Charge Fractionalization in the Two-Channel Kondo Effect.

The phenomenon of charge fractionalization describes the emergence of novel excitations with fractional quantum numbers, as predicted in strongly correlated systems such as spin liquids. We elucidate that precisely such an unusual effect may occur in the simplest possible non-Fermi liquid, the two-channel Kondo effect. To bring this concept down to experimental test, we study nonequilibrium transport through a device realizing the charge two-channel Kondo critical point in a recent experiment by Iftikhar et al. [Nature (London) 526, 233 (2015)NATUAS0028-083610.1038/nature15384]. The shot noise at low voltages is predicted to result in a universal Fano factor e^{*}/e=1/2. This allows us to experimentally identify elementary transport processes of emergent fermions carrying half-integer charge.

Universality and Scaling in a Charge Two-Channel Kondo Device.

We study a charge two-channel Kondo model, demonstrating that recent experiments [Z. Iftikhar et al, Nature (London) 526, 233 (2015)] realize an essentially perfect quantum simulation-not just of its universal physics, but also nonuniversal effects away from the scaling limit. Numerical renormalization group (RG) calculations yield conductance line shapes encoding RG flow to a critical point involving a free Majorana fermion. By mimicking the experimental protocol, the experimental curve is reproduced quantitatively over 9 orders of magnitude, although we show that far greater bandwidth/temperature separation is required to obtain the universal result. Fermi liquid instabilities are also studied: In particular, our exact analytic results for nonlinear conductance provide predictions away from thermal equilibrium, in the regime of existing experiments.

Towards Realistic Implementations of a Majorana Surface Code.

Surface codes have emerged as promising candidates for quantum information processing. Building on the previous idea to realize the physical qubits of such systems in terms of Majorana bound states supported by topological semiconductor nanowires, we show that the basic code operations, namely projective stabilizer measurements and qubit manipulations, can be implemented by conventional tunnel conductance probes and charge pumping via single-electron transistors, respectively. The simplicity of the access scheme suggests that a functional code might be in close experimental reach.

Cross-sectional and longitudinal association of the secretoglobin 1A1 gene A38G polymorphism with asthma phenotype in the Perth Infant Asthma Follow-up cohort.

BACKGROUND: Associations between Clara cell secretory protein gene variants (SCGB1A1, also known as CC16, CC10, CCSP and uteroglobin) and the asthma phenotype have been found in five out of eight studies world-wide. No study has investigated the contribution of SCGB1A1 polymorphisms to the development and/or persistence of the asthma phenotype in a birth cohort followed over time. OBJECTIVE: The aim of this study was to determine the role of the SCGB1A1 gene in the development of the asthma phenotype. METHODS: The Perth Infant Asthma Follow-up (PIAF) cohort (n=231 unrelated infants, unselected for asthma and recruited at birth) were seen at 1 month, 6 and 11 years of age, and had a questionnaire, lung function, airway responsiveness (AR) and skin prick tests (SPTs) completed. Blood was taken at 6 and 11 years for total and specific immunoglobulin E (sIgE) and DNA extraction. SPT positivity had at least one positive SPT. SIgE>4 kU/L had at least one sIgE above 4 kU/L. SCGB1A1 A38G (rs3741240), that alters gene transcription, was genotyped using Sau96I restriction digestion of exon 1 PCR products. RESULTS: At 6 and 11 years of age, 33.0% and 29.7% of those genotyped had doctor-diagnosed asthma, and 35.8% and 52.1% had SPT positivity. In cross-sectional analyses, children with 38G/38A or 38A/38A had increased AR at 1 month (1.72-fold, P=0.013); sIgE>4 kU/L [odds ratio (OR)=6.95, 95% confidence interval (CI)=1.35-35.91, P=0.021]; house dust mite (HDM) SPT positivity (OR=7.21, 95% CI=1.09-47.78, P=0.041) and sIgE (4.57-fold, P=0.045) at 6 years; and doctor-diagnosed asthma (OR=3.93, 95% CI=1.24-12.47, P=0.02) and cat SPT positivity (OR=4.34, 95% CI=1.01-18.77, P=0.049) at 11 years. Longitudinal analyses of 6 and 11 years paired data showed that children with 38A/38A had increased persistent sIgE>4 kU/L (OR=11.87, 95% CI=1.97-71.53, P=0.007) and persistent HDM SPT positivity (OR=7.84, 95% CI=1.04-58.92, P=0.045). CONCLUSION: SCGB1A1 A38G may play a role in the development and persistence of the asthma phenotype in childhood.

Associations between postnatal weight gain, change in postnatal pulmonary function, formula feeding and early asthma.

BACKGROUND: A study was undertaken to examine factors that might influence lung function during infancy and to test the hypothesis that change in weight during infancy is negatively associated with change in lung function. METHODS: Weight, length and maximal flow at functional residual capacity (V'maxFRC) were measured at ages 1 and 12 months. V'maxFRC was adjusted for length. Asthma symptoms and age at introduction of formula feeds were identified from questionnaires. Groups were dichotomised by V'maxFRC at 1 month and change in V'maxFRC. RESULTS: 154 infants were assessed at ages 1 and 12 months. The change in V'maxFRC was inversely associated with change in weight (r = -0.18, r2 = 0.13, p<0.001). The group with lower V'maxFRC at 1 month and reduced change in V'maxFRC over infancy had the greatest weight gain (p = 0.003) and increased risk for asthma symptoms by 3 years (p = 0.017) but not afterwards. Exclusive breast feeding to 6 months was associated with a mean reduction in weight gain at age 12 months in comparison with earlier introduction of formula milk (mean difference 0.65 kg, p = 0.001), and was also associated with reduced asthma symptoms at 3 years (odds ratio 0.44, p = 0.043) but not at 6 or 11 years of age. CONCLUSIONS: Weight gain in infancy is inversely associated with change in lung function during infancy. Postnatal weight gain may be indirectly associated with early transient asthma symptoms via an influence on lung growth during infancy, and this is potentially modifiable by breast feeding. These associations could be relevant to the clinically recognised syndrome of the "fat happy wheezer".

Association of haplotypes of beta2-adrenoceptor polymorphisms with lung function and airway responsiveness in a pediatric cohort.

We evaluated the influence of haplotypes of beta(2)-adrenergic receptor (ADRB2) polymorphisms on lung function and airway responsiveness (AR) in a pediatric cohort recruited before birth and followed up to 11 years of age. The subjects (180) were the participants in a prospective study of lung function and AR. They have been assessed five times (at 1 month, 6 months, 12 months, 6 and 11 years of age) for lung function and AR. The two ADRB2 single nucleotide polymorphisms (SNPs): Arg16Gly and Gln27Glu were genotyped by PCR-RLFP and their haplotypes inferred using the program PHASE. An association between the haplotype arg16gln27 and the prevalence of positive AR was found at age 6 years (P = 0.009). The gly16gln27 haplotype was associated with higher FEV1 (P = 0.015) at age 6 and both higher FEV1 and FVC (P = 0.018 and P = 0.001, respectively) at age 11. In contrast, arg16gln27 was associated with both lower FEV1 and FVC (P = 0.028 and P = 0.011, respectively) at age 11. Children with the gly16gln27 haplotype were less likely to have asthma-ever or doctor-diagnosed asthma at age 11 (OR: 0.38; P = 0.019 and OR: 0.31; P = 0.041, respectively). In conclusion, haplotypes of beta(2)-adrenoceptor polymorphisms are associated with lung function, AR, and asthma susceptibility in childhood.

Placental weight and placental ratio as predictors of later blood pressure in childhood.

OBJECTIVE: A significant inverse relationship between blood pressure and birth weight is firmly established. This association may be the result of fetal adaptations to an adverse intrauterine environment. Further markers of intrauterine growth include the weight of the placenta and the placental ratio (the ratio of placental weight to birth weight). A number of studies suggest that a decreased placental weight or an elevated placental ratio may be independent risk factors for subsequent high blood pressure. The overall evidence for this is, however, inconclusive. The purpose of the present study was to clearly define the relationships between placental weight, placental ratio and subsequent blood pressure during childhood. DESIGN: Prospective cohort study of 2507 singleton children, born at term during 1989-1992. Blood pressures were recorded at ages 1, 3 and 6 years, using a semi-automated oscillometric device. RESULTS: Inverse relationships existed between both systolic and diastolic blood pressure and placental weight, adjusted for current weight at ages 1, 3 and 6 years. The relationships between placental weight and systolic blood pressure were statistically significant at ages 1 and 3 years. There was no consistent relationship between placental weight and later blood pressure within birth weight categories. No clinically or statistically significant association was seen between the placental ratio and either systolic or diastolic blood pressures at any age. CONCLUSIONS: Birth weight, rather than placental weight or their ratio, is the early life factor most importantly related to subsequent blood pressure in childhood.

Adjustment for current weight and the relationship between birth weight and blood pressure in childhood.

OBJECTIVE: To determine the role of current weight in mediating the relationship between birth weight and blood pressure within the context of the 'fetal origins' hypothesis. DESIGN: Prospective cohort study of 2507 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia between 1989 and 1992. The study commenced at 16 weeks gestation with serial weight and blood pressure measurements recorded through early childhood. RESULTS: Inverse associations were found between birth weight and systolic blood pressure at ages 1, 3 and 6. The effect of birth weight on systolic blood pressure at age 6 reached statistical significance and was increased fourfold in magnitude to -2.3 mmHg [95% confidence interval = (-3.3 to -1.3), P < 0.01] after adjustment for current weight. The interaction term for birth weight and current weight was not statistically significant. Including intermediate weights did not produce a statistically significantly better model but did increase the magnitude of the estimated regression coefficient of birth weight on blood pressure, and only the birth weight and current weight terms were significant CONCLUSIONS: Adjustment for current weight serves to highlight the relationship between birth weight and blood pressure in childhood. Nevertheless, birth weight, rather than birth weight adjusted for current weight, is still the relevant predictor of later blood pressure within the context of the 'fetal origins' hypothesis.

Flow-volume curves in infants with lung disease.

Partial expiratory flow-volume maneuvers have been performed on nine occasions on six infants with a variety of pulmonary problems using a new technique for thoracic compression. The infants were placed within an inflatable bag that was, itself, within a canvas bag. By sudden controlled inflation of the inner bag at end inspiration, partial expiratory flow-volume curves were generated and recorded by means of a face mask and pneumotachograph. By comparing these flow results with those airway resistance and lung volume measurements obtained from the infants in whole body plethysmography and by noting the effect of inhaling a helium/oxygen gas mixture, it was possible to partition the airway obstruction between large and small airways. The presence of small airway obstruction was noted in the absence of changes in airway resistance or lung volume in several instances. A complete evaluation of airway function should include this test of forced expiration for greater understanding and treatment of lung disease in infancy.

Effect of compression pressure on forced expiratory flow in infants.

The effect of the force of compression on expiratory flow was evaluated in 19 infants (2-13 mo of age) with respiratory illnesses of varying severity. An inflatable cuff was used to compress the chest and abdomen. Expiratory flow and volume, airway occlusion pressure, cuff pressure (Pc), and functional residual capacity were measured. Transmission of pressure from cuff to pleural space was assessed by a noninvasive occlusion technique. Close correlations (P less than 0.001) were found between Pc and the change in pleural pressure with cuff inflation (delta Ppl,c). Pressure transmission was found to vary between two cuffs of different design and between infants. Several forced expirations were then performed on each infant at various levels of delta Ppl,c. Infants with low maximal expiratory flows at low lung volumes required relatively gentle compression to achieve flow limitation and showed decreased flow for firmer compressions. Flow-volume curves in each infant tended to become more concave as delta Ppl,c increased. These findings underline the importance of knowledge of delta Ppl,c in interpreting expiratory flow-volume curves in infants.

Longitudinal analysis of lung function growth in healthy children and adolescents.

Lung function and height in 242 8-yr-old and 299 12-yr-old children without known or suspected predisposition to lung disease were measured annually over 6 and 8 yr, respectively. Growth of forced expiratory volume in 1 s (FEV1), vital capacity, and expiratory flow after expiring 50% of vital capacity were statistically modeled by age and height by use of a multivariate normal model for longitudinal data. This method has the flexibility to fit an appropriate (not necessarily linear) mathematical description of average lung function while concurrently modeling the covariance between measures on the same individual. Differences in lung function growth between girls and boys, pre- and post-puberty, showed that girls had a steadier though less pronounced increase in lung function with height. In boys, before puberty there was deficit in lung volume relative to height (not evident in girls), which was compensated for by rapid growth after puberty. The standard error of FEV1 predictions based on current height and age were more than halved when measurements of FEV1, age, and height taken 1 yr before were incorporated. We found evidence for dysanaptic growth in childhood. Fitted models have application to early detection of departures from healthy lung function.

Prenatal ultrasound biometry related to subsequent blood pressure in childhood.

STUDY OBJECTIVE: To relate measures of fetal growth/size other than birth weight with subsequent blood pressure measured on the same individuals within the context of the "fetal origins of adult disease". DESIGN: A prospective cohort study in which measurements of fetal dimensions obtained by serial ultrasound imaging between 18 and 38 weeks gestation were analysed with reference to systolic blood pressure measurements on the offspring at age 6 years. SETTING: Perth, Western Australia. PARTICIPANTS: A subgroup of 707 eligible mother-fetus pairs from a cohort of 2876 pregnant women and their offspring. The number of mother-fetus pairs varied at each gestational age and by measurement of fetal dimension. Subsequent blood pressure recordings were obtained on approximately 300 of the offspring at age 6 years. MAIN RESULTS: The findings confirmed the inverse association between birth weight and systolic blood pressure at age 6. There was, also, an inverse relation between fetal femur length and systolic blood pressure at age 6, adjusted for current height. Furthermore, an inverse association was demonstrated between a statistically derived measure of fetal growth (conditional z score) between 18 and 38 weeks gestation and later systolic blood pressure at age 6. The effect sizes for all three relations were in the order of 1-2 mm Hg per standard deviation change. CONCLUSION: The mechanisms underpinning the "fetal origins" hypothesis may be operative early in pregnancy and may be reflected in the length of the fetal femur in early to mid-pregnancy.

Peripheral iridectomy in closed angle glaucoma-- late complications.

Of 70 eyes with therapeutic peripheral iridectomy (PI), 51% suffered a loss of two or more lines on the Snellen chart; 57% developed posterior synechiae (PS) and 57% showed lens opacities. Thirty-three per cent of eyes that underwent PI prophylactically had a vision drop of two lines or more, 39% developed PS and 42% showed varying degrees of lens opacities. Although vision drop, lens opacities and PS were less marked in the prophylactic group, it appears that PI is a surgical procedure not without its hazards. We therefore suggest that peripheral iridectomy should not be performed routinely on the second eye not suffering an acute attack. This procedure should be undertaken only in cases with positive provocative tests and/or clinical signs of closed angle glaucoma.

Diurnal variation in bronchial responsiveness in asthmatic children.

To establish the presence of a diurnal variation in bronchial responsiveness in asthmatic children, the increase of peak expiratory flow rate (PEFR) following sympathomimetic inhalation and the response to bronchial provocation with histamine and hyperventilation of cold dry air (HVCDA) were studied. Twenty-nine patients (20 boys, nine girls, aged 9.3 to 17.8 years) measured PEFR before and after sympathomimetic inhalation three times a day for four weeks. A further 15 patients (eight boys, seven girls, aged 6.9 to 18.0 years) underwent bronchial provocation testing every six hours for 24 hours. A diurnal variation in bronchodilator responsiveness was demonstrated in 55% of the first group. Mean amplitude was 60.8% of patients' mean increase in PEFR following bronchodilators. On grouped data, bronchodilation was greater in the morning than in the afternoon (p less than 0.0005) or in the evening (p less than 0.0005). A diurnal variation in the response to bronchial provocation was also found in the second group, but the timing of the rhythm depended on the stimulus used. On grouped data, airways were most sensitive to histamine at 0400 hours and most sensitive to HVCDA at 1600 hours. The diurnal variation demonstrated in bronchial responsiveness could not be attributed to changes in baseline airway caliber and was present, despite the patients' taking sufficient medication to control their asthmatic symptoms.

Does nifedipine affect the diurnal variation of asthma in children?

Diurnal variations in airway caliber and in bronchial reactivity have been described. The mechanisms underlying these variations are not known. The hypothesis that these variations can be diminished by calcium channel blockers was tested by giving 22 asthmatic children 10 mg of nifedipine or identical placebo three times a day for 4 weeks in a double-blind, randomized, crossover-designed study. Treatment with nifedipine did not diminish the diurnal variations in airway caliber, judged from peak expiratory flow rates, or in bronchial reactivity, judged from bronchodilator responsiveness. Group mean amplitude of the diurnal variation in airway caliber was 10.5% on nifedipine and 10.6% on placebo. Group mean amplitude of the diurnal variation in bronchodilator responsiveness was 75.4% on nifedipine and 69.5% on placebo. There were no differences in mean peak expiratory flow rate between nifedipine and placebo periods. This study did not find any evidence to support the hypothesis that the diurnal variations in airway caliber and in bronchial reactivity can be diminished by calcium channel blockers.

Refractoriness to bronchoconstriction following hyperventilation with cold dry air.

Fifteen subjects undertook repeated periods of hyperventilation of cold dry air and hyperventilation of warm humidified air followed by cold dry air. Hyperventilation of cold dry air induced a biphasic response with initial bronchodilatation followed by bronchoconstriction. However, exercise produced a greater rise in forced expiratory volume in 1 second (FEV1) than hyperventilation alone. Hyperventilation of cold dry air resulted in a period of refractoriness to a second stress of the same type. Refractoriness induced by exercise or hyperventilation of cold dry air may be the result of refractoriness of the trigger site in the large airways.

Gender related differences in airway tone in children.

The effects of gender, volume history, and inhaled atropine and isoproterenol on lung mechanics were assessed in 16 normal boys and 14 normal girls using lung volumes, flow-volume curves, and oscillatory resistances. Flows were measured from full and partial forced expiratory flow-volume curves. Six girls and 6 boys were studied before and after inhaled atropine, and 10 boys and 8 girls before and after inhaled isoproterenol. Girls demonstrated a significant increase in flows on full and partial curves with a deep inspiration [Vmax-partial 0.73 +/- 0.34 (SD) to Vmax-full 0.80 +/- 0.37 and 0.83 +/- 0.20 to 1.06 +/- 0.29 TLC/s in each group] and following inhalation of isoproterenol on the partial curves only (0.73 +/- 0.34 to 0.93 +/- 0.40 TLC/s). Boys showed a small but significant increase in Vmax with isoproterenol on full curves but not on partial curves. Following atropine, boys demonstrated a significant increase in Vmax on partial flow-volume curves (0.78 +/- 0.28 to 1.00 +/- 0.35 TLC/s) and a significant decrease in specific respiratory resistance (7.6 +/- 2.7 to 5.1 +/- 0.9 cmH2O/s), whereas girls had no such changes. These data suggest that boys have greater resting airway tone than girls and that this tone is less responsive to deep inspiration and isoproterenol independently, although a combination of isoproterenol and a deep inspiration will produce increased flows in boys. Atropine reduces airway tone predominantly in boys, suggesting that the increased resting airway tone in boys is partially mediated via the vagus nerve.

The effect of age on bronchodilator responsiveness.

The relationship between age and bronchodilator responsiveness (BDR) in children has not been studied using objective parameters. The aim of this study was to seek such a relationship in young asthmatic children using dose-response curves (DRC). Fourteen asthmatic subjects (age 3-9 years) with a forced expiratory volume in 1 sec (FEV1) less than 80% predicted were studied after being trained to use a spirometer reliably. Each subject completed a DRC by inhaling 5 doses of salbutamol (albuterol) at 15 min intervals until a cumulative total of 6.84 mg of salbutamol had been administered. FEV1, forced vital capacity (FVC), and forced expiratory flow at mid vital capacity (FEF25-75) were measured before and after each nebulization. In addition, arterial oxygen saturation (SaO2) and heart rate (HR) were measured in some of the subjects. All lung function parameters, SaO2 and HR increased significantly between baseline and completion of the DRC. A significant age effect on BDR was detected in FEV1 and FVC, with older children showing a greater response than young ones. The response had plateaued after the maximum dose in the younger but not in the older children. These findings suggest that the level of response to a bronchodilator increases significantly with increasing age in young asthmatics.

Gender differences in lung growth.

Annual measurements of lung volumes and forced expiratory flows were made in 281 boys and girls from 8 to 12 years and in another cohort of 287 from 12 to 20 years to measure longitudinal lung growth. Gender differences in growth of lung function were documented, with girls generating greater volume-standardized maximal expiratory flows until age 18.5 years. Beyond that age boys generated higher expiratory flows in proportion to total lung capacity (TLC). There was a time lag of up to 1 year between the age of peak growth velocity in lung volume and peak growth velocity in height. Age at peak growth in flow lagged another year behind that in volume. This was noted more in boys than girls. Dysanaptic lung growth was found with differing rates of growth of maximal expiratory flow compared with TLC or vital capacity (VC).

Management of children hospitalized for laryngotracheobronchitis.

During a 12-month period, 527 consecutive admissions for laryngotracheobronchitis (LTB) were reviewed to determine the epidemiology of hospitalized LTB patients and to better define patients who may benefit from therapy other than close observation. Viral cultures were obtained in 442 patients and were positive in 70%. Disease severity at the time of admission was unrelated to patient age or sex. Duration of hospitalization, however, was inversely related to age (p less than 0.001). Laboratory investigations were rarely abnormal or of therapeutic value. Patients who on admission had stridor without sternal and chest wall retractions recovered rapidly and spontaneously; they were frequently discharged within 48 hours and never required artificial airways. Children who had sternal and chest wall retractions on admission experienced longer hospitalizations, frequently received medical intervention such as aqueous mist therapy or racemic epinephrine, and had a 6% risk of requiring artificial airway support. This group of children should be studied selectively for the benefits of specific medical therapies and diagnostic evaluations.