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BACKGROUND: Novel preventive therapies are needed for postoperative delirium, which especially affects older patients. A mouse model is presented that captures inflammation-associated cortical slow wave activity (SWA) observed in patients, allowing exploration of the mechanistic role of prostaglandin-adenosine signalling. METHODS: EEG and cortical cytokine measurements (interleukin 6, monocyte chemoattractant protein-1) were obtained from adult and aged mice. Behaviour, SWA, and functional connectivity were assayed before and after systemic administration of lipopolysaccharide (LPS)+piroxicam (cyclooxygenase inhibitor) or LPS+caffeine (adenosine receptor antagonist). To avoid the confounder of inflammation-driven changes in movement which alter SWA and connectivity, electrophysiological recordings were classified as occurring during quiescence or movement, and propensity score matching was used to match distributions of movement magnitude between baseline and post-LPS administration. RESULTS: LPS produces increases in cortical cytokines and behavioural quiescence. In movement-matched data, LPS produces increases in SWA (likelihood-ratio test: χ(2)(4)=21.51, P

Introduction The primary objective of this study was to describe the immediate post-procedural outcomes in dogs with severe pulmonary stenosis that were treated with low-pressure balloon valvuloplasty (BV) at a single institution. Animals, materials and methods Retrospective case series; medical records of dogs that underwent BV performed with a balloon dilation catheter >20 mm in diameter and a burst pressure of less than 4 atm (atm) were retrospectively reviewed. Twenty animals were identified fitting the criteria. Pre-procedural and post-procedural echocardiograms and peri-procedural angiograms were reviewed. Procedural success was defined as greater than 50% reduction in echocardiographically derived transpulmonary systolic pressure gradient (TPPG) or post-procedural TPPG of less than 50 mmHg. Results The median percent reduction from initial TPPG was 53% (range = 15−90%). Sixty percent of the dogs met the pre-specified criteria for a successful outcome. Post-procedural TPPG was not different based on valve types A or B (p=0.67), presence or absence of additional supravalvular (p=0.23) or subvalvular (p=0.83) obstructive components. Discussion The proportion of dogs that reach the successful outcome were not different based on valve type A or B. No relationship was noted between immediate outcomes and bodyweight or pulmonary annulus diameter. Conclusion Dogs with severe pulmonic stenosis that underwent low-pressure BV had good immediate outcomes with no difference in outcome based on valve morphology. Further randomized controlled studies are needed to compare the outcomes of different strategies for BV in dogs with large-diameter pulmonary annulus.

The influence of heating rate on the microstructural evolution of a cold-rolled AA7075 alloy sheet during solution heat treatment was examined using electrical conductivity, scanning electron microscopy, X-ray diffraction, transmission electron microscopy and electron backscatter diffraction. The results indicate that the dissolution of soluble phases takes place during the heating process. The heating rates affect the dissolution process of soluble phases, and these phases completely dissolve into matrix after solution treatment. Recrystallized and elongated grains are produced after solution treatment by both fast and slow heating rates, while the grains of the rapidly heated sample are much finer. The elongated grains are attributed to the difference in the pinning pressure of boundary migration between the rolling and normal directions. The {111} texture, as well as typical recrystallization textures, were found in both fast and slowly heated samples after solution treatment, but the textures, especially the {111} component in the slow-heated sample, are much stronger, leading to an anisotropy in the tensile properties after artificial aging.

INTRODUCTION: Carbon monoxide (CO) is a toxic gas with potential for detriment to spaceflight operations. An analytical model was developed to investigate if a maximum CO contamination of 1 ppm in the oxygen (O₂) supply reached dangerous levels during extravehicular activity (EVA). Occupational monitoring pre- and postsuited exposures provided supplementary data for review.METHODS: The analytical model estimated O₂ and CO concentrations in the extravehicular mobility unit (EMU) based on O₂ and CO flow rates into and out of the system. The model was based on 3 h of prebreathe at 15.2 psia, 8 h of EVA at 4.3 psia, and 1 h at 15.2 psia for suit doffing. The Coburn-Forster-Kane equation was used to calculate crewmember carboxyhemoglobin saturation (COHb%) as a function of time. Monitoring of hemoglobin CO saturation (Spco) with a CO-oximeter was conducted pre- and post-EVA during operations on the International Space Station and in ground-based analog environments.RESULTS: The model predicted a maximum PCO in the EMU of 0.061 mmHg and a maximum crewmember COHb% of 2.1%. Operational Spco measurements in mean ± SD during ground-based analog testing were 0.7% ± 1.8% pretest and 0.5% ± 1.5% posttest. Spco values on the ISS were 1.5% ± 0.7% pre-EVA and 1.1% ± 0.3% post-EVA.DISCUSSION: The model predicted that astronauts are not exposed to toxic levels of CO during EVA and operational measurements did not show significant differences between Spco levels between pre- and post-EVA.Makowski MS, Norcross JR, Alexander D, Sanders RW, Conkin J, Young M. Carbon monoxide levels in the extravehicular mobility unit by modeling and operational testing. Aerosp Med Hum Perform. 2019; 90(2):84-91.

This cohort study examines major surgical admissions and quality of life.

BACKGROUND: Impaired consciousness has been associated with impaired cortical signal propagation after transcranial magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy. METHODS: Eight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced time–frequency responses and evoked response potentials were used to investigate propofol's effects on connectivity between regions. RESULTS: Sensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital, parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward responses in cross-frequency theta/alpha–gamma coupling and within frequency theta coupling (F contrast, family-wise error corrected P

INTRODUCTION: A review of decompression sickness (DCS) cases associated with the NASA altitude physiological training (APT) program at the Johnson Space Center (JSC) motivated us to place our findings into the larger context of DCS prevalence from other APT centers.METHODS: We reviewed JSC records from 1999 to 2016 and 14 publications from 1968 to 2004 about DCS prevalence in other APT programs. We performed a meta-analysis of 15 APT profiles (488 cases / 385,116 exposures). We used meta-regression to evaluate the relation between estimated exposures and probability of DCS in a test group, accounting for the heterogeneity between studies.RESULTS: Our in-house review identified 6 Type I DCS (1 from an inside observer) and 1 Type II DCS. There were 6 cases in 9560 student hypobaric exposures from 3 NASA training flights; a student pooled prevalence rate of 0.44 cases / 1000 exposures compared to 1.44 cases / 1000 from 12 published APT profiles. The overall pooled DCS prevalence rate was 1.16 cases / 1000 exposures. There was substantial heterogeneity in DCS prevalence across studies. Denitrogenation time, exposure pressure, and exposure time were associated with probability of DCS in the meta-regression model.CONCLUSIONS: While the overall DCS prevalence rate is relatively low, there is marked heterogeneity among profiles. The pooled DCS prevalence rate estimate for the NASA profiles was lower than the overall rate. Variability in APT profile DCS prevalence could be further explained given student level and additional test-level covariates.Conkin J, Sanders RW, Koslovsky MD, Wear ML, Kozminski AG, Abercromby AFJ. A systematic review and meta-analysis of decompression sickness in altitude physiological training. Aerosp Med Hum Perform. 2018; 89(11):941-951.

Based on landmark trials, international guidelines had for years promoted the use of beta-blockers in the setting of non-cardiac surgery. In 2011, concerns were raised regarding the integrity of some of the landmark trials, as the Dutch Erasmus Medical Center found some of them to be scientifically incorrect. Based on the remaining studies that were to be trusted, investigations showed that, in contrast to prior beliefs, the widespread use of perioperative beta-blockers might be harmful. A call for further investigations into the matter ushered in several observational studies evaluating the safety of perioperative beta-blocker therapy in specific patient subgroups. Within this review, we discuss important aspects for making these decisions, and compare the major observational studies and specific estimates of risk in subgroups of interest. We conclude that patients at high risk with heavy co-morbidities, such as heart failure, may benefit from beta-blocker therapy, whereas low-risk patients, such as patients with uncomplicated hypertension, may be at increased risk with beta-blocker therapy. We provide a critical review of current perioperative guidelines in view of the new observational data, suggesting that the recommended schematics, such as the Revised Cardiac Risk Index, for risk stratification of patients in this setting may be suboptimal. Further, we provide discussions of other aspects, including risk of sepsis, type of beta-blocker, and the potential of perioperative beta-blocker withdrawal, which may be important in guiding future studies. Summarising the current evidence, we argue that, after a precarious decade, we may just now, be back on safe ground.

Astronauts training for extravehicular activity (EVA) operations can spend many hours submerged underwater in a pressurized suit, called an extravehicular mobility unit (EMU), exposed to pressures exceeding 2 atmospheres absolute (ATA). To minimize the risk of decompression sickness (DCS) a 46% nitrox mixture is used. This limits the nitrogen partial pressure, decreasing the risk of DCS. The trade-off with using a 46% nitrox mixture is the increased potential for oxygen toxicity, which can lead to severe neurologic symptoms including seizures. Suited runs, which typically expose astronauts of 0.9-1.1 ATA for longer than six hours, routinely exceed the recommendation for central nervous system oxygen toxicity limits (CNSOTL) published by the National Oceanic and Atmospheric Administration (NOAA). Fortunately, in over 50,000 hours of suited training dives spanning 20 years of EVA training operations at NASA’s Neutral Buoyancy Laboratory (NBL) there has never been an occurrence of oxygen toxicity. This lends support to anecdotal sentiment among certain members of the hyperbaric community that the NOAA CNSOTL recommendations might be overly conservative, at least for the oxygen pressure and time regime in which NBL operates. The NOAA CNSOTL recommendations are the result of expert consensus with a focus on safety and do not necessarily reflect rigorous experimental evidence. The data from the NBL suited dive operations provide a foundation of evidence that can help inform the expert discussion on dive-related neurologic oxygen toxicity performance and over-night recovery in young, healthy males.

The present work studied the effects of quenching rate and aging conditions on the microstructure and mechanical properties of AA6016 automotive sheet. Significant differences in mechanical properties were observed after solution treatment and quenching at three different rates. The rapidly quenched alloy showed a better combination of properties compared to the slowly quenched material in both naturally and artificially aged tempers. Slow quenching resulted in coarse Si and Mg2Si precipitates along the grain boundaries that affected fracture behavior during 180° bending of T4 material. After artificial aging, a separate type of bending test indicated that the energy absorption capability of alloy 6016 is seriously impacted at slow quench rates. Electrical conductivity (EC), Vickers micro-hardness (HV), scanning electron microscopy (SEM), transmission electron microscopy (TEM), as well as bending tests were used to follow microstructure and mechanical property changes during natural and artificial aging.

Summary Background Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure. Methods In this multicentre, phase 2 trial, we enrolled children younger than 3 years with newly diagnosed medulloblastoma at six centres in the USA and Australia. Children aged 3–5 years with newly diagnosed, non-metastatic medulloblastoma without any high-risk features were also eligible. Eligible patients were required to start therapy within 31 days from definitive surgery, had a Lansky performance score of at least 30, and did not receive previous radiotherapy or chemotherapy. Patients were stratified postoperatively by clinical and histological criteria into low-risk, intermediate-risk, and high-risk treatment groups. All patients received identical induction chemotherapy (methotrexate, vincristine, cisplatin, and cyclophosphamide), with high-risk patients also receiving an additional five doses of vinblastine. Induction was followed by risk-adapted consolidation therapy: low-risk patients received cyclophosphamide (1500 mg/m 2 on day 1), etoposide (100 mg/m 2 on days 1 and 2), and carboplatin (area under the curve 5 mg/mL per min on day 2) for two 4-week cycles; intermediate-risk patients received focal radiation therapy (54 Gy with a clinical target volume of 5 mm over 6 weeks) to the tumour bed; and high-risk patients received chemotherapy with targeted intravenous topotecan (area under the curve 120–160 ng-h/mL intravenously on days 1–5) and cyclophosphamide (600 mg/m 2 intravenously on days 1–5). After consolidation, all patients received maintenance chemotherapy with cyclophosphamide, topotecan, and erlotinib. The coprimary endpoints were event-free survival and patterns of methylation profiling associated with progression-free survival. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy); biological analyses included all patients with tissue available for methylation profiling. This trial is registered with ClinicalTrials.gov, number NCT00602667, and was closed to accrual on April 19, 2017. Findings Between Nov 27, 2007, and April 19, 2017, we enrolled 81 patients with histologically confirmed medulloblastoma. Accrual to the low-risk group was suspended after an interim analysis on Dec 2, 2015, when the 1-year event-free survival was estimated to be below the stopping rule boundary. After a median follow-up of 5·5 years (IQR 2·7–7·3), 5-year event-free survival was 31·3% (95% CI 19·3–43·3) for the whole cohort, 55·3% (95% CI 33·3–77·3) in the low-risk cohort (n=23) versus 24·6% (3·6–45·6) in the intermediate-risk cohort (n=32; hazard ratio 2·50, 95% CI 1·19–5·27; p=0·016) and 16·7% (3·4–30·0) in the high-risk cohort (n=26; 3·55, 1·66–7·59; p=0·0011; overall p=0·0021). 5-year progression-free survival by methylation subgroup was 51·1% (95% CI 34·6–67·6) in the sonic hedgehog (SHH) subgroup (n=42), 8·3% (95% CI 0·0–24·0%) in the group 3 subgroup (n=24), and 13·3% (95% CI 0·0–37·6%) in the group 4 subgroup (n=10). Within the SHH subgroup, two distinct methylation subtypes were identified and named iSHH-I and iSHH-II. 5-year progression-free survival was 27·8% (95% CI 9·0–46·6; n=21) for iSHH-I and 75·4% (55·0–95·8; n=21) for iSHH-II. The most common adverse events were grade 3–4 febrile neutropenia (48 patients [59%]), neutropenia (21 [26%]), infection with neutropenia (20 [25%]), leucopenia (15 [19%]), vomiting (15 [19%]), and anorexia (13 [16%]). No treatment-related deaths occurred. Interpretation The risk-adapted approach did not improve event-free survival in young children with medulloblastoma. However, the methylation subgroup analyses showed that the SHH subgroup had improved progression-free survival compared with the group 3 subgroup. Moreover, within the SHH subgroup, the iSHH-II subtype had improved progression-free survival in the absence of radiation, intraventricular chemotherapy, or high-dose chemotherapy compared with the iSHH-I subtype. These findings support the development of a molecularly driven, risk-adapted, treatment approach in future trials in young children with medulloblastoma. Funding American Lebanese Syrian Associated Charities, St Jude Children's Research Hospital, NCI Cancer Center, Alexander and Margaret Stewart Trust, Sontag Foundation, and American Association for Cancer Research.

OBJECTIVE To determine the frequency and complexity of ventricular arrhythmias in a group of healthy Salukis evaluated by means of continuous Holter monitoring for 7 days. DESIGN Prospective case series. ANIMALS 25 healthy Salukis > 18 months old. PROCEDURES In all dogs, a history was obtained and a physical examination and transthoracic echocardiography were performed to verify the absence of structural cardiac disease. Dogs then underwent Holter monitoring for 7 days. Data recorded included heart rate parameters and the occurrence of conduction disturbances, ventricular premature complexes, ventricular couplets, ventricular triplets, ventricular bigeminy, ventricular trigeminy, and ventricular tachycardia. RESULTS 25 dogs (13 sexually intact females, 2 spayed females, and 10 sexually intact males) were enrolled in the study. All 25 dogs had at least one 24-hour period during which ventricular premature complexes were detected. Median number of ventricular premature complexes during any 24-hour period in all dogs was 2 (interquartile [25th to 75th percentile] range, 0 to 4). There were no significant differences between males and females in regard to median number of ventricular premature complexes per 24-hour period or recorded heart rate parameters. CONCLUSIONS AND CLINICAL RELEVANCE For Salukis in the study population, 7-day Holter monitoring revealed infrequent ventricular arrhythmias. These findings suggested that detection of a ventricular arrhythmia in a healthy Saluki may be an indication for further diagnostic evaluation.

The influences of intensity and repeated exposure to ultraviolet-B radiation (UVB), photoreactivating repair radiation (PRR), and temperature on the scuticociliate Parauronema acutum were explored under laboratory conditions. Population growth was negatively affected after exposure to the equivalent of one sunny summer day of ambient UVB, especially in the absence of PRR. Repeated daily exposure to UVB severely compromised ciliate survival. UVB-exposed treatments without PRR recovered slower and reached lower final abundances than treatments receiving PRR. Reducing the daily UVB exposure approximately 25% improved ciliate recovery after exposure. In the single exposure treatments, temperature effects were not consistent, except that growth was slowest for control and treatments at the lowest temperature (15 °C). These data suggest that dark repair and/or photoprotection are present in P. acutum, but photoenzymatic repair was the more effective mechanism in reversing UVB damage. Repeated exposure treatments without PRR had zero or declining growth at all temperatures (15, 20 and 25 °C), as did those with PRR at 15 °C. Significant temperature/dose differences were identified in the repeated exposure treatments; ciliates subjected to the higher UVB intensity with PRR survived only at 25 °C, while ciliate populations under reduced UVB increased at 20 and 25 °C.

This study has a theoretical and an empirical part. In the theoretical part, we focus on an issue underlying studies of what language learners must learn to interact competently in L2. These studies do not consider what learners already know that we refer to as basic interactional competence (BIC), a putative universal that begins developing in pre-linguistic infancy as part of human rationality. BIC is knowledge of the way successive utterances/actions can be substantively interconnected that forms them into an interaction and not a random collection. We regard BIC as the basis on which learners infer and adopt the practices and norms of native speakers in a host culture, as well as interact competently with other learners in L2 as a lingua franca. In the empirical part of this study, we examine naturally occurring interactions between learners of English and native speakers to identify some aspects of learners’ participation that rest directly on BIC. We assigned participants a topic they could discuss without asymmetries of knowledge of the topic, or of culture- and institution-specific norms, techniques, practices, and roles. We found that learners took an active part in making their interactions succeed in ways that have gone unnoticed and unheralded. Their responses to questions, self-editing of word choices, and detecting and remedying understanding troubles, are attributable to their having tacitly analyzed the substantive interactions among utterance/actions.

Transthoracic echocardiography (TTE) is a valuable non-invasive imaging research technique. In ovine models of cardiac disease, restraint for TTE often involves sedation even with currently available restraint equipment; our goal was to determine the feasibility of using a commercial restraint device, commonly known as the sheep chair, in minimizing animal stress and the need for sedation while achieving a complete TTE examination. A total of 10 healthy adult Dorset sheep were restrained in a sheep chair for TTE and observed for signs of stress. No animals displayed overt evidence of stress and none required sedation. While individual anatomic variation existed, image quality was sufficient to determine cardiac function. These observations suggest that a sheep chair is a useful aid in minimizing the need for sedation to acquire a full TTE study in ovine subjects.

Background The outcomes of emergent noncardiac, nonintracranial surgery in patients with previous stroke remain unknown. Methods All emergency surgeries performed in Denmark (2005 to 2011) were analyzed according to time elapsed between previous ischemic stroke and surgery. The risks of 30-day mortality and major adverse cardiovascular events were estimated as odds ratios (ORs) and 95% CIs using adjusted logistic regression models in a priori defined groups (reference was no previous stroke). In patients undergoing surgery immediately (within 1 to 3 days) or early after stroke (within 4 to 14 days), propensity-score matching was performed. Results Of 146,694 nonvascular surgeries (composing 98% of all emergency surgeries), 5.3% had previous stroke (mean age, 75 yr [SD = 13]; 53% women, 50% major orthopedic surgery). Antithrombotic treatment and atrial fibrillation were more frequent and general anesthesia less frequent in patients with previous stroke (all P < 0.001). Risks of major adverse cardiovascular events and mortality were high for patients with stroke less than 3 months (20.7 and 16.4% events; OR = 4.71 [95% CI, 4.18 to 5.32] and 1.65 [95% CI, 1.45 to 1.88]), and remained increased for stroke within 3 to 9 months (10.3 and 12.3%; OR = 1.93 [95% CI, 1.55 to 2.40] and 1.20 [95% CI, 0.98 to 1.47]) and stroke more than 9 months (8.8 and 11.7%; OR = 1.62 [95% CI, 1.43 to 1.84] and 1.20 [95% CI, 1.08 to 1.34]) compared with no previous stroke (2.3 and 4.8% events). Major adverse cardiovascular events were significantly lower in 323 patients undergoing immediate surgery (21%) compared with 323 successfully propensity-matched early surgery patients (29%; P = 0.029). Conclusions Adverse cardiovascular outcomes and mortality were greatly increased among patients with recent stroke. However, events were higher 4 to 14 days after stroke compared with 1 to 3 days after stroke.

Background Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. Methods We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004–13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs Results A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01–1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03–1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. Conclusions In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality.

The solution heat treatment of AA6014 sheet is important to meet the required dent resistance in assembled automotive structures. In this study, the effect of solution heat treatment conditions on the Mg2Si particle size distribution and volume fraction were quantitatively investigated using SEM observations, electrical conductivity, and hardness measurements. Precipitation during artificial aging was studied by DSC analysis. After soaking at 570 °C for 1min, the volume fraction of soluble Mg2Si was reduced dramatically from 1.58% to nearly zero. Hardness measurements, EC, and SEM characterization of T4 samples were compared as measures of Mg2Si dissolution.

American marten are associated with forests that are characteristically late successional, closed canopy, and diverse in structure; these attributes meet their habitat requirements and provide resting sites. However, the small populations of marten in Michigan's Northern Lower Peninsula face modern habitat conditions that are fragmented and considerably altered from presettlement environments. Resting site structures are required habitat components that are used daily and provide protection from predation and inclement weather but may be limiting and require active management to preserve. We identified resting site characteristics of American marten in the Manistee National Forest from May 2011 to December 2013. Twenty-five marten (15 male and 10 female) were monitored to identify resting sites. We identified 522 unique resting site structures; tree cavities (n = 255, 48.9%), branches (n = 162, 31%), and nests (n = 90, 17.2%) were most commonly observed. During the summer (April–September) marten...

Growing and consistent preclinical evidence, combined with early clinical epidemiological observations, suggest potentially neurotoxic effects of commonly used anesthetic agents in the developing brain. This has prompted the FDA to issue a safety warning for all sedatives and anesthetics approved for use in children under three years of age. Recent studies have identified dexmedetomidine, the potent α2-adrenoceptor agonist, and xenon, the noble gas, as effective anesthetic adjuvants that are both less neurotoxic to the developing brain, and also possess neuroprotective properties in neonatal and other settings of acute ongoing neurologic injury. Dexmedetomidine and xenon are effective anesthetic adjuvants that appear to be less neurotoxic than other existing agents and have the potential to be neuroprotective in the neonatal and pediatric settings. Although results from recent clinical trials and case reports have indicated the neuroprotective potential of xenon and dexmedetomidine, additional randomized clinical trials corroborating these studies are necessary. By reviewing both the existing preclinical and clinical evidence on the neuroprotective effects of dexmedetomidine and xenon, we hope to provide insight into the potential clinical efficacy of these agents in the management of pediatric surgical patients.

Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior; e.g., hearing a siren, we expect to see an ambulance and quickly make way. While theoretical and computational frameworks for prediction exist, circuit and receptor-level mechanisms are unclear. Using high-density EEG and Bayesian modeling, we show that trial history and frontal alpha activity account for reaction times (a proxy for predictions) on a trial-by-trial basis in an audio-visual prediction task. Low-dose ketamine, a NMDA receptor blocker – but not the control drug dexmedetomidine – perturbed predictions, their representation in frontal cortex, and feedback to posterior cortex. This study suggests predictions depend on frontal alpha activity and NMDA receptors, and ketamine blocks access to learned predictive information. One Sentence Summary Predictions depend on NMDA receptors, representation in frontal cortex, and feedback to sensory cortex for comparison with sensory evidence.

Neuroimaging is increasingly being used as a tool to gain a greater understanding of the pathogenesis of delirium. While initial neuroimaging investigations of delirium centered on qualitative analysis of brain computerized tomography (CT) or magnetic resonance imaging (MRI) lesions, voxel-based morphometry studies were the first to show specific gray and white matter structural correlates related to delirium. More recently, diffusion tensor imaging has offered insights into alterations in white matter pathways that may underlie delirium. Cerebral blood flow measurements using Xenon CT and MRI techniques have shown both regional and global decreases during delirium compared to baseline. Resting-state functional MRI has also been used to identify changes in functional cortical connectivity. Most recently, positron emission tomography (PET) MRI has given clues to pathologic protein alterations in delirium. Given the constraints of neuroimaging, research must proceed in a focused, hypothesis-driven manner.

Background Postoperative delirium (POD) is a severe brain dysfunction. Although data indicate a high relevance, no survey has investigated the routine practice to monitor delirium outside the ICU setting after surgery. Prior to publishing of the new European Society of Anaesthesiology (ESA) guidelines on POD, an international survey was conducted to assess current practice. Methods European Society of Anaesthesiology-endorsed online survey; Trial Registration: NCT-identifier: 02513537. Results In total, 566 respondents from 62 countries accessed, and 564 (99.6%) completed the survey (completion rate). Overall, 385 (68%) of the respondents reported that delirium is either "very relevant" or "relevant" for their daily clinical practice. In all, 38 (7%) of the respondents routinely monitor for delirium in >50% of all patients. Asked on the monitoring time point, more than half (n = 308, 55%) indicated to screen before or at recovery room discharge, 235 (42%) up to the first postoperative day, 143 (25%) up to 3 days, and 77 (14%) up to 5 postoperative days. Although there is a lack of long-term monitoring, nearly all respondents (n = 530, 94%) reported to treat delirium. Availability of EEG/EMG-based monitoring to assess the depth of anaesthesia was high in the study group (n = 547, 97%) and was used by more than one-third of the respondents to reduce risk of burst suppression (n = 189, 34%). Conclusion Although delirium is perceived as a relevant condition among anaesthesiologists, there is a high demand for implementing monitoring strategies after publishing of the POD Guideline. The survey shows that tools necessary for POD Guideline implementation are available in the centres represented by the respondents.

Electroencephalography signatures of amyloid-β, tau and neurodegenerative pathologies would aid in screening for, tracking progression of, and critically, understanding the pathogenesis of dementia. We hypothesized that slowing of the alpha peak frequency, as a signature of hyperpolarization-activated cyclic nucleotide gated ‘pacemaker’ channel activity, would correlate with amyloid and tau pathology burden measured by amyloid (Pittsburgh Compound B) and tau (MK-6240) positron emission tomography or CSF biomarkers. We also hypothesized that EEG power would be associated with neurodegeneration (CSF neurofilament light and hippocampal volume). Wakeful high-density EEG data were collected from 53 subjects. Both amyloid-β and tau pathology were associated with slowing in the alpha peak frequency [Pittsburgh Compound B (+) vs. Pittsburgh Compound B (−) subjects, P = 0.039 and MK-6240 (+) vs. MK-6240 (−) subjects, P = 0.019]. Furthermore, slowing in the peak alpha frequency correlated with CSF Aβ42/40 ratio (r2 = 0.270; P = 0.003), phosphoTau (pTau181, r2 = 0.290; P = 0.001) and pTau181/Aβ42 (r2 = 0.343; P, EEG signatures of amyloid-β, tau, and neurodegenerative pathologies would aid in the understanding the pathogenesis of dementia. Both amyloid-β and tau pathology were associated with slowing in the alpha peak frequency while neurodegeneration was associated with lower EEG power., Graphical Abstract Graphical Abstract

The objective of this study was to evaluate the accuracy of short duration electrocardiographic (ECG) recordings extracted from ambulatory continuous ECG (Holter) to assess 24-hour mean heart rate in dogs with atrial fibrillation. In this retrospective study, Holter recordings obtained from 20 dogs with atrial fibrillation were selected for analysis. Ten out of 20 dogs were receiving drugs to control heart rate at the time of Holter evaluation. From the Holter recordings, heart rate averages were calculated for various sample durations (five-minutes, 30 minutes, one-hour, two-hours, and three-hours) for each dog. Percentage of these shorter duration ECG obtained HR averages that fell within ±10%, ±15% and ± 20% of 24-hour mean heart rate was determined for each sample duration and for each dog. Seventy five percent of heart rate averages obtained from three-hour ECG recordings fell within ±10% of 24-hour mean HR. All the heart rate averages obtained from two-hour ECG recordings fell within ±20% of 24-hour mean heart rate. Based on the results of this study it can be concluded that the duration of the ECG recording affects the prediction accuracy for 24-hour Holter mean HR. Only two and three hours of Holter recordings provided all heart rate averages within ±20% of 24-hour mean heart rate. No significant differences were noted in the prediction accuracy of shorter duration ECG recordings based on rate control therapy status. Further prospective studies are needed to assess the accuracy of HR obtained at home using various ECG recording devices to predict 24-hour mean heart rate in dogs with atrial fibrillation.

Purpose of review Hemodynamic instability is common in the perioperative period because of obligate physiologic changes that occur with surgery. Despite the frequency of such hemodynamic changes and the potential harm associated with them, particularly in the elderly, guidelines to optimize perioperative blood pressure are lacking. The present review examines recent evidence for perioperative blood pressure management in the elderly. Recent findings Hypotension has been associated with poor outcomes, particularly renal injury, myocardial injury, and increased mortality, in the perioperative period. Hypertension, tachycardia, frequency of blood pressure monitoring, and management of chronic antihypertensive medications may also affect patient outcomes. Elderly patients may be especially prone to adverse events associated with perioperative hemodynamic instability. Summary Precise and intentional management of hemodynamic parameters, medication regimens, and blood pressure monitoring may reduce adverse events in elderly patients undergoing surgery. Further investigation is required to identify the exact hemodynamic parameters that mitigate risk.

We described the use of IV nitroglycerin as adjunctive therapy in three canine patients with left congestive heart failure secondary to degenerative mitral valve disease. All three dogs were admitted for signs of respiratory distress and all were determined to be in left congestive heart failure by history, exam findings, thoracic radiographs, and echocardiography. In addition to standard therapy for left congestive heart failure, IV nitroglycerin was administered as a constant rate infusion at a dose of 1–6 mcg/kg/min. No adverse events attributable to the drug were noted. This is the first reported use of IV nitroglycerin in clinical veterinary patients. Further studies are warranted to investigate the safety, efficacy, and optimal dosing of IV nitroglycerin infusions in dogs with left congestive heart failure.

Cortical thickness is traditionally derived from T1-weighted MRI images. Recent studies have shown an improvement in segmentation with the combination of T1 + T2-FLAIR images. MRI data from 54 adults (mean: 71 years, 65–81 years, 48% females) that are part of an ongoing cohort study were analyzed to investigate whether T1 + T2-FLAIR cortical thickness measurements were superior to those derived from T1-weighted images in identifying age-related atrophy. T1-weighted and T2-FLAIR MRI images were processed through FreeSurfer v6.0. Data was extracted using the Desikan-Killiany (DKT) atlas. FreeSurfer’s GUI QDEC examined age-related atrophy. Nonparametric tests, effect sizes, and Pearson correlations examined differences between T1-only and T1 + T2-FLAIR cortical thickness data. These analyses demonstrated that T1 + T2-FLAIR processed images significantly improved the segmentation of gray matter (chi-square x2, p

Summary Background In non-surgical settings, covert stroke is more common than overt stroke and is associated with cognitive decline. Although overt stroke occurs in less than 1% of adults after non-cardiac surgery and is associated with substantial morbidity, we know little about perioperative covert stroke. Therefore, our primary aim was to investigate the relationship between perioperative covert stroke (ie, an acute brain infarct detected on an MRI after non-cardiac surgery in a patient with no clinical stroke symptoms) and cognitive decline 1 year after surgery. Methods NeuroVISION was a prospective cohort study done in 12 academic centres in nine countries, in which we assessed patients aged 65 years or older who underwent inpatient, elective, non-cardiac surgery and had brain MRI after surgery. Two independent neuroradiology experts, masked to clinical data, assessed each MRI for acute brain infarction. Using multivariable regression, we explored the association between covert stroke and the primary outcome of cognitive decline, defined as a decrease of 2 points or more on the Montreal Cognitive Assessment from preoperative baseline to 1-year follow-up. Patients, health-care providers, and outcome adjudicators were masked to MRI results. Findings Between March 24, 2014, and July 21, 2017, of 1114 participants recruited to the study, 78 (7%; 95% CI 6–9) had a perioperative covert stroke. Among the patients who completed the 1-year follow-up, cognitive decline 1 year after surgery occurred in 29 (42%) of 69 participants who had a perioperative covert stroke and in 274 (29%) of 932 participants who did not have a perioperative covert stroke (adjusted odds ratio 1·98, 95% CI 1·22–3·20, absolute risk increase 13%; p=0·0055). Covert stroke was also associated with an increased risk of perioperative delirium (hazard ratio [HR] 2·24, 95% CI 1·06–4·73, absolute risk increase 6%; p=0·030) and overt stroke or transient ischaemic attack at 1-year follow-up (HR 4·13, 1·14–14·99, absolute risk increase 3%; p=0·019). Interpretation Perioperative covert stroke is associated with an increased risk of cognitive decline 1 year after non-cardiac surgery, and perioperative covert stroke occurred in one in 14 patients aged 65 years and older undergoing non-cardiac surgery. Research is needed to establish prevention and management strategies for perioperative covert stroke. Funding Canadian Institutes of Health Research; The Ontario Strategy for Patient Oriented Research support unit; The Ontario Ministry of Health and Long-Term Care; Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region, China; and The Neurological Foundation of New Zealand.

© 2019 John Wiley & Sons Ltd Aim: Most protist plankton are mixotrophic, with potential to engage in photoautotrophy and phagotrophy; however, the ecology of these organisms has been misdiagnosed for over a century. A large proportion of these organisms are constitutive mixotrophs (CMs), with an innate ability to photosynthesize. Here, for the first time, an analysis is presented of the biogeography of CMs across the oceans. Location: Global marine ecosystems. Time period: 1970–2018. Major taxa studied: Marine planktonic protists. Methods: Records for CM species, primarily from the Ocean Biogeographic Information System (OBIS), were grouped by taxonomy and size to evaluate sampling efforts across Longhurst's oceanic provinces. Biases were evaluated through nonparametric tests and multivariate analysis. Biogeographies of CMs from OBIS data were compared with data from studies that specifically targeted these organisms. Results: Constitutive mixotrophs of different taxonomic groups, across all size ranges, are ubiquitous. However, strong database biases were detected with respect to organism size, taxonomic groups and region. A strong bias was seen towards dinophytes. Species

Introduction The primary objective of this study was to test whether seven-day Holter recording improves the sensitivity of detecting dilated cardiomyopathy (DCM) predictive criteria (DCMp) compared with 24-h Holter recording in asymptomatic Doberman Pinscher (DP) dogs. Animals Twenty-eight asymptomatic DP dogs with normal echocardiographic examinations. Methods Dogs with normal echocardiographic examinations underwent seven-day Holter monitoring. The presence of ≥50 ventricular premature complexes and or ≥ one couplet/one triplet/one episode of ventricular tachycardia per 24-h period was considered positive for DCMp. Results Five dogs were positive on the first day, and an additional six dogs tested positive from day two to seven of the Holter recording. The number of dogs positive for DCMp detected by four days was significantly different (p = 0.031) compared with the first-day Holter recording. Conclusions Seven-day Holter recording detected significantly more dogs with DCMp compared with the first-day Holter recording. Follow-up studies are warranted to evaluate the long-term accuracy of multiple-day Holter analysis in predicting the development of DCM in DP dogs.

The effects of 0.1 wt.% Sc and 0.1 wt.% Zr addition in AA5182 on microstructure and mechanical properties were investigated. Results show that Al3(ScxZr1−x) dispersoids formed in AA5182. Observation of ingots microstructures showed that the grain size of 5182-Sc-Zr alloy was 56% lower than that of based AA5182. Isothermal annealing between 230 °C and 500 °C for 2 h was performed to study the recrystallization, tensile properties and dispersoid coarsening. The recrystallization was inhibited by the dispersoids, and the alloy microstructure remained deformed after annealing. Al3(ScxZr1−x) in AA5182 was stable when annealing below 400 °C, while parts of dispersoids coarsened significantly when heating at 500 °C. The addition of Sc and Zr allowed YS of 5182 alloy to achieve 247.8 MPa, which is 100 MPa higher than the corresponding AA5182. The contributions of Orowan strengthening and grain boundary strengthening were obtained by calculation.

Background The isolated forearm technique allows assessment of consciousness of the external world (connected consciousness) through a verbal command to move the hand (of a tourniquet-isolated arm) during intended general anesthesia. Previous isolated forearm technique data suggest that the incidence of connected consciousness may approach 37% after a noxious stimulus. The authors conducted an international, multicenter, pragmatic study to establish the incidence of isolated forearm technique responsiveness after intubation in routine practice. Methods Two hundred sixty adult patients were recruited at six sites into a prospective cohort study of the isolated forearm technique after intubation. Demographic, anesthetic, and intubation data, plus postoperative questionnaires, were collected. Univariate statistics, followed by bivariate logistic regression models for age plus variable, were conducted. Results The incidence of isolated forearm technique responsiveness after intubation was 4.6% (12/260); 5 of 12 responders reported pain through a second hand squeeze. Responders were younger than nonresponders (39 ± 17 vs. 51 ± 16 yr old; P = 0.01) with more frequent signs of sympathetic activation (50% vs. 2.4%; P = 0.03). No participant had explicit recall of intraoperative events when questioned after surgery (n = 253). Across groups, depth of anesthesia monitoring values showed a wide range; however, values were higher for responders before (54 ± 20 vs. 42 ± 14; P = 0.02) and after (52 ± 16 vs. 43 ± 16; P = 0.02) intubation. In patients not receiving total intravenous anesthesia, exposure to volatile anesthetics before intubation reduced the odds of responding (odds ratio, 0.2 [0.1 to 0.8]; P = 0.02) after adjustment for age. Conclusions Intraoperative connected consciousness occurred frequently, although the rate is up to 10-times lower than anticipated. This should be considered a conservative estimate of intraoperative connected consciousness.

Background The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. Methods In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. Results Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. Conclusions Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

Nanoflagellates are recognized as fundamental members of the planktonic microbial food web due to their contribution to photosynthetic fixation of carbon and phagotrophic ingestion of bacteria. Although the presence, and often dominance, of mixotrophic nutrition among phytoflagellates has been well documented within a variety of aquatic ecosystems and in a range of taxa, few studies have assessed the abundance and grazing impact of mixotrophs in comparison to their photosynthetic and heterotrophic counterparts across seasons at multiple depths. Abundance and, as appropriate, bacterivory of phototrophic, heterotrophic, and mixotrophic nanoflagellates were quantified at three depths over a 15-month period in Lake Lacawac (Pocono Mountains, Pennsylvania, U.S.A.) via microscopic analysis of ingested bacterial surrogates. The absolute and relative abundances of all nanoflagellate trophic groups varied with season and depth, likely as a result of differences in physiological tolerance. Whereas the abundance of phototrophic and heterotrophic nanoflagellates varied with depth in both the presence and absence of thermal stratification, mixotrophic protists were evenly distributed throughout the water column during mixis. The abundances of phototrophic and mixotrophic protists were significantly correlated, but only in surface waters during periods of thermal stratification. Grazing rate and consequent impact by bacterivorous nanoflagellates varied with depth across season, particularly during thermal stratification. Mixotrophic bacterivory exceeded that of heterotrophs in the epi- and metalimnion during stratification, removing an estimated maximum of 80% of the bacterial standing stock d−1. The relative contribution of heterotrophic nanoflagellates to community bacterivory increased with depth, even during mixis, and dominated the grazing impact in the hypolimnion.

Alloy 5182 has been extensively used in the O temper for automotive sheet parts requiring high formability and moderate strength. The grain size of the sheet has been shown to impact strength, formability, and Lüdering behavior during forming. The present study examined the effect of heating rate on the recrystallization behavior of the alloy. Various heating rates, recovery treatments and annealing temperatures were used to manipulate the final grain size. Metallographic observations, EBSD and hardness tests were used during the research. The results are discussed in terms of operative recrystallization mechanisms for this alloy.

Between September of 2013 and September of 2016 an intermittent survey of the cicada diversity and distribution in Oklahoma was conducted. The results of this survey are presented here as a current updated annotated checklist. Seven species in four genera are newly recorded as resident in Oklahoma: Diceroprocta texana (Davis, 1916), Megatibicen figuratus (Walker, 1858), Neotibicen davisi harnedi (Davis, 1918), Neotibicen linnei (Smith & Grossbeck, 1907), Neotibicen robinsonianus (Davis, 1922), Okanagana viridis Davis, 1918, and Pacarina shoemakeri Sanborn and Heath, 2012. This brings the total number of species inhabiting the state to 41. Discussed are seven additional species possibly occurring in the state and Oklahoma's cicada diversity.