Dobutamine and Goal-Directed Fluid Therapy for Improving Tissue Oxygenation in Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction Surgery: Protocol for a Randomized Controlled Trial.

BACKGROUND: Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the patient's own tissue). The latter creates a more natural breast mound and avoids the long-term need for surgical revision-more often associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is considered the gold standard approach in autologous breast reconstruction. However, complications do occur with DIEP flap surgery and can stem from poor flap tissue perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (eg, goal-directed perioperative fluid therapy) is essential. Current perioperative fluid therapy is traditionally guided by subjective criteria, which leads to wide variations in clinical practice. OBJECTIVE: The main objective of this trial is to determine whether the use of minimally invasive cardiac output (CO) monitoring for guiding intravenous fluid administration, combined with low-dose dobutamine infusion (via a treatment algorithm), will increase tissue oxygenation in patients undergoing DIEP flap surgery. METHODS: With appropriate institutional ethics board and Health Canada approval, patients undergoing DIEP flap surgery are randomly assigned to receive CO monitoring for the guidance of intraoperative fluid therapy in addition to a low-dose dobutamine infusion (which potentially improves flap oxygenation) versus the current standard of care. The primary outcome is tissue oxygenation measured via near-infrared spectroscopy at the perfusion zone furthest from the perforator vessels 45 minutes after vascular reanastomosis of the DIEP flap. Low dose (2.5 µg/kg/hr) dobutamine infusion continues for up to 4 hours postoperatively, provided there are no associated complications (ie, persistent tachycardia). Flap oxygenation, hemodynamic parameters, and any medication-associated side effects/complications are monitored for up to 48 hours postoperatively. Complications, rehospitalizations, and patient satisfaction are also collected until 30 days postoperatively. RESULTS: Funding and regulatory approvals were obtained in 2019, but the study recruitment was interrupted by the COVID-19 pandemic. As of October 4, 2023, 34 participants have been recruited. Because of the significant delays associated with the pandemic, the expected completion date was extended. We expect the study to be completed and ready for potential news release (as appropriate) and publication by July 2024. No patients have suffered any adverse effects/complications from participating in this study, and none have been lost to follow-up. CONCLUSIONS: CO-directed fluid therapy in combination with a low-dose dobutamine infusion via a treatment algorithm has the potential to improve DIEP flap tissue oxygenation and reduce complications following DIEP flap breast reconstruction surgery. However, given that the investigators remain blinded to group randomization, no comment can be made regarding the efficacy of this intervention for improving tissue oxygenation at this time. Nevertheless, no patients have been withdrawn for safety concerns thus far, and compliance remains high. TRIAL REGISTRATION: Clinicaltrials.gov NCT04020172; https://clinicaltrials.gov/study/NCT04020172.

Many foods are more acid-forming than acid-alkaline formulas indicate.

Foods contain substances impacting the acid-base balance. The Western diet is often viewed as being overly acid due to its high-level of animal-based protein and low-level of vegetable intake. Meanwhile, with ageing the ability to excrete acid compounds is reduced as kidney function declines and so there is a risk of acid retention and subsequent interstitial acidosis. Two systems used for calculating the Dietary Acid Load (DAL): the potential acid load of foods (PRAL) and the net endogenous acid production (NEAP). This report outlines weaknesses in these formulas and concludes that dietitians and nutritionists lack the necessary tools to research the acid-base hypothesis. Additionally, the report emphasizes the importance of food selection in the ageing population. Background: Foods contain substances impacting the acid-base balance. The Western diet is often viewed as being overly acid due to its high-level of animal-based protein and low-level of vegetable intake. There are concerns that the disproportionate acid intake promotes low-grade metabolic acidosis in the interstitial fluid, interstitial acidosis, and may lead to chronic disease. Two formulas are used for calculating the DAL: the PRAL and the NEAP. Both PRAL and NEAP are based on levels of protein and minerals. Aim: To identify additional food constituents that impact DAL. Methods: Review of the literature concerning the acid-forming and alkaline-forming constituents of foods. Results: Five additional food constituents were identified as potentially having a meaningful impact on DAL. The oxidation of taurine and the metabolism of fructose and purines increase acidity, whereas organic acids increase alkalinity. Additionally, polyphenols affect the microbiota which break down uric acid excreted in the intestinal tract. Conclusions: Neither PRAL nor NEAP provides complete assessments of the impact of foods on DAL. These formulas could be improved by the inclusion of dietary amino acids rather than protein, taurine, purines, fructose, organic acids and polyphenols. Currently, dietitians and nutritionists lack the necessary tools both to research the acid-base hypothesis and recommend managed diets. Managed diets are of particular importance for the elderly because of their reduced kidney function which increases the risk of acid retention and subsequent interstitial acidosis.

Anticoagulation use in perioperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Perioperative atrial fibrillation is associated with an increased risk of stroke, myocardial infarction, and death after noncardiac surgery. Anticoagulation therapy is effective for stroke prevention in nonsurgical atrial fibrillation, but its efficacy and safety in perioperative atrial fibrillation are unknown. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception until January 2022. We included studies comparing anticoagulation versus no anticoagulation use in patients with perioperative atrial fibrillation after noncardiac surgery. Our study outcomes included stroke ± systemic embolism, bleeding, mortality, myocardial infarction, and venous thromboembolism. We pooled studies using fixed-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable-adjusted results. RESULTS: Seven observational studies but no randomised trials were included. Of the 27,822 patients, 29.1% were prescribed therapeutic anticoagulation. Anticoagulation use was associated with a lower risk of stroke ± systemic embolism (RR 0.73; 95% CI, 0.62-0.85; I2 = 81%; 3 studies) but a higher risk of bleeding (RR 1.14; 95% CI, 1.04-1.25; 1 study). There was a lower risk of mortality associated with anticoagulation use (RR 0.45; 95% CI, 0.40-0.51; I2 = 80%; 2 studies). There was no difference in the risk of myocardial infarction (RR 2.19; 95% CI, 0.97-4.96; 1 study). The certainty of the evidence was very low across all outcomes. CONCLUSION: Anticoagulation is associated with a reduced risk of stroke and death but an increased risk of bleeding. The quality of the evidence is very poor. Randomised trials are needed to better determine the effects of anticoagulation use in this population.

Archetypes of inflorescence: genome-wide association networks of panicle morphometric, growth, and disease variables in a multiparent oat population.

There is limited information regarding the morphometric relationships of panicle traits in oat (Avena sativa) and their contribution to phenology and growth, physiology, and pathology traits important for yield. To model panicle growth and development and identify genomic regions associated with corresponding traits, 10 diverse spring oat mapping populations (n = 2,993) were evaluated in the field and 9 genotyped via genotyping-by-sequencing. Representative panicles from all progeny individuals, parents, and check lines were scanned, and images were analyzed using manual and automated techniques, resulting in over 60 unique panicle, rachis, and spikelet variables. Spatial modeling and days to heading were used to account for environmental and phenological variances, respectively. Panicle variables were intercorrelated, providing reproducible archetypal and growth models. Notably, adult plant resistance for oat crown rust was most prominent for taller, stiff stalked plants having a more open panicle structure. Within and among family variance for panicle traits reflected the moderate-to-high heritability and mutual genome-wide associations (hotspots) with numerous high-effect loci. Candidate genes and potential breeding applications are discussed. This work adds to the growing genetic resources for oat and provides a unique perspective on the genetic basis of panicle architecture in cereal crops.

A Randomized Controlled Pilot Study of Topical Ropivacaine for Prevention of Post-POEM Pain.

Background and Aims: Although usually mild to moderate in severity, postoperative pain after peroral endoscopic myotomy (POEM) is common. There are no studies that have addressed minimizing postoperative pain in patients undergoing POEM for achalasia. We hypothesized that intraoperative topical intra-tunnel irrigation with ropivacaine would result in a significant reduction in pain scores in the postoperative period. Methods: A double-blind, randomized, placebo-controlled trial was conducted at the Kingston Health Sciences Center. Patients received either 30 mL of 0.2% ropivacaine or 30 mL of placebo irrigated topically into the POEM tunnel after completing the myotomy and prior to closing the mucosal incision. The primary outcome was pain post-POEM at 6 h assessed by the Numeric Rating Scale (NRS). Secondary objectives included assessing pain score at 0.5, 1, 2, 4 h post-POEM and on discharge, Quality of Recovery (QoR-15) scores at discharge, narcotic requirement, adverse events, and patients' willingness to have the procedure done on an outpatient basis. Results: A total of 20 patients were enrolled. For the primary outcome of pain post-POEM at 6 h, the NRS was 1.1 in the placebo group and 2.4 in the ropivacaine group (95% CI of the difference: -3.2 to 0.6, P = 0.171). No statistical difference was seen in the pain scores. Overall usage of post-procedural narcotics was low with no differences between the two groups. Fifty percent of patients in both groups were willing to have the procedure done as an outpatient. Conclusion: The addition of intra-procedural tunnel irrigation with 30 mL 0.2% ropivacaine did not lead to reduced post-POEM pain.

A simple technique to assess postoperative epidural functionality.

To describe an alternative method of measuring the Epidural Waveform Analysis (EWA), a technique through which anesthesiologists can confirm the position of a needle and/or catheter tip in the epidural space. EWA consists of epidural catheter transduction with a pressure system typically used for invasive arterial blood pressure monitoring which generates a characteristic oscillatory waveform (provided the catheter tip is within the epidural space) in synchrony with the pulsatile epidural circulation. The technique requires a double-male connector, a 3-way stopcock and an arterial pressure extension tubing along with the patient's existing arterial line setup while ensuring a meticulously sterile technique to mitigate the risks of neuraxial infection. The technique described herein has been successfully and routinely applied within our institution to measure EWA with the advantage of being potentially less wasteful. EWA allows anesthesiologists to confirm the correct position of an epidural needle/catheter. We describe a method of successfully measuring EWA while reducing wastefulness.

Sensitivity and specificity of waveform analysis for assessing postoperative epidural function.

STUDY OBJECTIVES: To characterize the accuracy of epidural waveform analysis (EWA) in assessing the functionality of thoracic epidural catheters in the immediate postoperative period (primary objective), and to determine the inter-rater reliability between EWA waveform observers (secondary outcome). DESIGN: Single center, prospective diagnostic accuracy cohort study. SETTING: Post-anesthetic care unit of a university teaching hospital. PATIENTS: 84 adult patients undergoing elective thoracic, gynecologic, vascular, urologic, or general surgery with preoperative placement of a thoracic epidural catheter for perioperative analgesia. INTERVENTIONS: EWA tracings were video recorded in the immediate postoperative period through the epidural catheter in the post-anesthetic care unit. MEASUREMENTS: Postoperative EWA tracings were compared with clinical assessments of the sensory block to ice produced by epidural local anesthetic in the immediate postoperative period. Additionally, intra-class correlation analysis of agreement between 3 independent (and blinded) EWA waveform observers was carried out. RESULTS: Among 80 patients with thoracic epidurals who completed the study protocol, 73 demonstrated postoperative functional epidurals with sensory block to ice and 7 demonstrated non-functional epidurals. EWA yielded 65 true positives, 6 true negatives, 8 false negatives, and 1 false positive. Postoperative EWA sensitivity, specificity, positive predictive value and negative predictive value, along with the 95% confidence intervals (CI) were 89% (79-95%), 86% (42-100%), 98% (92-100%), and 43% (18-71%) respectively. Intra-class correlation between waveform assessors was 0.870 (95% CI 0.818-0.910, p < 0.001). CONCLUSIONS: EWA is useful in assessing the position of thoracic epidural catheters in the immediate postoperative period, demonstrating high sensitivity and specificity as well as robust inter-rater reliability. For patients in whom sensory block to ice cannot be reliably assessed postoperatively, EWA may provide a useful adjunct for assessing epidural functionality.

The Genetic Architecture of Milling Quality in Spring Oat Lines of the Collaborative Oat Research Enterprise.

Most oat grains destined for human consumption must possess the ability to pass through an industrial de-hulling process with minimal breakage and waste. Uniform grain size and a high groat to hull ratio are desirable traits related to milling performance. The purpose of this study was to characterize the genetic architecture of traits related to milling quality by identifying quantitative trait loci (QTL) contributing to variation among a diverse collection of elite and foundational spring oat lines important to North American oat breeding programs. A total of 501 lines from the Collaborative Oat Research Enterprise (CORE) panel were evaluated for genome-wide association with 6 key milling traits. Traits were evaluated in 13 location years. Associations for 36,315 markers were evaluated for trait means across and within location years, as well as trait variance across location years, which was used to assess trait stability. Fifty-seven QTL influencing one or more of the milling quality related traits were identified, with fourteen QTL mapped influencing mean and variance across location years. The most prominent QTL was Qkernel.CORE.4D on chromosome 4D at approximately 212 cM, which influenced the mean levels of all traits. QTL were identified that influenced trait variance but not mean, trait mean only and both.

Examining the accuracy of residents' self-assessments and faculty assessment behaviours in anesthesiology.

BACKGROUND: Residents' accurate self-assessment and clinical judgment are essential for optimizing their clinical skills development. Evidence from the medical literature suggests that residents generally do poorly at self-assessing their performance, often due to factors relating to learners' personal backgrounds, cultures, the specific contexts of the learning environment and rater bias or inaccuracies. We evaluated the accuracy of anesthesiology residents' self-assessed Global Entrustment scores and determined whether differences between faculty and resident scores varied by resident seniority, faculty leniency, and/or year of assessment. METHODS: We employed variance components modeling techniques and analyzed 329 pairs of faculty and self-assessed entrustment scores among 43 faculty assessors and 15 residents. Using faculty scores as the gold standard, we compared faculty scores with residents' scores (xi(faculty)-xi(resident)), and determined residents' accuracy, including over- and under-confidence. RESULTS: The results indicate that residents were respectively over- and under-confident in 10.9% and 54.4% of the assessments but more consistent in their individual self-assessments (rho = 0.70) than faculty assessors. Faculty scores were significantly higher (α = 0.396; z = 4.39; p < 0.001) than residents' self-assessed scores. Being a lenient/dovish (ß = 0.121, z = 3.16, p < 0.01) and a neutral (ß = 0.137, z = 3.57, p < 0.001) faculty assessor predicted a higher likelihood of resident under-confidence. Senior residents were significantly less likely to be under-confident compared to junior residents (ß = -0.182, z =-2.45, p < 0.05). The accuracy of self-assessments did not significantly vary during the two years of the study period. CONCLUSIONS: The majority of residents' self-assessments were inaccurate. Our findings may help identify the sources of such inaccuracies.

CONTEXTE: L'autoévaluation adéquate et le jugement clinique des résidents sont essentiels pour optimiser le développement de leurs compétences cliniques. Les données probantes de la littérature médicale indiquent que les résidents ont généralement du mal à s'auto-évaluer, souvent en raison de facteurs liés à leur passé personnel, à la culture, aux contextes spécifiques de l'environnement d'apprentissage et aux préjugés ou inexactitudes des évaluateurs. Nous avons évalué l'exactitude des scores d'autoévaluation par échelles de confiance globalepar des résidents en anesthésiologie et déterminé si les différences entre les scores des enseignants et des résidents variaient en fonction du niveau de formation des résidents, de l'indulgence des enseignants ou de l'année d'évaluation. MÉTHODES: Nous avons utilisé des techniques de modélisation des composantes de la variance et analysé 329 paires de scores de confiance des enseignants et d'autoévaluation avec la participation de 43 évaluateurs du corps professoral et 15 résidents. Prenant les scores des enseignants comme référence, nous avons comparé les leurs avec ceux des résidents (xi(enseignant) -xi(résident)), et déterminé l'exactitude chez les résidents, y compris l'excès et le manque de confiance. RÉSULTATS: Les résultats indiquent que les résidents étaient trop confiants dans 10,9 % des évaluations, et pas assez confiants dans 54,4 % des cas, mais qu'ils étaient plus cohérents dans leurs autoévaluations (rho = 0,70) que ne l'étaient les enseignants. Les scores du corps professoral étaient significativement plus élevés (α = 0,396 ; z = 4,39 ; p < 0,001) que les scores d'autoévaluation des résidents. Le fait d'être un évaluateur indulgent (ß = 0,121, z = 3,16, p < 0,01) et neutre (ß = 0,137, z = 3,57, p < 0,001) prédisait une probabilité plus élevée de sous-confiance des résidents. Les résidents seniors étaient significativement moins susceptibles de manquer de confiance en eux que les résidents juniors (ß = -0,182, z = -2,45, p < 0,05). L'exactitude des autoévaluations n'a pas varié de manière significative au cours des deux années de la période d'étude. CONCLUSIONS: La majorité des autoévaluations des résidents étaient inexactes. Nos résultats peuvent aider à identifier les sources de ces inexactitudes.

Correction: Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize.

[This corrects the article DOI: 10.1371/journal.pgen.1007019.].

Adductor canal block with or without added magnesium sulfate following total knee arthroplasty: a multi-arm randomized controlled trial.

PURPOSE: Postoperative analgesia following total knee arthroplasty (TKA) often includes intrathecal opioids, periarticular injection (PAI) of local anesthetic, systemic multimodal analgesia, and/or peripheral nerve blockade. The adductor canal block (ACB) provides analgesia without muscle weakness and magnesium sulphate (MgSO4) may extend its duration. The purpose of this trial was to compare the duration and quality of early post-TKA analgesia in patients receiving postoperative ACB (± MgSO4) in addition to standard care. METHODS: Elective TKA patients were randomized to: 1) sham ACB, 2) ropivacaine ACB, or 3) ropivacaine ACB with added MgSO4. All received spinal anesthesia with intrathecal morphine, intraoperative PAI, and multimodal systemic analgesia. Patients and assessors remained blinded to allocation. Anesthesiologists knew whether patients had received sham or ACB but were blinded to MgSO4. The primary outcome was time to first analgesic (via patient-controlled analgesia [PCA] with iv morphine) following ACB. Secondary outcomes were morphine consumption, side effects, visual analogue scale pain scores, satisfaction until 24 hr postoperatively, and length of stay. RESULTS: Of 130 patients, 121 were included. Nine were excluded post randomization: four were protocol violations, three did not meet inclusion criteria, and two had severe pain requiring open label blockade. There were no differences in the median [interquartile range] time to first PCA request: sham, 310 min [165-550]; ropivacaine ACB, 298 min [120-776]; and ropivacaine ACB with MgSO4, 270 min [113-780] (P = 0.96). Similarly, we detected no differences in resting pain, opioid consumption, length of stay, or associated side effects until 24 hr postoperatively. CONCLUSION: We found no analgesic benefit of a postoperative ACB, with or without added MgSO4, in TKA patients undergoing spinal anesthesia and receiving intrathecal morphine, an intraoperative PAI, and multimodal systemic analgesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02581683); registered 21 October 2015.

RéSUMé: OBJECTIF: L'analgésie postopératoire suivant une arthroplastie totale du genou (ATG) inclut souvent des opioïdes intrathécaux, une injection périarticulaire (IPA) d'anesthésique local, une analgésie multimodale systémique, et/ou des blocs des nerfs périphériques. Le bloc du canal des adducteurs (BCA) permet une analgésie sans faiblesse musculaire et le sulfate de magnésium (MgSO4) pourrait prolonger sa durée. L'objectif de cette étude était de comparer la durée et la qualité de l'analgésie post-ATG précoce chez les patients recevant un BCA postopératoire (± MgSO4) en plus des soins standard. MéTHODE: Des patients devant subir une ATG non urgente ont été randomisés à recevoir : 1) un BCA placebo (groupe témoin), 2) un BCA avec ropivacaïne, ou 3) un BCA avec ropivacaïne et MgSO4. Tous ont reçu une rachianesthésie avec morphine intrathécale, une IPA peropératoire, et une analgésie multimodale systémique. L'allocation a été faite à l'insu des patients et des évaluateurs. Les anesthésiologistes savaient si les patients avaient reçu un placebo ou un BCA, mais n'étaient pas informés de l'ajout ou non de MgSO4. Le critère d'évaluation principal était le temps jusqu'à la première prise d'analgésique (via une analgésie contrôlée par le patient [ACP] avec de la morphine iv) après le BCA. Les critères secondaires comprenaient la consommation de morphine, les effets secondaires, les scores de douleur sur l'échelle visuelle analogue, la satisfaction jusqu'à 24 heures postopératoires, et la durée de séjour. RéSULTATS: Sur 130 patients, 121 ont été inclus. Neuf ont été exclus après la randomisation : quatre l'ont été en raison de violations du protocole, trois ne répondaient pas aux critères d'inclusion, et deux ont ressenti des douleurs graves nécessitant un bloc sans insu. Aucune différence n'a été observée dans le temps médian [écart interquartile] jusqu'à la première demande d'ACP : placebo, 310 min [165-550]; BCA ropivacaïne, 298 min [120-776]; et BCA ropivacaïne avec MgSO4, 270 min [113-780] (P = 0,96). De la même manière, nous n'avons détecté aucune différence dans la douleur au repos, la consommation d'opioïdes, la durée de séjour, ou les effets secondaires associés jusqu'à 24 heures postopératoires. CONCLUSION: Nous n'avons trouvé aucun avantage analgésique à un BCA postopératoire, avec ou sans ajout de MgSO4, chez les patients subissant une ATG sous rachianesthésie et recevant de la morphine intrathécale, une IPA peropératoire, et une analgésie multimodale systémique. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02581683); enregistrée le 21 octobre 2015.

Curcumin/Turmeric: Their Effect on Serum Uric Acid Remains Unknown.

Various studies have investigated whether turmeric, or isolated curcumin, affects serum levels of uric acid. However, some studies have been hampered by problems in reliably measuring serum uric acid. For example, in one trial lasting 8 weeks, serum uric acid levels decreased (p < 0.01) for the control group, while in another 8-week trial serum uric acid levels increased (p < 0.01) for the control group.

A Tale of 2 Tubes for Emergency Management of Airway Obstruction From an Anterior Mediastinal Mass: A Case Report.

Anterior mediastinal masses are challenging. As induction of general anesthesia may result in complete airway obstruction or hemodynamic collapse, maintaining spontaneous ventilation and advancing the endotracheal tube (ETT) distal to the mass are recommended. We discuss the emergency management of an anterior mediastinal mass-induced near-complete airway obstruction at the carina. Despite maintaining spontaneous ventilation, airway obstruction persisted following placement of the ETT proximal to the obstruction. After advancing the ETT into the right mainstem bronchus distal to the mass, hypoxemia persisted, prompting placement of a second ETT into the left mainstem bronchus to overcome the obstruction and provide adequate oxygenation.

Dominance Effects and Functional Enrichments Improve Prediction of Agronomic Traits in Hybrid Maize.

Single-cross hybrids have been critical to the improvement of maize (Zea mays L.), but the characterization of their genetic architectures remains challenging. Previous studies of hybrid maize have shown the contribution of within-locus complementation effects (dominance) and their differential importance across functional classes of loci. However, they have generally considered panels of limited genetic diversity, and have shown little benefit from genomic prediction based on dominance or functional enrichments. This study investigates the relevance of dominance and functional classes of variants in genomic models for agronomic traits in diverse populations of hybrid maize. We based our analyses on a diverse panel of inbred lines crossed with two testers representative of the major heterotic groups in the U.S. (1106 hybrids), as well as a collection of 24 biparental populations crossed with a single tester (1640 hybrids). We investigated three agronomic traits: days to silking (DTS), plant height (PH), and grain yield (GY). Our results point to the presence of dominance for all traits, but also among-locus complementation (epistasis) for DTS and genotype-by-environment interactions for GY. Consistently, dominance improved genomic prediction for PH only. In addition, we assessed enrichment of genetic effects in classes defined by genic regions (gene annotation), structural features (recombination rate and chromatin openness), and evolutionary features (minor allele frequency and evolutionary constraint). We found support for enrichment in genic regions and subsequent improvement of genomic prediction for all traits. Our results suggest that dominance and gene annotations improve genomic prediction across diverse populations in hybrid maize.

Simulation-based evaluation of anaesthesia residents: optimising resource use in a competency-based assessment framework.

Introduction: Simulation training in anaesthesiology bridges the gap between theory and practice by allowing trainees to engage in high-stakes clinical training without jeopardising patient safety. However, implementing simulation-based assessments within an academic programme is highly resource intensive, and the optimal number of scenarios and faculty required for accurate competency-based assessment remains to be determined. Using a generalisability study methodology, we examine the structure of simulation-based assessment in regard to the minimal number of scenarios and faculty assessors required for optimal competency-based assessments. Methods: Seventeen anaesthesiology residents each performed four simulations which were assessed by two expert raters. Generalisability analysis (G-analysis) was used to estimate the extent of variance attributable to (1) the scenarios, (2) the assessors and (3) the participants. The D-coefficient and the G-coefficient were used to determine accuracy targets and to predict the impact of adjusting the number of scenarios or faculty assessors. Results: We showed that multivariate G-analysis can be used to estimate the number of simulations and raters required to optimise assessment. In this study, the optimal balance was obtained when four scenarios were assessed by two simulation experts. Conclusion: Simulation-based assessment is becoming an increasingly important tool for assessing the competency of medical residents in conjunction with other assessment methods. G-analysis can be used to assist in planning for optimal resource use and cost-efficacy.

Interscalene Block in an Anesthetized Adult with Hypertrophic Obstructive Cardiomyopathy Undergoing Clavicle Fracture Reduction.

Whether regional anesthesia procedures should be performed in heavily sedated/anesthetized adults remains controversial. One of the purported advantages of performing regional nerve blocks in conversant patients is early warning against major nerve injury and, arguably, early detection of local anesthetic systemic toxicity. A 60-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) underwent a clavicle fracture repair under general anesthesia. Intraoperative transesophageal echocardiography revealed dynamic left ventricular outflow track obstruction and systolic anterior motion of the posterior mitral valve leaflet. In part based on such echo findings, he received an ultrasound-guided interscalene plus a superficial cervical plexus block for postoperative analgesia prior to emergence from general anesthesia. Given the lack of robust data on the safety of ultrasound-guided regional techniques in heavily sedated/anesthetized adults, we use the example of echographic evidence of significant HOCM to argue for a pragmatic and individualized approach when faced with unusual situations in which the pros of such an approach may outweigh the cons - in this case for performing an interscalene block on an anesthetized adult.

Water-deficit responsive microRNAs in the primary root growth zone of maize.

BACKGROUND: MicroRNA-mediated gene regulatory networks play a significant role in plant growth and development and environmental stress responses. RESULTS: We identified 79 microRNAs (miRNAs) and multiple miRNA variants (isomiRs) belonging to 26 miRNA families in the primary root growth zone of maize seedlings grown at one of three water potentials: well-watered (- 0.02 MPa), mild water deficit stress (- 0.3 MPa), and severe water deficit stress (- 1.6 MPa). The abundances of 3 miRNAs (mild stress) and 34 miRNAs representing 17 families (severe stress) were significantly different in water-deficit stressed relative to well-watered controls (FDR < 0.05 and validated by stem loop RT-qPCR). Degradome sequencing revealed 213 miRNA-regulated transcripts and trancriptome profiling revealed that the abundance of 77 (miRNA-regulated) were regulated by water-defecit stress. miR399e,i,j-3p was strongly regulated by water-defcit stress implicating the possibility of nutrient deficiency during stress. CONCLUSIONS: We have identified a number of maize miRNAs that respond to specific water deficits applied to the primary root growth zone. We have also identified transcripts that are targets for miRNA regulation in the root growth zone under water-deficit stress. The miR399e,i,j-3p that is known to regulate phosphate uptake in response to nutrient deficiencies responds to water-deficit stress, however, at the seedling stage the seed provides adequate nutrients for root growth thus miR399e,i,j-3p may play a separate role in water-deficit responses. A water-deficit regulated maize transcript, similar to known miR399 target mimics, was identified and we hypothesized that it is another regulatory player, moderating the role of miR399e,i,j-3p, in primary root growth zone water deficit responses.

Optimal Designs for Genomic Selection in Hybrid Crops.

Improved capacity of genomics and biotechnology has greatly enhanced genetic studies in different areas. Genomic selection exploits the genotype-to-phenotype relationship at the whole-genome level and is being implemented in many crops. Here we show that design-thinking and data-mining techniques can be leveraged to optimize genomic prediction of hybrid performance. We phenotyped a set of 276 maize hybrids generated by crossing founder inbreds of nested association mapping populations for flowering time, ear height, and grain yield. With 10 296 310 SNPs available from the parental inbreds, we explored the patterns of genomic relationships and phenotypic variation to establish training samples based on clustering, graphic network analysis, and genetic mating scheme. Our analysis showed that training set designs outperformed random sampling and earlier methods that either minimize the mean of prediction error variance or maximize the mean of generalized coefficient of determination. Additional analyses of 2556 wheat hybrids from an early-stage hybrid breeding system and 1439 rice hybrids from an established hybrid breeding system validated the approaches. Together, we demonstrated that effective genomic prediction models can be established with a training set 2%-13% of the size of the whole set, enabling an efficient exploration of enormous inference space of genetic combinations.

Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize.

Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of complementation for segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding.