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Stress elicits adaptive responses from the brain, but it can also lead to maladaptive consequences. For example, stress can precipitate mental illness, including depression. Prolonged stress also causes damage to neurons in the hippocampus. Antidepressant drugs must be evaluated, not only for their ability to potentiate adaptive responses, but also to inhibit maladaptive consequences of stress. Ongoing research in our laboratory has compared the atypical tricyclic antidepressant, tianeptine, with the typical tricyclics, desipramine and imipramine, with respect to the effects of isolation and repeated restraint stress. Tianeptine and desipramine similarly attenuated isolation stress-induced increases in locus coeruleus and midbrain tyrosine hydroxylase mRNA levels and isolation-stress induced decreases in preproenkephalin mRNA levels in striatum and nucleus accumbens. However, tianeptine and imipramine differed in their effects in the cerebral cortex and hippocampus on 5HT2, and 5HT1A receptor levels but, surprisingly, produced similar effects on levels of the serotonin transporter labelled with [3H] paroxetine. Tianeptine also prevented stress-induced reductions in the length and number of branchpoints of dendrites of CA3 pyramidal neurons in hippocampus; comparison with effects of typical tricyclics are ongoing. Tianeptine also blocked effects of corticosterone treatment to reduce branching and length of CA3 dendrites. These actions of tianeptine may be due to interactions between 5HT and excitatory amino acids in the mossy fiber terminals on CA3 pyramidal neurons. Taken together, these results indicate that tianeptine has unique properties compared to some other antidepressant drugs, but shares in common with those drugs the ability to attenuate stress effects on tyrosine hydroxylase gene expression and on the serotonin transporter. It remains to be seen whether these actions are the basis of a common antidepressant action.
Recent studies have shown that it is important to understand the brain mechanism specifically by focusing on the common and unique functional connectivity in each disorder including depression.
To specify the biomarker of major depressive disorder (MDD), we applied the sparse machine learning algorithm to classify several types of affective disorders using the resting state fMRI data collected in multiple sites, and this study shows the results of depression as a part of those results.
The aim of this study is to understand some specific pattern of functional connectivity in MDD, which would support diagnosis of depression and development of focused and personalized treatments in the future.
The neuroimaging data from patients with major depressive disorder (MDD, n = 100) and healthy control adults (HC: n = 100) from multiple sites were used for the training dataset. A completely separate dataset (n = 16) was kept aside for testing. After all preprocessing of fMRI data, based on one hundred and forty anatomical region of interests (ROIs), 9730 functional connectivities during resting states were prepared as the input of the sparse machine-learning algorithm.
As results, 20 functional connectivities were selected with the classification performance of Accuracy: 83.0% (Sensitivity: 81.0%, Specificity: 85.0%). The test data, which was completely separate from the training data, showed the performance accuracy of 83.3%.
The selected functional connectivities based on the sparse machine learning algorithm included the brain regions which have been associated with depression.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
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.
To characterise the dissemination patterns of uropathogenic Escherichia coli (UPEC) in a community, we conducted a study utilising molecular and fundamental descriptive epidemiology. The subjects, consisted of women having community-acquired acute urinary tract infection (UTI), were enrolled in the study from 2011 to 2012. UPEC isolates were subjected to antibacterial-susceptibility testing, O serogrouping, phylotyping, multilocus-sequence typing with phylogenetic-tree analysis and pulsed-field-gel electrophoresis (PFGE). From the 209 unique positive urinary samples 166 UPEC were isolated, of which 129 were fully susceptible to the tested antibiotics. Of the 53 sequence types (STs), the four most prevalent STs (ST95, ST131, ST73 and ST357) accounted for 60% of all UPEC strains. Antimicrobial resistance was less frequently observed for ST95 and ST73 than for the others. A majority of rare STs and a few common STs constituted the diversity pattern within the population structure, which was composed of the two phylogenetically distinct clades. Eleven genetically closely related groups were determined by PFGE, which accounted for 42 of the 166 UPEC isolates, without overt geo-temporal clustering. Our results indicate that a few major lineages of UPEC, selected by unidentified factors, are disseminated in this community and contribute to a large fraction of acute UTIs.
Death ideation (thinking about/wishing for one's own death, thinking that one would be better off dead) is linked to an increased mortality risk. However, comparatively little is known about more general thoughts of death (GTOD) where no wish to die or life value is expressed. This study examined whether GTOD predicted mortality in a community-based cohort of older adults.
Data came from the Komo-Ise cohort study in Gunma prefecture, Japan. The analytic sample comprised 8208 individuals (average age 61.3 (range 47–77)) who were asked in wave 2 of the study in 2000 if they had ‘Thought about death more than usual, either your own, someone else's or death in general?’ in the past 2 weeks. Death data were obtained from the municipal resident registration file. Cox proportional hazards regression analysis was used to examine associations.
During the follow-up period (2000–2008), there were 672 deaths. In a model adjusted for baseline covariates, GTOD were significantly associated with all-cause mortality (hazards ratio 1.66, 95% confidence interval 1.20–2.29). Stratified analyses showed an association between GTOD and mortality in men, older subjects (⩾70 years), married individuals and those with higher social support.
GTOD are associated with an increased mortality risk among older citizens in Japan. Research is now needed to determine the factors underlying this association and assess the clinical relevance of screening for GTOD in older individuals.
Recently, many superflares on solar-type stars were discovered as white-light flares (WLFs). A correlation between the energies (E) and durations (t) of superflares is derived as t∝E0.39, and this can be theoretically explained by magnetic reconnection (t∝E1/3). In this study, we carried out a statistical research on 50 solar WLFs with SDO/HMI to examine the t-E relation. As a result, the t-E relation on solar WLFs (t∝E0.38) is quite similar stellar superflares, but the durations of stellar superflares are much shorter than those extrapolated from solar WLFs. We present the following two interpretations; (1) in solar flares, the cooling timescale of WL emission may be longer than the reconnection one, and the decay time can be determined by the cooling timescale; (2) the distribution can be understood by applying a scaling law t∝E1/3B−5/3 derived from the magnetic reconnection theory.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
The influence of baseline severity has been examined for antidepressant
medications but has not been studied properly for cognitive–behavioural
therapy (CBT) in comparison with pill placebo.
To synthesise evidence regarding the influence of initial severity on
efficacy of CBT from all randomised controlled trials (RCTs) in which
CBT, in face-to-face individual or group format, was compared with
pill-placebo control in adults with major depression.
A systematic review and an individual-participant data meta-analysis
using mixed models that included trial effects as random effects. We used
multiple imputation to handle missing data.
We identified five RCTs, and we were given access to individual-level
data (n = 509) for all five. The analyses revealed that
the difference in changes in Hamilton Rating Scale for Depression between
CBT and pill placebo was not influenced by baseline severity (interaction
P = 0.43). Removing the non-significant interaction
term from the model, the difference between CBT and pill placebo was a
standardised mean difference of –0.22 (95% CI –0.42 to –0.02,
P = 0.03, I2 = 0%).
Patients suffering from major depression can expect as much benefit from
CBT across the wide range of baseline severity. This finding can help
inform individualised treatment decisions by patients and their
This study determined the occurrence of legionellae in private houses for which there were no available data on aquatic environments other than the water supply system. From June 2013 to November 2014, we collected 138 water and 90 swab samples from aquatic environments in 19 houses. Legionella DNA was detected via a loop-mediated isothermal amplification assay in 66 (47·8%) water and 17 (18·9%) swab samples. High Legionella DNA detection rates were observed in water samples from washing machines and aquariums. Legionella spp. was isolated from 9 (6·5%) water and 3 (3·3%) swab samples. Legionella pneumophila SG 1 was detected from the outlet water of a bathtub spout and a bath sponge. Use of amoebic co-culture effectively increased legionellae and Legionella DNA detection rates from all sample types. A logistic regression analysis revealed that the heterotrophic plate count was significantly related to Legionella contamination. Our findings indicate that there is a risk of legionellosis from exposure to Legionella spp. in a variety of aquatic environments in residential houses. Control measures for legionellae in houses should include frequent cleaning and disinfecting to reduce heterotrophic bacteria in water and, where possible, preventing aerosolization from aquatic environments.
Public stigma alters attitudes towards people with mental illness, and is a particular concern for young people since most mental health problems occur in adolescence and young adulthood. However, little is known about the long-term effects of repeated filmed social contact (FSC) on reducing mental health-related stigma among young adults in the general population, compared with self-instructional Internet search (INS) and control interventions.
This study is a parallel-group randomised controlled trial over 12 months conducted in Tokyo, Japan. A total of 259 university students (male n = 150, mean age = 20.0 years, s.d. = 1.2) were recruited from 20 colleges and universities between November 2013 and July 2014, without being provided information about the mental health-related survey or trial. Participants were assigned to one of three groups before completion of the baseline survey (FSC/INS/control = 89/83/87). The FSC group received a computer-based 30-min social contact film with general mental health education and five follow-up web-based FSCs at 2-month intervals. The INS group undertook a 30-min search for mental health-related information with five follow-up web-based reminders for self-instructional searches at 2-month intervals. The control group played PC games and had no follow-up intervention. The main outcome measures were the future (intended behaviour) domain of the Reported and Intended Behaviour Scale at 12 months after the intervention. Analysis was conducted in September 2015.
At the 12-month follow-up, 218 participants completed the survey (84.1%, 75:70:73). The FSC group showed the greatest change at the 12-month follow-up (FSC: mean change 2.11 [95% CI 1.49, 2.73], INS: 1.04 [0.29, 1.80], control: 0.71 [0.09, 1.33]; FSC v. INS p = 0.037, FSC v. controls p = 0.004). No adverse events were reported during the follow-up period.
FSC was more successful in reducing stigma at 12 months after intervention than INS or control interventions. FSC could be used to reduce stigma in educational lectures and anti-stigma campaigns targeted at young people.
This study is registered at UMIN-CTR (No. UMIN000012239).
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.
Gyrokinetic simulations of electromagnetic turbulence in magnetically confined torus plasmas including tokamak and heliotron/stellarator are reviewed. Numerical simulation of turbulence in finite beta plasmas is an important task for predicting the performance of fusion reactors and a great challenge in computational science due to multiple spatio-temporal scales related to electromagnetic ion and electron dynamics. The simulation becomes further challenging in non-axisymmetric plasmas. In finite beta plasmas, magnetic perturbation appears and influences some key mechanisms of turbulent transport, which include linear instability and zonal flow production. Linear analysis shows that the ion-temperature gradient (ITG) instability, which is essentially an electrostatic instability, is unstable at low beta and its growth rate is reduced by magnetic field line bending at finite beta. On the other hand, the kinetic ballooning mode (KBM), which is an electromagnetic instability, is destabilized at high beta. In addition, trapped electron modes (TEMs), electron temperature gradient (ETG) modes, and micro-tearing modes (MTMs) can be destabilized. These instabilities are classified into two categories: ballooning parity and tearing parity modes. These parities are mixed by nonlinear interactions, so that, for instance, the ITG mode excites tearing parity modes. In the nonlinear evolution, the zonal flow shear acts to regulate the ITG driven turbulence at low beta. On the other hand, at finite beta, interplay between the turbulence and zonal flows becomes complicated because the production of zonal flow is influenced by the finite beta effects. When the zonal flows are too weak, turbulence continues to grow beyond a physically relevant level of saturation in finite-beta tokamaks. Nonlinear mode coupling to stable modes can play a role in the saturation of finite beta ITG mode and KBM. Since there is a quadratic conserved quantity, evaluating nonlinear transfer of the conserved quantity from unstable modes to stable modes is useful for understanding the saturation mechanism of turbulence.
A fully coherent free electron laser (FEL) seeded with a higher-order harmonic (HH) pulse from high-order harmonic generation (HHG) is successfully operated for a sufficiently prolonged time in pilot user experiments by using a timing drift feedback. For HHG-seeded FELs, the seeding laser pulses have to be synchronized with electron bunches. Despite seeded FELs being non-chaotic light sources in principle, external laser-seeded FELs are often unstable in practice because of a timing jitter and a drift between the seeding laser pulses and the accelerated electron bunches. Accordingly, we constructed a relative arrival-timing monitor based on non-invasive electro-optic sampling (EOS). The EOS monitor made uninterrupted shot-to-shot monitoring possible even during the seeded FEL operation. The EOS system was then used for arrival-timing feedback with an adjustability of 100 fs for continual operation of the HHG-seeded FEL. Using the EOS-based beam drift controlling system, the HHG-seeded FEL was operated over half a day with an effective hit rate of 20%–30%. The output pulse energy was
at the 61.2 nm wavelength. Towards seeded FELs in the water window region, we investigated our upgrade plan to seed high-power FELs with HH photon energy of 30–100 eV and lase at shorter wavelengths of up to 2 nm through high-gain harmonic generation (HGHG) at the energy-upgraded SPring-8 Compact SASE Source (SCSS) accelerator. We studied a benefit as well as the feasibility of the next HHG-seeded FEL machine with single-stage HGHG with tunability of a lasing wavelength.
Stress Corrosion Cracking (SCC) has been detected in Boiling Water Reactors (BWRs) on core shrouds and primary water re-circulation piping made of low carbon stainless steels. Material hardening strongly affects SCC propagation behavior, and SCC growth rates increase with increasing hardness of austenitic stainless steels caused by cold work or neutron irradiation.
Research work has been conducted in the authors’ laboratories with the aim of improving SCC resistance using chemical composition control of stainless steels. It has been previously reported that high stacking fault energy (SFE) materials showed better SCC resistance than low SFE materials due to hardening being suppressed in high SFE materials. In the present study, SCC growth rate (CGR) tests were performed using 15% cold worked Types 316L and 25Cr-20Ni stainless steels in a simulated BWR water environment. The 25Cr-20Ni stainless steel used has high SFE value due to chemical composition control and measured SCC growth rates were lower than those of low SFE stainless steels.
However, oxidation behavior is one of the more important factors influencing SCC of austenitic stainless steels in addition to material hardening behavior, and the influence of the chemical composition control necessary to increase SFE on oxidation behavior in BWR primary coolants is still unclear. In this study, therefore, immersion tests using Types 316L and 25Cr-20Ni stainless steel specimens were also conducted in the simulated BWR water environment. The surface oxide films on the specimens were then analyzed with micro-Raman spectroscopy and glow discharge optical emission spectroscopy in order to help clarify the oxidation behavior.
The results of these tests and analyses showed that the NiFe2O4 content of the outer oxide layers on the high SFE stainless steels was higher than that on the low SFE stainless steels. The inner oxide film on the 25Cr-20Ni stainless steel also had a high chromium content.
Based on the above results, SCC resistance and oxidation behavior of high SFE austenitic stainless steels in a simulated BWR water environment will be discussed.
We analyze photoluminescence (PL) and electroluminescence (EL) using a hyperspectral imager that records spectrally resolved luminescence images of solar cell absorbers. The system is calibrated to yield the luminescence flux in absolute values. This system enables to quantitatively image physical parameters such as the photovoltage with an uncertainty of less than 30mV. The wide field illumination, low power excitation and fast acquisition brings new insights compared to classical setups such as confocal microscope. Several types of absorbers have been analyzed. For instance, we can investigate spatial fluctuations of the Quasi Fermi Levels splitting in CIGS polycristalline absorbers and link those fluctuations to transport properties. The method is general to the point that third generation PV cells absorbers can also be evaluated. We illustrate the great potential of our setup by imaging carrier temperature in Hot Carriers Solar cells absorbers and quasi Fermi levels splitting in Intermediate Band Solar cells.