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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.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
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 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.
Liposomal drug delivery products have been already commercialized in tumor therapeutics, which can realize passive tumor targeting via enhanced permeability and retention (EPR) effect resulting from the leaky tumor vasculature. To control drug release out of the liposomes, thermo-sensitive liposomes (TSLs) have been developed so that an abrupt exposure of highly concentrated drugs to tumor tissues was enabled by locally treated thermal stimuli. As interests upon TSL have increased along with ongoing clinical trials, some types of TSLs with different physical properties in pharmacokinetics and the mechanism of drug release have been formulated. However, there are few protocols established with a desirable heat source to maximize the efficacy of different TSLs as treating tumors. In this study, we examined different protocols for the most effective application of different TSLs to tumor therapy. First, we examined if enhancing the accumulation of TSLs within tumor tissues prior to bursting drugs out of TSLs could lead to increasing anti-tumor efficacy. Second, we compared the efficiency of two different heat sources on the use of TSL, a warm water bath (42°C) and high intensity focused ultrasound (HIFU). Our study suggests that the specified protocol be setup for TSLs with different physical properties to optimally function in tumor therapies.
Prior studies have suggested that major depressive disorder (MDD) with pre-adult onset represents a distinct subtype with greater symptom severity and higher rates of suicidal ideation. Whether these patients have poorer response to various types of antidepressant treatment than those with adult-onset MDD is unclear.
A total of 665 psychiatric and primary care out-patients (aged 18–75 years) with non-psychotic chronic or recurrent MDD participated in a single-blind, randomized trial that compared the efficacy of escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine. We compared participants who self-reported MDD onset (before age 18) to those with a later onset (adult onset) with respect to baseline characteristics and treatment/outcome variables at 12 and 28 weeks.
Early-onset chronic/recurrent MDD was associated with a distinct set of sociodemographic (female, younger age) and clinical correlates (longer duration of illness, greater number of prior episodes, greater likelihood of atypical features, higher rates of suicidality and psychiatric co-morbidity, fewer medical problems, poorer quality of life, greater history of child abuse/neglect). However, results from unadjusted and adjusted analyses showed no significant differences in response, remission, tolerability of medications, quality of life, or retention at 12 or 28 weeks.
Although early-onset chronic/recurrent MDD is associated with a more severe clinical picture, it does not seem to be useful for predicting differential treatment response to antidepressant medication. Clinicians should remain alert to an increased risk of suicidality in this population.
Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes.
This cohort study recruited out-patients aged 18–75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as: chronic (index episode >2 years) and recurrent (n=398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n=387). Acute treatment was up to 14 weeks of citalopram (⩽60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology – Self-Rated (QIDS-SR16) ⩽5] or response (⩾50% reduction from baseline in QIDS-SR16) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) ⩾11].
Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse.
Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes.
The present study assessed the relationship between breakfast frequency and measures of obesity in Hong Kong Chinese children aged 9–18 years. A total of 11 570 children (50 % boys) underwent anthropometric measurements and completed a simple self-administered dietary behaviour questionnaire. Their parents completed a questionnaire providing demographic information. Breakfast frequency was assessed by a single question, ‘How many days over the past week did you have breakfast?’ Children were categorised into three groups: skippers (ate breakfast 0–2 times/week); semi-skippers (ate breakfast 3–4 times/week); non-skippers (ate breakfast 5–7 times/week), to assess all associated characteristics. Of the 3644 primary and 7926 secondary school students, 8 % (8·7 % of boys and 6·9 % of girls) and 14 % (14 % of boys and 15 % of girls), respectively, were breakfast skippers. The prevalence of obesity among breakfast skippers, semi-skippers and non-skippers was, respectively, 9·8, 10·6 and 3·8 % (P < 0·001) for primary school students and 3·9, 3·1 and 2·4 % (P < 0·001) for secondary school students. The 12 % of Hong Kong children aged 9–18 years who skipped breakfast had higher BMI, BMI z-scores and percentage of body fat (PBF) than their counterparts. The dose effects of breakfast frequency (unstandardised regression coefficient, P < 0·001) on BMI and PBF were, respectively, − 0·125 kg/m2 and − 0·219 % for boys and − 0·165 kg/m2 and − 0·353 % for girls, adjusting for physical activity per additional breakfast meal per week. Further study is recommended to elucidate whether regular breakfast consumption may have a role in the prevention of childhood obesity.
We present ultraviolet (UV) properties of dwarf galaxies in the Fornax and Ursa Major clusters in comparison with the Virgo cluster. Most of the dwarf galaxies in the Fornax cluster show red UV colors which is consistent with that the Fornax is dynamically evolved cluster with large fraction of early-type galaxies. Meanwhile, majority of dwarf galaxies of Ursa Major cluster are late-type with blue UV colors, indicating prevalence of strong star formation activities in the low density environment.
We present a new catalog of dwarf galaxies in the Virgo cluster using SDSS DR7 data. Basically, morphologies of galaxies are classified based on the image and spectral feature of SDSS data. We secure 994 dwarf galaxies as members of the Virgo cluster, from which 492 galaxies are new objects not included in the previous catalog. By matching with GALEX GR5 data, we present ultraviolet properties of various dwarf galaxies in the Virgo cluster. We suggest that there are different star formation histories among different subclasses of early-type dwarf galaxies in the Virgo cluster related with their morphology and environment.
We present a mass-metallicity (M–Z) relation of 412 blue compact dwarf galaxies at z = 0.2 ~ 0.5 using the Sloan Digital Sky Survey (SDSS) DR7 spectroscopic data. We found a variation of mass-metallicity relations depending on the redshift in which metallicity evolution of low mass galaxies appear to be stronger than that of high mass galaxies. The specific star formation rate (SSFR) shows tight correlation with galaxy mass in the sense that low mass galaxies have substantially high SSFR. We also discuss environmental effect in the SSFR vs galaxy mass relation. At a given mass, merging system shows systematically higher SSFR than isolated one.
A population-based telephone survey of acute gastroenteritis (AG) was conducted in Hong Kong from August 2006 to July 2007. Study subjects were recruited through random digit-dialling with recruitments evenly distributed weekly over the 1-year period. In total, 3743 completed questionnaires were obtained. An AG episode is defined as diarrhoea ⩾3 times or any vomiting in a 24-h period during the 4 weeks prior to interview, in the absence of known non-infectious causes. The prevalence of AG reporting was 7%. An overall rate of 0·91 (95% CI 0·81–1·01) episodes per person-year was observed with women having a slightly higher rate (0·94, 95% CI 0·79–1·08) than men (0·88, 95% CI 0·73–1·04). The mean duration of illness was 3·6 days (s.d.=5·52). Thirty-nine percent consulted a physician, 1·9% submitted a stool sample for testing, and 2·6% were admitted to hospital. Of the subjects aged ⩾15 years, significantly more of those with AG reported eating raw oysters (OR 2·4, 95% CI 1·3–4·4), buffet meals (OR 1·8, 95% CI 1·3–2·5), and partially cooked beef (OR 1·8, 95% CI 1·2–2·7) in the previous 4 weeks compared to the subjects who did not report AG. AG subjects were also more likely to have had hot pot, salad, partially cooked or raw egg or fish, sushi, sashimi, and ‘snacks bought at roadside’ in the previous 4 weeks. This first population-based study on the disease burden of AG in Asia showed that the prevalence of AG in Hong Kong is comparable to that experienced in the West. The study also revealed some ‘risky’ eating practices that are more prevalent in those affected with AG.
The epidemiological, clinical and virological features of 1220 children with acute bronchiolitis admitted to the Prince of Wales Hospital, Hong Kong, from 1985 to 1988 are reported. They accounted for 6·6% of total paediatric admissions and provided a case incidence of bronchiolitis requiring admission to hospital of approximately 21 per 1000 children 0–24 months of age.
The clinical course and outcome was in general benign. The average hospital stay was 5 days and there were no deaths. Ten per cent of patients were repeatedly admitted to hospital with recurrent wheezing after discharge. Two infants developed bronchiolitis obliterans.
Respiratory syncytial virus (RSV) was shown by direct immunofluorescence, virus culture and serology to be the commonest cause of acute bronchiolitis in Hong Kong. Other aetiological agents included parainfluenza and influenza viruses, adenoviruses, and Mycoplasma pneumoniae.
In contrast to western countries, a seasonal variation of bronchiolitis was found with a peak incidence in the summer months. The significance of these observations is discussed.
Piezoresistors are commonly used in microsystems for transducing force, displacement, pressure and acceleration. Silicon piezoresistors can be fabricated using ion implantation, diffusion or epitaxy and are widely used for their low cost and electronic readout. However, the design of piezoresistive cantilevers is complicated by coupling between design parameters as well as fabrication and application constraints. Here we discuss analytical models and design optimization for piezoresistive cantilevers, and describe several applications ranging from studying electron movement using scanning gate microscopy to measuring the biomechanics of whole organisms.
Echinacea purpurea has been introduced in to Taiwan and grown successfully. However, information regarding the effects of the growing climate on its active constituents (e.g. caffeoyl derivatives) and biomass production is very limited. In this study the biomass of field-grown E. purpurea plants harvested during three different crop seasons was compared. The content of caffeoyl phenols and the production of aerial plant parts were also assayed. The results indicated that both morphological and agronomic traits were affected by crop season, with spring-grown plants producing more stems and flowers but fewer leaves than autumn-grown plants. Autumn-grown plants produced more caffeoyl phenols, particularly cichoric acid and caftaric acid, in leaf and flower tissues than spring grown plants. Thus, transplanting E. purpurea seedlings in the autumn and harvesting the aerial parts at the beginning of winter first, and then harvesting the rhizome-regenerated plants again in the following summer are technically feasible. This farming system would give commercial cultivation of E. purpurea in Taiwan a great competitive advantage over other growing regions, provided that an environmentally suitable population is selected and established in Taiwan.