Lower oxygen saturation targets in preterm infants are not associated with increased rates of pulmonary hypertension.

BACKGROUND: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants. METHODS: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94-98% (n = 126); cohort 2, 92-97% (n = 121). Groups compared by Chi-square test, t-test, and multivariable logistic regression. RESULTS: When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, p = 0.38), ROP (4% vs. 3%, p = 0.49), or PH (2% vs. 4%, p = 0.44). CONCLUSION: An oxygen saturation target of 92-97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94-98%.

Formation of a High Pressure Staircase Pedestal with Suppressed Edge Localized Modes in the DIII-D Tokamak.

We observe the formation of a high-pressure staircase pedestal (≈16-20 kPa) in the DIII-D tokamak when large amplitude edge localized modes are suppressed using resonant magnetic perturbations. The staircase pedestal is characterized by a flattening of the density and temperature profiles in midpedestal creating a two-step staircase pedestal structure correlated with the appearance of midpedestal broadband fluctuations. The pedestal oscillates between the staircase and single-step structure every 40-60 ms, correlated with oscillations in the heat and particle flux to the divertor. Gyrokinetic analysis using the cgyro code shows that when the heat and particle flux to the divertor decreases, the pedestal broadens and the E×B shear at the midpedestal decreases, triggering a transport bifurcation from the kinetic ballooning mode (KBM) to trapped electron mode (TEM) limited transport that flattens the density and temperature profiles at midpedestal and results in the formation of the staircase pedestal. As the heat flux to the divertor increases, the pedestal narrows and the E×B shear at the midpedestal increases, triggering a back transition from TEM to KBM limited transport. The pedestal pressure increases during the staircase phase, indicating that enhanced midpedestal turbulence can be beneficial for confinement.

Achievement of Reactor-Relevant Performance in Negative Triangularity Shape in the DIII-D Tokamak.

Plasma discharges with a negative triangularity (δ=-0.4) shape have been created in the DIII-D tokamak with a significant normalized beta (ß_{N}=2.7) and confinement characteristic of the high confinement mode (H_{98y2}=1.2) despite the absence of an edge pressure pedestal and no edge localized modes (ELMs). These inner-wall-limited plasmas have a similar global performance as a positive triangularity (δ=+0.4) ELMing H-mode discharge with the same plasma current, elongation and cross sectional area. For cases both of dominant electron cyclotron heating with T_{e}/T_{i}>1 and dominant neutral beam injection heating with T_{e}/T_{i}=1, turbulent fluctuations over radii 0.5<ρ<0.9 were reduced by 10-50% in the negative triangularity shape compared to the matching positive triangularity shape, depending on the radius and conditions.

Microvascular endothelial function and regional differences in vasodilation in the human cutaneous microcirculation in primary open angle glaucoma

Objective:Blood flow in the optic nerve head and finger skin are related in subjects with a primary vascular dysregulation (PVD). Since PVD may also occur in glaucoma, the aim of this study was to investigate the responses of the microcirculatory blood flow at the finger and forearm skin to iontophoresis of endothelial-dependent (acetylcholine - ACh) and endothelial-independent (sodium nitroprusside - SNP) vasodilators in primary open angle glaucoma (POAG). Design and Methodology: We studied 22 patients with POAG and 27 control subjects. The vasodilator responses to iontophoresis of ACh and SNP performed at the finger and forearm skin were determined, with skin microcirculatory blood flow being expressed as cutaneous red cell flux (RCF) as measured by Laser Doppler Flowmetry. Results: ACh and SNP induced significant increases in RCF from baseline (p<0.001) at both the finger and forearm skin sites in POAG patients and controls, but there was no difference in vasodilation between the subject groups. Within controls and POAG patients, for both ACh and SNP, the baseline RCF was higher in the finger than in the forearm skin (p<0.05). The vasodilatory response to ACh in the finger was also higher than in the forearm skin (p<0.05) i controls and POAG. The mean vasodilatory response to SNP in the finger was higher than in forearm skin (p<0.05) in controls and POAG. Conclusions: The vasodilatory responses to acetylcholine in POAG suggest normal microvascular endothelial function. The higher baseline RCF and vasodilatory responses in the finger than in forearm skin sites may reflect the difference in vascularity between these sites.

Non-obstructive vas deferens and epididymis loss in cystic fibrosis rats.

This study utilizes morphological and mechanistic endpoints to characterize the onset of bilateral atresia of the vas deferens in a recently derived cystic fibrosis (CF) rat model. Embryonic reproductive structures, including Wolffian (mesonephric) duct, Mullerian (paramesonephric) duct, mesonephric tubules, and gonad, were shown to mature normally through late embryogenesis, with involution of the vas deferens and/or epididymis typically occurring between birth and postnatal day 4 (P4), although timing and degree of atresia varied. No evidence of mucus obstruction, which is associated with pathology in other CF-affected tissues, was observed at any embryological or postnatal time point. Reduced epididymal coiling was noted post-partum and appeared to coincide with, or predate, loss of more distal vas deferens structure. Remarkably, α smooth muscle actin expression in cells surrounding duct epithelia was markedly diminished in CF animals by P2.5 when compared to wild type counterparts, indicating reduced muscle development. RNA-seq and immunohistochemical analysis of affected tissues showed disruption of developmental signaling by Wnt and related pathways. The findings have relevance to vas deferens loss in humans with CF, where timing of ductular damage is not well characterized and underlying mechanisms are not understood. If vas deferens atresia in humans begins in late gestation and continues through early postnatal life, emerging modulator therapies given perinatally might preserve and enhance integrity of the reproductive tract, which is otherwise absent or deficient in 97% of males with cystic fibrosis.

Observation of Critical-Gradient Behavior in Alfvén-Eigenmode-Induced Fast-Ion Transport.

Experiments in the DIII-D tokamak show that fast-ion transport suddenly becomes stiff above a critical threshold in the presence of many overlapping small-amplitude Alfvén eigenmodes (AEs). The threshold is phase-space dependent and occurs when particle orbits become stochastic due to resonances with AEs. Above threshold, equilibrium fast-ion density profiles are unchanged despite increased drive, and intermittent fast-ion losses are observed. Fast-ion Dα spectroscopy indicates radially localized transport of the copassing population at radii that correspond to the location of midcore AEs. The observation of stiff fast-ion transport suggests that reduced models can be used to effectively predict alpha profiles, beam ion profiles, and losses to aid in the design of optimized scenarios for future burning plasma devices.

Using neutral beams as a light ion beam probe (invited).

By arranging the particle first banana orbits to pass near a distant detector, the light ion beam probe (LIBP) utilizes orbital deflection to probe internal fields and field fluctuations. The LIBP technique takes advantage of (1) the in situ, known source of fast ions created by beam-injected neutral particles that naturally ionize near the plasma edge and (2) various commonly available diagnostics as its detector. These born trapped particles can traverse the plasma core on their inner banana leg before returning to the plasma edge. Orbital displacements (the forces on fast ions) caused by internal instabilities or edge perturbing fields appear as modulated signal at an edge detector. Adjustments in the q-profile and plasma shape that determine the first orbit, as well as the relative position of the source and detector, enable studies under a wide variety of plasma conditions. This diagnostic technique can be used to probe the impact on fast ions of various instabilities, e.g., Alfvén eigenmodes (AEs) and neoclassical tearing modes, and of externally imposed 3D fields, e.g., magnetic perturbations. To date, displacements by AEs and by externally applied resonant magnetic perturbation fields have been measured using a fast ion loss detector. Comparisons with simulations are shown. In addition, nonlinear interactions between fast ions and independent AE waves are revealed by this technique.

ß-2 adrenergic receptor gene methylation is associated with decreased asthma severity in inner-city schoolchildren: asthma and rhinitis.

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.

Enhanced localized energetic-ion losses resulting from single-pass interactions with Alfvén eigenmodes.

We report the first observation of prompt neutral beam-ion losses due to nonresonant scattering induced by toroidal and reversed shear Alfvén eigenmodes in the DIII-D tokamak. The coherent losses are of full energy beam ions expelled from the plasma on their first poloidal orbit. The first-orbit loss mechanism causes enhanced, concentrated losses on the first wall exceeding nominal levels of prompt losses. The loss amplitude scales linearly with the mode amplitude. The data provide a novel and direct measure of the radial excursion or scatter of particles induced by individual modes and may shed light on the mechanism for the scattering of energetic particles in interstellar medium.

Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post-traumatic stress disorder.

OBJECTIVE: This study sought to address the link between attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) in youth by providing a comprehensive comparison of clinical correlates of ADHD subjects with and without PTSD across multiple non-overlapping domains of functioning and familial patterns of transmission. METHOD: Participants were 271 youths with ADHD and 230 controls without ADHD of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric comorbidity, psychosocial, educational, and cognitive parameters. RESULTS: Post-traumatic stress disorder was significantly higher in ADHD probands vs. controls (5.2% vs. 1.7%, χ(2) (1) = 4.36, P = 0.04). Irrespective of the comorbidity with PTSD, ADHD subjects had similar ages at onset of ADHD, similar type and mean number of ADHD symptoms, and similar ADHD-associated impairments. PTSD in ADHD probands was significantly associated with a higher risk of psychiatric hospitalization, school impairment, poorer social functioning and higher prevalences of mood, conduct disorder, and anxiety disorders. The mean onset of PTSD (12.6 years) was significantly later than that of ADHD and comorbid disorders (all P < 0.05). Siblings of ADHD and ADHD + PTSD probands had higher prevalences of ADHD vs. siblings of controls (35% vs. 18%, z = 4.00, P < 0.001 and 67% vs. 18%, z = 4.02, P < 0.001 respectively) and siblings of ADHD+PTSD probands had a significantly higher prevalence of PTSD compared with the siblings of ADHD and control probands (20% vs. 3% and 3%, z = 2.99, P = 0.003 and z = 2.07, P = 0.04 respectively). CONCLUSION: Findings indicate that the comorbidity with PTSD in ADHD leads to greater clinical severity as regards psychiatric comorbidity and psychosocial dysfunction. ADHD is equally familial in the presence of PTSD in the proband indicating that their co-occurrence is not owing to diagnostic error.

Observation of a critical gradient threshold for electron temperature fluctuations in the DIII-D Tokamak.

A critical gradient threshold has been observed for the first time in a systematic, controlled experiment for a locally measured turbulent quantity in the core of a confined high-temperature plasma. In an experiment in the DIII-D tokamak where L(T(e))(-1) = |∇T(e)|/T(e) and toroidal rotation were varied, long wavelength (k(θ)ρ(s) ≲ 0.4) electron temperature fluctuations exhibit a threshold in L(T(e))(-1): below, they change little; above, they steadily increase. The increase in δT(e)/T(e) is concurrent with increased electron heat flux and transport stiffness. Observations were insensitive to rotation. Accumulated evidence strongly enforces the identification of the experimentally observed threshold with ∇T(e)-driven trapped electron mode turbulence.

Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study.

OBJECTIVE: This study sought to examine the age-dependent persistence of attention deficit hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood. METHOD: Participants were girls with (N=96) and without (N=91) ADHD and were 6-17 years old at the baseline assessment (mean age, 11 years) and 15-30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning. RESULTS: At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning, and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline. CONCLUSION: These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier.

Deficient emotional self-regulation and pediatric attention deficit hyperactivity disorder: a family risk analysis.

BACKGROUND: Although deficient emotional self-regulation (DESR) is associated with attention deficit hyperactivity disorder (ADHD), little research investigates this association and little is known about its etiology. Family studies provide a method of clarifying the co-occurrence of clinical features, but no family studies have yet addressed ADHD and DESR in children. METHOD: Subjects were 242 children with ADHD and 224 children without ADHD. DESR was operationalized using an aggregate score ≥180 and <210 in the anxious/depressed, attention and aggression scales (AAA profile) of the Child Behavior Checklist (CBCL), termed the CBCL-DESR profile. The CBCL-bipolar (CBCL-BP) profile was defined as ≥210 on the CBCL-AAA scale. We examined the familial transmission of ADHD and the CBCL-AAA scale in families selected through probands with and without these conditions. RESULTS: We found a linear increase in the prevalence of CBCL-DESR in siblings as indexed by the Control, ADHD, ADHD+CBCL-DESR and ADHD+CBCL-BP proband groups. While the ADHD siblings were at elevated risk for both the CBCL-DESR and CBCL-BP compared with non-ADHD siblings, a significantly higher rate of CBCL-BP in the siblings of ADHD+CBCL-BP probands was found compared with siblings of the Control probands. CONCLUSIONS: ADHD shows the same degree of familial transmission in the presence or absence of DESR. CBCL-DESR and CBCL-BP are familial, but further work is needed to determine if these definitions are distinctly familial or represent a continuum of the same psychopathology.

Magnetohydrodynamic interference with the edge pedestal motional Stark effect diagnostic on DIII-D.

Accurate measurement of internal magnetic field direction using motional Stark effect (MSE) polarimetry in the edge pedestal is desired for nearly all tokamak scenario work. A newly installed 500 kHz 32-channel digitizer on the MSE diagnostic of DIII-D allows full spectral information of the polarimeter signal to be recovered for the first time. Fourier analysis of this data has revealed magnetohydrodynamic (MHD) fluctuations in the plasma edge pedestal at ρ ≥ 0.92. By correlating edge localized mode fluctuations seen on lock-in amplifier outputs with MSE spectrograms, it has been shown that edge pedestal tearing mode fluctuations cause interference with MSE second harmonic instrument frequencies. This interference results in unrecoverable errors in the real-time polarization angle measurement that are more than an order of magnitude larger than typical polarimeter uncertainties. These errors can cause as much as a 38% difference in local q. By using a redundant measure of the linear polarization found at the fourth harmonic photo-elastic modulator (PEM) frequency, MHD interference can be avoided. However, because of poorer signal-to-noise the fourth harmonic signal computed polarization angle shows no improvement over the MHD polluted second harmonics. MHD interference could be avoided in future edge pedestal tokamak polarimeters by utilizing PEMs with higher fundamental frequencies and a greater separation between their frequencies.

Evidence for fast-ion transport by microturbulence.

Cross-field diffusion of energetic ions by microturbulence is measured during neutral-beam injection into the DIII-D tokamak. Fast-ion D(alpha), neutron, and motional Stark effect measurements diagnose the fast-ion distribution function. As expected for transport by plasma turbulence, anomalies relative to the classical prediction are greatest in high temperature plasmas, at low fast-ion energy, and at larger minor radius. Theoretical estimates of fast-ion diffusion are comparable to experimental levels.

Infection with murine gammaherpesvirus 68 exacerbates inflammatory bowel disease in IL-10-deficient mice.

OBJECTIVE: We questioned whether infection with murine gammaherpesvirus 68 (HV-68) might exacerbate inflammatory bowel disease using mice deficient in IL-10 (IL-10-/-) as a model of developing colitis. METHODS: Groups of C57BL/6 mice and IL-10-/- mice were mock-treated or infected with HV-68. Two months following infection, mice were euthanized and a variety of parameters were measured to quantify the extent of inflammation and the presence of virus. Measurements included survival, body weight, splenomegaly, colonic disease scores, liver histopathology, viable bacteria in the liver, and splenic viral burden. RESULTS: IL-10-/- mice infected with HV-68 displayed reduced survival, lower body weights, increased splenomegaly, exacerbated colonic disease scores, increased numbers of viable bacteria in the liver, and increased leukocyte liver infiltration when compared to mock-treated IL-10-/- mice or HV-68 infected C57BL/6 mice. Surprisingly, levels of infectious or latent virus were not significantly different between the groups of mice exposed to HV-68. CONCLUSIONS: The presence of HV-68 in IL-10-/- mice exacerbates the developing clinical disease in this animal model of colitis.

Magnetic-flux pumping in high-performance, stationary plasmas with tearing modes.

Analysis of the change in the magnetic field pitch angles during edge localized mode events in high performance, stationary plasmas on the DIII-D tokamak shows rapid (<1 ms) broadening of the current density profile, but only when a m/n=3/2 tearing mode is present. This observation of poloidal magnetic-flux pumping explains an important feature of this scenario, which is the anomalous broadening of the current density profile that beneficially maintains the safety factor above unity and forestalls the sawtooth instability.

Neurocognitive impairment in unaffected siblings of youth with bipolar disorder.

BACKGROUND: There is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and 'executive' functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis. METHOD: Subjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey-Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test-Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Principal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged > or =12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor. CONCLUSIONS: Neurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition.

The long-term longitudinal course of oppositional defiant disorder and conduct disorder in ADHD boys: findings from a controlled 10-year prospective longitudinal follow-up study.

BACKGROUND: A better understanding of the long-term scope and impact of the co-morbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in attention deficit hyperactivity disorder (ADHD) youth has important clinical and public health implications. METHOD: Subjects were assessed blindly at baseline (mean age=10.7 years), 1-year (mean age=11.9 years), 4-year (mean age=14.7 years) and 10-year follow-up (mean age=21.7 years). The subjects' lifetime diagnostic status of ADHD, ODD and CD by the 4-year follow-up were used to define four groups (Controls, ADHD, ADHD plus ODD, and ADHD plus ODD and CD). Diagnostic outcomes at the 10-year follow-up were considered positive if full criteria were met any time after the 4-year assessment (interval diagnosis). Outcomes were examined using a Kaplan-Meier survival function (persistence of ODD), logistic regression (for binary outcomes) and negative binomial regression (for count outcomes) controlling for age. RESULTS: ODD persisted in a substantial minority of subjects at the 10-year follow-up. Independent of co-morbid CD, ODD was associated with major depression in the interval between the 4-year and the 10-year follow-up. Although ODD significantly increased the risk for CD and antisocial personality disorder, CD conferred a much larger risk for these outcomes. Furthermore, only CD was associated with significantly increased risk for psychoactive substance use disorders, smoking, and bipolar disorder. CONCLUSIONS: These longitudinal findings support and extend previously reported findings from this sample at the 4-year follow-up indicating that ODD and CD follow a divergent course. They also support previous findings that ODD heralds a compromised outcome for ADHD youth grown up independently of the co-morbidity with CD.

Stability of executive function deficits into young adult years: a prospective longitudinal follow-up study of grown up males with ADHD.

OBJECTIVE: Although individuals with attention deficit-hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions that greatly increase the morbidity of the disorder, all available information on the subject is cross sectional. METHOD: Males (n = 85) 9-22 years with ADHD followed over 7 years into young adulthood were assessed on measures of sustained attention/vigilance, planning and organization, response inhibition, set shifting and categorization, selective attention and visual scanning, verbal and visual learning, and memory. A binary definition of executive function deficits (EFDs) was defined based on a subject manifesting at least two abnormal tests 1.5 standard deviations from controls. RESULTS: The majority of subjects maintained EFDs over time (kappa: 0.41, P < 0.001; sensitivity: 55%, specificity: 85%, positive predictive value: 69%, and negative predictive value: 75%). CONCLUSION: Considering the morbidity of EFDs, these findings stress the importance of their early recognition for prevention and early intervention strategies. EFDs are stable over time.