Use of the false discovery rate for evaluating clinical safety data

Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed 'Double FDR' approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term 'Double FDR'.     

A new analytical-empirical model for the instantaneous diffuse radiation and experimental investigation of its validity

Most of the diffuse fraction correlations are based on hourly or daily data. However, the performance of solar collectors depends on instantaneous solar radiation. Moreover, in most cases the diffuse fraction is defined as , or , where I_g and G_g are hourly, and daily global radiation. But in many cases it is more suitable to define the diffuse fraction as or , as was done in the ASHRAE model. At present there are some fairly accurate methods, e.g. the parameterization method, to predict direct beam radiation, I_bn. In combination with an accurate model for diffuse fraction defined as , these methods would allow the prediction of instantaneous, hourly and daily beam, diffuse, ground reflected, and total solar radiation. The model developed in this paper allows the calculation of instantaneous diffuse radiation directly from the extraterrestrial radiation. According to this model, the instantaneous diffuse radiation and fraction can be simulated with the help of the following formulae:

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High-Gain Chemically Gated Organic Electrochemical Transistor

Organic electrochemical transistors (OECTs) have exhibited promising performance as transducers and amplifiers of low potentials due to their exceptional transconductance, enabled by the volumetric charging of organic mixed ionic/electronic conductors (OMIECs) employed as the channel material. OECT performance in aqueous electrolytes as well as the OMIECs’ redox activity has spurred a myriad of studies employing OECTs as chemical transducers. However, the OECT's large (potentiometrically derived) transconductance is not fully leveraged in common approaches that directly conduct chemical reactions amperometrically within the OECT electrolyte with direct charge transfer between the analyte and the OMIEC, which results in sub-unity transduction of gate to drain current. Hence, amperometric OECTs do not truly display current gains in the traditional sense, falling short of the expected transistor performance. This study demonstrates an alternative device architecture that separates chemical transduction and amplification processes on two different electrochemical cells. This approach fully utilizes the OECT's large transconductance to achieve current gains of 10³ and current modulations of four orders of magnitude. This transduction mechanism represents a general approach enabling high-gain chemical OECT transducers.     

Synthesis and characterization of Ru doped CuO thin films for supercapacitor based on Bronsted acidic ionic liquid

The synthesis of nanostructured ruthenium (Ru) doped copper oxide (CuO) thin films by colloidal solution method and ionic liquid are presented. The prepared colloidal solution was spin coated on the stainless steel substrates. The coated films were used to measure the specific capacitance in the task specific Bronsted acidic that is in 3-carboxymethyl-1-methylimidazolium bisulfate [CMIM] [HSO₄] ionic liquid (IL). Further, the films were characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier transform Raman spectroscopy (FT-Raman) and cyclic voltammetry (CV). The Ru doped CuO films exhibit higher specific capacitance, C_sp (C_sp = ratio of average current in CV and a product of scan rate and mass deposited on the film) with the larger potential window as compared to undoped CuO film. The highest C_sp of 406 F g⁻¹ was observed for 15 volume percent of Ru doping concentration. This is the first successful step towards development of ecofriendly CuO based supercapacitors in task specific IL synthesized by green technology.     

Enrichment of enhanced assumed strain approximations for representing strong discontinuities: addressing volumetric incompressibility and the discontinuous patch test

We present a geometrically non‐linear assumed strain method that allows for the presence of arbitrary, intra‐finite element discontinuities in the deformation map. Special attention is placed on the coarse‐mesh accuracy of these methods and their ability to avoid mesh locking in the incompressible limit. Given an underlying mesh and an arbitrary failure surface, we first construct an enriched approximation for the deformation map with the non‐linear analogue of the extended finite element method (X‐FEM). With regard to the richer space of functions spanned by the gradient of the enriched approximation, we then adopt a broader interpretation of variational consistency for the construction of the enhanced strain. In particular, in those elements intersected by the failure surface, we construct enhanced strain approximations which are orthogonal to piecewise‐constant stress fields. Contrast is drawn with existing strong discontinuity approaches where the enhanced strain variations in localized elements were constructed to be orthogonal to constant nominal stress fields. Importantly, the present formulation gives rise to a symmetric tangent stiffness matrix, even in localized elements. The present modification also allows for the satisfaction of a discontinuous patch test, wherein two different constant stress fields (on each side of the failure surface) lie in the solution space. We demonstrate how the proposed modifications eliminate spurious stress oscillations along the failure surface, particularly for nearly incompressible material response. Additional numerical examples are provided to illustrate the efficacy of the modified method for problems in hyperelastic fracture mechanics. Copyright © 2003 John Wiley & Sons, Ltd.     

Photoelectrochemically active surfactant free single step hydrothermal mediated titanium dioxide nanorods

Titanium dioxide (TiO₂) nanorods have been successfully synthesized by a simple and cost-effective hydrothermal deposition method onto the conducting glass substrates. Effect of reaction temperature on the growth of TiO₂ nanorods have been investigated by varying the reaction temperature from 140 to 200 °C. The optical, structural, compositional, morphological properties of the synthesized films are studied. X-ray diffraction patterns reveal the formation of polycrystalline TiO₂ with the tetragonal crystal structure possessing rutile phase. The chemical composition and valence states of the constituent elements were analysed by X-ray photoelectron spectroscopy. Field emission scanning electron microscopy images shows the formation of nanorod-like structure with variation in diameter. The optical band gap energy was found to increase from 3.07 to 3.15 eV with the increase in reaction temperature exhibiting a blue shift. The films were photo electrochemically active with the maximum current density of 216 µA/cm² for the sample prepared at 180 °C.     

Automated texture‐based characterization of fibrosis and carcinoma using low‐dose lung CT images

Lung cancer is the most common cause of cancer deaths worldwide and account for 1.38 million deaths per year. Patients with lung cancer are often misdiagnosed as pulmonary tuberculosis (TB) leading to delay in the correct diagnosis as well as exposure to inappropriate medication. The diagnosis of TB and lung cancer can be difficult as symptoms of both diseases are similar in computed tomography (CT) images. However, treating TB leads to inflammatory fibrosis in some of the patients. There comes the need of an efficient computer aided diagnosis (CAD) of the fibrosis and carcinoma diseases. To design a fully automated CAD for characterizing fibrous and carcinoma tissues without human intervention using lung CT images. The 18 subjects in this study include seven healthy, two fibrosis and eight carcinoma, and one necrosis cases. The dataset is built by CT cuts representing healthy is 113, fibrosis is 103, necrosis is 39, and carcinoma is 185 totalling 440 images. The gray‐level spatial dependence matrix and gray level run length matrix approach are used for extracting texture‐based features. These features are given to neural network classifier and statistical classifier. These classifier performances are evaluated using receiver‐operating characteristics (ROC). The proposed method characterizes these tissues without human intervention. Sensitivity, specificity, precision, and accuracy followed by ROC curves were obtained and also studied. Thus, the proposed automated image‐based classifier could act as a precursor to histopathological analysis, thereby creating a way to class specific treatment procedures.     

Two-dimensional single-crystalline Zn hexagonal nanoplates: size-controllable synthesis and X-ray diffraction study

We synthesized two-dimensional (2D) Zn hexagonal nanoplates using the thermal metal-vapor deposition technique. An increase and decrease in the surface area and thickness of the 2D Zn hexagonal nanoplates were shown with elevated annealing temperatures, indicating their sizes to be controlled using the annealing treatment. X-Ray diffractometry (XRD) studies revealed the crystalline nature of the 2D Zn hexagonal nanoplates and the diffraction intensity of the (002) lattice plane, which increased parabolically with elevated annealing temperatures.     

Ultrasound‐Propelled Nanoporous Gold Wire for Efficient Drug Loading and Release

Ultrasound (US)‐powered nanowire motors based on nanoporous gold segment are developed for increasing the drug loading capacity. The new highly porous nanomotors are characterized with a tunable pore size, high surface area, and high capacity for the drug payload. These nanowire motors are prepared by template membrane deposition of a silver‐gold alloy segment followed by dealloying the silver component. The drug doxorubicin (DOX) is loaded within the nanopores via electrostatic interactions with an anionic polymeric coating. The nanoporous gold structure also facilitates the near‐infrared (NIR) light controlled release of the drug through photothermal effects. Ultrasound‐driven transport of the loaded drug toward cancer cells followed by NIR‐light triggered release is illustrated. The incorporation of the nanoporous gold segment leads to a nearly 20‐fold increase in the active surface area compared to common gold nanowire motors. It is envisioned that such US‐powered nanomotors could provide a new approach to rapidly and efficiently deliver large therapeutic payloads in a target‐specific manner.