Identifying intraoperative events in a simulated laparotomy video: a multinational study of inattentional blindness among anesthesiologists.

PURPOSE: Medical errors may be occasionally explained by inattentional blindness (IB), i.e., failing to notice an event/object that is in plain sight. We aimed to determine whether age/experience, restfulness/fatigue, and previous exposure to simulation education may affect IB in the anesthetic/surgical setting. METHODS: In this multicentre/multinational study, a convenience sample of 280 anesthesiologists watched an attention-demanding video of a simulated trauma patient undergoing laparotomy and (independently/anonymously) recorded the abnormalities they noticed. The video contained four expected/common abnormalities (hypotension, tachycardia, hypoxia, hypothermia) and two prominently displayed unexpected/rare events (patient's head movement, leaky central venous line). We analyzed the participants' ability to notice the expected/unexpected events (primary outcome) and the proportion of expected/unexpected events according to age group and prior exposure to simulation education (secondary outcomes). RESULTS: Anesthesiologists across all ages noticed fewer unexpected/rare events than expected/common ones. Overall, younger anesthesiologists missed fewer common events than older participants did (P = 0.02). There was no consistent association between age and perception of unexpected/rare events (P = 0.28), although the youngest cohort (< 30 yr) outperformed the other age groups. Prior simulation education did not affect the proportion of misses for the unexpected/rare events but was associated with fewer misses for the expected/common events. Self-perceived restfulness did not impact perception of events. CONCLUSION: Anesthesiologists noticed fewer unexpected/rare clinical events than expected/common ones in an attention-demanding video of a simulated trauma patient, in keeping with IB. Prior simulation training was associated with an improved ability to notice anticipated/expected events, but did not reduce IB. Our findings may have implications for understanding medical mishaps, and efforts to improve situational awareness, especially in acute perioperative and critical care settings.

RéSUMé: OBJECTIF: Les erreurs médicales peuvent parfois s'expliquer par la cécité d'inattention, soit le fait de ne pas remarquer un événement/objet qui est à la vue de tous et toutes. Notre objectif était de déterminer si l'âge/l'expérience, le repos/la fatigue et l'exposition antérieure à l'enseignement par simulation pouvaient affecter la cécité d'inattention dans le cadre de l'anesthésie/chirurgie. MéTHODE: Dans cette étude multicentrique/multinationale, un échantillon de convenance de 280 anesthésiologistes ont visionné une vidéo exigeant l'attention portant sur un patient de trauma simulé bénéficiant d'une laparotomie et ont enregistré (de manière indépendante/anonyme) les anomalies qu'ils et elles ont remarquées. La vidéo contenait quatre anomalies attendues/courantes (hypotension, tachycardie, hypoxie, hypothermie) et deux événements inattendus/rares bien en vue (mouvement de la tête du patient, fuite du cathéter veineux central). Nous avons analysé la capacité des participant·es à remarquer les événements attendus/inattendus (critère d'évaluation principal) et la proportion d'événements attendus/inattendus selon le groupe d'âge et l'exposition antérieure à l'enseignement par simulation (critères d'évaluation secondaires). RéSULTATS: Les anesthésiologistes de tous âges ont remarqué moins d'événements inattendus/rares que d'événements attendus/courants. Globalement, les anesthésiologistes plus jeunes ont manqué moins d'événements courants que leurs congénères plus âgé·es (P = 0,02). Il n'y avait pas d'association constante entre l'âge et la perception d'événements inattendus ou rares (P = 0,28), bien que la cohorte la plus jeune (< 30 ans) ait surpassé les autres groupes d'âge. La formation antérieure par simulation n'a pas eu d'incidence sur la proportion d'inobservation des événements inattendus ou rares, mais a été associée à moins de cécité d'inattention envers les événements attendus ou courants. Le repos perçu n'a pas eu d'impact sur la perception des événements. CONCLUSION: Les anesthésiologistes ont remarqué moins d'événements cliniques inattendus/rares que d'événements attendus/courants dans une vidéo exigeant l'attention portant sur la simulation d'un patient traumatisé, ce qui s'inscrit dans la cécité d'inattention. La formation préalable par simulation était associée à une meilleure capacité à remarquer les événements anticipés/attendus, mais ne réduisait pas la cécité d'inattention. Nos résultats peuvent avoir des implications pour la compréhension des accidents médicaux et les efforts visant à améliorer la conscience situationnelle, en particulier dans les contextes de soins périopératoires aigus et de soins intensifs.

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.].

Improved maize reference genome with single-molecule technologies.

Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes.

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.

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.

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.

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.

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.

Graph Quality in Top Medical Journals.

STUDY OBJECTIVE: Well-designed graphs can portray complex data and relationships in ways that are easier to interpret and understand than text and tables. Previous investigations of reports of clinical research showed that graphs are underused and, when used, often depict summary statistics instead of the data distribution. This descriptive study aims to evaluate the quantity and quality of graphs in the current medical literature across a broad range of better journals. METHODS: We performed a cross-sectional survey of 10 randomly selected original research articles per journal from the 2012 issues of 20 highly cited journals. We identified which figures were data graphs and limited analysis to a maximum of 5 randomly selected data graphs per article. We then described the graph type, data density, completeness, visual clarity, special features, and dimensionality of each graph in the sample. RESULTS: We analyzed 342 data graphs published in 20 journals. Our sample had a geometric mean data density index across all graphs of 1.18 data elements/cm2. More than half (54%) of the data graphs were simple univariate displays such as line or bar graphs. When analyzed by journal, excellence in one domain (completeness, visual clarity, or special features) was not strongly predictive of excellence in the other domains. CONCLUSION: Despite that graphs can efficiently and effectively convey complex study findings, we found their infrequent use and low data density to be the norm. The majority of graphs were univariate ones that failed to display the overall distribution of data.

Assessing severity, immediacy, and ideal setting in ED patients: a pilot study on interrater reliability.

OBJECTIVES: We conducted a pilot study to test the interrater reliability of emergency department (ED) physician assessments of 3 ED visit attributes-severity, immediacy, and ideal setting, with the long-term goal of developing a novel ED categorization system. METHODS: Using 2010 National Hospital Ambulatory Care Survey data, we randomly selected 300 ED patient records for review by 6 emergency medicine physicians. Each record was assessed by 2 physicians for severity and immediacy using a 7-point scale; "ideal" setting was chosen among 6 possible settings. κ-Weighted and unweighted-and interclass correlation coefficients were used to test interrater agreement. RESULTS: For severity, immediacy, and ideal setting, there was "fair" agreement in assessments with a weighted κ of 0.33 (95% confidence interval [CI], 0.27-0.40), 0.30 (95% CI, 0.23-0.36), and nonweighted κ of 0.28 (95% CI, 0.21-0.34), respectively. When both raters were "very certain" about their assessments, weighted κ increased to 0.42 (95% CI, 0.34-0.51) for severity and 0.35 (95% CI, 0.27-0.44) for immediacy. Interclass correlation coefficients showed similar results. There was agreement on ideal setting for 162 (54%) of 300 scenarios. Scenarios with poor agreement on ideal setting in general involved care for nonspecific symptoms rather than specific diagnoses. CONCLUSIONS: Rater agreement among ED physicians when assessing clinical data on specific ED visits was fair for severity and immediacy ratings. Raters agreed on ideal treatment settings half the time. In general, there was greater agreement when a specific diagnosis was found rather than negative workups for symptoms. This demonstrates a validity issue when it comes to developing and using categorization systems for ED visits and assessing setting appropriateness.

Intraperitoneal ketorolac for post-cholecystectomy pain: a double-blind randomized-controlled trial.

PURPOSE: Ketorolac is a parenterally active nonsteroidal anti-inflammatory drug with localized anti-inflammatory properties. We examine the postoperative analgesic efficacy of locally administered intraperitoneal (IP) ketorolac compared with intravenous (IV) ketorolac during laparoscopic cholecystectomy. METHODS: With institutional ethics approval, 120 patients undergoing elective laparoscopic cholecystectomy were randomized to receive intraoperative 1) IP ketorolac 30 mg + intravenous saline (IP group), 2) intraperitoneal saline + IV ketorolac 30 mg (IV group), or 3) intraperitoneal saline + intravenous saline (Control group) under standardized anesthesia. The primary and secondary outcomes were postoperative fentanyl requirements in the postanesthesia care unit and the time to first analgesic request, respectively. Other outcomes examined included abdominal pain (at rest and with coughing), shoulder pain, nausea, vomiting, and any other postoperative complications. RESULTS: On average, patients receiving IP ketorolac required less (mean difference, 29 µg; 95% confidence interval [CI], 2 to 56; P = 0.04) fentanyl than patients in the Control group but a similar (mean difference, 16 µg; 95% CI, 12 to 43; P = 0.27) amount compared to patients in the IV group. There was an increase in the median (interquartile range [IQR]) time to first request in the IP group (43[30-52] min) compared with the Control group (35 [27-49]min; P = 0.04) but no difference between the IP group compared with the IV group (47 [40-75] min; P = 0.22). Shoulder pain and resting pain were reduced with IP and IV ketorolac compared with Control, but there was no difference between the IP and IV groups. No differences were observed in any other outcomes, side effects, or complications attributable to opioids or ketorolac at any time points. CONCLUSION: This study did not demonstrate any advantage for the off-label topical intraperitoneal administration of ketorolac in this surgical population. Intraperitoneal and IV ketorolac showed comparable analgesic efficacy following laparoscopic cholecystectomy.

Identification of QTL for resistance to Mediterranean corn borer in a maize tropical line to improve temperate germplasm.

BACKGROUND: A QTL mapping study for maize resistance to the Mediterranean corn borer (MCB) was performed with a RIL population derived from the cross B73 × CML103. To develop commercial inbreds of maize resistant to the MCB for use in Europe, it would be useful to transfer resistance from tropical germplasm like the subtropical inbred CML103 to temperate lines. The inbred B73 was chosen as representative of the Stiff Stock heterotic group, a major heterotic group used in hybrid grown in both North American and Europe. The objectives were to study the architecture of genetic factors for resistance to MCB and to check the feasibility of using marker-assisted selection (MAS) for transferring those genetic factors. RESULTS: Eight quantitative trait loci (QTL) were declared significant for resistance traits and eight QTL were located for agronomic traits. Alleles from CML103 at QTL significant for tunnel length could reduce tunnel length made for MCB in inbred B73 in more than 8 cm; favorable alleles for yield were also found in CML103 and no genetic correlation coefficient between tunnel length and yield was detected. CONCLUSIONS: MAS for transferring resistance genes to corn borer attack from CML103 to B73 could be successful based on cross validation results and a negative effect on yield would not be expected.

Prolonged expression of the BX1 signature enzyme is associated with a recombination hotspot in the benzoxazinoid gene cluster in Zea mays.

Benzoxazinoids represent preformed protective and allelopathic compounds. The main benzoxazinoid in maize (Zea mays L.) is 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA confers resistance to herbivores and microbes. Protective concentrations are found predominantly in young plantlets. We made use of the genetic diversity present in the maize nested association mapping (NAM) panel to identify lines with significant benzoxazinoid concentrations at later developmental stages. At 24 d after imbibition (dai), only three lines, including Mo17, showed effective DIMBOA concentrations of 1.5mM or more; B73, by contrast, had low a DIMBOA content. Mapping studies based on Mo17 and B73 were performed to reveal mechanisms that influence the DIMBOA level in 24 dai plants. A major quantitative trait locus mapped to the Bx gene cluster located on the short arm of chromosome 4, which encodes the DIMBOA biosynthetic genes. Mo17 was distinguished from all other NAM lines by high transcriptional expression of the Bx1 gene at later developmental stages. Bx1 encodes the signature enzyme of the pathway. In Mo17×B73 hybrids at 24 dai, only the Mo17 Bx1 allele transcript was detected. A 3.9kb cis-element, termed DICE (distal cis-element), that is located in the Bx gene cluster approximately 140 kb upstream of Bx1, was required for high Bx1 transcript levels during later developmental stages in Mo17. The DICE region was a hotspot of meiotic recombination. Genetic analysis revealed that high 24 dai DIMBOA concentrations were not strictly dependent on high Bx1 transcript levels. However, constitutive expression of Bx1 in transgenics increased DIMBOA levels at 24 dai, corroborating a correlation between DIMBOA content and Bx1 transcription.

A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.

Pericarp Color1 (P1) encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize (Zea mays) silks and red phlobaphene pigments in pericarps and other floral tissues, which makes P1 an important visual marker. Using genome-wide expression analyses (RNA sequencing) in pericarps and silks of plants with contrasting P1 alleles combined with chromatin immunoprecipitation coupled with high-throughput sequencing, we show here that the regulatory functions of P1 are much broader than the activation of genes corresponding to enzymes in a branch of flavonoid biosynthesis. P1 modulates the expression of several thousand genes, and ∼1500 of them were identified as putative direct targets of P1. Among them, we identified F2H1, corresponding to a P450 enzyme that converts naringenin into 2-hydroxynaringenin, a key branch point in the P1-controlled pathway and the first step in the formation of insecticidal C-glycosyl flavones. Unexpectedly, the binding of P1 to gene regulatory regions can result in both gene activation and repression. Our results indicate that P1 is the major regulator for a set of genes involved in flavonoid biosynthesis and a minor modulator of the expression of a much larger gene set that includes genes involved in primary metabolism and production of other specialized compounds.

ZmCCT and the genetic basis of day-length adaptation underlying the postdomestication spread of maize.

Teosinte, the progenitor of maize, is restricted to tropical environments in Mexico and Central America. The pre-Columbian spread of maize from its center of origin in tropical Southern Mexico to the higher latitudes of the Americas required postdomestication selection for adaptation to longer day lengths. Flowering time of teosinte and tropical maize is delayed under long day lengths, whereas temperate maize evolved a reduced sensitivity to photoperiod. We measured flowering time of the maize nested association and diverse association mapping panels in the field under both short and long day lengths, and of a maize-teosinte mapping population under long day lengths. Flowering time in maize is a complex trait affected by many genes and the environment. Photoperiod response is one component of flowering time involving a subset of flowering time genes whose effects are strongly influenced by day length. Genome-wide association and targeted high-resolution linkage mapping identified ZmCCT, a homologue of the rice photoperiod response regulator Ghd7, as the most important gene affecting photoperiod response in maize. Under long day lengths ZmCCT alleles from diverse teosintes are consistently expressed at higher levels and confer later flowering than temperate maize alleles. Many maize inbred lines, including some adapted to tropical regions, carry ZmCCT alleles with no sensitivity to day length. Indigenous farmers of the Americas were remarkably successful at selecting on genetic variation at key genes affecting the photoperiod response to create maize varieties adapted to vastly diverse environments despite the hindrance of the geographic axis of the Americas and the complex genetic control of flowering time.

A unified mixed-model method for association mapping that accounts for multiple levels of relatedness.

As population structure can result in spurious associations, it has constrained the use of association studies in human and plant genetics. Association mapping, however, holds great promise if true signals of functional association can be separated from the vast number of false signals generated by population structure. We have developed a unified mixed-model approach to account for multiple levels of relatedness simultaneously as detected by random genetic markers. We applied this new approach to two samples: a family-based sample of 14 human families, for quantitative gene expression dissection, and a sample of 277 diverse maize inbred lines with complex familial relationships and population structure, for quantitative trait dissection. Our method demonstrates improved control of both type I and type II error rates over other methods. As this new method crosses the boundary between family-based and structured association samples, it provides a powerful complement to currently available methods for association mapping.

Distinct genetic architectures for male and female inflorescence traits of maize.

We compared the genetic architecture of thirteen maize morphological traits in a large population of recombinant inbred lines. Four traits from the male inflorescence (tassel) and three traits from the female inflorescence (ear) were measured and studied using linkage and genome-wide association analyses and compared to three flowering and three leaf traits previously studied in the same population. Inflorescence loci have larger effects than flowering and leaf loci, and ear effects are larger than tassel effects. Ear trait models also have lower predictive ability than tassel, flowering, or leaf trait models. Pleiotropic loci were identified that control elongation of ear and tassel, consistent with their common developmental origin. For these pleiotropic loci, the ear effects are larger than tassel effects even though the same causal polymorphisms are likely involved. This implies that the observed differences in genetic architecture are not due to distinct features of the underlying polymorphisms. Our results support the hypothesis that genetic architecture is a function of trait stability over evolutionary time, since the traits that changed most during the relatively recent domestication of maize have the largest effects.

Genetic architecture of maize kernel composition in the nested association mapping and inbred association panels.

The maize (Zea mays) kernel plays a critical role in feeding humans and livestock around the world and in a wide array of industrial applications. An understanding of the regulation of kernel starch, protein, and oil is needed in order to manipulate composition to meet future needs. We conducted joint-linkage quantitative trait locus mapping and genome-wide association studies (GWAS) for kernel starch, protein, and oil in the maize nested association mapping population, composed of 25 recombinant inbred line families derived from diverse inbred lines. Joint-linkage mapping revealed that the genetic architecture of kernel composition traits is controlled by 21-26 quantitative trait loci. Numerous GWAS associations were detected, including several oil and starch associations in acyl-CoA:diacylglycerol acyltransferase1-2, a gene that regulates oil composition and quantity. Results from nested association mapping were verified in a 282 inbred association panel using both GWAS and candidate gene association approaches. We identified many beneficial alleles that will be useful for improving kernel starch, protein, and oil content.

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.

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.