Summary Background Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50–60% of patients after traumatic brain ...injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable neurological outcome. Methods We did a prospective, observational, multicentre study at seven neurological centres. We enrolled 109 adults who needed neurosurgery for acute TBI. Spreading depolarisations were monitored by electrocorticography during intensive care and were classified as cortical spreading depression (CSD) if they took place in spontaneously active cortex or as isoelectric spreading depolarisation (ISD) if they took place in isoelectric cortex. Investigators who treated patients and assessed outcome were masked to electrocorticographic results. Scores on the extended Glasgow outcome scale at 6 months were fitted to a multivariate model by ordinal regression. Prognostic score (based on variables at admission, as validated by the IMPACT studies) and spreading depolarisation category (none, CSD only, or at least one ISD) were assessed as outcome predictors. Findings Six individuals were excluded because of poor-quality electrocorticography. A total of 1328 spreading depolarisations arose in 58 (56%) patients. In 38 participants, all spreading depolarisations were classified as CSD; 20 patients had at least one ISD. By multivariate analysis, both prognostic score (p=0·0009) and spreading depolarisation category (p=0·0008) were significant predictors of neurological outcome. CSD and ISD were associated with an increased risk of unfavourable outcome (common odds ratios 1·56 95% CI 0·72–3·37 and 7·58 2·64–21·8, respectively). Addition of depolarisation category to the regression model increased the proportion of variance in outcome that could be attributed to predictors from 9% to 22%, compared with the prognostic score alone. Interpretation Spreading depolarisations were associated with unfavourable outcome, after controlling for conventional prognostic variables. The possibility that spreading depolarisations have adverse effects on the traumatically injured brain, and therefore might be a target in the treatment of TBI, deserves further research. Funding US Army CDMRP PH/TBI research programme.
Interest in nanowires continues to grow, fuelled in part by applications in nanotechnology. The ability to engineer nanowire properties makes them especially promising in nanoelectronics. Most ...silicon nanowires are grown using the vapour–liquid–solid (VLS) mechanism, in which the nanowire grows from a gold/silicon catalyst droplet during silicon chemical vapour deposition. Despite over 40 years of study, many aspects of VLS growth are not well understood. For example, in the conventional picture the catalyst droplet does not change during growth, and the nanowire sidewalls consist of clean silicon facets. Here we demonstrate that these assumptions are false for silicon nanowires grown on Si(111) under conditions where all of the experimental parameters (surface structure, gas cleanliness, and background contaminants) are carefully controlled. We show that gold diffusion during growth determines the length, shape, and sidewall properties of the nanowires. Gold from the catalyst droplets wets the nanowire sidewalls, eventually consuming the droplets and terminating VLS growth. Gold diffusion from the smaller droplets to the larger ones (Ostwald ripening) leads to nanowire diameters that change during growth. These results show that the silicon nanowire growth is fundamentally limited by gold diffusion: smooth, arbitrarily long nanowires cannot be grown without eliminating gold migration.
Ocean acidification (OA) is predicted to have widespread implications for marine organisms, yet the capacity for species to acclimate or adapt over this century remains unknown. Recent ...transgenerational studies have shown that for some marine species, exposure of adults to OA can facilitate positive carryover effects to their larval and juvenile offspring that help them to survive in acidifying oceanic conditions. But whether these positive carryover effects can persist into adulthood or the next generation is unknown. Here we tested whether positive carryover effects found in larvae of the oyster, Saccostrea glomerata following transgenerational exposure to elevated CO2, could persist into adulthood and whether subsequent transgenerational exposure of adults to elevated CO2 would facilitate similar adaptive responses in the next generation of larvae and juveniles. Following our previous transgenerational exposure of parental adults and first generation (F1) larvae to ambient (385 μatm) and elevated (856 μatm) CO2, newly settled F1 juveniles were transferred to the field at ambient CO2 for 14 months, until they reached reproductive maturity. At this time, the F1 adults were returned to the laboratory and the previous transgenerational CO2 exposure was repeated to produce F2 offspring. We found that the capacity of adults to regulate extracellular pH at elevated CO2 was improved if they had a prior history of transgenerational exposure to elevated CO2. In addition, subsequent transgenerational exposure of these adults led to an increase in the resilience of their larval and juvenile offspring. Offspring with a history of transgenerational exposure to elevated CO2 had a lower percentage abnormality, faster development rate, faster shell growth and increased heart rate at elevated CO2 compared with F2 offspring with no prior history of exposure to elevated CO2. Our results suggest that positive carryover effects originating during parental and larval exposure will be important in mediating some of the impacts of OA for later life-history stages and generations.
Liquid cell electron microscopy has emerged as a powerful technique for in situ studies of nanoscale processes in liquids. An accurate understanding of the interactions between the electron beam and ...the liquid medium is essential to account for, suppress, and exploit beam effects. We quantify the interactions of high energy electrons with water, finding that radiolysis plays an important role, while heating is typically insignificant. For typical imaging conditions, we find that radiolysis products such as hydrogen and hydrated electrons achieve equilibrium concentrations within seconds. At sufficiently high dose-rate, the gaseous products form bubbles. We image bubble nucleation, growth, and migration. We develop a simplified reaction-diffusion model for the temporally and spatially varying concentrations of radiolysis species and predict the conditions for bubble formation by H2. We discuss the conditions under which hydrated electrons cause precipitation of cations from solution and show that the electron beam can be used to “write” structures directly, such as nanowires and other complex patterns, without the need for a mask.
A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess ...whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study.
Randomized prospective clinical trial.
Ten ICUs in the United States.
One hundred nineteen severe traumatic brain injury patients.
Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended.
A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p < 0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy.
Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.
Splicing varies across brain regions, but the single-cell resolution of regional variation is unclear. We present a single-cell investigation of differential isoform expression (DIE) between brain ...regions using single-cell long-read sequencing in mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 ( www.isoformAtlas.com ). Isoform tests for DIE show better performance than exon tests. We detect hundreds of DIE events traceable to cell types, often corresponding to functionally distinct protein isoforms. Mostly, one cell type is responsible for brain-region specific DIE. However, for fewer genes, multiple cell types influence DIE. Thus, regional identity can, although rarely, override cell-type specificity. Cell types indigenous to one anatomic structure display distinctive DIE, e.g. the choroid plexus epithelium manifests distinct transcription-start-site usage. Spatial transcriptomics and long-read sequencing yield a spatially resolved splicing map. Our methods quantify isoform expression with cell-type and spatial resolution and it contributes to further our understanding of how the brain integrates molecular and cellular complexity.
Severe drought can cause lagged effects on tree physiology that negatively impact forest functioning for years. These “drought legacy effects” have been widely documented in tree‐ring records and ...could have important implications for our understanding of broader scale forest carbon cycling. However, legacy effects in tree‐ring increments may be decoupled from ecosystem fluxes due to (a) postdrought alterations in carbon allocation patterns; (b) temporal asynchrony between radial growth and carbon uptake; and (c) dendrochronological sampling biases. In order to link legacy effects from tree rings to whole forests, we leveraged a rich dataset from a Midwestern US forest that was severely impacted by a drought in 2012. At this site, we compiled tree‐ring records, leaf‐level gas exchange, eddy flux measurements, dendrometer band data, and satellite remote sensing estimates of greenness and leaf area before, during, and after the 2012 drought. After accounting for the relative abundance of tree species in the stand, we estimate that legacy effects led to ~10% reductions in tree‐ring width increments in the year following the severe drought. Despite this stand‐scale reduction in radial growth, we found that leaf‐level photosynthesis, gross primary productivity (GPP), and vegetation greenness were not suppressed in the year following the 2012 drought. Neither temporal asynchrony between radial growth and carbon uptake nor sampling biases could explain our observations of legacy effects in tree rings but not in GPP. Instead, elevated leaf‐level photosynthesis co‐occurred with reduced leaf area in early 2013, indicating that resources may have been allocated away from radial growth in conjunction with postdrought upregulation of photosynthesis and repair of canopy damage. Collectively, our results indicate that tree‐ring legacy effects were not observed in other canopy processes, and that postdrought canopy allocation could be an important mechanism that decouples tree‐ring signals from GPP.
Legacy effects in tree rings were large in response to a severe drought in a temperate forest. Despite this postdrought suppression of tree growth, ecosystem fluxes were not affected, likely due to dynamic C allocation away from stem growth towards the canopy.
Experimental studies assessing climatic effects on ecological communities have typically applied static warming treatments. Although these studies have been informative, they have usually failed to ...incorporate either current or predicted future, patterns of variability. Future climates are likely to include extreme events which have greater impacts on ecological systems than changes in means alone. Here, we review the studies which have used experiments to assess impacts of temperature on marine, freshwater and terrestrial communities, and classify them into a set of ‘generations’ based on how they incorporate variability. The majority of studies have failed to incorporate extreme events. In terrestrial ecosystems in particular, experimental treatments have reduced temperature variability, when most climate models predict increased variability. Marine studies have tended to not concentrate on changes in variability, likely in part because the thermal mass of oceans will moderate variation. In freshwaters, climate change experiments have a much shorter history than in the other ecosystems, and have tended to take a relatively simple approach. We propose a new ‘generation’ of climate change experiments using down‐scaled climate models which incorporate predicted changes in climatic variability, and describe a process for generating data which can be applied as experimental climate change treatments.
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