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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.
Background: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers’ levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I2 statistic. Results: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. Conclusions: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.
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.
Poly (lactic acid) (PLA) bioplastics are recyclable and biodegradable thermoplastics. They are derived from environmentally friendly sources such as potatoes, cornstarch and sugarcane. However, PLA is inherently brittle with low impact strength. The goal of this study is to improve mechanical properties of PLA by the addition of calcium carbonate (CaCO3) fillers. PLA composites were prepared by injection molding conventional limestone (LS) and white chicken eggshell (WES) powders with particle sizes of 63 μm and 32 μm in amounts of 5 wt. %, 10 wt. % and 20 wt. %. Mechanical properties such as, tensile strength, tensile modulus, and Charpy impact strengths were investigated. These three properties were evaluated and the results statistically analyzed using ANOVA F-test. For both particle sizes, the tensile strength decreased as the filler content increased, but was highest for a filler loading of 5 wt. %. In general, the 32 μm powder fillers had better tensile strengths than 63 μm sized fillers. The tensile modulus increased with filler content and was highest at 20 wt. % for both particle sizes. The LS/PLA composites had better toughness than the WES/PLA composites. The particle filler morphology and fractured surfaces were observed by scanning electron microscopy (SEM) and determined to have well dispersed particles with smooth fractured surfaces. Water absorption behavior of PLA/CaCO3 composites were studied by immersion in distilled water at room temperature for 56 days. Virgin PLA absorbed the least amount of water while the water absorption of CaCO3 composites were a function of powder type and content.
Depression is a significant problem and it is vital to understand its underlying causes and related policy implications. Neighborhood characteristics are implicated in depression but the nature of this association is unclear. Unobserved or unmeasured factors may confound the relationship. This study addresses confounding in a twin study investigating neighborhood-level effects on depression controlling for genetics, common environment, and gene×environment (G × E) interactions.
Data on neighborhood deprivation and depression were gathered from 3155 monozygotic twin pairs and 1275 dizygotic pairs (65.7% female) between 2006 and 2013. The variance for both depression and neighborhood deprivation was decomposed into three components: additive genetic variance (A); shared environmental variance (C); and non-shared environmental variance (E). Depression was then regressed on neighborhood deprivation to test the direct association and whether that association was confounded. We also tested for a G × E interaction in which the heritability of depression was modified by the level of neighborhood deprivation.
Depression and neighborhood deprivation showed evidence of significant A (21.8% and 15.9%, respectively) and C (13.9% and 32.7%, respectively) variance. Depression increased with increasing neighborhood deprivation across all twins (p = 0.009), but this regression was not significant after controlling for A and C variance common to both phenotypes (p = 0.615). The G × E model showed genetic influences on depression increasing with increasing neighborhood deprivation (p < 0.001).
Neighborhood deprivation is an important contributor to depression via increasing the genetic risk. Modifiable pathways that link neighborhoods to depression have been proposed and should serve as targets for intervention and research.
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.
Livestock production is a major consumer of fresh water, and the influence of livestock production on global fresh water resources is increasing because of the growing demand for livestock products. Increasing water use efficiency of livestock production, therefore, can contribute to the overall water use efficiency of agriculture. Previous studies have reported significant variation in livestock water productivity (LWP) within and among farming systems. Underlying causes of this variation in LWP require further investigation. The objective of this paper was to identify the factors that explain the variation in LWP within and among farming systems in Ethiopia. We quantified LWP for various farms in mixed-crop livestock systems and explored the effect of household demographic characteristics and farm assets on LWP using ANOVA and multilevel mixed-effect linear regression. We focused on water used to cultivate feeds on privately owned agricultural lands. There was a difference in LWP among farming systems and wealth categories. Better-off households followed by medium households had the highest LWP, whereas poor households had the lowest LWP. The variation in LWP among wealth categories could be explained by the differences in the ownership of livestock and availability of family labor. Regression results showed that the age of the household head, the size of the livestock holding and availability of family labor affected LWP positively. The results suggest that water use efficiency could be improved by alleviating resource constraints such as access to farm labor and livestock assets, oxen in particular.
Understanding the nutritional demands on serving military personnel is critical to inform training schedules and dietary provision. Troops deployed to Afghanistan face austere living and working environments. Observations from the military and those reported in the British and US media indicated possible physical degradation of personnel deployed to Afghanistan. Therefore, the present study aimed to investigate the changes in body composition and nutritional status of military personnel deployed to Afghanistan and how these were related to physical fitness. In a cohort of British Royal Marines (n 249) deployed to Afghanistan for 6 months, body size and body composition were estimated from body mass, height, girth and skinfold measurements. Energy intake (EI) was estimated from food diaries and energy expenditure measured using the doubly labelled water method in a representative subgroup. Strength and aerobic fitness were assessed. The mean body mass of volunteers decreased over the first half of the deployment ( − 4·6 (sd 3·7) %), predominately reflecting fat loss. Body mass partially recovered (mean +2·2 (sd 2·9) %) between the mid- and post-deployment periods (P< 0·05). Daily EI (mean 10 590 (sd 3339) kJ) was significantly lower than the estimated daily energy expenditure (mean 15 167 (sd 1883) kJ) measured in a subgroup of volunteers. However, despite the body mass loss, aerobic fitness and strength were well maintained. Nutritional provision for British military personnel in Afghanistan appeared sufficient to maintain physical capability and micronutrient status, but providing appropriate nutrition in harsh operational environments must remain a priority.
The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae, and orphan afterglows of gamma-ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of 5 s and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.
We recently demonstrated that decline in fluid intelligence is a substantial contributor to frontal deficits. For some classical ‘executive’ tasks, such as the Wisconsin Card Sorting Test (WCST) and Verbal Fluency, frontal deficits were entirely explained by fluid intelligence. However, on a second set of frontal tasks, deficits remained even after statistically controlling for this factor. These tasks included tests of theory of mind and multitasking. As frontal dysfunction is the most frequent cognitive deficit observed in early Parkinson's disease (PD), the present study aimed to determine the role of fluid intelligence in such deficits.
We assessed patients with PD (n=32) and control subjects (n=22) with the aforementioned frontal tests and with a test of fluid intelligence. Group performance was compared and fluid intelligence was introduced as a covariate to determine its role in frontal deficits shown by PD patients.
In line with our previous results, scores on the WCST and Verbal Fluency were closely linked to fluid intelligence. Significant patient–control differences were eliminated or at least substantially reduced once fluid intelligence was introduced as a covariate. However, for tasks of theory of mind and multitasking, deficits remained even after fluid intelligence was statistically controlled.
The present results suggest that clinical assessment of neuropsychological deficits in PD should include tests of fluid intelligence, together with one or more specific tasks that allow for the assessment of residual frontal deficits associated with theory of mind and multitasking.
Human height and body mass index are influenced by a large number of genes, each with small effects, along with environment. To identify common genetic variants associated with these traits, we performed genome-wide association studies in 11,536 individuals composed of Australian twins, family members, and unrelated individuals at ∼550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (P value = 1.06 × 10–9) located in HHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (P values < 1 × 10–6): ADAMTSL3, EFEMP1, GPR126, and HMGA2; and BMI (P values < 1 × 10–4): FTO and MC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI.
Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Multidrug resistance gene-deficient (mdr1a− / − ) mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet–gene interactions and potential effects of foods on remission or development of IBD. The present study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a− / − mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets (control (AIN-76A), control +0·2 % curcumin or control +0·1 % rutin) and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a− / − mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways, probably mediated by pregnane X receptor (Pxr) and peroxisome proliferator-activated receptor α (Ppara) activation of retinoid X receptor (Rxr). These results indicate the potential of global gene expression and pathway analyses to study and better understand the effect of foods in modulating colonic inflammation.
Increasing evidence implicates reactive oxygen species, particularly hydrogen peroxide (H2O2), as intracellular and intercellular messengers in the brain. This raises the question of how the antioxidant network in the brain can be sufficiently permissive to allow messages to be conveyed yet, at the same time, provide adequate protection against oxidative damage. Here we present evidence that this is accomplished in part by differential antioxidant compartmentalization between glia and neurons. Based on the rationale that the glia-to-neuron ratio is higher in guinea-pig brain than in rat brain, we examined the neuroprotective role of the glial antioxidant network by comparing the consequences of H2O2 elevation in slices of guinea-pig and rat brain. The effects of exogenously applied H2O2 on evoked population spikes in hippocampal slices and on edema formation in forebrain slices were assessed. In contrast to the epileptiform activity observed in rat hippocampal slices after H2O2 exposure, no pathophysiology was seen in guinea-pig hippocampal slices. Similarly, elevated H2O2 caused edema in rat brain slices but not in guinea-pig brain tissue. The resistance of guinea-pig brain tissue to H2O2 challenge was lost, however, when glutathione (GSH) synthesis was inhibited (by buthionine sulfoximine), GSH peroxidase activity was inhibited (by mercaptosuccinate) or catalase was inhibited (by 3-amino-1, 2, 4, -triazole). Strikingly, exogenously applied ascorbate, a predominantly neuronal antioxidant, could compensate for the loss of any other single component of the antioxidant network. Together, these data imply significant roles for glial antioxidants and neuronal ascorbate in the prevention of pathophysiological consequences of the endogenous neuromodulator H2O2.
Despite the large body of research concerned with the near wake of a circular cylinder, the far wake, which extends beyond about 100 diameters downstream, is relatively unexplored, especially at low Reynolds numbers. We have recently shown that the structure of the far wake is exquisitely sensitive to free-stream noise, and is precisely dependent on the frequency and scale of the near wake; indeed it is shown that the presence of extremely low-amplitude peaks in the free-stream spectrum, over a remarkably wide range of frequencies, are sufficient to trigger an “oblique wave resonance” in the far wake.
We show, in the upper photograph of Fig. 1, a nonlinear interaction between oblique shedding waves generated from upstream (to the left) and 2–D waves amplified downstream from free-stream disturbances (in the central region). We use the “smoke-wire” technique (placed 50 diameters down-stream), and the wake is viewed in planview, with flow to the right. This two-wave interaction triggers a third wave, namely an “oblique resonance wave” at a large oblique angle, to grow through nonlinear effects (in the right half of the photograph), in preference to the original two waves. If smoke is introduced 100 diameters downstream, in the lower photograph (under slightly different conditions), then all that is seen is a set of such large-angle oblique resonance waves.
This work is supported by the Office of Naval Research.
Visualization of different transition mechanisms
The sequence of photos in Figs. 1(a)-1(d) illustrates the different types of boundary-layer transitions that occur as a function of Tollmien-Schlichting (T-S) wave amplitude and fetch.