Carbon coating of fine particles of Li4Ti5O12 synthesized under hydrothermal condition is carried out by amphiphilic carbonaceous material (ACM) in aqueous solution, followed by carbonization at ...800°C for 2h. The particles prepared are comprised of highly-crystalline spinel-type Li4Ti5O12 with the size in the range of 100–400nm without any agglomeration, of which surface is uniformly covered by a thin carbon layer. Their electrochemical performance as an anode in lithium-ion batteries is evaluated. The initial discharge capacity of carbon-coated Li4Ti5O12 at 20C rate is 137mAhg−1 and remains as high as 125mAhg−1 after 100 cycles (91% retention), exhibiting good rate and cyclic performance. Carbon coating by using ACM as carbon precursor gives the Li4Ti5O12 particles an enhanced performance as an anode in lithium-ion batteries, owing to the improvement in electrical conductivity, polarization and ability of dispersion. This non-organic coating process may present a new economic, facile, and green pathway for the preparation of carbon-coated Li4Ti5O12 as a high power anode material in lithium-ion batteries.
► Carbon-coated Li4Ti5Ol2 was prepared by using ACM as a carbon precursor. ► The obtained Li4Ti5Ol2 electrode presents high-rate capability and cyclic stability. ► This economic, facile, and green synthesis method enables the production on a large scale.
Amphiphilic carbonaceous material (ACM), with nanoscale dispersion in alkaline aqueous solutions, is synthesized from green needle coke. As a special precursor with small particle size, plenty of ...functional groups and widened
d
002 simultaneously, ACM guarantees subsequent ACM-based activated carbons (AACs) with high specific surface area over 3000
m
2
g
−1 as well as well-developed mesoporous structure after KOH activation. Such pore properties enable AACs’ high performances as electrode materials for electric double-layer capacitors (EDLCs). In particular, surface area up to 3347
m
2
g
−1 together with notable mesopore proportion (26.9%) gives sample AAC814 outstanding EDLC behaviors during a series of electrochemical tests including galvanostatic charge/discharge, CV and electrochemical impedance spectroscopy. The electrode gets satisfactory gravimetric and volumetric specific capacitance at the current density of 50
mA
g
−1, up to 348
F
g
−1 and 162
F
cm
−3, respectively. Furthermore, for the mesoporosity, there is only a slight capacitance reduction for AAC814 as the current density reaches 1000
mA
g
−1, indicating its good rate performance. It is all the ACM's unique characteristics that make AACs a sort of competitive EDLC electrode materials, both in terms of specific capacitance and rate capability.
Background Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various ...metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed. Methods Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non–small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years. Results Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval CI = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects. Conclusions Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.
To handle composite endpoints, the win ratio has been applied to data analysis and design of clinical trials. Its interpretation, however, is not always clear, and it could handle ties differently. ...We address these two aspects. First, we express the win ratio as a ratio of two proportions, namely, the proportion of patient-level comparisons in which the experimental treatment "wins" over the control divided by the proportion of "wins" for the control, taking into account the priority order of the components. This equivalent form, the ratio of proportions, can ease communication to clinical trial stakeholders-especially when the win proportions themselves are reported. We recommend such presentations. In some simple cases, we connect the win ratio to the odds ratio, the hazard ratio, the Mann-Whitney U, and the mean difference. In exploring the role of ties, we introduce the win odds, as an extension of the Mann-Whitney odds under the framework of prioritized pairwise comparisons. Finally, we discuss some practical aspects of the win ratio, including rules for defining winners (or losers) and ties, dependence on censoring, win ratio estimands, and benefit-risk assessments, as well as applications to two clinical studies.
Schizophrenia is a common psychiatric disease with high hereditary. The identification of schizophrenia risk genes (SRG) has shed light on its pathophysiological mechanisms. Mouse genetic models have ...been widely used to study the function of SRG in the brain with a cell type specific fashion. However, whether the cellular expression pattern of SRG is conserved between human and mouse brain is not thoroughly studied.
We analyzed the single-cell transcription of 180 SRG from human and mouse primary visual cortex (V1). We compared the percentage of glutamatergic, GABAergic and non-neuronal cells that express each SRG between mouse and human V1 cortex. Thirty percent (54/180) of SRG had significantly different expression rate in glutamatergic neurons between mouse and human V1 cortex. By contrast, only 5.6% (10/180) of SRG showed significantly different expression in GABAergic neurons, which is similar with the ratio of SRG (15/180) with species difference in total cell populations. Strikingly, the percentage of non-neuronal cells expressing all SRG are indistinguishable between human and mouse V1 cortex. We further analyzed the biological significance of differentially expressed SRG by gene ontology. The species-different SRG in glutamatergic neurons are highly expressed in dendrite and axon. They are enriched in the biological process of response to stimulus. However, the differentially expressed SRG in GABAergic neurons are enriched in the regulation of organelle organization.
GABAergic neurons are more conserved in the expression of SRG than glutamatergic neurons while the non-neuronal cells show the species conservation for the expression of all SRG. It should be cautious to use mouse models to study those SRG which show different cellular expression pattern between human and mouse cortex.
ABSTRACT IMPACT: Our findings could potentially identify CVD at-risk persons living with HIV who might benefit from aggressive risk-reduction. OBJECTIVES/GOALS: PWH have higher rates of CVD than the ...general population yet CVD risk prediction models rely on traditional risk factors and fail to capture the heterogeneity of CVD risk in PWH. Here we identify protein biomarkers that are able to discriminate between CVD cases and controls in PWH, and we assess their added benefit beyond traditional risk factors. METHODS/STUDY POPULATION: We analyzed 459 baseline protein expression levels from five OLINK panels in a matched CVD (MI, coronary revascularization, stroke, CVD death) case-control study with 390 PWH from INSIGHT trials (131 cases, 259 controls). We formed 200 datasets via bootstrap. For each bootstrap set, a two-component partial least squares discriminant model (PLSDA) was fit. The importance of each variable in the discrimination of cases and controls in the PLSDA projection was assessed by the variable importance in projection (VIP) score. Proteins with average VIP scores > 1 were used in penalized logistic regression models with elastic net penalty, and proteins were ranked based on the number of times the protein had a nonzero coefficient. Proteins in the top 25th percentile were considered to have high discrimination. RESULTS/ANTICIPATED RESULTS: Participants had mean age 47 years, 13% were females, 4.9% had CVD at baseline and 69% were on ART at baseline. Eight proteins including the hepatocyte growth factor and interleukin-6 were identified as able to distinguish between CVD cases and controls within PWH. A protein score (PS) of the top-ranked proteins was developed using the bootstrap (for weights) and the entire data. The PS was found to be predictive of CVD independent of established CVD and HIV factors (Odds ratio: 2.17 CI: 1.58-2.99). A model with the PS and traditional risk factors had a 5.9% improvement in AUC over the baseline model (AUC=0.731 vs 0.69), which is an increase in model predictive power of 18%. Individuals with a PS above the median score were 3.1 (CI: 1.83- 5.41) times more likely to develop CVD than those with a protein score below the median score. DISCUSSION/SIGNIFICANCE OF FINDINGS: A protein score developed improved discrimination of PWH with CVD and those without, and helped identify PWH with high risk for developing CVD. If validated, this score and/or the individual proteins could be used in addition with established factors to identify CVD at-risk individuals who might benefit from aggressive risk-reduction.
Statistical approaches that successfully combine multiple datasets are more powerful, efficient, and scientifically informative than separate analyses. To address variation architectures correctly ...and comprehensively for high-dimensional data across multiple sample sets (ie, cohorts), we propose multiple augmented reduced rank regression (maRRR), a flexible matrix regression and factorization method to concurrently learn both covariate-driven and auxiliary structured variations. We consider a structured nuclear norm objective that is motivated by random matrix theory, in which the regression or factorization terms may be shared or specific to any number of cohorts. Our framework subsumes several existing methods, such as reduced rank regression and unsupervised multimatrix factorization approaches, and includes a promising novel approach to regression and factorization of a single dataset (aRRR) as a special case. Simulations demonstrate substantial gains in power from combining multiple datasets, and from parsimoniously accounting for all structured variations. We apply maRRR to gene expression data from multiple cancer types (ie, pan-cancer) from The Cancer Genome Atlas, with somatic mutations as covariates. The method performs well with respect to prediction and imputation of held-out data, and provides new insights into mutation-driven and auxiliary variations that are shared or specific to certain cancer types.
Traditional synthesis methods of mesoporous carbon include hard templates (e.g., metal oxides, metal salts and mesoporous silica) and soft templates (e.g., surfactant and block copolymer). However, ...complicated and time-consuming procedures, high template costs, and harsh preparation conditions hinder the scale-up of these methods. Here, we report a simple and bottom-up strategy to synthesize mesoporous carbon by using the sodium-assisted carbonization of bromobenzene without additional templates added. Depending on the pyrolysis temperature, the obtained material with nanorod structures has a high surface area of 1902 m2 g−1, a large pore volume of 1.21 cm3 g−1 and a high degree of graphitization. Meanwhile, the pore-forming mechanism of this strategy is explored and attributed to the “in situ templating” effect of NaBr. The resultant material at 800 °C shows considerable rate performance, long lifetime and high power density. Additionally, the versatility and feasibility of the technique are validated via carbonization of six halogenated aromatic hydrocarbons by three alkali metals. Compared with lithium and potassium, sodium has better pore-forming effect and the obtained products possess a high surface area (1450–2100 m2 g−1) and a large pore volume (1.1–1.6 cm3 g−1). Furthermore, these mesoporous carbons show high adsorption capacity on dye macromolecules.
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Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug ...conjugate targeting folate receptor α (FRα). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC.
SORAYA enrolled FRα-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point.
One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively.
MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.
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