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Highlights• A novel numerical approach has been proposed to retrieve the hydraulic transmissivity of elliptical rock fractures in triaxial shear-flow experiments.• The accuracy of different methods for estimation of hydraulic transmissivity of elliptical rock fractures has been evaluated and discussed.• The numerical approach and electrical analogy are recommended for accurate evaluation of hydraulic transmissivity of elliptical rock fractures.

Continuous increasing discharge of industrial oily wastewater and frequent occurrence of oil spill accidents have taken heavy tolls on global environment and human health. Organic-inorganic modifications can fabricate superhydrophilic/submerged superoleophobic membranes for efficient oil-water separation/treatment though they still suffer from complex operation, non-environmental friendliness, expensive cost or uneven distribution. Herein, a new strategy regarding tannic acid (TA)-Ti(IV) coating and CaCO

While ethylenediamine tetramethylenephosphonic acid (EDTMPA) has been emerged as a stronger chelating agent than ethylene diamine tetraacetic acid (EDTA) for fouling mitigation, and transparent exopolymer particles (TEP) is a major foulant in membrane-based water treatment process, effects of EDTMPA on TEP fouling and the underlying mechanism have been not yet studied. In this study, Flory-Huggins lattice theory was combined with density functional theory (DFT) technology to explore this subject at molecular level. Filtration experiments showed a unimodal pattern of specific filtration resistance (SFR) of TEP sample with Ca

Aim: To comprehensively understand microbiota-regulated lincRNA–miRNA–mRNA networks in psychiatric disorders. Materials & methods: Integrated analyses of lincRNAs, mRNAs and miRNAs, obtained by microarray analysis of hippocampus from specific pathogen-free, germ-free and colonized germ-free mice, were performed. Results: Expression of 139 mRNAs, seven miRNAs and one lincRNA was restored following colonization. The restored transcripts were mainly involved in CREB and Ras/MAPK signaling pathways. RNA transcription and post-transcriptional regulation were the primary perturbed functions. Finally, 12 lincRNAs, six miRNAs and 47 mRNAs were included in a lincRNA–miRNA–mRNA network, and lincRNA0926-miR-190a-5p-Celf4 interactions may play a pivotal role in this regulatory network. Conclusion: This study provides clues for understanding the molecular basis of gut microbiota–brain interactions in depressive- and anxiety-like behaviors.

While transparent exopolymer particles (TEP) is a major foulant, and ethylene diamine tetraacetic acid (EDTA) is a strong chelating agent frequently used for fouling mitigation in membrane-based water treatment processes, little has been known about TEP-associated membrane fouling affected by EDTA. This work was performed to investigate roles of EDTA addition in TEP (Ca-alginate gel was used as a TEP model) associated fouling. It was interestingly found that, TEP had rather high specific filtration resistance (SFR) of 2.49 × 10

Post-stroke depression (PSD) is the most common and severe neuropsychiatric complication after stroke. However, the molecular mechanism of PSD is still unclear. Previous studies have identified peripheral tissues metabolites associated with PSD using metabolomics techniques. We searched and systematically summarized metabolites that may be involved in metabolic changes in peripheral tissues of patients with PSD from the Metabolite Network of Depression Database (MENDA) and other biomedical databases. MetaboAnalyst5.0 software was used for pathway analysis and enrichment analysis of differential metabolites, and subgroup analyses were performed according to tissue types and metabolomics techniques. We identified 47 metabolites that were differentially expressed between patients with and without PSD. Five differential metabolites were found in both plasma and urine, including L-glutamic acid, pyroglutamic acid, palmitic acid, L-phenylalanine, and L-tyrosine. We integrated these metabolites into metabolic pathways, and six pathways were significantly altered. These pathways could be roughly divided into three modules including amino acid metabolism, nucleotide metabolism, and glucose metabolism. Among them, the most significantly altered pathway was “phenylalanine metabolism” and the pathway containing the most associated molecules was “aminoacyl-tRNA biosynthesis”, which deserve further study to elucidate their role in the molecular mechanism of PSD. In summary, metabolic changes in peripheral tissues are associated with PSD, especially the disruption of “phenylalanine metabolism” and “aminoacyl-tRNA biosynthesis” pathways. This study provides clues to the metabolic characteristics of patients with PSD, which may help to elucidate the molecular pathogenesis of PSD.

Major depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of l-acetylcarnitine, creatinine, l-asparagine, l-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, l-serine, oleic acid, myo-inositol, dodecanoic acid, l-methionine, hypoxanthine, palmitic acid, l-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. l-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of l-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan–kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased l-tryptophan and kynurenic acid levels, and alterations in the tryptophan–kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.

Depression is a seriously disabling psychiatric disorder with a significant burden of disease. Metabolic abnormalities have been widely reported in depressed patients and animal models. However, there are few systematic efforts that integrate meaningful biological insights from these studies. Herein, available metabolic knowledge in the context of depression was integrated to provide a systematic and panoramic view of metabolic characterization. After screening more than 10 000 citations from five electronic literature databases and five metabolomics databases, we manually curated 5675 metabolite entries from 464 studies, including human, rat, mouse and non-human primate, to develop a new metabolite-disease association database, called MENDA (http://menda.cqmu.edu.cn:8080/index.php). The standardized data extraction process was used for data collection, a multi-faceted annotation scheme was developed, and a user-friendly search engine and web interface were integrated for database access. To facilitate data analysis and interpretation based on MENDA, we also proposed a systematic analytical framework, including data integration and biological function analysis. Case studies were provided that identified the consistently altered metabolites using the vote-counting method, and that captured the underlying molecular mechanism using pathway and network analyses. Collectively, we provided a comprehensive curation of metabolic characterization in depression. Our model of a specific psychiatry disorder may be replicated to study other complex diseases.

Background Depression is a leading cause of disability worldwide. There is increasing evidence showing that depression is associated with the pathophysiology in amygdala; however, the underlying mechanism remains poorly understood. Method We established a rat model of chronic social defeat stress (CSDS) and conducted a series of behavior tests to observe behavioral changes. Then liquid chromatography mass spectrometry (LC–MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed to detect metabolomes and proteomes in the amygdala, respectively. Ingenuity pathway analysis (IPA) and other bioinformatic analyses were used to analyze differentially expressed metabolites and proteins. Results The significantly lower sucrose preference index in the sucrose preference test and longer immobile time in the forced swim test were observed in the CSDS rats compared with control rats. In the multi-omics analysis, thirty-seven significantly differentially expressed metabolites and 123 significant proteins were identified. Integrated analysis of differentially expressed metabolites and proteins by IPA revealed molecular changes mainly associated with synaptic plasticity, phospholipase c signaling, and glutamine degradation I. We compared the metabolites in the amygdala with those in the hippocampus and prefrontal cortex from our previous studies and found two common metabolites: arachidonic acid and N-acetyl- l -aspartic acid among these three brain regions. Conclusion Our study revealed the presence of depressive-like behaviors and molecular changes of amygdala in the CSDS rat model, which may provide further insights into the pathogenesis of depression, and help to identify potential targets for antidepressants.

Objective To investigate the efficacy and acceptability of virtual reality (VR) with time-dose-matched conventional therapy (CT) in patients poststroke with upper limb dysfunction. Data Sources Cochrane, PubMed, Web of Science, Embase, and ProQuest were systematically searched up to May 24, 2021. Study Selection Randomized controlled trials comparing VR with time-dose-matched CT in patients poststroke with upper limb dysfunction were included. Data Extraction The extracted data included efficacy (mean change in structure/function, activity, and participation scores), acceptability (dropouts for all reasons), adverse events, and characteristics of the included studies. The Cochrane risk of bias assessment tool was used to assess the risk of bias. Data Synthesis Thirty-one randomized controlled trails were included. VR was superior to time-dose-matched CT in terms of the World Health Organization's International Classification of Functioning, Disability and Health structure/function, with a standardized mean difference (SMD) of 0.35, but not activity and participation. Subgroup analyses demonstrated that virtual environment was superior to CT in structure/function (SMD=0.38) and activity (SMD=0.27), whereas there were no significant differences between commercial gaming and CT in any World Health Organization International Classification of Functioning, Disability and Health domain. VR mixed with CT was more effective than time-dose-matched CT in structure/function (SMD=0.56), whereas VR only was not significantly different from CT. There were no significant differences in the incidence of adverse events and dropout rates between VR and CT. Conclusions The results suggest that VR is superior to time-dose-matched CT in terms of recovery of upper extremity motor function, especially when a virtual environment is used or VR is mixed with CT. However, VR (VR only or mixed with CT) does not improve patients’ daily activity performance and participation compared with CT. Overall, VR appears to be safe and acceptable as CT. Large-scale definitive trials are needed to verify or refute these findings.

Effects of calcium ions and polyaluminum chloride (PACl) on membrane fouling in coagulation-ultrafiltration (UF) process were investigated in this study. Filtration tests demonstrated three interesting filtration behaviors: 1) high specific filtration resistance (SFR) of alginate solution with low CaCl2 or PACl addition (e. g. 3.51×1015 m·kg -1 under the condition of 1.5 mM CaCl2 addition); 2) unimodal pattern of alginate SFR with PACl or CaCl2 addition alone; 3) synergistic effects between CaCl2 and PACl on alginate SFR. It was found that, the foulant morphological changes driven by the thermodynamic mechanisms based on Flory-Huggins lattice theory take the critical roles in these filtration behaviors. Density functional theory (DFT) calculations showed that initial coordination of Ca2+ and Al3+ ions with alginates tended to form tetrahedron geometry and geometry of coordinating three terminal carboxyl groups, respectively, which facilitated to elongate the alginate chains (without clustering the flocs) and form more stable gel, increasing SFR. Improving Ca2+ and Al3+ dosages triggered transition to other geometries for clustering polymeric network and flocculation, reducing SFR. Due to the higher binding affinity of Ca2+ over Al3+, Ca2+ and Al3+ sequentially take roles of enlarging polymeric network and clustering the coordination compounds, and then facilitate to form large size flocs and reduce SFR, causing the synergistic effects between CaCl2 and PACl additions. The proposed thermodynamic mechanisms satisfactorily explained these interesting fouling behaviors, allowing to further optimize coagulation-UF process.

This paper studies the synchronous multiple change-point detection problem involving multiple signals. The original signals are fitted by a piecewise linear regression with Group Lasso constraints to ensure the synchronism of the change points. Then, first-order difference is used to determine the candidate set of change points for the resultant fitted curve, and then the Bayesian information criterion (BIC) is utilized to determine change points from the candidate set. Monte Carlo simulation-based experiments are used to compare the new method with three commonly-used multi-signal synchronous change-point detection methods. The results show that the proposed method is superior in detecting both the number and the position of change points. The performance in real multiple vibration signals of cutting tools data further verifies the effectiveness of the method.

Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism—particularly the polyunsaturated fatty acids metabolism, and purine metabolism—that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.

In this paper, GT suite software is used to model the cooling system of military special vehicles with multiple power sources. The power drive system is composed of main engine, auxiliary engine and four hub motors. By constructing modular cooling unit, the volume of radiator and the layout of cooling unit are changed. While the total volume of radiator is unchanged, the cooling capacity of cooling system is improved. Firstly, the problem is simplified and modeled by high-temperature and low-temperature double circuit. The main engine with power of 600kW and auxiliary engine with power of 200kW are combined into a high-temperature circuit. The water temperature of the circuit is higher, about 90 ºC; Four hub motors with power of 440kw and their electrical components are combined into a low temperature circuit. The water temperature of this circuit is about 60 ºC. By modifying the volume, layout and number of radiators, the temperature of the dual circuit is analyzed, and it is found that when the total radiator volume remains the same, the cooling effect of the multi-radiator layout is better.

Major depressive disorder (MDD) is a heterogeneous and multi-factorial disorder, and the underlying molecular mechanisms remain largely unknown. However, many studies have indicated that the molecular mechanisms underlying depression in response to different stress may differ. After screening, 28–30 rats were included in each model of depression (chronic unpredictable mild stress (CUMS); learned helplessness (LH); chronic restraint stress (CRS); or social defeat (SD)). Non-targeted gas chromatography-mass spectrometry was used to profile the metabolic changes in the hippocampus. As a result, all four models exhibited significant depression-like behavior. A total of 30, 24, 19, and 25 differential metabolites were identified in the CUMS, LH, CRS, and SD models, respectively. Interestingly, the hierarchical clustering results revealed two patterns of metabolic changes that are characteristic of the response to cluster 1 (CUMS, LH) and cluster 2 (CRS, SD) stress, which represent physical and psychological stress, respectively. Bioinformatic analysis suggested that physical stress was mainly associated with lipid metabolism and glutamate metabolism, whereas psychological stress was related to cell signaling, cellular proliferation, and neurodevelopment, suggesting the molecular changes induced by physical and psychological stress were different. Nine shared metabolites were opposite in the directions of change between physical and psychological models, and these metabolites were associated with cellular proliferation and neurodevelopment functions, indicating the response to physical and psychological stress was different in the activation and deactivation of the final common pathway to depression. Our results provide a further understanding of the heterogeneity in the molecular mechanisms of MDD that could facilitate the development of personalized medicine for this disorder.

Effects of iron(III) ion level and ionic strength on membrane fouling in coagulation-ultrafiltration (UF) process were explored in this study. Two interesting filtration phenomena during the filtration process were observed: extremely reduced specific filtration resistance (SFR) of alginate solution complexed with iron (III) ions level from 0.1 to 2.0 mM (phenomenon I), and different change trends of alginate SFR with ionic strength between two iron(III) ion levels (remarkable increase trend of alginate SFR with ionic strength at 0.1 mM ions level while almost remaining unchanged trend at 2.0 mM ions level) (phenomenon II). Experimental characterizations indicated that the two phenomena were closely linked to changes of zeta potential, viscosity and morphology of the related foulants. It was proposed that iron(III) ions at low level (0.1 mM) preferentially coordinate the terminal carboxyl groups of alginate chains and form gel layer. The chemical potential gap described by Flory-Huggins lattice theory is responsible for the extremely high SFR of gel layer. Coordinating the non-terminal carboxyl groups at high iron(III) ion level (2.0 mM) causes transition from gel layer to cake layer formation during filtration, and lots of interstices in cake layer correspond to low SFR, well interpreting phenomenon I. Meanwhile, electrostatic double layer compression caused by the increased ionic strength makes the gel layer shrunk and denser for low iron(III) ion level, but less affects the number and size of interstices in the cake layer for high iron(III) ion level, reasonably explaining phenomenon II. This study revealed essential and comprehensive thermodynamic fouling mechanisms and facilitated to optimize coagulation-UF/MF process.

We aimed to provide an overview of psychotherapy in young anxious children (mean age

Influences of fractal dimension (Df) of membrane surface on interfacial interactions related to membrane fouling in a membrane bioreactor were investigated based on thermodynamic methods. It was found that membrane surface had significant fractal features, and its fractal dimension could be characterized by the power spectrum method. The modified Weierstrass-Mandelbrot (WM) function was found to be effective to model the fractal membrane surface, and higher Df corresponded to higher number of fine asperities in the modeled surface. Moreover, the modeled surface roughness exponentially decreased with Df. Interaction calculations according to a novel method showed that the interactions for fractal membrane surface were elongated and weakened as compared with smooth membrane surface. It was interestingly found that the absolute value of total interaction monotonically decreased with Df of membrane surface. As Df is a measure of substance stiffness, this result indicates that softer surface is more susceptible to adhesion by sludge foulant. The results offered new insights into membrane fouling mechanisms and alleviation.

In this study, we evaluate the efficacy and safety of interpersonal psychotherapy (IPT) for adolescents with depression. We searched our existing database and electronic databases, including PubMed, Cochrane, EMBASE, PsycINFO, Web of Science, and CINAHL databases (from inception to May 2016). We included randomized controlled trials comparing IPT with various control conditions, including waitlist, psychological placebo, treatment as usual, and no treatment, in adolescents with depression. Finally, we selected seven studies comprising 538 participants comparing IPT with three different control conditions. Pooled analyses suggested that IPT was significantly more effective than control conditions in reducing depressive symptoms at post-treatment and follow-up, and increasing the response/remission rate at post-treatment. IPT was also superior to control conditions for all-cause discontinuation and quality of life/functioning improvement outcomes. However, there was no evidence that IPT reduces the risk of suicide from these data. Meta-analysis demonstrated publication bias for primary efficacy, while the adjusted standardized mean difference using the trim-and-fill method indicated IPT was still significantly superior to the control conditions. Current evidence indicates IPT has a superior efficacy and acceptability compared with control conditions in treating adolescents with depression.

Summary Background Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (–0·78, 95% CrI −1·55 to −0·01) and psychodynamic therapy (–1·14, −2·20 to −0·08), but not more effective than fluoxetine alone (–0·22, −0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from −1·73 to −0·51); and only interpersonal therapy was more effective than all psychological controls (–1·37 to −0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as “low” to “very low” in terms of confidence of evidence according to Confidence In Network Meta-Analysis. Interpretation Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. Funding National Key Research and Development Program of China.

Background Few meta-analyses have focused on the effect of cognitive behavioral therapy (CBT) for depression in children. Study Selection Randomized controlled trials comparing CBT with control conditions for depression in children (≤13 years old) were included. Data Sources Seven electronic databases (PubMed, Embase, CENTRAL, Web of Science, PsycINFO, CINAHL, and LiLACS) were searched from inception to September 2015. Data Extraction and Synthesis The primary efficacy was defined as mean change scores in depressive symptoms, and the second efficacy (remission) was a score below the threshold for a diagnosis of depression, both after treatment and at the end of follow-up. We also measured acceptability by the proportion of participants who discontinued treatment up to posttreatment. Results Nine studies with 306 participants were selected for this analysis. At posttreatment, CBT was significantly more effective than control conditions in terms of primary efficacy (standardized mean difference, −0.41; 95% confidence interval [CI], −0.64 to −0.18) and secondary efficacy (odds ratio [OR], 2.16; 95% CI, 1.24 to 3.78). At follow-up, the results were consistent with those of efficacy outcomes at posttreatment, with a standardized mean difference of −0.34 and an OR of 2.04. CBT had no statistical more all-cause discontinuations than the control group (OR, 0.69; 95% CI, 0.26 to 1.82). However, subgroup analyses found that CBT was only significantly more effective than nontreatment, while it was not better than wait list or psychological placebo. Conclusions CBT seems to be more beneficial in the treatment of depression in children than nontreatment; however, this finding is limited by the small size of the trials and low literature quality.

While the adsorptive fouling in membrane bioreactors (MBRs) is highly dependent of the surface morphology, little progress has been made on modeling biocake layer surface morphology. In this study, a novel method, which combined static light scattering method for fractal dimension (Df) measurement with fractal method represented by the modified two-variable Weierstrass-Mandelbrot function, was proposed to model biocake layer surface in a MBR. Characterization by atomic force microscopy showed that the biocake surface was stochastic, disorder, self-similarity, and with non-integer dimension, illustrating obvious fractal features. Fractal dimension (Df) of sludge suspension experienced a significant change with operation of the MBR. The constructed biocake layer surface by the proposed method was quite close to the real surface, showing the feasibility of the proposed method. It was found that Df was the critical factor affecting surface morphology, while other factors exerted moderate or minor effects on the roughness of biocake layer.

Background Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. Methods We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. Findings We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference −0·51, 95% credible interval [CrI] −0·99 to −0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I2 values were 33·21% for efficacy and 0% for tolerability. Interpretation When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated.

Women are an important part of the medical workforce, yet little is known about gender differences in psychological morbidity, burnout, job stress and job satisfaction among neurologists. This study assessed gender differences in a large national sample of Chinese neurologists. Multivariate analyses were performed to examine associations. A total of 5558 neurologists were included in the analysis. Compared with their male counterparts, female neurologists were generally younger; were less likely to be married or to have children; had higher levels of education; were in practice for a shorter period of time; were less likely to hold senior roles; and had lower incomes. Male and female neurologists worked similar hours and spent a similar number of nights on call. No gender differences were found in psychological morbidity, burnout, and high levels of job stress for female and male, respectively. Women had higher emotional exhaustion scores, while men were more likely to have low levels of job satisfaction. The multivariate analysis showed that factors independently associated with psychological morbidity, burnout, high levels of job stress and low levels of job satisfaction were generally similar for women and men. These findings increase our understanding of gender differences in psychological morbidity, burnout, job stress, and job satisfaction among neurologists. As more women join the medical profession, these differences may be useful in designing medical training and practice.

In this study, in situ water injection tests and numerical modeling in conjunction with core logs and television image measurements were applied for an investigation of the hydraulic properties of the rock mass around underground excavations. The aim of our work was to investigate the influence of rock structure and water pressure on the hydraulic conductivity of the rock mass around underground excavations. Thus, water injection tests were conducted in four boreholes that were drilled in the rock mass in underground tunnels in China. Seepage connection initiation and steady state seepage were proposed to identify the seepage evolution course within the rock mass by combining the results of pressure and hydraulic conductivity. Generally, hydraulic conductivity is strongly related to rock structure and water pressure. The results also revealed that a rearrangement of rock structure would occur in the damage zone, resulting in an increase in hydraulic conductivity of nearly one to several orders of magnitude. The results from the modified numerical model showed that the pore water distribution and the groundwater inflow rate are affected by both the hydraulic conductivity and the thickness of the damage zone and they are influenced more by the thickness of this zone.

Key Points Question What is the best psychotherapeutic approach for anxiety disorders in children and adolescents in terms of efficacy and acceptability? Findings This network meta-analysis included 101 unique trials with 6625 unique participants who received 11 different psychotherapies and 4 control conditions. Only group cognitive behavioral therapy was significantly more effective in reducing anxiety symptoms than other psychotherapies and all control conditions posttreatment and at short-term follow-up. Meaning Group cognitive behavioral therapy may be the initial choice of psychotherapy for anxiety disorders in children and adolescents, after replication in future research with focus on disorder-specific psychotherapies and identification of moderators of treatment effect., This network meta-analysis compares and ranks the different types of psychotherapies and the different ways of delivering psychological treatments for anxiety disorders in children and adolescents., Importance Anxiety disorders are common in children and adolescents, and uncertainty remains regarding the optimal strategy of psychotherapies in this population. Objective To compare and rank the different types of psychotherapies and the different ways of delivering psychological treatments for anxiety disorders in children and adolescents. Data Sources PubMed, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ProQuest Dissertations, LILACS (Literatura Latino Americana em Ciências da Saúde), international trial registers, and US Food and Drug Administration reports were searched from inception to November 30, 2017. Study Selection Randomized clinical trials that compared any structured psychotherapy with another psychotherapy or a control condition for anxiety disorders in children and adolescents were selected. Data Extraction and Synthesis Four researchers independently performed data extraction and quality assessment. Pairwise meta-analyses and Bayesian network meta-analysis within the random-effects model were used to synthesize data. Main Outcomes and Measures Efficacy (change in anxiety symptoms) posttreatment and at follow-up, acceptability (all-cause discontinuation), and quality of life and functional improvement were measured. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Results A total of 101 unique trials including 6625 unique participants compared 11 different psychotherapies with 4 specific control conditions. The certainty of evidence was rated as low or very low for most comparisons. For efficacy, most psychotherapies were significantly more effective than the wait list condition posttreatment (standardized mean difference [SMD], −1.43 to −0.61) and at the longest follow-up (SMD, −1.84 to −1.64). However, only group cognitive behavioral therapy (CBT) was significantly more effective than the other psychotherapies and all control conditions posttreatment. For acceptability, bibliotherapy CBT had significantly more all-cause discontinuations than some psychotherapies and control conditions (range of odds ratios, 2.48-9.32). In terms of quality of life and functional improvement, CBT (delivered in different ways) was significantly beneficial compared with psychological placebo and the wait list condition (SMDs, 0.73 to 1.99). Conclusions and Relevance Group CBT would be the more appropriate choice of psychotherapy for anxiety disorders in children and adolescents, based on these findings. Other types of psychotherapies and different ways of delivering psychological treatment can be alternative options. Further research is needed to explore specific anxiety disorders, disorder-specific psychotherapy, and moderators of treatment effect. Trial Registration PROSPERO Identifier: CRD42015016283

In recent years, whether, when and how to use antidepressants to treat depressive disorder in children and adolescents has been hotly debated. Relevant evidence on this topic has increased rapidly. In this paper, we present the construction and content of a database of randomised controlled trials of antidepressants to treat depressive disorder in children and adolescents. This database can be freely accessed via our website and will be regularly updated. Major bibliographic databases (PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO and LiLACS), international trial registers and regulatory agencies’ websites were systematically searched for published and unpublished studies up to April 30, 2017. We included randomised controlled trials in which the efficacy or tolerability of any oral antidepressant was compared with that of a control group or any other treatment. In total, 7377 citations from bibliographical databases and 3289 from international trial registers and regulatory agencies’ websites were identified. Of these, 53 trials were eligible for inclusion in the final database. Selected data were extracted from each study, including characteristics of the participants (the study population, setting, diagnostic criteria, type of depression, age, sex, and comorbidity), characteristics of the treatment conditions (the treatment conditions, general information, and detail of pharmacotherapy and psychotherapy) and study characteristics (the sponsor, country, number of sites, blinding method, sample size, treatment duration, depression scales, other scales, and primary outcome measure used, and side-effect monitoring method). Moreover, the risk of bias for each trial were assessed. This database provides information on nearly all randomised controlled trials of antidepressants in children and adolescents. By using this database, researchers can improve research efficiency, avoid inadvertent errors and easily focus on the targeted subgroups in which they are interested. For authors of subsequent reviews, they could only use this database to insure that they have completed a comprehensive review, rather than relied solely on the data from this database. We expect this database could help to promote research on evidence-based practice in the treatment of depressive disorder in children and adolescents. The database could be freely accessed in our website: http://xiepengteam.cn/research/evidence-based-medicine .

Infiltration usually plays a significant role in construction failures and transfer of contaminants. Therefore, it is very important to monitor underground water migration. In this study, a soil infiltration experiment was carried out using an indoor model test. The water infiltration characteristics were recorded and analyzed based on the response of the geoelectric field, including the primary field potential, self-potential, excitation current and apparent resistivity. The phreatic water surface and the infiltration velocity were determined. The inversion results were compared with direct observations. The results showed that the changes in the geoelectric field parameters explain the principles of groundwater flow. The infiltration velocity and the phreatic surface can be determined based on the primary field potential response and the excitation current. When the phreatic surface reached the location of the electrodes, the primary field potential and self-potential decreased rapidly whereas the excitation current increased rapidly. The height of the phreatic surface and the infiltration time exhibited a linear relationship for both the observation data and the calculations of the excitation current. The apparent resistivity described the infiltration status in the soil and tracked the phreatic surface accurately.

IntroductionPost-traumatic stress disorder (PTSD) is common among children and adolescents who are exposed to trauma, and it is often associated with significant negative impacts on their psychosocial functioning and quality of life. Many types of psychotherapies have been found to be effective for PTSD in children and adolescents. However, due to the lack of direct comparisons between different psychotherapies, the hierarchy of treatment efficacy is still unclear. Therefore, we plan to conduct a systematic review and network meta-analysis to evaluate the efficacy and acceptability of various types of psychotherapies for PTSD in children and adolescents.Methods and analysisA systematic search will be conducted among eight electronic databases, including PubMed, Cochrane, Embase, Web of Science, PsycINFO, Cumulative Index of Nursing and Allied Health, Published International Literature on Traumatic Stress (PILOTS) and ProQuest Dissertations, from inception to October 2017. Randomised controlled trials, regardless of language, publication year and publication type, comparing any psychotherapies for PTSD to any control condition or alternative treatment in children and adolescents (18 years old or less) diagnosed with full or subclinical PTSD will be included. Study duration and the number of treatment sessions will not be limited. The primary outcome will be PTSD symptom severity at post-treatment as measured by a rating scale reported by the child, parent or a clinician. The secondary outcomes will include: (1) efficacy at follow-up; (2) acceptability (all-cause discontinuation); (3) anxiety symptom severity; (4) depressive symptom severity and (5) quality of life and functional improvement. Bayesian network meta-analyses for all relative outcome measures will be performed. We will conduct subgroup and sensitivity network meta-analyses to determine whether the findings are affected by study characteristics. The quality of the evidence contributing to network estimates of the primary outcome will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluations framework.Ethics and disseminationNo ethical issues are foreseen. The results will be published in a peer-reviewed journal, which will be disseminated electronically and in print. This network meta-analysis may be updated to inform and guide the clinical management of PTSD in children and adolescents.PROSPERO registration numberCRD42016051786.

This chapter is an overview of recent progress in the design of Pt(IV) prodrugs. These kinetically-inert octahedral prodrugs can be reduced in cancer cells to active squareplanar Pt(II) complexes, for example by intracellular reducing agents such as glutathione or by photoexcitation. The additional axial ligands in Pt(IV) complexes which are released on reduction, allow bioactive molecules to be delivered which can act synergistically with Pt(II) in killing cancer cells, or act as targeting vectors, allow attachment to polymer and nanoparticle delivery systems, or labelling with fluorescent probes. Pt(IV) prodrugs have yet to be approved for clinical use, although some offer the promise of increased efficacy and reduced side effects.

Vanadium compounds have been known to have beneficial therapeutic properties since the turn of the century, but it was not until 1965 when it was discovered that those effects could be extended to treating cancer. Some vanadium compounds can combat common markers of cancer, which include metabolic processes that are important to initiating and developing the phenotypes of cancer. It is appropriate to consider vanadium as a treatment option due to the similarities in some of the metabolic pathways utilized by both diabetes and cancer and therefore is among the few drugs that are effective against more than one disease. The development of vanadium compounds as protein phosphatase inhibitors for the treatment of diabetes may be useful for potential applications as an anticancer agent. Furthermore, the ability of vanadium to redox cycle is also important for biological properties and is involved in the pathways of reactive oxygen species. Early agents including vanadocene and peroxovanadium compounds have been investigated in detail, and the results can be used to gain a better understanding of how some vanadium compounds are modifying the metabolic pathways potentially developing cancer. Considering the importance of coordination chemistry to biological responses, it is likely that proper consideration of compound formulation will improve the efficacy of the drug. Future development of vanadium-based drugs should include consideration of drug formulation at earlier stages of drug development.