Sleep disorders in pediatric patients with agenesis of the corpus callosum.

STUDY OBJECTIVES: There is limited information about sleep in agenesis of the corpus callosum (ACC). We aim to describe the sleep architecture and respiratory parameters of children with ACC. METHODS: We performed a retrospective study of 20 patients with ACC who had polysomnography (PSG) between 2000-2023. Demographic data, BMI or weight for length, associated conditions, and PSG findings were collected. National Sleep Foundation (NSF) sleep quality indicators as well as increased PSG arousal index ≥10/h were used in the analysis. Fisher's exact test or unpaired t-test was used to compare groups. RESULTS: Average age was 5.9 ± 5.4 years old; 12/20 patients were male. 6/20 were overweight/obese. 14/20 had complete ACC, and 6/20 had partial ACC. 8/20 had seizures. 15/20 had ≥1 NSF poor sleep quality indicator (decreased SE (45%), decreased REM (53%)) and 9/20 had increased arousals. Between complete and partial ACC, there was no difference in presence of ≥1 poor sleep quality indicator (p= 0.61), SE (p=0.34), REM (p=0.28), and arousals (p=1.0). 11/18 had obstructive sleep apnea (OSA); 5/11 had associated central sleep apnea. There was no difference in OSA between those with complete and partial ACC (p=1.0). OSA was associated with children <3 years old (p=0.01). CONCLUSIONS: Children with ACC have poor sleep quality, and many have OSA. There was no difference in sleep quality or presence of OSA between those with complete and partial ACC. OSA was seen more in younger children. Our study supports the need for screening of sleep-related disorders in patients with ACC.

Sleep-related breathing disorders in infants with spina bifida repaired prenatally and postnatally.

STUDY OBJECTIVES: Advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair. METHODS: We performed a retrospective study of 46 infants <1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t-test and Chi-square Test were used to analyze results. RESULTS: 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01).There was no difference in PSG findings between the two groups: CAI (p=0.11), OAHI (p=0.64), average SpO2 baseline (p=0.91), average SpO2 nadir (p=0.17), average PETCO2 baseline (p=0.87), and average PETCO2 maximum (p=0.54). There were no significant differences in the proportion of patients on supplemental O2 (p=0.25), CSA or OSA between groups. CONCLUSIONS: Patients with SB who've undergone closure of neural tube defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair.

Retrospective study of serial polysomnograms of bronchopulmonary dysplasia patients with oxygen dependence.

INTRODUCTION: This retrospective study describes characteristics of serial polysomnograms (PSGs) of BPD patients on home oxygen therapy and describes PSG parameters associated with discontinuation of supplemental oxygen. METHODS: A single-center study was performed at Children's Hospital Los Angeles, where serial PSGs for 44 patients with BPD infants discharged on home oxygen therapy were extracted for maximum of five PSGs or until oxygen discontinuation. Clinical and polysomnography data was collected. Characteristics of PSG1 were compared amongst the patients who were weaned from oxygen after PSG2 and PSG3. RESULTS: Of 44 patients, 68.2% of patients were males with median birth gestational age of 26 weeks (IQR: 24.6-28.1), median birthweight of 777.5 g (IQR: 632.5-1054 g) and 77.3% of the cohort had severe BPD. A total of 138 PSGs were studied between all 44 patients serially. When comparing PSG1 and PSG2 parameters, statistically significant improvement was noted in multiple parameters. Median baseline SpO2, peak RR, and average PETCO2 were found to be potential predictors of prolonged oxygen use. Gestational age and birth weight were not associated with prolonged oxygen use after PSG3. The median age of oxygen discontinuation was calculated to be about 2 years of age. CONCLUSIONS: The severity of hypoxia and tachypnea on initial infant PSG are associated with prolonged oxygen therapy past 2 years of age. Growth and development of lungs with maturation of control of breathing help improve these parameters over time regardless of BPD severity. The study may inform discussions between providers and parents for patients discharged home on oxygen therapy.

Tree architecture: A strigolactone-deficient mutant reveals a connection between branching order and auxin gradient along the tree stem.

Due to their long lifespan, trees and bushes develop higher order of branches in a perennial manner. In contrast to a tall tree, with a clearly defined main stem and branching order, a bush is shorter and has a less apparent main stem and branching pattern. To address the developmental basis of these two forms, we studied several naturally occurring architectural variants in silver birch (Betula pendula). Using a candidate gene approach, we identified a bushy kanttarelli variant with a loss-of-function mutation in the BpMAX1 gene required for strigolactone (SL) biosynthesis. While kanttarelli is shorter than the wild type (WT), it has the same number of primary branches, whereas the number of secondary branches is increased, contributing to its bush-like phenotype. To confirm that the identified mutation was responsible for the phenotype, we phenocopied kanttarelli in transgenic BpMAX1::RNAi birch lines. SL profiling confirmed that both kanttarelli and the transgenic lines produced very limited amounts of SL. Interestingly, the auxin (IAA) distribution along the main stem differed between WT and BpMAX1::RNAi. In the WT, the auxin concentration formed a gradient, being higher in the uppermost internodes and decreasing toward the basal part of the stem, whereas in the transgenic line, this gradient was not observed. Through modeling, we showed that the different IAA distribution patterns may result from the difference in the number of higher-order branches and plant height. Future studies will determine whether the IAA gradient itself regulates aspects of plant architecture.

Artificial selection reveals complex genetic architecture of shoot branching and its response to nitrate supply in Arabidopsis.

Quantitative traits may be controlled by many loci, many alleles at each locus, and subject to genotype-by-environment interactions, making them difficult to map. One example of such a complex trait is shoot branching in the model plant Arabidopsis, and its plasticity in response to nitrate. Here, we use artificial selection under contrasting nitrate supplies to dissect the genetic architecture of this complex trait, where loci identified by association mapping failed to explain heritability estimates. We found a consistent response to selection for high branching, with correlated responses in other traits such as plasticity and flowering time. Genome-wide scans for selection and simulations suggest that at least tens of loci control this trait, with a distinct genetic architecture between low and high nitrate treatments. While signals of selection could be detected in the populations selected for high branching on low nitrate, there was very little overlap in the regions selected in three independent populations. Thus the regulatory network controlling shoot branching can be tuned in different ways to give similar phenotypes.

Obstructive sleep apnea as a presentation of congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome is a rare disorder due to a mutation in the PHOX2B gene, characterized by a failure in autonomic control of breathing with diminished or absent response to hypoxia and hypercapnia, which is most pronounced during sleep. Most patients present from birth with central apneas and hypoventilation, or later in the setting of a physiologic stress. Recent literature in mice with a Phox2b27Ala/+ mutation suggests a predisposition to obstructive apneas likely due to hypoglossal dysgenesis. We report on three patients with obstructive sleep apneas with absent or mild hypoventilation. Our cases propose that obstructive apneas can be the primary presentation in patients who subsequently develop the classic phenotype of congenital central hypoventilation syndrome and emphasize their close monitoring and surveillance. CITATION: Kagan O, Zhang C, McElyea C, Keens TG, Davidson Ward SL, Perez IA. Obstructive sleep apnea as a presentation of congenital central hypoventilation syndrome. J Clin Sleep Med. 2023;19(9):1697-1700.

Identifying Posterior Fossa Abnormality in Pediatric Aerodigestive Patients, a Case Series.

OBJECTIVES: Multidisciplinary clinics like Aerodigestive programs focus on issues associated with airway, pulmonary, and gastrointestinal issues. Rarely, significant neurological issues like posterior fossa abnormality are identified as the primary etiology. We describe 3 such patients and compare their clinical presentation to the other patients seen in Aerodigestive clinic. METHODS: A retrospective chart review was conducted to review the 3 posterior fossa patients and the remainder of children that were referred to the Aerodigestive Clinic at Children's Hospital Los Angeles from June 2016 to August 2018. Clinical characteristics including triple endoscopies and sleep studies were recorded. RESULTS: Of the 110 patients included for review, 3 patients (3%) had an underlying posterior fossa abnormality; all of whom had symptoms of sleep disordered breathing along with dysphagia compared with 30% incidence of this symptom profile in the remaining Aerodigestive population. CONCLUSION: Presence of sleep disordered breathing and dysphagia, with underlying vomiting history, warrants considering evaluation for posterior fossa abnormalities in addition to traditional workup for aerodigestive disorders. Due to the rarity of this presentation and small sample size, future studies with multicenter collaboration may help better describe identifiers to delineate this population with similar aerodigestive symptoms and clarify diagnostic algorithms.

Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is a rare yet serious complication of obstructive sleep apnea (OSA). Echocardiographic screening for PH is recommended in children with severe OSA, but the health care burden of universal screening is high. We sought to determine the prevalence of PH on echocardiogram among children with severe OSA and identify variables associated with a positive PH screen. METHODS: Retrospective study of 318 children with severe OSA (obstructive apnea-hypopnea index ≥ 10 events/h) and echocardiogram within 1 year of polysomnogram. PH-positive echocardiogram was defined by peak tricuspid regurgitation velocity ≥ 2.5 m/s and/or 2 or more right-heart abnormalities suggestive of elevated pulmonary artery pressure. Patient characteristics and polysomnogram data were compared to identify factors associated with PH. RESULTS: Twenty-six children (8.2%; 95% confidence interval [CI] 5.4-11.8%) had echocardiographic evidence of PH. There was no difference in age, sex, body mass index, obstructive apnea-hypopnea index, or oxygenation indices between patients with and without PH. Sleep-related hypoventilation (end-tidal CO2 > 50 mmHg for > 25% of total sleep time) was present in 25% of children with PH compared with 6.3% of children without PH (adjusted prevalence ratio = 2.73; 95% CI 1.18-6.35). Forty-six percent of children (12/26) with PH had Down syndrome vs 14% (41/292) without PH (adjusted prevalence ratio = 3.11; 95% CI 1.46-6.65). CONCLUSIONS: There was a relatively high prevalence of PH on echocardiogram in our cohort of children with severe OSA. The findings of increased PH prevalence among children with sleep-related hypoventilation or Down syndrome may help inform the development of targeted screening recommendations for specific pediatric OSA populations. CITATION: Maloney MA, Davidson Ward SL, Su JA, et al. Prevalence of pulmonary hypertension on echocardiogram in children with severe obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1629-1637.

Children with Congenital Central Hypoventilation Syndrome Do Not Wake up to Ventilator Alarms.

PURPOSE: Congenital Central Hypoventilation Syndrome (CCHS) requires lifelong ventilatory support during sleep. Subjects with CCHS are vulnerable to sleep disturbances associated with treatments, monitoring alarms, and care they receive. We hypothesized that sleep would be disrupted in patients  with CCHS due to ventilatory support and other treatments at night. METHODS: An anonymous survey of patients with CCHS, age up to 17 years was conducted through REDCAP. Subjects were recruited in person, by flyer, email, and social media. Data collected included demographics, PHOX2B genotype, ventilatory support, treatments, nursing, and sleep parameters. RESULTS: We received 23 responses (35% female, 8.1 years ± 5.6). PHOX2B genotypes were 20/24 PARM (2), 20/25 PARM (4), 20/26 PARM (2), 20/27 PARM (9), ≥ 20/28 PARM (2), and NPARM (2). Two subjects did not indicate the PHOX2B genotype. 13/23 were ventilated by PPV via tracheostomy, 7 by NIPPV, 2 by diaphragm pacing, and 1 did not indicate. Additional treatments received at night included suctioning (9), aerosol (1), G-tube feeding (2), and none (11). Only 9 received nursing at night. 13 used pulse oximetry for monitoring, and 9 used both pulse oximetry and end tidal CO2 monitor. 17/23 rarely woke up due to ventilator or monitor alarms. 11/23 usually or sometimes woke up at least once a night; only 2/11 woke up due to alarms. 5/17 who rarely woke up to the alarms had night nursing. CONCLUSION: Most subjects with CCHS did not awaken to ventilator or monitoring alarms and a majority of these patients did not have nighttime nursing. (Mathur et al. in Sleep 43(Supplement_1):A333, 2020).

Characterization of sleep habits of children with Sotos syndrome.

Sotos syndrome (SS) is a genetic disorder characterized by accelerated growth in childhood, developmental deficits, and characteristic craniofacial features. While clinicians and parents have reported unusual sleep habits, only one study by Rutter and Cole in 1991 mentioned sleep complaints (Rutter and Cole, Developmental Medicine and Child Neurology, 1991, 33, 898-902). This study aimed to characterize the sleep habits of individuals with SS. We performed a cross-sectional study of individuals with a definite, probable, or possible diagnosis of Sotos syndrome. Participants were asked to complete the Children's Sleep Habits Questionnaire (CHSQ). We compared our data to historical data available from the literature. Subjects with SS showed more sleep disturbance than typically developing individuals (TD), although their sleep onset was less likely to be delayed and their sleep duration was longer. Participants with SS also showed different sleep patterns compared to children with other forms of intellectual and developmental disabilities (IDD). Individuals with SS exhibited early bed and rise times, frequently used transitional objects, displayed repetitive motion at sleep onset, and did not show a decrease in sleep duration with age. The majority of participants fell asleep at the same time each night, in their own bed, and within 20 min, and rarely showed signs of sleepwalking or night terrors. These results improve our understanding of sleep habits of individuals with SS and may be used to guide treatment and provide normalization for children with SS.

Retrospective analysis of inpatient polysomnogram characteristics and discharge outcomes in infants with bronchopulmonary dysplasia requiring home oxygen therapy.

RATIONALE: Little is known about the polysomnogram (PSG) characteristics in infants with bronchopulmonary dysplasia (BPD), especially severe BPD, who do not need home ventilatory support but are at increased risk for chronic hypoxia and are vulnerable to its effects. OBJECTIVE: This study aims to assess PSG characteristics and change in discharge outcomes in premature infants with BPD who required oxygen therapy at discharge. METHODS: This is a retrospective chart review of premature infants with BPD who were admitted to a quaternary newborn and infant intensive care unit from January 1, 2012 to December 31, 2015 and who underwent polysomnography before discharge. MEASUREMENTS AND MAIN RESULTS: Data from 127 patients were analyzed. The median gestational age of our patients was 26 weeks and 1 day (interquartile range [IQR]: 24.71, 28.86). The majority of the patients had moderate-to-severe BPD. The median obstructive apnea-hypopnea index was 5.3 events/h (IQR: 2.2, 10.1). The median oxygen desaturation index was 15.7 events/h (IQR: 4.7, 35). Nadir oxygen saturation measured by pulse oximeter was 81% (IQR: 76-86) and the arousal/awakening index was 21.9 (IQR: 13.3-30.9). No statistically significant difference was noted between severe and nonsevere BPD groups for PSG characteristics. However, average end-tidal CO2 was significantly higher in the severe BPD group (p = .0438). Infants in the severe BPD group were intubated longer than infants with nonsevere BPD (p = .0082). The corrected gestational age (CGA) at the time of discharge (CGA-PSG) and PSG (CGA-DC) was higher in severe BPD patients but not statistically different. The majority of premature infants who underwent a PSG were discharged home with oxygen, and 69% required a titration of their level of support based on results from the PSG. CONCLUSION: Our results highlight the presence of abnormal PSG characteristics in BPD patients, as early as 43 weeks CGA. These findings have not been previously described in this patient population prior to initial discharge from the hospital. A severe BPD phenotype tends to be associated with higher respiratory morbidity compared with a nonsevere BPD phenotype for the comparable CGA. PSG, when available, may be helpful for individualizing and streamlining treatment in preparation for discharge home and mitigating the effects of intermittent hypoxic episodes.

Comparison of SIMV+PS and AC modes in chronically ventilated children and effects on speechg.

BACKGROUND: Two modes of ventilation commonly used in children requiring chronic home mechanical ventilation (HMV) via tracheostomy are Assist Control (AC) and Synchronized Intermittent Mandatory Ventilation with Pressure Support (SIMV+PS). There has been no study comparing these two modes of ventilation in children requiring chronic HMV. METHODS: We studied children requiring HMV capable of completing speech testing. Study participants were blinded to changes and studied on both modes, evaluating their oxygen saturation, end tidal carbon dioxide (PET CO2 ), heart rate, respiratory rate, and respiratory pattern. Subjects completed speech testing and answered subjective questions about their level of comfort, ease of breathing, and ease of speech. RESULTS: Fifteen children aged 12.3±4.8 years were tested. There was no difference in mean oxygen saturation, minimum oxygen saturation, mean PET CO2 , maximum PET CO2 , mean heart rate, and mean respiratory rate. The maximum heart rate on AC was significantly lower than SIMV+PS, p=0.047. Subjects breathed significantly above the set rate on SIMV+PS (p=0.029), though not on AC. Subjects found it significantly easier to speak on AC, though there was no statistically significant difference in speech testing. Four subjects had multiple prolonged PS breaths on SIMV+PS. Many subjects exhibited an abnormal cadence to speech, with some speaking during both inhalation and exhalation phases of breathing. CONCLUSIONS: There were few differences between AC and SIMV+PS, with a few parameters favoring AC that may not be clinically significant. This includes subjective perception of ease of speech. We also found unnatural patterns of speech in children requiring HMV. This article is protected by copyright. All rights reserved.

Comparison of SIMV + PS and AC modes in chronically ventilated children and effects on speech.

BACKGROUND: Two modes of ventilation commonly used in children requiring chronic home mechanical ventilation (HMV) via tracheostomy are Assist Control (AC) and Synchronized Intermittent Mandatory Ventilation with Pressure Support (SIMV + PS). There has been no study comparing these two modes of ventilation in children requiring chronic HMV. METHODS: We studied children requiring HMV capable of completing speech testing. Study participants were blinded to changes and studied on both modes, evaluating their oxygen saturation, end-tidal carbon dioxide (PETCO2), heart rate, respiratory rate, and respiratory pattern. Subjects completed speech testing and answered subjective questions about their level of comfort, ease of breathing, and ease of speech. RESULTS: Fifteen children aged 12.3 ± 4.8 years were tested. There was no difference in mean oxygen saturation, minimum oxygen saturation, mean PETCO2, maximum PETCO2, mean heart rate, and mean respiratory rate. The maximum heart rate on AC was significantly lower than SIMV + PS, p = .047. Subjects breathed significantly above the set rate on SIMV + PS (p = .029), though not on AC. Subjects found it significantly easier to speak on AC, though there was no statistically significant difference in speech testing. Four subjects had multiple prolonged PS breaths on SIMV + PS. Many subjects exhibited an abnormal cadence to speech, with some speaking during both inhalation and exhalation phases of breathing. CONCLUSIONS: There were few differences between AC and SIMV + PS, with a few parameters favoring AC that may not be clinically significant. This includes the subjective perception of ease of speech. We also found unnatural patterns of speech in children requiring HMV.

Congenital Heart Disease in Patients With Cleft Lip/Palate and Its Impact on Cleft Management.

OBJECTIVE: To evaluate characteristics of congenital heart disease (CHD) in patients with cleft lip and/or palate (CL/P) and assess potential associations with cleft outcomes. DESIGN: Retrospective review of all patients with CL/P who underwent primary cleft treatment from 2009 to 2015. SETTING: Children's Hospital Los Angeles, a tertiary hospital. PATIENTS: Exclusion criteria included microform cleft lip diagnosis, international patients, and patients presenting for secondary repair or revision after primary repair at another institution. MAIN OUTCOMES MEASURED: Patient demographics, prenatal and birth characteristics, CL/P characteristics, syndromic status, postoperative complications, and other outcomes were analyzed relative to CHD diagnoses and management. Patients with CL/P with (+CHD) were compared to those without (-CHD) CHD using χ2 tests and analysis of variance. RESULTS: Among 575 patients with CL/P, 83 (14.4%) had CHD. Congenital heart disease rates were significantly higher in patients with cleft palate (CP) compared to other cleft types (χ2, P = .009). Eighty-one (97.6%) out of 83 +CHD patients were diagnosed prior to initial CL/P surgical assessment. Twenty-three (27.7%) +CHD patients required surgical repair of 10 cardiac anomalies prior to cleft care. Congenital heart disease was associated with delayed CP repair and increased rates of fistula in isolated patients with CP. CONCLUSIONS: Congenital heart disease is known to be more prevalent in patients with CL/P. These data suggest the condition is particularly increased in patients with CP. Severe forms of CHD are diagnosed and treated prior to cleft care however postoperative fistula may be more common in patients with CHD. Therefore, careful attention is required for patient optimization and palatal flap dissection in patients with coexisting CHD and CL/P.

Evaluation of Obstructive Sleep Apnea in Prone Versus Nonprone Body Positioning With Polysomnography in Infants With Robin Sequence.

OBJECTIVE: Management of obstructive sleep apnea in infants with Robin sequence (RS) includes prone positioning during sleep, which conflicts with safe infant sleep data. We examined changes in polysomnography (PSG) parameters for prone versus nonprone body positions in these infants. DESIGN: Pre-post interventional, nonblinded study. PARTICIPANTS: Infants with RS referred for PSG were recruited from craniofacial clinic and inpatient units at Children's Hospital Los Angeles, a tertiary pediatric center. Fourteen infants were recruited, and 12 studies were completed on both body positions; 11 studies were used in the analysis. INTERVENTIONS: The PSG was divided into nonprone and prone sleep, moving from their usual sleep position to the other position midway in the study. MAIN OUTCOME MEASURES: Data was collected in each position for obstructive apnea-hypopnea index (oAHI), central apnea index (CAI), sleep efficiency (SE), and arousal index (AI). Signed rank test was used to evaluate the change in body position. RESULTS: All infants were term except 1, age 7 to 218 days (mean: 55 days; standard deviation: 58 days), and 8 (57%) of 14 were female. From nonprone to prone sleep position, the median oAHI (16.0-14.0), CAI (2.9-1.0), and AI (28.0-19.9) decreased (P = .065); SE increased (67.4-85.2; P = .227). CONCLUSIONS: Prone positioning may benefit some infants with RS. However, even those with significant improvement in obstructive sleep apnea did not completely resolve their obstruction. The decision to use prone positioning as a therapy should be objectively evaluated in individual infants.

Academic Correlates of Unwanted Sexual Contact, Intercourse, Stalking, and Intimate Partner Violence: An Understudied but Important Consequence for College Students.

Sexual assault, partner abuse, and stalking are major problems on college campuses. Past research has demonstrated a host of physiological and psychological outcomes associated with victimization; however, there has been little research conducted on the potential academic outcomes associated with victimization. The purpose of this study was to measure the relation between academic outcomes and experiences of sexual violence, intimate partner violence, and stalking victimization among college students. A sample of 6,482 undergraduate students currently enrolled at one of eight universities in New England was surveyed using items from the subscales of the College Persistence Questionnaire (Academic Efficacy, Collegiate Stress, Institutional Commitment, and Scholastic Conscientiousness). All four types of victimization were associated with significant differences on academic outcomes after controlling for sex and year in school, with victimized students reporting lower academic efficacy, higher college-related stress, lower institutional commitment, and lower scholastic conscientiousness. Polyvictimization was also significantly correlated with outcomes, with the greater number of types of victimization experienced by students being associated with more negative academic outcomes. Implications for future research and campus response were discussed.

Rapid Response and Code Events in Hospitalized Children on Home Mechanical Ventilation.

BACKGROUND: There is limited knowledge of rapid-response (RR) events and code events for children receiving home mechanical ventilation (HMV) via a tracheostomy in a non-ICU respiratory care unit. The purpose of this study was to describe the demographic and clinical factors leading to deterioration among these children and to identify the incidence and outcomes following rapid-response and code events. METHODS: A retrospective review was conducted on hospitalized HMV children who had RR/code events in a non-ICU respiratory care unit. RESULTS: There were a total of 50 RR events, and the primary clinical problem was acute respiratory distress, with 27 subjects (54%) needing ventilator adjustments. Twenty (40%) RR events occurred among children who were awaiting initial home discharge. Of 18 total code events, 7 (39%) children needed a tracheostomy-related intervention. There were 10 (56%) codes among children on mechanical ventilation awaiting initial home discharge. Children on HMV had 8.73 RR events per 1,000 patient days, whereas all other hospitalized children had 4.61 RR events per 1,000 patient days. In addition, children on HMV had 3.14 codes per 1,000 patient days, whereas all other hospitalized children had 0.74 codes per 1,000 patient days. All children were discharged from the hospital, and no deaths were associated with RR/code events for the index hospitalization. CONCLUSIONS: The overall incidence of RR/code events in children on HMV was higher than among non-HMV hospitalized children. Children on HMV preparing for their initial hospital discharge had the greatest number of RR/code events. The most prevalent interventions among children with RR events were ventilator setting adjustments, and among children with codes the most frequent actions were tracheostomy-related interventions. Developing strategies to predict risk factors for RR/code events may help decrease harm among children on HMV.

Natural variation in Arabidopsis shoot branching plasticity in response to nitrate supply affects fitness.

The capacity of organisms to tune their development in response to environmental cues is pervasive in nature. This phenotypic plasticity is particularly striking in plants, enabled by their modular and continuous development. A good example is the activation of lateral shoot branches in Arabidopsis, which develop from axillary meristems at the base of leaves. The activity and elongation of lateral shoots depends on the integration of many signals both external (e.g. light, nutrient supply) and internal (e.g. the phytohormones auxin, strigolactone and cytokinin). Here, we characterise natural variation in plasticity of shoot branching in response to nitrate supply using two diverse panels of Arabidopsis lines. We find extensive variation in nitrate sensitivity across these lines, suggesting a genetic basis for variation in branching plasticity. High plasticity is associated with extreme branching phenotypes such that lines with the most branches on high nitrate have the fewest under nitrate deficient conditions. Conversely, low plasticity is associated with a constitutively moderate level of branching. Furthermore, variation in plasticity is associated with alternative life histories with the low plasticity lines flowering significantly earlier than high plasticity lines. In Arabidopsis, branching is highly correlated with fruit yield, and thus low plasticity lines produce more fruit than high plasticity lines under nitrate deficient conditions, whereas highly plastic lines produce more fruit under high nitrate conditions. Low and high plasticity, associated with early and late flowering respectively, can therefore be interpreted alternative escape vs mitigate strategies to low N environments. The genetic architecture of these traits appears to be highly complex, with only a small proportion of the estimated genetic variance detected in association mapping.