The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

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.

Environmental influence of problematic social relationships on adolescents' daily cortisol secretion: a monozygotic twin-difference study.

BACKGROUND: This study investigated the potential environmental effects of peer victimization and the quality of relationships with parents and friends on diurnal cortisol secretion in mid-adolescence. METHOD: This study used the monozygotic (MZ) twin-difference design to control for genetic effects and thus estimate the unique environmental influences on diurnal cortisol. Participants were 136 MZ twin pairs (74 female pairs) for whom cortisol was assessed four times per day over four collection days grouped in a 2-week period in grade 8 (mean age = 14.07 years). Participants also provided self-reports of peer victimization from grade 4 to grade 8 and of the relationship quality with the mother, father and best friend in grade 8. RESULTS: The expected pattern of diurnal cortisol secretion was observed, with high levels at awakening followed by an increase 30 min later and a progressive decrease subsequently. Controlling for a host of confounders, only within-twin pair differences in peer victimization and a problematic relationship with the mother were significantly linked to twin differences in diurnal cortisol secretion. Specifically, whereas a more problematic mother-child relationship was associated with morning cortisol secretion, peer victimization was linked to cortisol secretion later in the day (diurnal slope). CONCLUSIONS: Controlling for genetic influences and other confounders, stressful relationships with peers and the mother exert unique and time-specific environmental influences on the pattern of diurnal cortisol secretion in mid-adolescence.

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

BACKGROUND: Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. METHOD: Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. RESULTS: The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. CONCLUSIONS: Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

The effect of A-site substitution of Ce and La on the magnetic and electronic properties of Sr(Ti0.6Fe0.4)O(3-δ) films.

The structure and magnetic properties of epitaxial (Ce(x)Sr(1-x))(Ti(0.6)Fe(0.4))O(3-δ) (x = 0, 0.1, 0.2 and 0.3) and (La(x)Sr(1-x))(Ti(0.6)Fe(0.4))O(3-δ) (x = 0, 0.1, 0.2, 0.3 and 0.4) perovskite-structure thin films deposited by pulsed laser deposition on (LaAlO(3))(0.3)(Sr(2)AlTaO(6))(0.7) (LSAT) substrates are reported. Both La and Ce ions showed a dominant 3+ valence state and acted as donors on the Sr(2+) site (A site) in the perovskite lattice. The optical band gap widened, and the Fermi level moved toward the vacuum level with increased Ce or La content; meanwhile the Ti and particularly the Fe ions were driven to a lower valence state, resulting in a higher Fe(2+) concentration. The materials were magnetic at room temperature with up to 0.8 µ(B)/Fe and a magnetoelastic out-of-plane anisotropy. Ce and La lowered the coercivity while raising both the Faraday rotation at 1550 nm and the optical absorption at near-infrared wavelengths.

Lexical and grammatical development: a behavioural genetic perspective.

The relation of lexical and grammatical knowledge is at the core of many controversies in linguistics and psycholinguistics. Recent empirical findings that the two are highly correlated in early language development have further energized the theoretical debate. Behavioural genetics provides an illuminating new tool to explore this question, by addressing the question of whether the empirical correlation simply reflects the fact that environments which facilitate one aspect of language growth also facilitate the other, or whether the same underlying acquisition mechanisms, influenced by the same genes, are responsible for the correlation. We explored this issue in a study of 2898 pairs of two-year-old twins born in England and Wales. Language development was assessed by their parents using an adapted version of the MacArthur Communicative Development Inventory which assesses vocabulary and grammar. Moderate heritabilities were found for both. As in previous studies, measures of vocabulary and sentence complexity were substantially correlated (r = 0.66). Behaviour-genetic modelling of the relation of vocabulary and grammar produced an estimated value of 0.61 for the genetic correlation, a measure of the overlap of the genetic effects that contribute to the two aspects of language development. In contrast, a measure of nonverbal cognitive development, the PARCA, was only weakly correlated at both the phenotypic level and at the level of genetic correlations with the language measures. Thus, although the distinction between verbal and nonverbal skills has a genetic basis underlying the phenotypic dissociation, there is little evidence either genetically or phenotypically for a dissociation between vocabulary and grammar within language.

Impact of diabetes on crash risks of truck-permit holders and commercial drivers.

OBJECTIVE: The U.S. and some Canadian government agencies have waived commercial license restrictions for some insulin-using diabetic drivers. However, the U.S. Federal Highway Administration is no longer giving waivers. Scientific evidence to support such regulations has been sparse. This article presents detailed analyses of crash risks for users and nonusers of insulin among diabetic truck-permit holders in Québec, Canada. RESEARCH DESIGN AND METHODS: Diabetic truck-permit holders were group-matched by age to a random sample of healthy permit holders. Data on permits, medical conditions, and crashes involving 13,453 permit holder-years in 1987-1990 were extracted from the files of the public insurer for automobile injuries in Québec. Additional health status data were obtained from the provincial public health insurer. A telephone survey was conducted to collect data on driving patterns and exposure. Risk ratios were estimated using negative binomial regression models. RESULTS: Risk ratios for crashes vary by category of diabetes. Permit holders for single-unit trucks (STs) who are diabetic without complications and not using insulin have an increased crash risk of 1.68 when compared with healthy permit holders of the same permit class. When controlling for risk exposure, commercial drivers with an ST permit and the same diabetic condition have an increased risk of 1.76. Insulin use is not associated with higher crash risk. CONCLUSIONS: The increased crash risk for the group with uncomplicated diabetes not using insulin is a new finding. The lack of consistent increases in crash risks among diabetic commercial drivers with complications or who use insulin may be a "healthy worker effect" masking the real risk, because these licensees have a lower participation rate as professional drivers.

Taxi drivers' accidents: how binocular vision problems are related to their rate and severity in terms of the number of victims.

Recent studies do not agree on the possible relationship between medical conditions and traffic safety; most of them do not control for exposure factors. In this study, we estimate the effect of binocular vision problems on taxi drivers' distributions of crashes (frequency). Moreover, given a crash, we estimate the effect of binocular vision problems on the distributions of the number of victims per crash (dead or injured). Our data and models permit the simultaneous consideration of many variables: age, medical condition, exposure factors measured by distance driven and time behind the wheel, qualitative risk factors, other characteristics of the driver, and crash circumstances in the models for the number of victims. Results show that taxi drivers have a large average number of crashes per year, larger for those with binocular vision problems compared with healthy ones, but not more severe in terms of the number of victims. The driver's past record (number of crashes and demerit points in the previous year) is a significant predictor of the number of crashes. Age is associated significantly with the number and the severity of crashes with older drivers having a better record than the youngest group (30 years old or less).

Medical conditions and the severity of commercial motor vehicle drivers' road accidents.

In this research we studied the association between commercial motor vehicle drivers' medical conditions and crash severity. Some aspects of medical condition were considered. To our knowledge, no study has ever isolated this association. The severity of a crash was measured by the total number of victims (injured and dead). We estimated nonlinear regression models (specifically, Poisson and negative binomial) which incorporated, simultaneously, information on drivers' characteristics, crash circumstances and health status, in order to isolate the association between health status and crash severity. Our results show that crashes of truck drivers with binocular vision problems and bus drivers with hypertension are more severe than those of healthy drivers. No other medical condition considered in this study was significantly associated with crash severity. Many variables describing crash circumstances were also significant.

Medical conditions, risk exposure, and truck drivers' accidents: an analysis with count data regression models.

Recent studies do not agree on the possible relationship between medical conditions and traffic safety; most of them do not control for exposure factors. This problem has become more pertinent for scientific studies because of litigation that showed that present regulations about access to driver permits might contravene human rights legislation. In our study, we estimate the effect of different medical conditions on truck drivers' distributions of accidents. Our data and our models permit simultaneous control for age; medical conditions; exposure factors measured by hours, kilometer, and qualitative factors; and other characteristics of truck drivers. Our results show that diabetic truck drivers of the permit class for straight trucks have more accidents than drivers in good health. No other studied medical condition has a significant effect on individual accident distributions. Many risk exposure variables are also significant. The effect of age is discussed in detail.

Further studies on the adjuvanticity of stearyl tyrosine and amide analogues.

Stearly tyrosine has been described in the literature as a candidate adjuvant for human vaccines. More recently, other stearyl esters have been reported to be adjuvant-active. This preliminary study assesses the adjuvanticity of stearyl amides, including the amide analogue of stearyl tyrosine: tyrosyl stearylamine. This study indicates that phenylalanylethanolamine O-stearate induces a significant antibody response and a favourable isotype distribution.

Magnetic resonance imaging in moyamoya disease.

The authors describe the characteristic magnetic resonance imaging (MRI) findings of moyamoya disease in a 51-year-old woman; the disease was confirmed by angiography. MRI demonstrated well the occlusions and collateral vessels that typically occur secondary to this rare disease. Although hemorrhagic complications often result in a poor prognosis for patients with moyamoya disease, the patient described here recovered.

Preoperative prediction of pulmonary complications following thoracic surgery.

The ability of preoperative quality-of-life and physiologic variables to predict postoperative complications was tested in 117 consecutive patients undergoing thoracotomy for possible or definite lung cancer. Preoperatively, quality of life was globally assessed by the QLI and Sickness Impact Profile. Dyspnea was assessed by the Clinical Dyspnea Index and a modified Pneumoconiosis Research Unit question. Spirometry and maximal exercise testing were carried out in 115 and 46 subjects, respectively. Thirty-seven percent experienced at least one respiratory complication (eg, pneumonia, atelectasis prompting bronchoscopy, pulmonary embolism). Twofold or greater increases in respiratory complications were associated with current smoking (p < 0.05), cancer as the final pathologic condition (p < 0.10), at least moderate dyspnea (p < 0.10), FEV 1 < 60 percent of predicted (p < 0.05), ventilatory reserve < 25 L (p < 0.05), and VO2max < 1.25 L (p < 0.05). Twofold increases in the incidence of any complication (respiratory, cardiac, etc) were associated with age > or = 75 years (p < 0.05) and cancer as the final pathologic condition (p < 0.05). We conclude that simple historic information (age, smoking status, cancer status, dyspnea) indicates the risk of postoperative morbidity. General quality-of-life measures were not good predictors of morbidity. Our findings corroborate the few studies supporting the value of VO2max and suggest that the usefulness of the ventilatory reserve deserves further attention.

Further studies on the adjuvanticity of stearyl tyrosine and ester analogues.

A new family of immunoadjuvants, long-chain stearyl esters of amino acids and peptides, are described and examined with bacterial and viral vaccines. The parent compound, stearyl tyrosine, displayed significant adjuvant activity with these vaccines. Stearyl glycyl glycine displayed superior activity with viral vaccines. A number of analogues of stearyl tyrosine were adjuvant-active. Further, these adjuvants were able to elicit a neutralizing antibody response. Stearyl tyrosine and stearyl ester analogues represent promising adjuvants for human vaccines.

Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.

We selected in vitro human immunodeficiency virus type 1 variants that are resistant to each of 2',3'-dideoxycytidine (ddC) and the racemic mixture of 2',3'-dideoxy-3'-thiacytidine (BCH-189). The median effective concentrations of ddC and BCH-189 obtained for the resistant viruses ranged between 10 and 50 times above those for parental wild-type strains, and extensive cross-resistance was observed against 2',3'-dideoxyinosine (ddI) but not 3'-azido-3'-deoxythymidine (AZT). Two dimer compounds, in which either AZT and ddI or AZT and BCH-189 were linked through phosphodiester linkages, did not permit the emergence of variants resistant to BCH-189, ddI, or AZT but were ineffective at inhibiting the replication of AZT-resistant viruses.

Laparoscopic cholecystectomy and choledocholithiasis.

Between November 1990 and March 1991, five patients with cholelithiasis and associated choledocholithiasis were treated by laparoscopic cholecystectomy and common-bile-duct exploration (CBDE). Three patients had a successful CBDE, but in two common-bile-duct stones had to be extracted surgically. Two patients had formal laparoscopic CBDE, and three patients had CBDE performed through the cystic duct. All patients recovered from surgery without complication. Laparoscopic CBDE is difficult to perform because of lack of adequate instrumentation and limited experience. Although the authors do not recommend that this procedure be performed widely at present, they believe it will eventually replace many open CBDEs. The authors review the pertinent literature and evaluate diagnostic means for preoperative and peroperative detection of choledocholithiasis. They discuss the alternatives to laparoscopic CBDE, their advantages and disadvantages. Finally, they summarize their own policy with respect to laparoscopic CBDE.

Adjuvanticity of stearyl tyrosine on the antibody response to peptide 503-535 from HIV gp160.

In this present report we compare the humoral immune response induced by immunization with an HIV-1 gp160 peptide corresponding to amino acid sequence 503-535 complexed with different adjuvants. Specifically, the antipeptide, anti-HIV-1 gp160 and neutralizing antibody responses were measured in groups of mice and baboons that received peptide 503-535 conjugated to a carrier protein in either saline, alum, or stearyl tyrosine. The highest antibody responses were induced when mice and baboons were immunized with peptide adsorbed on stearyl tyrosine. These data indicate that stearyl tyrosine represents a potent candidate as a nontoxic adjuvant not only for subunit viral vaccines, but also for HIV peptides.

Induction of antibodies to the envelope protein of the human immunodeficiency virus by immunization with monoclonal anti-idiotypes.

Anti-idiotypes that possess the internal image of antigen can induce protective humoral immunity toward microbes. Herein we demonstrate antigen mimicry by monoclonal anti-idiotypes of a distinct epitope of the human immunodeficiency virus (HIV) envelope protein that is defined by a synthetic peptide. This peptide, corresponding to amino acid residues 503-535 (peptide 503-535) of HIV-1 IIIB gp160, induced antibodies in three mammalian species that interacted with HIV-1 gp120 and inhibited in vitro syncytium formation caused by HIV-1, IIIB and MN isolates. Three monoclonal anti-idiotypes were generated against rabbit anti-gp120 antibodies specific for peptide 503-535. These anti-idiotypes recognize an interspecies cross-reactive idiotype expressed on mouse, chimpanzee, baboon, rabbit, and human anti-gp120 antibodies specific for peptide 503-535. The interaction with the cross-reactive idiotype is inhibited by synthetic peptide and HIV-1 gp160. Furthermore, rabbits immunized with the monoclonal anti-idiotypes produced antibodies that also bind HIV-1 gp120 and gp160 and recognized the epitope defined by peptide 503-535.

Hot-tip laser angioplasty for peripheral vascular disease: clinical experience with 18 patients.

Between May 1988 and March 1989, the authors treated 18 patients who suffered from disabling claudication or rest pain. They used the laser hot-tip angioplasty technique, in which a metal tip on the laser transforms laser energy into heat. Nineteen lower extremities were so treated. Six patients had suffered iliac occlusion, 11 had disease in the superficial femoral artery and 1 in the popliteal artery. Laser angioplasty was successful in 7 of 13 lower limbs with infrailiac lesions and in 4 of the 6 limbs with iliac artery occlusion; the other 2 underwent bypass grafting (aortoiliac in 1 and aortobifemoral in the other). No loss or limb or death occurred, but immediate complications of perforation or dissection were frequent.

The adjuvant effect of stearyl tyrosine on a recombinant subunit hepatitis B surface antigen.

We describe the enhancement of the antibody response against hepatitis B surface Ag by octadecyl L-tyrosine, a synthetic adjuvant designed to exert its adjuvant effect in a manner similar to that of alum because it binds soluble Ag and releases it slowly from the site of injection. Our data demonstrate that octadecyl L-tyrosine showed a significant enhancement of the antihepatitis B surface Ag response compared to that of alum in the secondary response. The most striking difference between octadecyl L-tyrosine and alum in the antihepatitis B surface Ag antibody response was the absence of IgE-specific antibodies subsequent to immunization of the Ag in octadecyl L-tyrosine. Both the optical isomers of the octadecyl esters of tyrosine were adjuvant active, however, the racemic mixture showed a significantly lowe adjuvant activity. This adjuvant has great potential to be used in humans because it is devoid of side effects as assessed by the lack of acute and chronic toxicity in mice and rats, pyrogenicity in rabbits, formation of granuloma in cats, and adjuvant arthritis in rats.