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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.
Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case–control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09–0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05–2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23–17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.
Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT–PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87·9%) and 2 were BA10 genotype (6·1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2·8, 95% CI 1·6–5·1) and wheezing (OR = 2·8, 95% CI 1·7–4·4). The ON1 genotype was significantly associated with phlegm (OR = 11·8, 95% CI 3·8–46·7), while the NA1 genotype was associated with the pediatric patients’ gender (males, OR = 2·4, 95% CI 1·1–5·4) and presence of chills (OR = 5·1, 95% CI 1·1–27·2). RSV subgroup B was showed association with nasal obstruction (OR = 4·6, 95% CI 1·2–20·0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47·2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines.
In-spiraling supermassive black holes should emit gravitational waves, which would produce characteristic distortions in the time of arrival residuals from millisecond pulsars. Multiple national and regional consortia have constructed pulsar timing arrays by precise timing of different sets of millisecond pulsars. An essential aspect of precision timing is the transfer of the times of arrival to a (quasi-)inertial frame, conventionally the solar system barycenter. The barycenter is determined from the knowledge of the planetary masses and orbits, which has been refined over the past 50 years by multiple spacecraft. Within the North American Nanohertz Observatory for Gravitational Waves (NANOGrav), uncertainties on the solar system barycenter are emerging as an important element of the NANOGrav noise budget. We describe what is known about the solar system barycenter, touch upon how uncertainties in it affect gravitational wave studies with pulsar timing arrays, and consider future trends in spacecraft navigation.
We present a photometric study of the stars in ionizing star clusters embedded in several giant H II regions of M33 (CC93, IC 142, NGC 595, MA2, NGC 604 and NGC 588). Our photometry is based on the HST-WFPC2 images of these clusters. Color-magnitude diagrams and color-color diagrams of these clusters are obtained and are used for estimating the reddenings and ages of the clusters. The luminosity functions (LFs) and initial mass functions (IMFs) of the massive stars in these clusters are also derived. The slopes of the IMFs range from Γ = −0.5 to −2.1. Interestingly, it is found that the IMFs get steeper with increasing galactocentric distance and with decreasing [O/H] abundance.
The distribution of molecular markers in sediments provides a reservoir of unique information concerning biogeochemical processes in the geological past, and how these processes respond to environmental change. However, sedimentary systems themselves are biologically dynamic and these markers, and their precursors, have been subjected to bacterial degradation and modification. Recent research indicates that key changes in sedimented organic matter take place during the earliest stages of sediment burial and diagenesis where bacterial activity is also intense. Hence, effective interpretation of the distribution of biomarkers from deep sediment layers and sedimentary rocks requires knowledge of the rates and processes of bacterial decomposition under a range of environmental conditions.
Algae are important primary producers in the marine environment. The prymnesiophyte alga Emiliania huxleyi was selected as a subject for study as it is a source of long chain ketones which are geochemically important biomarkers. The ratio of the ketones C37:2 to C37:3 is temperature sensitive and has been used as a palaeotemperature indicator (UK37).
Preliminary sediment slurry incubations were carried out to optimize experimental design (concentration of decay organism, concentration of sediment in slurry, ability to obtain defined microbial environments over long term incubations, aerobic and anaerobic), and quantitative analytical scheme (extraction and separation technique, type and concentration of internal standards). Subsequent experiments on aerobic bacterial degradation of E. huxleyi demonstrated rapid increase in bacterial activity and biomass. This was accompanied by major changes in lipid classes. The dominant aliphatic hydrocarbons, three isomers of nC31:2, were rapidly degraded and completely removed by 78 days. In contrast, in preliminary anaerobic incubations, the same compounds remained unchanged. By 78 days a significant reduction in the total algal sterols was accompanied by a small increase in total stanols; hence the cholestanol/cholesterol ratio increased markedly. The abundance of the long chain unsaturated ketone C37:3 decreased relative to C37:2 resulting in an increase in the UK37 ratio. The reasons for these changes are unclear. However, they indicate that bacterial degradation may have to be taken into account in the interpretation of UK37 ratios in terms of paleotemperatures.
Further experiments are in progress to clarify the interpretation of these results and provide information on the more recalcitrant biomarkers.
Host–parasite associations are complex interactions dependent on aspects of hosts (e.g. traits, phylogeny or coevolutionary history), parasites (e.g. traits and parasite interactions) and geography (e.g. latitude). Predicting the permissive host set or the subset of the host community that a parasite can infect is a central goal of parasite ecology. Here we develop models that accurately predict the permissive host set of 562 helminth parasites in five different parasite taxonomic groups. We developed predictive models using host traits, host taxonomy, geographic covariates, and parasite community composition, finding that models trained on parasite community variables were more accurate than any other covariate group, even though parasite community covariates only captured a quarter of the variance in parasite community composition. This suggests that it is possible to predict the permissive host set for a given parasite, and that parasite community structure is an important predictor, potentially because parasite communities are interacting non-random assemblages.
Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography–mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
When children have marked problems with motor coordination, they often have problems with attention and impulse control. Here, we map the neuroanatomic substrate of motor coordination in childhood and ask whether this substrate differs in the presence of concurrent symptoms of attention-deficit/hyperactivity disorder (ADHD).
Participants were 226 children. All completed Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)-based assessment of ADHD symptoms and standardized tests of motor coordination skills assessing aiming/catching, manual dexterity and balance. Symptoms of developmental coordination disorder (DCD) were determined using parental questionnaires. Using 3 Tesla magnetic resonance data, four latent neuroanatomic variables (for the cerebral cortex, cerebellum, basal ganglia and thalamus) were extracted and mapped onto each motor coordination skill using partial least squares pathway modeling.
The motor coordination skill of aiming/catching was significantly linked to latent variables for both the cerebral cortex (t = 4.31, p < 0.0001) and the cerebellum (t = 2.31, p = 0.02). This effect was driven by the premotor/motor cortical regions and the superior cerebellar lobules. These links were not moderated by the severity of symptoms of inattention, hyperactivity and impulsivity. In categorical analyses, the DCD group showed atypical reduction in the volumes of these regions. However, the group with DCD alone did not differ significantly from those with DCD and co-morbid ADHD.
The superior cerebellar lobules and the premotor/motor cortex emerged as pivotal neural substrates of motor coordination in children. The dimensions of these motor coordination regions did not differ significantly between those who had DCD, with or without co-morbid ADHD.
Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene–environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD.
In 102 children with ADHD (age 6–15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated.
A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temproral regions.
Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.
Plasmas are ubiquitous in nature, surround our local geospace environment, and permeate the universe. Plasma phenomena in space give rise to energetic particles, the aurora, solar flares and coronal mass ejections, as well as many energetic phenomena in interstellar space. Although plasmas can be studied in laboratory settings, it is often difficult, if not impossible, to replicate the conditions (density, temperature, magnetic and electric fields, etc.) of space. Single-point space missions too numerous to list have described many properties of near-Earth and heliospheric plasmas as measured both in situ and remotely (see http://www.nasa.gov/missions/#.U1mcVmeweRY for a list of NASA-related missions). However, a full description of our plasma environment requires three-dimensional spatial measurements. Cluster is the first, and until data begin flowing from the Magnetospheric Multiscale Mission (MMS), the only mission designed to describe the three-dimensional spatial structure of plasma phenomena in geospace. In this paper, we concentrate on some of the many plasma phenomena that have been studied using data from Cluster. To date, there have been more than 2000 refereed papers published using Cluster data but in this paper we will, of necessity, refer to only a small fraction of the published work. We have focused on a few basic plasma phenomena, but, for example, have not dealt with most of the vast body of work describing dynamical phenomena in Earth's magnetosphere, including the dynamics of current sheets in Earth's magnetotail and the morphology of the dayside high latitude cusp. Several review articles and special publications are available that describe aspects of that research in detail and interested readers are referred to them (see for example, Escoubet et al. 2005Multiscale Coupling of Sun-Earth Processes, p. 459, Keith et al. 2005Sur. Geophys.26, 307–339, Paschmann et al. 2005Outer Magnetospheric Boundaries: Cluster Results, Space Sciences Series of ISSI. Berlin: Springer, Goldstein et al. 2006Adv. Space Res.38, 21–36, Taylor et al. 2010The Cluster Mission: Space Plasma in Three Dimensions, Springer, pp. 309–330 and Escoubet et al. 2013Ann. Geophys.31, 1045–1059).
To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas.
Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53.
Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours.
The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.