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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.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Evidence-based psychosocial treatments for schizophrenia founded on Western belief systems and values may not be efficacious in different cultures without adaptation. This systematic review analyses the nature and outcomes of culturally-adapted psychosocial interventions in schizophrenia, examining how interventions have been adapted, their efficacy and what features drive heterogeneity in outcome.
Articles identified by searching electronic databases from inception to 3 March 2016, reference lists and previous reviews were independently screened by two authors for eligible controlled trials. Data on the nature of adaptations was analysed inductively using thematic analyses. Meta-analyses were conducted using random effects models to calculate effect sizes (Hedges’ g) for symptoms.
Forty-six studies with 7828 participants were included, seven adapted for minority populations. Cultural adaptations were grouped into nine themes: language, concepts and illness models, family, communication, content, cultural norms and practices, context and delivery, therapeutic alliance, and treatment goals. Meta-analyses showed significant post-treatment effects in favour of adapted interventions for total symptom severity (n = 2345, g: −0.23, 95% confidence interval (CI) −0.36 to −0.09), positive (n = 1152, g: −0.56, 95% CI −0.86 to −0.26), negative (n = 855, g: −0.39, 95% CI −0.63 to −0.15), and general (n = 525, g: −0.75, CI −1.21 to −0.29) symptoms.
The adaptation process can be described within a framework that serves as a benchmark for development or assessment of future adaptations. Culturally adapted interventions were more efficacious than usual treatment in proportion to the degree of adaptation. There is insufficient evidence to show that adapted interventions are better than non-adapted interventions. Features of context, intervention and design influenced efficacy. Investigating whether adaptation improves efficacy, most importantly amongst ethnic minorities, requires better designed trials with comparisons against unadapted interventions.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents.
To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia.
A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg, oral aripiprazole (10–30 mg/day) or aripiprazole once-monthly 50mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: clinicaltrials.gov, NCT00706654.)
A total of 1118 patients were screened, and 662 responders to oral aripiprazole were randomised. Kaplan–Meier estimated impending relapse rates at week 26 were 7.12% for aripiprazole once-monthly 400mg and 7.76% for oral aripiprazole. This difference (−0.64%, 95% CI −5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to aripiprazole once-monthly 50mg (21.80%, P⩽0.001).
Aripiprazole once-monthly 400mg was non-inferior to oral aripiprazole, and the reduction in Kaplan–Meier estimated impending relapse rate at week 26 was statistically significant v. aripiprazole once-monthly 50 mg.
Our aim was to describe the epidemiology and incidence of community-onset invasive S. aureus disease in children presenting to our hospital, and to compare the clonal complexes and virulence genes of S. aureus strains causing invasive and non-invasive disease. The virulence gene repertoire of invasive disease isolates was characterized using DNA microarray and compared with the virulence gene repertoire of non-invasive S. aureus isolates. Over the study period, 163 children had an invasive S. aureus infection. There was no difference in the distribution of clonal complexes or in the prevalence of genes encoding virulence factors between invasive and non-invasive isolates. Future research should include a strong focus on identifying the host and environmental factors that, along with organism virulence factors, are contributing to the patterns of invasive S. aureus disease observed in New Zealand.
Due to the discontinuation of the widely used low-dose rate (LDR) Caesium afterloader units, many centres in the past 10 years have moved from LDR Selectron treatments to Iridium 192 afterloaders. While the majority of UK centres have opted for high-dose rate (HDR) units, the Christie have invested in two pulsed dose rate (PDR) afterloaders alongside a move to full 3D-planned gynaecological brachytherapy.
To share the experience and learning curve involved in the implementation of a 3D-guided PDR brachytherapy service.
The specific logistical and practical challenges of implementing a PDR service are discussed alongside the more general challenges of implementing 3D-guided magnetic resonance (MR) based brachytherapy. A multidisciplinary approach was undertaken to streamline the patient pathway and give all disciplines a forum to discuss service improvements and resolve problems.
The lessons learned throughout this experience can inform the decisions of departments that may wish to implement a PDR service or indeed a 3D image-guided HDR brachytherapy service in the future. The focus on the utilisation of lean principles to the patient pathway, improved multidisciplinary working and enhancing service efficiency is of interest to all centres.
Coalescing black-hole binaries are expected to be the strongest sources of gravitational waves for ground-based interferometers, as well as the space-based interferometer LISA. Recent progress in numerical relativity now makes it possible to calculate the waveforms from the strong-field dynamical merger, and is revolutionizing our understanding of these systems. We review these dramatic developments, emphasizing applications to issues in gravitational wave observations. These new capabilities also make possible accurate calculations of the recoil or kick imparted to the final remnant black hole when the merging components have unequal masses, or unequal or unaligned spins. We highlight recent work in this area, focusing on results of interest to astrophysics.
Gravitational wave astronomy will open a new observational window on the universe. Since large masses concentrated in small volumes and moving at high velocities generate the strongest, and therefore most readily detectable waves, the final coalescence of blackhole binaries is expected to be one of the strongest sources. During the last century, the opening of the full electromagnetic spectrum to astronomical observation greatly expanded our understanding of the cosmos. In this new century, observations across the gravitational wave spectrum will provide a wealth of new knowledge, including accurate measurements of binary black-hole masses and spins.
The high frequency part of the gravitational wave spectrum, ~10 Hz ≲ f ≲ 103 Hz, is being opened today through the pioneering efforts of first-generation ground-based interferometers such as the Laser Interferometer Gravitational-Wave Observatory (LIGO), currently operating at design sensitivity.
Developments in technology and software engineering are making many types of traditional jobs, such as bookkeeping, accounting, routine design, and document indexing, virtually obsolete (Rasmussen, 2000). The rapid improvements in technology and automated work methods challenge even the traditional idea of stable job competence, as well as the ability to predict the length and the nature of current or future professional careers. Today's work conditions require ongoing adaptations by employees and entrepreneurs to new demands and competitive opportunities through continuing education and training. Technological innovations, such as the World Wide Web, broadband communication, and highly portable communication and work devices, have reduced the constraints of geography on work. Today, many services can be provided with an equivalent level of quality irrespective of whether the provider is in the office next door or on a different continent. It is, indeed, becoming an age of global consumerism in which one can “work with anyone, anytime, anywhere.” Additionally, many specialized skills previously performed by human beings are now the purview of automated systems, and can often be conducted anywhere in the world at a fraction of the cost if carried out in Western Europe and North America. This technological revolution suggests that the competitive advantage of any country aspiring to economic prosperity is increasingly dependent on the capability of both its research and development groups and its skilled workforce, not only to create and develop new and improved products that are at the cutting edge, but also to quickly react and adapt to market forces.