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Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.
A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.
Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3–0.6%) and 0.05% (95% CI 0.03–0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.
The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.
Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD.
A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed.
In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27–34%], 1-year prevalence was 8% (95% CI 3–14%) and 1-month prevalence was 24% (95% CI 15–34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting.
This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.
An updated compilation of published and new data of major-ion (Ca, Cl, K, Mg, Na, NO3, SO4) and methylsulfonate (MS) concentrations in snow from 520 Antarctic sites is provided by the national ITASE (International Trans-Antarctic Scientific Expedition) programmes of Australia, Brazil, China, Germany, Italy, Japan, Korea, New Zealand, Norway, the United Kingdom, the United States and the national Antarctic programme of Finland. The comparison shows that snow chemistry concentrations vary by up to four orders of magnitude across Antarctica and exhibit distinct geographical patterns. The Antarctic-wide comparison of glaciochemical records provides a unique opportunity to improve our understanding of the fundamental factors that ultimately control the chemistry of snow or ice samples. This paper aims to initiate data compilation and administration in order to provide a framework for facilitation of Antarctic-wide snow chemistry discussions across all ITASE nations and other contributing groups. The data are made available through the ITASE web page (http://www2.umaine.edu/itase/content/syngroups/snowchem.html) and will be updated with new data as they are provided. In addition, recommendations for future research efforts are summarized.
Δ14C values of leaves of deciduous trees provide a means to map the regional-scale fossil fuel ratio in the atmosphere. We collected a batch of ginkgo (Ginkgo biloba Linnaeus, a deciduous tree) leaf samples from across Korea in the month of July in both 2010 and 2011 to obtain the regional distribution of Δ14C. The Δ14C values of the samples were measured using accelerator mass spectrometry (AMS) at the Korea Institute of Geoscience and Mineral Resources (KIGAM). The average of the Δ14C values from clean air sites in Korea in 2011 measured slightly lower than the average of Δ14C values in 2010. Distribution maps of Δ14C of 2011 and 2010 in Korea were made based on a series of Δ14C values of ginkgo leaf samples from Korea using the Geostatistical and Spatial analyst tools in ESRI's ArcMap software. The distribution maps of Δ14C showed that Δ14C values in the western part of Korea are lower than those in the eastern part of Korea. This is because the western part of Korea is densely populated and contains many industrial complexes, and also because westerly winds from China, containing CO2 from fossil fuel use, blow into Korea. We compared the distribution maps of 2010 and 2011 and tried to find traces of the Fukushima power plant accident in Japan.
Various carbon structures, including carbon nanofilament (CNF), single-wall carbon nanotube (SWCNT), multi-wall carbon nanotube (MWCNT), and pyrolytic graphite sheet (PGS), were exposed in air to determine how they vary according to carbon structure and air temperature. CNF is the carbon structure used in accelerator mass spectrometry (AMS) radiocarbon dating (Santos et al. 2007). When CNF and MWCNT were exposed in cold air (3 or −18 °C) for longer than 6 hr, their 14C/12C ratio increased (>5 × 10–14). When heated in an oven (200 or 250 °C) for longer than 12 hr, their 14C/12C ratio decreased. However, when SWCNT and PGS were exposed in air cooled to 3 °C for 12 hr, their 14C/12C ratio did not increase. This phenomenon is very curious, and is useful for the development of a storage method for carbon samples made by reduction reactions of CO2.
This study evaluated whether primary tumour characteristics are associated with specific features of metastatic lymph nodes in papillary thyroid carcinoma patients.
A retrospective review of 411 patients with pathologically diagnosed cervical lymph node metastasis was conducted.
A metastatic lymph node focus size of at least 2 mm was independently associated with a primary tumour size of at least 1 cm (hazard ratio 1.962) and with male sex (hazard ratio 1.947). A number of at least five lymph node metastases was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.863), extrathyroidal extension (hazard ratio 1.737) and male sex (hazard ratio 1.689). Extranodal extension was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.288), extrathyroidal extension (2.201) and male sex (hazard ratio 1.733).
Primary papillary thyroid carcinoma characteristics are related to the pathological features of lymph node metastases.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For the success of PAL-XFEL, two critical systems, namely a low emittance injector and a variable gap out-vacuum undulator, are under development. In order to realize the target emittance of the PAL-XFEL injector we carried out an optimization study of various parameters, such as the laser beam transverse profile, the laser pulse length, the laser phase, and the gun energy. The transverse emittance measured at the Injector Test Facility (ITF) is
. An undulator prototype based on the EU-XFEL design and modified for PAL-XFEL was built and tested. A local-
pole tuning procedure was developed and tested. A significant reduction (90%) of the local-
fluctuation was observed. The requirement of undulator field reproducibility better than
and the undulator gap setting accuracy below
were achieved for the prototype. The optical phase jitter after the pole height tuning at the tuning gap was calculated to be
rms, which satisfies the requirement of
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
A novel nano-scale manipulator capable of handling low-dimensional materials with three-dimensional linear motion, gripping action, and push–pull action of the gripper was developed for an in situ experiment in transmission electron microscopy. X-Y-Z positioning and push–pull action were accomplished by a piezotubing system, combined with a specially designed assembly stage that consisted of a lever-action gripping tip backed by a push–pull piezostack. The gripper tip consisted of tungsten wire fabricated by electrochemical etching followed by a focused ion beam process. Performance of the nano-scale manipulator was demonstrated in a grab-and-pick test of a single silver nanowire and in an in situ tensile test of a pearlitic steel sample with a specific orientation.
Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.
Depression is common after acute coronary syndrome (ACS) with adverse effects on prognosis. There is little evidence on whether depression treatment improves quality of life (QoL) in ACS patients. The aim of this study was to investigate the effects of co-morbid depression and its treatment on QoL in ACS.
In total, 1152 patients were recruited at baseline, 2–14 weeks after a confirmed ACS episode, and 828 were followed 1 year thereafter. Of 446 baseline participants with co-morbid depressive disorders, 300 were randomized to a 24-week double blind trial of escitalopram or placebo, while the remaining 146 received medical treatment only (MTO). QoL was measured by the World Health Organization Quality of Life –Abbreviated form (WHOQOL-BREF).
At baseline, QoL was significantly lower in patients with co-morbid depressive disorder than those without. QoL improvement was significantly greater in those receiving escitalopram than those receiving placebo over the 24-week treatment period. In the 1-year follow-up, the better outcomes associated with escitalopram remained evident against both placebo and MTO.
Depression was significantly associated with worse QoL even in patients with recently developed ACS. Depression treatment was associated with QoL improvement in ACS patients in the 24-week treatment period, the effects of which extended to 1 year.
Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children.
A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated.
Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri.
The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.
A new dataset of the highest quality specimens of fully articulated, juvenile and mature exoskeletons of the Czech middle Silurian trilobite Aulacopleura koninckii offers improved resolution of original morphology by all measures considered. The degree of variation in both size and shape among later meraspid instars was constant, and suggesting targeted growth in both attributes. Size-related changes in the shape of the dorsal exoskeleton and of the segment-invariant cephalon were detected in the meraspid stage, but in the holaspid phase marked allometry was detected only in the trunk region, with the pygidium showing notable expansion in relative size. Meraspid cranidial allometry was subtle, with significant changes in instar form detectable only after several molts. This trilobite developed gradually throughout meraspid and holaspid ontogeny, with the synchronous cessation of trunk segment appearance and release at the onset of the holaspid phase. Precise development of shape and size occurs in the context of marked variability in the number of trunk segments at maturity, illustrating complex patterns of character variation within a species. A new systematic description establishes the synonymy of several subspecies with A. koninckii.
Discovery of ultra-compact dwarfs (UCDs) in the past 15 years blurs the once thought clear division between classic globular clusters (GCs) and early-type galaxies. The intermediate nature of UCDs, which are larger and more massive than typical GCs but more compact than typical dwarf galaxies, has triggered hot debate on whether UCDs should be considered galactic in origin or merely the most extreme GCs. Previous studies of various scaling relations, stellar populations and internal dynamics did not give an unambiguous answer to the primary origin of UCDs. In this contribution, we present the first ever detailed study of global dynamics of 97 UCDs (rh ≳ 10 pc) associated with the central cD galaxy of the Virgo cluster, M87. We found that UCDs follow a different radial number density profile and different rotational properties from GCs. The orbital anisotropies of UCDs are tangentially-biased within ~ 40 kpc of M87 and become radially-biased with radius further out. In contrast, the blue GCs, which have similar median colors to our sample of UCDs, become more tangentially-biased at larger radii beyond ~ 40 kpc. Our analysis suggests that most UCDs in M87 are not consistent with being merely the most luminous and extended examples of otherwise normal GCs. The radially-biased orbital structure of UCDs at large radii is in general agreement with the scenario that most UCDs originated from the tidally threshed dwarf galaxies.
After an outbreak of pandemic influenza A/H1N1 (pH1N1) virus, we had previously reported the emergence of a recombinant canine influenza virus (CIV) between the pH1N1 virus and the classic H3N2 CIV. Our ongoing routine surveillance isolated another reassortant H3N2 CIV carrying the matrix gene of the pH1N1 virus from 2012. The infection dynamics of this H3N2 CIV variant (CIV/H3N2mv) were investigated in dogs and ferrets via experimental infection and transmission. The CIV/H3N2mv-infected dogs and ferrets produced typical symptoms of respiratory disease, virus shedding, seroconversion, and direct-contact transmissions. Although indirect exposure was not presented for ferrets, CIV/H3N2mv presented higher viral replication in MDCK cells and more efficient transmission was observed in ferrets compared to classic CIV H3N2. This study demonstrates the effect of reassortment of the M gene of pH1N1 in CIV H3N2.
The non-recurrent laryngeal nerve is subject to potential injury during thyroid surgery. Intra-operative identification and preservation of this nerve can be challenging. Its presence is associated with an aberrant subclavian artery and the developmental absence of the brachiocephalic trunk. This study aimed to evaluate the incidence of non-recurrent laryngeal nerves and present a new classification system for the course of these nerves.
Non-recurrent laryngeal nerves were identified on the right side in 15 patients who underwent thyroidectomy. The incidence of non-recurrent laryngeal nerves (during thyroidectomy) and aberrant subclavian arteries (using neck computed tomography) was evaluated, and the course of the nerves was classified according to their travelling patterns.
The overall incidence of non-recurrent laryngeal nerves was 0.68 per cent. The travelling patterns of the nerves could be classified as: descending (33 per cent), vertical (27 per cent), ascending (20 per cent) or V-shaped (20 per cent).
Clinicians need to be aware of these variations to avoid non-recurrent laryngeal nerve damage. A retroesophageal subclavian artery (on neck computed tomography) virtually assures a non-recurrent laryngeal nerve. This information is important for preventing vocal fold paralysis. Following a review of non-recurrent laryngeal nerve travelling patterns, a new classification was devised.
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally?
Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus.
Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct.
MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.
We observed an area of sky located within the SDSS Stripe 82 field at 1.6 GHz with the European VLBI Network (EVN). There are fifteen mJy/sub-mJy radio sources within the primary beam of a typical 30-m class EVN radio telescope. Our aim was to obtain information on compact radio structures of all VLBI-detectable sources within this primary beam area. The source of particular interest is the recently identified radio quasar J222843.54+011032.2 (J2228+0110) at z = 5.95. The data correlation was performed at the EVN software correlator at JIVE (SFXC). Three targets (J2228+0110, J222851.45+011203.4, J222941.76+011428.5) were detected, all three with position offsets not exceeding the 3σ accuracy of the original low-resolution radio surveys. The detection rate of 20% is consistent with other wide-field VLBI experiments carried out recently (e.g. Middelberg et al. 2013). The project presented here demonstrates the ability of EVN in multiple-phase-centre experiments and paves the way for future large-scale EVN surveys of compact structures in extragalactic radio sources using the multiple-phase-centre VLBI technique.