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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Obestatin is a gastrointestinal peptide having wide-ranging effects on cell proliferation; however, its mechanism of action remains poorly understood. Thus, the aim of the study was to elucidate the effect of exogenous obestatin on the postnatal structural development of the small intestine. Seven-day-old piglets with an average BW of 1.56 ± 0.23 kg were divided into four groups (n = 10) that received intragastrically obestatin (2, 10 or 15 μg/kg BW) or vehicle. After a 6-day experimental period, morphological analysis of gastrointestinal tract and small intestine wall (mitosis and apoptosis indexes, histomorphometry of mucosa and muscularis layers) was performed. The study revealed a seemingly incoherent pattern of the histological structure of the small intestine among the experimental groups, suggesting that the effect of obestatin is both intestinal segment specific and dose dependent. Histomorphometric analysis of the small intestine showed that higher doses of obestatin seem to promote the structural development of the duodenum while simultaneously hindering the maturation of more distal parts of the intestine. Intragastric administration of obestatin increased the crypt mitotic index in all segments of the small intestine with the strongest pro-mitotic activity following the administration of obestatin at a dose of 10 and 15 μg/kg BW. The significant differences in the number of apoptotic cells in the intestinal villi among the groups were observed only in proximal jejunum and ileum. In conclusion, it seems that obestatin shows a broad-spectrum of activity in the gastrointestinal tract of newborn piglets, being able to accelerate its structural development. However, the varied effect depending on the intestinal segment or the concentration of exogenous obestatin causes that further research is needed to clarify the exact mechanism of this phenomenon.
We present a case of SLE psychosis with a characteristic symptom mainly concernd to time dysorientation.
A lady of 17 years old without any previous history is hospitalised to Jichi Medical University Hospital, because of covulsion. After this problem is disappeared, she became inactive, however, sometimes irritated without any specific reason. Brain imaging (MRI, CT) was normal, but EEG revealed slow waves as basal rhythme. Her physical state and labodatas fulfilled the criteria of SLE. She was treated with Steroid-pulse therapy (Methylpredonisolone 1.000 mg/day for 3 days), predonisolone 90mg/day (for two weeks) and finally betamethasone 8mg/day (for three weeks) which made her consciousness clear, and her behavior coherent.
During the periode of the steroid pulse therapy and the start of betamethasone, this patient repeated to say "the date is wrong". She believed that one year had already passed since her admission. She appeared to be perplexed continuously between the two different time standards (wrong standard of her own and the right one of common world). We could not correct her misunderstanding until her consciousness became clear.
This symptom of misunderstanding and perplexion derives from continuous dysorientation. We may call this "time gap experience". We could observe this type of dysorientation in a very slight consciousness clouding which continues stably during certain period. Therefore, “time gap experience” can be a key to find a psychosis based on somatic disease like SLE.
Catatonia is a complication of bipolar disorder, which is a constellation of symptoms such as catalepsy, mutism, and stupor. Standard therapy for catatonia contains benzodiazepines and electroconvulsive therapy. An uncomplicated catatonia is usually a benign condition. On the other hand, malignant catatonia is a life-threatening condition that is complicated with fever, autonomic instability, delirium, and rigidity. The syndrome is typically fulminant and progresses rapidly within a few days without appropriate intervention. Several previous reports suggested that some catatonia are associated with the overstimulation of N-methyl-D-aspartate (NMDA) receptor, and that amantadine may have an effectiveness for catatonia, as a NMDA receptor antagonist. We report a case of successful treatment for malignant catatonia refractory to benzodiazepines, by using amantadine.
Materials and methods/case
A 64-year-old Japanese woman with bipolar disorder was referred to our hospital because of 8-week prolonged fever. On admission, she was in febrile and stuporous states. Severe rigidity was observed in her extremities. Blood tests, lumbar puncture, and blood cultures were all negative. Brain MRI was normal. Consequently, we reached a diagnosis of malignant catatonia, and thus we gave additional benzodiazepines for her catatonic symptoms. However, there was no improvement, and we finally add a 50 mg/day amantadine for her malignant catatonic state.
Her fever resolved in a few days. Gradual dose-titration of amantadine led her clinical manifestation to completely disappeared.
Amantadine can be a potential option as one of the pharmacological therapies for refractory malignant catatonia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The syndrome of emotional burnout is developed in people whose profession requires a lot of communication, and the effectiveness of their work depends on its quality. The aim of our study was to determine the influence of burnout on relational maintenance strategies.8 professors of università della Svizzera italiana, Lugano, Switzerland participated in this research. We used Maslach Burnout Inventory and The relational maintenance strategies scale. Moderate level of emotional exhaustion was detected in the majority of the participants. This condition is characterized by the urge towards finding a place to stay alone and get some rest from everything and everybody. It is accompanied by the feeling of emptiness, depression, and apathy. These indicate pronounced tiredness, disappointment, and unwillingness to work among our participants. The high level of Lack of personal accomplishments phase is being developed in all the participants. It indicates the pronounced doubts in the necessity to keep performing the work and in the fact that the work is needed and recognized by other people. We demonstrated that among the professors with burnout such strategies as conflict management, openness, assurances and positivism are the most widespread. Our data indicate that the readiness to work together on certain project or scientific problem (Openness), the willingness to support a student (Advice Giving) and the help to find necessary support outside of current academic environment (Social Networks) decreases with the development of emotional burnout. Understating the level of one's self-appraisal, observed during the development of burnout, ruins effective collaboration between professors and their PhD students, and formalizes their relationships. Thus, burnout is an important mediating variable between interpersonal aspects of work environment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
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.
Diabetes mellitus is a global epidemic, characterised as a heterogeneous group of metabolic disorders associated with high risk of CVD. Green banana biomass, which is composed of resistant starches (RS) and cannot be hydrolysed by amylases, delays gastric emptying and modulates insulin sensitivity, thus contributing to improve metabolic disorders. The aim of the present study was to investigate the effects of consumption of RS from green banana biomass on body composition, fasting plasma glucose, glycated Hb (HbA1c) and homeostasis model assessment of insulin resistance in subjects with pre-diabetes or type 2 diabetes on top of treatment. Middle-aged subjects (n 113) of both sexes with pre-diabetes (HbA1c: 5·7–6·4 %) or diabetes (HbA1c ≥ 6·5 %) were randomised to receive nutritional support plus green banana biomass (40 g) (RS: approximately 4·5 g, G1, n 62) or diet alone (G2, n 51) for 24 weeks. Body composition, biochemical analyses and dietary intake were evaluated at the beginning and end of the study. In the experimental group (G1), consumption of RS was associated with reduction in HbA1c (P = 0·0001), fasting glucose (P = 0·021), diastolic blood pressure (P = 0·010), body weight (P = 0·002), BMI (P = 0·006), waist and hip circumferences (P < 0·01), fat mass percentage (P = 0·001) and increase in lean mass percentage (P = 0·011). In controls (G2), reductions were observed in waist and hip circumferences (P < 0·01), HbA1c (P = 0·002) and high-density lipoprotein-cholesterol (P = 0·020). In pre-diabetes or diabetes, non-significant differences were observed in the percentage reduction in HbA1c and fasting glucose in exploratory analyses. Our results indicate that the consumption of bioactive starches is a good dietary strategy to improve metabolic control and body composition.
The naturalization of alien Reeves's muntjacs (Muntiacus reevesi) on Izu-Oshima Island, Tokyo, Japan, has proceeded intensively over the last five decades. To clarify whether the gastrointestinal helminths of these animals were brought from their original endemic area or were newly acquired in Japan, 32 Reeves's muntjacs trapped on the island were parasitologically examined. In addition to Gongylonema pulchrum in the oesophagus (34.4% prevalence), Chabaudstrongylus ninhae (Dróżdż, 1967) (Trichostrongylidae: Cooperiinae) and Oesophagostomum muntiacum Jian, 1989 (Chabertiidae: Oesophagostominae) were prevalent in the small (28.1%) and large (46.9%) intestines, respectively. For the first time, these trichostrongylid or chabertiid worms were genetically characterized based on partial nucleotide sequences of the nuclear ribosomal RNA gene (rDNA) and mitochondrial DNA cytochrome c oxidase subunit 1 gene (cox-1), and the phylogenetic relationships with other members of their family were explored. Since these two intestinal nematode species are inherent in muntjacs, this study demonstrates a new distribution of exotic helminth species in Japan in accordance with the naturalization of alien mammalian hosts. The molecular genetic data collected here could assist the taxonomic assessment of morphological variants in different Muntiacus spp. and/or of different geographical origins. Furthermore, our data may help to define the phylogenetic relationships among such isolates.
The number of tests performed is an important surveillance indicator. We illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa, two prefectures with high HIV notification rates in Japan. Restricting to data reported from local public health centres and affiliate centres where testing data are accessible, we assessed HIV surveillance data during 2007–2014, based on the annual HIV notification rate (per 100 000 population), HIV testing rate (per 100 000 population) and proportion testing HIV-positive (positivity). Nationally, testing activity and positivity showed an inverse relationship; in 2008, the testing rate peaked, but positivity was lowest. While notification rates were higher for Tokyo (median = 0.98, range = 0.89–1.33) than Okinawa (median = 0.61, range = 0.42–1.09), Okinawa had slightly higher testing rates (median = 187, range = 158–274) relative to Tokyo (median = 172, range = 163–210). Positivity was substantially lower in Okinawa (median = 0.34%, range = 0.24–0.45%) compared with Tokyo (median = 0.57%, range = 0.46–0.67%). Relative to the national testing rate (median = 85, range = 80–115) and positivity (median = 0.34%, range = 0.28–0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa, all three indicators increased, providing a strong reason to be concerned as positivity increased despite more testing. Together with other information, accounting for testing and positivity improve interpretation of surveillance data to guide public health assessments.
Root rots are one of the main biotic constraints to common bean (Phaseolus vulgaris L.) production, causing losses estimated at 221 000 metric tons a year in sub-Saharan Africa. Until recently, root rots in Ugandan common bean agroecologies were mostly caused by Pythium and Fusarium spp., especially in high altitude areas. But now, severe root rots are observed in low and medium altitude agroecologies characterized by dry and warm conditions. The objective of our study was therefore to ascertain the current prevalence and incidence of common bean root rot diseases in Ugandan common bean agroecologies. Our results show that root rots were present in all seven agroecologies surveyed. Overall, the most rampant root rot was southern blight caused by Sclerotium rolfsii Sacc., followed by root rots caused by Fusarium spp., Pythium spp. and Rhizoctonia solani, respectively. Our study clearly showed the influence of environmental conditions on the prevalence and incidence of common bean root rots. While Fusarium and Pythium root rots are favoured under low air temperature and high air humidity in highland areas, high incidence of southern blight is favoured by warm and moist conditions of lowland areas. The prevalence and incidence of common bean root rots was mapped, providing a reliable baseline for future studies. Similarly, hotspots identified for common bean root rots will be a very useful resource for evaluation of germplasm and breeding lines for resistance to root rots.
The Global Muon Detector Network (GMDN) is composed by four ground cosmic ray detectors distributed around the Earth: Nagoya (Japan), Hobart (Australia), Sao Martinho da Serra (Brazil) and Kuwait city (Kuwait). The network has operated since March 2006. It has been upgraded a few times, increasing its detection area. Each detector is sensitive to muons produced by the interactions of ~50 GeV Galactic Cosmic Rays (GCR) with the Earth′s atmosphere. At these energies, GCR are known to be affected by interplanetary disturbances in the vicinity of the earth. Of special interest are the interplanetary counterparts of coronal mass ejections (ICMEs) and their driven shocks because they are known to be the main origins of geomagnetic storms. It has been observed that these ICMEs produce changes in the cosmic ray gradient, which can be measured by GMDN observations. In terms of applications for space weather, some attempts have been made to use GMDN for forecasting ICME arrival at the earth with lead times of the order of few hours. Scientific space weather studies benefit the most from the GMDN network. As an example, studies have been able to determine ICME orientation at the earth using cosmic ray gradient. Such determinations are of crucial importance for southward interplanetary magnetic field estimates, as well as ICME rotation.
We report on the formation of shallow junctions with high activation in both n+/p and p+/n Ge junctions using ion implantation and Flash Lamp Annealing (FLA). The shallowest junction depths (Xj) formed for the n+/p and p+/n junctions were 7.6 nm and 6.1 nm with sheet resistances (Rs) of 860 ohms/sq. and 704 ohms/sq., respectively. By reducing knocked-on oxygen during ion implantation in the n+/p junctions, Rs was decreased by between 5% and 15%. The lowest Rs observed was 235 ohms/sq. with a junction depth of 21.5 nm. Hall measurements clearly revealed that knocked-on oxygen degraded phosphorus activation (carrier concentration). In the p+/n Ge junctions, we show that ion implantation damage induced high boron activation. Using this technique, Rs can be reduced from 475 ohms/sq. to 349 ohms/sq. These results indicate that the potential for forming ultra-shallow n+/p and p+/n junctions in the nanometer range in Ge devices using FLA is very high, leading to realistic monolithically-integrated Ge CMOS devices that can take us beyond Si technology.
In this paper, the robustness of the dynamic instability mitigation mechanism is first examined, and then the instability mitigation phenomenon is demonstrated in a deuterium–tritium (DT) fuel target implosion by wobbling heavy-ion beams (HIBs). The results presented here show that the mechanism of the dynamic instability mitigation is rather robust against changes in the phase, the amplitude and the wavelength of the wobbling perturbation applied. In general instability would emerge from the perturbation of the physical quantity. Normally the perturbation phase is unknown, so that the instability growth rate is discussed. However, if the perturbation phase is known, the instability growth can be controlled by a superposition of perturbations imposed actively: if the perturbation is induced by, for example, a driving beam axis oscillation or wobbling, the perturbation phase could be controlled and the instability growth is mitigated by the superposition of the growing perturbations. In this paper, we realize the superposition of the perturbation by the wobbling HIBs’ illumination onto a DT fuel target in heavy-ion inertial fusion (HIF). Our numerical fluid implosion simulations present that the implosion non-uniformity is mitigated successfully by the wobbling HIBs illumination in HIF.
In inertial fusion, one of scientific issues is to reduce an implosion non-uniformity of a spherical fuel target. The implosion non-uniformity is caused by several factors, including the driver beam illumination non-uniformity, the Rayleigh–Taylor instability (RTI) growth, etc. In this paper, we propose a new control method to reduce the implosion non-uniformity; the oscillating implosion acceleration δg(t) is created by pulsating and dephasing heavy-ion beams (HIBs) in heavy-ion inertial fusion (HIF). The δg(t) would reduce the RTI growth effectively. The original concept of the non-uniformity control in inertial fusion was proposed in [Laser Part. Beams (1993) 11, 757–768]. In this paper, it was found that the pulsating and dephasing HIBs illumination provide successfully the controlled δg(t) and that δg(t) induced by the pulsating HIBs reduces well the implosion non-uniformity. Consequently the pulsating HIBs improve a pellet gain remarkably in HIF.
In this paper, a study on a fusion reactor core is presented in heavy-ion inertial fusion (HIF), including the heavy-ion beam (HIB) transport in a fusion reactor, an HIB interaction with a background gas, the reactor cavity gas dynamics, the reactor gas backflow to the beam lines, and an HIB fusion reactor design. The HIB has remarkable preferable features to release the fusion energy in inertial fusion: in particle accelerators HIBs are generated with a high driver efficiency of about 30–40%, and the HIB ions deposit their energy inside of materials. Therefore, a requirement for the fusion target energy gain is relatively low, that would be ~50 to operate an HIF fusion reactor with a standard energy output of 1 GW of electricity. In a fusion reactor, the HIB charge neutralization is needed for a ballistic HIB transport. Multiple mechanical shutters would be installed at each HIB port at the reactor wall to stop the blast waves and the chamber gas backflow, so that the accelerator final elements would be protected from the reactor gas contaminant. The essential fusion reactor components are discussed in this paper.
In order to investigate the distinguishability about the progenitors of FeCCSNe and ECSNe, we calculate the luminosities and spectra of their pre-SN neutrinos and estimate the number of events at neutrino detectors.
We studied GeTe structures in topological switching random access memories (TRAMs) with a [GeTe/Sb2Te3] superlattice by using X-ray diffraction (XRD) analysis. We examined the electrical characteristics of the TRAMs deposited at different temperatures. We found that XRD spectra differed between the films deposited at 200 and 240°C and that the differences corresponded to the differences in the GeTe sequences in the films.