Multi-target genome editing reduces polyphenol oxidase activity in wheat (Triticum aestivum L.) grains.

Introduction: Polyphenol oxidases (PPO) are dual activity metalloenzymes that catalyse the production of quinones. In plants, PPO activity may contribute to biotic stress resistance and secondary metabolism but is undesirable for food producers because it causes the discolouration and changes in flavour profiles of products during post-harvest processing. In wheat (Triticum aestivum L.), PPO released from the aleurone layer of the grain during milling results in the discolouration of flour, dough, and end-use products, reducing their value. Loss-of-function mutations in the PPO1 and PPO2 paralogous genes on homoeologous group 2 chromosomes confer reduced PPO activity in the wheat grain. However, limited natural variation and the proximity of these genes complicates the selection of extremely low-PPO wheat varieties by recombination. The goal of the current study was to edit all copies of PPO1 and PPO2 to drive extreme reductions in PPO grain activity in elite wheat varieties. Results: A CRISPR/Cas9 construct with one single guide RNA (sgRNA) targeting a conserved copper binding domain was used to edit all seven PPO1 and PPO2 genes in the spring wheat cultivar 'Fielder'. Five of the seven edited T1 lines exhibited significant reductions in PPO activity, and T2 lines had PPO activity up to 86.7% lower than wild-type. The same construct was transformed into the elite winter wheat cultivars 'Guardian' and 'Steamboat', which have five PPO1 and PPO2 genes. In these varieties PPO activity was reduced by >90% in both T1 and T2 lines. In all three varieties, dough samples from edited lines exhibited reduced browning. Discussion: This study demonstrates that multi-target editing at late stages of variety development could complement selection for beneficial alleles in crop breeding programs by inducing novel variation in loci inaccessible to recombination.

30-Day Readmissions and Coordination of Care Following Endoscopic Transsphenoidal Pituitary Surgery: Experience with 409 Patients.

Objective The study aimed to (1) quantify readmission rates and common causes of readmission following endoscopic transsphenoidal pituitary surgery (ETPS); (2) identify risk factors that may predict readmission within 30 days; (3) assess postoperative care coordination with endocrinology follow-up; and (4) identify patients for whom targeted interventions may reduce 30-day readmissions. Methods Retrospective quality improvement review of patients with pituitary adenoma who underwent ETPS from December 2010 to 2018 at a single tertiary care center. Results A total of 409 patients were included in the study, of which 57 (13.9%) were readmitted within 30 days. Hyponatremia was the most common cause of readmission (4.2%) followed by pain/headache (3.9%), cerebrospinal fluid leak (3.4%), epistaxis (2.7%), hypernatremia (1.2%), and adrenal insufficiency (1.2%). Patients with hyponatremia were readmitted significantly earlier than other causes (4.3 ± 2.2 vs. 10.6 ± 10.9 days from discharge, p = 0.032). Readmitted patients had significantly less frequent outpatient follow-up with an endocrinologist than the nonreadmitted cohort (56.1 vs. 70.5%, p = 0.031). Patients who had outpatient follow-up with an endocrinologist were at lower risk of readmission compared with those without (odds ratio: 0.46; 95% confidence interval: 0.24-0.88). Conclusion Delayed hyponatremia is one of the most common causes of 30-day readmission following ETPS. Postoperative follow-up with an endocrinologist may reduce risk of 30-day readmission following ETPS. Implications for Clinical Practice A multidisciplinary team incorporating otolaryngologist, neurosurgeons, and endocrinologist may identify patients at risk of 30-day readmissions. Protocols checking serum sodium within 1 week of surgery in conjunction with endocrinologist to tailor fluid restriction may reduce readmissions from delayed hyponatremia.

Indications and outcomes for elective dissection of level V in primary parotid cancer.

BACKGROUND: The extent of cervical lymphadenectomy required for primary parotid cancer is not well-established. METHODS: In this retrospective case-control study, 84 patients who underwent primary parotidectomy and neck dissection for primary parotid cancer between 2010 and 2019 were identified and analyzed. RESULTS: Of the 84 patients, 37 underwent elective level V neck dissection. All six (16.0%) who had occult level V nodes had clinically evident, preoperative anterior cervical metastases, a statistically significant finding. No other clinical factors are correlated with posterior neck involvement. There was no significant difference in disease-free or overall survival for patients with occult level V disease relative to positive lymph nodes in other levels. CONCLUSIONS: Patients with clinically evident anterolateral cervical lymphatic metastases from parotid cancer preoperatively have high rates of occult level V nodes. Level V neck dissection can be avoided in cN0 patients and offered no survival advantage.

Identification and validation of a QTL for spikelet number on chromosome arm 6BL of common wheat (Triticum aestivum L.).

To provide food security for a growing world population, it will be necessary to increase yields of staple crops such as wheat (Triticum aestivum L.). Yield is a complex, polygenic trait influenced by grain weight and number, which are negatively correlated with one another. Spikelet number is an important determinant of grain number, but allelic variants impacting its expression are often associated with heading date, constraining their use in wheat germplasm that must be adapted for specific environments. Identification and characterization of genetic variants affecting spikelet number will increase selection efficiency through their deployment in breeding programs. In this study, a quantitative trait locus (QTL) on chromosome arm 6BL for spikelet number was identified and validated using an association mapping panel, a recombinant inbred line population, and seven derived heterogeneous inbred families. The superior allele, QSn.csu-6Bb, was associated with an increase of 0.248 to 0.808 spikelets per spike across multiple environments that varied for mean spikelet number. Despite epistatic interactions between QSn.csu-6B and three other loci (WAPO-A1, VRN-D3, and PPD-B1), genotypes with a greater number of superior alleles at these loci consistently exhibit higher spikelet number. The frequency of superior alleles at these loci varies among winter wheat varieties adapted to different latitudes of the US Great Plains, revealing opportunities for breeders to select for increased spikelet number using simple molecular markers. This work lays the foundation for the positional cloning of the genetic variant underlying the QSn.csu-6B QTL to strengthen our understanding of spikelet number determination in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01288-7.

Development of the Wheat Practical Haplotype Graph database as a resource for genotyping data storage and genotype imputation.

To improve the efficiency of high-density genotype data storage and imputation in bread wheat (Triticum aestivum L.), we applied the Practical Haplotype Graph (PHG) tool. The Wheat PHG database was built using whole-exome capture sequencing data from a diverse set of 65 wheat accessions. Population haplotypes were inferred for the reference genome intervals defined by the boundaries of the high-quality gene models. Missing genotypes in the inference panels, composed of wheat cultivars or recombinant inbred lines genotyped by exome capture, genotyping-by-sequencing (GBS), or whole-genome skim-seq sequencing approaches, were imputed using the Wheat PHG database. Though imputation accuracy varied depending on the method of sequencing and coverage depth, we found 92% imputation accuracy with 0.01× sequence coverage, which was slightly lower than the accuracy obtained using the 0.5× sequence coverage (96.6%). Compared to Beagle, on average, PHG imputation was ∼3.5% (P-value < 2 × 10-14) more accurate, and showed 27% higher accuracy at imputing a rare haplotype introgressed from a wild relative into wheat. We found reduced accuracy of imputation with independent 2× GBS data (88.6%), which increases to 89.2% with the inclusion of parental haplotypes in the database. The accuracy reduction with GBS is likely associated with the small overlap between GBS markers and the exome capture dataset, which was used for constructing PHG. The highest imputation accuracy was obtained with exome capture for the wheat D genome, which also showed the highest levels of linkage disequilibrium and proportion of identity-by-descent regions among accessions in the PHG database. We demonstrate that genetic mapping based on genotypes imputed using PHG identifies SNPs with a broader range of effect sizes that together explain a higher proportion of genetic variance for heading date and meiotic crossover rate compared to previous studies.

Changes in Single-Specialty Postoperative Opioid Prescribing Patterns in Response to Legislation: Single-Institution Analysis Over Time.

OBJECTIVES: To determine changes in the prescriptions of postoperative opioids in response to Florida state legislation restricting the number of days for which these medications could be prescribed to 3 days in most circumstances or 7 days at provider discretion. STUDY DESIGN: A retrospective review was performed for all patients undergoing 7 common outpatient otolaryngology surgical procedures. SETTING: Single-institution academic center in Florida. METHODS: Query of the state's online prescription drug monitoring program was used to compare prescription habits 3 months before and after the law and then again 1 year later. RESULTS: A total of 561 patients were identified meeting criteria. The number of days that opioids were prescribed decreased significantly, from 6.42 to 4.48 to 3.03 days. There was a significant decrease in the proportion of patients receiving any postoperative opioid prescription, from 0.80 to 0.52 to 0.32. The total morphine milligram equivalents prescribed decreased from 28.4 before the law to 18.4 at 1 year after. CONCLUSIONS: Legislative restrictions on the length of opioid prescriptions were associated with significant decreases in the proportion of patients receiving any opioids, the number of days that opioids were prescribed, and the total morphine milligram equivalents 3 months after the law went into effect, with even more dramatic changes at the 1-year time point. We opine that these changes are due to providers learning that many procedures do not require postoperative opioids and therefore increasingly considering and utilizing nonopioid alternatives in this setting.

Gradual polyploid genome evolution revealed by pan-genomic analysis of Brachypodium hybridum and its diploid progenitors.

Our understanding of polyploid genome evolution is constrained because we cannot know the exact founders of a particular polyploid. To differentiate between founder effects and post polyploidization evolution, we use a pan-genomic approach to study the allotetraploid Brachypodium hybridum and its diploid progenitors. Comparative analysis suggests that most B. hybridum whole gene presence/absence variation is part of the standing variation in its diploid progenitors. Analysis of nuclear single nucleotide variants, plastomes and k-mers associated with retrotransposons reveals two independent origins for B. hybridum, ~1.4 and ~0.14 million years ago. Examination of gene expression in the younger B. hybridum lineage reveals no bias in overall subgenome expression. Our results are consistent with a gradual accumulation of genomic changes after polyploidization and a lack of subgenome expression dominance. Significantly, if we did not use a pan-genomic approach, we would grossly overestimate the number of genomic changes attributable to post polyploidization evolution.

False-positive reverse transcriptase polymerase chain reaction screening for SARS-CoV-2 in the setting of urgent head and neck surgery and otolaryngologic emergencies during the pandemic: Clinical implications.

BACKGROUND: No reports describe falsepositive reverse transcriptase polymerase chain reaction (RT-PCR) for novel coronavirus in preoperative screening. METHODS: Preoperative patients had one or two nasopharyngeal swabs, depending on low or high risk of viral transmission. Positive tests were repeated. RESULTS: Forty-three of 52 patients required two or more preoperative tests. Four (9.3%) had discrepant results (positive/negative). One of these left the coronavirus disease (COVID) unit against medical advice despite an orbital abscess, with unknown true disease status. The remaining 3 of 42 (7.1%) had negative repeat RT-PCR. Although ultimately considered falsepositives, one was sent to a COVID unit postoperatively and two had urgent surgery delayed. Assuming negative repeat RT-PCR, clear chest imaging, and lack of subsequent symptoms represent the "gold standard," RT-PCR specificity was 0.97. CONCLUSIONS: If false positives are suspected, we recommend computed tomography (CT) of the chest and repeat RT-PCR. Validated serum immunoglobulin testing may ultimately prove useful.

Controversies in free tissue transfer for head and neck cancer: A review of the literature.

BACKGROUND: Microvascular free tissue transfer provides superior functional outcomes when reconstructing head and neck cancer defects. Careful patient selection and surgical planning is necessary to ensure success, as many preoperative, intraoperative, and postoperative patient and technical factors may affect outcome. AIMS: To provide a concise, yet thorough, review of the current literature regarding free flap patient selection and management for the patient with head and neck. MATERIALS AND METHODS: PubMed and Cochrane databases were queried for publications pertaining to free tissue transfer management and outcomes. RESULTS: Malnutrition and tobacco use are modifiable patient factors that negatively impact surgical outcomes. The use of postoperative antiplatelet medications and perioperative antibiotics for greater than 24 hours have not been shown to improve outcomes, although the use of clindamycin alone has been shown to have a higher risk of flap failure. Liberal blood transfusion should be avoided due to higher risk of wound infection and medical complications. DISCUSSION: There is a wide range of beliefs regarding proper management of patients undergoing free tissue transfer. While there is some data to support these practices, much of the data is conflicting and common practices are often continued out of habit or dogma. CONCLUSION: Free flap reconstruction remains a highly successful surgery overall despite as many different approaches to patient care as there are free flap surgeons. Close patient monitoring remains a cornerstone of surgical success.

Identification of a candidate gene for a QTL for spikelet number per spike on wheat chromosome arm 7AL by high-resolution genetic mapping.

KEY MESSAGE: A high-resolution genetic map combined with haplotype analyses identified a wheat ortholog of rice gene APO1 as the best candidate gene for a 7AL locus affecting spikelet number per spike. A better understanding of the genes controlling differences in wheat grain yield components can accelerate the improvements required to satisfy future food demands. In this study, we identified a promising candidate gene underlying a quantitative trait locus (QTL) on wheat chromosome arm 7AL regulating spikelet number per spike (SNS). We used large heterogeneous inbred families ( > 10,000 plants) from two crosses to map the 7AL QTL to an 87-kb region (674,019,191-674,106,327 bp, RefSeq v1.0) containing two complete and two partial genes. In this region, we found three major haplotypes that were designated as H1, H2 and H3. The H2 haplotype contributed the high-SNS allele in both H1 × H2 and H2 × H3 segregating populations. The ancestral H3 haplotype is frequent in wild emmer (48%) but rare (~ 1%) in cultivated wheats. By contrast, the H1 and H2 haplotypes became predominant in modern cultivated durum and common wheat, respectively. Among the four candidate genes, only TraesCS7A02G481600 showed a non-synonymous polymorphism that differentiated H2 from the other two haplotypes. This gene, designated here as WHEAT ORTHOLOG OF APO1 (WAPO1), is an ortholog of the rice gene ABERRANT PANICLE ORGANIZATION 1 (APO1), which affects spikelet number. Taken together, the high-resolution genetic map, the association between polymorphisms in the different mapping populations with differences in SNS, and the known role of orthologous genes in other grass species suggest that WAPO-A1 is the most likely candidate gene for the 7AL SNS QTL among the four genes identified in the candidate gene region.

Dissociable Effects of Aging and Mild Cognitive Impairment on Bottom-Up Audiovisual Integration.

Effective audiovisual sensory integration involves dynamic changes in functional connectivity between superior temporal sulcus and primary sensory areas. This study examined whether disrupted connectivity in early Alzheimer's disease (AD) produces impaired audiovisual integration under conditions requiring greater corticocortical interactions. Audiovisual speech integration was examined in healthy young adult controls (YC), healthy elderly controls (EC), and patients with amnestic mild cognitive impairment (MCI) using McGurk-type stimuli (providing either congruent or incongruent audiovisual speech information) under conditions differing in the strength of bottom-up support and the degree of top-down lexical asymmetry. All groups accurately identified auditory speech under congruent audiovisual conditions, and displayed high levels of visual bias under strong bottom-up incongruent conditions. Under weak bottom-up incongruent conditions, however, EC and amnestic MCI groups displayed opposite patterns of performance, with enhanced visual bias in the EC group and reduced visual bias in the MCI group relative to the YC group. Moreover, there was no overlap between the EC and MCI groups in individual visual bias scores reflecting the change in audiovisual integration from the strong to the weak stimulus conditions. Top-down lexicality influences on visual biasing were observed only in the MCI patients under weaker bottom-up conditions. Results support a deficit in bottom-up audiovisual integration in early AD attributable to disruptions in corticocortical connectivity. Given that this deficit is not simply an exacerbation of changes associated with healthy aging, tests of audiovisual speech integration may serve as sensitive and specific markers of the earliest cognitive change associated with AD.

Predictors for lymph nodes involvement in low risk endometrial cancer.

Neutrophil-lymphocyte ratio (NLR) and BMI were examined as pre-operative predictors for lymph node metastases in patients with low-risk endometrial cancer. The study was a retrospective analysis of 534 endometrial cancer patients that underwent hysterectomy and lymph node dissection. Included subjects had a preoperative diagnosis of a grade 1 or 2 endometrioid carcinoma and no macroscopic extrauterine disease. We compared node-negative to node-positive patients to identify correlates of node-positive disease. The node-positive group presented with lower BMI than the node-negative group, 31.5 and 34.4, respectively (p = .03). The mean NLR was higher in the node-positive group 3.4 vs 2.9 (p = .08), showing a trend towards significance on univariate analysis. On multivariate analysis, lower BMI was found to be an independent predictor for nodal metastasis. Our data suggest that lower BMI is a risk factor for lymph nodes involvement in low-risk endometrial cancer. Impact statement Most endometrial cancer patients have low-risk disease with low risk for lymph nodes metastasis. In order to reduce the number of patients that will undergo unnecessary lymph node dissection, different types of preoperative predictors for lymph node involvement were studied. CA 125 and different imaging modalities were found as useful predictors for more advanced disease. Less studied predictors are the systemic inflammatory response markers and patient's BMI. This study suggests that lower BMI is a risk factor for lymph node involvement in low-risk endometrial cancer. The neutrophil to lymphocyte ratio was close to significance as a predictor for lymph node involvement. In practice, physicians might favour comprehensive lymph node dissection when there is a doubt regarding the procedure but the patient is lean. The study's conclusion can be utilised for triaging patients to general gynaecologist vs gynaecologic oncologist. Further research should focus on combining predictors such as age, BMI, NLR, CA 125 and imaging to better predict lymph nodes involvement in low-risk endometrial cancer.

The Role of Crowdsourcing in Assessing Surgical Skills.

BACKGROUND: Assessing surgical skill is critical in improving patient care while reducing medical errors, length of stay, and readmission rates. Crowdsourcing provides 1 potential method for accurately assessing this; only recently has crowdsourcing been studied as a valid way to provide feedback to surgeons. The results of such studies are explored. DATA SOURCES: A systematic literature search was performed on PubMed to identify studies that have attempted to validate crowdsourcing as a method for assessing surgical skill. Through a combination of abstract screening and full-length review, 9 studies that met the inclusion criteria were reviewed. CONCLUSIONS: Crowdsourcing has been validated as an important way to provide feedback for surgical skill. It has been demonstrated to be effective in both dry-lab and live surgery, for a variety of tasks and methods. However, more studies must be performed to ensure that crowdsourcing can provide quality feedback in a wider variety of scenarios.

The Role of Barbiturates for Alcohol Withdrawal Syndrome.

BACKGROUND: Benzodiazepine-resistant cases of alcohol withdrawal syndrome are common, and therefore alternate treatments are needed. OBJECTIVE: Our aim was to conduct a systematic review of published reports on the use of barbiturates for alcohol withdrawal syndrome. METHODS: We performed a systematic literature search of PUBMED for relevant citations that described the use of barbiturates either alone or in conjunction with other pharmacological agents to treat alcohol withdrawal syndrome. RESULTS: A total of 15 citations were identified; 2 citations looked at barbiturates alone; 1 found barbiturates effective in an emergency department setting at treating seizures and preventing return visits. A second showed that barbiturates caused a relatively low rate of respiratory depression. Further, 5 citations compared barbiturates with benzodiazepines; 1 suggested that they were better at treating severe withdrawal, and another showed they were more effective at preventing seizures; 4 citations found they were as effective as benzodiazepines, but 1 found a higher rate of respiratory depression. Also, 3 citations compared a combination of barbiturates and benzodiazepines to benzodiazepines alone; 1 showed decreased ventilation, another showed fewer intensive care unit admissions, and a third showed better symptom control; 3 citations described detailed reports of barbiturate protocols. Lastly, 2 citations compared barbiturates with other agents and found them equivalent. CONCLUSION: Barbiturates provide effective treatment for alcohol withdrawal syndrome. In particular, they show promise for use in the emergency department and for severe withdrawal in the intensive care unit. Respiratory depression does not appear to be exceedingly common. Additional studies are needed to clarify the role of barbiturates in alcohol withdrawal syndrome.

The influence of multicultural counseling competence and anti-Black prejudice on therapists' outcome expectancies.

The broad goal of this study was to examine multiple potential predictors of anti-Black bias among counselors. Specifically, in an online survey of 173 trainees and professionals in mental health, this study used 3 measures related to cultural sensitivity as predictors of therapists' expectancies for bond and prognosis with African American clients compared with White clients. The Multicultural Counseling Inventory (MCI; Sodowsky, Taffe, Gutkin, & Wise, 1994) was used to measure global multicultural competence. The Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) served as a measure of automatic prejudice toward Blacks. Additionally, a new self-report measure of anti-Black clinical prejudice was created specifically for this study. The Balanced Inventory of Desirable Responding (Paulhus, 1984) was included to control for socially desirable responding. Each predictor of cultural sensitivity uniquely explained variance in anti-Black bias in bond ratings, with the IAT accounting for more variance than the 2 self-reports. Our novel measure of clinical prejudice accounted for anti-Black bias in prognosis ratings, but the MCI and the IAT did not. Researchers studying cultural competence are encouraged to consider the roles of automatic and deliberate prejudice in determining disparities in clinical expectancies and cross-racial therapeutic alliances. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Carbon dioxide elimination and gas displacement vary with piston position during high-frequency oscillatory ventilation.

INTRODUCTION: Alterations in gas displacement in pediatric patients ventilated with the SensorMedics 3100A high-frequency oscillator are most commonly manipulated by adjusting the amplitude, frequency, and percent inspiratory time. The piston-position-and-displacement indicator is commonly centered and subsequently not adjusted. That practice may limit the clinician's ability to optimize carbon dioxide elimination. We hypothesized that varying the piston position would alter gas displacement and carbon dioxide elimination. METHODS: We conducted an observational study in a tertiary pediatric intensive care unit and a correlated bench study. In the clinical study, 24 patients were ventilated with a SensorMedics 3100A high-frequency oscillator. Transcutaneously measured carbon dioxide ((tCO(2))) values were documented with the piston-position-and-displacement indicator in left, center, and right positions. In the bench study the oscillator was set and maintained at: mean airway pressure 15 cm H(2)O, inspiratory time 33% of respiratory-cycle time, bias flow 20 L/min. A pneumotachometer attached to a respiratory mechanics monitor was placed between the ventilator circuit and a test lung. Data were collected with the piston-position-and-displacement indicator at the left, center, and right positions with frequencies of 4-14 Hz and amplitudes of 25-55 cm H(2)O. Data were collected over a 3-minute time period for each combination of frequency, amplitude, and piston-position-and-displacement-indicator position. We compared the data with repeated-measures analysis of variance. Pairwise comparisons were performed with a 2-tailed Student's test with Bonferroni correction. RESULTS: Among the 24 patients (tCO(2)) was significantly associated with the position of the piston (p < 0.007). In the bench study, gas displacement was higher when the piston-position-and-displacement indicator was positioned to the left (than when at the center position) 91.7% of the time (p < 0.0001). When the piston-position-and-displacement indicator was positioned to the right (as compared to the center position), gas displacement was lower 75% of the time (p < 0.0001). CONCLUSION: Adjusting the oscillator piston alters the volume of gas displaced and provides an additional means for titrating carbon dioxide elimination. .

Heliox does not affect gas exchange during high-frequency oscillatory ventilation if tidal volume is held constant.

OBJECTIVE: To compare gas exchange with heliox and oxygen-enriched air during high-frequency oscillatory ventilation, while controlling for tidal volume, in a pediatric swine model of acute lung injury. We hypothesized that when tidal volume delivery is held constant, heliox does not alter gas exchange. DESIGN: Randomized, crossover trial. SETTING: University animal research laboratory. SUBJECTS: Ten swine (4.4-5.4 kg). INTERVENTIONS: Acute lung injury (A-a gradient of >300 mm Hg) was created using repeated saline lavage during conventional mechanical ventilation. The animals were then administered high-frequency oscillatory ventilation and ventilated with 60% oxygen/40% helium and 60% oxygen/40% nitrogen in a randomized, crossover trial. When changing gas mixtures within each animal, mean airway pressure (Paw = 16.8 +/- 0.3 cm H(2)O) and frequency (10 Hz) were held constant. Oscillation amplitude (DeltaP) was adjusted to maintain constant tidal volume delivery as measured by respiratory inductive plethysmography. Next, the animals were ventilated with 40% oxygen/60% helium and 40% oxygen/60% nitrogen in a randomized crossover trial, again controlling for tidal volume. MEASUREMENTS AND MAIN RESULTS: Gas exchange was assessed by arterial blood gas analysis after ventilation with each gas mixture. We demonstrated no significant difference in Paco(2) or Pao(2) between the heliox and oxygen-enriched air with either the 40% or 60% oxygen mixtures. The oscillation amplitude required to achieve the same tidal volume delivery was significantly less with heliox. CONCLUSIONS: We conclude that if tidal volume delivery is maintained constant, heliox does not alter gas exchange when compared with oxygen-enriched air. However, to achieve the same tidal volume delivery, a lower oscillation amplitude is required with heliox. The clinical benefit of heliox administration during high-frequency oscillatory ventilation has yet to be determined. Possible advantages of heliox include improved ventilation of larger patients when approaching the power limitations of the Sensormedics 3100A oscillator and a potential reduction in the oscillation amplitude delivered to the more proximal gas exchange units.