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Surface waves called meniscus waves often appear in systems that are close to the capillary length scale. Since the meniscus shape determines the form of the meniscus waves, the resulting streaming circulation has features distinct from those caused by other capillary–gravity waves recently reported in the literature. In the present study, we produce symmetric and antisymmetric meniscus shapes by controlling boundary wettability and excite meniscus waves by oscillating the meniscus vertically. The symmetric and antisymmetric configurations produce different surface capillary–gravity wave modes and streaming flow structures. The root-mean-square speed of the streaming circulation increases with the second power of the forcing amplitude in both configurations. The flow symmetry of streaming circulation is retained under the symmetric meniscus, while it is lost under the antisymmetric meniscus. The streaming circulation pattern beneath the meniscus observed in our experiments is qualitatively explained using the method introduced by Nicolás & Vega (Fluid Dyn. Res., vol. 32 (4), 2003, pp. 119–139) and Gordillo & Mujica (J. Fluid Mech., vol. 754, 2014, pp. 590–604).
There seems to be geographical differences in decisions about breast conserving surgery (BCS) in breast cancer patients. This study was to evaluate patients’ attitude to BCS and to assess the factors affecting cancer practice in West China.
A structured questionnaire was distributed to 184 patients, eliciting information about the patients’ characteristics, occupation, education, family life, recognition of illness, knowledge about BCS, the main means of gaining surgery information, selecting surgery approaches, preferences to breast reservation.
In all, 163 patients completed the questionnaire. The results indicated that only 7.4% of patients received BCS and 23% of the remaining patients desired to have BCS and the affecting factors were significantly associated with their family life, recognition of illness and the main means of gaining surgery information (P < 0.05). No associations were between BCS selecting and the other variables studied. The most frequent reasons for selecting BCS were keeping the female shape and improving quality of life (71%), the second most were postoperative recovery, minimal influence of physical function (47%) and patients’ knowledge about BCS (42%). The most frequent reasons for not selecting BCS were uncertainty about BCS results and worry about recurrence (81%), the second most was the elderly age unnecessary for BCS (40%).
The findings indicate that breast cancer patients in West China do not take BCS as the first choice as the best treatment method. It is warranted that further study of more patients, attitude of patients’ partners and physicians to BCS.
Brexpiprazole is a serotonin-noradrenaline-dopamine agent that binds with high affinity to multiple serotonin, norepinephrine and dopamine receptors. In particular, Brexpiprazole is a partial agonist at dopamine D2/D3 and 5-HT1A receptors and an antagonist at 5-HT2A and norepinephrine alpha1B receptors.
We assessed the efficacy and safety of brexpiprazole versus placebo as adjunctive therapy to anti-depressant therapy (ADT) in subjects with MDD who demonstrated inadequate response to ADT.
This trial had 3 phases: a screening phase (7-28 days); a prospective phase (Phase A): 8-week, single-blind placebo plus an investigator-determined, open-label ADT; a randomized phase (Phase B): 6-week, double-blind, adjunctive brexpiprazole (2 mg/day) vs. placebo in patients with an inadequate response to ADT.
The primary efficacy endpoint was the change from the end of Phase A (Week 8) to the end of Phase B (Week 14) in MADRS Total Score. The key secondary endpoint was the change in mean SDS score. Other secondary endpoints were mean change in CGI-S, IDS-R, HAMD and HAMA.
Of 379 randomized patients, completion rates at Week 14 were high (92.9%). Statistically significant improvements in mean MADRS Total score were observed for subjects receiving adjunctive brexpiprazole 2mg/day compared with placebo (p=0.0001) at endpoint. In addition, on all secondary endpoints Brexpiprazole showed a statistically significant advantage over placebo.
Commonly reported adverse events in the brexpiprazole group (>5% and more than twice placebo) were weight gain (8.0%), akathisia (7.4%).
Brexpiprazole was effective and well tolerated as adjunctive treatment for MDD patients with an inadequate response to ADT.
Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.
To evaluate the efficacy, safety, and tolerability of brexpiprazole in patients with acute schizophrenia in a meta-analysis of three phase 3 studies with brexpiprazole.
The primary endpoint was change from baseline to week 6 in PANSS total score.
Data from the 3 clinical studies in patients with acute schizophrenia were combined and analyzed using individual patient data meta-analysis. In two similarly designed studies (NCT01396421; NCT01393613), patients with acute schizophrenia were randomized to fixed-doses of brexpiprazole 2 mg/day, 4 mg/day or placebo (a low-dose treatment group was included in each study [0.25 mg and 1.0 mg]; not included in the meta-analysis). In the third study (NCT01810380), patients were randomized to flexible dosing of brexpiprazole (2 to 4 mg/day), placebo, or an active reference (quetiapine extended release). Changes from baseline for brexpiprazole vs. placebo were analyzed using an MMRM approach.
Brexpiprazole 2–4 mg (n = 868) was superior to placebo (n = 517) in change from baseline in PANSS total score (−20.1 vs. −14.3; estimated treatment difference to placebo: −5.8 [95% CI: −8.0; −3.6]; P < 0.001). The proportions of patients reporting TEAEs were similar between the brexpiprazole and placebo treatment groups (57.9% vs. 57.5%). No unexpected safety concerns were observed.
This meta-analysis supports evidence from three individual trials that brexpiprazole is efficacious and safe in treating patients with acute schizophrenia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Bipolar disorder (BD) is characterized by unusual shifts in mood and energy and affects 1 to 3% of the general population. Lithium (Li) can prevent patients from depression and mania, as well as reduce the risk of suicide. Unfortunately, a high rate of patients do not respond positively to Li treatment. In line with various studies, Li treatment is also associated with potentially severe adverse reactions, including renal dysfunctions. Specifically, it has been reported that Li may induce reduction of glomerular filtration rate (GFR) in long-term treated BD patients.
The aim of our study was to evaluate the contribution of genetic variants in Li-induced reduction of the estimated GFR (eGFR) in bipolar patients, under long term Li therapy.
We screened the literature to identify genes previously shown to be associated with kidney function or Li mechanism of action and genotyped tag SNPs covering these genes.
The sample comprised 70 Sardinian bipolar patients genotyped for 46 SNPs, located in 33 genes, with Invader assay and Sanger sequencing.
Our results showed that a SNP (rs378448) located in Acid Sensing Ion Channel Neurona-1 (ACCN1) gene, significantly interacted with years of Li treatment in reducing eGFR (F = 4.166, P = 0.046).
Our preliminary findings suggest that ACCN1 (ASIC2) gene could be involved in modulating the susceptibility of BD patients to develop renal dysfunctions induced by chronic Li treatment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
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.
Stars ejected from the Galactic Center can be used to place important constraints on the Milky Way potential. We have used Hills stars to constrain models for the Galactic potential, demonstrating that meaningful constraint can be obtained if we have samples of around 50 nearby Hills stars.
This paper poses a hypothetical WTO challenge to the Passenger Name Records (PNR) Transfer Agreements the European Union has signed with the United States (as well as Australia and Canada). The focus will be on a possible citation of GATS Article XIV National Security Exception by the EU, and the viability of such a defense. Because of the absence of case law, this paper will also attempt to synthesize an acceptable standard for assessing GATS National Security Exception citations.
Music or other background sounds are often played in barns as environmental enrichment for animals on farms or to mask sudden disruptive noises. Previous studies looking at the effects of this practice on non-human animal well-being and productivity have found contradictory results. However, there is still a lack of discussion on whether piglets have the ability to distinguish different types of music. In this study, we exposed piglets to different music conditions to investigate whether the piglets preferred certain music types, in which case those types would have the potential to be used as environmental enrichment. In total, 30 piglets were tested for music type preference to determine whether growing pigs respond differently to different types of music. We used music from two families of instruments (S: string, W: wind) and with two tempos (S: slow, 65 beats/min (bpm); F: fast, 200 bpm), providing four music-type combinations (SS: string-slow; SF: string-fast; WS: wind-slow; WF: wind-fast). The piglets were given a choice between two chambers, one with no music and the other with one of the four types of music, and their behaviour was observed. The results showed that SS and WF music significantly increased residence time (P<0.01) compared with the other music conditions. Compared with the control group (with no music), the different music conditions led to different behavioural responses, where SS music significantly increased lying (P<0.01) and exploration behaviour (P<0.01); SF music significantly increased tail-wagging behaviour (P<0.01); WS music significantly increased exploration (P<0.01); and WF music significantly increased walking, lying, standing and exploration (all P<0.01). The results also showed that musical instruments and tempo had little effect on most of the behaviours. Fast-tempo music significantly increased walking (P=0.02), standing (P<0.01) and tail wagging (P=0.04) compared with slow-tempo music. In conclusion, the results of this experiment show that piglets are more sensitive to tempo than to musical instruments in their response to musical stimulation and seem to prefer SS and WF music to the other two types. The results also suggest a need for further research on the effect of music types on animals.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
A multichannel calorimeter system is designed and constructed which is capable of delivering single-shot and broad-band spectral measurement of terahertz (THz) radiation generated in intense laser–plasma interactions. The generation mechanism of backward THz radiation (BTR) is studied by using the multichannel calorimeter system in an intense picosecond laser–solid interaction experiment. The dependence of the BTR energy and spectrum on laser energy, target thickness and pre-plasma scale length is obtained. These results indicate that coherent transition radiation is responsible for the low-frequency component (
1 THz) of BTR. It is also observed that a large-scale pre-plasma primarily enhances the high-frequency component (
3 THz) of BTR.
We numerically study the impact of a compound drop on a hydrophobic substrate using a ternary-fluid diffuse-interface method, aiming to understand how the presence of the inner droplet affects the spreading dynamics and maximal spreading of the compound drop. First, it is interesting to see that the numerical results for an impacting pure drop agree well with the universal rescaling of maximal spreading ratio proposed by Lee et al. (J. Fluid Mech., vol. 786, 2016, R4). Second, two flow regimes have been identified for an impacting compound drop: namely jammed spreading and joint rim formation. The maximal spreading ratio of the compound drop is found to depend on the volume fraction of the inner droplet
, the surface tension ratio
, the Weber number and the flow regime. Moreover, we propose a universal rescaling of maximal spreading ratio for compound drops, by integrating the one for pure drops with a corrected Weber number that takes
and the flow regime into account. The predictions of the universal rescaling are in good agreement with the numerical results for impacting compound drops.
Charge Exchange (CEX) ion is the main factor causing the plume pollution. The distribution of CEX ions is determined by the distribution of beam ions and neutral atoms. Hence, the primary problem in the study of the plume is how to accurately simulate the distribution of beam ions and neutral atoms. At present, the most commonly used model utilised for the plume simulation is the analytical model proposed by Roy for the plume simulation of the NASA Solar Technology Application Readiness (NSTAR) ion thruster. However, this analytical model can only be applied to the ion beam with small divergence angles. In addition, the analytical model is no longer applicable to the simulation for the plume of a new type of ion thruster that appeared recently, which is called the annular ion thruster. In this paper, a 3D particle model is proposed for the plume simulation of ion thrusters consisting of the particle model for beam ions, the Direct Simulation Monte Carlo (DSMC) model for neutral atoms and the Immersed Finite Element-Particle In Cell-Monte Carlo Collision (IFE-PIC-MCC) model for CEX ions. Then, the plume of the NSTAR ion thruster is simulated by both Roy's model and the 3D particle model. The simulation results of both models are then compared with the experimental results. It is shown that the numerical results of the 3D particle model agree well with those of the analytical model and the experimental data. And this 3D particle model can also be used for other electric thrusters.
Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.
Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
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.
Giant electromagnetic pulses (EMP) generated during the interaction of high-power lasers with solid targets can seriously degrade electrical measurements and equipment. EMP emission is caused by the acceleration of hot electrons inside the target, which produce radiation across a wide band from DC to terahertz frequencies. Improved understanding and control of EMP is vital as we enter a new era of high repetition rate, high intensity lasers (e.g. the Extreme Light Infrastructure). We present recent data from the VULCAN laser facility that demonstrates how EMP can be readily and effectively reduced. Characterization of the EMP was achieved using B-dot and D-dot probes that took measurements for a range of different target and laser parameters. We demonstrate that target stalk geometry, material composition, geodesic path length and foil surface area can all play a significant role in the reduction of EMP. A combination of electromagnetic wave and 3D particle-in-cell simulations is used to inform our conclusions about the effects of stalk geometry on EMP, providing an opportunity for comparison with existing charge separation models.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Thirty angiosperm species in 20 families, collected in Nam Kading National Protected Area, are recorded in Laos for the first time. Because the flora of Nam Kading is rich in endemic species, the area represents one of the core sites of plant biodiversity in Laos. To elucidate the plant diversity accurately, further intensive floristic surveys are required.