Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

Bending properties of Ag nanowires with pre-existing surface defects

Materials used in the engineering always contain imperfections or defects which significantly affect their performances. Based on the large-scale molecular dynamics simulation and the Euler–Bernoulli beam theory, the influence from different pre-existing surface defects on the bending properties of Ag nanowires (NWs) is studied in this paper. It is found that the nonlinear-elastic deformation, as well as the flexural rigidity of the NW is insensitive to different surface defects for the studied defects in this paper. On the contrary, an evident decrease of the yield strength is observed due to the existence of defects. In-depth inspection of the deformation process reveals that, at the onset of plastic deformation, dislocation embryos initiate from the locations of surface defects, and the plastic deformation is dominated by the nucleation and propagation of partial dislocations under the considered temperature. Particularly, the generation of stair-rod partial dislocations and Lomer–Cottrell lock are normally observed for both perfect and defected NWs. The generation of these structures has thwarted attempts of the NW to an early yielding, which leads to the phenomenon that more defects does not necessarily mean a lower critical force.

Distinguishing between mean-field, moment dynamics and stochastic descriptions of birth-death-movement processes

Mathematical descriptions of birth–death–movement processes are often calibrated to measurements from cell biology experiments to quantify tissue growth rates. Here we describe and analyze a discrete model of a birth–death-movement process applied to a typical two–dimensional cell biology experiment. We present three different descriptions of the system: (i) a standard mean–field description which neglects correlation effects and clustering; (ii) a moment dynamics description which approximately incorporates correlation and clustering effects, and; (iii) averaged data from repeated discrete simulations which directly incorporates correlation and clustering effects. Comparing these three descriptions indicates that the mean–field and moment dynamics approaches are valid only for certain parameter regimes, and that both these descriptions fail to make accurate predictions of the system for sufficiently fast birth and death rates where the effects of spatial correlations and clustering are sufficiently strong. Without any method to distinguish between the parameter regimes where these three descriptions are valid, it is possible that either the mean–field or moment dynamics model could be calibrated to experimental data under inappropriate conditions, leading to errors in parameter estimation. In this work we demonstrate that a simple measurement of agent clustering and correlation, based on coordination number data, provides an indirect measure of agent correlation and clustering effects, and can therefore be used to make a distinction between the validity of the different descriptions of the birth–death–movement process.

Young women's recent experience of labour and birth care in Queensland

Background Young parenthood continues to be an issue of concern in terms of clinical and psychosocial outcomes for mothers and their babies, with higher rates of medical complications such as preterm labour and hypertensive disease and a higher risk of depression. The aim of this study was to investigate how young age impacts on women's experience of intrapartum care. Methods Secondary analysis of data collected in a population based survey of women who had recently given birth in Queensland, comparing clinical and interpersonal aspects of the intrapartum maternity care experience for 237 eligible women aged 15–20 years and 6534 aged more than 20 years. Descriptive and multivariate analyses were undertaken. Results In the univariate analysis a number of variables were significantly associated with clinical aspects of labour and birth and perceptions of care: young women were more likely to birth in a public facility, to travel for birth and to live in less economically advantaged areas, to have a normal vaginal birth and to have one carer through labour. They were also less likely to report being treated with respect and kindness and talked to in a way they could understand. In logistic regression models, after adjustment for parity, other socio-demographic factors and mode of birth, younger mothers were still more likely to birth in a public facility, to travel for birth, to be more critical about interpersonal and aspects of care and the hospital or birth centre environment. Conclusion This study shows how experience of care during labour and birth is different for young women. Young women reported poorer quality interpersonal care which may well reflect an inferior care experience and stereotyping by health professionals, indicating a need for more effective staff engagement with young women at this time.

Assessment of damages for wrongful birth and consolidation in advance care directives

The recent decision of Waller v James involved a claim by the plaintiff parents for damages for wrongful birth against the defendant doctor, Dr James, a gynaecologist with a practice in infertility and IVF procedures, who had been consulted by the plaintiffs. The second plaintiff, Mr Waller suffered an inherited anti-thrombin deficiency (ATD), a condition which results in a propensity for the blood to clot, at least in adults. Dr James subsequently recommended IVF treatment. The first plaintiff, Mrs Waller became pregnant after the first cycle of IVF treatment. Her son Keeden was born on 10 August 2000 with a genetic anti-thrombin deficiency. Keeden was released from hospital on 14 August 2000. However, he was brought back to the hospital the next day with cerebral thrombosis (CSVT). As a result of the thrombosis, he suffered permanent brain damage, cerebral palsy and related disabilities. The plaintiffs alleged that the defendant was in breach of contract and his common law duty of care to the plaintiffs in failing to inform them, or cause them to be informed, of the hereditary aspects of ATD. They further alleged that, had they been properly informed, they would not have proceeded to conceive a child using the male plaintiff’s sperm and therefore avoided the harm that had befallen them. The plaintiffs claimed damages to compensate them for their losses, including psychiatric and physical injuries and the costs of having, raising and caring for Keeden. The defendant was held to be not liable in negligence by Justice Hislop of the Supreme Court of New South Wales because a finding was made on medical causation which was adverse to the plaintiffs claim.

Environments For Healthy Living (EFHL) Griffith birth cohort study : characteristics of sample and profile of antenatal exposures

Background The Environments for Healthy Living (EFHL) study is a repeated sample, longitudinal birth cohort in South East Queensland, Australia. We describe the sample characteristics and profile of maternal, household, and antenatal exposures. Variation and data stability over recruitment years were examined. Methods Four months each year from 2006, pregnant women were recruited to EFHL at routine antenatal visits on or after 24 weeks gestation, from three public maternity hospitals. Participating mothers completed a baseline questionnaire on individual, familial, social and community exposure factors. Perinatal data were extracted from hospital birth records. Descriptive statistics and measures of association were calculated comparing the EFHL birth sample with regional and national reference populations. Data stability of antenatal exposure factors was assessed across five recruitment years (2006–2010 inclusive) using the Gamma statistic for ordinal data and chi-squared for nominal data. Results Across five recruitment years 2,879 pregnant women were recruited which resulted in 2904 live births with 29 sets of twins. EFHL has a lower representation of early gestational babies, fewer still births and a lower percentage of low birth weight babies, when compared to regional data. The majority of women (65%) took a multivitamin supplement during pregnancy, 47% consumed alcohol, and 26% reported having smoked cigarettes. There were no differences in rates of a range of antenatal exposures across five years of recruitment, with the exception of increasing maternal pre-pregnancy weight (p=0.0349), decreasing rates of high maternal distress (p=0.0191) and decreasing alcohol consumption (p<0.0001). Conclusions The study sample is broadly representative of births in the region and almost all factors showed data stability over time. This study, with repeated sampling of birth cohorts over multiple years, has the potential to make important contributions to population health through evaluating longitudinal follow-up and within cohort temporal effects.

The role of defects, or active states, in surface electrochemistry with particular reference to gold in neutral solution

Metastable, active, or nonequilibrium states due to the presence of abnormal structures and various types of defects are well known in metallurgy. The role of such states at gold surfaces in neutral aqueous media (an important electrode system in the microsensor area) was explored using cyclic voltammetry. It was demonstrated that, as postulated in earlier work from this laboratory, there is a close relationship between premonolayer oxidation, multilayer hydrous oxide reduction and electrocatalytic behaviour in the case of this and other metal electrode systems. Some of the most active, and therefore most important, entities at surfaces (e.g., metal adatoms) are not readily imageable or detectable by high resolution surface microscopy techniques. Cyclic voltammetry, however, provides significant, though not highly specific, information about such species. The main conclusion is that further practical and theoretical work on active states of metal surfaces is highly desirable as their behaviour is not simple and is of major importance in many electrocatalytic processes.

Effect of defects on fracture strength of graphene sheets

With a hexagonal monolayer network of carbon atoms, graphene has demonstrated exceptional electrical 22 and mechanical properties. In this work, the fracture of graphene sheets with Stone–Wales type defects and vacancies were investigated using molecular dynamics simulations at different temperatures. The initiation of defects via bond rotation was also investigated. The results indicate that the defects and vacancies can cause significant strength loss in graphene. The fracture strength of graphene is also affected by temperature and loading directions. The simulation results were compared with the prediction from the quantized fracture mechanics.

Maternal exposure to heatwave and preterm birth in Brisbane, Australia

Objective To quantify the short-term effects of maternal exposure to heatwave on preterm birth. Design An ecological study. Setting: A population-based study in Brisbane, Australia. Population All pregnant women who had a spontaneous singleton live birth in Brisbane between November and March in 2000–2010 were studied. Methods Daily data on pregnancy outcomes, meteorological factors, and ambient air pollutants were obtained. The Cox proportional hazards regression model with time-dependent variables was used to examine the short-term impact of heatwave on preterm birth. A series of cut-off temperatures and durations were used to define heatwave. Multivariable analyses were also performed to adjust for socio-economic factors, demographic factors, meteorological factors, and ambient air pollutants. Main outcome measure Spontaneous preterm births. Results The adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03–1.24) to 2.00 (95% CI 1.37–2.91) by using different heatwave definitions, after controlling for demographic, socio-economic, and meteorological factors, and air pollutants. Conclusions Heatwave was significantly associated with preterm birth: the associations were robust to the definitions of heatwave. The threshold temperatures, instead of duration, could be more likely to influence the evaluation of birth-related heatwaves. The findings of this study may have significant public health implications as climate change progresses.

Birth control : to what extent do women report being informed and involved in decisions about pregnancy and birth procedures?

Background: Health policy, guidelines, and standards advocate giving patients comprehensive information and facilitating their involvement in health-related decision-making. Routine assessment of patient reports of these processes is needed. Our objective was to examine decision-making processes, specifically information provision and consumer involvement in decision-making, for nine pregnancy, labour, and birth procedures, as reported by maternity care consumers in Queensland, Australia. Methods: Participants were women who had a live birth in Queensland in a specified time period and were not found to have had a baby that died since birth, who completed the extended Having a Baby in Queensland Survey, 2010 about their maternity care experiences, and who reported at least one of the nine procedures of interest. For each procedure, women answered two questions that measured perceived (i) receipt of information about the benefits and risks of the procedure and (ii) role in decision-making about the procedure. Results: In all, 3,542 eligible women (34.2%) completed the survey. Between 4% (for pre-labour caesarean section) and 60% (for vaginal examination) of women reported not being informed of the benefits and risks of the procedure they experienced. Between 2% (epidural) and 34% (episiotomy) of women reported being unconsulted in decision-making. Over one quarter (26%) of the women who experienced episiotomy reported being neither informed nor consulted. Conclusions: There is an urgent need for interventions that facilitate information provision and consumer involvement in decision-making about several perinatal procedures, especially those performed within the time-limited intrapartum care episode.

Wrongful birth assessment of damages : judgment pending

Damages issues regarding the costs of raising the child argued in a case currently before the NSW Supreme Court - Waller v James litigation pre-dated the Health Care Liability Act 2001 and the Civil Liability Act 2002.

Wrongful birth assessment of damages : judgment pending

Wrongful birth - assessment of damages - overview of damages issues raised in current and previous litigation - breach of duty and causation - cost of raising a child - key damages assessment issues - application of civil liability legislation.

Associations between area-level disadvantage and DMFT among a birth cohort of Indigenous Australians

Background Individual-level factors influence DMFT, but little is known about the influence of community environment. This study examines associations between community-level influences and DMFT among a birth cohort of Indigenous Australians aged 16–20 years. Methods Data were collected as part of Wave 3 of the Aboriginal Birth Cohort study. Fifteen community areas were established and the sample comprised 442 individuals. The outcome variable was mean DMFT with explanatory variables including diet and community disadvantage (access to services, infrastructure and communications). Data were analysed using multilevel regression modelling. Results In a null model, 13.8% of the total variance in mean DMFT was between community areas, which increased to 14.3% after adjusting for sex, age and diet. Addition of the community disadvantage variable decreased the variance between areas by 4.8%, indicating that community disadvantage explained one-third of the area-level variance. Residents of under-resourced communities had significantly higher mean DMFT (β=3.86, 95% CI 0.02¬, 7.70) after adjusting for sex, age and diet. Conclusions Living in under-resourced communities was associated with greater DMFT among this disadvantaged population, indicating that policies aiming to reduce oral health-related inequalities among vulnerable groups may benefit from taking into account factors external to individual-level influences.

Born in another country : women's experience of labour and birth in Queensland, Australia

Background Women born outside Australia make up more than a fifth of the Queensland birthing population and like migrants in other parts of the world face the challenges of cultural dislocation and possible language barriers. Recognising that labour and birth are major life events the aim was to investigate the experiences of these women in comparison to native-born English speaking women. Methods Secondary analysis of data from a population based survey of women who had recently birthed in Queensland. Self-reported clinical outcomes and quality of interpersonal care of 481 women born outside Australia who spoke a language other than English at home were compared with those of 5569 Australian born women speaking only English. Results After adjustment for demographic factors and type of birthing facility, women born in another country were less likely to be induced, but more likely to have constant electronic fetal monitoring (EFM), to give birth lying on their back or side, and to have an episiotomy. Most women felt that they were treated as an individual and with kindness and respect. However, women born outside Australia were less likely to report being looked after ‘very well’ during labour and birth and to be more critical of some aspects of care. Conclusion In comparing the labour and birth experiences of women born outside the country who spoke another language with native-born English speaking women, the present study presents a largely positive picture. However, there were some marked differences in both clinical and interpersonal aspects of care.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.