Stridor and severe subglottic stenosis: emergency tracheostomy for a neonate with a pinhole trachea.

Congenital subglottic stenosis is a rare but potentially catastrophic condition. In this report, we describe the management of a term neonate who was noted to have biphasic stridor during preassessment for correction of an imperforate anus at 26 hours of life. The neonate was found to have a pinhole trachea secondary to congenital subglottic stenosis. It was impossible to pass an endotracheal tube, so the neonate underwent an emergency surgical tracheostomy with a good outcome. A high index of suspicion led to appropriate steps being taken to safely anaesthetise the neonate.

Altered tongue muscle contractile properties coincide with altered swallow function in the adult Ts65Dn mouse model of down syndrome.

Purpose: Down syndrome (DS) is a developmental disability associated with difficulties in deglutition. The adult Ts65Dn mouse model of DS has been previously shown to have differences in measures of swallowing compared with euploid controls. However, the putative mechanisms of these differences in swallowing function are unclear. This study tested the hypothesis that the Ts65Dn genotype is associated with atypical measures of tongue muscle contractile properties, coinciding with atypical swallow function. Methods: Adult (5-month-old) Ts65Dn (n = 15 female, 14 male) and euploid sibling controls (n = 16 female, 14 male) were evaluated through videofluoroscopy swallow studies (VFSS) to quantify measures of swallowing performance including swallow rate and inter-swallow interval (ISI). After VFSS, retrusive tongue muscle contractile properties, including measures of muscle fatigue, were determined using bilateral hypoglossal nerve stimulation. Results: The Ts65Dn group had significantly slower swallow rates, significantly greater ISI times, significantly slower rates of tongue force development, and significantly greater levels of tongue muscle fatigue, with lower retrusive tongue forces than controls in fatigue conditions. Conclusion: Tongue muscle contractile properties are altered in adult Ts65Dn and coincide with altered swallow function.

Ynamide and Azaalleneyl. Acid-Base Promoted Chelotropic and Spin-State Rearrangements in a Versatile Heterocumulene [(Ad)NCC(tBu)].

We introduce the heterocumulene ligand [(Ad)NCC(tBu)]- (Ad=1-adamantyl (C10H15), tBu=tert-butyl, (C4H9)), which can adopt two forms, the azaalleneyl and ynamide. This ligand platform can undergo a reversible chelotropic shift using Brønsted acid-base chemistry, which promotes an unprecedented spin-state change of the [VIII] ion. These unique scaffolds are prepared via addition of 1-adamantyl isonitrile (C≡NAd) across the alkylidyne in complexes [(BDI)V≡CtBu(OTf)] (A) (BDI-=ArNC(CH3)CHC(CH3)NAr), Ar=2,6-iPr2C6H3) and [(dBDI)V≡CtBu(OEt2)] (B) (dBDI2-=ArNC(CH3)CHC(CH2)NAr). Complex A reacts with C≡NAd, to generate the high-spin [VIII] complex with a κ1-N-ynamide ligand, [(BDI)V{κ1-N-(Ad)NCC(tBu)}(OTf)] (1). Conversely, B reacts with C≡NAd to generate a low-spin [VIII] diamagnetic complex having a chelated κ2-C,N-azaalleneyl ligand, [(dBDI)V{κ2-N,C-(Ad)NCC(tBu)}] (2). Theoretical studies have been applied to better understand the mechanism of formation of 2 and the electronic reconfiguration upon structural rearrangement by the alteration of ligand denticity between 1 and 2.

General Surgery Resident Participation in a Mandatory Wellness Program: Six Years Later.

INTRODUCTION: Following the approval of a resident-created physician wellness program in 2016, an initial survey demonstrated majority support for the implementation of a mandatory curriculum. The purpose of this study is to survey surgical residents about the wellness curriculum six years after implementation and re-evaluate preference for mandatory participation. METHODS: In 2016, the CORE7 Wellness Program didactic sessions were integrated into the general surgery resident education curriculum. A comparison between 2016 and 2022 resident survey results was done to examine overall approval and resident experience. RESULTS: A total of 25 general surgery residents responded to the 2022 survey which equaled to a response rate of 67.5% compared to a response rate of 87.1% in 2016. Similar to the results in 2016, there was unanimous support (100%, n = 25) in favor of the ongoing development of a general surgery wellness program. The majority of residents (88% versus 85.2% in 2016) preferred quarterly "wellness half-days" remain a mandatory component of the program. In 2016, most of the residents (50%) stated that the reason for mandatory preference for wellness half-days was ease of explanation to faculty. In 2022, the reason changed to a combination of reasons with most residents (59%) selecting ease of explanation to attendings, feeling too guilty otherwise to leave the shift, and forcing the resident to think about self-care. Complaints about taking a wellness half-day from other team members increased from 29% in 2016 to 48% in 2022. CONCLUSIONS: Six years after implementation, there is unanimous support for the mandatory components of a general surgery residency wellness curriculum. Increased perceived complaints from faculty and staff about resident wellness present an opportunity for improvement.

Minimally-invasive airway management and early cleft palate repair in infants born with Robin sequence.

The objective of this study was to report outcomes of early cleft palate repair in infants born with Robin sequence (RS). A retrospective case series in a tertiary referral paediatric hospital was carried out, examining a consecutive series of 69 infants born with RS and cleft palate. A minimally invasive approach was taken to upper airway obstruction, with liberal nasopharyngeal airway (NPA) and non-invasive ventilation (NIV) use, guided by sleep studies. The palate was repaired between 6 and 9 months with a modified Malek technique. The most frequently used airway adjunct (59.4% of patients) was an NPA and the median duration of use was 5.6 months. All patients underwent a modified Malek cleft palate repair at a median of 7 months of age. Overnight oximetry demonstrated higher mean oxygen saturation (SpO2) across the group from initial neonatal admission to discharge (median 96.5% (interquartile range [IQR] 95-98%) vs 97.45% (IQR 96.5-98%) (P = 0.2, N = 34). Of those with a cardiorespiratory polysomnogram, the obstructive apnoea-hypopnea index (OAHI) was significantly lower postoperatively (5.9 vs 2.8, P = 0.028). This study supports the use of non-surgical airway strategies and early cleft palate repair in infants born with RS and cleft palate.

Histological, chemical and gene expression differences between western redcedar seedlings resistant and susceptible to cedar leaf blight.

Introduction: Western redcedar (Thuja plicata) is an important species in the Cupressaceae both at economic and cultural levels in the Pacific Northwest of North America. In adult trees, the species produces one of the most weathering-resistant heartwoods among conifers, making it one of the preferred species for outdoor applications. However, young T. plicata plants are susceptible to infection with cedar leaf blight (Didymascella thujina), an important foliar pathogen that can be devastating in nurseries and small-spaced plantations. Despite that, variability in the resistance against D. thujina in T. plicata has been documented, and such variability can be used to breed T. plicata for resistance against the pathogen. Objective: This investigation aimed to discern the phenotypic and gene expression differences between resistant and susceptible T. plicata seedlings to shed light on the potential constitutive resistance mechanisms against cedar leaf blight in western redcedar. Methods: The study consisted of two parts. First, the histological differences between four resistant and four susceptible families that were never infected with the pathogen were investigated. And second, the differences between one resistant and one susceptible family that were infected and not infected with the pathogen were analyzed at the chemical (C, N, mineral nutrients, lignin, fiber, starch, and terpenes) and gene expression (RNA-Seq) levels. Results: The histological part showed that T. plicata seedlings resistant to D. thujina had constitutively thicker cuticles and lower stomatal densities than susceptible plants. The chemical analyses revealed that, regardless of their infection status, resistant plants had higher foliar concentrations of sabinene and α-thujene, and higher levels of expression of transcripts that code for leucine-rich repeat receptor-like protein kinases and for bark storage proteins. Conclusion: The data collected in this study shows that constitutive differences at the phenotypic (histological and chemical) and gene expression level exist between T. plicata seedlings susceptible and resistant to D. thujina. Such differences have potential use for marker-assisted selection and breeding for resistance against cedar leaf blight in western redcedar in the future.

Vanadium Alkylidyne Initiated Cyclic Polymer Synthesis: The Importance of a Deprotiovanadacyclobutadiene Moiety.

Reported is the catalytic cyclic polymer synthesis by a 3d transition metal complex: a V(V) alkylidyne, [(dBDI)V≡CtBu(OEt2)] (1-OEt2), supported by the deprotonated ß-diketiminate dBDI2- (dBDI2- = ArNC(CH3)CHC(CH2)NAr, Ar = 2,6-iPr2C6H3). Complex 1-OEt2 is a precatalyst for the polymerization of phenylacetylene (PhCCH) to give cyclic poly(phenylacetylene) (c-PPA), whereas its precursor, complex [(BDI)V≡CtBu(OTf)] (2-OTf; BDI- = [ArNC(CH3)]2CH, Ar = 2,6-iPr2C6H3, OTf = OSO2CF3), and the zwitterion [((C6F5)3B-dBDI)V≡CtBu(OEt2)] (3-OEt2) exhibit low catalytic activity despite having a neopentylidyne ligand. Cyclic polymer topologies were verified by size-exclusion chromatography (SEC) and intrinsic viscosity studies. A component of the mechanism of the cyclic polymerization reaction was probed by isolation and full characterization of 4- and 6-membered metallacycles as model intermediates. Metallacyclobutadiene (MCBD) and deprotiometallacyclobutadiene (dMCBD) complexes (dBDI)V[C(tBu)C(H)C(tBu)] (4-tBu) and (BDI)V[C(tBu)CC(Mes)] (5-Mes), respectively, were synthesized upon reaction with bulkier alkynes, tBu- (tBuCCH) and Mes-acetylene (MesCCH), with 1-OEt2. Furthermore, the reaction of the conjugate acid of 1-OEt2, [(BDI)V≡CtBu(OTf)] (2-OTf), with the conjugated base of phenylacetylene, lithium phenylacetylide (LiCCPh), yields the doubly deprotio-metallacycle complex, [Li(THF)4]{(BDI)V[C(Ph)CC(tBu)CC(Ph)]} (6). Protonation of the doubly deprotio-metallacycle complex 6 yields 6-H+, a catalytically active species toward the polymerization of PhCCH, for which the polymers were also confirmed to be cyclic by SEC studies. Computational mechanistic studies complement the experimental observations and provide insight into the mechanism of cyclic polymer growth. The noninnocence of the supporting dBDI2- ligand and its role in proton shuttling to generate deprotiometallacyclobutadiene (dMCBD) complexes that proposedly culminate in the formation of catalytically active V(III) species are also discussed. This work demonstrates how a dMCBD moiety can react with terminal alkynes to form cyclic polyalkynes.

Tongue and laryngeal exercises improve tongue strength and vocal function outcomes in a Pink1-/- rat model of early Parkinson disease.

Parkinson disease (PD) causes voice and swallow dysfunction even in early stages of the disease. Treatment of this dysfunction is limited, and the neuropathology underlying this dysfunction is poorly defined. Targeted exercise provides the greatest benefit for offsetting voice and swallow dysfunction, and previous data suggest the hypoglossal nucleus and noradrenergic-locus coeruleus (LC) may be involved in its early pathology. To investigate relationships between targeted exercise and neuropathology of voice and swallow dysfunction, we implemented a combined exercise paradigm that included tongue force and vocalization exercises early in the Pink1-/- rat model. We tested the hypotheses that (1) tongue and vocal exercise improves tongue force and timing behaviors and vocalization outcomes, and (2) exercise increases optical density of serotonin (5-HT) in the hypoglossal nucleus, and tyrosine hydroxylase immunoreactive (Th-ir) cell counts in the LC. At two months of age Pink1-/- rats were randomized to exercise or non-exercise treatment. Age-matched wildtype (WT) control rats were assigned to non-exercise treatment. Tongue force and timing behaviors and ultrasonic vocalizations were measured at baseline (two months) and final (four months) timepoints. Optical density of 5-HT in the hypoglossal nucleus and TH-ir cell counts in the LC were obtained. Pink1-/- rats produced greater tongue forces, faster tongue contraction, and higher-intensity vocalization following exercise. There were no differences in LC TH-ir. The non-exercised Pink1-/- group had reduced density of 5-HT in the hypoglossal nucleus compared to the WT control group. The changes to tongue function and vocalization after targeted exercise suggests exercise intervention may be beneficial in early PD.

International pediatric otolaryngology group (IPOG) consensus on approach to aspiration.

OBJECTIVE: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration. METHODS: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step. RESULTS: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children. CONCLUSION: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options.

Metallacyclobuta-(2,3)-diene: A Bidentate Ligand for Stream-line Synthesis of First Row Transition Metal Catalysts for Cyclic Polymerization of Phenylacetylene.

Described here is a direct entry to two examples of 3d transition metal catalysts that are active for the cyclic polymerization of phenylacetylene, namely, [(BDI)M{κ2 -C,C-(Me3 SiC3 SiMe3 )}] (2-M) (BDI=[ArNC(CH3 )]2 CH- , Ar=2,6-i Pr2 C6 H3 ; M=Ti, V). Catalysts are prepared in one step by the treatment of [(BDI)MCl2 ] (1-M, M=Ti, V) with 1,3-dilithioallene [Li2 (Me3 SiC3 SiMe3 )]. Complexes 2-M have been spectroscopically and structurally characterized and the polymers that are catalytically formed from phenylacetylene were verified to have a cyclic topology based on a combination of size-exclusion chromatography (SEC) and intrinsic viscosity studies. Two-electron oxidation of 2-V with nitrous oxide (N2 O) cleanly yields a [VV ] alkylidene-alkynyl oxo complex [(BDI)V(=O){κ1 -C-(=C(SiMe3 )CC(SiMe3 ))}] (3), which lends support for how this scaffold in 2-M might be operating in the polymerization of the terminal alkyne. This work demonstrates how alkylidynes can be circumvented using 1,3-dianionic allene as a segue into M-C multiple bonds.

Age-related sex differences in tongue strength and muscle morphometry in a rat model.

OBJECTIVE: To investigate potential effects of sex on voluntary tongue strength, evoked twitch and tetanic tension, speed of contraction, and muscle fiber cross-sectional area in the muscles of the rat tongue. Additionally, we aimed to determine whether estrous cycle stage impacts any of the dependent variables as a pilot investigation into the use of female rats in a model of tongue exercise and aging. DESIGN: Fischer 344-Brown Norway male and female rats in two age groups (16 middle-aged, 16 young-adult) were trained to use a tongue force operandum. Tongue muscle contraction, myosin heavy chain (MyHC) composition, and cross section area of the genioglossus and styloglossus muscles were examined. Vaginal lavage determined estrous cycle stage of the female rats daily. RESULTS: The female group had significantly lower evoked twitch and tetanic tension, longer contraction times, and a smaller proportion of MyHC type IIa and MyHC type IIx in the styloglossus muscle. There was no significant sex effect in maximal voluntary tongue force (MVTF) despite a significant weight difference between the male and female groups. There were no significant age or sex effects in the genioglossus. Estrous cycle stage did not have a significant effect on any of the dependent variables. CONCLUSIONS: Sex and age both have a significant effect on tongue muscle structure and physiology. While the female group showed reduced contraction speed and maximal twitch and tetanic tension relative to the male group, differences in muscle morphology appeared to vary by muscle.

PAUSE: principled feature attribution for unsupervised gene expression analysis.

As interest in using unsupervised deep learning models to analyze gene expression data has grown, an increasing number of methods have been developed to make these models more interpretable. These methods can be separated into two groups: post hoc analyses of black box models through feature attribution methods and approaches to build inherently interpretable models through biologically-constrained architectures. We argue that these approaches are not mutually exclusive, but can in fact be usefully combined. We propose PAUSE ( https://github.com/suinleelab/PAUSE ), an unsupervised pathway attribution method that identifies major sources of transcriptomic variation when combined with biologically-constrained neural network models.

Comprehensive management of anterior drooling: An International Pediatric Otolaryngology Group (IPOG) consensus statement.

OBJECTIVE: To provide guidance for the comprehensive management of children referred for anterior drooling. The mission of the International Pediatric Otolaryngology Group (IPOG) is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. METHODS: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). The recommendations are derived from current expert consensus and critical review of the literature. RESULTS: Consensus recommendations include initial care and approach recommendations for health care providers who commonly evaluate children with drooling. This includes evaluation and treatment considerations for commonly debated issues in drooling management, initial work-up of children referred for anterior drooling, treatment recommendations, indications and contra-indications for rehabilitation, medical, and surgical management, as well as pros and cons of different surgical procedures in the hands of drooling management experts. CONCLUSION: Anterior drooling consensus recommendations are aimed at improving patient-centered care in children referred for sialorrhea.

Genetic architecture of terpene chemistry and growth traits and the impact of inbreeding on these traits in western redcedar (Thuja plicata).

Western redcedar (WRC; Thuja plicata) is a conifer of the Pacific Northwest of North America prized for its durable and rot-resistant wood. WRC has naturally low outcrossing rates and readily self-fertilizes in nature. Challenges faced in WRC breeding and propagation involve selecting trees for accelerated growth while also ensuring enhanced heartwood rot resistance and resistance to ungulate browsing, as well as mitigating potential effects of inbreeding depression. Terpenes, a large and diverse class of specialized metabolites, confer both rot and browse resistance in the wood and foliage of WRC, respectively. Using a Bayesian modelling approach, we isolated single nucleotide polymorphism (SNP) markers estimated to be associated with three different foliar terpene traits and four different heartwood terpene traits, as well as two growth traits. We found that all traits were complex, being associated with between 1700 and 3600 SNPs linked with putatively causal loci, with significant polygenic components. Growth traits tended to have a larger polygenic component while terpene traits had larger major gene components; SNPs with small or polygenic effect were spread across the genome, while larger-effect SNPs tended to be localized to specific linkage groups. To determine whether there was inbreeding depression for terpene chemistry or growth traits, we used mixed linear models for a genomic selection training population to estimate the effect of the inbreeding coefficient F on foliar terpenes, heartwood terpenes and several growth and dendrochronological traits. We did not find significant inbreeding depression for any assessed trait. We further assessed inbreeding depression across four generations of complete selfing and found that not only was inbreeding depression not significant but that selection for height growth was the only significant predictor for growth during selfing, suggesting that inbreeding depression due to selfing during operational breeding can be mitigated by increased selection intensity.

International Pediatric Otolaryngology Group: Consensus guidelines on the diagnosis and management of non-tuberculous mycobacterial cervicofacial lymphadenitis.

INTRODUCTION: Non-tuberculous mycobacterial (NTM) infection commonly manifests as subacute or chronic cervicofacial lymphadenitis in immunocompetent children. The optimal management of this pathology remains controversial. OBJECTIVES: This international consensus guideline aims to understand the practice patterns for NTM cervicofacial lymphadenitis and to address the primary diagnostic and management challenges. METHODS: A modified three-iterative Delphi method was used to establish expert recommendations on the diagnostic considerations, expectant or medical management, and operative considerations. The recommendations herein are derived from current expert consensus and critical review of the literature. SETTING: Multinational, multi-institutional, tertiary pediatric hospitals. RESULTS: Consensus recommendations include diagnostic work-up, goals of treatment and management options including surgery, prolonged antibiotic therapy and observation. CONCLUSION: The recommendations formulated in this International Pediatric Otolaryngology Group (IPOG) consensus statement on the diagnosis and management of patients with NTM lymphadenitis are aimed at improving patient care and promoting future hypothesis generation.

Tocilizumab for the treatment of chronic antibody mediated rejection in kidney transplant recipients.

BACKGROUND: Chronic active antibody-mediated rejection (CAAMR) constitutes a dominant form of late allograft failure. Several treatment strategies directed at CAAMR have been attempted but proven ineffective at delaying kidney function decline or reducing donor-specific antibodies (DSA). We describe our single-center experience using tocilizumab in patients with CAAMR. METHODS: This is a retrospective analysis using electronic medical records. 38 kidney transplant recipients at Columbia University Irving Medical Center who had been prescribed tocilizumab and followed for at least 3 months between August 2013 through December 2019 were included. RESULTS: Tocilizumab use was associated with a decrease in the rate of estimated glomerular filtration rate (eGFR) decline in the 6 months following treatment initiation as compared to the 3 months before tocilizumab was initiated (difference between slopes before and after initiation of treatment = 2.6 mL/min/1.73 m2 (SE = .8, p = .002) per month for up to 6 months following Tocilizumab initiation). Allograft biopsies showed significant improvement in interstitial inflammation scores (score 1(0,1) to 0 (0,1), p = .03) while other histologic scores remained stable. There was no significant change in proteinuria or DSA titers post-treatment with tocilizumab. CONCLUSIONS: Treatment of CAAMR with tocilizumab was associated with a decrease in the rate of eGFR decline and a reduction in interstitial inflammation scores in patients with CAAMR.

Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of ß-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated TgF344-AD (F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans. Objectives: The overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the TgF344-AD rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits. Methods: USVs were collected from male TgF344-AD (N = 19) and wildtype (WT) Fischer-344 rats (N = 19) at 6 months (N = 38; WT: n = 19; TgF344-AD: n = 19) and 9 months of age (N = 18; WT: n = 10; TgF344-AD: n = 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male TgF344-AD rats (n = 6) and WT rats (n = 6) at 12 months of age. Results: This study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in TgF344-AD rats compared to WT controls. Additionally, significant downregulation of AD-related genes Uqcrc2, Bace2, Serpina3n, and Igf2, as well as downregulation of pro-inflammatory gene Myd88 was found in the TA muscle of TgF344-AD rats at 12 months of age. Discussion: Our findings demonstrate early and progressive vocal deficits in the TgF344-AD rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of TgF344-AD rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology.

Genomic selection reveals hidden relatedness and increased breeding efficiency in western redcedar polycross breeding.

Western redcedar (WRC) is an ecologically and economically important forest tree species characterized by low genetic diversity with high self-compatibility and high heartwood durability. Using sequence capture genotyping of target genic and non-genic regions, we genotyped 44 parent trees and 1520 offspring trees representing 26 polycross (PX) families collected from three progeny test sites using 45,378 SNPs. Trees were phenotyped for eight traits related to growth, heartwood and foliar chemistry associated with wood durability and deer browse resistance. We used the genomic realized relationship matrix for paternity assignment, maternal pedigree correction, and to estimate genetic parameters. We compared genomics-based (GBLUP) and two pedigree-based (ABLUP: polycross and reconstructed full-sib [FS] pedigrees) models. Models were extended to estimate dominance genetic effects. Pedigree reconstruction revealed significant unequal male contribution and separated the 26 PX families into 438 FS families. Traditional maternal PX pedigree analysis resulted in up to 51% overestimation in genetic gain and 44% in diversity. Genomic analysis resulted in up to 22% improvement in offspring breeding value (BV) theoretical accuracy, 35% increase in expected genetic gain for forward selection, and doubled selection intensity for backward selection. Overall, all traits showed low to moderate heritability (0.09-0.28), moderate genotype by environment interaction (type-B genetic correlation: 0.51-0.80), low to high expected genetic gain (6.01%-55%), and no significant negative genetic correlation reflecting no large trade-offs for multi-trait selection. Only three traits showed a significant dominance effect. GBLUP resulted in smaller but more accurate heritability estimates for five traits, but larger estimates for the wood traits. Comparison between all, genic-coding, genic-non-coding and intergenic SNPs showed little difference in genetic estimates. In summary, we show that GBLUP overcomes the PX limitations, successfully captures expected historical and hidden relatedness as well as linkage disequilibrium (LD), and results in increased breeding efficiency in WRC.

The western redcedar genome reveals low genetic diversity in a self-compatible conifer.

We assembled the 9.8-Gbp genome of western redcedar (WRC; Thuja plicata), an ecologically and economically important conifer species of the Cupressaceae. The genome assembly, derived from a uniquely inbred tree produced through five generations of self-fertilization (selfing), was determined to be 86% complete by BUSCO analysis, one of the most complete genome assemblies for a conifer. Population genomic analysis revealed WRC to be one of the most genetically depauperate wild plant species, with an effective population size of approximately 300 and no significant genetic differentiation across its geographic range. Nucleotide diversity, π, is low for a continuous tree species, with many loci showing zero diversity, and the ratio of π at zero- to fourfold degenerate sites is relatively high (approximately 0.33), suggestive of weak purifying selection. Using an array of genetic lines derived from up to five generations of selfing, we explored the relationship between genetic diversity and mating system. Although overall heterozygosity was found to decline faster than expected during selfing, heterozygosity persisted at many loci, and nearly 100 loci were found to deviate from expectations of genetic drift, suggestive of associative overdominance. Nonreference alleles at such loci often harbor deleterious mutations and are rare in natural populations, implying that balanced polymorphisms are maintained by linkage to dominant beneficial alleles. This may account for how WRC remains responsive to natural and artificial selection, despite low genetic diversity.

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Evaluation and management of congenital tracheal stenosis.

OBJECTIVES: To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS: Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS: Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION: These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.