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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.
Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
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.
Geophysical granular flows, such as avalanches, debris flows, lahars and pyroclastic flows, are always strongly influenced by the basal topography that they flow over. In particular, localised bumps or obstacles can generate rapid changes in the flow thickness and velocity, or shock waves, which dissipate significant amounts of energy. Understanding how a granular material is affected by the underlying topography is therefore crucial for hazard mitigation purposes, for example to improve the design of deflecting or catching dams for snow avalanches. Moreover, the interactions with solid boundaries can also have important applications in industrial processes. In this paper, small-scale experiments are performed to investigate the flow of a granular avalanche over a two-dimensional smooth symmetrical bump. The experiments show that, depending on the initial conditions, two different steady-state regimes can be observed: either the formation of a detached jet downstream of the bump, or a shock upstream of it. The transition between the two cases can be controlled by adding varying amounts of erodible particles in front of the obstacle. A depth-averaged terrain-following avalanche theory that is formulated in curvilinear coordinates is used to model the system. The results show good agreement with the experiments for both regimes. For the case of a shock, time-dependent numerical simulations of the full system show the evolution to the equilibrium state, as well as the deposition of particles upstream of the bump when the inflow ceases. The terrain-following theory is compared to a standard depth-averaged avalanche model in an aligned Cartesian coordinate system. For this very sensitive problem, it is shown that the steady-shock regime is captured significantly better by the terrain-following avalanche model, and that the standard theory is unable to predict the take-off point of the jet. To retain the practical simplicity of using Cartesian coordinates, but have the improved predictive power of the terrain-following model, a coordinate mapping is used to transform the terrain-following equations from curvilinear to Cartesian coordinates. The terrain-following model, in Cartesian coordinates, makes identical predictions to the original curvilinear formulation, but is much simpler to implement.
A new method of electromagnetic sounding in resistive electrical environments has been developed for use in lunar exploration. It is applicable to the study of terrestrial glaciers and ice sheets. A horizontal electric dipole antenna on the ground is used to transmit power at frequencies of 1, 2, 4, 8, 16 and 32 MHz. A set of orthogonal receiving coils is mounted on a vehicle which traverses away from the transmitter. Field strength is recorded as a function of distance. Waves which travel above the surface interfere with waves from the subsurface, generating interference patterns which can be used to determine the dielectric constant, the loss tangent, and depth to reflecting horizons.
The technique was tested on the Athabasca Glacier in western Canada. At 1, 2 and 4 MHz the ice was found to have a dielectric constant of about 3.3, a loss tangent (tan δ) which is roughly inversely proportional to frequency giving values of f tan δ in the range 0.25 to 0.35 (where f is in MHz). These values correspond well with the known properties of ice near 0° C, which is a temperature typical of temperate glaciers. It has been possible to determine the depth of the ice but results are not always consistent with previous seismic and gravity surveys and with drilling. At frequencies of 16 and 32 MHz, scattering is the dominant feature of the results. At 8 MHz there is a transition from clear-cut interference patterns to the scattering patterns. From these findings, we suggest that the Athabasca Glacier has a large number of dielectric scatterers with dimensions less than about 35 m, probably due in large part to crevasses.
Geophysical granular flows, such as landslides, pyroclastic flows and snow avalanches, consist of particles with varying surface roughnesses or shapes that have a tendency to segregate during flow due to size differences. Such segregation leads to the formation of regions with different frictional properties, which in turn can feed back on the bulk flow. This paper introduces a well-posed depth-averaged model for these segregation-mobility feedback effects. The full segregation equation for dense granular flows is integrated through the avalanche thickness by assuming inversely graded layers with large particles above fines, and a Bagnold shear profile. The resulting large particle transport equation is then coupled to depth-averaged equations for conservation of mass and momentum, with the feedback arising through a basal friction law that is composition dependent, implying greater friction where there are more large particles. The new system of equations includes viscous terms in the momentum balance, which are derived from the
-rheology for dense granular flows and represent a singular perturbation to previous models. Linear stability calculations of the steady uniform base state demonstrate the significance of these higher-order terms, which ensure that, unlike the inviscid equations, the growth rates remain bounded everywhere. The new system is therefore mathematically well posed. Two-dimensional simulations of bidisperse material propagating down an inclined plane show the development of an unstable large-rich flow front, which subsequently breaks into a series of finger-like structures, each bounded by coarse-grained lateral levees. The key properties of the fingers are independent of the grid resolution and are controlled by the physical viscosity. This process of segregation-induced finger formation is observed in laboratory experiments, and numerical computations are in qualitative agreement.
In the year 1000 the Emperor Otto III went on a grandiose pilgrimage to Gnesen, to the tomb of his friend St Adalbert of Prague, martyred by the Prussians on the borders of their country on St George’s Day, 997. This visit has been seen as a significant moment in the development of the emperor’s imperial policies, but it may also be taken to mark the end of the first great age in the history of Christendom. By the time that Otto came to pay his respects at the shrine of this Germanized Bohemian, St Vojtiekh, and to raise it to metropolitan rank, Europe was outwardly Christian. The tenth century had completed the process begun with the first urban apostolic missions, and had seen the absorption of the Viking settlers into the Christian community, the conversion of the Magyars, the establishment of the faith in Bohemia, Poland, Russia and Denmark, the beginnings of successful missionary activity in the more northerly Scandinavian lands, and the reconversion of Crete. Whatever problems might remain in Islamic Spain, or with the tenacious paganism of the eastern Baltic, by the year 1000 Europe was Christian, and the missionary millennium was over.
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.
We investigated the prevalence, diversity, and antimicrobial resistance (AMR) profiles of non-typhoidal Salmonella (NTS) and associated risk factors on 341 pig, chicken, and duck farms in Dong Thap province (Mekong Delta, Vietnam). Sampling was stratified by species, district (four categories), and farm size (three categories). Pooled faeces, collected using boot swabs, were tested using ISO 6575: 2002 (Annex D). Isolates were serogrouped; group B isolates were tested by polymerase chain reaction to detect S. Typhimurium and (monophasic) serovar 4,,12:i:- variants. The farm-level adjusted NTS prevalence was 64·7%, 94·3% and 91·3% for chicken, duck and pig farms, respectively. Factors independently associated with NTS were duck farms [odds ratio (OR) 21·2], farm with >50 pigs (OR 11·9), pig farm with 5–50 pigs (OR 4·88) (vs. chickens), and frequent rodent sightings (OR 2·3). Both S. Typhimurium and monophasic S. Typhimurium were more common in duck farms. Isolates had a high prevalence of resistance (77·6%) against tetracycline, moderate resistance (20–30%) against chloramphenicol, sulfamethoxazole-trimethoprim, ampicillin and nalidixic acid, and low resistance (<5%) against ciprofloxacin and third-generation cephalosporins. Multidrug resistance (resistance against ⩾3 classes of antimicrobial) was independently associated with monophasic S. Typhimurium and other group B isolates (excluding S. Typhimurium) and pig farms. The unusually high prevalence of NTS on Mekong Delta farms poses formidable challenges for control.
In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
The effect of prenatal distress on the risk of a small for gestational age (SGA) infant is uncertain. We have addressed the influences of prenatal stress, anxiety and depression on the risk of SGA. We also examined the effects of infant sex and timing of distress during pregnancy on any observed associations.
The study population comprised 5606 healthy nulliparous pregnant women who participated in the international prospective Screening for Obstetric and Pregnancy Endpoints (SCOPE) study. Women completed the Perceived Stress Scale (PSS), the short form of the Spielberger State–Trait Anxiety Inventory (STAI) and the Edinburgh Postnatal Depression Scale (EPDS) at 15 ± 1 and 20 ± 1 weeks' gestation. SGA was defined as birthweight below the 10th customized percentile. Logistic regression was used for data analysis, adjusting for several potential confounders such as maternal age, body mass index (BMI), smoking, socio-economic status and physical exercise.
The risk of SGA was increased in relation to mild [adjusted odds ratio (aOR) 1.35, 95% confidence interval (CI) 1.07–1.71], moderate (aOR 1.26, 95% CI 1.06–1.49), high (aOR 1.45, 95% CI 1.08–1.95) and very high stress scores (aOR 1.56, 95% CI 1.03–2.37); very high anxiety score (aOR 1.45, 95% CI 1.13–1.86); and very high depression score (aOR 1.14, 95% CI 1.05–1.24) at 20 ± 1 weeks' gestation. Sensitivity analyses showed that very high anxiety and very high depression increases the risk of SGA in males but not in females whereas stress increases the risk of SGA in both males and females.
These findings suggest that prenatal stress, anxiety and depression measured at 20 weeks' gestation increase the risk of SGA. The effects of maternal anxiety and depression on SGA were strongest in male infants.
In 1969 David Easton argued that a new revolution was “underway in American political science.” This revolution, which he labelled the post-behavioral revolution, is motivated by a “deep dissatisfaction with political research and teaching, especially of the kind that is striving to convert the study of politics into a more rigorously scientific discipline modelled on the methodology of the natural sciences.” Specifically, post-behavioralists, according to Easton, attack the abstractness, irrelevance, “methodological purity” and conservatism of the existing literature, and argue that political scientists as well as the associations of which they are a part, must take a more active role in the solution of contemporary social problems. In short, post-behavioralists seek to “help create a ‘new political science’ that will not be trivial or misleading.” But, what is the nature of the support within the profession for this goal? In other words, what kinds of attitudes do American political scientists hold about this new revolution? In addition, what are their views on the behavioral revolution, the other major event in the recent history of the discipline?
To answer these questions we recently conducted a mail survey of 176 political scientists in the Mountain West (i.e. Arizona, Colorado, Idaho, Montana, Nevada, New Mexico, Utah and Wyoming.) Our questionnaire included twenty three items dealing with professional and related issues.
During an unusually massive filament eruption on 7 June 2011, SDO/AIA imaged for the first time significant EUV emission around a magnetic reconnection region in the solar corona. The reconnection occurred between magnetic fields of the laterally expanding CME and a neighbouring active region. A pre-existing quasi-separatrix layer was activated in the process. This scenario is supported by data-constrained numerical simulations of the eruption. Observations show that dense cool filament plasma was re-directed and heated in situ, producing coronal-temperature emission around the reconnection region. These results provide the first direct observational evidence, supported by MHD simulations and magnetic modelling, that a large-scale re-configuration of the coronal magnetic field takes place during solar eruptions via the process of magnetic reconnection.