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Temperature resulting from the joule heating power and the turn-on and turn-off dissipation of high-power, high-frequency applications is the root cause of their thermal instability, electrical performance degradation, and even thermal-fatigue failure. Thus, the study presents thermal and electrical characterizations of the power MOSFET module packaged in SOT-227 under natural convection and forced convection through three-dimensional (3D) thermal-electric (TE) coupled field analysis. In addition, the influences of some key parameters like electric loads, ambient conditions, thermal management considerations (heat sink, heat spreader) and operation conditions (duty cycle and switching frequency) on the power loss and thermal performance of the power module are addressed. The study starts from a suitable estimation of the power losses, where the conduction losses are calculated using the temperature- and gate-voltage-dependent on-state resistance and drain current through the device, and the switching losses are predicted based on the ideal switching waveforms of the power MOSFETs applied. The effectiveness of the theoretical predictions in terms of device’s power losses and temperatures is demonstrated through comparison with the results of circuit simulation and thermal experiment.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Hemostasis, a process which causes bleeding to stop, can be enhanced using chitosan; but the detailed mechanism is unclear. Red blood cells (RBCs) adhere to chitosan because of their opposite charges, but the adhesion force is small, 3.83 pN as measured here using an optical tweezer, such that the direct adhesion cannot be the sole cause for hemostasis. However, it was observed in this study that layer structures of aggregated RBCs were formed next to chitosan objects in both static and flowing environments, but not formed next to cotton and rayon yarns. The layer structure is the clue for the initiation of hemostatsis. Through the supporting measurements of zeta potentials of RBCs and pH's using blood-chitosan mixtures, it is proposed here that the formation of the RBC layer structure next to chitosan objects is due to the reduction of repulsive electric double layer force between RBCs, because of the association of H+ deprotonated from chitosan with COO− on RBC membrane, under the DLVO (Derjaguin-Landau-Verwey-Overbeek) theory. The results are beneficial for designing effective chitosan-based wound dressings, and also for general biomedical applications.
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.
Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial activities, and has shown highly protective effects against enteropathogenic bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal pathogenic mycotoxins. The possible effect of curcumin on the alleviation of enterotoxicity induced by OTA is unknown. The effects of dietary curcumin supplementation on OTA-induced oxidative stress, intestinal barrier and mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex 1-day-old White Pekin ducklings with initial BW (43.4±0.1 g) were randomly assigned into controls (fed only the basal diet), a group fed an OTA-contaminated diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400 mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30 ducklings and treatment lasted for 21 days. There was a significant decrease in average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05); curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA group (P<0.05). Histopathological and ultrastructural examination showed clear signs of enterotoxicity caused by OTA, but these changes were largely prevented by curcumin supplementation. Curcumin decreased the concentrations of interleukin-1β, tumor necrosis factor-α and malondialdehyde, and increased the activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight junction protein 1 mRNA and protein levels, and decreased those of ρ-associated protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression of apoptosis-related genes, and downregulated mitochondrial transcription factors A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial (P<0.05). These results indicated that curcumin could protect ducks from OTA-induced impairment of intestinal barrier function and mitochondrial integrity.
The dopamine transporter gene (DAT1) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory.
We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV).
The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus; and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus.
Our findings suggest that the DAT1-related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.
The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Hepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5′ UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.
The linear stability boundaries of journal bearings lubricated with a non-Newtonian fluid have been investigated in this paper. Based on the Rabinowitsch fluid model, a non-Newtonian dynamic Reynolds equation for journal bearings is derived and then applied to analyze the linear dynamic characteristics of short journal bearings. Comparing with the Newtonian-lubricant case, the non-Newtonian rheology of dilatant lubricants provides a larger area of linearly stable region. However, the non-Newtonian properties of pseudo-plastic lubricants results in a reverse trend for the short journal bearing.
The present research aimed to investigate the efficacy of a multifaceted intervention that included motivational interviewing (MI) and psychoeducation in improving medication adherence (MA) among patients with bipolar disorder (BD).
A multicenter, cluster randomized, observer-blind, controlled, parallel-group trial was conducted in ten academic centers in Iran. Patients with BD were randomly assigned to the experimental group (EXP; n = 136) or the usual care group (UC; n = 134). The EXP group received five sessions of MI and psychoeducation together with their family members. The primary outcome measure was changes in scores on the Medication Adherence Rating Scale from baseline to 6 months post-intervention. Other outcome measures included serum levels of mood stabilizers, clinical symptoms, quality of life, as well as measures of intention, beliefs about medicine, perceived behavioral control, automaticity, action and coping planning, and adverse reactions.
Medication adherence improved over time in both groups, but patients in the EXP group improved more (baseline score: 6.03; score at the sixth month: 9.55) than patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67). In addition, patients in the EXP group showed greater improvement than patients in the UC group in almost all secondary outcomes 6 months following the intervention.
Multifaceted interventions that include motivational-interviewing and psychoeducation can significantly improve MA and clinical and functional outcomes in patients with BD.
The present research brings psychometric evidences for the Unidimensional Relationship Closeness Scale (URCS), aiming at verifying its adequacy for use in the Brazilian context. Participants were 468 university students with mean age of 21.2 years. They completed a survey composed by the URCS, the Basic Values Survey (BSV), and demographic questions. Through Exploratory (Eigenvalue = 6.61) and Confirmatory Factor Analysis (CFI = .937, TLI = .923), the results showed that the same one-factor structure from the original version of the scale was found. These results were also invariant across gender and relationship status (∆SRMR < .03), and presented evidences of internal consistence (α = .94), temporal stability (ICC = .903, p < .001), and convergent validity (rmale = .32, rfemale = .25, p < .001). In conclusion, this measure has shown to be psychometrically adequate for use in Brazil.
A compact hybrid rocket motor design that incorporates a dual-vortical-flow (DVF) concept is proposed. The oxidizer (nitrous oxide, N2O) is injected circumferentially into various sections of the rocket motor, which are sectored by several solid fuel “rings” (made of hydroxyl-terminated polybutadiene, HTPB) that are installed along the central axis of the motor. The proposed configuration not only increases the residence time of the oxidizer flow, it also implies an inherent “roll control” capability of the motor. Based on a DVF motor geometry with a designed thrust level of 11.6 kN, the characteristics of the turbulent reacting flow within the motor and its rocket performance were analyzed with a comprehensive numerical model that implements both real-fluid properties and finite-rate chemistry. Data indicate that the vacuum specific impulse (Isp) of the DVF motor could reach 278 s. The result from a preliminary ground test of a lab-scale DVF hybrid rocket motor (with a designed thrust level of 3,000 N) also shows promising performance. The proposed DVF concept is expected to partly resolve the issue of scalability, which remains challenging for hybrid rocket motors development.
There has been wide-spread use of plane wave theory in muffler design in industry. However, This has led to an underestimation of acoustical performances at higher frequencies. To overcome the above drawback, the finite element and boundary element methods have been developed. Nevertheless, the time consumed in calculating the noise level is unacceptable. Moreover, considering the acoustical effect and necessity of space-constrained situation in industry, a compact design of reverse mufflers which may improve the acoustical efficiency is then proposed.
In this paper, a numerical assessment of rectangular mufflers hybridized with straight/reverse chambers using eigen function, four-pole matrix, and genetic algorithm under limited space is developed. Before the optimization is performed, an accuracy check of the mathematical models for the muffler will be carried out. Results reveal that the noise reduction will increase when the number of chambers increases. In addition, the acoustical performance of the mufflers is reversely proportional to the diameter of the inlet/outlet tubes. Also, the TL of the mufflers will be improved when using more number of target tones in the objective function. Consequently, a successful approach in searching optimal shaped rectangular straight/reverse mufflers using an eigen function and a genetic algorithm method within a constrained space has been demonstrated.
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males.
The 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference.
We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers.
Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
To examine the incidence of asthma in adult patients with major depressive disorder (MDD).
From the National Health Insurance database of Taiwan, we identified 30 169 adult patients who were newly diagnosed with MDD between 2000 and 2010. Individuals without depression were randomly selected four times and frequency matched for sex, age and year of diagnosis. Both cohorts were followed-up for the occurrence of asthma up to the end of 2011. Adjusted hazard ratios (aHRs) of asthma were estimated using the Cox proportional hazards method.
The overall incidence of asthma was 1.91-fold higher in the MDD cohort than in the non-depression cohort (7.55 v. 3.96 per 1000 person-years), with an aHR of 1.66 (95% confidence interval (CI) 1.55–1.78). In both cohorts, the incidence of asthma was higher in patients and controls who were female, aged, with comorbidities and users of aspirin or beta-adrenergic receptor blockers. No significant difference was observed in the occurrence of asthma between patients with MDD treated with selective serotonin reuptake inhibitors (SSRIs) and those treated with non-SSRIs (SSRIs to non-SSRIs aHR = 1.03, 95% CI 0.91–1.17).
Adult patients with MDD are at a higher risk of asthma than those without depression are.