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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
To evaluate differences in interstage growth of pulmonary arteries between use of polytetrafluoroethylene and femoral vein homograft as Sano shunt during stage-I Norwood palliation.
A retrospective review of all patients who survived to the second stage following Norwood–Sano operation at two institutions was performed. Either polytetrafluoroethylene or the valved segment of femoral vein homograft was used for construction of the Sano shunt. The size of pulmonary arteries was compared at pre-Glenn catheterisation.
A total of 48 neonates with the diagnosis of hypoplastic left heart syndrome or its variants comprised the study population. Femoral vein homograft of 5–6 mm diameter was used in 14 and polytetrafluoroethylene graft of 5 mm was used in 34 patients. The two groups were comparable in terms of preoperative demographics and age at time of pre-Glenn catheterisation (3.9±0.7 versus 3.4±0.8 months, p=0.06). Patients who received femoral vein homograft demonstrated a significantly higher pre-Glenn Nakata index [264 (130–460) versus 165 (108–234) mm2/m2, p=0.004]. The individual branch pulmonary arteries were significantly larger in the femoral vein group (right, 7.8±3.6 versus 5.0±1.2, p=0.014; left, 7.2±2.1 versus 5.6±1.9, p=0.02). There were no differences in cardiac index, Qp:Qs, ventricular end-diastolic pressure or systemic oxygen saturations.
Utilisation of a valved segment of femoral vein homograft as right ventricle to pulmonary artery conduit during Norwood–Sano operation confers better interstage growth of the pulmonary arteries. Further studies are needed to evaluate the impact of femoral vein homograft on single ventricle function.
Over the last two decades, there has been a rapid increase of studies testing the efficacy and acceptability of virtual reality in the assessment and treatment of mental health problems. This systematic review was carried out to investigate the use of virtual reality in the assessment and the treatment of psychosis. Web of Science, PsychInfo, EMBASE, Scopus, ProQuest and PubMed databases were searched, resulting in the identification of 638 articles potentially eligible for inclusion; of these, 50 studies were included in the review. The main fields of research in virtual reality and psychosis are: safety and acceptability of the technology; neurocognitive evaluation; functional capacity and performance evaluation; assessment of paranoid ideation and auditory hallucinations; and interventions. The studies reviewed indicate that virtual reality offers a valuable method of assessing the presence of symptoms in ecologically valid environments, with the potential to facilitate learning new emotional and behavioural responses. Virtual reality is a promising method to be used in the assessment of neurocognitive deficits and the study of relevant clinical symptoms. Furthermore, preliminary findings suggest that it can be applied to the delivery of cognitive rehabilitation, social skills training interventions and virtual reality-assisted therapies for psychosis. The potential benefits for enhancing treatment are highlighted. Recommendations for future research include demonstrating generalisability to real-life settings, examining potential negative effects, larger sample sizes and long-term follow-up studies. The present review has been registered in the PROSPERO register: CDR 4201507776.
Numerous advances in surgical techniques and understanding of single-ventricle physiology have resulted in improved survival. We sought to determine the influence of various demographic, perioperative, and patient-specific factors on the survival of single-ventricle patients following stage 1 palliation at our institution.
We conducted a retrospective study of all single-ventricle patients who had undergone staged palliation at our institution over an 8-year period. Data were collected from the Society of Thoracic Surgeons Congenital Heart Surgery database and from patient charts. Information on age, weight at stage 1 palliation, prematurity, genetic abnormalities, non-cardiac anomalies, ventricular dominance, and type of palliation was collected. Information on mortality and unplanned reinterventions was also collected.
A total of 72 patients underwent stage 1 palliation over an 8-year period. There were 12 deaths before and one death after stage 2 palliation. There was no hospital mortality following Glenn or Fontan procedures. On univariate analysis, low weight at the time of stage 1 palliation and prematurity were found to be risk factors for mortality following stage 1 palliation. However, multivariable Cox regression analysis revealed weight at stage 1 palliation to be a strong predictor of mortality. The type of stage 1 palliation did not have any influence on the outcome. No difference in survival was noted following the Glenn procedure.
Low weight has a deleterious impact on survival following stage 1 palliation. This is mitigated by stage 2 palliation. The type of stage 1 palliation itself has no bearing on the outcome.
The porcine small intestinal extracellular matrix reportedly has the potential to differentiate into viable myocardial cells. When used in tetralogy of Fallot repair, it may improve right ventricular function. We evaluated right ventricular function after repair of tetralogy of Fallot with extracellular matrix versus bovine pericardium.
Subjects with non-transannular repair of tetralogy of Fallot with at least 1 year of follow-up were selected. The extracellular matrix and bovine pericardium groups were compared. We used three-dimensional right ventricular ejection fraction, right ventricle global longitudinal strain, and tricuspid annular plane systolic excursion to assess right ventricular function.
The extracellular matrix group had 11 patients, whereas the bovine pericardium group had 10 patients. No differences between the groups were found regarding sex ratio, age at surgery, and cardiopulmonary bypass time. The follow-up period was 28±12.6 months in the extracellular matrix group and 50.05±17.6 months in the bovine pericardium group (p=0.001). The mean three-dimensional right ventricular ejection fraction (55.7±5.0% versus 55.3±5.2%, p=0.73), right ventricular global longitudinal strain (−18.5±3.0% versus −18.0±2.2%, p=0.44), and tricuspid annular plane systolic excursions (1.59±0.16 versus 1.59±0.2, p=0.93) were similar in the extracellular matrix group and in the bovine pericardium group, respectively. Right ventricular global longitudinal strain in healthy children is reported at −29±3% in literature.
In a small cohort of the patients undergoing non-transannular repair of tetralogy of Fallot, there was no significant difference in right ventricular function between groups having extracellular matrix versus bovine pericardium patches followed-up for more than 1 year. Lower right ventricular longitudinal strain noted in both the groups compared to healthy children.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
We have built an imaging polarimeter for use at mid-infrared wavelengths (i.e. N band or 8–13 μm). The detecting element is a 128 × 128 element Si:Ga Focal Plane Array, supplied by Amber Engineering, USA. The polarimeter itself provides diffraction limited images on a 4-m class telescope and has a field of view of about 32 arcsec of sky with 0·25 arcsec pixels. We describe the optical design, control electronics, observing modes and detector sensitivities. Also presented are some observational results to demonstrate the power of this new imaging polarimetric system.
The evidence underpinning the developmental origins of health and disease (DOHaD) is overwhelming. As the emphasis shifts more towards interventions and the translational strategies for disease prevention, it is important to capitalize on collaboration and knowledge sharing to maximize opportunities for discovery and replication. DOHaD meetings are facilitating this interaction. However, strategies to perpetuate focussed discussions and collaborations around and between conferences are more likely to facilitate the development of DOHaD research. For this reason, the DOHaD Society of Australia and New Zealand (DOHaD ANZ) has initiated themed Working Groups, which convened at the 2014–2015 conferences. This report introduces the DOHaD ANZ Working Groups and summarizes their plans and activities. One of the first Working Groups to form was the ActEarly birth cohort group, which is moving towards more translational goals. Reflecting growing emphasis on the impact of early life biodiversity – even before birth – we also have a Working Group titled Infection, inflammation and the microbiome. We have several Working Groups exploring other major non-cancerous disease outcomes over the lifespan, including Brain, behaviour and development and Obesity, cardiovascular and metabolic health. The Epigenetics and Animal Models Working Groups cut across all these areas and seeks to ensure interaction between researchers. Finally, we have a group focussed on ‘Translation, policy and communication’ which focusses on how we can best take the evidence we produce into the community to effect change. By coordinating and perpetuating DOHaD discussions in this way we aim to enhance DOHaD research in our region.
Common pulmonary vein atresia is a rare and usually fatal congenital anomaly, in which the pulmonary veins come together to form a confluence that does not connect to the left atrium. We report our experience with three cases of common pulmonary vein atresia and review the literature on this anomaly. The diagnosis of common pulmonary vein atresia must be entertained in any newborn that presents with cyanosis, refractory acidosis, and decreased systemic perfusion within the first 48 hours of life. Echocardiography is a useful screening tool, but cardiac catheterisation is the preferred diagnostic tool. Common pulmonary vein atresia can be fatal without surgical intervention, but survival after surgery continues to be poor.
In February 1957 the U.S. Naval Research Laboratory was successful in obtaining radar echoes from the moon by using a short-pulse radar . Although the signal-to-noise ratio was not as large as desired, the leading edge of the echo was sufficiently well defined to make possible an accurate measurement of the radar distance to the moon. It was hoped that geodetic information could be extracted from such distance measurements. Hence in October and November, 1957, the radar distance to the moon was measured with a radar mounted in the 50-foot steerable parabola at NRL.
The definition of ultra-high risk (UHR) for psychosis was derived from community-based help-seeking populations. Prisoners have high rates of psychosis and other severe mental health (MH) problems. They also have high rates of risk factors for psychiatric morbidity and yet they are among the populations who are less likely to seek help in the community. Despite a policy of equivalence of care for individuals in prison there are no early intervention services for psychosis in prisons in the UK. This was a study exploring feasibility of introducing such a service into a local London prison. This paper discusses the differences in MH profile of prisoners who met criteria for at-risk mental state compared with those who did not.
A two-stage procedure was used. Participants in a local London prison were routinely screened in the first week of arrival in prison with the Prodrome Questionnaire – Brief Version (PQ-B; Loewy et al. 2011). Those that screened positive as well as a small sample of those who screened negative underwent a further semi-structured assessment to see whether they met criteria for UHR state. Data on self-harm and suicide attempt, family psychiatric history, and anxiety and depression was also collected.
A total of 891 prisoners were screened, 44% of whom screened positive. A total of 354 underwent second stage assessment, 60 of whom had screened negative. Four groups were identified: those that had no MH problems, a group experiencing First Episode Psychosis, those at UHR of psychosis and a group with other MH problems. The UHR state and Psychotic groups had very similar MH profiles of symptoms and distress. Prisoners with no MH problems were at the other end of the spectrum with few symptoms and little distress. The Other group fell in between this group and the psychotic spectrum group in terms of symptomology and distress.
This study is the first to examine risk for psychosis in an adult male prison population. We identified a broad spectrum of MH disorder for which there is little current service provision in prisons. Screening early in the custodial process has the potential to identify unmet MH need and has implications for keeping individuals safe in custody. A long-term strategic approach is required to address MH need in prisons.
Toxoplasma gondii is a globally distributed parasite infecting humans and warm-blooded animals. Although many surveys have been conducted for T. gondii infection in mammals, little is known about the detailed distribution in localized natural populations. In this study, host genotype and spatial location were investigated in relation to T. gondii infection. Wood mice (Apodemus sylvaticus) were collected from 4 sampling sites within a localized peri-aquatic woodland ecosystem. Mice were genotyped using standard A. sylvaticus microsatellite markers and T. gondii was detected using 4 specific PCR-based markers: SAG1, SAG2, SAG3 and GRA6 directly from infected tissue. Of 126 wood mice collected, 44 samples were positive giving an infection rate of 34·92% (95% CI: 27·14–43·59%). Juvenile, young adults and adults were infected at a similar prevalence, respectively, 7/17 (41·18%), 27/65 (41·54%) and 10/44 (22·72%) with no significant age-prevalence effect (P = 0·23). Results of genetic analysis of the mice showed that the collection consists of 4 genetically distinct populations. There was a significant difference in T. gondii prevalence in the different genotypically derived mouse populations (P = 0·035) but not between geographically defined populations (P = 0·29). These data point to either a host genetic/family influence on parasite infection or to parasite vertical transmission.
Scanning acoustic microscopy (SAM), when applied to biological samples has the potential to resolve the longitudinal acoustic wave speed and hence stiffness of discrete tissue components. The heterogeneity of biological materials combined with the action of cryosectioning and rehydrating can, however, create variations in section topography. Here, we set out to determine how variations in specimen thickness influence apparent acoustic wave speed measurements
Cryosections (5μm nominal thickness) of human skin biopsies were adhered to glass slides before washing and rehydrating in water. Multiple regions (200x200 μm; n = 3) were imaged by SAM to generate acoustic wave speed maps. Subsequently co-localised 30x30 μm sub-regions were imaged by atomic force microscopy (AFM) in fluid. The images were then registered using Image J. Each pixel was allocated both a height and wave speed value before their relationship was then plotted on a scattergram. The mean section thickness measured by AFM was 3.48 ± 1.12 (SD) μm. Regional height variations influenced apparent wave speed measurements. A 3.5 μm height difference was associated with a 400 ms-1 increase in wave speed. In the present study we show that local variations in specimen thickness influence apparent wave speed. We also show that a true measure of wave speed can be calculated if the thickness of the specimen is known at each sampling point.
There is evidence that a range of socio-environmental exposures is associated with an increased risk of psychosis. However, despite the fact that such factors probably combine in complex ways to increase risk, the majority of studies have tended to consider each exposure separately. In light of this, we sought to extend previous analyses of data from the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study on childhood and adult markers of disadvantage to examine how they combine to increase risk of psychosis, testing both mediation (path) models and synergistic effects.
All patients with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK (n = 390) and a series of community controls (n = 391) were included in the AESOP study. Data relating to clinical and social variables, including parental separation and loss, education and adult disadvantage, were collected from cases and controls.
There was evidence that the effect of separation from, but not death of, a parent in childhood on risk of psychosis was partially mediated through subsequent poor educational attainment (no qualifications), adult social disadvantage and, to a lesser degree, low self-esteem. In addition, there was strong evidence that separation from, but not death of, a parent combined synergistically with subsequent disadvantage to increase risk. These effects held for all ethnic groups in the sample.
Exposure to childhood and adult disadvantage may combine in complex ways to push some individuals along a predominantly sociodevelopmental pathway to psychosis.