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.

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.

Ligand-receptor interactions via hydrogen-bond formation. Synthesis and pharmacological evaluation of pyrrolo and pyrido analogues of the cardiotonic agent 7-hydroxycyclindole.

The syntheses of N,N-dimethyl-6,7,8,9-tetrahydro-3H,10H-pyrrolo[3,2-a] carbazol-7-amine (8), N,N-dimethyl-7,8,9,10-tetrahydro-11H-pyrido[3,2-a] carbazol-8-amine (9a), and the N,N,11-trimethyl analogue (9b) are described. The in vitro inotropic activity of these compounds, as well as the known cardiotonics amrinone and 7-hydroxycyclindole (7), was investigated. Compound 8, a pyrrolo analogue of 7, was devoid of inotropic activity, while the pyrido analogues 9 were equiactive to 7 and amrinone. These results suggest that the hydroxyl group of 7 functions as an H-bond acceptor, rather than a donor, and that on interaction of 7, and the pyrido analogues 9, with a common receptor, an orbital occupied by one of the oxygen lone pair electrons of 7 must assume the same orientation as the orbital occupied by the pyridine nitrogen lone pair.

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.

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.

New fine structural observations in testicular malakoplakia: role of the Sertoli cell.

A case of testicular malakoplakia is described in which cells other than histiocytes were involved in the tissue response. The abundant cell junctions, some closely related to mitochondria, and the peripheral displacement of rough endoplasmic reticulum by abundant phagolysosomes, suggest involvement of Sertoli cells, in addition to histiocytes. It is suggested that, perhaps, some forms of granulomatous orchitis and malakoplakia represent a single disease process observed at a different stage in its evolution.

Doctors and their workshops. A review article.

In this paper we present a theoretical framework for reviewing the main points treated by Pauly (1980). Moreover, we isolate the issues which still need further research. Finally, we briefly discuss the overall message of Pauly's book: Standard Economic Models Can Explain Behavior in the Medical Care Industry.

More on the geographical distribution of physicians.

This paper presents more empirical evidence on the geographical distribution of physicians. Probit procedure and data for the Province of Quebec were used. The results are consistent with the standard location theory and therefore with those of Newhouse et al. (1982a). They also show that quality of leisure, distance to central city areas, average income and presence of a hospital are significant in explaining the probability that at least one physician (specialist or general practitioner) is present in a given town. Other variables were also considered.

Patient mobility for elective surgical interventions.

In this study, we address the question of patient mobility by defining three types of mobility and testing them with a Probit model. First, we have forced mobility (shortage of resources), second, physician-induced mobility (hospital affiliations) and finally, the mobility chosen by patients. We isolate explanatory variables for observed patient mobility for the year 1977-1978 in Quebec, Canada, and present the results for two specific surgical interventions. We found that forced and induced mobility are statistically significant in explaining the movements of patients in search of specific medical services. However, the mobility chosen by patients requires further investigation.

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.

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.

Tonofilaments in normal human bronchial epithelium and in squamous cell carcinoma.

Tonofilaments in the cells of squamous cell carcinoma of human bronchial epithelium were observed and compared to those in normal bronchial epithelium in 2 patients. In the normal tissue, only small numbers of tonofilaments were observed, and these were found only in the basal cells of the epithelium. In the tumor cells, the quantity of filaments increased considerably. They appeared in the cytoplasm both as branching and anastomosing bundles (tonofibrils) and also as single filaments about 40 A in thickness. These bundles were particularly well developed in the core of narrow cytoplasmic processes of tumor cells. The thickness and appearance of single tonofilaments were similar to those of the cytoplasmic microfilaments also observed in this study. It is suggested that the development of tonofilament bundles in the cytoplasmic processes of tumor cells may provide direct motive force for the deformation of the shape of the cell and potential invasiveness of these tumor cells.

A scanning electron microscopic study of diffuse mesothelioma and some lung carcinomas.

Seventeen cancers from lung and pleura were studied with scanning, transmission electron, and light microscopy (SEM, TEM and LM). Diffuse mesothelioma mimics bronchioloalveolar carcinoma at LM but shaggy microvilli were found on the cellular surface of the former, and short sprouts densely packed or loosely scattered, on that of the latter. Neolumen formation was found in both. Oat cell carcinoma had a smooth surface with occasional tiny projections and minute surface depressions. The cellular projections of squamous cell carcinoma were quite irregular. Differentiation between diffuse mesothelioma and bronchioloalveolar carcinoma appears feasible with SEM in tissue appropriately fixed either with formaldehyde or glutaraldehyde. The role SEM can play in diagnostic pathology is yet to be explored.

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.