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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.
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.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
To assess race-specific validity of food and food group intakes measured using an FFQ.
Calibration study participants were randomly selected from the Adventist Health Study-2 (AHS-2) cohort by church, and then by subject-within-church. Intakes of forty-seven foods and food groups were assessed using an FFQ and then compared with intake estimates measured using six 24 h dietary recalls (24HDR). We used two approaches to assess the validity of the questionnaire: (i) cross-classification by quartile and (ii) de-attenuated correlation coefficients.
Seventh-day Adventist church members geographically spread throughout the USA and Canada.
Members of the AHS-2 calibration study (550 whites and 461 blacks).
The proportion of participants with exact quartile agreement in the FFQ and 24HDR averaged 46 % (range: 29–87 %) in whites and 44 % (range: 25–88 %) in blacks. The proportion of quartile gross misclassification ranged from 1 % to 11 % in whites and from 1 % to 15 % in blacks. De-attenuated validity correlations averaged 0·59 in whites and 0·48 in blacks. Of the forty-seven foods and food groups, forty-three in whites and thirty-three in blacks had validity correlations >0·4.
The AHS-2 questionnaire has good validity for most foods in both races; however, validity correlations tend to be higher in whites than in blacks.
There has been a tireless quest by the designers of micro- and nanoelectro mechanical systems (MEMS/NEMS) to find a suitable material alternative to conventional silicon. This is needed to develop robust, reliable, and long-endurance MEMS/NEMS with capabilities for working under demanding conditions, including harsh environments, high stresses, or with contacting and sliding surfaces. Diamond is one of the most promising candidates for this because of its superior physical, chemical, and tribomechanical properties. Ultrananocrystalline diamond (UNCD) and nanocrystalline diamond (NCD) thin films, the two most studied forms of diamond films in the last decade, have distinct growth processes and nanostructures but complementary properties. This article reviews the fundamental and applied science performed to understand key aspects of UNCD and NCD films, including the nucleation and growth, tribomechanical properties, electronic properties, and applied studies on integration with piezoelectric materials and CMOS technology. Several emerging diamond-based MEMS/NEMS applications, including high-frequency resonators, radio frequency MEMS and photonic switches, and the first commercial diamond MEMS product—monolithic diamond atomic force microscopy probes—are discussed.
We present the first reported case in the English language literature of an inflammatory myofibroblastic tumour of the right tonsil in a young, pregnant woman, and we report a management strategy for this enigmatic entity.
A 28-year-old, pregnant woman presented with a 10-day history of odynophagia despite a course of antibiotics. Examination revealed a grade II, erythematous right tonsil with ulceration on the upper pole. A biopsy was arranged, and initial evaluation was suggestive of spindle cell carcinoma. However, this diagnosis was reviewed after immunohistochemical staining confirmed an inflammatory myofibroblastic tumour. Subsequent complete excision was undertaken using CO2 laser.
Clinically, inflammatory myofibroblastic tumour of the tonsil is known to be locally aggressive and can present in a manner not dissimilar to a high grade carcinoma of the tonsil. As a result, the recommended treatment is complete local excision with careful follow up.
To validate a 204-item quantitative FFQ for measurement of nutrient intake in the Adventist Health Study-2 (AHS-2).
Calibration study participants were randomly selected from the AHS-2 cohort by church, and then subject-within-church. Each participant provided two sets of three weighted 24 h dietary recalls and a 204-item FFQ. Race-specific correlation coefficients (r), corrected for attenuation from within-person variation in the recalls, were calculated for selected energy-adjusted macro- and micronutrients.
Adult members of the AHS-2 cohort geographically spread throughout the USA and Canada.
Calibration study participants included 461 blacks of American and Caribbean origin and 550 whites.
Calibration study subjects represented the total cohort very well with respect to demographic variables. Approximately 33 % were males. Whites were older, had higher education and lower BMI compared with blacks. Across fifty-one variables, average deattenuated energy-adjusted validity correlations were 0·60 in whites and 0·52 in blacks. Individual components of protein had validity ranging from 0·40 to 0·68 in blacks and from 0·63 to 0·85 in whites; for total fat and fatty acids, validity ranged from 0·43 to 0·75 in blacks and from 0·46 to 0·77 in whites. Of the eighteen micronutrients assessed, sixteen in blacks and sixteen in whites had deattenuated energy-adjusted correlations ≥0·4, averaging 0·60 and 0·53 in whites and blacks, respectively.
With few exceptions validity coefficients were moderate to high for macronutrients, fatty acids, vitamins, minerals and fibre. We expect to successfully use these data for measurement error correction in analyses of diet and disease risk.
To investigate a pseudo-outbreak of “Mycobacterium paraffinicum” (unofficial taxon) infection and/or colonization, using isolates recovered from clinical and environmental specimens.
University-affiliated, tertiary-care hospital.
M. paraffinicum, a slow-growing, nontuberculous species of mycobacteria, was recovered from 21 patients and an ice machine on a single patient care unit over a 2.5-year period. The clinical, epidemiological, and environmental investigation of this pseudo-outbreak is described.
Twenty-one patients with pulmonary symptoms and possible risk factors for tuberculosis were admitted to inpatient rooms that provided airborne isolation conditions in 2 adjacent hospital buildings. In addition, 1 outpatient had induced sputum cultured for mycobacteria in the pulmonary function laboratory. Of the samples obtained from these 21 patients, 26 isolates from respiratory samples and 1 isolate from a stool sample were identified as M. paraffinicum. Environmental isolates obtained from an ice machine in the patient care unit where the majority of the patients were admitted were also identified as M. paraffinicum.
An epidemiological investigation that used molecular tools confirmed the suspicion of a pseudo-outbreak of M. paraffinicum infection and/or colonization. The hospital water system was identified as the source of contamination.
With the advent of large wide-field cameras and deep, CCD-based “all-sky” surveys, the study of the structure of the Milky Way (MW) through its stellar populations has become feasible. We are developing tools to apply CMD fitting techniques for this purpose. Here we present two applications. First we constrain the properties of the old and young stellar populations of the Canis Major overdensity. Secondly, we demonstrate how CMD fitting can be used to detect faint overdensities in the halo of the MW and determine their properties, using data from the Sloan Digital Sky Survey (SDSS).
All mainstream primary schools in Cardiff were invited in July 1998 to participate in a prevalence survey of autistic spectrum disorder. Teachers of each class filled in a questionnaire based on ICD-10 criteria for autistic disorders. The Autism Spectrum Screening Questionnaire (ASSQ) was completed on children identified with problems identified by the questionnaire. A total of 11692 children born between 1 September 1986 and 31 August 1990 were screened: 234 (2%) children were identified as requiring an ASSQ; 151 of 234 (65%) ASSQs were returned. Of the 151, 60 children (52 male, 8 female; 40%) scored 22 or more. Their notes and the involved professionals were consulted. Thirty-five children, unknown to specialist services or with complex features, required additional assessment. Seventeen children (all male) were found to be on the autistic spectrum. When the overall rubric was disentangled we found a diverse population of affected children including a handful who did not fit easily into ICD-10 classification. Correcting for incomplete ascertainment we found a minimum prevalence of 20.2 out of every 10000 (SE=4.5) for autistic spectrum disorder in this population.
An epidemiological and microbiological investigation of a cluster of eight cases of
Legionnaires' disease in Los Angeles County in November 1997 yielded conflicting results. The
epidemiological part of the investigation implicated one of several mobile cooling towers used
by a film studio in the centre of the outbreak area. However, water sampled from these cooling
towers contained L. pneumophila serogroup 1 of another subtype than the strain that was
recovered from case-patients in the outbreak. Samples from two cooling towers located
downwind from all of the case-patients contained a Legionella strain that was indistinguishable
from the outbreak strain by four subtyping techniques (AP-PCR, PFGE, MAb, and MLEE). It
is unlikely that these cooling towers were the source of infection for all the case-patients, and
they were not associated with risk of disease in the case-control study. The outbreak strain also
was not distinguishable, by three subtyping techniques (AP-PCR, PFGE, and MAb), from a
L. pneumophila strain that had caused an outbreak in Providence, RI, in 1993. Laboratory
cross-contamination was unlikely because the initial subtyping was done in different
In this investigation, microbiology was helpful for distinguishing the outbreak cluster from
unrelated cases of Legionnaires' disease occurring elsewhere. However, multiple subtyping
techniques failed to distinguish environmental sources that were probably not associated with
the outbreak. Persons investigating Legionnaires' disease outbreaks should be aware that
microbiological subtyping does not always identify a source with absolute certainty.
It is shown that star disclinations can be a significant source of stress in chemical vapor deposited (CVD) diamond. This purely geometrical origin contrasts with other sources of stress that have been proposed previously. The effectiveness is demonstrated of the use of electron irradiation using a transmission electron microscope (TEM) to displace atoms from their equilibrium sites to investigate intrinsic defects and impurities in CVD diamond. After irradiation, the samples are studied by low temperature photoluminescence microscopy using UV or blue laser illumination. Results are given that are interpreted as arising from isolated <100> split self-interstitials and positively charged single vacancies. Negatively charged single vacancies can also be revealed by this technique. Nitrogen and boron impurities may also be studied similarly. In addition, a newly developed liquid gallium source scanned ion beam mass spectrometry (SIMS) instrument has been used to map out the B distribution in B doped CVD diamond specimens. The results are supported by micro-Raman spectroscopy.
To investigate a cluster of cases of legionnaires' disease among patients at a hospital.
A university hospital that is a regional transplant center.
Retrospective review of microbiology and serology data from the hospital laboratories and prospective surveillance via the radiology department; a case-control study and environmental sampling within the hospital and from nearby cooling towers.
Diagnosis of seven cases of legionnaires' disease in the first 9 months of 1996 led to recognition of a nosocomial outbreak that may have begun as early as 1979. Review of charts from 1987 through September 1996 identified 25 culture-confirmed cases of nosocomial or possibly nosocomial legionnaires' disease, including 18 in bone marrow and heart transplant patients. Twelve patients (48%) died. During the first 9 months of 1996, the attack rate was 6% among cardiac and bone marrow transplant patients. For cases that occurred before 1996, intubation was associated with increased risk for disease. High-dose corticosteroid medication was strongly associated with the risk for disease, but other immunosuppressive therapy or cancer chemotherapy was not. Several species and serogroups of Legionella were isolated from numerous sites in the hospital's potable water system. Six of seven available clinical isolates were identical and were indistinguishable from environmental isolates by pulsed-field gel electrophoresis. Initial infection control measures failed to interrupt nosocomial acquisition of infection. After extensive modifications to the water system, closely monitored repeated hyperchlorinations, and reduction of patient exposures to aerosols, transmission was interrupted. No cases have been identified since September 1996.
Legionella can colonize hospital potable water systems for long periods of time, resulting in an ongoing risk for patients, especially those who are immunocompromised. In this hospital, nosocomial transmission possibly occurred for more than 17 years and was interrupted in 1996, after a sudden increase in incidence led to its recognition. Hospitals specializing in the care of immunocompromised patients (eg, transplant centers) should prioritize surveillance for cases of legionnaires' disease. Aggressive control measures can interrupt transmission of this disease successfully.