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We examined the efficacy and safety of low vs. moderate olanzapine doses for the treatment of borderline personality disorder (BPD) in the largest controlled clinical trial ever conducted in this population.
This 12-week, double-blind trial involved patients 18-65 years with a diagnosis of DSM-IV BPD randomized to receive 2.5mg/day olanzapine (N=150), 5-10mg/day olanzapine (N=148), or placebo (N=153). The primary efficacy measure was the change from baseline-to-endpoint (last-observation-carried-forward) on the Zanarini Rating Scale for BPD (ZAN-BPD) total score. Rate of response and time-to-response were also examined (response defined as a >=50% reduction in ZAN-BPD total score).
Mean baseline ZAN-BPD total scores ranged from 17.01 to 17.42, indicating moderate symptom severity. Treatment with OLZ5-10 was associated with significantly greater mean change from baseline-to-endpoint in ZAN-BPD total score than placebo (-8.50 vs. -6.79, p=.010). Response rates were significantly higher for OLZ5-10 (73.6%) than for OLZ2.5 (60.1%, p=.018) and placebo (57.8%, p=.006). Time-to-response was significantly shorter for OLZ5-10 than placebo (p=.028). Treatment-emergent adverse events seen more frequently in the olanzapine groups included somnolence, increased appetite, and weight gain. Mean weight change from baseline-to-endpoint was 2.09kg for OLZ 2.5, 3.17kg for OLZ5-10, and 0.02kg for placebo.
The results of this study suggest that moderate doses of olanzapine (5-10mg/day) are effective in the treatment of overall borderline psychopathology. Also, the types of adverse events observed with olanzapine treatment were similar to those seen previously in adult populations.
Altered levels of phenylalanine and its metabolites in blood and cerebrospinal fluid have previously been reported in schizophrenia. This study attempted to examine whether phenylalanine kinetics is altered in schizophrenia using the 13C-phenylalanine breath test (13C-PBT).
Subjects were 20 patients with schizophrenia and the same number of controls. 13C-phenylalanine was administered and then 13CO2 concentration in breath was monitored for 120 minutes. The Δ 13CO2 at each collecting time, the maximal Δ 13CO2 (Cmax), the time to reach Cmax (Tmax), the area under the curve of time course of Δ13CO2 (AUC), the cumulative recovery rate (CRR) at each collecting time of the 13C-PBT were calculated for each subject.
Body weight (BW) and diagnostic status were significant predictors for Cmax. BW, age and diagnostic status were significant predictors for AUC and CRR at 120 minutes (CRR0-120). A repeated measures ANCOVA controlling for age and BW revealed a different pattern of change in CRR over time between the patients and controls and that Δ13CO2 in schizophrenia were lower than that in healthy control at all sampling point during 120 min, with an overall significant differences between healthy control and schizophrenia. The ANCOVA controlling for age and BW, showed that Cmax, AUC and CRR0-120 were significantly lower in schizophrenics than in controls.
Our data indicate the different change of Δ13CO2 and CRR over time and the decreased Cmax, AUC and CRR0-120 of 13C-PBT in schizophrenia patients compared to healthy controls, suggesting the altered phenylalanine kinetics in schizophrenia.
Attention deficit/hyperactivity disorder (ADHD) often presents as an impairing lifelong condition in adults, yet it is currently under-diagnosed and under-treated in many European countries.
To establish the characteristics of the European (EU) adult ADHD patient relative to adult patients outside the EU (OEU).
To compare the baseline characteristics of patients with ADHD in regions where adult ADHD is relatively well established (e.g., USA), with EU adult ADHD patients.
Baseline data was used from the open-label acute treatment period of a multicenter, randomized, withdrawal trial of atomoxetine in adult patients with ADHD (N = 2017; EU, n = 1217; OEU, n = 800). All enrolled patients were included in the baseline analyses.
The demographics for patients in the EU region and regions OEU were comparable. Patients in the EU region had a somewhat lower percentage of prior exposure to psychostimulants compared to the region OEU (32.7% versus 38.9%, p = .005). Conners’ Adult ADHD Rating Scale-Investigator Rated: Screening Version with adult ADHD prompts (18 item total, inattentive and hyperactive/impulsive subscales, and index) were comparable. The adult ADHD Quality of Life life outlook and life productivity domain scores were different between groups (p ≤ .0004). The EuroQol-5 Dimension UK and US population-based Index score, and health state score were comparable between groups.
There were some subtle differences between study groups; however, overall, the adult ADHD patients were not substantially different between the EU region and regions OEU, suggesting that baseline features of ADHD in adult EU patients manifest comparable to those in patients OEU.
Public health checkups are conducted on 3-year-old children in Japan. However, it is often difficult to detect or provide ongoing support to children with developmental disorders without MR. Therefore we have conducted health checkups on 5 year olds.
The objectives are to describe the results and follow-up of health checkups in 5-year-old children and examine the utility of such checkups.
The aims are to make clear the utility of health checkups in 5-year-old children for screening for developmental disorders.
The subjects were 303 children of 5-year-old that lived in Kanie-cho and participated in health checkups. in the checkups, a child psychiatrist examined the children, and made a provisional diagnosis of a developmental disorder.
Eighty-two children were provisionally diagnosed as having developmental disorders. the follow-up allowed final diagnosis of developmental disorders (suspect diagnosis included) to be made in 39 children (12.9%), and pinpointed 19 children with ADHD, 9 children with PDD, 9 children with mild MR, and 2 children with motor skills disorder.
All children with PDD had already been informed about the possible occurrence of developmental disorders at 3 years of age. However, most of ADHD, mild MR, and motor function disorder were diagnosed in these children during the checkups at the age of 5 years.
The health checkup in 5-year-old children is useful not only as a tool to detect developmental disorders that are difficult to diagnose at the age of 3 years but also as an approach in patients lost to follow-up.
Children with Learning Disorders (LD) are susceptible to decreased self-esteem and willingness because of their difficulty learning, which can lead to exacerbation of the learning difficulty in a vicious cycle. Appropriate learning supports may help not only in terms of learning, but also psychologically.
The purpose of this study was to investigate the psychological effect of learning supports for children with LD.
The aims are to make clear that psychological changes occur for children by the learning supports.
We conducted 10 learning support sessions for 12 children (age 8–11 years) diagnosed as LD. Afterward, we gave a questionnaire on motivation and self-efficacy in learning to the children and their parents, and a questionnaire on positive participation in class to the children's teachers.
The children's responses showed increased intrinsic motivation with high autonomy, and decreased extrinsic motivation with low autonomy and self-efficacy after supports. the parents’ responses indicated increased self-efficacy and decreased motivation overall after supports, while the teachers’ responses indicated increased positive class participation after supports.
Parents and teachers see that willingness for learning improve through learning supports, but the children themselves feel decreased efficacy. At the same time, the children came to have more autonomous intrinsic motivation for learning. Both of motivation and willigness increased through learning supports, but conversely the children came to notice their own weaknesses (true abilities), which is thought to have led to decreased self-efficacy. with continuing support improvement of true efficacy may be expected.
We explored the factors promoting long-term mental health among adolescent survivors of the 2008 Wenchuan earthquake in China. We examined the associations of their long-term mental health with disaster-related storytelling and school-based psychoeducation, and of school-based psychoeducation with disaster-related storytelling.
A secondary school-based cross-sectional survey was conducted 6 years after the disaster. Participants with traumatic experiences such as injury, loss, witnessing someone's death/injury and home destruction (N = 1028, mean age 15, standard deviation 1.38, male 51%) were eligible. Mental health/disaster education (MHE/DE) was defined as taking one or more lessons in MHE and/or DE at school since the earthquake. Experiences of storytelling about the disaster involved expressing distressing memories and feelings regarding the earthquake since the disaster happened, according to four groups: never expressed distressing memories and feelings, expressed them through writing/drawing, expressed them through talking to lay supporters and expressed them through talking to health professionals. Analysis of covariance was used to compare mean scores on five selected subscales of the Symptom Checklist-90 (SCL-90), the Athens Insomnia Scale (AIS) and the Psychotic-Like Experiences (PLEs) scale among the four storytelling groups. Linear regression analysis was used to identify the relationships between MHE/DE and current mental health as measured by the SCL-90, AIS and PLEs. The relationship between education and storytelling was probed by χ2 test.
The talked-to-lay-supporters group showed better mental health on the SCL-90 (p ⩽ 0.001), AIS (p < 0.001) and PLEs (p = 0.004), while the consulted-health-professionals group showed worse mental health on the three dimensions of the SCL-90: depression (p = 0.05), anxiety (p = 0.02) and fear (p = 0.04), and on PLEs (p = 0.02) compared with the never-expressed group. MHE and DE were inversely associated with SCL-90, AIS and PLE scores. Participants who received these forms of education talked about their disaster experiences to lay supporters more than those who did not.
MHE and DE at school may promote adolescents’ mental health after a disaster. Experience of storytelling about the disaster to lay supporters may be helpful for long-term psychological recovery, and may be a potential mediating factor for school-based education and better mental health. Because of the cross-sectional nature of this study, causality cannot be inferred; therefore, further prospective intervention studies are needed to elucidate the effect of these factors on adolescent survivors’ mental health.
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.
The formation of nanosized porous oxide layers on titanium (Ti) by asymmetric alternating current anodizing in sulfuric acid has been studied using electrochemical techniques. In order to prevent spark discharge at Ti electrode upon its anodization in 1.0 M H2SO4 solution, the magnitude of the cathodic current is reduced using a special electrical circuit consisting of a variable resistor and two diodes. The unique surface treatment approach gives rise to the formation of nanosized porous layer in a very short period of time and without spark discharge. The surface of porous layers thus obtained has in vitro apatite-forming ability.
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
We aimed to verify the effectiveness of real-time reverse transcription (rRT) polymerase chain reaction (PCR) for detecting cases of modified measles (M-Me) and for predicting super-spreader candidates through the experience of a measles outbreak dominated by M-Me in Yamagata, Japan, during March–April 2017. We applied rRT-PCR to specimens from 35 cases of M-Me, nine cases of typical measles (T-Me) and nine cases of prodromal stage of T-Me (P-Me). From rRT-PCR among the M-Me cases, peripheral blood mononuclear cells (PBMC) showed the highest positive rate (80.0%), followed by throat swab (48.6%), urine (33.3%) and serum (3.1%). The negative result of PBMC in M-Me cases was recovered by the result of a throat swab. In specimens of PBMC, throat swab and urine, M-Me group showed the significantly higher cycle of threshold (i.e., lower viral load) in the rRT-PCR than T-Me and P-Me groups, respectively. Furthermore, three super-spreaders in T-Me or P-Me showed an extremely low cycle of threshold in their throat swab specimens. rRT-PCR using PBMC and throat swab might be helpful for clinical management and measles control by certain detection of M-Me cases and by predicting super-spreading events resulting from measles cases with the high viral load.
To assess the diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess.
Mean platelet volume and other laboratory data were retrospectively investigated.
Mean platelet volume was significantly lower in the tonsillitis group (7.8 per cent ± 0.7 per cent) than in the control group (8.7 per cent ± 0.6 per cent; p < 0.0001), and it was significantly lower in the abscess group (7.5 per cent ± 0.6 per cent) than in the no abscess group (8.0 per cent ± 0.7 per cent; p = 0.0277). White blood cell counts and C-reactive protein levels were not significantly different between patients with an abscess and those without. The mean platelet volume cut-off values for the diagnosis of tonsillitis and peritonsillar abscess were 7.95 fl and 7.75 fl, respectively.
Our results suggest that a decreased mean platelet volume is associated with the development and severity of tonsillitis. This finding provides useful diagnostic information for physicians treating patients with tonsillitis.
An easily understandable index that measures the quality of carbohydrate may aid people in adopting dietary habits that improve their glucose tolerance. We aimed to evaluate the relationship between a ratio of dietary fibre to carbohydrate intakes (fibre:carbohydrate ratio (F:C-R)) and glucose tolerance cross-sectionally and longitudinally. Subjects were 190 Japanese men and women without type 2 diabetes (mean age 55·4 years) who participated in a 5-month diet and exercise programme. We compared baseline anthropometric, dietary and metabolic profiles between those with higher F:C-R and those with lower ratios. Multivariable regression analyses were performed to examine the associations between the F:C-R and homoeostasis model of assessment for insulin resistance (HOMA-IR) and HbA1c at baseline and between changes in the F:C-R and changes in HOMA-IR and HbA1c over the 5-month period. At baseline, the higher F:C-R group had significantly lower body weight, lean body mass, fasting insulin level and HOMA-IR as compared with the lower F:C-R group. The two groups had similar intakes of carbohydrate and fat, whereas protein intake was greater in the high F:C-R group. Baseline F:C-R was not significantly associated with HOMA-IR or HbA1c at the beginning of the study in multivariable models. Increases in the ratio during the 5-month programme was associated with reductions in HbA1c (P<0·001). These findings highlight the potential utility of the F:C-R in strategies aimed at type 2 diabetes prevention.
We initiated a long-term and highly frequent monitoring project toward 442 methanol masers at 6.7 GHz (Dec >−30 deg) using the Hitachi 32-m radio telescope in December 2012. The observations have been carried out daily, monitoring a spectrum of each source with intervals of 9–10 days. In September 2015, the number of the target sources and intervals were redesigned into 143 and 4–5 days, respectively. This monitoring provides us complete information on how many sources show periodic flux variations in high-mass star-forming regions, which have been detected in 20 sources with periods of 29.5–668 days so far (e.g., Goedhart et al. 2004). We have already obtained new detections of periodic flux variations in 31 methanol sources with periods of 22–409 days. These periodic flux variations must be a unique tool to investigate high-mass protostars themselves and their circumstellar structure on a very tiny spatial scale of 0.1–1 au.
The overview of the recent results for discovery and investigations of a very exotic phenomenon – optical mirage in the X-ray spectral range – is presented. It was found that the mirage could be created in the form of coherent virtual point source, emerging in the vicinity of the second plasma in two-stage oscillator-amplifier X-ray laser. The X-ray source-mirage, rigidly phased with the initial radiation of generator, occurs only when amplification takes place in the amplifier plasma and leads to the appearance of the interference pattern in the form of concentric rings in the spatial profile of the output X-ray laser beam. The equation describing the emergence of X-ray mirage was found, numerical solution of which shows that its formation is similar to that of the optical mirages observed at propagation of light rays through an inhomogeneously heated air. Obtained results have already demonstrated novel comprehension into the physical nature of amplification of X-ray radiation, opening additional opportunities for X-ray interferometry, holography, and other applications, which require multiple rigidly phased sources of coherent radiation.
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.
We previously reported an association between human parechovirus type 3 (HPeV3) and epidemic myalgia with myositis in adults during summers in which an HPeV3 outbreak occurred in children. However, this disease association has not yet been reported elsewhere. We have since continued our surveillance to accumulate data on this disease association and to confirm whether myalgia occurs in children as well as adults. Between June and August 2014, we collected 380 specimens from children with infectious diseases. We also collected clinical specimens from two adult and three paediatric patients suspected of myalgia. We then performed virus isolation and reverse-transcription–PCR using the collected specimens. We detected HPeV3 in 26 children with infectious diseases, which we regarded as indicating an outbreak. We also confirmed HPeV3 infection in all patients suspected of myalgia. In particular the symptoms in two boys, complaining of myalgia and fever, closely matched the criteria for adult myalgia. Based on our findings from 2008, 2011 and 2014, we again urge that clinical consideration be given to the relationship between myalgia and HPeV3 infections during HPeV3 outbreaks in children. Furthermore, our observations from 2014 suggest that epidemic myalgia and myositis occur not only in adults but also in children.
The transport of relativistic electron beam in compressed cylindrical targets was studied from a numerical and experimental point of view. In the experiment, cylindrical targets were imploded using the Gekko XII laser facility of the Institute of Laser Engineering. Then the fast electron beam was created by shooting the LFEX laser beam. The penetration of fast electrons was studied by observing Kα emission from tracer layers in the target.
Heptavalent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2010. We investigated the impact of PCV7 on childhood community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP). Children aged <5 years living in Chiba city, Japan, who were admitted to hospitals were enrolled to estimate the incidence of CAP based on the mid-year population. PP was determined by the presence of Streptococcus pneumoniae in cultured blood and/or sputum samples of CAP patients. The incidence of CAP and S. pneumoniae isolated from PP patients was compared before (April 2008–March 2009) and after (April 2012–March 2013) the introduction of PCV7 immunization. The annual incidence of CAP was reduced [incidence rate ratio 0·81, 95% confidence interval (CI) 0·73–0·90]. When comparing post-vaccine with pre-vaccine periods, the odds ratio for PP incidence was 0·60 (95% CI 0·39–0·93, P = 0·024). PCV7-covered serotypes markedly decreased (66·6% in pre-vaccine vs. 15·6% in post-vaccine, P < 0·01), and serotypes 6C, 15A, 15C and 19A increased. Multidrug-resistant international clones in the pre-vaccine period (Spain6B-2/ST90, Taiwan19F-14/ST236) decreased, while Sweden15A-25/ST63 was the dominant clone in the post-vaccine period. A significant reduction in the incidence of both CAP hospitalizations and culture-confirmed PP of vaccine serotypes was observed at 2 years after PCV7 vaccination.
In this study, we conducted the in-situ observations of the magnetic domain structure change in Nd2Fe14B magnets at elevated temperature by transmission electron microscopy (TEM) / Lorentz microscopy. The in-situ observations in Nd2Fe14B magnets revealed that the magnetization reversal easily occurred at the elevated temperature. At more than 180°C, the magnetic domain wall motion could be observed by applying the magnetic field of less than 20 mT. The motion of the magnetic domain wall was discontinuous and the domain wall jumped to one grain boundary to the neighboring grain boundary at 180°C. On the other hand, the continuous domain wall motion within grain interior as well as discontinuous domain wall motion was observed at 225°C, and some grain boundaries showed still strong pinning effect even at 225°C. The temperature dependence of the pinning effect of grain boundaries would not uniform.