Strong coupling between a microwave photon and a singlet-triplet qubit.

Combining superconducting resonators and quantum dots has triggered tremendous progress in quantum information, however, attempts at coupling a resonator to even charge parity spin qubits have resulted only in weak spin-photon coupling. Here, we integrate a zincblende InAs nanowire double quantum dot with strong spin-orbit interaction in a magnetic-field resilient, high-quality resonator. The quantum confinement in the nanowire is achieved using deterministically grown wurtzite tunnel barriers. Our experiments on even charge parity states and at large magnetic fields, allow us to identify the relevant spin states and to measure the spin decoherence rates and spin-photon coupling strengths. We find an anti-crossing between the resonator mode in the single photon limit and a singlet-triplet qubit with a spin-photon coupling strength of g/2π = 139 ± 4 MHz. This coherent coupling exceeds the resonator decay rate κ/2π = 19.8 ± 0.2 MHz and the qubit dephasing rate γ/2π = 116 ± 7 MHz, putting our system in the strong coupling regime.

Performance of high impedance resonators in dirty dielectric environments.

High-impedance resonators are a promising contender for realizing long-distance entangling gates between spin qubits. Often, the fabrication of spin qubits relies on the use of gate dielectrics which are detrimental to the quality of the resonator. Here, we investigate loss mechanisms of high-impedance NbTiN resonators in the vicinity of thermally grown SiO2 and Al2O3 fabricated by atomic layer deposition. We benchmark the resonator performance in elevated magnetic fields and at elevated temperatures and find that the internal quality factors are limited by the coupling between the resonator and two-level systems of the employed oxides. Nonetheless, the internal quality factors of high-impedance resonators exceed 103 in all investigated oxide configurations which implies that the dielectric configuration would not limit the performance of resonators integrated in a spin-qubit device. Because these oxides are commonly used for spin qubit device fabrication, our results allow for straightforward integration of high-impedance resonators into spin-based quantum processors. Hence, these experiments pave the way for large-scale, spin-based quantum computers.

Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients.

BACKGROUND AND OBJECTIVES: Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. METHODS: An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. RESULTS: A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. CONCLUSIONS: We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.

Validation of NICE diagnostic guidance for rule out of myocardial infarction using high-sensitivity troponin tests.

OBJECTIVE: To validate the National Institute for Health and Care Excellence (NICE) recommended algorithms for high-sensitivity troponin (hsTn) assays in adults presenting with chest pain. METHODS: International post hoc analysis of three prospective, observational studies from tertiary hospital emergency departments. The primary endpoint was cardiac death or acute myocardial infarction (AMI) within 24 hours of presentation, and the secondary endpoint was major adverse cardiac events (MACE) at 30 days. RESULTS: 15% of patients were diagnosed with non-ST elevation myocardial infarction (MI) on admission. The hsTnI algorithm classified 2506/3128 (80.1%) of patients as 'ruled out' with 50 (2.0%) missed MI. 943/3128 (30.1%) of patients had a troponin I level below the limit of detection on admission with 2 (0.2%) missed MI. For the hsTnT algorithm, 1794/3374 (53.1%) of patients were 'ruled out' with 7 (0.4%) missed MI. 490/3374 (14.5%) of patients had a troponin T below the limit of blank on admission with no MI. MACE at 30 days occurred in 10.7% and 8.5% of patients 'ruled out' defined by the hsTnI and hsTnT algorithms, respectively. CONCLUSIONS: The NICE algorithms could identify patients with low probability of AMI within 2 hours; however, neither strategy performed as predicted by the NICE diagnostic guidance model. Additionally, the rate of MACE at 30 days was sufficiently high that the algorithms should only be used as one component of a more extensive model of risk stratification. TRIAL REGISTRATION NUMBER: ACTRN12611001069943, NCT00470587; post-results.

Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study.

BACKGROUND AND AIMS: There is a growing body of evidence supporting the nephrovascular toxicity of indoxyl sulphate (IS) and p-cresyl sulphate (PCS). Nonetheless, a comprehensive description of how these toxins accumulate over the course of chronic kidney disease (CKD) is lacking. METHODS AND RESULTS: This cross-sectional observational study included a convenience sample of 327 participants with kidney function categorised as normal, non-dialysis CKD and end-stage kidney disease (ESKD). Participants underwent measurements of serum total and free IS and PCS and assessment of cardiovascular history and structure (carotid intima-media thickness [cIMT, a measure of arterial stiffness]), and endothelial function (brachial artery reactivity [flow-mediated dilation (BAR-FMD); glyceryl trinitrate (BAR-GTN)]). Across the CKD spectrum there was a significant increase in both total and free IS and PCS and their free fractions, with the highest levels observed in the ESKD population. Within each CKD stage, concentrations of PCS, total and free, were significantly greater than IS (all p < 0.01). Both IS and PCS, free and total, were correlated with BAR-GTN (ranging from r = -0.33 to -0.44) and cIMT (r = 0.19 to 0.21), even after adjusting for traditional risk factors (all p < 0.01). Further, all toxins were independently associated with the presence of cardiovascular disease (all p < 0.02). CONCLUSION: More advanced stages of CKD are associated with progressive increases in total and free serum IS and PCS, as well as increases in their free fractions. Total and free serum IS and PCS were independently associated with structural and functional markers of cardiovascular disease. Studies of therapeutic interventions targeting these uraemic toxins are warranted.

Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.

Pitfalls of using estimations of glomerular filtration rate in an intensive care population.

BACKGROUND: Accurate knowledge of the glomerular filtration rate (GFR) is imperative in the intensive care unit (ICU) as renal status is important for medical decisions, including drug dosing. AIMS: Recently, an estimation of GFR (eGFR) was suggested as a method of estimating GFR. How well this formula predicts GFR in unwell patients with normal initial serum creatinine concentrations has not been examined. METHODS: The accuracy of the eGFR (before and after adjustment for actual body surface area (BSA)) was compared with measured and with estimated creatinine clearance using the Cockcroft Gault (CG) formula adjusted for total and lean body weight. RESULTS: A total of 237 observations was recorded in 47 subjects. These were initially analysed independently, and then using the first observation only. Overall the mean difference between measured creatinine clearance and eGFR was -12 mL/min (95% confidence interval (CI) -20 to -3), between measured creatinine clearance and CG +17 mL/min (95% CI 9-24), between measured creatinine clearance and CG adjusted for ideal body weight +12 mL/min (95% CI 4-21) and between measured creatinine clearance and eGFR 'unadjusted' for BSA 5 mL/min (95% CI -2-13). CONCLUSIONS: Using either eGFR or CG formulae to estimate renal function in ICU subjects with normal serum creatinine concentrations is inaccurate. Although correcting for BSA improves the eGFR, this requirement to measure height and weight removes a major attraction for its use. We suggest that eGFR should not be automatically calculated in the ICU setting.

Gonadotrophin-independent precocious puberty in an eight-year-old boy due to ectopic human chorionic gonadotrophin from the central nervous system.

We present the case of an eight-year-old boy with advanced isosexual precocity associated with an elevated serum total-beta human chorionic gonadotrophin (HCG) and markedly elevated serum total testosterone. Radiological investigation discovered a lesion in the left thalamus and no peripheral tumour. Serum:cerebrospinal fluid (CSF) HCG ratio was approximately 1:1, consistent with a central nervous system source of HCG, with thalamic germinoma strongly suspected. Consent was not obtained for biopsy of the lesion. The patient underwent multiagent chemotherapy with return of serum HCG to normal. We discuss mechanisms of HCG-mediated sexual precocity in both boys and girls and the importance of CSF HCG.

The effect of maternal depression and marital adjustment on young children's internalizing and externalizing behaviour problems.

BACKGROUND: The present study aimed to clarify the circumstances under which maternal depression is associated with adverse outcomes in pre-school-aged children, and to explore the additional impact of the marital relationship in a socio-economically low-risk sample. METHODS: Ninety-two mothers recruited into a longitudinal study were assessed for symptoms of depression when their children were 4, 12 and 15 months, and later at 4 years of age. At 4 years of age, mothers were also asked to report on marital adjustment. Mothers, fathers and pre-school teachers were asked to report on children's internalizing and externalizing behaviour problems. RESULTS: Children exposed to chronic maternal depression were rated by their parents as significantly more problematic on internalizing and externalizing behaviours. This association was not mediated or moderated by low marital satisfaction. No parent-reported effects were evident for children exposed to transient depression. Ten per cent of the children had internalizing scores in the clinical range, and 7% had externalizing scores in the clinical range. Almost all of the children with clinically elevated scores had been exposed to chronic maternal depression. Teacher reports of internalizing behaviours corroborated parent reports; however, teachers tended to report significantly lower levels of behaviour problems. Although there was a tendency for teachers to rate children exposed to any depression as more problematic on internalizing behaviours, the subgroup differences were not significant. CONCLUSIONS: Findings confirm that depression chronicity is important in determining child behavioural outcomes, and that depression effects cannot be accounted for by low marital adjustment. Results are discussed with reference to transmission of risk models, and treatment implications are considered.

Behaviour problems in extremely low birthweight children at 5 and 8 years of age.

This study explored the prevalence and stability of behaviour problems and their prediction from neonatal, medical and family context factors in a group of extremely low birthweight (ELBW) infants assessed at 5 and 8 years of age. Behaviour problems were identified on the basis of several measures: the Total Behaviour Problem Scale and the Adaptive Function Scale of the Child Behaviour Checklist, and the Hyperactivity Index and Hyperactivity Scale from the Conners' Rating Scale. In this group of ELBW infants, the prevalence of behaviour difficulties was somewhat lower than that reported in other studies, and varied according to the measure and informant (parent vs. teacher) used. Also, there was little continuity between those children identified by their parents at 5 years of age as having behaviour problems and those children identified by parent and/or teacher report at 8 years of age. Most of the children identified with behaviour difficulties at 8 years were also reported to have academic difficulties. None of the neonatal or medical factors predicted behaviour difficulties at 8 years of age. In contrast, two family context factors, maternal level of education and family stress, were related to behaviour difficulties at 8 years. These findings indicate that ELBW and the often associated medical complications may not necessarily predispose infants to develop subsequent behaviour difficulties later on in childhood.

Significance of cerebrospinal fluid adenosine deaminase isoenzymes in tuberculous (TB) meningitis.

Adenosine deaminase (ADA) exists as two isoenzymes, ADA(1) and ADA(2). It appears that the ADA(2) isoenzyme originates mainly from monocytes and macrophages. In tuberculous pleural effusions most of the ADA activity consists of ADA(2). The aim of this prospective study was to analyse ADA isoenzymes in the CSF of patients with meningitis to investigate whether the expected rise of the ADA(2) isoenzyme would occur in tuberculous meningitis. ADA isoenzyme analysis was performed on the CSF of 15 patients with tuberculous and 11 patients with bacterial meningitis by an automated kinetic enzyme coupled assay in the presence and absence of a specific ADA inhibitor. The ratio of ADA(2)/ADA(Total) was > 0.8 in 14/15 patients with tuberculous meningitis. In bacterial meningitis the ratio was > or =0.8 in 10/11 patients. The ADA(2) isoenzyme is the major contributor to increased ADA activity in the CSF of patients with tuberculous meningitis, probably reflecting the monocyte-macrophage origin of the ADA.

The mother-child relationship following in vitro fertilisation (IVF): infant attachment, responsivity, and maternal sensitivity.

Infant attachment and mother-child interaction were evaluated for 65 primiparous women and their singleton infants conceived through in vitro fertilisation (IVF) and a control group of 61 women and their infants conceived naturally. The sample was enrolled during pregnancy as part of a longitudinal study. At 12 months postpartum, security of infant attachment was assessed using the Strange Situation procedure, and mother-child interaction was assessed in a free play context using the Emotional Availability Scales. IVF children demonstrated predominantly secure attachment relationships with their mothers (64.6% IVF, 55.9% controls), and there were no significant between-group differences in the proportion of IVF compared to control group children classified in any of the secure or insecure attachment groups. Furthermore, there were no significant group differences on maternal (sensitivity, structuring, hostility) or child (responsivity, involving) dimensions of interaction during play. The majority of IVF mothers (86%) were sensitive and their infants responsive (91%). Contrary to expectation, mother's ratings of greater anticipated infant difficultness assessed during pregnancy and higher ratings of infant temperament and behaviour difficulty assessed at 4 and 12 months postpartum were associated with secure attachment relationships and more optimal mother-child interaction in both the IVF and control groups.

Paternal and maternal depressed mood during the transition to parenthood.

BACKGROUND: The course of postnatal depression was examined in first-time mothers and fathers with emphasis on the role of personality and parental relationships as risk factors. METHOD: 157 couples were assessed at four points: antenatally and at 6, 12 and 52 weeks postnatally. Various measures of mood and personality were administered at each of these assessment points. RESULTS: Examination of the factors associated with depressed mood suggested that a woman's relationship with her own mother was important in the early postpartum stage, and also her level of interpersonal sensitivity and neuroticism. For the father, his relationship with either his mother or father and his level of neuroticism were associated with his mood level early on. By the end of the first year couple morbidity increased, with rates of distress being at their highest for both parents, and factors associated with depressed mood being linked to partner relationship variables, at least for mothers. At most time points, antenatal mood and partner relationship were significant predictor variables for the postnatal mood of both mothers and fathers. LIMITATIONS: The sample had a relatively high level of education and this should be taken into account when considering the generalisation of findings to less educated populations. At the time of conducting this study, the Edinburgh Postnatal Depression Scale (EPDS) had only been validated for use in the first few months postpartum, and thus we used another scale to measure the mother's mood at the other assessment points (the Beck Depression Inventory). Current research would suggest that the EPDS is valid both antenatally and at other times in the first year postpartum. CONCLUSION: Whilst there was some consistency for mothers and fathers in the variables that predict their postpartum adjustment, these being antenatal mood and partner relationship, there is also evidence that adjustment to parenthood was related to different variables at different times. Early adjustment was related to the couple's relationship with their own parents, as well as their own personality. Later adjustment was related to the couple's functioning and relationship.

Parental adjustment and attitudes to parenting after in vitro fertilization.

OBJECTIVE: To examine the psychosocial and parenthood-specific adjustment and attitudes to parenting at 1 year postpartum of IVF parents. DESIGN: Prospective, controlled study. SETTING: Volunteers in a teaching hospital environment. PATIENT(S): Sixty-five primiparous women with singleton IVF pregnancies and their partners, and a control group of 61 similarly aged primiparous women with no history of infertility and their partners. INTERVENTION(S): Completion of questionnaires and interviews. MAIN OUTCOME MEASURE(S): Parent reports of general and parenthood-specific adjustment and attitudes to parenting. RESULT(S): The IVF mothers tended to report lower self-esteem and less parenting competence than control mothers. Although there were no group differences on protectiveness, IVF mothers saw their children as significantly more vulnerable and "special" compared with controls. The IVF fathers reported significantly lower self-esteem and marital satisfaction, although not less competence in parenting. Both IVF mothers and fathers did not differ from control parents on other measures of general adjustment (mood) or those more specific to parenthood (e.g., attachment to the child and attitudes to child rearing). CONCLUSION(S): The IVF parents' adjustment to parenthood is similar to naturally conceiving comparison families. Nonetheless, there are minor IVF differences that reflect heightened child-focused concern and less confidence in parenting for mothers, less satisfaction with the marriage for the fathers, and vulnerable self-esteem for both parents.

Elevated adenosine deaminase activity in patients with HIV and tuberculous peritonitis.

OBJECTIVE: To evaluate the diagnostic potential of the ADA(T), ADA isoenzymes (ADA1 and ADA2) and the interferon-gamma (IFN-gamma) test in HIV-seropositive patients with tuberculous peritonitis. METHODS: Ascitic ADA(T), ADA1, ADA2 and IFN-gamma were prospectively evaluated in HIV-seronegative patients with tuberculous peritonitis (n = 17), HIV-seropositive patients with tuberculous peritonitis (n = 6) and in patients with cirrhosis (n = 22) and malignancy (n = 5). RESULTS: ADA(T) and ADA2 isoenzyme activities of HIV-seronegative (ADA(T) = 109 U/l; ADA2 = 94 U/l) and HIV-seropositive (ADA(T) = 109.5 U/l; ADA2 = 95.5 U/l) patients with tuberculous peritonitis, respectively, were significantly different (P < 0.001) from patients with cirrhosis (ADA(T) = 10.5 U/l; ADA2 = 8 U/l) and malignancy (ADA(T) = 13 U/l; ADA2 = 11 U/l). There was no significant difference in ADA(T) and ADA2 activities between HIV-seropositive and seronegative patients with tuberculous peritonitis. There was no significant correlation between ADA, its isoenzymes and IFN-gamma. CONCLUSIONS: The diagnosis of tuberculous peritonitis can be made by a sensitive, relatively non-invasive procedure in both HIV-seronegative and seropositive patients with minimal risk to the patient and the investigator. The diagnostic value of ADA(T) is not enhanced by measuring ADA isoenzymes or IFN-gamma.

Development, behaviour and temperament: a prospective study of infants conceived through in-vitro fertilization.

The development, behaviour and temperament of 65 singleton infants conceived through in-vitro fertilization (IVF) and 63 matched controls were compared at 1 year postpartum. Primiparous women were recruited during pregnancy and their infants' development was assessed at 1 year. In addition, test-taking behaviour was evaluated by an examiner using the Bayley behaviour rating scale and mothers completed a behaviour problem checklist and temperament scale. Mental, motor, speech and social development were appropriate for age, with no significant group differences. While receptive language development was in the normal range, IVF infants scored lower than control infants. Across both groups, mothers reported low levels of behaviour difficulty and mean temperament ratings were in the general population range. There were no group differences in observed test-taking behaviour. However, IVF mothers rated their children at a higher level of behaviour difficulty and more reactive than the ratings given by control mothers. Overall, singleton children conceived through IVF demonstrate appropriate general development at 1 year of age. The higher reported behaviour difficulty experienced by IVF mothers may reflect their concerns about the well-being and adjustment of their child during the first year.

Psychosocial adjustment and the quality of the mother-child relationship at four months postpartum after conception by in vitro fertilization.

OBJECTIVE: To examine psychological adjustment to early motherhood at 4 months postpartum in mothers who conceived by IVF-ET. DESIGN: Controlled clinical study. SETTING: Healthy human volunteers in an academic research environment. PATIENT(S): Sixty-five primiparous women undergoing IVF-ET and 62 age-matched primiparous women with no history of infertility. INTERVENTION(S): Completion of questionnaires, interviews, and videotaped interaction. MAIN OUTCOME MEASURE(S): Maternal self-reports of psychosocial adjustment and behavioral ratings of quality of mother-infant interaction based on a videotaped observation scored blind to IVF-ET status. RESULT(S): Mothers who conceived by IVF-ET did not differ from control mothers on measures of anxiety, postnatal depression, marital satisfaction, or use of support services. However, they reported lower self-esteem and lower maternal self-efficacy, and they rated their infants as more temperamentally difficult. (Ratings of temperament difficulty for the infants of mothers who conceived by IVF-ET are within the normal range when compared with Australian normative data for this age group.) The videotapes revealed no group differences in maternal behaviors, but the infants of mothers who conceived by IVF-ET displayed more negative behaviors in response to an interactive stress. Group differences were accounted for largely by those mothers who underwent more than one treatment cycle and by their infants. CONCLUSION(S): Overall, the results are reassuring for parents who conceive by IVF-ET. However, specific adjustment measures reveal some minor difficulties and suggest that mothers who conceive by IVF-ET may benefit from increased support in the early postpartum months.

Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception.

The aim of this study was to compare 70 couples who had conceived by in-vitro fertilization (IVF) with 63 matched controls for the prevalence of anxiety and quality of attachment to the baby during pregnancy. Results for mothers showed no group differences using a global measure of anxiety, the Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific measures revealed significantly higher levels of anxiety in IVF mothers about the survival and normality of their unborn babies, about damage to their babies during childbirth and about separating from their babies after birth. When IVF mothers were differentiated according to the number of treatment cycles, more differences in anxiety level were revealed, with most increases occurring in mothers who had experienced two or more treatment cycles. IVF fathers did not differ from controls on the global anxiety measure. No data on pregnancy-specific anxiety were available for fathers. Neither IVF mothers nor IVF fathers differed from controls on measures of attachment to the baby during pregnancy. Results are discussed in the context of the need for researchers to employ differentiated and issue-specific measures to identify concerns that may be unique to IVF couples. Clinical implications regarding the need for psychological support during pregnancy are also discussed.