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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.
The asymptotic phase θ of an initial point x in the stable manifold of a limit cycle (LC) identifies the phase of the point on the LC to which the flow φt(x) converges as t → ∞. The infinitesimal phase response curve (iPRC) quantifies the change in timing due to a small perturbation of a LC trajectory. For a stable LC in a smooth dynamical system, the iPRC is the gradient ∇x(θ) of the phase function, which can be obtained via the adjoint of the variational equation. For systems with discontinuous dynamics, the standard approach to obtaining the iPRC fails. We derive a formula for the iPRCs of LCs occurring in piecewise smooth (Filippov) dynamical systems of arbitrary dimension, subject to a transverse flow condition. Discontinuous jumps in the iPRC can occur at the boundaries separating subdomains, and are captured by a linear matching condition. The matching matrix, M, can be derived from the saltation matrix arising in the associated variational problem. For the special case of linear dynamics away from switching boundaries, we obtain an explicit expression for the iPRC. We present examples from cell biology (Glass networks) and neuroscience (central pattern generator models). We apply the iPRCs obtained to study synchronization and phase-locking in piecewise smooth LC systems in which synchronization arises solely due to the crossing of switching manifolds.
Human bocaviruses (HBoVs) have been detected in human gastrointestinal infections worldwide. In 2005, HBoV was also discovered in infants and children with infections of the lower respiratory tract. Recently, several genotypes of this parvovirus, including HBoV genotype 2 (HBoV2), genotype 3 (HBoV3) and genotype 4 (HBoV4), were discovered and found to be closely related to HBoV. HBoV2 was first detected in stool samples from children in Pakistan, followed by detection in other countries. HBoV3 was detected in Australia and HBoV4 was identified in stool samples from Nigeria, Tunisia and the USA. Recently, HBoV infection has been on the rise throughout the world, particularly in countries neighbouring South Korea; however, there have been very few studies on Korean strains. In this study, we characterised the whole genome and determined the phylogenetic position of CUK-BC20, a new clinical HBoV strain isolated in South Korea. The CUK-BC20 genome of 5184 nucleotides (nt) contains three open-reading frames (ORFs). The genotype of CUK-BC20 is HBoV2, and 98.77% of its nt sequence is identical with those of other HBoVs, namely Rus-Nsc10-N386. Especially, the ORF3 amino acid sequences from positions 212–213 and 454 corresponding to a variable region (VR)1 and VR5, respectively, showed genotype-specific substitutions that distinguished the four HBoV genotypes. As the first whole-genome sequence analysis of HBoV in South Korea, this information will provide a valuable reference for the detection of recombination, tracking of epidemics and development of diagnosis methods for HBoV.
The aims of this study were to investigate the effects of either hearing, vision or dual sensory impairment on depressive symptoms and to identify subgroups that are vulnerable and significantly affected.
Data from the 2006–2014 Korean Longitudinal Study of Aging (KLoSA) were used and a total of 5832 individuals were included in this study. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D10) scale. Sensory impairment was assessed according to the levels of self-reported hearing or vision, which were categorised as either good (excellent, very good or good) or poor (fair or poor). The changes in hearing or vision from records of previous survey were investigated. Changes from good to poor, which indicates new onset, were defined as hearing impairment or vision impairment. Interactions of changes in hearing and vision were considered in the analysis. Dual sensory impairment was indicated when hearing impairment and vision impairment both developed at the same time. Demographic, socioeconomic and health-related factors were considered as potential confounders and were adjusted for in the generalised estimating equation model.
Individuals with hearing impairment demonstrated significantly more severe depressive symptoms [β = 0.434, standard errors (s.e.) = 0.097, p < 0.001] than those who had good hearing. Those with vision impairment also showed significantly elevated depressive symptoms (β = 0.253, s.e. = 0.058, p < 0.001) than those with good vision. When the interactions between hearing and vision were considered, participants with dual sensory impairment showed significantly more severe depressive symptoms (β = 0.768, s.e. = 0.197, p < 0.001) than those with good hearing and vision. The effect of a single and dual sensory impairment on depressive symptoms was significant in both sexes and across age groups, except for vision impairment in male participants.
Hearing, vision and dual sensory impairment are significantly associated with depressive symptoms. Our results suggest that treatment or rehabilitation of either hearing or vision impairment would help prevent depression.
This study evaluated the annual prevalence of anogenital warts (AGW) caused by human papillomavirus (HPV) and analysed the trend in annual per cent changes (APC) by using national claims data from the Health Insurance Review and Assessment of Korea, 2007–2015. We also estimated the socio-economic burden and co-morbidities of AGW. All analyses were performed based on data for primary A63.0, the specific diagnosis code for AGW. The socio-economic cost of AGW was calculated based on the direct medical cost, direct non-medical cost and indirect cost. The overall AGW prevalence and socio-economic burden has increased during the last 9 years. However, the prevalence of AGW differed significantly by sex. The female prevalence increased until 2012, and decreased thereafter (APC + 3·6%). It would fall after the introduction of routine HPV vaccination, principally for females, in Korea. The male prevalence increased continuously over time (APC + 11·6%), especially in those aged 20–49 years. Referring to the increasing AGW prevalence and its disease burden, active HPV infection control surveillance and prevention in males are worth consideration.
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.
This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.
Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.
Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.
In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.
Noroviruses (NoVs) are major causal agents of acute gastroenteritis in humans. NoV GII.4 is the predominant genotype globally. However, uncommon and minor types of NoVs are consistently detected and some have been shown to dominate over GII.4. Therefore, the prevalence of dominant and uncommon NoVs makes the identification of these viruses important for the prediction and prevention of pandemics. In this study, the full-genome sequence of a NoV (strain JW) detected in Korea was extensively characterized. The full-length genome was 7510 nucleotides long, and phylogenetic analysis based on the whole-genome sequences, including open reading frame (ORF)1, ORF2, and ORF3, indicated that it belonged to the GII.21 genotype. Strain JW showed maximum identity with strain YO284; however, comparison of the amino acid sequence of ORF2, which functions as an antigen, showed substitutions in several amino acids. GII.21 is not a prevalent epidemiological agent of acute gastroenteritis in humans, but it is consistently found in gastroenteritis patients from several countries. The present study provides the first full-genome sequence analysis of NoV GII.21 isolated from a patient in Korea. Our findings provide not only valuable genome information but also data for epidemiology studies, epidemic prevention, and vaccine development strategies.
A radiocarbon (14C) dating technique with accelerator mass spectrometry (AMS) was applied to estimate the year of death and the year of birth of unidentified human remains. Because many of the samples have been preserved in formaldehyde, it was necessary to evaluate the influence of formaldehyde on carbon ages. Samples intentionally preserved in formaldehyde during the known period were measured, and their Δ14C values were compared with results obtained from fresh samples. The influence of formaldehyde on soft tissue was 14 times larger than that on cortical bone. Unfortunately, an effective method for removing the influence of formaldehyde has not yet been found. 14C ages could be obtained only from the samples not preserved in formaldehyde. The years of birth were determined by the ages of the dentin samples, while the years of death were determined by the ages of the bone and soft tissue samples. Multiple sampling from a body provides an advantage in determination of one of two possible ages of a sample obtained using the bomb peak. Victims of the Korean War were ascertained by the year of death. The year of death and the age at death of unidentified bodies were also determined for forensic investigation.
Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.
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.
While it is customary to use solid samples for measuring the 14C/12C ratio, it is sometimes necessary to handle liquid or gas samples. Motivated by a scientific purpose to count radiocarbon yields in deuterated acetone irradiated with energetic neutrons, we developed a new combustion system to treat liquid or gas samples. In contrast with the typical combustion system using CuO for solid samples, the new combustion system uses high-purity O2 (99.999%) gas. As an initial investigation, we combusted deuterated acetone (acetone-d6, certified 100.0 atm % D) to make CO2 under the ambient O2 pressure. The resulting CO2 gas then went through the reduction process to form graphite for further accelerator mass spectrometry (AMS) measurement.
The relationship between temperature and time required for collagenization using modern bone samples was investigated. Gelatinized samples of bone collagen were filtered to selectively collect different molecular weight fractions. The results of this study suggest that heating to 70 ° for a duration of 12 hr provides the optimal conditions for gelatinization.
The accelerator mass spectrometry facility at the Seoul National University (SNU-AMS) was completed in December 1998 and a report was presented at the Vienna AMS conference in September 1999. At the conference, we described the basic components of our accelerator system and reported the results of the performance test. Since then, extensive testing of the accuracy and reproducibility of the system has been carried out, and about 200 unknown samples have been measured so far. We obtained a precision of 4‰ for modern samples, and an accuracy of approximately 40 yr was demonstrated by analyzing samples that were previously dated with a conventional technique and by other AMS laboratories. We present these results here, together with detailed descriptions of our data-taking and analysis procedures.
We have observed A14C concentrations in the northern hemisphere temperate region in the bomb pulse period, using cross-dated tree ring samples. The tree-ring samples were taken from one 70-year-old and two 50-year-old red pines (Pinus densiflora) on Mt Chiak, Korea and from a 50-year-old red pine (Pinus densiflora) on Mt Kyeryong, Korea. Twenty-two tree-ring samples from four red pines ranging from 1950 to 2000 AD were pretreated to obtain holo-cellulose, combusted to CO2 by an element analyzer (EA) and converted to graphite for δ14C measurement using the accelerator mass spectrometry (AMS) facility at Seoul National University. Our results for δ14C showed good agreement with those measured by other researchers at similar latitudes. The observed steady decrease of δ14C from 1965 to 2000 AD is described by a single exponential function with a lifetime τ = 15.99 ± 0.43 yr. This lifetime is similar to that of the high-latitude region in Europe.
The development of radiocarbon dating for degraded bone samples collected at Korean archaeological sites has been successful through the characterization of raw bone C/N ratios and application of an ultrafiltration method. It was found that the C/N ratios of raw bone samples are inversely proportional to the carbon content and residue amount after gelatinization. We have examined a few dozen Korean archaeological bone samples for this study. Well-preserved bone samples are found to be physically dense. The range of C/N ratios of Korean raw bone samples ranged from 3.4 to 74. We found that the C/N ratios of degraded raw bone samples can be used to determine whether 14C samples are acceptable for normal pretreatment processing and eventual dating. The results of this study support that even if the C/N ratio of a degraded raw bone sample is 11, extraction of collagen for bone dating is feasible by a carefully designed ultrafiltration process. Our preliminary 14C dating results of a depth profile of Gunang-gul Cave, an archaeological site in Danyang, Korea, indicate that this site has been either geologically or anthropologically disturbed in the past, with 14C ages ranging from 28,910 ± 200 to 48,090 ± 1050 yr BP. The C/N ratios of the collagen samples of Gunang-gul were determined to be 3.2–3.6. Our study establishes a new guide for the pretreatment of degraded bone samples such as those collected in Korea for 14C dating.
The accelerator mass spectrometry facility at Seoul National University (SNU-AMS) began functioning in December 1998 and was first reported at the Vienna AMS conference in October 1999 and at the 17th International Radiocarbon Conference in Israel in June 2000. At the Vienna conference, we reported our accelerator system (Kim et al. 2000) and details of the basic sample preparation system (Lee et al. 2000), such as the combustion line to produce CO2; the catalytic reduction line for the graphitization of CO2; and the pretreatment procedures for wood, charcoal, and peat samples. The recent progress of the AMS facility (Kim et al. 2001) and the extension of the sample pretreatment system to iron and bone samples were reported at the 17th International Radiocarbon Conference (Cheoun et al. 2001). In the meantime, extensive testing of accuracy and reproducibility has been carried out, and ∼1000 unknown archaeological and geological samples have been measured every year. In this report, the archaeological, geological, and environmental data carried out in 1999 are presented in terms of yr BP.
The accelerator mass spectrometry facility at Seoul National University (SNU-AMS) began functioning in December 1998 and was first reported at the Vienna AMS conference in October 1999 and at the 17th Radiocarbon Conference in Israel in June 2000. At the Vienna conference, we reported our accelerator system (Kim et al. 2000) and the basic sample preparation system (Lee et al. 2000), including the combustion line to produce CO2; the catalytic reduction line for the graphitization of CO2; and also pretreatment procedures for wood, charcoal, and peat samples. Recent progress of the AMS facility (Kim et al. 2001) and extension of the sample pretreatment system to iron and bone samples were reported at the 17th Radiocarbon Conference (Cheoun et al. 2001). In the meantime, extensive testing of accuracy and reproducibility has been carried out, and ∼1000 unknown archaeological and geological samples have been measured every year. A report of data carried out in 1999 is presented by Kim et al. (this issue). In this report, the archaeological, geological, and environmental data carried out in 2000 are presented in terms of yr BP.
Since iron artifacts generally contain trace amounts of carbon, an iron sample needs to be relatively large, as compared to other materials, and a specially designed combustion system is required. An elemental analyzer (EA) was used for the combustion of iron without any special chemical treatment. CO2 gas with 1 mg of carbon was obtained from the combustion of an iron artifact by using an EA and reduced to graphite for accelerator mass spectrometry (AMS) measurement. In this work, AMS dating results done at the Korea Institute of Geoscience and Mineral Resources (KIGAM) for several ancient iron artifacts are presented and compared with independently estimated ages. This method was found to be useful for the pretreatment of iron artifacts that contained >0.1% carbon. A simple pretreatment method using an EA was also applied to calcium carbonate (CaCO3) samples. Samples were preheated overnight at 100–300 °C, without any special chemical treatment. This removed modern CO2 contamination and the background level decreased to a comparable value measured in samples treated with phosphoric acid under vacuum.
We present the current status of accelerator mass spectrometry (AMS) dating of iron artifacts at Seoul National University (SNU). In ancient iron production, charcoal was widely used as carbon for the smelting process, whereas coal is used in modern times. If reliable data could be obtained from carbon by using AMS, ancient iron artifacts could be traced to their production age. In normal acid treatment, it is not easy to extract carbon due to its colloidal property. The negative charge property of the carbon colloid, however, makes it possible for it to be precipitated with positive ions by dissolving the iron chemically. An extraction yield of the carbon incorporated in modern cast iron of about 70% is attained. More refined methods to increase the extraction rate are under progress for archaeological applications.