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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.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
We present a high-resolution transmission electron microscopy study, on the unit-cell scale, of the degree of tetragonality and the displacements of cations away from the centrosymmetry positions in an ultra-thin epitaxial PbZr0.2Ti0.8O3 film on a SrRuO3 electrode layer deposited on a SrTiO3 substrate. TEM results show that the lattice is highly tetragonal at the centre of the film with a c/a ratio of about 1.08, while it shows a reduced degree of tetragonality in the regions close to the interfaces. Most strikingly, we find that the maximum off-centre displacements for the central area of the film do not scale with the tetragonality in comparison with the bulk materials. The calculated switched polarization from the measured cationic displacement is 80 ìC/cm2 , and thus only half of the nominal bulk value. It is in very good agreement with electrical measurements of the switched polarization obtained via the PUND method. Furthermore, a systematic reduction of the atomic displacements is measured at the interfaces. This suggests that interface-induced suppression of the ferroelectric polarization plays a critical role in the size effect of nanoscale ferroelectrics. These issues will be discussed further in this presentation. This work was partially supported by the National Science Foundation (NSF) under Grants DMR-0132918, NSF-MRSEC DMR-0080008, and an NSF US-Europe program DMR-0244288. V.N also acknowledges the support of the Alexander von Humboldt Foundation for his stay in Germany and the financial support of an Australian Research Council Discovery Grant 0666231.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.
Molecular dynamics simulations of different defective kaolinites under tension were performed to reveal the effects of defect location, type, density and temperature on their mechanical properties. Four types of defective kaolinite with Si vacancies were constructed. Based on the atomic-scale deformation and failure processes of defective kaolinite and its stress–strain curves, the Young's moduli and tensile strengths in three crystal directions were obtained and compared with the existing theoretical values from the literature. The defect location at each layer does not affect the mechanical properties of kaolinite and the cracks initiated at the defective sites. The atom density of each model was calculated in order to investigate the defect-type effect on the mechanical properties of kaolinite. The simulation results also showed that kaolinite exhibits brittle failure behaviour and the mechanical properties degrade significantly with increasing defect density and temperature. The influence of temperature on the mechanical properties of defective kaolinite is discussed in detail.
The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.
Atom probe tomography (APT) is rising in influence across many parts of materials science and engineering thanks to its unique combination of highly sensitive composition measurement and three-dimensional microstructural characterization. In this invited article, we have selected a few recent applications that showcase the unique capacity of APT to measure the local composition at structural defects. Whether we consider dislocations, stacking faults, or grain boundary, the detailed compositional measurements tend to indicate specific partitioning behaviors for the different solutes in both complex engineering and model alloys we investigated.
High Na intake and chronically elevated cortisol levels are independently associated with the development of chronic diseases. In adults, high Na intake is associated with high levels of urinary cortisol. We aimed to determine the association between urinary Na and K and urinary cortisol in a cross-sectional sample of Australian schoolchildren and their mothers. Participants were a sample of Australian children (n 120) and their mothers (n 100) recruited through primary schools. We assessed Na, K, free cortisol and cortisol metabolites in one 24 h urine collection. Associations between 24 h urinary electrolytes and 24 h urinary cortisol were assessed using multilevel mixed-effects linear regression models. In children, urinary Na was positively associated with urinary free cortisol (β=0·31, 95 % CI 0·19, 0·44) and urinary cortisol metabolites (β=0·006, 95 % CI 0·002, 0·010). Positive associations were also observed between urinary K and urinary free cortisol (β=0·65, 95 % CI 0·23, 1·07) and urinary cortisol metabolites (β=0·02, 95 % CI 0·03, 0·031). In mothers, urinary Na was positively associated with urinary free cortisol (β=0·23, 95 % CI 0·01, 0·50) and urinary cortisol metabolites (β=0·008, 95 % CI 0·0007, 0·016). Our findings show that daily Na and K intake were positively associated with cortisol production in children and their mothers. Investigation of the mechanisms involved and the potential impact of Na reduction on cortisol levels in these populations is warranted.
Hydrogen is an important intermediate that is produced during carbohydrate fermentation to volatile fatty acid and utilized by methanogens to produce methane in the rumen. Ruminal volatile fatty acid and dissolved methane concentrations are more than 500 times greater than dissolved hydrogen concentration. Therefore, we hypothesized that dissolved hydrogen might have a higher sensitivity in response to dietary changes compared with volatile fatty acid and dissolved methane. Using goats, we investigated the effects of increasing dietary starch content (maize replaced with wheat bran) and supplementing with rhubarb rhizomes and roots on the relationships among dissolved hydrogen, dissolved methane and other fermentation end products. The study was conducted in a replicated 4×4 Latin square with a 2×2 factorial arrangement of four treatments: two starch levels (220 v. 320 g/kg dry matter (DM)), without and with rhubarb supplement (0% v. 2.8% of total mixed ration). Increased dietary starch and rhubarb supplementation did not alter volatile fatty acid concentrations or methane emissions in terms of g/day, g/g DM intake and g/g organic matter digested. However, goats fed the high-starch diet had greater dissolved hydrogen (P=0.005) and relative abundance of Selenomonas ruminantium (P<0.01), and lower (P=0.02) copy number of protozoa than those fed the low-starch diet. Rhubarb increased ruminal dissolved H2 (P=0.03) and total volatile fatty acid concentration (P<0.001), but decreased copies of bacteria (P=0.002). In conclusion, dissolved hydrogen appears to be more sensitive to dietary changes with starch content and rhubarb supplementation, when compared with volatile fatty acid concentrations and methane production.
Cultivated pastures in southern China are being used to improve forage productivity and animal performance, but studies on grazing behaviour of goats in these cultivated pastures are still rare. In the current study, the grazing behaviour of Yunling black goats under low (5 goats/ha) and high (15 goats/ha) stocking rates (SRs) was evaluated. Data showed that the proportion of time goats spent on activities was: eating (0.59–0.87), ruminating (0.05–0.35), walking (0.03–0.06) and resting (0.01–0.03). Compared with low SR, goats spent more time eating and walking, and less time ruminating and resting under high SR. Goats had similar diet preferences under both SR and preferred to eat grasses (ryegrass and cocksfoot) more than a legume (white clover). The distribution of eating time on each forage species was more uniform under high v. low SR. Bites/step, bite weight and daily intake were greater under low than high SR. Results suggest that the SR affects grazing behaviour of goats on cultivated pasture, and identifying an optimal SR is critical for increasing bite weight and intake.
The gastrointestinal tract (GIT) of animals is capable of sensing various kinds of nutrients via G-protein coupled receptor-mediated signaling transduction pathways, and the process is known as ‘gut nutrient chemosensing’. GPR40, GPR41, GPR43 and GPR119 are chemoreceptors for free fatty acids (FFAs) and lipid derivatives, but they are not well studied in small ruminants. The objective of this study is to determine the expression of GPR40, GPR41, GPR43 and GPR119 along the GIT of kid goats under supplemental feeding (S) v. grazing (G) during early development. In total, 44 kid goats (initial weight 1.35±0.12 kg) were slaughtered for sampling (rumen, abomasum, duodenum, jejunum, ileum, cecum, colon and rectum) between days 0 and 70. The expression of GPR41 and GPR43 were measured at both mRNA and protein levels, whereas GPR40 and GPR119 were assayed at protein level only. The effects of age and feeding system on their expression were variable depending upon GIT segments, chemoreceptors and expression level (mRNA or protein), and sometimes feeding system × age interactions (P<0.05) were observed. Supplemental feeding enhanced expression of GPR40, GPR41 and GPR43 in most segments of the GIT of goats, whereas G enhanced expression of GPR119. GPR41 and GPR43 were mainly expressed in rumen, abomasum and cecum, with different responses to age and feeding system. GPR41 and GPR43 expression in abomasum at mRNA level was greatly (P<0.01) affected by both age and feeding system; whereas their expression in rumen and abomasum at protein level were different, feeding system greatly (P<0.05) affected GPR41 expression, but had no effect (P>0.05) on GPR43 expression; and there were no feeding system×age interactions (P>0.05) on GPR41 and GPR43 protein expression. The expression of GPR41 and GPR43 in rumen and abomasum linearly (P<0.01) increased with increasing age (from days 0 to 70). Meanwhile, age was the main factor affecting GPR40 expression throughout the GIT. These outcomes indicate that age and feeding system are the two factors affecting chemoreceptors for FFAs and lipid derivatives expression in the GIT of kids goats, and S enhanced the expression of chemoreceptors for FFAs, whereas G gave rise to greater expression of chemoreceptors for lipid derivatives. Our results suggest that enhanced expression of chemoreceptors for FFAs might be one of the benefits of early supplemental feeding offered to young ruminants during early development.
Moringa oleifera seeds are currently being used as a livestock feed across tropical regions of the world due to its availability and palatability. However, limited knowledge exists on the effects of the raw seeds on ruminant metabolism. As such, the rumen stimulation technique was used to evaluate the effects of substituting increasing concentrations of ground Moringa seeds (0, 100, 200 and 400 g/kg concentrate dry matter (DM)) in the diet on rumen fermentation and methane production. Two identical, Rusitec apparatuses, each with eight fermenters were used with the first 8 days used for adaptation and days 9 to 16 used for measurements. Fermenters were fed a total mixed ration with Urochloa brizantha as the forage. Disappearance of DM, CP, NDF and ADF linearly decreased (P<0.01) with increasing concentrations of Moringa seeds in the diet. Total volatile fatty acid production and the acetate to propionate ratio were also linearly decreased (P<0.01). However, only the 400 g/kg (concentrate DM basis) treatment differed (P<0.01) from the control. Methane production (%), total microbial incorporation of 15N and total production of microbial N linearly decreased (P<0.01) as the inclusion of Moringa seeds increased. Though the inclusion of Moringa seeds in the diet decreased CH4 production, this arose from an unfavourable decrease in diet digestibility and rumen fermentation parameters.
Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (investigational, extended-release of 5-fluorocytosine) into 5-fluorouracil. In preclinical models, 5-fluorouracil kills infected dividing cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activation against the tumor. In this dose ascending Ph1 trial (NCT01470794), Toca 511 was injected into the resection cavity wall of patients with rHGG, followed by courses of oral Toca FC. Additional cohorts included combination with bevacizumab or lomustine. Across the Ph1 program, the safety profile remains favorable. Objective responses (ORs) were assessed by IRR using MRI scans prior to Toca FC treatment as baseline. ORs occurred 6-19 months after Toca 511 administration, suggesting an immunologic mechanism. The ORs were observed in 4 patients with IDH1-wildtype and 2 patients with IDH1-mutant tumors, including 5 complete responses (CRs) with the investigational therapy alone, and 1 CR in combination with bevacizumab. The median duration of response (mDoR) was 35.1+ months. As of AUG2017, all responders were CR and remain alive. In a 23-patient subgroup who received high doses of Toca 511 and met Ph3 trial criteria, mOS was 14.4 months, 3-year survival rate was 26.1%, and mDoR was 35.7+ months with a durable response rate of 21.7%. Data suggest a positive association of durable response with OS.
This study investigates how CEO behavior and incentives change during the CEO's final years in office, known as the horizon problem. We examine how the horizon problem alters managerial slack, a measure of operational inefficiency and managerial value diversion. Using data on Chinese publicly traded firms between 2003 and 2011, we find that managerial slack increases in the last two years of CEO tenure compared to earlier years. We also show that the increase in managerial slack in CEO final years in office is smaller in privately controlled firms than in state-owned enterprises, smaller in firms with CEO equity ownership and more independent boards compared to those without. We conclude that higher quality corporate governance mechanisms ameliorate the perverse incentives associated with the CEO horizon problem, and reduce CEOs’ tendency to increase managerial slack during their final years in office.
Masulis and Mobbs (2014), (2015) find that independent directors with multiple directorships allocate their monitoring efforts unequally based on a directorship’s relative prestige. We investigate whether bank loan contract terms reflect such unequal allocation of directors’ monitoring effort. We find that bank loans of firms with a greater proportion of independent directors for whom the board is among their most prestigious have lower spreads, longer maturities, fewer covenants, lower syndicate concentration, lower likelihood of collateral requirement, lower annual loan fees, and higher bond ratings. Our evidence indicates that independent directors’ attention is associated with lower cost of borrowing.
The increasing tropospheric ozone concentration [O3] strongly affects plant growth. However, the response of belowground processes in rice (Oryza sativa L.) systems to higher O3 is not well understood. The grain production, belowground biomass partitioning, root morphology and activity of rice (cv. Shanyou 63) were investigated in a free-air O3 enrichment platform at four key growth stages. Elevated O3 (EO3, 50% above the ambient O3) significantly decreased the grain yield and total biomass at the grain milky mature stage, root biomass at the tillering stage and root to shoot ratios (RRS) at the flowering and grain filling stages. The effects of EO3 on root morphology and activity varied among rice growth stage. EO3 significantly decreased root length, density, area, diameter and volume at the flowering stage, but EO3 significantly decreased various root morphological indices at the tillering, grain filling and milky mature stages. EO3 significantly increased the specific root respiration rate (root activity) and root respiration rate (autotrophic respiration) at grain filling and milky mature stages. Higher root autotrophic respiration and lower RRS in response to EO3 would reduce allocation of assimilated carbon to root growth, adversely affecting rice productivity. Our findings are critical for understanding the O3-induced impairment of belowground processes and carbon cycling in rice cropping systems and breeding of O3-tolerant cultivars under higher [O3] scenarios.