Impact of depth of response on survival in patients treated with cobimetinib ± vemurafenib: pooled analysis of BRIM-2, BRIM-3, BRIM-7 and coBRIM.

BackgroundThis pooled analysis investigated the prognostic value of depth of response in two cohorts of patients with BRAFV600-mutated metastatic melanoma treated with vemurafenib or cobimetinib plus vemurafenib.MethodsThe data were pooled from BRIM-2, BRIM-3, BRIM-7 and coBRIM. Association of depth of response with survival was estimated by Cox proportional hazards regression, adjusted for clinically relevant covariates. Depth of response was analysed in previously identified prognostic subgroups based on disease characteristics and gene signatures.ResultsGreater tumour reduction and longer time to maximal response were significantly associated with longer progression-free survival (PFS) and overall survival (OS) when evaluated as continuous variables. Patients with the deepest responses had long-lasting survival outcomes (median PFS: 14 months; OS: 32 months with vemurafenib; not estimable with cobimetinib plus vemurafenib). Cobimetinib plus vemurafenib improved depth of response versus vemurafenib monotherapy regardless of other prognostic factors, including gene signatures.ConclusionsGreater depth of response was associated with improved survival, supporting its utility as a measure of treatment efficacy in melanoma and further evaluation of its incorporation into existing prognostic models. Cobimetinib plus vemurafenib improved outcomes across quartiles of response regardless of prognostic factors or gene signatures and provided durable survival benefits in patients with deep responses

Astragalus Granule Prevents Ca 2+

Background. Astragalus was broadly used for treating heart failure (HF) and arrhythmias in East Asia for thousands of years. Astragalus granule (AG), extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L) in HF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). Methods. HF mice were induced by thoracic aortic constriction (TAC). After 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte was then isolated and whole-cell patch clamp was used to record action potential (AP) and ICa-L. The expressions of L-type calcium channel alpha 1C subunit (Cav1.2), CaMKII, and phosphorylated protein kinase A (p-PKA) were examined by western blot. Results. The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition, AG treatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. Conclusion. AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Cooperative Localization Algorithm for Multiple Mobile Robot System in Indoor Environment Based on Variance Component Estimation

The Multiple Mobile Robot (MMR) cooperative system is becoming a focus of study in various fields due to its advantages, such as high efficiency and good fault tolerance. However, the uncertainty and nonlinearity problems severely limit the cooperative localization accuracy of the MMR system. Thus, to solve the problems mentioned above, this manuscript presents a cooperative localization algorithm for MMR systems based on Cubature Kalman Filter (CKF) and adaptive Variance Component Estimation (VCE) methods. In this novel algorithm, a nonlinear filter named CKF is used to enhance the cooperative localization accuracy and reduce the computational load. On the other hand, the adaptive VCE method is introduced to eliminate the effects of unknown system noise. Furthermore, the performance of the proposed algorithm is compared with that of the cooperative localization algorithm based on normal CKF by utilizing the real experiment data. In addition, the results demonstrate that the proposed algorithm outperforms the CKF cooperative localization algorithm both in accuracy and consistency

An Adaptive Initial Alignment Algorithm Based on Variance Component Estimation for a Strapdown Inertial Navigation System for AUV

As a typical navigation system, the strapdown inertial navigation system (SINS) is crucial for autonomous underwater vehicles (AUVs) since the SINS accuracy determines the performance of AUVs. Initial alignment is one of the key technologies in SINS, and initial alignment time and initial alignment accuracy affect the performance of SINS directly. As actual systems are nonlinear, the nonlinear filter is widely used to improve the accuracy of the initial alignment. Due to its higher precision and lower computational load, the cubature Kalman filter (CKF) has done well in state estimation. However, the noise characteristics need to be known exactly as prior knowledge, which is difficult or even impossible to achieve. Thus, the adaptive filter should be introduced in the initial alignment algorithm to suppress the uncertainty effect caused by the unknown system noise. Therefore, taking the nonlinearity and uncertainty into account, a novel initial alignment algorithm for AUVs is proposed in this manuscript, based on CKF and the adaptive variance components estimation (VCE) filter (VCKF). Additionally, the simulation and experiment results show that not only the accuracy, but also the convergence speed can be improved with this proposed method. The validity and superiority of this novel adaptive initial alignment algorithm based on VCKF are verified