentacoordinate heme form (pKa2). In this study, site-directed variants at the 41 and 48 positions in the 40-57 ω-loop and at the 81 and 83 positions in the 71-85 ω-loop reveal that conformational transitions in the 71-85 ω-loop, leading to the alkaline or peroxidatic conformers, are controlled by the 40-57 ω-loop. We find that the variants causing thrombocytopenia, G41S and Y48H, lower the pKtriggerand increase pKa2. Our results are presented in a mechanistic framework, depicted by a cube, that accounts for the pH dependencies of the equilibrium and kinetic parameters governing the alkaline transition of the native protein and ω-loop variants. The data are most consistent with the trigger for Met80 replacement by a lysine being a deprotonation within a hydrogen bonded unit that links the two ω-loops rather than an individual group. Such a proposal aligns with the entatic contribution made by the same unit in controlling the Met80-Fe(III) bond strength