Individualized Treatment Effects of Bougie versus Stylet for Tracheal Intubation in Critical Illness.

Rationale: A recent randomized trial found that using a bougie did not increase the incidence of successful intubation on first attempt in critically ill adults. The average effect of treatment in a trial population, however, may differ from effects for individuals. Objective: We hypothesized that application of a machine learning model to data from a clinical trial could estimate the effect of treatment (bougie vs. stylet) for individual patients based on their baseline characteristics ("individualized treatment effects"). Methods: This was a secondary analysis of the BOUGIE (Bougie or Stylet in Patients Undergoing Intubation Emergently) trial. A causal forest algorithm was used to model differences in outcome probabilities by randomized group assignment (bougie vs. stylet) for each patient in the first half of the trial (training cohort). This model was used to predict individualized treatment effects for each patient in the second half (validation cohort). Measurements and Main Results: Of 1,102 patients in the BOUGIE trial, 558 (50.6%) were the training cohort, and 544 (49.4%) were the validation cohort. In the validation cohort, individualized treatment effects predicted by the model significantly modified the effect of trial group assignment on the primary outcome (P value for interaction = 0.02; adjusted qini coefficient, 2.46). The most important model variables were difficult airway characteristics, body mass index, and Acute Physiology and Chronic Health Evaluation II score. Conclusions: In this hypothesis-generating secondary analysis of a randomized trial with no average treatment effect and no treatment effect in any prespecified subgroups, a causal forest machine learning algorithm identified patients who appeared to benefit from the use of a bougie over a stylet and from the use of a stylet over a bougie using complex interactions between baseline patient and operator characteristics.

Defining Successful Intubation on the First Attempt Using Both Laryngoscope and Endotracheal Tube Insertions: A Secondary Analysis of Clinical Trial Data.

STUDY OBJECTIVES: Successful intubation on the first attempt has historically been defined as successful placement of an endotracheal tube (ETT) using a single laryngoscope insertion. More recent studies have defined successful placement of an ETT using a single laryngoscope insertion followed by a single ETT insertion. We sought to estimate the prevalence of first-attempt success using these 2 definitions and estimate their associations with the duration of intubation and serious complications. METHODS: We performed a secondary analysis of data from 2 multicenter randomized trials of critically ill adults being intubated in the emergency department or ICU. We calculated the percent difference in successful intubations on the first attempt, median difference in the duration of intubation, and percent difference in the development of serious complications by definition. RESULTS: The study population included 1,863 patients. Successful intubation on the first attempt decreased by 4.9% (95% confidence interval 2.5% to 7.3%) when defined as 1 laryngoscope insertion followed by 1 ETT insertion (81.2%) compared with when defined as only 1 laryngoscope insertion (86.0%). When successful intubation with 1 laryngoscope and 1 ETT insertion was compared with 1 laryngoscope and multiple ETT insertions, the median duration of intubation decreased by 35.0 seconds (95% confidence interval 8.9 to 61.1 seconds). CONCLUSION: Defining successful intubation on the first attempt as placement of an ETT in the trachea using 1 laryngoscope and 1 ETT insertion identifies attempts with the shortest apneic time.

Laryngoscopy and Tracheal Intubation: Does Use of a Video Laryngoscope Facilitate Both Steps of the Procedure?

STUDY OBJECTIVE: To compare the effect of the use of a video laryngoscope versus a direct laryngoscope on each step of emergency intubation: laryngoscopy (step 1) and intubation of the trachea (step 2). METHODS: In a secondary observational analysis of data from 2 multicenter, randomized trials that enrolled critically ill adults undergoing tracheal intubation but did not control for laryngoscope type (video laryngoscope vs direct laryngoscope), we fit mixed-effects logistic regression models examining the 1) the association between laryngoscope type (video laryngoscope vs direct laryngoscope) and the Cormack-Lehane grade of view and 2) the interaction between grade of view, laryngoscope type (video laryngoscope vs direct laryngoscope), and the incidence of successful intubation on the first attempt. RESULTS: We analyzed 1,786 patients: 467 (26.2%) in the direct laryngoscope group and 1,319 (73.9%) in the video laryngoscope group. The use of a video laryngoscope was associated with an improved grade of view as compared with a direct laryngoscope (adjusted odds ratio for increasingly favorable grade of view 3.14, 95% confidence interval [CI] 2.47 to 3.99). Successful intubation on the first attempt occurred in 83.2% of patients in the video laryngoscope group and 72.2% of patients in the direct laryngoscope group (absolute difference 11.1%, 95% CI 6.5% to 15.6%). Video laryngoscope use modified the association between grade of view and successful intubation on the first attempt such that intubation on the first attempt was similar between video laryngoscope and direct laryngoscope at a grade 1 view and higher for video laryngoscope than direct laryngoscope at grade 2 to 4 views (P<.001 for interaction term). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, the use of a video laryngoscope was associated both with a better view of the vocal cords and with a higher probability of successfully intubating the trachea when the view of the vocal cords was incomplete in this observational analysis. However, a multicenter, randomized trial directly comparing the effect of a video laryngoscope with a direct laryngoscope on the grade of view, success, and complications is needed.

Bag-Mask Ventilation Versus Apneic Oxygenation During Tracheal Intubation in Critically Ill Adults: A Secondary Analysis of 2 Randomized Trials.

Background: Hypoxemia is common during tracheal intubation in intensive care units. To prevent hypoxemia during intubation, 2 methods of delivering oxygen between induction and laryngoscopy have been proposed: bag-mask ventilation and supplemental oxygen delivered by nasal cannula without ventilation (apneic oxygenation). Whether one of these approaches is more effective for preventing hypoxemia during intubation of critically ill patients is unknown. Methods: We performed a secondary analysis of data from 138 patients enrolled in 2, consecutive randomized trials of airway management in an academic intensive care unit. A total of 61 patients were randomized to receive bag-mask ventilation in a trial comparing bag-mask ventilation to none, and 77 patients were randomized to receive 100% oxygen at 15 L/min by nasal cannula in a trial comparing apneic oxygenation to none. Using multivariable linear regression accounting for age, body mass index, severity of illness, and oxygen saturation at induction, we compared patients assigned to bag-mask ventilation with those assigned to apneic oxygenation regarding lowest oxygen saturations from induction to 2 min after intubation. Results: Patients assigned to bag-mask ventilation and apneic oxygenation were similar at baseline. The median lowest oxygen saturation was 96% (interquartile range [IQR] 89%-100%) in the bag-mask ventilation group and 92% (IQR 84%-99%) in the apneic oxygenation group. After adjustment for prespecified confounders, bag-mask ventilation was associated with a higher lowest oxygen saturation compared to apneic oxygenation (mean difference, 4.2%; 95% confidence interval, 0.7%-7.8%; P = .02). The incidence of severe hypoxemia (oxygen saturation<80%) was 6.6% in the bag-mask ventilation group and 15.6% in the apneic oxygenation group (adjusted odds ratio, 0.33; P = .09). Conclusions: This secondary analysis of patients assigned to bag-mask ventilation and apneic oxygenation during 2 clinical trials suggests that bag-mask ventilation is associated with higher oxygen saturation during intubation compared to apneic oxygenation.

The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites.

Mechanistic roles for many lncRNAs are poorly understood, in part because their direct interactions with genomic loci and proteins are difficult to assess. Using a method to purify endogenous RNAs and their associated factors, we mapped the genomic binding sites for two highly expressed human lncRNAs, NEAT1 and MALAT1. We show that NEAT1 and MALAT1 localize to hundreds of genomic sites in human cells, primarily over active genes. NEAT1 and MALAT1 exhibit colocalization to many of these loci, but display distinct gene body binding patterns at these sites, suggesting independent but complementary functions for these RNAs. We also identified numerous proteins enriched by both lncRNAs, supporting complementary binding and function, in addition to unique associated proteins. Transcriptional inhibition or stimulation alters localization of NEAT1 on active chromatin sites, implying that underlying DNA sequence does not target NEAT1 to chromatin, and that localization responds to cues involved in the transcription process.

Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial.

Importance: For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer ("bougie") increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain. Objective: To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt. Design, Setting, and Participants: The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021. Interventions: Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546). Main Outcomes and Measures: The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%. Results: Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group. Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet. Trial Registration: ClinicalTrials.gov Identifier: NCT03928925

A patient with lower extremity weakness after recent endovascular repair of an abdominal aortic aneurysm.

BACKGROUND: Thrombosis of an endovascular aortic repair (EVAR) is a devastating complication of a common surgical procedure that can lead to serious morbidity and mortality if not promptly recognized. This is the first case report of an EVAR graft thrombosis in the emergency medicine literature. CASE REPORT: We present a case of a patient with lower extremity paraplegia secondary to thrombosis of an EVAR graft who presented to the emergency room with acute stroke-like symptoms after a recent EVAR procedure. Endovascular repair of abdominal aortic aneurisms is becoming more frequent, and an increased number of patients with recent abdominal aortic aneurism repair by endovascular grafts will be evaluated by emergency physicians in the future. Emergency physicians should be aware that signs of limb ischemia, which may masquerade as acute ischemic stroke-like symptoms, is one of the more serious complications that can occur with abdominal aortic vascular grafts. Among patients with lower extremity neurological deficits in the recent setting of EVAR presenting to an emergency department, there should be a high degree of suspicion for EVAR graft thrombosis, which can be diagnosed via the gold standard of CT angiography or ultrasonography. Prompt vascular surgery consultation is essential to minimize permanent disability.

Novel Use of a Gas Analyzer Can Reliably Predict the Arterial Oxygen among Emergency Department Patients Undergoing Rapid Sequence Intubation.

BACKGROUND: To our knowledge, no study has assessed the correlation of fraction of inspired oxygen (FiO2) and end-tidal oxygen (EtO2) values obtained from a gas analyzer during the preoxygenation period of rapid sequence intubation (RSI) to predict partial pressure of oxygen (PaO2) among patients requiring intubation in the emergency department (ED). OBJECTIVE: The purpose of this study was to determine whether a simple equation using EtO2 and FiO2 at time of induction could reliably estimate minimal PaO2 in ED patients undergoing RSI. METHODS: We conducted an observational pilot study performed in an adult ED utilizing a gas analyzer to obtain EtO2 and FiO2 values in ED patients undergoing RSI from data collectors blinded to our objective. The Pearson correlation coefficient was calculated between the equation's predicted PaO2 and the PaO2 drawn from an arterial blood gas shortly after intubation. A Bland-Altman plot analysis was performed to identify any additional bias. RESULTS: Seventy-five patients were enrolled. The equation's mean predicted minimal PaO2 and mean PaO2 from an arterial blood gas within 3 min after intubation was 178 mm Hg (95% confidence interval [CI] 145-211 mm Hg) and 209 mm Hg (95% CI 170-258 mm Hg), respectively. The Pearson correlation coefficient between the predicted minimal PaO2 and post-intubation PaO2 demonstrated a strong correlation (r2 = 0.89). The Bland-Altman plot indicated no bias affecting the correlation between the predicted and actual PaO2. CONCLUSIONS: Among ED patients undergoing RSI, the use of a gas analyzer to measure EtO2 and FiO2 can provide a reliable measure of the minimal PaO2 at the time of induction during the RSI phase of preoxygenation.

Biochar amendment suppresses N2 O emissions but has no impact on 15 N site preference in an anaerobic soil.

RATIONALE: Biochar amendments often decrease N2 O gas production from soil, but the mechanisms and magnitudes are still not well characterized since N2 O can be produced via several different microbial pathways. We evaluated the influence of biochar amendment on N2 O emissions and N2 O isotopic composition, including 15 N site preference (SP) under anaerobic conditions. METHODS: An agricultural soil was incubated with differing levels of biochar. Incubations were conducted under anaerobic conditions for 10 days with and without acetylene, which inhibits N2 O reduction to N2 . The N2 O concentrations were measured every 2 days, the SPs were determined after 5 days of incubation, and the inorganic nitrogen concentrations were measured after the incubation. RESULTS: The SP values with acetylene were consistent with N2 O production by bacterial denitrification and those without acetylene were consistent with bacterial denitrification that included N2 O reduction to N2 . There was no effect of biochar on N2 O production in the presence of acetylene between day 3 and day 10. However, in the absence of acetylene, soils incubated with 4% biochar produced less N2 O than soils with no biochar addition. Different amounts of biochar amendment did not change the SP values. CONCLUSIONS: Our study used N2 O emission rates and SP values to understand biochar amendment mechanisms and demonstrated that biochar amendment reduces N2 O emissions by stimulating the last step of denitrification. It also suggested a possible shift in N2 O-reducing microbial taxa in 4% biochar samples.

Use of End Tidal Oxygen Monitoring to Assess Preoxygenation During Rapid Sequence Intubation in the Emergency Department.

STUDY OBJECTIVE: Preoxygenation is important to prevent oxygen desaturation during emergency airway management. The purpose of this study is to describe the use of end tidal oxygen (eto2) during rapid sequence intubation in the emergency department. METHODS: This study was carried out in 2 academic centers in Sydney, Australia, and New York City. We included patients undergoing rapid sequence intubation in the emergency department. A standard gas analyzer was used to measure eto2. Preoxygenation methods included nonrebreather mask and bag-valve-mask ventilation. We measured eto2 before preoxygenation and at administration of rapid sequence intubation medications. We also characterized peri-intubation SpO2, identifying instances of SpO2 less than 90%. RESULTS: We included 100 patients during a 6-month period. Median eto2 level before and after preoxygenation was 53% (interquartile range [IQR] 43% to 65%) and 78% (IQR 64% to 86%), respectively. One fourth of patients achieved an eto2 level greater than 85%. Median eto2 level achieved varied with preoxygenation method, ranging from 80% (IQR 60% to 87%) for the nonrebreather mask group to 77% (IQR 65% to 86%) for the bag-valve-mask group. The method with the highest median eto2 level was nonrebreather mask at flush rate (86%; IQR 80% to 90%) and the lowest median eto2 level was nonrebreather mask at 15 L/min (57%; IQR 53% to 60%). Eighteen patients (18%) experienced oxygen desaturation (SpO2 <90%); of these, 14 (78%) did not reach an eto2 level greater than 85% at induction. CONCLUSION: ETO2 varied with different preoxygenation techniques employed in the emergency department. Most patients undergoing rapid sequence intubation did not achieve maximal preoxygenation. Measuring ETO2 in the emergency department may be a valuable adjunct for optimizing preoxygenation during emergency airway management.

Groundwater drawdown drives ecophysiological adjustments of woody vegetation in a semi-arid coastal ecosystem.

Predicted droughts and anthropogenic water use will increase groundwater lowering rates and intensify groundwater limitation, particularly for Mediterranean semi-arid ecosystems. These hydrological changes may be expected to elicit differential functional responses of vegetation either belowground or aboveground. Yet, our ability to predict the impacts of groundwater changes on these ecosystems is still poor. Thus, we sought to better understand the impact of falling water table on the physiology of woody vegetation. We specifically ask (a) how is woody vegetation ecophysiological performance affected by water table depth during the dry season? and (b) does the vegetation response to increasing depth to groundwater differ among water-use functional types? We examined a suite of physiological parameters and water-uptake depths of the dominant, functionally distinct woody vegetation along a water-table depth gradient in a Mediterranean semi-arid coastal ecosystem that is currently experiencing anthropogenic groundwater extraction pressure. We found that groundwater drawdown did negatively affect the ecophysiological performance of the woody vegetation. Across all studied environmental factors, depth to groundwater was the most important driver of ecophysiological adjustments. Plant functional types, independent of groundwater dependence, showed consistent declines in water content and generally reduced C and N acquisition with increasing depths to groundwater. Functional types showed distinct operating physiological ranges, but common physiological sensitivity to greater water table depth. Thus, although differences in water-source use exist, a physiological convergence appeared to happen among different functional types. These results strongly suggest that hydrological drought has an important impact on fundamental physiological processes, constraining the performance of woody vegetation under semi-arid conditions. By disentangling the functional responses and vulnerability of woody vegetation to groundwater limitation, our study establishes the basis for predicting the physiological responses of woody vegetation in semi-arid coastal ecosystems to groundwater drawdown.

Applying the principles of isotope analysis in plant and animal ecology to forensic science in the Americas.

The heart of forensic science is application of the scientific method and analytical approaches to answer questions central to solving a crime: Who, What, When, Where, and How. Forensic practitioners use fundamentals of chemistry and physics to examine evidence and infer its origin. In this regard, ecological researchers have had a significant impact on forensic science through the development and application of a specialized measurement technique-isotope analysis-for examining evidence. Here, we review the utility of isotope analysis in forensic settings from an ecological perspective, concentrating on work from the Americas completed within the last three decades. Our primary focus is on combining plant and animal physiological models with isotope analyses for source inference. Examples of the forensic application of isotopes-including stable isotopes, radiogenic isotopes, and radioisotopes-span from cotton used in counterfeit bills to anthrax shipped through the U.S. Postal Service and from beer adulterated with cheap adjuncts to human remains discovered in shallow graves. Recent methodological developments and the generation of isotope landscapes, or isoscapes, for data interpretation promise that isotope analysis will be a useful tool in ecological and forensic studies for decades to come.

Peri-intubation factors affecting emergency physician choice of paralytic agent for rapid sequence intubation of trauma patients.

INTRODUCTION: No study has assessed predictors of physician choice between the succinylcholine (Succ) and rocuronium (Roc) for rapid sequence intubation (RSI) during the initial resuscitation of trauma patients in the emergency department (ED). METHODS: We retrospectively evaluated of the use of Succ and Roc for adult trauma patients undergoing RSI at a Level 1 trauma center. The primary outcome was to identify factors affecting physician choice of paralytic agent for RSI analyzed by cluster analysis using pre-intubation vital signs and early mortality. The secondary outcome was to identify factors influencing physician choice of paralytic agent using a logistic regression model reported as adjusted odds ratios (aOR). RESULTS: The analysis included 215 patients, including 148 receiving Succ and 67 receiving Roc. The two groups were similar in regard to age, provider level of training, mean GCS (10 vs. 10) and median ISS (27 vs. 27). Cluster analysis using peri-intubation patient vital signs and early mortality indicates that patients with predominantly abnormal vital signs and early mortality were more likely to receive Roc (74%) than those without abnormal vital signs prior to intubation or early mortality (24%). Hypoxemia prior to RSI (aOR 12.3 [2.5-60.9]) and the use of video laryngoscopy (VL) (aOR 5.5 [1.2-24.6]) were associated with the choice to use Roc. CONCLUSIONS: Roc was more frequently chosen for paralysis in the patient cluster with predominantly abnormal peri-intubation vital signs and higher rate of early ED mortality. The use of Roc was associated with hypoxemia prior to RSI and VL.

Waveform capnography: an alternative to physician gestalt in determining optimal intubating conditions after administration of paralytic agents.

PURPOSE: We sought to evaluate the utility of waveform capnography (WC) in detecting paralysis, by using apnoea as a surrogate determinant, as compared with clinical gestalt during rapid sequence intubation. Additionally, we sought to determine if this improves the time to intubation and first pass success rates through more consistent and expedient means of detecting optimal intubating conditions (ie, paralysis). METHODS: A prospective observational cohort study of consecutively enrolled patients was conducted from April to June 2016 at an academic, urban, level 1 trauma centre in New York City. Nasal cannula WC was used to determine the presence of apnoea as a surrogate measure of paralysis versus physician gestalt (ie, blink test, mandible relaxation, and so on). RESULTS: One hundred patients were enrolled (50 in the WC group and 50 in the gestalt group). There were higher proportions of failure to determine optimal intubating conditions (ie, paralysis) in the gestalt group (32%, n=16) versus the WC group (6%, n=3), absolute difference 26, 95% CI 10 to 40. Time to intubation was longer in the gestalt group versus the WC group (136 seconds vs 116 seconds, absolute difference 20 seconds 95% CI 14 to 26). First pass success rates were higher in the WC group verses the gestalt group (92%, 95% CI 85 to 97 vs 88%, 95% CI 88 to 95, absolute difference 4%, 95% CI 1 to 8). CONCLUSION: These preliminary results demonstrate WC may be a useful objective measure to determine the presence of paralysis and optimal in tubating conditions in RSI.

Bryophyte gas-exchange dynamics along varying hydration status reveal a significant carbonyl sulphide (COS) sink in the dark and COS source in the light.

Carbonyl sulphide (COS) is a potential tracer of gross primary productivity (GPP), assuming a unidirectional COS flux into the vegetation that scales with GPP. However, carbonic anhydrase (CA), the enzyme that hydrolyses COS, is expected to be light independent, and thus plants without stomata should continue to take up COS in the dark. We measured net CO2 (AC ) and COS (AS ) uptake rates from two astomatous bryophytes at different relative water contents (RWCs), COS concentrations, temperatures and light intensities. We found large AS in the dark, indicating that CA activity continues without photosynthesis. More surprisingly, we found a nonzero COS compensation point in light and dark conditions, indicating a temperature-driven COS source with a Q10 (fractional change for a 10°C temperature increase) of 3.7. This resulted in greater AS in the dark than in the light at similar RWC. The processes underlying such COS emissions remain unknown. Our results suggest that ecosystems dominated by bryophytes might be strong atmospheric sinks of COS at night and weaker sinks or even sources of COS during daytime. Biotic COS production in bryophytes could result from symbiotic fungal and bacterial partners that could also be found on vascular plants.

The effect of the apneic period on the respiratory physiology of patients undergoing intubation in the ED.

OBJECTIVES: We sought to examine the physiological impact the apneic period has on the respiratory physiology of patients undergoing intubation in the emergency department and whether DAO, the delivery of 15L oxygen by nasal cannula during apnea, can affect the development of respiratory acidosis. METHODS: This was a prospective observational cohort study conducted at an urban academic level 1 trauma center. A convenience sample of 100 patients was taken. Timed data collection forms were completed during the periintubation period. We report the mean ABG and end-tidal CO2 (EtCO2) values between those with normal and prolonged apnea times (>60s) and between those who received DAO and those who did not. RESULTS: 100 patients met our inclusion criteria. There were no significant differences in the pre-RSI ABG values between those who received DAO and those who did not and between those with apnea times less than or >60s. Only in the group of patients with apnea times >60s did significant changes in respiratory physiology occur. DAO did not alter the trend in respiratory acidosis during the periintubation period. EtCO2 increased as apnea times were prolonged, and DAO altered this trend. CONCLUSIONS: Post-RSI EtCO2 increased as apnea times were prolonged. DAO may alter this trend. Statistically significant changes in pH and PaCO2 (mean differences of 0.15 and 12.5, respectively) occurred in the group of patients who had mean apnea times of >60s but not in those with apnea times <60s.

BAF250a Protein Regulates Nucleosome Occupancy and Histone Modifications in Priming Embryonic Stem Cell Differentiation.

The unique chromatin signature of ES cells is fundamental to the pluripotency and differentiation of ES cells. One key feature is the poised chromatin state of master developmental genes that are transcriptionally repressed in ES cells but ready to be activated in response to differentiation signals. Poised chromatin in ES cells contains both H3 Lys-4 trimethylation (H3K4me3) and H3 Lys-27 trimethylation (H3K27me3) methylation, indicating activating and repressing potential. However, the contribution of non-covalent chromatin structure to the poised state is not well understood. To address whether remodeling of nucleosomes is important to the poised state, we characterized the function of BAF250a, a key regulatory subunit of the ES cell ATP-dependent Brahma-associated factor (BAF) chromatin remodeling complex (esBAF). Acute deletion of BAF250a disrupted the differentiation potential of ES cells by altering the expression timing of key developmental genes and pluripotent genes. Our genome-wide nucleosome and histone modification analyses indicated that the disruption of gene expression timing was largely due to changes of chromatin structures at poised genes, particularly those key developmental genes mediated by BAF250a. Specifically, BAF250a deletion caused a nucleosome occupancy increase at H3K4me3- and/or H3K27me3-associated promoters. Moreover, H3K27me3 levels and the number of bivalent promoter genes were reduced in BAF250a KO ES cells. We revealed that BAF250a ablation led to elevated Brg1 but reduced Suz12 recruitment at nucleosome occupancy-increased regions, indicating an unexpected and complicated role of BAF250a in regulating esBAF and Polycomb repressive complex (PRC) activities. Together, our studies identified that BAF250a mediates esBAF and PRC functions to establish the poised chromatin configuration in ES cells, which is essential for the proper differentiation of ES cells.

Stable isotopes in leaf water of terrestrial plants.

Leaf water contains naturally occurring stable isotopes of oxygen and hydrogen in abundances that vary spatially and temporally. When sufficiently understood, these can be harnessed for a wide range of applications. Here, we review the current state of knowledge of stable isotope enrichment of leaf water, and its relevance for isotopic signals incorporated into plant organic matter and atmospheric gases. Models describing evaporative enrichment of leaf water have become increasingly complex over time, reflecting enhanced spatial and temporal resolution. We recommend that practitioners choose a model with a level of complexity suited to their application, and provide guidance. At the same time, there exists some lingering uncertainty about the biophysical processes relevant to patterns of isotopic enrichment in leaf water. An important goal for future research is to link observed variations in isotopic composition to specific anatomical and physiological features of leaves that reflect differences in hydraulic design. New measurement techniques are developing rapidly, enabling determinations of both transpired and leaf water δ(18) O and δ(2) H to be made more easily and at higher temporal resolution than previously possible. We expect these technological advances to spur new developments in our understanding of patterns of stable isotope fractionation in leaf water.

Shrubland resilience varies across soil types: implications for operationalizing resilience in ecological restoration.

In ecosystems with alternative stable states, restoration success can be thought of as overcoming the resilience of an undesirable state to promote an alternative state that yields greater ecosystem services. Since greater resilience of undesirable states translates into reduced restoration potential, quantifying differences in resilience can enhance restoration planning. In the context of shrub-encroached rangeland restoration, shrubland resilience is the capacity of a woody vegetated state to absorb management interventions designed to produce a more desirable grass-dominated state, and remain within its current regime. Therefore, differences in the resilience of a state can be quantified in a relative sense by measuring whether a state switches to an alternate state following perturbation or remains in its current stability domain. Here we designed an experimental manipulation to assess the contribution of soils to differences in the relative resilience of a shrub-invaded state. In this large-scale experiment, we repeated perturbations across a gradient of soil textures to inform restoration practitioners of differences in the relative resilience of shrubland occurring on different soil types to common rangeland restoration practices. On each soil type, we compared the relative ability of the shrubland state to withstand chemical and mechanical brush control treatments, commonly employed in this study region, to untreated controls. While the shrubland community composition did not differ prior to the study, its capacity to absorb and recover from brush removal treatments depended on soil type. Shrubland resilience to chemical and mechanical brush removal was highest on coarse soils. On these soils, brush removal temporarily restored grassland dominance, but woody plants quickly regained pretreatment levels of dominance. However, shrublands on fine soils did not recover following treatments, continuing to be grass-dominated for the duration of the study. This study highlights a simple approach for prioritizing restoration actions by mapping the locations of different soil attributes that support shrub-dominated states with differing levels of resilience to brush control. This experimental approach provides a basis for operationalizing resilience in restoration and prioritizing management actions across a range of environmental conditions, which is critical given the economic constraints associated with broad-scale mechanical and chemical interventions for rangeland restoration.

Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey.

BACKGROUND: Published data from 1998 revealed that most patients treated for migraine in an emergency department received opioids. Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of non-opioid alternatives. Expert opinion during these years has cautioned against use of opioids for migraine. Our objectives were to compare current frequency of use of various medications for acute migraine in US emergency departments with use of these same medications in 1998 and to identify factors independently associated with opioid use. METHODS: We analyzed National Hospital Ambulatory Medical Care Survey data from 2010, the most current dataset available. The National Hospital Ambulatory Medical Care Survey is a public dataset collected and distributed by the Centers for Disease Control and Prevention. It is a multi-stage probability sample from randomly selected emergency departments across the country, designed to be representative of all US emergency department visits. We included in our analysis all patients with the ICD9 emergency department discharge diagnosis of migraine. We tabulated frequency of use of specific medications in 2010 and compared these results with the 1998 data. Using a logistic regression model, into which all of the following variables were entered, we explored the independent association between any opioid use in 2010 and sex, age, race/ethnicity, geographic region, type of hospital, triage pain score and history of emergency department use within the previous 12 months. RESULTS: In 2010, there were 1.2 (95% confidence interval 0.9, 1.4) million migraine visits to US emergency departments. Including opioid-containing oral analgesic combinations, opioids were administered in 59% of visits (95% confidence interval 51, 67). The most commonly used parenteral agent, hydromorphone, was used in 25% (95% confidence interval 19, 33) of visits in 2010 versus less than 1% (95% confidence interval 0, 3) in 1998. Conversely, use of meperidine had decreased markedly over the same timeframe. In 2010, it was used in just 7% (95% confidence interval 4, 12) of visits compared to 37% (95% confidence interval 29, 45) in 1998. Metoclopramide, the most commonly used anti-dopaminergic, was administered in 17% (95% confidence interval 12, 23) of visits in 2010 and 3% (95% confidence interval 1, 6) of visits in 1998. Use of any triptan was relatively uncommon in 2010 (7% (95% confidence interval 4, 11) of visits) and in 1998 (10% (95% confidence interval 6, 15) of visits). Of the predictor variables listed above, only emergency department use within the previous 12 months was associated with opioid administration (adjusted odds ratio: 2.87 (95% confidence interval 1.03, 7.97)). CONCLUSIONS: In spite of recommendations to the contrary, opioids are still used in more than half of all emergency department visits for migraine. Though use of meperidine has decreased markedly between 1998 and 2010, it has largely been replaced by hydromorphone. Opioid use in migraine visits is independently associated with prior visits to the same emergency department in the previous 12 months.