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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.
Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and three-dimensional particle-in-cell simulations. With the existence of a periodic structure on the target surface, the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density. The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target. Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron ‘islands’ formed by the surface plasma waves on the target surfaces. In other words, the radiation with the fundamental frequency is actually ‘surface emission’ on the target rear surface. Besides the intensity of the component with the fundamental frequency, the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target. The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.
Direct numerical simulation of intense laser–solid interactions is still of great challenges, because of the many coupled atomic and plasma processes, such as ionization dynamics, collision among charged particles and collective electromagnetic fields, to name just a few. Here, we develop a new particle-in-cell (PIC) simulation code, which enables us to calculate laser–solid interactions in a more realistic way. This code is able to cover almost ‘all’ the coupled physical processes. As an application of the new code, the generation and transport of energetic electrons in front of and within the solid target when irradiated by intense laser beams are studied. For the considered case, in which laser intensity is
and pre-plasma scale length in front of the solid is
, several quantitative conclusions are drawn: (i) the collisional damping (although it is very weak) can significantly affect the energetic electrons generation in front of the target, (ii) the Bremsstrahlung radiation will be enhanced by 2–3 times when the solid is dramatically heated and ionized, (iii) the ‘cut-off’ electron energy is lowered by an amount of 25% when both collision damping and Bremsstrahlung radiations are included, and (iv) the resistive electromagnetic fields due to Ohmic heating play nonignorable roles and must be taken into account in such interactions.
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.
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.
The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data.
Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI).
Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes).
The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.
We report new laboratory experiments of a flow accelerating from an initially turbulent state following the opening of a valve, together with large eddy simulations of the experiments and extended Stokes first problem solutions for the early stages of the flow. The results show that the transient flow closely resembles an accelerating laminar flow superimposed on the original steady turbulent flow. The primary consequence of the acceleration is the temporal growth of a boundary layer from the wall, gradually leading to a strong instability causing transition. This extends the findings of previous direct numerical simulations of transient flow following a near-step increase in flow rate. In this interpretation, the initial turbulence is not the primary characteristic of the resulting transient flow, but can be regarded as noise, the evolution of which is strongly influenced by the development of the boundary layer. We observe the spontaneous appearance of turbulent spots and discontinuities in the velocity signals in time and space, revealing rich detail of the transition process, including a striking contrast between streamwise and wall-normal fluctuating velocities.
Hepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5′ UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.
Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.
A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).
Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB.
IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.
Mitochondria plays an important role in the regulation of energy homeostasis. Moreover, mitochondrial biogenesis accompanies skeletal myogenesis, and we previously reported that maternal high-energy diet repressed skeletal myogenesis in pig fetuses. Therefore, the aim of this study was to evaluate the effects of moderately increased maternal energy intake on skeletal muscle mitochondrial biogenesis and function of the pig fetuses. Primiparous purebred Large White sows were allocated to a normal energy intake group (NE) as recommended by the National Research Council (NRC) and a high energy intake group (HE, 110% of NRC recommendations). On day 90 of gestation, fetal umbilical vein blood and longissimus (LM) muscle were collected. Results showed that the weight gain of sows fed HE diet was higher than NE sows on day 90 of gestation (P<0.05). Maternal HE diet increased fetal umbilical vein serum triglyceride and insulin concentrations (P<0.05), and tended to increase the homeostasis model assessment index (P=0.08). Furthermore, HE fetuses exhibited increased malondialdehyde concentration (P<0.05), and decreased activities of antioxidative enzymes (P<0.05) and intracellular NAD+ level (P<0.05) in LM muscle. These alterations in metabolic traits of HE fetuses were accompanied by reduced mitochondrial DNA amount (P<0.05) and down-regulated messenger RNA expression levels of genes responsible for mitochondrial biogenesis and function (P<0.05). Our results suggest that moderately increased energy supply during gestation decreases mitochondrial biogenesis, function and antioxidative capacity in skeletal muscle of pig fetuses.
A direct numerical simulation investigation of a transient flow in a channel with a smooth top wall and a roughened bottom wall made of close-packed pyramids is presented. An initially stationary turbulent flow is accelerated rapidly to a new flow rate and the transient flow behaviour after the acceleration is studied. The equivalent roughness heights of the initial and final flows are
and 41.5, respectively. Immediately after the acceleration ends, the induced change behaves in a ‘plug-flow’ manner. Above the roughness crests, the additional velocity due to the perturbation flow is uniform; below the crest, it reduces approximately linearly to zero at the bottom of the roughness elements. The interaction of the perturbation flow with the rough wall is characterised by a series of events that resemble those observed in roughness-induced laminar–turbulent transitions. The process has two broad stages. In the first of these, large-scale vortices, comparable in extent to the roughness wavelength, develop around each roughness element and high-speed streaks form along the ridge lines of the elements. After a short time, each vortex splits into two, namely (i) a standing vortex in front of the element and (ii) a counter-rotating hairpin vortex behind it. The former is largely inactive, but the latter advects downstream with increasing strength, and later lifts away from the wall. These hairpin vortices wrap around strong low-speed streaks. The second stage of the overall process is the breakdown of the hairpin vortices into many smaller multi-scale vortices distributed randomly in space, leading eventually to a state of conventional turbulence. Shortly after the beginning of the first stage, the three components of the r.m.s of the velocity fluctuation all increase significantly in the near-wall region as a result of the vortical structures, and their spectra bear strong signatures of the surface topology. During the second stage, the overall turbulence energy in this region varies only slightly, but the spectrum evolves significantly, eventually approaching that of conventional turbulence. The direct effect of roughness on the flow is confined to a region up to approximately three element heights above the roughness crests. Turbulence in the core region does not begin to increase until after the transition near the wall is largely complete. The processes of transition over the smooth and rough walls of the channel are practically independent of each other. The flow over the smooth wall follows a laminar–turbulent transition and, as known from previous work, resembles a free-stream turbulence-induced boundary layer bypass transition.
The objectives of this study were to determine: (1) the effect of wheat dried distillers grain with solubles (DDGS) inclusion, and (2) dietary feed enzyme (FE; Econase XT) supplementation in a finishing diet containing wheat DDGS on fatty acid profile of the pars costalis diaphragmatis muscle of beef cattle. A total of 160 crossbred yearling steers with initial BW of 495±38 kg were blocked by BW and randomized into 16 pens (10 head/pen). The pens were randomly assigned to one of the four treatments: (1) control (CON; 10% barley silage and 90% barley grain-based concentrate, dry matter (DM) basis); (2) diet containing 30% wheat DDGS in place of barley grain without FE (WDG); (3) WDG diet supplemented with low FE (WDGL; 1 ml FE/kg DM); and (4) WDG diet supplemented with high FE (2 ml FE/kg DM). The pars costalis diaphragmatis muscle samples were collected from cattle at slaughter at the end of the finishing period (120 days) with a targeted live weight of 650 kg. No differences in organic matter intake, final BW and average daily gain were observed among treatments. However, steers fed WDG had greater (P<0.01) feed conversion ratio than those fed CON, and increasing FE application in wheat DDGS-based diets tended (P<0.10) to linearly decrease feed conversion ratio. In assessing the effects of including WDG diets without FE, concentration of total polyunsaturated fatty acids (PUFA) in muscle tended to be greater (P<0.10) for steers fed WDG than steers fed CON. In addition, inclusion of wheat DDGS into the diet increased (P<0.05) concentration of CLA and vaccenic acid (VA) in muscle and also resulted in a higher (P<0.05) ratio of n-6/n-3 PUFA compared with that from steers fed CON diet. Increasing FE application in wheat DDGS-based diets did not modify the concentrations of individual or total fatty acids. These results suggest that inclusion of wheat DDGS in finishing diets may improve fatty acid profile of beef muscle which could benefit human health.
To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD).
Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI).
45.7% of respondents with lifetime MDD (32.0–46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8–54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9–47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ21 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ21 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ21 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ21 = 11.7, p < 0.001).
Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6–74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.
To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.
Graphene nanoplatelets (GNPs) functionalised with platinum were explored as the active material in a high specific surface area ink. The ink had a transmission at 550nm (T550) = 85% and a charge transfer resistance (Rct) of 6Ω/cm2. Although the Rct is higher than required for laboratory cells having a Jsc of 20mA/cm2 under 1 sun test conditions it is sufficient for industrially produced reverse devices, especially when utilised for indoor applications where light conditions will be lower than 100W/m2. This was demonstrated by reverse illuminated DSC efficiencies with flexible cathodes which were equivalent to cells with sputtered platinum catalysts when subjected to 300W/m2 lighting or less. A modification to the ink, suitable for catalysing a Co2+/3+ electrolyte having an Rct of 2Ω/cm2 and T550= 85% was undertaken. This demonstrates potential for use in high efficiency cobalt mediated DSCs. The work shows that printed graphene catalysts are a versatile low cost replacement to sputtered platinum in reverse illuminated DSCs for dye sensitised solar cells.
MicroRNAs are endogenous ~22nt RNAs that negatively regulate gene expression at the posttranscriptional level via binding to the 3′-untranslated region (3′UTR) of target mRNAs. The microRNA miR-27a was reported to depress the expression of myostatin, a critical inhibitor of skeletal myogenesis, by binding to its 3′UTR in mouse. In this study, we cloned the full-length 3′UTR of porcine myostatin by rapid amplification of 3′-cDNA ends (3′-RACE) and demonstrated that the 3′UTR of porcine myostatin is targeted by miR-27a. The phenomenon that the level of myostatin inversely correlated with miR-27a was observed in fat and heart of pigs and also in proliferating porcine myoblasts. Besides, overexpression of miR-27a in porcine myoblasts promoted cell proliferation by reducing the expression of myostatin. Our data suggest that miR-27a positive regulates porcine myoblast proliferation via targeting myostatin.