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Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI = 25–29.9) without metabolic syndrome or diabetes has not been thoroughly investigated.
To assess the metabolic health of overweight patients receiving antipsychotic drugs.
We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes.
Compared with the normal weight subjects (n = 286), overweight patients (n = 212) had higher fasting insulin resistance as assessed with the homeostatic model (P = 0.023), insulin secretion during the oral glucose tolerance test (P = 0.0037), triglycerides (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0089), and lower levels of high-density lipoprotein cholesterol (P = 0.0014). The obese (n = 50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P = 0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups.
Overweight (BMI = 25–29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
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.
We present high-resolution implicit large eddy simulation (iLES) of the turbulent air-entraining flow in the wake of three-dimensional rectangular dry transom sterns with varying speeds and half-beam-to-draft ratios
. We employ two-phase (air/water), time-dependent simulations utilizing conservative volume-of-fluid (cVOF) and boundary data immersion (BDIM) methods to obtain the flow structure and large-scale air entrainment in the wake. We confirm that the convergent-corner-wave region that forms immediately aft of the stern wake is ballistic, thus predictable only by the speed and (rectangular) geometry of the ship. We show that the flow structure in the air–water mixed region contains a shear layer with a streamwise jet and secondary vortex structures due to the presence of the quasi-steady, three-dimensional breaking waves. We apply a Lagrangian cavity identification technique to quantify the air entrainment in the wake and show that the strongest entrainment is where wave breaking occurs. We identify an inverse dependence of the maximum average void fraction and total volume entrained with
. We determine that the average surface entrainment rate initially peaks at a location that scales with draft Froude number and that the normalized average air cavity density spectrum has a consistent value providing there is active air entrainment. A small parametric study of the rectangular geometry and stern speed establishes and confirms the scaling of the interface characteristics with draft Froude number and geometry. In Part 2 (Hendrikson & Yue, J. Fluid Mech., vol. 875, 2019, pp. 884–913) we examine the incompressible highly variable density turbulence characteristics and turbulence closure modelling.
A new generation of high power laser facilities will provide laser pulses with extremely high powers of 10 petawatt (PW) and even 100 PW, capable of reaching intensities of
in the laser focus. These ultra-high intensities are nevertheless lower than the Schwinger intensity
at which the theory of quantum electrodynamics (QED) predicts that a large part of the energy of the laser photons will be transformed to hard Gamma-ray photons and even to matter, via electron–positron pair production. To enable the investigation of this physics at the intensities achievable with the next generation of high power laser facilities, an approach involving the interaction of two colliding PW laser pulses is being adopted. Theoretical simulations predict strong QED effects with colliding laser pulses of
focused to intensities
Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by serotypes of the enterovirus (EV) family. HFMD reinfection occurs commonly in lack of cross-protection between different EV serotypes. In this study, we investigated the hazards of HFMD reinfection using Cox-proportional hazard model. Retrospective data of 95 209 HFMD cases in Wuhan during 2008–2015 was used. Kaplan–Meier survival methods and Cox-proportional hazard model were used to estimate the hazard probabilities. Of the all HFMD cases, about 2% experienced reinfection (1842/95 209). Kaplan–Meier curves revealed the reinfection risk sharply increased before 40 months from first infection. Higher hazards of reinfection were detected among those who were males, aged 3 years and below, scattered children, belonging to urban areas and first infected with coxsackievirus (CV)-A16 compared with their respective counterparts. Cox-proportional hazard model suggested that gender, age, group, living area and serotypes of first infection had significant effect on reinfection even after adjusting for potential confounding effects of other selected factors considered in the study. These results indicate that boys aged 3 years and below, especially those living in urban areas and first infected with CV-A16 are more prone to reinfection. Interventions should be imposed on these high-risk populations.
We discuss specific aspects of space-ground VLBI (SVLBI) data processing of spectral line experiments (H2O & OH masers) in Radioastron project. In order to meet all technical requirements of the Radioastron mission a new software FX correlator (ASCFX) and the unique data archive which stores raw data from all VLBI stations for all experiments of the project were developed in Astro Space Center. Currently all maser observations conducted in Radioastron project were correlated using the ASCFX correlator. Positive detections on the space-ground baselines were found in 38 sessions out of 144 (detection rate of about 27%). Finally, we presented upper limits on the angular size of the most compact spots observed in two galactic H2O masers, W3OH(H2O) and OH043.8-0.1.
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.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression of target messenger RNAs (mRNAs) and miRNAs have been proven to play vital roles in skeletal muscle development. The miRNA-499-5p has been reported to be negatively related with the expression of Sox6, a critical transcription factor for the maintenance of fast-twitch skeletal muscle. In this study, we amplified a length of 2012-bp mRNA that contains a 1512-bp porcine Sox6 (pSox6) 3'UTR from skeletal muscle of a Duroc×Landrace×Yorkshire pig. By luciferase reporter assay we verified that pSox6 is a target of miR-499-5p. In extensor digitorum longus and Soleus muscles of pigs, the expression levels of miR-499-5p and pSox6 mRNA were also inversely correlated. Besides, overexpression of miR-499-5p in porcine satellite cells promoted the expression of MyHC I and MyHC IIa mRNA, along with a reduction of pSox6 mRNA. Taken together, these results indicate that miR-499-5p may facilitate the oxidative myofibers formation by downregulating pSox6 expression.
This conference paper reports the recent discoveries of two hot Jupiters (hJs) around weak-line T Tauri stars (wTTS) V830 Tau and TAP 26, through the analysis of spectropolarimetric data gathered within the Magnetic Topologies of Young Stars and the Survival of massive close-in Exoplanets (MaTYSSE) observation programme. HJs are thought to form in the outskirts of protoplanetary discs, then migrate inwards close to their host stars as a result of either planet-disc type II migration or planet-planet scattering. Looking for hJs around young forming stars provides key information on the nature and time scale of such migration processes, as well as how their migration impacts the subsequent architecture of their planetary system. Young stars are however extremely active, to the point that their radial velocity (RV) jitter is around an order of magnitude larger than the potential signatures of close-in gas giants, making them difficult to detect with velocimetry. Three techniques to filter out this activity jitter are presented here, two using Zeeman Doppler Imaging (ZDI) and one using Gaussian Process Regression (GPR).
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.
Mitochondria plays an important role in the regulation of energy homeostasis. Moreover, mitochondrial biogenesis accompanies skeletal myogenesis, and we previously reported that maternal high-energy diet repressed skeletal myogenesis in pig fetuses. Therefore, the aim of this study was to evaluate the effects of moderately increased maternal energy intake on skeletal muscle mitochondrial biogenesis and function of the pig fetuses. Primiparous purebred Large White sows were allocated to a normal energy intake group (NE) as recommended by the National Research Council (NRC) and a high energy intake group (HE, 110% of NRC recommendations). On day 90 of gestation, fetal umbilical vein blood and longissimus (LM) muscle were collected. Results showed that the weight gain of sows fed HE diet was higher than NE sows on day 90 of gestation (P<0.05). Maternal HE diet increased fetal umbilical vein serum triglyceride and insulin concentrations (P<0.05), and tended to increase the homeostasis model assessment index (P=0.08). Furthermore, HE fetuses exhibited increased malondialdehyde concentration (P<0.05), and decreased activities of antioxidative enzymes (P<0.05) and intracellular NAD+ level (P<0.05) in LM muscle. These alterations in metabolic traits of HE fetuses were accompanied by reduced mitochondrial DNA amount (P<0.05) and down-regulated messenger RNA expression levels of genes responsible for mitochondrial biogenesis and function (P<0.05). Our results suggest that moderately increased energy supply during gestation decreases mitochondrial biogenesis, function and antioxidative capacity in skeletal muscle of pig fetuses.
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.
Bitter gourd (Momordica charantia L.) is an important market vegetable in the tropics. The objectives of this study were to (1) conduct a preliminary evaluation of genetic diversity in bitter gourd flesh (without seeds) for phytonutrient (carotenoid, ascorbic acid and tocopherol) contents with the aim to understand which phytonutrients might be increased through breeding, (2) assess the association between fruit traits and phytonutrient contents and (3) evaluate the effect of the fruit harvest stage on phytonutrient contents. A total of 17 diverse bitter gourd entries of various commercial market types were evaluated for fruit traits and phytonutrient contents for 2 years. Significant differences (P= 0.05) among the entries were detected for total carotenoids, total tocopherols, dry matter and fruit traits. Mean total carotenoid contents of the entries ranged from 10 to 1335 μg/100 g fresh weight in year 1 and 10 to 1185 μg/100 g fresh weight in year 2. Mean ascorbic acid contents were 69 and 61 mg/100 g fresh weight in year 1 and year 2, respectively. Total tocopherol contents among the entries ranged from 480 to 1345 and 445 to 2145 μg/100 g fresh weight in year 1 and year 2, respectively. Total carotenoid and ascorbic acid contents were highest at 12 days after fruit set (DAFS), but total tocopherol contents were highest from 14 to 20 DAFS. A 100 g portion of bitter gourd fruit can meet 190, 17 and 8% of the recommended daily allowances of vitamin C, vitamin E and vitamin A, respectively, for adults.
Transcatheter pulmonary valve implantation is usually performed from a femoral venous – transfemoral – approach, but this may not be the optimal vascular access option in some patients. This study aimed to determine which group of patients might benefit from an internal jugular – transjugular – approach for transcatheter pulmonary valve implantation.
This multicentre retrospective study included all patients who underwent attempted transcatheter pulmonary valve placement in the right ventricular outflow tract between April 2010 and June 2012 at two large congenital heart centres. Patients were divided into two groups based on venous access site – transfemoral or transjugular. Patient characteristics, procedural outcomes, and complications were compared between groups.
Of 81 patients meeting the inclusion criteria (median age 16.4 years), the transjugular approach was used in 14 patients (17%). The transjugular group was younger (median age 11.9 versus 17.3 years), had lower body surface area (mean 1.33 versus 1.61 m2), more often had moderate or greater tricuspid regurgitation (29% versus 7%), and had a higher ratio of right ventricle-to-systemic systolic pressure (mean 82.4 versus 64.7). Patients requiring a transjugular approach after an unsuccessful transfemoral approach had longer fluoroscopic times and procedure duration.
The transjugular approach for transcatheter pulmonary valve implantation is used infrequently but is more often used in younger and smaller patients. Technical limitations from a transfemoral approach may be anticipated if there is moderate or greater tricuspid regurgitation or higher right ventricular pressures. In these patients, a transjugular approach should be considered early.
Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother–offspring cohort were assayed at 26–28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.
The aim of this study was to investigate the variations in meat quality, lipid metabolism-related genes, myosin heavy chain (MyHC) isoform genes and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) gene mRNA expressions in longissimus dorsi muscle (LM) of two different pig breeds. Six Rongchang and six Landrace barrows were slaughtered at 161 days of age. Subsequently, meat quality traits and gene expression levels in LM were observed. Results showed that Rongchang pigs not only exhibited greater pH, CIE a*24 h and intramuscular fat content but also exhibited lower body weight, carcass weight, dressing percentage, LM area and CIE b*24 h compared with Landrace pigs (P<0.05). Meanwhile, the mRNA expression levels of the lipogenesis (peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and fatty acid synthase) and fatty acid uptake (lipoprotein lipase)-related genes were greater in the Rongchang (P<0.05), whereas the lipolysis (adipose triglyceride lipase and hormone sensitive lipase) and fatty acid oxidation (carnitine palmitoyltransferase-1B)-related genes were better expressed in the Landrace. Moreover, compared with the Landrace, the mRNA expression levels of MyHCI, MyHCIIa and MyHCIIx were greater, whereas the mRNA expression levels of MyHCIIb were lower in the Rongchang pigs (P<0.05). In addition, the mRNA expression levels of PGC-1α were greater in Rongchang pigs than in the Landrace (P<0.05), which can partly explain the differences in MyHC isoform gene expressions between Rongchang and Landrace pigs. Although the small number of samples does not allow to obtain a definitive conclusion, we can suggest that Rongchang pigs possess better meat quality, and the underlying molecular mechanisms responsible for the better meat quality in fatty pigs may be partly due to the higher mRNA expression levels of lipogenesis and fatty acid uptake-related genes, as well as the oxidative and intermediate muscle fibers, and due to the lower mRNA expression levels of lipolysis and fatty acid oxidation-related genes, as well as the glycolytic muscle fibers.