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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: Canadian Stroke Guidelines recommend that Transient Ischemic Attack (TIA) patients at highest risk of stroke recurrence should undergo immediate vascular imaging. Computed tomography angiography (CTA) of the head and neck is recommended over carotid doppler because it allows for enhanced visualization of the intracranial and posterior circulation vasculature. Imaging while patients are in the emergency department (ED) is optimal for high-risk patients because the risk of stroke recurrence is highest in the first 48 hours. Aim Statement: At our hospital, a designated stroke centre, less than 5% of TIA patients meet national recommendations by undergoing CTA in the ED. We sought to increase the rate of CTA in high risk ED TIA patients from less than 5% to at least 80% in 10 months. Measures & Design: We used a multi-faceted approach to improve our adherence to guidelines including: 1) education for staff ED physicians; 2) agreements between ED and radiology to facilitate rapid access to CTA; 3) agreements between ED and neurology for consultations regarding patients with abnormal CTA; and 4) the creation of an electronic decision support tool to guide ED physicians as to which patients require CTA. We measured the rate of CTA in high risk patients biweekly using retrospective chart review of patients referred to the TIA clinic from the ED on a biweekly basis. As a balancing measure, we also measured the rate of CTA in non-high risk patients. Evaluation/Results: Data collection is ongoing. An interim run chart at 19 weeks shows a complete shift above the median after implementation, with CTA rates between 70 and 100%. At the time of submission, we had no downward trends below 80%, showing sustained improvement. The CTA rate in non-high risk patients did also increase. Disucssion/Impact: After 19 weeks of our intervention, 112 (78.9%) of high risk TIA patients had a CTA, compared to 10 (9.8%) in the 19 weeks prior to our intervention. On average, 10-15% of high risk patients will have an identifiable lesion on CTA, leading to immediate change in management (at minimum, an inpatient consultation with neurology). Our multi-faceted approach could be replicated in any ED with the engagement and availability of the same multi-disciplinary team (ED, radiology, and neurology), access to CTA, and electronic orders.
This project compares the degree of tracheal collapse determined by rigid and flexible bronchoscopy in paediatric patients with tracheomalacia.
A total of nine patients with tracheomalacia underwent both rigid and flexible video bronchoscopy. All patients were breathing spontaneously. Cross-sectional images of the airway were processed using the ImageJ program and analysed via colour histogram mode technique in order to delineate the luminal area. Paired t-tests (conducted using Stata software version 13.0) quantified differences between rigid and flexible bronchoscopes regarding the ratios of luminal pixels at maximum airway collapse to expansion. Correlation between both techniques in terms of airway collapse to expansion ratios was determined by calculating the Pearson correlation coefficient (R).
The difference in ratios of maximum collapse to expansion between rigid and flexible bronchoscopy was not statistically significant (p = 0.4656) and was positively correlated (R = 0.523).
The ratios suggest that rigid and flexible bronchoscopy are equally efficacious in assessing tracheomalacia severity, and may be used interchangeably in a clinical setting.
Cow routines and behavioral responses are altered substantially following the installation of robot milking. The present study was designed to analyze the effect that switching from milking parlor to automatic milking system (AMS) had on the culling rate (due to various causes) of dairy cattle. For this purpose, culling records and causes for culling were tracked in 23 dairy farms in the Galicia region (NW Spain). The animals in these farms were monitored for 5 years. For the present study, that length of time was divided into three different stages, as follows: 2 years before switching from a milking parlor to AMS (stage 1), the 1st year following the implementation of AMS (stage 2) and the 2nd and 3rd years succeeding the implementation of AMS (stage 3). Cox models for survival analysis were used to estimate the time to culling due to different reasons during stage 1 in relation to stages 2 and 3. The data indicated that the risk of loss due to death or emergency slaughter decreased significantly following the installation of AMS. In contrast, the risk of culling due to low production, udder problems, infertility or lameness increased significantly. Low-production cows (such as cows in advanced lactation due to infertility) or sick cows (such as mastitic or lame cows) allegedly have a noticeable effect both on the performance and the amortization of the cost of AMS, which in turn would lead to a higher probability of elimination than in conventional systems.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Carotid artery aneurysm is a potentially fatal complication of skull base osteomyelitis. It is important to know the warning signs for this complication, as early diagnosis is of great importance. This report aimed to determine whether the pattern of cranial nerve involvement may predict the occurrence of aneurysm involving the internal carotid artery in skull base osteomyelitis.
Two diabetic patients with skull base osteomyelitis were incidentally diagnosed with pseudo-aneurysm of the petrous internal carotid artery on follow-up magnetic resonance imaging. They presented with lower cranial nerve palsy; however, facial nerve function was almost preserved in both cases. Computed tomography angiography confirmed aneurysms at the junction of the horizontal and vertical segments of the petrous carotid artery.
Internal carotid artery trapping was conducted using coil embolisation. Post-coiling magnetic resonance imaging demonstrated no procedure-related complications. Regular follow up has demonstrated that patients’ symptoms are improving.
One should be mindful of this potentially fatal complication in skull base osteomyelitis patients with lower cranial nerve palsies, with or without facial nerve involvement, especially in the presence of intracranial thromboembolic events or Horner's syndrome.
Previous studies showed that butyrate played benefit roles in the health and metabolism of animals. However, little information on the effects of butyrate on the metabolism of piglets at the extraintestinal level is available. The present study investigated transcriptomic and metabolomic responses in the livers of pigs to evaluate the effects of intravenous sodium butyrate (SB) on the body’s metabolism at the extraintestinal level. A total of 12 Duroc×Landrace×Large White growing barrows (60 days of age) fitted with jugular vein cannula were randomly allocated to either the SB group or the control (CO) group. Pigs in the SB group were intravenously infused with 10 ml SB (200 mmol/l) for 7 days, whereas pigs in the CO group were treated with the same amount of saline. The livers of pigs were collected for gene expression and metabolome analyses. The RNA sequencing (RNA-Seq) analysis showed that the mRNA expression of Acyl-CoA synthetase long-chain family member 1 (ACSL1), carnitine palmitoyltransferase 1A (CPT1A), acetyl-CoA acyltransferase 2 (ACAA2) and phosphoenolpyruvate carboxykinase 1 (PCK1) were downregulated (Q<0.05), whereas fatty acid binding protein 1 (FABP1) and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) were upregulated (P<0.05) by SB treatment, indicating a decrease in fatty acid oxidation and gluconeogenesis and an increase in fatty acid transportation and cholesterol metabolism. Gas chromatography-mass spectrometry analysis showed that raffinose was enriched in the SB group compared with the CO group, indicating a decrease in metabolism of galactose. Moreover, SB treatment significantly decreased the concentration of blood cholesterol. The results suggest that a short-term intravenous infusion of SB could modulate hepatic lipid metabolism by decreasing fatty acid oxidation and increasing fatty acid transportation and cholesterol metabolism.
The human retina is supplied by two vascular systems: the highly vascular choroidal, situated behind the retina; and the retinal, which is dependent on the restriction that the light path must be minimally disrupted. Between these two circulations, the avascular retinal layers depend on diffusion of metabolites through the tissue. Oxygen supply to these layers may be threatened by diseases affecting microvasculature, for example diabetes and hypertension, which may ultimately cause loss of sight.
An accurate model of retinal blood flow will therefore facilitate the study of retinal oxygen supply and, hence, the complications caused by systemic vascular disease. Here, two simple models of the blood flow and exchange of hydrogen with the retina are presented and compared qualitatively with data obtained from experimental measurements. The models capture some interesting features of the exchange and highlight effects that will need to be considered in a more sophisticated model and in the interpretation of experimental results.
About 30,000 astronomical photographic plates were digitised between 2012–2017 with a special digitising machine that has high precision in both astrometry and photometry. All the images from the plates, together with plate information and measured coordinates of all the objects on the plates, have been stored in the Chinese Virtual Observatory.
The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.
OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.
EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).
Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.
The loss of a close relative is one of the most stressful life events. In pregnancy, this experience has been associated with a higher risk of fetal death and under-five mortality, but little is known about potential effects on long-term mortality in offspring. We examined the association between prenatal maternal bereavement and mortality in a cohort of 5.3 million children followed until up to 37 years of age.
The population-based cohort study included 5 253 508 live singleton births in Denmark (1973–2004) and Sweden (1973–2006). Children born to mothers who lost a child, spouse, sibling, or parent during or 1 year before pregnancy were categorized as exposed.
Prenatal maternal bereavement was associated with a 10% increased all-cause mortality risk in offspring [mortality rate ratio (MRR) 1.10, 95% confidence interval (CI) 1.03–1.18]. The association was the most pronounced for children of mothers who lost a child/spouse (MRR 1.28, 95% CI 1.14–1.44) and was stronger during the first 10 years of life. Prenatal maternal bereavement may have stronger effects on natural causes of death in offspring, including infectious/parasitic disease (MRR 1.86, 95% CI 1.07–3.23), endocrine/nutritional/metabolic diseases (MRR 3.23, 95% CI 2.02–5.17), diseases of nervous system (MRR 3.36, 95% CI 2.47–4.58), and congenital malformations (MRR 1.39, 95% CI 1.08–1.80). No excess mortality risk in offspring was observed for unnatural causes of death.
Prenatal maternal bereavement was associated with an increased long-term mortality risk in offspring, particularly for selected natural causes of diseases and medical conditions. Our results support the fetal programming hypothesis that prenatal stress may contribute to ill health from physical diseases later in life.
H9 avian influenza virus played a key role during generation of the novel H7N9 virus. A surveillance programme was conducted to assess the H9 virus in relation to the risk of H7N9 virus contamination in the environment. Risk of H7N9 virus contamination in the presence of H9 virus was higher than without (adjusted odds ratio 4·49, 95% confidence interval 3·79–5·31). Adjusted odds ratios of the H7N9 virus associated with co-presence of H9 virus and interacting factors were 4·93 (rural vs. urban area), 46·80 (live poultry markets vs. other premises), 6·86 (Huzhou vs. Hangzhou prefecture), 40·67 (year 2015 vs. 2013), and 9·63 (sewage from cleaning poultry vs. poultry faeces). Regular surveillance on gene variability of H7N9 and H9 viruses should be conducted and extra measures are needed to reduce co-circulation of H7N9 and H9 viruses in the environment.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
Metsulfuron is used for POST control of spotted spurge in many warm-season
turfgrasses. A suspected resistant (R) biotype of spotted spurge was
collected from turfgrass in Georgia with a history of exclusive metsulfuron
use. Research was conducted to evaluate the resistance level of this biotype
to metsulfuron, efficacy of other mechanisms of action for control, and the
molecular basis for resistance. Compared with a susceptible (S) biotype, the
R biotype required >90 and >135 times greater metsulfuron rates to
reach 50% injury and reduce biomass 50% from the nontreated, respectively.
The R biotype was also resistant to trifloxysulfuron but was injured
equivalent to the S biotype from dicamba, glyphosate, and triclopyr. Gene
sequencing of the R biotype revealed a Trp574 to Leu substitution
that has conferred resistance to acetolactate synthase (ALS) inhibitors in
previous research. This is the first report of ALS resistance in spotted
spurge. More importantly, this is the first report of a herbicide-resistant
broadleaf weed from a turfgrass system in the United States.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Acetolactate synthase (ALS) inhibitors are widely used for POST control of
sedges in turfgrass. A suspected resistant (R) biotype of annual sedge was
collected from a bermudagrass turf in Georgia with a history of exclusive
use of halosulfuron. Research was conducted to evaluate the resistance level
of this biotype to halosulfuron, efficacy of ALS-inhibiting herbicides and
other mechanisms of action for control, and the molecular and physiological
basis for resistance. In greenhouse experiments, the halosulfuron rate
required to reduce shoot biomass 50% in comparison with the nontreated at 8
wk after treatment (WAT) were 8 and > 1,120 g ai ha−1 for the
S (susceptible) and R biotypes, respectively. Imazapic, sulfosulfuron, and
trifloxysulfuron reduced biomass of the S biotype greater than 60% at 8 WAT,
but biomass was reduced less than 20% for the R biotype. Glufosinate,
glyphosate, MSMA, and sulfentrazone reduced shoot biomass of the R biotype
by 93, 86, 97, and 45%, respectively. In laboratory experiments, the
halosulfuron concentration required to inhibit ALS activity by 50% in
excised leaf tissues was 5.8 and > 1,000 μM for the S and R biotypes,
respectively. Gene sequencing of the R biotype revealed a Pro-197-Ser
substitution that confers resistance to ALS inhibitors. This is the first
report of ALS-inhibitor resistance in annual sedge and herbicide resistance
in a sedge species from a turfgrass system.
Interfacial dislocations (IDs) and half-loop arrays (HLAs) present in the
epilayers of 4H-SiC crystal are known to have a deleterious effect on device
performance. Synchrotron X-ray Topography studies carried out on n-type 4H-SiC
offcut wafers before and after epitaxial growth show that in many cases BPD
segments in the substrate are responsible for creating IDs and HLAs during CVD
growth. This paper reviews the behaviors of BPDs in the substrate during the
epitaxial growth in different cases: (1) screw-oriented BPD segments
intersecting the surface replicate directly through the interface during the
epitaxial growth and take part in stress relaxation process by creating IDs and
HLAs (Matthews-Blakeslee model  ); (2) non-screw oriented BPD half loop
intersecting the surface glides towards and replicates through the interface,
while the intersection points convert to threading edge dislocations (TEDs) and
pin the half loop, leaving straight screw segments in the epilayer and then
create IDs and HLAs; (3) edge oriented short BPD segments well below the surface
get dragged towards the interface during epitaxial growth, leaving two long
screw segments in their wake, some of which replicate through the interface and
create IDs and HLAs. The driving force for the BPDs to glide toward the
interface is thermal stress and driving force for the relaxation process to
occur is the lattice parameter difference at growth temperature which results
from the doping concentration difference between the substrate and epilayer.
Neurological soft signs (NSS) have long been considered potential endophenotypes for schizophrenia. However, few studies have investigated the heritability and familiality of NSS. The present study examined the heritability and familiality of NSS in healthy twins and patient–relative pairs.
The abridged version of the Cambridge Neurological Inventory was administered to 267 pairs of monozygotic twins, 124 pairs of dizygotic twins, and 75 pairs of patients with schizophrenia and their non-psychotic first-degree relatives.
NSS were found to have moderate but significant heritability in the healthy twin sample. Moreover, patients with schizophrenia correlated closely with their first-degree relatives on NSS.
Taken together, the findings provide evidence on the heritability and familiality of NSS in the Han Chinese population.
To explore unilateral vocal fold paralysis patients' perception of a proposed randomised, controlled trial of laryngeal reinnervation versus thyroplasty, and to identify patients' concerns regarding their voice.
Seventeen patients from five voice clinics in London were identified as being eligible for the randomised, controlled trial. Eleven of these patients (9 females and 2 males; age range, 18–65 years) were interviewed using a semi-structured topic guide (they were given a minimum of 2 weeks to read through the study information sheet). The interviews were recorded, transcribed and analysed using thematic analysis.
The patients were satisfied with the clarity of the information sheet. Most of them perceived that reinnervation was a more ‘attractive’ option than thyroplasty. This may have been the result of certain phraseology used in the information sheet and by recruiters. Patients' main concern was reduced voice strength and the effects of this on work and social life.
Phraseology that needed changing was identified; these changes may optimise the recruitment process for a trial. We propose using the voice handicap index 10 as the primary measure of outcome in the proposed randomised, controlled trial.