Adaptation in auditory processing.

Adaptation is an essential feature of auditory neurons, which reduces their responses to unchanging and recurring sounds and allows their response properties to be matched to the constantly changing statistics of sounds that reach the ears. As a consequence, processing in the auditory system highlights novel or unpredictable sounds and produces an efficient representation of the vast range of sounds that animals can perceive by continually adjusting the sensitivity and, to a lesser extent, the tuning properties of neurons to the most commonly encountered stimulus values. Together with attentional modulation, adaptation to sound statistics also helps to generate neural representations of sound that are tolerant to background noise and therefore plays a vital role in auditory scene analysis. In this review, we consider the diverse forms of adaptation that are found in the auditory system in terms of the processing levels at which they arise, the underlying neural mechanisms, and their impact on neural coding and perception. We also ask what the dynamics of adaptation, which can occur over multiple timescales, reveal about the statistical properties of the environment. Finally, we examine how adaptation to sound statistics is influenced by learning and experience and changes as a result of aging and hearing loss.

Quantum critical dynamics in a 5,000-qubit programmable spin glass.

Experiments on disordered alloys1-3 suggest that spin glasses can be brought into low-energy states faster by annealing quantum fluctuations than by conventional thermal annealing. Owing to the importance of spin glasses as a paradigmatic computational testbed, reproducing this phenomenon in a programmable system has remained a central challenge in quantum optimization4-13. Here we achieve this goal by realizing quantum-critical spin-glass dynamics on thousands of qubits with a superconducting quantum annealer. We first demonstrate quantitative agreement between quantum annealing and time evolution of the Schrödinger equation in small spin glasses. We then measure dynamics in three-dimensional spin glasses on thousands of qubits, for which classical simulation of many-body quantum dynamics is intractable. We extract critical exponents that clearly distinguish quantum annealing from the slower stochastic dynamics of analogous Monte Carlo algorithms, providing both theoretical and experimental support for large-scale quantum simulation and a scaling advantage in energy optimization.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissue.

Annexin A11 mutations are a rare cause of amyotrophic lateral sclerosis (ALS), wherein replicated protein variants P36R, G38R, D40G and D40Y are located in a small-alpha helix within the long, disordered N-terminus. To elucidate disease mechanisms, we characterised the phenotypes induced by a genetic loss of function (LoF) and by misexpression of G38R and D40G in vivo. Loss of Annexin A11 results in a low-penetrant behavioural phenotype and aberrant axonal morphology in zebrafish homozygous knockout larvae, which is rescued by human WT Annexin A11. Both Annexin A11 knockout/down and ALS variants trigger nuclear dysfunction characterised by Lamin B2 mis-localisation. The Lamin B2 signature also presented in anterior horn, spinal cord neurons from post-mortem ALS+/-FTD patient tissue possessing G38R and D40G protein variants. These findings suggest mutant Annexin A11 acts as a dominant negative, revealing a potential early nucleopathy highlighting nuclear envelope abnormalities preceding behavioural abnormality in animal models.

NF2-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study.

OBJECTIVES: New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed. METHODS: The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed. RESULTS: 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1-related schwannomatosis and SMARCB1-related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4-18.4 times lower than NF2. CONCLUSIONS: This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling.

Gene discovery and virus-induced gene silencing reveal branched pathways to major classes of bioactive diterpenoids in Euphorbia peplus.

Most macro- and polycyclic Euphorbiaceae diterpenoids derive from the common C20 precursor casbene. While the biosynthetic pathway from casbene to the lathyrane jolkinol C is characterized, pathways to other more complex classes of bioactive diterpenoids remain to be elucidated. A metabolomics-guided transcriptomic approach and a genomics approach that led to the discovery of two casbene-derived diterpenoid gene clusters yielded a total of 68 candidate genes that were transiently expressed in Nicotiana benthamiana for activity toward jolkinol C and other lathyranes. We report two short-chain dehydrogenases/reductases (SDRs), identified by RNA sequencing to be highly expressed in Euphorbia peplus latex. One of these, EpSDR-5, is a C3-ketoreductase, converting jolkinol C to the lathyrane jolkinol E. Gene function of EpSDR-5 was further confirmed by heterologous expression in Saccharomyces cerevisiae. To investigate the in vivo role of EpSDR-5, we established virus-induced gene silencing (VIGS) in E. peplus, resulting in a significant reduction in jatrophanes and a corresponding increase in ingenanes. VIGS of Casbene Synthase results in a major reduction in both jatrophanes and ingenanes, the two most abundant classes of E. peplus diterpenoids. VIGS of CYP71D365 had a similar effect, consistent with the previously determined role of this gene in the pathway to jolkinol C. These results point to jolkinol C being a branch point intermediate in the pathways to ingenanes and jatrophanes with EpSDR-5 responsible for the first step from jolkinol C to jatrophane production.

Locally applied heat stress during exercise training may promote adaptations to mitochondrial enzyme activities in skeletal muscle.

There is some evidence for temperature-dependent stimulation of mitochondrial biogenesis; however, the role of elevated muscle temperature during exercise in mitochondrial adaptation to training has not been studied in humans in vivo. The purpose of this study was to determine the role of elevating muscle temperature during exercise in temperate conditions through the application of mild, local heat stress on mitochondrial adaptations to endurance training. Eight endurance-trained males undertook 3 weeks of supervised cycling training, during which mild (~ 40 °C) heat stress was applied locally to the upper-leg musculature of one leg during all training sessions (HEAT), with the contralateral leg serving as the non-heated, exercising control (CON). Vastus lateralis microbiopsies were obtained from both legs before and after the training period. Training-induced increases in complex I (fold-change, 1.24 ± 0.33 vs. 1.01 ± 0.49, P = 0.029) and II (fold-change, 1.24 ± 0.33 vs. 1.01 ± 0.49, P = 0.029) activities were significantly larger in HEAT than CON. No significant effects of training, or interactions between local heat stress application and training, were observed for complex I-V or HSP70 protein expressions. Our data provides partial evidence to support the hypothesis that elevating local muscle temperature during exercise augments training-induced adaptations to mitochondrial enzyme activity.

NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons.

The pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability, and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in bowel motility and a reduction in IBS-related pain; however, the mechanism by which tenapanor mediates these functions remains unclear. Here, the effects of tenapanor on colonic pain signaling and intestinal permeability were assessed through behavioral, electrophysiological, and cell culture experiments. Intestinal motility studies in rats and humans demonstrated that tenapanor increased luminal sodium and water retention and gastrointestinal transit versus placebo. A significantly reduced visceral motor reflex (VMR) to colonic distension was observed with tenapanor treatment versus vehicle in two rat models of visceral hypersensitivity (neonatal acetic acid sensitization and partial restraint stress; both P < 0.05), returning VMR responses to that of nonsensitized controls. Whole cell voltage patch-clamp recordings of retrogradely labeled colonic dorsal root ganglia (DRG) neurons from sensitized rats found that tenapanor significantly reduced DRG neuron hyperexcitability to capsaicin versus vehicle (P < 0.05), an effect not mediated by epithelial cell secretions. Tenapanor also attenuated increases in intestinal permeability in human colon monolayer cultures caused by incubation with proinflammatory cytokines (P < 0.001) or fecal supernatants from patients with IBS-C (P < 0.005). These results support a model in which tenapanor reduces IBS-related pain by strengthening the intestinal barrier, thereby decreasing permeability to macromolecules and antigens and reducing DRG-mediated pain signaling.NEW & NOTEWORTHY A series of nonclinical experiments support the theory that tenapanor inhibits IBS-C-related pain by strengthening the intestinal barrier. Tenapanor treatment reduced visceral motor responses to nonsensitized levels in two rat models of hypersensitivity and reduced responses to capsaicin in sensitized colonic nociceptive dorsal root ganglia neurons. Intestinal permeability experiments in human colon monolayer cultures found that tenapanor attenuates increases in permeability induced by either inflammatory cytokines or fecal supernatants from patients with IBS-C.

The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.

BACKGROUND: Primary and booster vaccinations are critical for mitigating COVID-19 transmission, morbidity, and mortality. Future booster vaccine campaigns rely on an increased understanding of vaccine hesitancy. OBJECTIVE: To evaluate self-reported allergic and skin vaccine reactions as factors potentially associated with vaccine hesitancy in a nationwide vaccine allergy registry. METHODS: Responses to survey questions concerning COVID-19 vaccine perceptions, coded from free text by 2 independent reviewers. Multivariable logistic regression models were used to determine the association between changed negative perception and respondent demographics, vaccination history, and reaction characteristics. RESULTS: A total of 993 individuals (median of 46 years [IQR, 36-59], 88% female, 82% White) self-reported reactions to COVID-19 vaccination. Reactions included the following: delayed large local skin reaction (40%), hives/urticaria (32%), immediate large local skin reaction (3%), swelling (3%), anaphylaxis (2%), and other or unspecified (20%). Most respondents were initially unconcerned about the safety of COVID-19 vaccines (56%). After reactions, 401 of 993 (40%) report negative change in perception of vaccination, with more than half of these respondents (n = 211, 53%) citing their reasoning as a negative experience with adverse effects. Of 102 individuals asked about future vaccination, 79 (77%) indicated that they were unlikely or very unlikely to receive future COVID-19 vaccinations. Increased negative perception after reaction was associated with younger age, later COVID-19 vaccination dose number, and reaction type. CONCLUSION: Our findings reveal that an individual's experience with allergic or cutaneous adverse effects after COVID-19 vaccination affects attitudes and decision-making regarding future vaccination, even in initially non-hesitant individuals. Further investigation of secondary vaccine hesitancy is necessary for adapting public health messaging to this important population.

Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21.

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.

Observation of topological phenomena in a programmable lattice of 1,800 qubits.

The work of Berezinskii, Kosterlitz and Thouless in the 1970s1,2 revealed exotic phases of matter governed by the topological properties of low-dimensional materials such as thin films of superfluids and superconductors. A hallmark of this phenomenon is the appearance and interaction of vortices and antivortices in an angular degree of freedom-typified by the classical XY model-owing to thermal fluctuations. In the two-dimensional Ising model this angular degree of freedom is absent in the classical case, but with the addition of a transverse field it can emerge from the interplay between frustration and quantum fluctuations. Consequently, a Kosterlitz-Thouless phase transition has been predicted in the quantum system-the two-dimensional transverse-field Ising model-by theory and simulation3-5. Here we demonstrate a large-scale quantum simulation of this phenomenon in a network of 1,800 in situ programmable superconducting niobium flux qubits whose pairwise couplings are arranged in a fully frustrated square-octagonal lattice. Essential to the critical behaviour, we observe the emergence of a complex order parameter with continuous rotational symmetry, and the onset of quasi-long-range order as the system approaches a critical temperature. We describe and use a simple approach to statistical estimation with an annealing-based quantum processor that performs Monte Carlo sampling in a chain of reverse quantum annealing protocols. Observations are consistent with classical simulations across a range of Hamiltonian parameters. We anticipate that our approach of using a quantum processor as a programmable magnetic lattice will find widespread use in the simulation and development of exotic materials.

Incidence of emergence agitation in children undergoing sevoflurane anesthesia compared to isoflurane anesthesia: An updated systematic review and meta-analysis.

BACKGROUND: Emergence agitation is a complex syndrome of altered consciousness after emergence from anesthesia. It can result in injury to patients and staff and is associated with other postoperative complications. Sevoflurane has been associated with emergence agitation, potentially due to low tissue solubility and therefore speed of emergence. Prior meta-analyses comparing emergence agitation incidence between sevoflurane and isoflurane anesthetics did not demonstrate a statistically significant difference. Given the publication of additional relevant studies not included in prior meta-analyses as well as improved diagnosis of emergence agitation, we aim to perform an updated, comprehensive meta-analysis comparing emergence agitation incidence between sevoflurane and isoflurane anesthetics in children. METHODS: We conducted an updated systematic review and meta-analysis of clinical trials comparing sevoflurane to isoflurane in children <18 years of age, reporting emergence agitation as an outcome, published before July 2023 using databases and registers. Our primary outcome was the incidence of emergence agitation. Secondary outcomes were time to extubation, awakening time, and length of stay in the postanesthetic care unit. We assessed the risk of bias using the Cochrane Risk of Bias tool version 2. We pooled the effect size for the outcomes using the fixed effects model if we had low heterogeneity, otherwise, we used a random-effects model. RESULTS: Eight randomized controlled trials (523 children) were included in the final analysis. The incidence of emergence agitation after isoflurane was significantly lower compared to sevoflurane (risk ratio: 0.62 (95% CI: [0.46-0.83]; I2 = 40.01%, p < .001)). Time to extubation, awakening times, and postanesthetic care unit duration were not significantly different. The protective effect of isoflurane compared to sevoflurane remained significant in subgroups of patients who received premedication or intraoperative systemic analgesics (risk ratios: (0.48 [0.28-0.82]; I2 = 60.78%, p = .01), (0.52 [0.37-0.75]; I2 = 0.00%, p < .001), respectively). CONCLUSION: The risk of emergence agitation in children after maintenance anesthesia with sevoflurane is significantly greater than with isoflurane; we did not find evidence of prolonged emergence or postanesthetic length of stay. When possible, isoflurane should be considered for maintenance anesthesia over sevoflurane in patients at high risk of emergence agitation.

A watch, wait, and rescan approach for incidental benign-appearing notochordal lesions of the skull base.

OBJECTIVE: The aim of this study was to describe the natural history of incidental benign-appearing notochordal lesions of the skull base with specific attention to features that can make differentiation from low-grade chordoma more difficult, namely contrast uptake and bone erosion. METHODS: In this retrospective case series, the authors describe the clinical outcomes of 58 patients with incidental benign-appearing notochordal lesions of the clivus, including those with minor radiological features of bone erosion or contrast uptake. RESULTS: All lesions remained stable during a median follow-up of almost 3 years. Thirty-seven (64%) patients underwent contrast-enhanced MRI; lesions in 14 (38%) of these patients exhibited minimal contrast enhancement. Twenty-seven (47%) patients underwent CT; lesions in 6 (22%) of these patients exhibited minimal bone erosion. CONCLUSIONS: These data make the case for monitoring selected cases of benign-appearing notochordal lesions of the clivus in the first instance even when there is minor contrast uptake or minimal bone erosion.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

A multi-population approach supports common patterns in marine growth and maturation decision in Atlantic salmon (Salmo salar L.) from southern Europe.

This study provides a regional picture of long-term changes in Atlantic salmon growth at the southern edge of their distribution, using a multi-population approach spanning 49 years and five populations. We provide empirical evidence of salmon life history being influenced by a combination of common signals in the marine environment and population-specific signals. We identified an abrupt decline in growth from 1976 and a more recent decline after 2005. As these declines have also been recorded in northern European populations, our study significantly expands a pattern of declining marine growth to include southern European populations, thereby revealing a large-scale synchrony in marine growth patterns for almost five decades. Growth increments during their sea sojourn were characterized by distinct temporal dynamics. At a coarse temporal resolution, growth during the first winter at sea seemed to gradually improve over the study period. However, the analysis of finer seasonal growth patterns revealed ecological bottlenecks of salmon life histories at sea in time and space. Our study reinforces existing evidence of an impact of early marine growth on maturation decision, with small-sized individuals at the end of the first summer at sea being more likely to delay maturation. However, each population was characterized by a specific probabilistic maturation reaction norm, and a local component of growth at sea in which some populations have better growth in some years might further amplify differences in maturation rate. Differences between populations were smaller than those between sexes, suggesting that the sex-specific growth threshold for maturation is a well-conserved evolutionary phenomenon in salmon. Finally, our results illustrate that although most of the gain in length occurs during the first summer at sea, the temporal variability in body length at return is buffered against the decrease in post-smolt growth conditions. The intricate combination of growth over successive seasons, and its interplay with the maturation decision, could be regulating body length by maintaining diversity in early growth trajectories, life histories, and the composition of salmon populations.

TGFß1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy.

The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGß1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFß1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

In situ synchrotron X-ray multimodal experiment to study polycrystal plasticity.

The microstructure of polycrystals is known to govern the performance of structural materials. This drives the need for mechanical characterization methods capable of probing large representative volumes at the grain and sub-grain scales. In this paper, the use of in situ diffraction contrast tomography (DCT) along with far-field 3D X-ray diffraction (ff-3DXRD) at the Psiché beamline of Soleil is presented and applied to study crystal plasticity in commercially pure titanium. A tensile stress rig was modified to comply with the DCT acquisition geometry and used for in situ testing. DCT and ff-3DXRD measurements were carried out during a tensile test of a tomographic Ti specimen up to 1.1% strain. The evolution of the microstructure was analyzed in a central region of interest comprising about 2000 grains. Using the 6DTV algorithm, DCT reconstructions were successfully obtained and allowed the characterization of the evolution of lattice rotation in the entire microstructure. The results are backed up by comparisons with EBSD and DCT maps acquired at ESRF-ID11 that allowed the validation of the orientation field measurements in the bulk. Difficulties at the grain boundaries are highlighted and discussed in line with increasing plastic strain during the tensile test. Finally, a new outlook is provided on the potential of ff-3DXRD to enrich the present dataset with access to average lattice elastic strain data per grain, on the possibility of performing crystal plasticity simulations from DCT reconstructions, and ultimately on comparisons between experiments and simulations at the scale of the grain.

Deformation of two-phase aggregates with in situ X-ray tomography in rotating Paris-Edinburgh cell at GPa pressures and high temperature.

High-pressure (>1 GPa) torsion apparatus can be coupled with in situ X-ray tomography (XRT) to study microstructures in materials associated with large shear strains. Here, deformation experiments were carried out on multi-phase aggregates at ∼3-5 GPa and ∼300-500°C, using a rotational tomography Paris-Edinburgh press (RoToPEc) with in situ absorption contrast XRT on the PSICHE beamline at Synchrotron SOLEIL. The actual shear strain reached in the samples was quantified with respect to the anvil twisting angles, which is γ ≤ 1 at 90° anvil twist and reaches γ ≃ 5 at 225° anvil twist. 2D and 3D quantifications based on XRT that can be used to study in situ the deformation microfabrics of two-phase aggregates at high shear strain are explored. The current limitations for investigation in real time of deformation microstructures using coupled synchrotron XRT with the RoToPEc are outlined.

Characterizing chemical signaling between engineered "microbial sentinels" in porous microplates.

Living materials combine a material scaffold, that is often porous, with engineered cells that perform sensing, computing, and biosynthetic tasks. Designing such systems is difficult because little is known regarding signaling transport parameters in the material. Here, the development of a porous microplate is presented. Hydrogel barriers between wells have a porosity of 60% and a tortuosity factor of 1.6, allowing molecular diffusion between wells. The permeability of dyes, antibiotics, inducers, and quorum signals between wells were characterized. A "sentinel" strain was constructed by introducing orthogonal sensors into the genome of Escherichia coli MG1655 for IPTG, anhydrotetracycline, L-arabinose, and four quorum signals. The strain's response to inducer diffusion through the wells was quantified up to 14 mm, and quorum and antibacterial signaling were measured over 16 h. Signaling distance is dictated by hydrogel adsorption, quantified using a linear finite element model that yields adsorption coefficients from 0 to 0.1 mol m-3 . Parameters derived herein will aid the design of living materials for pathogen remediation, computation, and self-organizing biofilms.