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Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
Given any rectangular polyhedron
$3$
-manifold
$\mathcal {P}$
tiled with unit cubes, we find infinitely many explicit directions related to cubic algebraic numbers such that all half-infinite geodesics in these directions are uniformly distributed in
$\mathcal {P}$
.
In alcoholism, one relevant mechanism contributing to relapse is the exposure to stimuli that are associated with alcohol intake. Such conditioned cues can elicit conditioned responses like alcohol craving and consumption. In the last decade, considerable progress has been made in identifying basic neuronal mechanisms that underlie cue-induced alcohol craving.
Objectives/ aims
We explored whether functional brain activation during exposure to alcohol-associated stimuli is related to the prospective relapse risk in detoxified alcohol-dependent patients.
Methods
46 alcohol-dependent and 46 healthy volunteers participated in a fMRI study using a cue reactivity paradigm, in which visual alcohol-related and control stimuli were presented. Patients were followed for 3 months. Afterwards data was analysed regarding the subsequent relapse, resulting in 16 abstainers and 30 relapsers.
Results
Alcohol-related versus neutral stimuli activated a frontocortical-limbic network including inferior, medial and middle frontal gyrus as well as putamen in the group of patients relative to healthy controls. Moreover, abstainers showed a stronger activation in orbitofrontal cortex as well as midbrain during the presentation of alcohol-related cues whereas relapsers revealed a stronger activation of cingulate gyrus.
Conclusions
This study suggests that cue-induced activation of orbitofrontal cortex and dopaminergic innervated midbrain is negatively associated with the prospective relapse risk in alcohol-dependent patients. This could indicate a more pronounced and conscious processing of alcohol cues which might serve as a warning signal and a behavioural controlling function. In contrast, prospective relapsers showed a stronger activation of cingulate gyrus, a region involved in the attribution of motivational value.
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.
Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.
Leafy spurge control with four herbicides was evaluated at nine sites in six Great Plains states. Sulfometuron alone did not control leafy spurge satisfactorily 12 mo after treatment (MAT). Sulfometuron plus dicamba at 105 plus 2240 g ai ha−1, when spring- or fall-applied, averaged 26 and 89% control and 31 and 86% grass injury, respectively, 12 MAT. Sulfometuron plus picloram at 105 plus 560 g ai ha−1, when spring- or fall-applied, averaged 63 and 92% control and 19 and 89% grass injury, respectively, 12 MAT.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. Results: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. Conclusions: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned. (JINS, 2016, 21, 293–302)
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.
This article discusses the magnitude and rate of change of radiocarbon reservoir ages from the surface ocean in the South Pacific during the Holocene. 14C reservoir ages are calculated from paired U/Th and 14C measurements. Seventeen pairs of coral dates were determined from samples collected on Rendova and Tetepare Islands, in the Solomon Islands, and from Espiritu Santo Island, Vanuatu. The samples are all Holocene in age, with 230Th ages ranging from about 400 to 9400 BP. Samples were collected as drill cores or surface outcrops. About half of the surface samples appear to have incorporated modern carbon through postdepositional recrystallization. Two of the core samples were also affected by carbon exchange. The Holocene 14C reservoir ages observed in this data set show stable values for the last 3000 yr, and substantial variability from 5000–6000 BP (~100 to ~950 14C yr). Persistent low values (<200 14C yr) were observed for samples from 7000–8000 BP. We attribute these variations to temporal changes in lateral advection and vertical mixing, and possibly to local environmental conditions related to the interplay between sea-level rise and episodic uplift, characteristic of all the coral localities.
The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4–10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time. (JINS, 2014, 20, 238–247)
We carried out an extensive photometric and spectroscopic investigation of the SPB binary, HD 25558 (see Fig. 1 for the time and geographic distribution of the observations). The ~2000 spectra obtained at 13 observatories during 5 observing seasons, the ground-based multi-colour light curves and the photometric data from the MOST satellite revealed that this object is a double-lined spectroscopic binary with a very long orbital period of about 9 years. We determined the physical parameters of the components, and have found that both lie within the SPB instability strip. Accordingly, both components show line-profile variations consistent with stellar pulsations. Altogether, 11 independent frequencies and one harmonic frequency were identified in the data. The observational data do not allow the inference of a reliable orbital solution, thus, disentangling cannot be performed on the spectra. Since the lines of the two components are never completely separated, the analysis is very complicated. Nevertheless, pixel-by-pixel variability analysis of the cross-correlated line profiles was successful, and we were able to attribute all the frequencies to the primary or secondary component. Spectroscopic and photometric mode-identification was also performed for several of these frequencies of both binary components. The spectroscopic mode-identification results suggest that the inclination and rotation of the two components are rather different. While the primary is a slow rotator with ~6 d rotation period, seen at ~60° inclination, the secondary rotates fast with ~1.2 d rotation period, and is seen at ~20° inclination. Our spectropolarimetric measurements revealed that the secondary component has a magnetic field with at least a few hundred Gauss strength, while no magnetic field was detected in the primary.
The detailed analysis and results of this study will be published elsewhere.
The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.
High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems, and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.