Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management

The potential impact of changes in lower stratospheric water vapour on stratospheric temperatures over the past 30 years

This study investigates the potential contribution of observed changes in lower stratospheric water vapour to stratospheric temperature variations over the past three decades using a comprehensive global climate model (GCM). Three case studies are considered. In the first, the net increase in stratospheric water vapour (SWV) from 1980–2010 (derived from the Boulder frost-point hygrometer record using the gross assumption that this is globally representative) is estimated to have cooled the lower stratosphere by up to ∼0.2 K decade−1 in the global and annual mean; this is ∼40% of the observed cooling trend over this period. In the Arctic winter stratosphere there is a dynamical response to the increase in SWV, with enhanced polar cooling of 0.6 K decade−1 at 50 hPa and warming of 0.5 K decade−1 at 1 hPa. In the second case study, the observed decrease in tropical lower stratospheric water vapour after the year 2000 (imposed in the GCM as a simplified representation of the observed changes derived from satellite data) is estimated to have caused a relative increase in tropical lower stratospheric temperatures by ∼0.3 K at 50 hPa. In the third case study, the wintertime dehydration in the Antarctic stratospheric polar vortex (again using a simplified representation of the changes seen in a satellite dataset) is estimated to cause a relative warming of the Southern Hemisphere polar stratosphere by up to 1 K at 100 hPa from July–October. This is accompanied by a weakening of the westerly winds on the poleward flank of the stratospheric jet by up to 1.5 m s−1 in the GCM. The results show that, if the measurements are representative of global variations, SWV should be considered as important a driver of transient and long-term variations in lower stratospheric temperature over the past 30 years as increases in long-lived greenhouse gases and stratospheric ozone depletion

Formation of Jets and Equatorial Superrotation on Jupiter

The zonal flow in Jupiter's upper troposphere is organized into alternating retrograde and prograde jets, with a prograde (superrotating) jet at the equator. Existing models posit as the driver of the flow either differential radiative heating of the atmosphere or intrinsic heat fluxes emanating from the deep interior; however, they do not reproduce all large-scale features of Jupiter's jets and thermal structure. Here it is shown that the difficulties in accounting for Jupiter's jets and thermal structure resolve if the effects of differential radiative heating and intrinsic heat fluxes are considered together, and if upper-tropospheric dynamics are linked to a magnetohydrodynamic (MHD) drag that acts deep in the atmosphere. Baroclinic eddies generated by differential radiative heating can account for the off-equatorial jets; meridionally propagating equatorial Rossby waves generated by intrinsic convective heat fluxes can account for the equatorial superrotation. The zonal flow extends deeply into the atmosphere, with its speed changing with depth, up to depths at which the MHD drag acts. The theory is supported by simulations with an energetically consistent general circulation model of Jupiter's outer atmosphere. A simulation that incorporates differential radiative heating and intrinsic heat fluxes reproduces Jupiter's observed jets and thermal structure and makes testable predictions about as-yet unobserved aspects thereof. A control simulation that incorporates only differential radiative heating but not intrinsic heat fluxes produces off-equatorial jets but no equatorial superrotation; another control simulation that incorporates only intrinsic heat fluxes but not differential radiative heating produces equatorial superrotation but no off-equatorial jets.Comment: 23 pages, 10 figure

Impact of long-range correlations on trend detection in total ozone

Total ozone trends are typically studied using linear regression models that assume a first-order autoregression of the residuals [so-called AR(1) models]. We consider total ozone time series over 60°S–60°N from 1979 to 2005 and show that most latitude bands exhibit long-range correlated (LRC) behavior, meaning that ozone autocorrelation functions decay by a power law rather than exponentially as in AR(1). At such latitudes the uncertainties of total ozone trends are greater than those obtained from AR(1) models and the expected time required to detect ozone recovery correspondingly longer. We find no evidence of LRC behavior in southern middle-and high-subpolar latitudes (45°–60°S), where the long-term ozone decline attributable to anthropogenic chlorine is the greatest. We thus confirm an earlier prediction based on an AR(1) analysis that this region (especially the highest latitudes, and especially the South Atlantic) is the optimal location for the detection of ozone recovery, with a statistically significant ozone increase attributable to chlorine likely to be detectable by the end of the next decade. In northern middle and high latitudes, on the other hand, there is clear evidence of LRC behavior. This increases the uncertainties on the long-term trend attributable to anthropogenic chlorine by about a factor of 1.5 and lengthens the expected time to detect ozone recovery by a similar amount (from ∼2030 to ∼2045). If the long-term changes in ozone are instead fit by a piecewise-linear trend rather than by stratospheric chlorine loading, then the strong decrease of northern middle- and high-latitude ozone during the first half of the 1990s and its subsequent increase in the second half of the 1990s projects more strongly on the trend and makes a smaller contribution to the noise. This both increases the trend and weakens the LRC behavior at these latitudes, to the extent that ozone recovery (according to this model, and in the sense of a statistically significant ozone increase) is already on the verge of being detected. The implications of this rather controversial interpretation are discussed

Decadal-scale periodicities in the stratosphere associated with the solar cycle and the QBO

An interactive two-dimensional model is used to analyze the response of the stratosphere to the 11-year solar cycle in the presence of a quasi-biennial oscillation (QBO). The purpose of the paper is to demonstrate how the solar cycle response of stratospheric ozone and temperature diagnosed from model simulations depends on the QBO. The analyses show that (1) the simulated response to the solar flux when no QBO is imposed is very similar in different periods, despite differences in the magnitude and variability of the solar forcing; (2) the apparent solar response of temperature and ozone is modified by the presence of an imposed QBO; and (3) the impact of the QBO on the derived solar response is greatly reduced when the observed QBO forcing is replaced by an idealized sinusoidal forcing. The impact of the QBO on the solar cycle analysis is larger when only two solar cycles are analyzed but is not negligible even for analysis of four solar cycles. Differences in the QBO contribution account for most of the differences in analyses of separate 22-year periods. The statistical significance is not always a reliable indicator that the QBO effect has been separated

On the statistical modeling of persistence in total ozone anomalies

Geophysical time series sometimes exhibit serial correlations that are stronger than can be captured by the commonly used first‐order autoregressive model. In this study we demonstrate that a power law statistical model serves as a useful upper bound for the persistence of total ozone anomalies on monthly to interannual timescales. Such a model is usually characterized by the Hurst exponent. We show that the estimation of the Hurst exponent in time series of total ozone is sensitive to various choices made in the statistical analysis, especially whether and how the deterministic (including periodic) signals are filtered from the time series, and the frequency range over which the estimation is made. In particular, care must be taken to ensure that the estimate of the Hurst exponent accurately represents the low‐frequency limit of the spectrum, which is the part that is relevant to long‐term correlations and the uncertainty of estimated trends. Otherwise, spurious results can be obtained. Based on this analysis, and using an updated equivalent effective stratospheric chlorine (EESC) function, we predict that an increase in total ozone attributable to EESC should be detectable at the 95% confidence level by 2015 at the latest in southern midlatitudes, and by 2020–2025 at the latest over 30°–45°N, with the time to detection increasing rapidly with latitude north of this range

Synaptic and peptidergic connectome of a neurosecretory centre in the annelid brain

This is the author accepted manuscript. The final version is available from eLife Sciences Publications via the DOI in this record.Neurosecretory centers in animal brains use peptidergic signaling to influence physiology and behavior. Understanding neurosecretory center function requires mapping cell types, synapses, and peptidergic networks. Here we use transmission electron microscopy and gene expression mapping to analyze the synaptic and peptidergic connectome of an entire neurosecretory center. We reconstructed 78 neurosecretory neurons and mapped their synaptic connectivity in the brain of larval Platynereis dumerilii, a marine annelid. These neurons form an anterior neurosecretory center expressing many neuropeptides, including hypothalamic peptide orthologs and their receptors. Analysis of peptide-receptor pairs in spatially mapped single-cell transcriptome data revealed sparsely connected networks linking specific neuronal subsets. We experimentally analyzed one peptide-receptor pair and found that a neuropeptide can couple neurosecretory and synaptic brain signaling. Our study uncovered extensive networks of peptidergic signaling within a neurosecretory center and its connection to the synaptic brain.The research leading to these results received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ European Research Council Grant Agreement 260821. The research was supported by a grant from the DFG - Deutsche Forschungsgemeinschaft (Reference no. JE 777/1)

The contribution of anthropogenic SO₂ emissions to the Asian tropopause aerosol layer

Recent observations reveal a seasonally occurring layer of aerosol located from 0° to 100°E, 20° to 45°N and extending vertically from about 13 km to 18 km; this has been termed the Asian tropopause aerosol layer (ATAL), and its existence is closely associated with the Asian summer monsoon circulation. Observational studies argue that the ATAL is a recent phenomenon, as the layer is not observed in the satellite record prior to 1998. This suggests that the ATAL may be of anthropogenic origin associated with a shift in the dominant regional emission of sulfur dioxide (SO₂) to China and India in the late 1990s. Here we test the hypothesis that SO₂ emitted from Asia led to the formation of the ATAL using an aerosol microphysical model coupled to a global chemistry climate model. This is the first modeling study to specifically examine the ATAL and its possible origin. From our results, we conclude that the ATAL is most likely due to anthropogenic emissions, but its source cannot solely be attributed to emissions from Asia. Specifically, the results indicate that Chinese and Indian emissions contribute ∼30% of the sulfate aerosol extinction in the ATAL during volcanically quiescent periods. We also show that even small volcanic eruptions preclude our ability to make any conclusions about the existence of the ATAL before 1998 with observations alone