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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.
The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.
Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs.
A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress–tension. We applied a recently developed twin regression methodology – Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) – to test for evidence consistent with the existence of ‘causal’ influences between the DASS factors.
There was evidence consistent with the stress–tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001).
Our findings suggest a critical role for stress–tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.
A conventional 14C system with either a 15cm3 or a 100cm3 methane gas proportional counting tube, each constructed from high purity copper, has been used at the Washington State University 14C laboratory for three years (Sheppard, Hopper, Westberg, 1981). The electronic components of this system included highly stable (John Fluke) power supplies, modified pre-amplifiers (Canberra), and NIM amplifiers, single channel analyzers, scalers, timers, etc, (ORTEC). Modules were selected for a highly stable low-noise system. The system was designed to minimize problems generated by ground-loops, electromagnetic noise pick-up, and line noise. It operates in a copper-lined basement room of a four-story brick and concrete building along with a second and older gas proportional system which has three 500cm3 copper counting tubes operated at 2 or 3 atmospheres of methane. Analysis of the older system's background data indicates that the background counting rate of 0.8 counts per minute is virtually independent of atmospheric pressure. It has not been possible to determine the pressure dependence of the small counting tubes.
Twins can help researchers disentangle the roles of genes from those of the environment on human traits, health, and diseases. To realize this potential, the Australian Twin Registry (ATR), University of Melbourne, and the Charles Perkins Centre (CPC), University of Sydney, established a collaboration to form the Twins Research Node, a highly interconnected research facility dedicated specifically to research involving twins. This collaboration aims to foster the adoption of twin designs as important tools for research in a range of health-related domains. The CPC hosted their Twins Research Node's launch seminar entitled ‘Double the power of your research with twin studies’, in which experienced twin researchers described how twin studies are supporting scientific discoveries and careers. The launch also featured twin pairs who have actively participated in research through the ATR. Researchers at the CPC were surveyed before the event to gauge their level of understanding and interest in utilizing twin research. This article describes the new Twins Research Node, discusses the survey's main results and reports on the launch seminar.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
The disease- and mortality-related difference between biological age based on DNA methylation and chronological age (Δage) has been found to have approximately 40% heritability by assuming that the familial correlation is only explained by additive genetic factors. We calculated two different Δage measures for 132 middle-aged female twin pairs (66 monozygotic and 66 dizygotic twin pairs) and their 215 sisters using DNA methylation data measured by the Infinium HumanMethylation450 BeadChip arrays. For each Δage measure, and their combined measure, we estimated the familial correlation for MZ, DZ and sibling pairs using the multivariate normal model for pedigree analysis. We also pooled our estimates with those from a former study to estimate weighted average correlations. For both Δage measures, there was familial correlation that varied across different types of relatives. No evidence of a difference was found between the MZ and DZ pair correlations, or between the DZ and sibling pair correlations. The only difference was between the MZ and sibling pair correlations (p < .01), and there was marginal evidence that the MZ pair correlation was greater than twice the sibling pair correlation (p < .08). For weighted average correlation, there was evidence that the MZ pair correlation was greater than the DZ pair correlation (p < .03), and marginally greater than twice the sibling pair correlation (p < .08). The varied familial correlation of Δage is not explained by additive genetic factors alone, implying the existence of shared non-genetic factors explaining variation in Δage for middle-aged women.
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.
Major vascular complications in patients with head and neck cancer have previously been thought of as terminal events. However, it is now possible to intervene in many situations, with benefits for quality of life as well as survival. Endovascular techniques have reduced morbidity and mortality in many situations, both emergency and elective.
We describe the techniques that can be employed in such situations, and present illustrative case reports. Life-threatening haemorrhage, carotid compression and radiation-induced carotid stenosis are all discussed.
It is possible to predict where complications may arise, and to take prophylactic steps to allow treatment to continue. Early intervention can reduce both morbidity and mortality in this high-risk patient group.
Ceramic coated carbon steel coupons were corrosion tested in water with dissolved salts to simulate exposure to evaporation concentrated groundwater in an underground nuclear repository. Metallography revealed no corrosion at the ceramic metal interface of dense coatings, even though electrical measurements demonstrated that the coatings were slightly porous. Experimental results and a model to predict corrosion rates influenced by a porous ceramic coating and coating lifetimes are presented.
No animals tested were positive for feline leukaemia virus antigen and Chlamydia psittaci antibodies, but all were positive for antibodies to feline calicivirus (FCV), feline herpesvirus 1 (FHV1) and rotavirus. They had antibodies to feline parvovirus (96%), feline coronavirus (84%) and cowpox virus (2%). Antibody to feline immunodeficiency virus (FIV) was found in 53% of animals, which were less likely to be infected with Haemobartonella felis, and had higher FHV antibody titres than cats without FIV. FCV was isolated from 51% cats and FHV1 and feline reovirus each from 4%. H. felis was present in 42% of animals, and antibody to Toxoplasma gondii in 62%. Clinical abnormality had a significant association with FIV and feline calicivirus infections, but sex, age, social status and feeding group had no significant association with prevalence of any parasites. Toxocara cati and Toxascaris leonina eggs were found, respectively, in 91% and 82% of animals tested.
Salmonella typhimurium 49a infection in a large dairy herd persisted for 3·5 years. Illness initially occurred in cows and calves but latterly although there were fewer clinical cases milk filters were culturally positive on 26 out of 73 samplings. Three associated human disease incidents occurred. Individual milk samples identified one cow as an excreter and the organism was recovered from the mammary gland of this animal at slaughter. Correlation between calving pattern, the times of calving and the occurrence of positive milk filters suggest that the cow may have been excreting the organism intermittently from the udder for 2·5 years.
Photodynamic therapy is an innovative modality in the treatment of malignant and non-malignant diseases. Owing to its widespread use, there will be an increase in the number of photosensitized patients presenting for both elective and emergency anaesthesia. As one of the few centres involved in providing this specialized treatment for maxillofacial conditions, we would like to highlight its main anaesthetic considerations.
Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia.
To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables.
Historic prospective study. Standardised assessments of course and outcome.
About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery.
A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.
The management of patients with ’field cancerization‘ of the oral mucosa, with multicentric foci of invasion, presents a considerable problem for the head and neck surgeon. Surgical resection of synchronous or metachronous primary squamous cell carcinomas, along with adjacent premalignant lesions, is likely to be associated with considerable mutilation. Photodynamic therapy (PDT) has been shown to be of value in the treatment of superficial tumours in the upper aerodigestive tract, with excellent healing of treated areas. This study reports the use of PDT to treat 11 patients with ’field cancerization‘ occurring in the oral cavity. Six patients had multiple primary cancers and five had single primary tumours. All had associated areas of leukoplakia. Each received Photofrin 2 mg/kg 48 hours prior to photoirradiation with 50–100 J/cm² red laser light by surface illumination. Six to eight weeks later treated areas in 10 of the 11 patients showed a complete response to PDT; one patient had areas of residual leukoplakia. Two patients developed further areas of leukoplakia or erythroplakia within 12 months but no patient has had evidence of recurrent invasive carcinoma in the treated areas. Longer term follow-up will be necessary to exclude further recurrence. It is concluded that PDT offers an effective repeatable treatment option, whether on its own or as an adjunct to local excision, for patients with ’field cancerization‘ of the oral cavity.
Amorphous carbon films were deposited on glass by dc magnetron sputtering from a graphite target in mixtures of argon and hydrogen. Hydrogen flow and other parameters affected the optical and mechanical properties of these films. Increasing hydrogen content caused the average visible transmittance to vary from 16% to 86% for 500-Å thick films. Maximum compressive stress and hardness occur between 0 and 1% hydrogen flow, resulting in rapid delamination. Low sputtering power moderately increases transmittance and hardness while relieving stress. Transparency is induced in both the high-hydrogen and low-power films by formation of sp3 C–C bonds. In the case of the hydrogenated films, however, a softer polymeric structure is formed.
Thin films of amorphous carbon (a–C) and amorphous hydrogenated carbon (a–C:H) were prepared using magnetron sputtering of a graphite target. The chemical structures of the films were characterized using electron energy loss spectroscopy (EELS) and Raman spectroscopy. The mass density, hardness, residual stress, optical band gap, and electrical resistivity were determined, and their relation to the film's chemical structure are discussed. It was found that the graphitic component increases with increasing sputtering power density. This is accompanied by a decrease in the electrical resistivity, optical band gap, mass density, and hardness. Increasing the hydrogen content in the sputtering gas mixture results in decreasing hardness (14 GPa to 3 GPa) and mass density, and increasing optical band gap and electrical resistivity. The variation in the physical properties and chemical structures of these films can be explained in terms of the changes in the volume of sp2-bonded clusters in the a–C films and changes in the termination of the graphitic clusters and sp3-bonded networks by hydrogen in the a–C:H films.