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Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.
Evidence suggests that skin picking disorder (SPD) could be a prevalent condition associated with comorbidity and psychosocial dysfunction. However, just a few studies have assessed the prevalence and correlates of SPD in samples from low- and middle-income countries. In addition, the impact of SPD on quality of life (QoL) dimension after multivariable adjustment to potential confounders remains unclear.
Data were obtained from a Brazilian anonymous Web-based research platform. Participants provided sociodemographic data and completed the modified Skin Picking–Stanford questionnaire, the Hypomania Checklist (HCL-32), the Patient Health Questionnaire-9 (PHQ-9), the Fagerström Test for Nicotine Dependence, Alcohol Use Disorder Identification Test (AUDIT), Symptom Checklist-90-Revised inventory (SCL-90R), early trauma inventory self report–short form, and the World Health Organization quality of life abbreviated scale (WHOQOL-Bref). Associations were adjusted to potential confounders through multivariable models.
For our survey, 7639 participants took part (71.3% females; age: 27.2±7.9 years). The prevalence of SPD was 3.4% (95% CI: 3.0–3.8%), with a female preponderance (P<0.001). In addition, SPD was associated with a positive screen for a major depressive episode, nicotine dependence, and alcohol dependence, as well as suicidal ideation. Physical and psychological QoL was significantly more impaired in participants with SPD compared to those without SPD, even after adjustment for comorbidity.
In this large sample, SPD was a prevalent condition associated with co-occurring depression, nicotine, and alcohol dependence. In addition, SPD was independently associated with impaired physical and psychological QoL. Public health efforts toward the early recognition and treatment of SPD are warranted.
Remission and recovery rates for people with first-episode psychosis (FEP) remain uncertain.
To assess pooled prevalence rates of remission and recovery in FEP and to investigate potential moderators.
We conducted a systematic review and meta-analysis to assess pooled prevalence rates of remission and recovery in FEP in longitudinal studies with more than 1 year of follow-up data, and conducted meta-regression analyses to investigate potential moderators.
Seventy-nine studies were included representing 19072 patients with FEP. The pooled rate of remission among 12301 individuals with FEP was 58% (60 studies, mean follow-up 5.5 years). Higher remission rates were moderated by studies from more recent years. The pooled prevalence of recovery among 9642 individuals with FEP was 38% (35 studies, mean follow-up 7.2 years). Recovery rates were higher in North America than in other regions.
Remission and recovery rates in FEP may be more favourable than previously thought. We observed stability of recovery rates after the first 2 years, suggesting that a progressive deteriorating course of illness is not typical. Although remission rates have improved over time recovery rates have not, raising questions about the effectiveness of services in achieving improved recovery.
High-redshift quasars are unique probes of the evolution of supermassive black holes and the intergalactic medium at the end of the epoch of reionization. We present the optical spectra of eight new z ~ 6 quasars selected from the Panoramic Survey Telescope & Rapid Response System 1 (Pan-STARRS1). Details of the selection strategy can be found in Bañados et al. (2014). With this work we increase the number of known quasars at z < 5.7 by more than 10%. The quasars discovered here span a large range of luminosities (19.6 ≤ zP1 ≤ 21.2) and are remarkably heterogeneous in their spectral features: half of them show bright emission lines whereas the other half show weak or no Lyα emission line. We find a larger fraction of weak–line emission quasars than in lower redshift studies, although still based on low number statistics, this may imply that the quasar population could be more diverse than previously thought.
Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self-reported data from twins aged 19 to 50 from seven countries that collaborated in the GenomEUtwin project: Australia, Denmark, Finland, Norway, Netherlands, Sweden and United Kingdom. Results confirmed the importance of genetic influences on physical activity in all countries and showed an age-related decrease in heritability for 4 countries. In the other three countries age did not interact with heritability but those samples were smaller or had a more restricted age range. Effects of shared environment were absent, except in older Swedish participants. The study confirms the importance of taking age effects into account when exploring the genetic and environmental contribution to physical activity. It also suggests that the power of genome-wide association studies to identify the genetic variants contributing to physical activity may be larger in young adult cohorts.
This investigation was to determine whether monoclonal antibodies (Mabs) could be used to differentiate coagulase-negative staphylococci (C-NS) at species and strain level. Mabs were produced to four Staphylococcus epidermidis strains, two S. haemolyticus strains, one S. saprophyticus strain and one S. warneri strain. A panel of nine antibodies was tested for species and strain specificity against five type strains and 65 clinical isolates of C-NS by enzyme-linked immunosorbent assay (ELISA). Species specificity was found with Mab D150 produced to one S. haemolyticus strain. Using Mab D150 and Mab D198 in conjunction, identification of 90% of S. haemolyticus isolates to species level was achieved. S. saprophyticus Mab K84 reacted with most other strains of C-NS tested but only three S. haemolyticus strains (16%). This finding provides further evidence that S. haemolyticus possesses different surface determinants to other C-NS which could form the basis of a typing scheme for S. haemolyticus using Mabs D150, D198 and K84.
The predominance of coagulase-negative staphylococci as normal skin flora is thought to be a factor in their association with episodes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. We investigated the prevalence of peritonitis-associated strains on the skin of 28 patients undergoing peritoneal dialysis. Coagulase-negative staphylococci were the most frequently isolated organisms. comprising 47% of peritoncal dialysis fluid isolates and 59% of body site isolates. A total of 142 coagulase-negative staphylococci were speciated. tested for their antimicrobial sensitivity and slime production. and identified by phage typing and plasmid-profile analysis. Staphylococcus epidermidis was the most commonly identified species from both peritoncal dialysis fluid (73%) and body sites (53%). Multiple antibiotic resistance was common, and the greater proportion of isolates were resistant to methicillin: 63·6% of peritoncal dialysis fluid isolates and 61·7% of body-site isolates.isolates. S. haemolyticus isolates were significantly more resistant to methicillin than other species. By phage typing and plasmid-profile analysis it was shown that peritonitis was rarely caused by skincolonizing strains. In only 3 of 14 patients were peritonitis-associated strains isolated as skin colonizers, and no patients developed peritonitis due to organisms previously isolated as skin colonizers.
Lunar laser ranging (LLR) has long provided many of our best measurements on the fundamental nature of gravity, including the strong equivalence principle, time -rate-of-change of the gravitational constant, the inverse square law, geodetic precession, and gravitomagnetism. This paper serves as a brief overview of APOLLO: a recently operational LLR experiment capable of millimeter-level range precision.
In the late 1980s The Netherlands Twin Register (NTR) was established by recruiting young twins and multiples at birth and by approaching adolescent and young adult twins through city councils. The Adult NTR (ANTR) includes twins, their parents, siblings, spouses and their adult offspring. The number of participants in the ANTR who take part in survey and / or laboratory studies is over 22,000 subjects. A special group of participants consists of sisters who are mothers of twins. In the Young NTR (YNTR), data on more than 50,000 young twins have been collected. Currently we are extending the YNTR by including siblings of twins. Participants in YNTR and ANTR have been phenotyped every 2 to 3 years in longitudinal survey studies, since 1986 and 1991 for the YNTR and ANTR, respectively. The resulting large population-based datasets are used for genetic epidemiological studies and also, for example, to advance phenotyping through the development of new syndrome scales based on existing items from other inventories. New research developments further include brain imaging studies in selected and unselected groups, clinical assessment of psychopathology through interviews, and cross-referencing the NTR database to other national databases. A large biobank enterprise is ongoing in the ANTR in which blood and urine samples are collected for genotyping, expression analysis, and meta-bolomics studies. In this paper we give an update on the YNTR and ANTR phenotyping and on the ongoing ANTR biobank studies.
Background. Subjective well-being (SWB) can be partitioned into the components life satisfaction and affect. Research on factors influencing these components of well-being has mainly focused on environmental characteristics. The aim of this study was to investigate the relative contribution of genes and environment to individual differences in life satisfaction in a large sample of Dutch twins and their singleton siblings.
Method. Life satisfaction of 5668 subjects registered with The Netherlands Twin Registry (NTR) was measured with a Dutch version of the self-reported Satisfaction with Life Scale. An extended twin design was used to obtain correlations in life satisfaction scores for monozygotic twins, dizygotic twins and sibling pairs and to estimate the contribution of genes and environment to the variation in life satisfaction.
Results. No differences between males and females were found in the mean level of life satisfaction. Broad-sense heritability was 38%. Non-additive genetic factors explained all or most of the genetic influences. The remaining 62% of the variance in life satisfaction could be attributed to unique environmental factors, both persistent and transitory, plus measurement error.
Conclusions. Individual differences in life satisfaction are determined in part by genetic factors that are largely or entirely non-additive in nature.
Background. Research on risk factors for burnout has mainly focused on circumstances at work and on personal characteristics. The aim of this study was to investigate whether burnout clusters within families and, if so, whether this is due to genetic influences or to environmental factors shared by family members. Finally, we tried to identify specific risk factors for burnout.
Method. In 2707 twins, 736 of their siblings and 575 of their spouses from a population-based twin-family sample, burnout was measured using a self-report questionnaire. Correlations in burnout scores were obtained for monozygotic and dizygotic twin pairs and sibling pairs conditional on the pairs' sex. Correlations for twins and their spouses were derived conditional on the length of the relationship.
Results. In the final model, correlations of the monozygotic and dizygotic twin pairs and sibling pairs were significantly different from zero, but not significantly different from each other. The correlation was estimated at 0·22. The correlation between spouses was also significant. This was mainly due to the group with a relationship longer than 5 years in which the correlation was 0·24. Burnout scores were higher in subjects whose parents had a high level of education.
Conclusions. There is familial clustering for burnout due to environmental factors shared by family members, explaining 22% of the variance. Genetic factors do not seem to be of importance. The significant correlation between spouses supports the conclusion that common environment plays a role in burnout. A high parental education is one of the familial risk factors.
We present the first results from our next-generation microlensing survey, the SuperMACHO project. We are using the CTIO 4m Blanco telescope and the MOSAIC imager to carry out a search for microlensing toward the Large Magellanic Cloud (LMC). We plan to ascertain the nature of the population responsible for the excess microlensing rate seen by the MACHO project. Our observing strategy is optimized to measure the differential microlensing rate across the face of the LMC. We find this derivative to be relatively insensitive to the details of the LMC's internal structure but a strong discriminant between Galactic halo and LMC self lensing. In December 2003 we completed our third year of survey operations. 2003 also marked the first year of real-time microlensing alerts and photometric and spectroscopic followup. We have extracted several dozen microlensing candidates, and we present some preliminary light curves and related information. Similar to the MACHO project, we find SNe behind the LMC to be a significant contaminant - this background has not been completely removed from our current single-color candidate sample. Our follow-up strategy is optimized to discriminate between SNe and true microlensing.To search for other articles by the author(s) go to: http://adsabs.harvard.edu/abstract_service.html
In 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a questionnaire at registration and afterwards when the children are 2, 3, 5, 7, 10 and 12 years of age. Teachers are asked to rate the behavior of the children at ages 7, 10 and 12 years. Adolescent and young-adult twins were recruited through City Councils in the early 1990s. These twins, their parents and siblings participate in longitudinal survey studies that include items about health, fertility, lifestyle, addiction, personality and psychopathology, religion, socioeconomic status, and educational attainment. The total number of twins and multiples registered with the NTR is currently over 60,000. Subgroups of twins and siblings take part in studies of cognitive development, brain function and neuropsychological indices of attention processes, and molecular genetic studies of classical and behavioral cardiovascular risk factors. DNA samples are currently collected in selected twin families for two large linkage studies, which aim to find QTLs for anxious depression and for nicotine addiction. Sisters who are mothers of DZ twins contribute DNA samples for a linkage study of DZ twinning. Large cohorts of phenotyped family members from the general population are very valuable for genetic epidemiological studies and permit selection of informative families for gene finding studies.
We present the preliminary results of a frequency analysis of 1457 fundamental mode RR Lyrae (RR0) stars in the Large Magellanic Cloud (LMC) from MACHO Project photometry. We find the same classes of pulsational behavior as were found in our earlier survey of first overtone RR Lyrae (RR1) stars. Variables whose prewhitened power spectra contain one or two peaks close to the main frequency component in the original power spectra are commonly known as Blazhko-type variables. The present analysis shows the overall frequency of Blazhko-type stars in the total RR0 population analysed to date to be ≈ 10%. This is lower than the often cited Galactic field/globular rate of 20-30% (Szeidl, 1988).
The incidence rate of Blazhko-type variability in the LMC appears to be about three times higher in RR0 stars than in RR1 stars. This puts important constraints on possible models of the Blazhko effect.
Pseudomonas fluorescens strain D7 (P. f. D7; NRRL B-18293) is a root-colonizing bacterium that inhibits downy brome (Bromus tectorum L. BROTE) growth. Before commercialization as a biological control agent, strain D7 must be tested for host plant specificity. Agar plate bioassays in the laboratory and plant–soil bioassays in a growth chamber were used to determine the influence of P. f. D7 on germination and root growth of 42 selected weed, cultivated or native plant species common in the western and midwestern United States. In the agar plate bioassay, all accessions of downy brome were inhibited by P. f. D7. Root growth of seven Bromus spp. was inhibited an average of 87% compared with that of controls in the agar plate bioassay. Root growth of non-Bromus monocots was reduced by 0 to 86%, and only 6 out of 17 plant species were inhibited 40% or greater. Among all plant species, only downy brome root growth from two accessions was significantly inhibited by P. f. D7 in plant–soil bioassays (42 and 64%). P. f. D7 inhibited root growth and germination in agar plate bioassays more than in plant–soil bioassays. Inhibition in plant–soil bioassays was limited to downy brome, indicating promise for P. f. D7 as a biocontrol agent that will not harm nontarget species.
This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal: noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.